METAL–CARBON (METAL = IRIDIUM(III) AND GOLD(III)) BOND
FORMATION UNDER TRANSMETALATION AND CATALYTIC CONDITIONS;
METALLONUCLEOSIDES AS ANTICANCER DRUGS AND BIO-PHOTONIC
PROBES; AND SYNTHESIS OF IRIDIUM FLUORIDE COMPLEXES
By
AYAN MAITY
Submitted in partial fulfillment of the requirements for
the Degree of Doctor of Philosophy
Thesis Advisor: Thomas G. Gray, Ph.D.
Department of Chemistry
CASE WESTERN RESERVE UNIVERSITY
January 2015 CASE WESTERN RESERVE UNIVERSITY
SCHOOL OF GRADUATE STUDIES
We hereby approve the thesis/dissertation of
Ayan Maity
candidate for the Doctor of Philosophy degree*.
(signed) Irene Lee, Ph.D. (Chair of the committee)
Thomas G. Gray, Ph. D.
Malcolm E. Kenney, Ph.D.
James D. Burgess, Ph.D.
Horst von Recum, Ph.D.
(date) 6th August, 2014
* We also certify that written approval has been obtained for any proprietary material contained therein.
ii
Dedicated to
all my teachers who taught me to love the subject and inspired me to decipher the
mysteries of chemistry, specially
Prof. Prasanta Ghosh and Prof. Ashish Kumar Nag;
and to my loving uncle ‘Chotomama’
iii TABLE OF CONTENTS
TABLE OF CONTENTS iv
LIST OF FIGURES ix
LIST OF SCHEMES xiv
LIST OF TABLES xv
LIST OF CHARTS xviii
ACKNOWLEDGEMENT xix
LIST OF ABBREVIATIONS xxi
ABSTRACT xxvi
Chapter 1. General Introduction 1
1.1. The Chemistry of Iridium 2
1.2. The Chemistry of Gold 7
1.3. Transmetalation Synthesis of Cyclometalated
Iridium(III) Complexes 12
1.4. 2-Deoxy-Ribose Sugar Complex of Cyclometalated
Iridium(III): Probe for Nucleosides Transporter 15
1.5. Transition Metal Fluorine Chemistry 18
1.6. Gold(I) Based Anticancer Drugs 20
1.7. Proposed Research 25
A. Application of Transmetalation Strategy to Synthesize
Cyclometalated Iridium(III) Complexes 25
B. Suzuki–Miyaura Coupling of Arylboronic Acids to Gold(III) 26
iv C. Cyclometalated Iridium(III) Complexes with Deoxyribose
Substituents 27
D. Synthesis of Bridging and Terminal Cyclometalated
Complexes of Iridium(III) 28
E. A Gold(I) Metallonuceloside as Anticancer Drug 30
1.8. References 31
Chapter 2. Application of Transmetalation Strategy to Synthesize
Cyclometalated Iridium(III) Complexes 42
2.1. Introduction 43
2.2. Results and Discussion 48
2.3. Conclusion 57
2.4. Experimental Section 57
2.4.1. Materials and Methods 57
+ 2.4.2. Synthesis of Bis-aquo Complexes [L2Ir(H2O)2] (a-e) 58
2.4.3. Synthesis of C^N Chelating Borylated Ligands 60
2.4.4. Base Promoted Transmetalation Reactions 62
2.4.4.1. Synthesis of Iridium Complexes With C^N
Chelating Ligands 62
2.4.4.2. Synthesis of Iridium Complexes with C^O
Chelating Ligands 71
2.4.5. Luminescence Measurements 82
2.5. References 82
Chapter 3. Suzuki–Miyaura Coupling of Arylboronic Acids to Gold(III) 87
v 3.1. Introduction 88
3.2. Results and Discussion 89
3.3. Conclusion 100
3.4. Experimental Section 102
3.4.1. Materials and Methods 102
3.4.2. Synthesis of [(C^N)AuCl2] 103
3.4.3. Synthesis of [(tpy)Au(aryl)2] 105
3.4.4. Synthesis of monoarylated products 119
3.5. References 122
Chapter 4. Cyclometalated Iridium(III) Complexes with
Deoxyribose Substituents 127
4.1. Introduction 128
4.2. Results and Discussion 131
4.3. Conclusion 136
4.4. Experimental Section 137
4.4.1. Materials and Methods 137
4.4.2. Synthesis of ligandoside 138
4.4.3. Synthesis of metallonucleosides 141
4.4.4. Luminescence Measurements 145
4.5. References 146
Chapter 5. Synthesis and Reactivity of Bridging and Terminal
Fluoride Complexes of Bis(cyclometalated) Iridium(III) 153
5.1. Introduction 154
vi 5.2. Results and Discussion 156
5.3. Conclusion 164
5.4. Experimental Section 164
5.4.1. Materials and Methods 164
5.4.2. Synthesis of Fluoride Bridged Ir(III) Cyclometalates 166
5.4.3. Synthesis of Terminal Fluoride Complexes of
Ir(III) Cyclometalates 167
5.4.4. Reactivity of [Ir(bt)2(F)(3,5-dimethylpyrazole)]
(2a) with Silylated Reagents 169
5.4.5. Fluorine Transfer Reaction with Carbon and
Sulfur Based Electrophile 173
5.4.6. X-ray Crystallography 174
5.4.7. Luminescence Measurements 174
5.5. References 175
Chapter 6. Synthesis and Cytotoxicity Studies of a Non-natural
Nucleoside Bearing (triphenylphosphine)gold(I) 179
6.1. Introduction 180
6.2. Results and Discussion 182
6.2.1. Synthesis 182
6.2.2. Cytotoxicity Studies 185
6.2.3. Flow-cytometric Analysis 189
6.2.4. Apoptosis Measurement 191
6.2.5. Mitochondrial Permeability Transition 192
vii 6.2.6. Inhibition of Thioredoxin Reductase (TrxR) 193
6.3. Conclusion 195
6.4. Experimental Section 195
6.4.1. Materials and Methods 195
6.4.2. Synthesis of gold(I) nucleosides 196
6.4.3. General Cell Culture Procedures 201
6.4.4. Cell Proliferation Assays 201
6.4.5. Measurements of Apoptosis 202
6.4.6. Cell Cycle Analyses 202
6.4.7. Assessment of the Mitochondrial Membrane Potential 203
6.4.8. Thioredoxin Reductase Inhibition 204
6.5. References 204
Chapter 7. Conclusion And Future Direction 207
Appendix 211
Bibliography 324
viii LIST OF FIGURES
Figure 1.1.1. Energy transfer mechanisms in the sensitized system. 5
Figure 1.1.2. Structure of facial-tris(2-phenylpyridinato,N,C2′)iridium(III), fac-Ir(ppy)3. 6
Figure 1.2.1. Position of gold in periodic table of elements. 7
Figure 1.2.2. Aurophilic interaction in dithiocarbamate complexes of gold(I). 11
Figure 1.4.1. Nucleoside transport processes in mammalian cells. 17
Figure 1.5.1. Electronic properties of halide ligands. 19
Figure 1.6.1. Structure of rheumatoid arthritis drug auranofin and proposed radiosensitizer. 22
Figure 1.6.3. Organophosphines and their cone 23
Figure 1.6.2. Models for the cytotoxic effects of gold-containing nucleosides. 24
Figure 2.1.1. Energy diagram for the working principle of OLEDs. 45
Figure 2.1.2. Crystal structure of the aldehyde complex [(F2ppy)2Ir(FoTol)] showing ellipsoids at the 50% probability level. 54
Figure 2.1.3. Crystal structure of the alcohol complex
[(F2ppy)2Ir(TolMeOH)] showing 50% probability ellipsoids. 55
Figure 2.1.4. UV-vis absorption and emission spectra of [(F2ppy)2Ir(FoTol)] in deaerated acetonitrile. 56
Figure 3.2.1. a) Crystal structure of [(tpy)Au(p-C6H5F)2], b) Crystal structure of [(tpy)Au(4-(trifluoromethyl)phenyl)2], c) Crystal structure of [(tpy)Au(3- nitrophenyl)2]. 95
Figure 3.2.2. a) Crystal structure of disordered [(tpy)Au(benzo[b]thien-2- 96
ix yl)2], b) Crystal structure of [(tpy)Au(o-tolyl)2].
Figure 3.2.3. a) Crystal structure of [(tpy)Au(4-isopropoxyphenyl)2], b)
Crystal structure of [(tpy)Au(Cl)( 4-fluorophenyl)], c) Crystal structure of
[(tpy)Au(Cl)(1-naphthyl)]. 97
Figure 3.2.4. Crystal structure of dichloro(2-(4- fluorophenyl)pyridine)gold(III) 98
Figure 3.2.5. Crystal structure of [(tpy)Au(2-acetylphenylato)]. 99
Figure 4.2.1. Thermal ellipsoid representation (50% probability) of the cation of [Ir(ppy)2(7)](PF6). 133
Figure 4.2.1. (a) Absorption spectra of metallonucleosides collected in acetonitrile solvent at 298K; (b) Normalized emission spectra (298 K) of new complexes in 2-methyltetrahydrofuran. 134
Figure 4.2.3. Normalized emission spectra (77 K) of new complexes in 2- methyltetrahydrofuran glass. 135
Figure 5.2.1. Crystal structure of the iridium(III) dimer [(bt)2Ir(µ-F)]2 (50%). 157
Figure 5.2.2. Crystal structure of [Ir(bt)2(F)(3,5-dimethylpyrazole)] (50% probability). 158
Figure 5.2.3. a) Crystal structure of [Ir(bt)2(Cl)(3,5-dimethylpyrazole)] (50% probability). b) Crystal structure of [Ir(bt)2(SPh)(3,5-dimethylpyrazole)] (50% probability). c) Crystal structure of [Ir(bt)2(N3)(3,5-dimethylpyrazole)] (50% probability). 160
Figure 5.2.4. Normalized, room-temperature emission spectra of [(bt)2Ir(µ-
F)]2 (solid) and [Ir(bt)2(F)(3,5-dimethylpyrazole)] (dashed) in 2- 163
x methyltetrahydrofuran.
Figure 6.1.1. Clinically established gold(I) anti-arthritic drugs. 181
Figure 6.1.2. Designing of gold(I) containing nucleoside. 182
Figure 6.2.1. Synthesized gold(I) containing nucleosides. 184
Figure 6.2.2. Crystal structure of the complex (9-(2-deoxy-β-D-erythro- pentofuranosyl)purine-6-thio)(tricyclohexylphosphine) -gold- (I), 8b showing ellipsoids at the 50% probability level. 185
Figure 6.2.3. CCRF CEM-7 cell proliferation after different concentration of drug treatment over 48 h. Compound 7 is represented as dR-MP and compound (9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6- thio)(triphenylphosphine)gold- (I) (8a) as dR-MP-AuPPh3. 186
Figure 6.2.4. Drug sensitivity profile of CCRF CEM-7 cells treated with 7 and 8a for 48 h. Compound 7 is represented as dR-MP and compound 8a as dR-MP-AuPPh3. 186
Figure 6.2.5. Cytotoxicity of 8a on Molt 4 cells after 48 h. Compound 8a as dr-MP-AuPPh3. 187
Figure 6.2.6. Induction of cell cycle arrest in the Molt 4 cancer cells after treatment with compound 7 and compound (9-(2-deoxy-β-D-erythro- pentofuranosyl)purine-6-thio)(triphenylphosphine)gold- (I), 8a. 190
Figure 6.2.7. Annexin-PI staining of Molt 4 cells treated with compound 8a for 48 hr. 191
Figure 6.2.8. Mitochondrial permeability transition assay performed with
HeLa cells. 192
xi Figure 6.2.9. The time course vs absorbance plot for thioredoxin reductase inhibition assay when treated with two different concentratopn of compound
8a along with positive (marked as DTNB+TrXR in the graph) and negative control (marked as DTNB control). 194
Figure 7.1. Various cyclometalating ligand that are available. 209
Figure AII.1. 1H NMR spectrum of 1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-
(2-pyridinyl))-1,2,3-triazole. 295
Figure AII.2. 13C NMR spectrum of 1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-
(2-pyridinyl))-1,2,3-triazole 296
1 Figure AII.3. H NMR spectrum of [Ir(ppy)2(7)]PF6 297
13 Figure AII.4. C NMR spectrum of [Ir(ppy)2(7)]PF6 298
1 Figure AII.5. H NMR spectrum of [Ir(tpy)2(7)]PF6 299
1 Figure AII.6. H NMR spectrum of [Ir(btp)2(7)]PF6 300
13 Figure AII.7. C NMR spectrum of [Ir(tpy)2(7)]PF6 301
1 Figure AII.8. H NMR spectrum of [Ir(bzq)2(7)]PF6 302
13 Figure AII.9. C NMR spectrum of [Ir(bzq)2(7)]PF6 303
1 Figure AII.10. H NMR spectrum of [Ir(pq)2(7)]PF6 304
13 Figure AII.11. C NMR spectrum of [Ir(pq)2(7)]PF6 305
1 Figure AII.12. H NMR spectrum of [(tpy)Au(p-C6H5F)2] 306
1 Figure AII.13. H NMR spectrum of [(tpy)Au(2,4-difluorophenyl)2] 307
1 Figure AII.14. H NMR spectrum of [(tpy)Au(4-(trifluoromethyl)phenyl)2] 308
19 Figure AII.15. F NMR spectrum of [(tpy)Au(4-(trifluoromethyl)phenyl)2] 309
1 Figure AII.16. H NMR spectrum of [(tpy)Au(3-nitrophenyl)2]. 310
xii 1 Figure AII.17. H NMR spectrum of [(tpy)Au(3-ethoxycarbonylphenyl))2]. 311
1 Figure AII.18. H NMR spectrum of [(tpy)Au(4-acetylphenyl))2]. 312
1 Figure AII.19. H NMR spectrum of [(tpy)Au(phenyl)2]. 313
1 Figure AII.20. H NMR spectrum of [(tpy)Au(2-naphthyl)2]. 314
1 Figure AII.21. H NMR spectrum of [(tpy)Au(benzo[b]thien-2-yl)2]. 315
1 Figure AII.22. H NMR spectrum of [(tpy)Au(m-tolyl)2]. 316
1 Figure AII.23. H NMR spectrum of [(tpy)Au(4-methoxyphenyl)2]. 317
1 Figure AII.24. H NMR spectrum of [{Ir(bt)2(µ-Cl)}2]. 318
1 Figure AII.25. H NMR spectrum of [{Ir(bt)2(µ-F)}2]. 319
19 Figure AII.26. F NMR spectrum of [{Ir(bt)2(µ-F)}2] 320
1 Figure AII.27. H NMR spectrum of [Ir(bt)2(F)(2,3-dimethylpyrazolato)]. 321
19 Figure AII.28. F NMR spectrum of [Ir(bt)2(F)(2,3-dimethylpyrazolato)] 322
1 Figure AII.29. H NMR spectrum of [Ir(bt)2(Cl)(2,3-dimethylpyrazolato)] 323
xiii LIST OF SCHEMES
Scheme 1.3.1. Cyclometalation via C–R bond activation. 13
Scheme 1.7.1. Synthesis of (tris)cyclometalated iridium(III) complexes. 25
Scheme 1.7.2. Reaction scheme for Suzuki–Miyaura coupling of arylboronic
acids extends gold(III) chlorides. 27
Scheme 1.7.3. Synthesis of typical nucleoside. 28
Scheme 1.7.4. Proposed reaction for synthesizing fluorobridged and terminal
fluoro complex of bis(cyclometalated) Ir(III) complexes. 29
Scheme 1.7.5. Synthesis of gold(I) nucleosides. 30
Scheme 2.1.1. Conventional synthesis of Ir(III) cyclometalates. 46
Scheme 2.1.2. Transmetalation strategy to synthesize Ir(III) cyclometalates. 47
Scheme 3.2.1. Proposed mechanism of gold(III) arylation. 100
Scheme 4.2.1. Synthesis of 1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-(2-
pyridinyl))-1,2,3-triazole, 7. 131
Scheme 4.2.2. Synthesis of typical metallonucleoside. 132
Scheme 5.2.1. Syntheses of cyclometalated iridium(III) fluoride complexes. 156
Scheme 5.2.2. Reactions of terminal fluoride complex [Ir(bt)2(F)(3,5-
dimethylpyrazole)] with organosilanes. 161
Scheme 5.2.3. Reactions of [Ir(bt)2(F)(3,5-dimethylpyrazole)] with sulphur-
and carbon-based electrophiles. 162
Scheme 6.2.1. Synthesis of gold(I) nucleosides. 183
Scheme 7.1. Developed synthetic protocol for Au(III)–Cl arylation 209
Scheme 7.2. Proposed reaction for iridium cyclometalation. 210
xiv LIST OF TABLES
Table 1.1.1. Physical and Mechanical Properties of Iridium. 3
Table 1.1.2. Oxidation States and Geometries of Organoiridium
Compounds. 4
Table 1.2.1. Physical Properties of Gold. 8
Table 2.1.1. Preliminary screening with variation of supporting base. 49
Table 2.1.2. Selected conditions for base promoted transmetalation
reaction. 50
Table 2.1. 3. Syntheses of iridium(III) complexes. 52
Table 2.1.4. Syntheses of cyclometalated ketone, aldehyde, and alcohol
complexes. 53
Table 2.1.5. Photophysical properties of Ir(III) ketone, aldehyde and
alcohol complexes. 56
Table 3.2.1. Optimization of reaction conditions for di-arylation of
dichlorogold(III) complexes. 90
Table 3.2.2. Screening of bases and solvents for di-arylation of
dichloro-gold(III) complexes. 92
Table 3.2.3. Gold(III) products and isolated yields. Carbon-gold bonds
formed are indicated in red. Et = ethyl; Ph = phenyl. 94
Table 4.2.1. Emission wavelengths λem, lifetimes τ, and quantum yields
– φem of iridium(III) complexes as PF6 salts at 295 K and 77 K in 2-
methyltetrahydrofuran. 136
Table 5.2.1. Emission wavelengths (Eem), quantum yields (φem) and
xv lifetimes (τ) of bridging and terminal fluoride complexes at 298 and 77 K
in 2-methyltetrahydrofuran. 163
Table 6.2.1. Summary of in vitro cytotoxicity in terms of LD50 and IC50
values for compounds 7, (9-(2-deoxy-β-D-erythro-
pentofuranosyl)purine-6-thio)(triphenylphosphine)gold- (I), 8a and
AuPPh3Cl against selected adherent and systemic cancer cell lines. 188
Table AI.1. X-ray crystallographic data for (9-(2-deoxy-β-D-erythro-
pentofuranosyl)purine-6-thio)(tricyclohexylphosphine) -gold- (I) (8b 211
Table AI.2. X-ray crystallographic data for [(Fppy)AuCl2] 222
Table AI.3. X-ray crystallographic data for [(tpy)AuI2] 225
Table AI.4. X-ray crystallographic data for [(tpy)Au(4-
isopropoxyphenyl)2] 228
Table AI.5. X-ray crystallographic data for [(tpy)Au(2-
acetylphenylato)] 233
Table AI.6. X-ray crystallographic data for [(tpy)Au(4-
(trifluoromethyl)phenyl)2] 237
Table AI.7. X-ray crystallographic data for [(tpy)Au(3-nitrophenyl)2] 241
Table AI.8. X-ray crystallographic data for [(tpy)Au(benzo[b]thien-2-
yl)2] 245
Table AI.9. X-ray crystallographic data for [(tpy)Au(o-tolyl)2] 254
Table AI.10. X-ray crystallographic data for [(tpy)Au(p-C6H5F)2] 258
Table AI.11. X-ray crystallographic data for [(tpy)Au(Cl)(1-naphthyl)] 268
Table AI.12. X-ray crystallographic data for [(tpy)Au(Cl)( 4-
xvi fluorophenyl)] 271
Table AI.13. X-ray crystallographic data for [Ir(bt)2(F)(3,5-
dimethylpyrazole)] 274
Table AI.14. X-ray crystallographic data for [Ir(bt)2(Cl)(3,5-
dimethylpyrazole)] 279
Table AI.15. X-ray crystallographic data for [Ir(bt)2(SPh)(3,5-
dimethylpyrazole)] 284
Table AI.16. X-ray crystallographic data for [{Ir(bt)2(µ-F)}2] 290
xvii LIST OF CHARTS
Chart 1.2.1. Coordination pattern of various gold centers at different
oxidation states. 9
Chart 1.7.1. Cyclometalating ligands on iridium(III) with their nomenclature. 26
Chart 2.1.1. Ligands and ligand precursors. 48
xviii Acknowledgement
Long is the road from conception to completion. The journey becomes easier when we travel together. This thesis is the result of years of research whereby I have been accompanied and supported by many people. At this juncture of completion, it is a pleasure to express my gratitude to all those who made it possible for me to complete this thesis.
I express my deep sense of gratitude and indebtedness to my mentor, Prof. Thomas G. Gray,
Department of Chemistry, Case Western Reserve University for his invaluable guidance, stimulating suggestions and constant encouragement throughout my tenure of PhD.
I would like to express my sincere gratitude to Prof. A.J. Berdis for his help and providing me the platform to carry out my biology related research.
I sincerely thank all the committee advisors, namely, Prof. Irene Lee, Prof. Malcolm E. Kenney and Prof. James D. Burgess for their fruitful suggestions. I also extend my thanks to Prof. Horst von
Recum to give his consent for being the external examiner.
I am thankful to the Gray, Berdis, Lee and Protasiewicz group members including Dr. David
Partyka, Dr. Miya Peay, Dr. James Updegraff, III., Dr. Lei Gao, Dr. Thomas J. Robilotto, Ms.
Amberle Browne, Mr. Jim Heckler, Ms. Amanda Sulicz, Mr. Robert Stanek, Dr. Sandra Craig and Dr.
Edward Motea.
Thanks to Dr. Matthias Zeller and Dr. Allen D. Hunter from Youngstown State University, Dr.
Arnold Rheingold and Dr. Curtis Moore from UC San Diego, and Dr. Nihal Deligonul for the help in
X-ray crystallography data collection. Thanks to Dr. Tom Teets from California Institute of
Technology and Mr. Bryce Anderson from Harvard University for their help in emission lifetime measurements.
xix Thanks to the faculty and staff members of the Department of chemistry at Case Western Reserve
University, in particular, Dr. Dale Ray for all the help in NMR spectroscopy.
I am greatly thankful to all my friends particularly, Mr. Adriel Jebaraj and Dr. Sanchita Basu who were constantly with me through all the thick and thin when I was miles away from my home.
I wish to thank my family for their support. Thanks to my brother-in-law, Dr. Arghya
Sadhukhan, my sister, Mrs. Arunima Sadhukhan and my brother, Mr. Apurba Maity for their constant encouragement. Last but not least, I wish to thank my parents, Late Kalyani Maity and Mr.
Narayan Chandra Maity for raising me and inculcating the urge to search for the unknown.
The financial support of National Science Foundation and the U.S. Department of Energy, are gratefully acknowledged.
Ayan Maity
Department of Chemistry,
Case Western Reserve University, CWRU
xx
LIST OF ABBREVIATIONS
a Length of unit cell axis (as in X-ray diffraction)
α Alpha angle (as in X-ray diffraction) between a and b axis
Å Angstrom
Ar Substituted aryl group b Length of unit cell axis (as in X-ray diffraction)
β Beta angle (as in X-ray diffraction) between a and c axis t-Bu tert-Butyl
Bpin 4,4,5,5-tetramethyl-1,3,2-dioxaborlyl
C Celsius c Length of unit cell axis (as in X-ray diffraction)
C6D6 Deuterobenzene
CDCl3 Deuterochloroform
CH2Cl2 Dichloromethane
CH3CN Acetonitrile cm-1 Reciprocal centimeters, wave numbers
CuAAC Copper-Catalyzed Cycloaddtion of Alkynes and Azides d Doublet (as in NMR spectroscopy)
δ Chemical shift (as in NMR spectroscopy)
Δ Heat (thermal reaction)
DCM Dichloromethane
xxi dd Doublet of doublet (as in NMR spectroscopy)
Dx Density (as in X-ray diffraction)
E Entgegen (as in E, Z nomenclature)
ε epsilon (molar extinction coefficient in UV-Vis spectroscopy)
Eq Equivalents
ESI Electro-spray ionization (as in mass spectrometry)
Et Ethyl
F Structure factor (as in X-ray diffraction)
Fc Calculated structure factor (as in X-ray diffraction)
Fo Observed structure factor (as in X-ray diffraction) g Grams
γ Gamma angle (as in X-ray diffraction) between b and c axis h Hour, Miller indices (as in X-ray diffraction)
H3PO4 phosphoric acid
Hz Hertz
HOMO Highest occupied molecular orbital
HPLC High-pressure liquid chromatography
J Coupling constant (as in NMR spectroscopy) in Hz
K Kelvin k Miller indices (as in X-ray diffraction) l Miller indices (as in X-ray diffraction)
L Ligand; liter
λmax lambda (wavelength of maximum adsorption in UV-Vis spectroscopy)
xxii LUMO Lowest unoccupied molecular orbital
µ Mu
M metal, molarity m multiplet (as in NMR) m/z mass-to-charge ration (as in mass spectrometry)
MALDI-TOF Matrix assisted laser desorption ionization-time of flight (as in mass
spectrometry)
Me Methyl
2-MeTHF 2-Methyltetrahydrofuran
MHz Megahertz mL Milliliters mm Millimeters
Mo Kα Molybdenum K alpha (as in X-ray diffraction) mol Mole mmol Millimole
Mr Molecular weight (as in X-ray diffraction) ms Millisecond
Mw Molecular weight
η Eta
N Normality
NBS N-bromosuccinimide
NHC N-Heterocyclic carbene nm nanometer
xxiii NMR Nuclear Magnetic Resonance o Ortho
OMe Methoxy
ORTEP Oak Ridge Thermal Ellipsiod Plot
π Bonding pi orbital
π* Anti-bonding pi orbital p Para
31P{1H} proton-decoupled phosphorus NMR
Ph- Phenyl
PPh3 Triphenylphosphine ppm Parts per million (as in NMR)
R Discrepancy index (as in X-ray diffraction)
Rf Retention factor (as in chromatography)
σ Bonding sigma orbital
S Goodness of fit (as in X-ray diffraction) s Singlet (as in NMR spectroscopy); strong (as in IR spectroscopy)
T Temperature
TLC Thin-layer chromatography
Tmin Minimum transmission (as in X-ray diffraction)
Tmax Maximum transmission ( as in X-ray diffraction)
ω Omega (e.g, measurement angle used in X-ray diffraction)
θ Theta (e.g., Angle between the incident and the diffracted beams, as in
X-ray diffraction)
xxiv θmax Theta (e.g., maximum Bragg angle as in X-ray diffraction) t Triplet (as in NMR spectroscopy)
THF Tetrahydrofuran
TPA Two-Photon Absorption
UV-Vis Ultraviolet visible (as in spectroscopy)
V Cell volume (as in X-ray diffraction) in vacuo High vacuum manifold wR Weighted discrepancy index (as in X-ray diffraction)
X Cl, Br, or I ligand
Z Number of molecules in unit cell (as in X-ray diffraction); total nuclear
charge; zusammen (as in E, Z nomenclature)
xxv Metal-Carbon (Metal = Iridium(III) and Gold(III)) Bond Formation Under
Transmetalation and Catalytic Conditions; Metallonucleosides as Anticancer Drugs
and Bio-photonic Probes; and Synthesis of Iridium Fluoride Complexes
Abstract
By
AYAN MAITY
Generation of metal–carbon σ-bonded complexes is a central challenge to organometallic chemistry. Metal-carbon σ-bonded compounds find applications in catalysis, luminescence, and bioimaging. The frequent air-and water sensitivity of the metal–carbon bond often impedes synthesis. Conventional preparations of cyclometalated organometallics rely on high temperature C–H bond activation; pyrophoric and toxic reagents are also commonly used. Substrate scopes are limited. Described here are new synthetic approaches that attain iridium(III)- and gold(III)-organometallics at room temperature in high yield.
Iridium(III) cyclometalates were synthesized by base promoted transmetalation from boronic acids or their pincol boronate esters to bis(aquo)iridium(III) cations.
Reaction conditions are mild, and fragile functional groups survive. Bis- and tris(cyclometalated) complexes of iridium(III) luminesce at room temperature if not quenched. Excited states decay on a microsecond time scale.
The Suzuki-Miyaura coupling reaction has become indispensible to organic synthesis. Coupling between boronic acids and alkyl, alkenyl, or alkynyl halide (or pseudohalide) partners are the norm. Little is known where metal halide is a coupling
xxvi partner. An unprecedented palladium-catalyzed reaction between gold(III) dichloride and boronic acids has been discovered. The reaction proceeds to diarylated products at room- temperature in presence of a supporting base. Screening experiments find palladium(II) acetate and tri-(t-butylphosphine) as an effective catalyst and ligand. Crystal structures of monoarylated products, formed by incomplete aryl transfer, show aryl substitution trans to the C^N nitrogen atom. This stereospecificity is counterintuitive given the trans- influence of carbon: the shorter Au–Cl bond disappears first. We propose Au(III)–C coupling reaction proceeds through oxidative addition of Au–Cl bond to palladium followed by aryl migration from palladium to gold. Reductive elimination generates monoaryl that re-enter the catalytic sequence to yield diaryls.
Emissive iridium(III) cyclometalates have been attached to a deoxyribose sugar.
They are potential photoactive surrogates of natural nucleosides; their biodisposition can be tracked optically. Gold(I) containing metallonucleosides have been synthesized and one of them has induced cytotoxicity by targeting mitochondrial TrxR.
In a separate effort, bridged and terminal fluoride of bis(cyclometalated)Ir(III) complexes have been synthesized. The terminal fluoro complex reacts with silyl reagents to afford azide, isothiocyanate, chloride and bromide complexes, among others.
xxvii Chapter 1
General Introduction
1 1.1. The Chemistry of Iridium
Iridium (Ir) is a third-row, relatively rare transition element, and a member of the platinum group of metals. Iridium, a congener of Co and Rh, was discovered by English chemist Smithson Tennant in 1803 as a residue when he was trying to dissolve crude platinum in aqua regia, a mixture of 25% nitric acid (HNO3) and 75% hydrochloric acid
(HCl).1 He named it after the Greek goddess Iris (“rainbow”) because of the variety of colors of iridium compounds. The abundance of iridium in the Earth’s crust is very low, about 0.001 ppm; and is produced as a by-product of nickel or copper production.2 There are two stable isotopes of iridium in nature: iridium-191 (37.3%) and iridium-193
(62.7%). The global demand for Ir in 2007 was 3700 kg, 50% being used for electrical and electrochemical applications and another 20% for catalysis.3
Iridium is the most corrosion-resistant of all metals, even insoluble in mineral acids including aqua regia. Iridium is also the second densest element after osmium.1 It has a very high melting point and is the only metal to maintain good mechanical properties in air at temperature above 1600 ºC–even unattacked by other molten metals or by silicates at high temperatures. Iridium’s great stability can be envisaged from its physical properties, outlined in Table 1.1.1.4 Pure iridium is very brittle and is almost impossible to machine. Its high modulus of elasticity and modulus of rigidity, together with the very low figure for Poisson’s Ratio indicate the high degree of stiffness and resistance to deformation.
Coordination numbers and coordination geometries of organoiridium complexes are illustrated in Table 1.1.2.5–8 Iridium can attain a variety of oxidation state ranging from –
3 to +6; most common of them are Ir+1, Ir+3 and Ir+4. The highest experimentally
2 established stable oxidation state of iridium is +6 and is represented by IrF6 and a few
6− 9 perovskites having the [IrO6] anion. The most common coordination numbers of iridium organometallics are 4 and 6.
Table 1.1.1. Physical and Mechanical Properties of Iridium.
Atomic number 77
Atomic weight 192.217(3)
Electron configuration [Xe]4f145d76s2
Electronegativity 2.2
Melting point/ °C 2443
Boiling point/ °C 4550 (±100)
Density 20 °C/ g cm-3 22.56
-1 ΔHfus/ kJ mol 26.4
-1 ΔHvap/ kJ mol 26.4
Electrical resistivity 0 °C/ µohm cm 4.71
Modulus of elasticity E/ MN m-2 516×103
Modulus of rigidity G/ MN m-2 210×103
Poisson’s ratio 0.26
3 Table 1.1.2. Oxidation States and Geometries of Organoiridium Compounds.
Oxidation State Example Geometry
–1 H[Ir(CO)4] tetrahedral
0 Ir(CO)4 tetrahedral
I CO square planer10 Ir I CO +1 PPh3 OC Ir CO trigonal bipyramidal OC PPh3
F F CN 6 +2 F CO pseudo-octahedral Ir F Ir F OC F F NC F
N +3 octahedral11 Ir N N
5 +4 Ir N pseudo-octahedral Cl N
4 +5 pseudo-octahedral7 Ir H H H H
Organometallic complexes as phosphorescent emitters in OLEDs: The term organic light-emitting device (OLED) refers to any light-emitting diode that is composed of either molecular or polymeric materials. Flat-panel displays that use OLEDs may one day replace liquid-crystal displays (LCDs) in mobile applications.12 OLEDs are composed of layers of carrier transporting and emitting regions, sandwiched between the electrodes.
Electrical charge produces hole and electrons, which are odd electron species and thus have a spin of +1/2 or −1/2. These carriers recombine, leading to formation of an electron-hole pair (exciton), which radiatively decays. The excitons formed by recombination of two odd-electron species are either spin-singlets or spin-triplets.
Exciton formation
Figure 1.1.1. Energy transfer mechanisms in the sensitized system.
Simple spin statistics predicts that the ratio of singlet to triplet excitons formed in this
5 process is 1:3 which limits efficiency, since triplet excitons in molecular or polymeric materials are typically non-emissive. Heavy metal containing phosphors harvest both singlet and triplet excitons, leading to high electroluminescence efficiencies.13,14
Phosphorescent transition-metal based OLEDs (also known as PhOLEDs) can improve electroluminescence (EL) quantum efficiencies compared to conventional fluorescent OLEDs.15 For phosphorescent complexes, relaxed spin selection rules allow intersystem crossing. Both singlet and triplet excitons contribute to radiative decay and
100% internal quantum efficiency can be achieved.16 This process is termed triplet harvesting (Figure 1.1.1). Iridium(III) complexes are most promising dopant used
OLEDs because of their efficient luminescence, microsecond excited-state lifetimes, and color tunability over the entire visible spectrum.17 The first example of a phosphorescent dopant with a comparatively short radiative lifetime and high luminance efficiency used
2′ in OLEDs was facial-tris(2-phenylpyridinato,N,C )iridium(III), fac-Ir(ppy)3, Figure
1.1.2.
N N Ir
N
2′ Figure 1.1.2. Structure of facial-tris(2-phenylpyridinato,N,C )iridium(III), fac-Ir(ppy)3.
18 This compound, first reported in 1985 , has a green emission (λmax = 520 nm) and a short radiative lifetime (τrad = 5 µs) in fluid solution at room temperature. The radiative decay rate is nearly two orders of magnitude larger and the PL efficiency is similar to
6 those of platinum octaethylporphyrin (PtOEP).19 The first OLEDs that incorporated fac-
Ir(ppy)3 dopant at an optimal doping level of 6% gave external efficiencies close to 9%
(internal efficiency > 40%).20
1.2. The Chemistry of Gold
Gold has the atomic number Z = 79. It has the electronic ground state configuration of
[Xe][4f14][5d10][6s1]; gold(I) has a closed-shell configuration [5d10], Figure 1.2.1.
Gold(I) dominates the chemistry of gold organometallics, as in the case of copper(I)
[3d10] and silver(I) [4d10]. However, the first ionization potential of the isolated gold atom (9.225 eV) in the gas phase is much higher compared to that of silver (7.576 eV) and generally the Au0–Au+1 oxidation potential of gold metal are unusually high which makes gold a non-corrosive, noble metal, while copper and silver will tarnish very quickly. Interestingly, powerful oxidants, such as aqua regia, chlorine, and bromine can dissolve gold and generate gold(III), not gold(II). These high oxidation states are unusually difficult to access for the other two coinage metals, copper and silver. Table
1.2.1 summarizes few physical properties of gold.
s2 s2 s1 d7 d8 d10
Fe CO Ni Cu Zn
Ru Rh Pd Ag Cd
Os Ir Pt Au Hg
Figure 1.2.1. Position of gold in periodic table of elements.
7 Gold is reducible to negative oxidation states in the absence of π-accepting ligands.
Noting that gold must have a very high electron affinity (2.039 eV for Au, 1.202 eV for
Ag), Zintl, Biltz and later Sommer have reacted elemental cesium with gold to obtain
Cs+Au−, where cesium forms a stable salt of auride anion.21–23
Table 1.2.1. Physical Properties of Gold4
Atomic number 79
Atomic weight 196.96655(2)
Electron configuration [Xe]4f145d106s1
Electronegativity 2.4
Melting point/ °C 1064
Boiling point/ °C 2808
Density 20 °C/ g cm-3 19.32
-1 ΔHfus/ kJ mol 12.8
-1 ΔHvap/ kJ mol 343(±11)
Electrical resistivity 0 °C/ µohm cm 2.35
Ionization Energy/ kJ mol-1 1st 889.9
2nd 1973.3
3rd (2895)
The organometallic chemistry of gold(I) complexes are the most intensely studied.
Coordinate complexes such as [L–Au–X], [X–Au–X]-/[L–Au–L]+, where L = neutral ligand and X = anioninc ligand, are usual for gold(I) compounds. Stable, linear
8 complexes of gold(I) are obtained when heavier donor atoms such as P, As and S are present.24 Trigonal planar coordination is found in phosphine (L) complexes of the
[AuL2X] type; but 4-coordinated gold(I) is rare. These compounds are usually strongly distorted, with the last incoming ligands residing at a longer distances from the metal center.25 The paucity of tri- and tetra-coordinated gold(I) stems from the fact that two- and three- coordinated gold(I) substrates are Meager Lewis acids. Comparatively, most copper(I) compounds are tetra- or tri-coordinated, and linear two coordinate Cu(I) complexes are relatively rare. The most prevalent coordination number for silver(I) is 4, along with 2 and 3 being abundant.26
Au(III) with a 5d8 electron configuration is often compared with the isoelectronic
8 – Pt(II) (5d ). Gold(III) complexes of [AuX4] type are square-planar. Very few mononuclear gold(II) compounds are known. Generally, Au(II) oxidation state is observed in a dinuclear and diamagnetic species where gold atoms are bonded in a
4+ 27,28 6 [Au2] unit. Au(V) complexes with a 5d electron configuration, are analogous to
Pt4+ (5d6) and Fe3+ (3d6). They tend to bind ligands in an octahedral fashion. Complexes of Au(V) are rare and only formed with fluorides of type AuF5 and [AuF6]–.29 Shown in
Chart 1.2.1 are the coordination patterns of different gold centers.
L–Au–L X L L X X L–Au–X X Au Au X Au Au L L X X X X–Au–X
Au(I) Au(II) Au(III) Au(V)
Chart 1.2.1. Coordination pattern of various gold centers at different oxidation states.
9 The unusual properties of gold arise from the combination of “lanthanide contraction” and the “relativistic effects”. The ionic radii of the elements in the lanthanide series from atomic number 58, cerium to 71, lutetium are smaller than otherwise expected ionic radii for the subsequent elements starting with 72, hafnium. This phenomenon is now as lanthanide contraction. The lanthanide contraction partially explains the relatively small radius of the gold atom, but it cannot explain why the element gold has the maximum redox potential and electron affinity relative to the other elements with atomic numbers Z
= 72–83.
From the special theory of relativity,30,31 when the velocity of a mass approaches speed of light (c), its relative mass increases, which can be expressed mathematically as
2 m = m0√{1-(v/c) } where m is the corrected mass, m0 is non-relativistic mass. For a given atom, the average radial velocity of the s electron is Vr = Z, with Z being the atomic number. Light speed c equals 137 a.u. (atomic unit). The Bohr’s radius of an electron is inversely proportional to its mass. As a result, the relativistic radius of 6s electron r =
2 r0√{1-(v/c) }. In Au, Z = 79 and v/c for the 6s electrons is 79/137 = 0.58. As a result, r =
0.81r0. The calculated relativistic contraction of the 6s orbital reaches a maximum at Au.
This effect applies to both s and p orbitals. This explains the high ionization energy of the
6s electron of Au. The relativistic s-orbital contraction and d-orbital expansion are very obvious when taking the relativistic effects into account.32,33 This explains why gold(I) is much smaller than silver(I). Actually, the gold(I) radius falls between copper and silver.34,35
In absence of effective steric hindrance from the neighboring ligands, Au(I) centers can approach each other to form metalophillic bonds with energy close to hydrogen
10 bonding, 7–11 kcal/mol.36,37 Often times this bond is sufficiently strong to persist in solution and play a role in guiding chemical reactions.38 The Au–Au distances are typically 2.8–3.3 Å that is well below the calculated sum of the van der Waals radii (ca.
3.6 Å). This interaction is termed as “aurophilic interaction”. This interaction is prevalent even in cationic and anionic complexes of gold where Coulombic factors would be expected to cause significant repulsion.39
S Au S NR R2N 2.8 Å 2 S Au S
Figure 1.2.2. Aurophilic interaction in dithiocarbamate complexes of gold(I).
As depicted in Figure 1.2.2, complexes with dithiocarbamates involve linear S–Au–S coordination but are dimeric and the Au–Au distance of 2.8 Å compared with 2.9 Å in the metal and 2.5 Å in gaseous Au2 is indicative of metal-metal bonding. The aurophilic interaction can also lead to the formation of trimers, tetramers, one-dimensional chains or even two-dimensional layers and three-dimensional networks. These supermolecular networks build up with monomers associated simply by Au–Au contacts. Many gold(I) complexes with aurophilic interaction exhibit strong luminescence. It is proposed that the aurophilic interaction stabilizes the excited states. The change of the environment,40 such as concentrations, solvents, different counter-ions, the incorporation of solvate molecules41 and even grinding42 in the solid state, which can modify the aurophilic interactions also induces different luminescence patterns. Intramolecular aurophilicity has
11 also been reported. These complexes can be tetrahedral,43 square-pyramidal,44 trigonal- bipyramidal,44 and octahedral.45 It has been shown that attractive aurophilic interactions are caused by a combination of correlation effects and relativistic effects.46
The unique properties of gold have initiated great research interest ranging from nanomaterials47–49 to catalysis50–52 and from cancer treatment53,54 to energy recovery.55,56
The two most common stable oxidation states of gold, Au(I) and Au(III), can be exploited for oxidation addition/reductive elimination cycle. Recently, Nocera and coworkers reported the halogen photoreductive elimination from gold(III) centers.55
LMCT excitation of solutions of monomeric complexes of the type Au(III)(PR3)X3 and
I,III III,III bimetallic complexes of the type Au2 [µ-CH2(R2P)2]X4 and Au2 [µ-CH2(R2P)2]X6 (R
= Ph, Cy; X = Cl–, Br–) led to Au(III)–X bond activation. Unprecedented two-electron photoelimination of X2 from a monomeric Au(III) center and four-electron photoelimination of X2 from a bimetallic center were observed. The quantum yields of X2 photoproduction are between 10% and 20%.
1.3. Transmetalation Synthesis of Cyclometalated Iridium(III) Complexes
Since the early discovery in 1960s,57,58 cyclometalation has become a convenient method to generate organometallic compounds featuring a metal–carbon σ bond.59,60 A typical reaction consists of two consecutive steps: heteroatom(E)-assisted chelation to metal center and a subsequent intramolecular activation of the C–R bond, where –R group is often a hydrogen (Scheme 1.3.1). Precoordination of the heteroatom is considered pivotal as it alters the electron density at the metal center and arrange C–R and metal center in proximity reducing the entropic and enthalpic costs of the subsequent
12 bond-activation step. As a result cyclometalated complexes form. The chelating group in the product imparts extra stability that supports an otherwise unstable M–C σ-bond.
E E
MXnLm MXn-1Lm-1 – L, – RX C–R C
C = Calkyl/aryl/alkenyl E = N, O, P, S, As, Se, C R = H, C, N, O, Si, P
Scheme 1.3.1. Cyclometalation via C–R bond activation.
Cyclometalated complexes of transition metal complexes are legion. Late second and third-row d-block elements (Ru, Os, Rh, Ir, Pd, and Pt) have received the most attention.
A significant amount of literature has been appeared on specific metals,61–65 on specific ligands66–70 and on mechanistic aspects70–72 of cyclometalation. Other than their fundamental interest, cyclometalation synthesis of organometallic entities has still remained highly attractive as they have been successfully applied in the catalytic activation of C-H bonds in unreactive alkanes,73–75 stabilization of reactive intermediates,76,77 active units in sensors,78,79 bioorganometallic applications,80,81 as optoelectronic materials,82–85 as gelators86 and in liquid crystalline materials,87,88 and as molecular89 or crystalline switches.90
Cyclometalation by direct C–H activation often requires harsh reaction conditions involving high temperature and longer reaction time. Alternatively cyclometalating complexes may be generated by oxidative addition of C–X (X = F, Cl, Br, I or OTf) bond91 and transmetalation, involving a C–Mʹ (Mʹ = Li, Mg, Sn, B, Ag, Au, Zn, Hg etc.)
13 bond activation.92,93 Other approaches often used for synthesizing metallacycles are elimination reactions,94 cycloaddition95 and by hydrometalation reaction.96
Transmetalation is described as “…the transfer of σ-bonded alyl, aryl, and alkynyl ligands and π-allyl ligands from one metal to another,…”.97 A variety of transmetalating reagents have been developed based on organolithium,98–101 organomagnesium (Grignard reagents),102–104 and organostannanes.105–109 However, the moisture sensitivity and the reactivity of organolithium and Grignard reagents limits functional group tolerance. The toxicity associated with organostannanes limits their uses in transmetalation.
Organoboron compounds110,111 are the reagents of choice for transmetalation in the syntheses of organometallic compounds of the d-block metals. Organoboronic acids are marginally toxic and can be handled in air. The seminal work112,113 by Suzuki on carbon- carbon bond forming reactions, which is now known as Suzuki–Miyaura cross-coupling reaction, has revolutionized chemical synthesis. Transmetalation is a major step of
Suzuki-Miyaura cross-coupling reaction where a aryl group is transferred from a boronic acid or a tetra-coordinated boronate species to palladium which subsequently undergoes reductive elimination. Inspired by that a considerable effort has been devoted to extend the transmetalation strategy from organoborons to mid to late d-block metals.
Stoichiometric and catalytic transmetalations are an efficient synthetic tool to attain organometallics with sensitive functional groups.114–116
Recently, Stahl and co-workers have disclosed a method of methoxylation of aryl boronic acids where transmetalation occurs from boronate anions to Cu(II).117 Swager and co-workers118 have explained aryl transfer from a Cu(I) to cyclometalated Ir(III). Le
Duc and co-workers 119 and Hartwig’s group 120 have independently shown that
14 palladium hydroxide complexes react with boronic acids in transmetalation step prior to cross coupling.
1.4. 2-Deoxy-Ribose Sugar Complex of Cyclometalated Iridium(III): Probe for
Nucleosides Transporter
Heavy-metal complexes, with d6 electronic structures including Re(I), Ru(II), Os(II),
Ir(III) and Rh(III) complexes; with d8 electronic structures including Pt(II) complexes; with d10 electronic structures including Au(I) and Cu(I) complexes are prominent phosphorescent materials that emits at room temperature.121,122 Unlike organic luminophores123 and luminescent lanthanide complexes,124,125 the excited state properties of heavy-metal complexes having d6,d8 and d10 electronic structures are not trivial. The possible excited states of heavy-metal complexes include metal-to-ligand charge-transfer
(MLCT), intraligand charge-transfer (ILCT), ligand-to-ligand charge-transfer (LLCT), metal-centered (MC) excited states, metal–metal-to-ligand charge-transfer (MMLCT), ligand-to-metal–metal charge-transfer (LMMCT) and metal-to-ligand-ligand charge- transfer (MLLCT) states. Among these, MLCT, ILCT and LLCT are the most commonly observed excited states. The rich excited state properties of heavy-metal complexes have attracted increasing interest because of their wide applicability in various fields such as organic light-emitting diodes, electrochemiluminescence, photovoltaics, chemical sensors and bioimaging probes.14,126,127
General requirements of luminescent probes for bioimaging: A successful bioimaging agent requires several property including excitation and emission wavelength, brightness and photostability.128 For cell imaging, excitation with blue or green light is
15 usually satisfactory. However, for whole-body small-animal imaging, the optimal excitation wavelength of a fluorophore should be in the deep red or near-infrared range
(650–950 nm).
The better the fluorescent brightness, the less excitation intensity that is needed and the more depth penetration that is expected. High photostability of a fluorophore is expected for long term observation.128 To date, several kinds of fluorescent materials, such as green fluorescent proteins,129 organic fluorophores,128 semiconductor quantum dots,130 upconversion nanophosphors,131,132 or emissive metal complexes, have been successfully applied as bioimaging probes.
Advantages of luminescent heavy-metal complexes as bioimaging probes: Even though small-molecular materials are still major component for bioimaging, phosphorescent heavy-metal complexes show some advantageous photophysical properties. Firstly, they exhibit high luminescence efficiency;133 secondly, the tunable excitation and emission wavelength over the whole visible (even near-infrared) range can be realized easily;134–136 thirdly, phosphorescent heavy-metal complexes exhibit significant Stokes shifts (often >5000 cm–1) that allows easy distinction between emission over excitation and elimination of self-quenching processes. Finally, relatively long lifetimes (in few microseconds, much greater than those of purely organic lumophores) can be observed.137 In particular, such long lifetime of the heavy-metal complexes can be utilized for eliminating autofluorescence from biological samples by time-resolved fluorescent imaging.127
Nucleosides play diverse roles in cell physiology by acting as the metabolic precursors of many fundamental biological molecules including ATP, DNA and RNA; as
16 signaling molecules and neuromodulators that contribute to the regulation of a broad range of cellular events.138 Since nucleosides are hydrophilic molecules and their passive diffusion across biological membranes is limited, passage of nucleosides across plasma membranes or between intracellular compartments occurs primarily via specialized nucleoside transporter (NT) proteins. Two major families, the equilibrative NTs (ENTs) and the concentrative NTs (CNTs), have been identified.139,140 Nucleoside transporters
(NTs) are important determinants for salvage of preformed nucleosides and mediated uptake of antimetabolite nucleoside drugs into target cells.
Extracellular
Nuc Na+ Nuc
CNT ENT
Nuc Na+ Nuc
Cytoplasm
Figure 1.4.1. Nucleoside transport processes in mammalian cells.
The ENTs move nucleosides along a concentration gradient, into or out of the cell.
CNTsζ ferry nucleosides inwards, against the gradient. For most CNTs, nucleoside transport is coupled to Na+ transport, and these proteins are sodium–nucleoside symporters. Another isoform, designated CNT3, utilizes Na+ and/or H+ to facilitate nucleoside transport. A rough sketch of nucleoside transport appears in Figure 1.4.1. For
17 equilibrative systems (ENT, on right), the direction of nucleoside (Nuc) transport is dependent solely upon the direction of the nucleoside concentration gradient across the membrane. On the other hand in concentrative systems (CNT, on left), nucleosides can be transported into the cell against their concentration gradients using energy derived from the Na+ gradient that exists across the plasma membrane.
Many chemotherapeutic drugs are nucleoside analogues,141,142 and their effectiveness depends on nucleoside transporters for cellular uptake. Mechanistic understanding of these glycoproteins is sparse, mainly because of limited structural information on such dynamic biomolecules. To date, there is a single report of a crystal structure of a CNT from the bacterium Vibrio cholerae.143
1.5. Transition Metal Fluorine Chemistry
The coordination chemistry of inorganic Lewis acids with neutral ligands developed over the last century is dominated by complexes of chlorides, bromides or iodides.144 In contrast, corresponding metal fluoride complexes were neglected for many years. Even among the few reports seen, the characterization was often poor and the properties were not investigated in any detail.145,146 Metal fluoride compounds often exhibit novel structures and reactivity146–148 as indicated by their involvement in C-F bond formation149,150 and cleavage,151 and their role as catalysts for stereo selective and asymmetric transformations.152
Fluorine is the most electronegative element and the electronegativities of the halogens increases as on going up the group, hence and the ability to form σ bonds increases down the group (Figure 1.5.1). In this context, in the absence of other
18 interactions between the halide and the metal, iodide would be expected to form the strongest bond and donate the most electron density to the metal by these σ interactions.
X M X M X Electronegativity
F 3.98
Cl 3.16
Br 2.96 σ donation trend donation trend I 2.66 π F < Cl < Br < I F > Cl > Br > I
X = halide, M = metal
Figure 1.5.1. Electronic properties of halide ligands.
But in reality, this is rarely the case because π interactions commonly occur between the halide lone-pair electrons and the metal d orbitals.153 The trends predicted by electronegativity can be observed when π interactions predominate and fluorine is the strongest π donor.154,155
Fluoride is normally classified as a σ- and π-donor ligand, and its bonds to other elements are usually highly polar. The properties of the M–F bond vary widely depending upon the oxidation state of M and its position on the periodic table. Fluoride is a modest
σ donor ligand towards medium and low oxidation state d-block metals, where as in medium oxidation states of the later d-block elements, the fluoride complexes are often only slightly different to those of the heavier halogens. For higher oxidation state d-block metals, short highly polar bonds are formed by s-and p-donation, the p component due to higher d electron count becoming less important towards the right of the block.156
19 Another feature which distinguishes fluorine as a ligand from the heavier halogens is its ability to form very strong bridges between metal centres of type M–F–M. These single bridges often approach linearity (due to significant π donation), whereas bridging involving the heavier halogens is less strong and often (non-linear) M–(X)2–M in type.
1.6. Gold(I) Based Anticancer Drugs
The antitumor activity of the tetrahedral Au(I) diphosphine complexes with the
+ 157 common form of [Au(dppe)2] was first reported two decades ago. Over the past five years, there have been numerous reports of active gold organometallics that show cytostatic and/or cytotoxic effects against various cancer cell lines.158–162 Many of these compounds are nonselective due to the soft Lewis acid nature of Au(I), that can bind to cysteine, selenocysteine, and (less so) histidine residues found in biological systems. One relevant example is auranofin, an orally administered anti-arthritic gold drug. Auranofin is a glucopyranose containing a triethylphosphine complex of Au(I) (Figure 1.6.1). It also produces cytostatic and cytotoxic effects against various cancer cells in vitro.54,163–165
Mechanistic studies have shown that auranofin induces apoptosis by inhibiting the mitochondrial enzyme thioredoxin reductase (TrxR),166 which has recently become a new target for drug development.
The activity is considered to be coming from their lipophilic, cationic properties which can lead to their accumulation in mitochondria. Substituting the phosphine ligands with N-heterocyclic carbenes allow for a generation of drugs with tunable dydrophilic/lipophilic properties.160 Square-planar Au(III) complexes, which are isostructural with square planar Pt(II) complexes also investigated for antitumor
20 activities. Expectation was they might form similar DNA adducts as cisplatin.167
However, Au(III) complexes can readily decompose into Au(I) under physiological conditions. Choice of appropriate ligands to stabilize the Au(III) oxidation state is important.168
About 60% of cancer patients undergo radiation therapy.169 The immediate target of therapeutic radiation is the water inside cancerous or healthy tissues; radiation does not select for either. Damage migrates to DNA, and programmed cell death (apoptosis) follows. Radiation treatments are most effective in amply oxygenated tissue. Long- lasting reactive oxygen species (ROS) form on contact with organic or hydroxyl radicals, and degrade DNA. Hypoxic tissues are thus radiation-resistant; they lack the O2 content that propagates radiation damage. Up to 30% of the mass of solid tumors is hypoxic.170
Oxygen-deficient volumes typically have inefficient vasculature; they are relatively inaccessible to blood-borne drugs. Thus, hypoxic cancer cells pose challenges to non- surgical cancer treatments. A feasible response is the design of chemotherapeutic agents that sensitize tumors to radiation damage. This research examines gold-bearing non- natural nucleosides that magnify the killing effect of radiation in hypoxic tumor masses.
Several observations combine to suggest nucleoside analogues as radiosensitizers.
First, some 14 purine and pyrimidine derivatives have FDA approval as chemotherapeutics.171 Second, non-natural nucleosides often retain the cytostatic and cytotoxic properties of the native biomolecules. Once inside the cell, nucleotide analogues can inhibit nucleic acid polymerases and impede transcription and replication.
Third, some non-natural nucleosides are kinase inhibitors that disrupt the cell cycle and induce apoptosis.
21 PPh3 Au S OAc N N AcO O N S N AcO Au O OAc P HO
HO
Auranofin 8a
Figure 1.6.1. Structure of rheumatoid arthritis drug auranofin and proposed radiosensitizer.
Why Gold-Containing Nucleoside Analogues?
Of the heavy transition elements, gold is the most biologically friendly. Gold(I) pro- drugs have a long history in treating rheumatoid arthritis. Auranofin, (Figure 1.6.1), is an orally ingested anti-arthritis pro-drug. The gold atom is the pharmacophore, and the capping phosphine ligand promotes membrane penetrability.172,10 Thus, the
(phosphine)gold(I) functionality and the gold(I)-thiolato sulfur bond are both drug-like.
Gold containing nucleosides will possess many of the same pharmacological properties as other nucleoside analogs. Organogold nucleosides are readily activated by ionizing radiation in low doses.
Figure 1.6.2 depicts a design concept for radiation sensitizers based on gold chemistry. The sensitizer, which augments the toxic effects of radiation, bears a gold- sulfur σ-bond and carries a passivating phosphine cap. Density-functional theory calculations (performed by Dr. Thomas G. Gray) predict that the homolytic dissociation energy of the gold(I)–mercaptopurine sulfur bond is 58 kcal/mol. For comparison, the homolytic dissociation energy of the C–C bond in ethane is 88 kcal mol–1, and that in
HO–H is 119 kcal mol–1.173 The gold-sulfur bond breaks more easily than do the common
22 covalent bonds in biology. Nominally ionizing radiation breaks the gold-sulfur bond to form a nucleotide radical and an odd-electron gold(0) (s1) complex. The damaged nucleic acid will ideally contribute to apoptosis. The gold(0) by-product may then cause further, secondary sensitization. (Phosphine)gold(0) centers may re-oxidize to gold(I), possibly in the oxidative burst associated with inflammation. Such gold(I) cations inhibit the mitochondrial enzyme thioredoxin reductase, and the resulting oxidative stress triggers apoptosis.157
Alternatively, gold(0) centers formed by homolysis may coalesce into gold nanoparticles. Nanogold is a known radiosensitizer; possibly through a photothermal effect.174 The added radiosensitization of gold nanoparticles can drive apoptosis or necrosis.
Figure 1.6.3 arranges six common phosphine ligands according to their Tolman cone angles.20 The phosphine ligand on auranofin is triethylphosphine, one of the smaller phosphines, with a cone angle of 132°. Aurated nucleosides with smaller and larger phosphines will be prepared.
Cone angle increases
CH3 CH3
H3C CH3 H3C H2C CH2 P P P P P P
CH3 CH3 CH2 H3C 110 122 132 145 176 182
Figure 1.6.3. Organophosphines and their cone angles (measure of their steric bulk).
23
Figure 1.6.2. Model for the cytotoxic effects of gold-containing nucleosides (graphics by courtesy of Dr. Gray).
Early experiments will use triethylphosphine as ancillary ligand because of its occurrence in auranofin. The overall sizes of the phosphine ligands vary with the structure of the alkyl or aryl substituents in it (Figure 1.6.3). Phosphines of varying size can be employed, to control the extent to which these phosphine ligands function to protect Au(I) from thiol exchange.
24 1.7. Proposed Research
A. Application of Transmetalation Strategy to Synthesize Cyclometalated Iridium(III)
Complexes
Conventional synthesis of (tris)cyclometalated iridium(III) complexes requires harsh reaction condition such as high boiling solvent such as ethylene glycol and long reaction time, often days. Functional group tolerance is a continuing challenge. Synthesis of cyclometalated iridium(III) complexes have been achieved using base-assisted transmetalation. Bis(aquo)iridium(III) precursors and or pinacolboronate esters are employed for preliminary study. Various supporting bases were screened for efficient synthesis at room temperature. Scheme 1.7.1 depicts the transmetalation strategy employed.
Scheme 1.7.1. Synthesis of (tris)cyclometalated iridium(III) complexes.
The ligands on iridium were varied to generate cyclometalated complexes of various colors. Chart 1.7.1 lists various ligands that will be used to cyclometalate iridium(III).
The new protocol was explored to synthesize iridium(III) complexes of aldehydes and alcohols, both bound through carbon and oxygen. Sensitive functional groups were tested with varied conditions. For homoleptic complexes, the kinetic mer-isomers result. The more stable fac complexes are readily made from these.
25
Chart 1.7.1. Cyclometalating ligands on iridium(III) with their nomenclature.
New complexes of iridium(III) cyclometalates were fully characterized by NMR (1H,
19F, and 13C{1H} when ever necessary), UV-vis, IR, fluorescence spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography whenever applicable. The binding of ketonyl, aldehyde and alcohol complex were given special attention due to sensitivity of those group in basic reaction conditions employed here.
B. Suzuki–Miyaura Coupling of Arylboronic Acids to Gold(III)
Gold(III) is prominent in catalysis and materials, but its organometallic chemistry continues to be restricted by synthesis. Metal-carbon bond formation often relies on organometallic complexes of electropositive elements, including lithium and magnesium.
The redox potential of gold(III) interferes with reactions of these classic reagents. Resort to toxic metals is common, including reagents based on mercury and thallium. We have reported that the palladium-catalyzed Suzuki-Miyaura coupling of arylboronic acids
26 extends to cyclometalated gold(III) chlorides. Scheme 1.7.2 describes a representative reaction condition for Au(III)–Cl arylation reaction.
Scheme 1.7.2. Reaction scheme for Suzuki–Miyaura coupling of arylboronic acids extends gold(III) chlorides.
Both monoarylated and di-arylated products were synthesized. Based on the geometry of the monoarylated products isolated it will be decided whether monoarylation occurs trans to pyridyl nitrogen or trans to carbon. A library of Pd-cataysts was screened along with varied base and solvents.
C. Cyclometalated Iridium(III) Complexes with Deoxyribose Substituents
Fundamental study of enzymatic nucleoside transport suffers for lack of optical probes that can be tracked noninvasively. Nucleoside transporters are integral membrane glycoproteins that mediate the salvage of nucleosides and their passage across cell membranes. The substrate recognition site for nucleoside transporter is the deoxyribose sugar, often with little distinction among nucleobases. We report here emissive nucleoside analogues where, cyclometalated iridium(III) complexes are “clicked” to C-1 of deoxyribose in place of canonical nucleobases.
27 N
N HO N + N N N O N N Cl HO Ir Ir Ir Cl N NH PF N N 4 6 N N N O Solvent OH
OH
Scheme 1.7.3. Synthesis of typical nucleoside.
Scheme 1.7.3 shows a typical synthesis of metallonucleoside. The synthesis of sugar
N^N chelate begins from commercially available 2-deoxy-D-ribose sugar. The pyridyl triazole moiety in the sugar starting material is assembled by a Cu-catalysed click chemistry with azide and alkyne. Warming up the reaction mixture may be necessary for the final chelation reaction with chloro-bridged dimer. New emissive iridium(III) nucleosides were characterized by NMR (1H, 19F, and 13C{1H} when ever necessary),
UV-vis, fluorescence spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography whenever applicable.
D. Synthesis of Bridging and Terminal Cyclometalated Complexes of Iridium(III)
Many electroluminescent devices rely on cyclometalated iridium(III). Surprisingly, fluoride complexes of cyclometalated Ir(III) are unreported. Syntheses of bridged and terminal fluorides were sought here. New compounds are expected to be luminescent and thermally reactive; they are characterized by ground-state and optical methods.
28 S S S S
N N N N Cl F AgF / solvent Ir Ir Ir Ir Cl F N N N N
S S S S
S S H S N N N N N (2.5 eq.) F F H Ir Ir Ir N N F solvent N N N
S S S
Scheme 1.7.4. Proposed reaction for synthesizing fluorobridged and terminal fluoro complex of bis(cyclometalated) Ir(III) complexes.
Shown in Scheme 1.7.4 is a typical synthesis of fluoro dimer [(bt)2Ir(µ-F)]2, (bt = 2- phenylbenzo[d]thiazolyl and its terminal fluoro analogue. Crystal structures were determined for bridging and one terminal fluoride complexes.
Attempt to synthesize terminal fluoro complex from (µ-F)2 dimers will be performed with triethylphosphine, tricyclohexylphosphine, pyridine, 3,5-difluoropyridine, acetonitrile, and tetrahydrothiophene. This method will be extended to synthesize complexes with various cyclometalating ligand around iridium. The terminal fluoride complex was sought using ligands having the ability to stabilize fluorine by intramolecular hydrogen bonding. Once achieved terminal fluoride complexes were reacted with carbon-, silicon-, and sulfur-based electrophiles.
Fluorobridged and terminal fluoro complex of bis(cyclometalated) Ir(III) complexes will be characterized by NMR (1H, 19F, and 13C{1H} when necessary), UV-vis,
29 fluorescence spectroscopy, elemental analysis and X-ray crystallography whenever applicable. The compounds herein are expected to be versatile phosphors having the ground-state reactivity of late metal fluorides.
E. A Gold(I) Metallonuceloside as Anticancer Drug
This part proposes development of new anti-cancer agents that enhances the therapeutic utility of low dose ionizing radiation as a treatment modality. Introduction of gold atom into the core purine-nucleoside thereby formation of relatively weak sulfur- gold bond will make it highly susceptible to homolysis by ionizing radiation. The radicals generated by this process are expected to damage nucleic acid and enzyme involved in nucleic acid metabolism to generate cytotoxic affect.
O O O OH MeOH / HCl O Pyridine OMe HCl / AcOH HO HO OMe TolO TolO Cl 92 % p-Toluoyl chloride 69 % HO HO TolO TolO 82 % 3 4 1 2
SH Cl Cl SH N N N N N N N N N N N N O N NH O N O N O NaHS / MeOH MeOH / NH3 TolO TolO TolO HO Cl 74 % 73 % TolO NaH / CH CN HO 3 TolO TolO 7 4 5 6 61 %
L Au SH S
N N N N
N N N N O LAuCl / Cs CO O HO 2 3 HO rt, 4 h HO HO 7
8a, 83 %, L = PPh3, 8b, 77 %, L = PCy3 8c, 75 %, L = 1,3-diisopropylimidazol-2-ylidene
Scheme 1.7.5. Synthesis of gold(I) nucleosides.
Scheme 1.7.5 depicts a synthetic strategy to achieve gold(I)-bearing nucleosides.
Nucleoside analogues have been synthesized using direct attachment of gold to a
30 peripheral sulfur atom present on purine nucleosides. We have varied the composition of ancillary gold ligand to produce different pharmacological effects by influencing which biological target is affected. Nucleoside analogues were characterized by NMR (1H, 31P, and 13C{1H} when ever necessary), UV-vis, fluorescence spectroscopy, elemental analysis and X-ray crystallography whenever applicable.
The triphenylphosphine analogue, shown in Scheme 1.7.5 was chosen for biological study. Cytotoxicity of compound 8a was evaluated against different human cancer cell lines. Annexin/PI dual staining experiments indicate the mechanism of cell death, whether through apoptosis or necrosis. Mitochondrial permeability transition assay and thioredoxin reductase inhibition assay were performed to predict if mitochondrial TrxR is a possible biological target as it is for most of the gold based drugs. All together the above findings indicate attachment of Au(I) to the nucleoside analog is a suitable strategy to obtain bioactive compound.
1.8. References
(1) Hunt, L. B. Platin. Met. Rev. 1987, 31, 32–41.
(2) Xiao, Z.; Laplante, A. R. Miner. Eng. 2004, 17, 961–979.
(3) Jollie, D. Platinum 2008; Johnson Matthey: Hertfordshire, U.K., 2008; pp. 42–43.
(4) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements (2nd ed.); Oxford: Butterworth–Heinemann, 1997; pp. 1113–1143.
(5) Brewster, T. P.; Blakemore, J. D.; Schley, N. D.; Incarvito, C. D.; Hazari, N.; Brudvig, G. W.; Crabtree, R. H. Organometallics 2011, 30, 965–973.
(6) Mak, K. H. G.; Chan, P. K.; Fan, W. Y.; Ganguly, R.; Leong, W. K. Organometallics 2013, 32, 1053–1059.
31 (7) Gilbert, T. M.; Bergman, R. G. Organometallics 1983, 2, 1458–1460.
(8) Iridium Catalysis (Topics in Organometallic Chemistry) Vol. 34; Andersson, P. G., Ed.; Springer-Verlag: Berlin, 2011.
(9) Riedel, S.; Kaupp, M. Coord. Chem. Rev. 2009, 253, 606–624.
(10) Sunley, G. J.; Watson, D. J. Catal. Today 2000, 58, 293–307.
(11) Sajoto, T.; Djurovich, P. I.; Tamayo, A. B.; Oxgaard, J.; Goddard, W. A.; Thompson, M. E. J. Am. Chem. Soc. 2009, 131, 9813–9822.
(12) Highly Efficient OLEDs with Phosphorescent Materials; Yersin, H., Ed.; Weinheim, Germany, 2008.
(13) Yersin, H., E. Highly Efficient OLEDs with Phosphorescent Materials; Wiley- VCH: Berlin, 2008.
(14) Lamansky, S.; Djurovich, P.; Murphy, D.; Abdel-Razzaq, F.; Lee, H.-E.; Adachi, C.; Burrows, P. E.; Forrest, S. R.; Thompson, M. E. J. Am. Chem. Soc. 2001, 123, 4304–4312.
(15) L. Xiao, Z. Chen, B. Qu, J. Luo, S. Kong, Q. Gong, J. K. Adv. Mater. 2011, 23, 926–952.
(16) Y. Kawamura, K. Goushi, J. Brooks, J.J. Brown, H. Sasabe, C. A. Appl. Phys. Lett. 2005, 86, 071104–1–071104–3.
(17) M.A. Baldo, M.E. Thompson, S. R. F. Nature 2000, 403, 750–753.
(18) Sprouse, S.; King, K. A.; Spellane, P. J.; Watts, R. J. J. Am. Chem. Soc. 1984, 106, 6647–6653.
(19) Baldo, M. A.; Forrest, S. R. 1998, 395, 151–154.
(20) Baldo, M. A.; Lamansky, S.; Burrows, P. E.; Thompson, M. E.; Forrest, S. R. Appl. Phys. Lett. 1999, 75, 4 – 6.
(21) Sommer, A. Nature 1943, 152, 215.
(22) Zintl, E.; Goubeau, J.; Dullenkopf, W. Z. Phys. Chem. A 1931, 154, 1.
(23) Biltz, W.; Weibke, F. Z. Anorg. Allg. Chem. 1938, 236, 12.
(24) Braunstein, P.; Muller, A.; Bogge, H. Inorg. Chem. 1986, 25, 2104–2106.
32 (25) Schwerdtfeger, P.; Hermann, H. L.; Schmidbaur, H. Inorg. Chem. 2003, 42, 1334– 1342.
(26) Carvajal, M. A.; Novoa, J. J.; Alvarez, S. J. Am. Chem. Soc. 2004, 126, 1465– 1477.
(27) Comprehensive Organometallic Chemistry II; Grohmann, A.; Schmidbaur, H.; W., A. E.; Stone, F. G. A.; Wilkinson, G., Eds.; Pergamon: New York, 1995.
(28) Van Zyl, W. E.; López-de-Luzuriaga, J. M.; Mohamed, A. A.; Staples, R. J.; Fackler, J. P. Inorg. Chem. 2002, 41, 4579–4589.
(29) Bartlett, N. 1998, 31, 22–25.
(30) McKelvey, D. R. J. Chem. Educ. 1983, 60, 112.
(31) Pitzer, K. S. Acc. Chem. Res. 1979, 12, 271–276.
(32) Hess, B. A. Relativistic Effects in Heavy-Element Chemistry and Physics; Wiley: Chichester, 2003.
(33) Pyykkö, P.; Desclaux, J. P. Acc. Chem. Res. 1979, 12, 276–281.
(34) Bayler, A.; Bowmaker, G. A.; Schmidbaur, H. Inorg. Chem. 1996, 35, 5959–5960.
(35) Tripathi, U. M.; Bauer, A.; Schmidbaur, H. J. Chem. Soc., Dalt. Trans. 1997, 2865 – 2868.
(36) Tzeng, B.-C.; Schier, A.; Schmidbaur, H. Inorg. Chem. 1999, 38, 3978–3984.
(37) Schneider, W.; Bauer, A.; Schmidbaur, H. Organometallics 1996, 15, 5445–5446.
(38) Balch, A. L.; Fung, E. Y.; Olmstead, M. M. J. Am. Chem. Soc. 1990, 112, 5181– 5186.
(39) Balch, A. L. Struct. Bond. 2007, 123, 1–40.
(40) Balch, A. L.; Fung, E. Y.; Olmstead, M. M. J. Am. Chem. Soc. 1990, 112, 5181– 5186.
(41) Rios, D.; Olmstead, M. M.; Balch, A. L. Inorg. Chem. 2009, 48, 5279–5287.
(42) Ito, H.; Saito, T.; Oshima, N.; Kitamura, N.; Ishizaka, S.; Hinatsu, Y.; Wakeshima, M.; Kato, M.; Tsuge, K.; Sawamura, M. J. Am. Chem. Soc. 2008, 130, 10044– 10045.
33 (43) Zeller, M.; Beruda, H. A., K.; Bissinger, P.; Riede, J.; Schmidbaur, H. Nature 1991, 352, 141–143.
(44) Technischen, A. I. Der; Miinchen, U. 1995, 14, 1080–1082.
(45) Scherbaum, F.; Grohmann, A.; Huber, B.; Krüger, C.; Schmidbaur, H. Angew. Chemie Int. Ed. English 1988, 27, 1544–1546.
(46) Pyykkö, P. Angew. Chem. Int. Ed. Engl. 2004, 43, 4412–4456.
(47) Daniel, M.-C.; Astruc, D. Chem. Rev. 2004, 104, 293–346.
(48) Grzelczak, M.; Perez-Juste, J.; Mulvaney, P.; Liz-Marzan, L. M. Chem. Soc. Rev. 2008, 37, 1783–1791.
(49) Cheng, Y.; Meyers, J. D.; Broome, A.-M.; Kenney, M. E.; Basilion, J. P.; Burda, C. J. Am. Chem. Soc. 2011, 133, 2583–2591.
(50) Hashmi, A. S. K. Angew. Chemie Int. Ed. 2008, 47, 6754–6756.
(51) Duan, H.; Sengupta, S.; Petersen, J. L.; Akhmedov, N. G.; Shi, X. J. Am. Chem. Soc. 2009, 131, 12100–12102.
(52) Hashmi, A. S. K.; Rudolph, M.; Siehl, H.-U.; Tanaka, M.; Bats, J. W.; Frey, W. Chem. – A Eur. J. 2008, 14, 3703–3708.
(53) Barnard, P. J.; Berners-Price, S. J. Coord. Chem. Rev. 2007, 251, 1889–1902.
(54) Cox, A. G.; Brown, K. K.; Arner, E. S. J.; Hampton, M. B. Biochem. Pharmacol. 2008, 76, 1097–1109.
(55) Teets, T. S.; Nocera, D. G. J. Am. Chem. Soc. 2009, 131, 7411–7420.
(56) Esswein, A. J.; Nocera, D. G. Chem. Rev. 2007, 107, 4022–4047.
(57) Omae, I. Organometallic Intramolecular Coordination Compounds; Elsevier: The Netherlands, Amsterdam, 1986.
(58) Cope, A. C.; Siekman, R. W. J. Am. Chem. Soc. 1965, 87, 3272–3273.
(59) Trofimenko, S. Inorg. Chem. 1973, 12, 1215–1221.
(60) The definition as applied here excludes reactions leading to complexes with chelating π-bound carbon ligands, as in (heteroatom-)function- alized Cp or arene complexes.
34 (61) Djukic, J.-P.; Sortais, J.-B.; Barloy, L.; Pfeffer, M. Eur. J. Inorg. Chem. 2009, 2009, 817–853.
(62) Djukic, J.-P.; Iali, W.; Hijazi, A.; Ricard, L. J. Organomet. Chem. 2011, 696, 2101–2107.
(63) Dupont, J.; Consorti, C. S.; Spencer, J. Chem. Rev. 2005, 105, 2527–2571.
(64) Rothwell, I. P. Acc. Chem. Res. 1988, 21, 153–159.
(65) Palladacycles; Dupont, J.; Pfeffer, M., Eds.; Wiley-VCH: Weinheim, Germany, 2008.
(66) The Chemistry of Pincer Compounds; Morales-Morales, D.; Jensen, C. M., Eds.; Elsevier: Amsterdam, The Netherlands, 2007.
(67) Rybtchinski, B.; Milstein, D. Angew. Chemie Int. Ed. 1999, 38, 870–883.
(68) Albrecht, M.; van Koten, G. Angew. Chemie Int. Ed. 2001, 40, 3750–3781.
(69) Van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103, 1759–1792.
(70) Omae, I. Coord. Chem. Rev. 2004, 248, 995–1023.
(71) Parshall, G. W. Acc. Chem. Res. 1970, 3, 139–144.
(72) Ryabov, A. D. Chem. Rev. 1990, 90, 403–424.
(73) M. Jensen, C. Chem. Commun. 1999, 2443–2449.
(74) Goldman, A. S.; Goldberg, K. I. ACS Symp. Ser. 885 2004, 1–43.
(75) Goldman, A. S.; Roy, A. H.; Huang, Z.; Ahuja, R.; Schinski, W.; Brookhart, M. Sci. 2006, 312 , 257–261.
(76) Abbenhuis, H. C. L.; Feiken, N.; Haarman, H. F.; Grove, D. M.; Horn, E.; Kooijman, H.; Spek, A. L.; van Koten, G. Angew. Chemie Int. Ed. English 1991, 30, 996–998.
(77) Powers, D. C.; Ritter, T. Nat Chem 2009, 1, 302–309.
(78) Albrecht, M.; van Koten, G. Adv. Mater. 1999, 11, 171–174.
(79) Zhao, Q.; Cao, T.; Li, F.; Li, X.; Jing, H.; Yi, T.; Huang, C. Organometallics 2007, 26, 2077–2081.
35 (80) Severin, K.; Bergs, R.; Beck, W. Angew. Chemie Int. Ed. 1998, 37, 1634–1654.
(81) Ryabov, A. D.; Sukharev, V. S.; Alexandrova, L.; Le Lagadec, R.; Pfeffer, M. Inorg. Chem. 2001, 40, 6529–6532.
(82) Dixon, I. M.; Collin, J.-P.; Sauvage, J.-P.; Flamigni, L.; Encinas, S.; Barigelletti, F. Chem. Soc. Rev. 2000, 29, 385–391.
(83) Thompson, M. E.; Djurovich, P. E.; Barlow, S.; Marder, S. In Comprehensive Organometallic Chemistry III; Mingos, D. M. P.; Crabtree, R. H., Eds.; Elsevier: Amsterdam, The Netherlands, 2007; p. 145.
(84) Williams, J. A. G. Chem. Soc. Rev. 2009, 38, 1783–1801.
(85) Wadman, S. H.; Lutz, M.; Tooke, D. M.; Spek, A. L.; Hartl, F.; Havenith, R. W. A.; van Klink, G. P. M.; van Koten, G. Inorg. Chem. 2009, 48, 1887–1900.
(86) Isozaki, K.; Takaya, H.; Naota, T. Angew. Chemie Int. Ed. 2007, 46, 2855–2857.
(87) Hudson, S. A.; Maitlis, P. M. Chem. Rev. 1993, 93, 861–885.
(88) Bruce, D. W.; Deschenaux, R.; Donnio, B.; Guillon, D. ComprehensiVe Organometallic Chemistry III; Mingos, D. M. P.; Crabtree, R. H., Eds.; Elsevier: Amsterdam, The Netherlands, 2007; p. 217.
(89) Sutter, J.-P.; Grove, D. M.; Beley, M.; Collin, J.-P.; Veldman, N.; Spek, A. L.; Sauvage, J.-P.; van Koten, G. Angew. Chemie Int. Ed. English 1994, 33, 1282– 1285.
(90) Albrecht, M.; Lutz, M.; Spek, A. L.; van Koten, G. Nature 2000, 406, 970–974.
(91) Grove, D. M.; Van Koten, G.; Ubbels, H. J. C.; Zoet, R.; Spek, A. L. Organometallics 1984, 3, 1003–1009.
(92) Longoni, G.; Fantucci, P.; Chini, P.; Canziani, F. J. Organomet. Chem. 1972, 39, 413–425.
(93) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chemie Int. Ed. 2006, 45, 8188–8191.
(94) Poznjak, A. L.; Pawlowski, V. I.; Schkolnikowa, L. M.; Djatlowa, N. M.; Iljuchin, A. B. J. Organomet. Chem. 1986, 314, C59–C62.
(95) Wenzel, A. G.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 16048–16049.
36 (96) Bijpost, E. A.; Zuideveld, M. A.; Meetsma, A.; Teuben, J. H. J. Organomet. Chem. 1998, 551, 159.
(97) Osakada, K. In Fundamentals of Molecular Catalysis; Yamamoto, A.; Kurosawa, H., Eds.; Elsevier: Amsterdam, The Netherlands, 2003; pp. 233–292.
(98) Kastner, M. E.; Coffey, K. F.; Clarke, M. J.; Edmonds, S. E.; Eriks, K. J. Am. Chem. Soc. 1981, 103, 5747–5752.
(99) Seidel, S. W.; Schrock, R. R.; Davis, W. M. Organometallics 1998, 17, 1058– 1068.
(100) Ohki, Y.; Hatanaka, T.; Tatsumi, K. J. Am. Chem. Soc. 2008, 130, 17174–17186.
(101) Scott, J.; Basuli, F.; Fout, A. R.; Huffman, J. C.; Mindiola, D. J. Angew. Chemie Int. Ed. 2008, 47, 8502–8505.
(102) Blicke, S. J. Am. Chem. Soc. 1929, 51, 3481.
(103) Rosset, J. M.; Floriani, C.; Mazzanti, M.; Chiesi-Villa, A.; Guastini, C. Inorg. Chem. 1990, 29, 3991–3996.
(104) Reagents, T. G. Organometallics 2009, 2, 1598–1605.
(105) Uson, R.; Vicente, J.; Cirac, J. A.; Chicote, M. T. J. Organomet. Chem. 1980, 198, 105.
(106) Gilges, H.; Schubert, U. Organometallics 1998, 17, 4760–4761.
(107) Smith, S. E.; Sasaki, J. M.; Bergman, R. G.; Mondloch, J. E.; Finke, R. G. J. Am. Chem. Soc. 2008, 130, 1839–1841.
(108) Yamago, S.; Watanabe, Y.; Iwamoto, T. Angew. Chemie Int. Ed. 2010, 49, 757– 759.
(109) Yasuda, S.; Yorimitsu, H.; Oshima, K. Organometallics 2009, 29, 273–274.
(110) Mikhailov, B. M.; Bubnov, Y. N. Organoboron Compounds in Organic Synthesis; Harwood Academic: Lausanne, Switzerland, 1984.
(111) Hall, D. G. Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine; Wiley-VCH: Weinheim, Germany, 2005.
(112) Miyuara, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979, 866.
(113) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 20, 3437.
37 (114) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169–196.
(115) Christoffers, J.; Koripelly, G.; Rosiak, A.; Rossle, M. Synthesis (Stuttg). 2007, 1279.
(116) In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E. - i., Ed.; John Wiley & Sons: New York, 2002; pp. 973–993.
(117) A. E. King, B. L. Ryland, T. C. B. and S. S. S. Organometallics 2012, 31, 7948– 7957.
(118) Swager, T. M. Inorg. Chem. 2011, 50, 7598–7609.
(119) C. Amatore, A. J. and G. L. D. Chem.–Eur. J. 2011, 17, 2492–2503.
(120) B. P. Carrow and J. F. Hartwig. J. Am. Chem. Soc. 2011, 133, 2116–2119.
(121) Chi, Y.; Chou, P.-T. Chem. Soc. Rev. 2007, 36, 1421–1431.
(122) Chen, Z.; Bian, Z.; Huang, C. Adv. Mater. 2010, 22, 1534–1539.
(123) Haugland, R. P. The Handbook. A Guide to Fluorescent Probes and Labeling Technologies, Molecular Probes; 10th ed.; Eugene: Oregon, 2005.
(124) Eliseeva, S. V; Bunzli, J.-C. G. Chem. Soc. Rev. 2010, 39, 189–227.
(125) Moore, E. G.; Samuel, A. P. S.; Raymond, K. N. Acc. Chem. Res. 2009, 42, 542– 552.
(126) Lo, K. K.-W.; Tsang, K. H.-K.; Sze, K.-S.; Chung, C.-K.; Lee, T. K.-M.; Zhang, K. Y.; Hui, W.-K.; Li, C.-K.; Lau, J. S.-Y.; Ng, D. C.-M.; Zhu, N. Coord. Chem. Rev. 2007, 251, 2292–2310.
(127) Zhao, Q.; Li, F.; Huang, C. Chem. Soc. Rev. 2010, 39, 3007–3030.
(128) Kobayashi, H.; Ogawa, M.; Alford, R.; Choyke, P. L.; Urano, Y. Chem. Rev. 2009, 110, 2620–2640.
(129) Tsien, R. Y. Angew. Chemie Int. Ed. 2009, 48, 5612–5626.
(130) Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan, G.; Wu, A. M.; Gambhir, S. S.; Weiss, S. Sci. 2005, 307 , 538–544.
(131) Xiong, L.-Q.; Chen, Z.-G.; Yu, M.-X.; Li, F.-Y.; Liu, C.; Huang, C.-H. Biomaterials 2009, 30, 5592–5600.
38 (132) Wang, F.; Banerjee, D.; Liu, Y.; Chen, X.; Liu, X. Analyst 2010, 135, 1839–1854.
(133) Tamayo, A. B.; Alleyne, B. D.; Djurovich, P. I.; Lamansky, S.; Tsyba, I.; Ho, N. N.; Bau, R.; Thompson, M. E. J. Am. Chem. Soc. 2003, 125, 7377–7387.
(134) Li, F. Chem. Soc. Rev. 2011, 40, 2508–2524.
(135) Chi, Y.; Chou, P.-T. Chem. Soc. Rev. 2010, 39, 638–655.
(136) You, Y.; Nam, W. Chem. Soc. Rev. 2012, 41, 7061–7084.
(137) Wu, C.-C. Angew. Chem. Int. Ed. Engl. 2008, 47, 4542–4545.
(138) Zhang, J.; Visser, F.; King, K. M.; Baldwin, S. a; Young, J. D.; Cass, C. E. Cancer Metastasis Rev. 2007, 26, 85–110.
(139) Kong, W.; Engel, K.; Wang, J. Curr. Drug Metab. 2004, 5, 63–84.
(140) Vickers, M. F.; Young, J. D.; Baldwin, S. A.; Cass, C. E. Emerg. Ther. Targets 2000, 4, 515–539.
(141) Berdis, A. J. Biochemistry 2008, 47.
(142) Parker, W.B.; Secrist III, J.A.; Waud, W. R. Curr. Opin. Investig. Drugs 2004, 5, 592–596.
(143) Johnson, Z. L.; Cheong, C. G.; Lee, S. Y. . Nature 2012, 483, 489–493.
(144) Advanced Inorganic Chemistry; Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M., Eds.; 6th ed.; Wiley: New York,, 1998.
(145) Doherty, N. M. 1991.
(146) Murphy, E. F.; Murugavel, R.; Roesky, H. W. Chem. Rev. 1997, 97, 3425–3468.
(147) Hascall, T.; Rabinovich, D.; Murphy, V. J.; Beachy, M. D.; Friesner, R. A.; Parkin, G. 1999, 2, 11402–11417.
(148) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160–171.
(149) Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; García-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Sci. 2009, 325 , 1661–1664.
(150) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chemie Int. Ed. 2013, 52, 8214– 8264.
39 (151) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183.
(152) Pagenkopf, B. L.; Carreira, E. M. Chem. – A Eur. J. 1999, 5, 3437–3442.
(153) Caulton, K. G. New J. Chem. 1994, 18, 25.
(154) Procopio, L. J.; Carroll, P. J.; Berry, D. H. J. Am. Chem. Soc. 1994, 116, 177–185.
(155) Lukens, W. W.; Smith, M. R.; Andersen, R. A. J. Am. Chem. Soc. 1996, 118, 1719–1728.
(156) Roesky, H. W. Chem. Rev. 1997, 97, 3425–3468.
(157) Barnard, P. J.; Berners-Price, S. J. Coord. Chem. Rev. 2007, 251, 1889–1902.
(158) Craig, S.; Gao, L.; Lee, I.; Gray, T.; Berdis, A. J. J. Med. Chem. 2012, 55, 2437– 2451.
(159) Sun, R. W.-Y.; Li, C. K.-L.; Ma, D.-L.; Yan, J. J.; Lok, C.-N.; Leung, C.-H.; Zhu, N.; Che, C.-M. Chemistry 2010, 16, 3097–3113.
(160) Berners-Price, S. J.; Filipovska, A. Metallomics 2011, 3, 863–873.
(161) Zhang, X.; Frezza, M.; Milacic, V.; Ronconi, L.; Fan, Y.; Bi, C.; Fregona, D.; Dou, Q. P. J. Cell. Biochem. 2010, 109, 162–172.
(162) Rubbiani, R.; Kitanovic, I.; Alborzinia, H.; Can, S.; Kitanovic, A.; Onambele, L. a; Stefanopoulou, M.; Geldmacher, Y.; Sheldrick, W. S.; Wolber, G.; Prokop, A.; Wölfl, S.; Ott, I. J. Med. Chem. 2010, 53, 8608–8618.
(163) Mohamed, A. a; Chen, J.; Bruce, A. E.; Bruce, M. R. M.; Krause Bauer, J. a; Hill, D. T. Inorg. Chem. 2003, 42, 2203–2205.
(164) Hill, D. T.; Isab, A. a; Griswold, D. E.; DiMartino, M. J.; Matz, E. D.; Figueroa, A. L.; Wawro, J. E.; DeBrosse, C.; Reiff, W. M.; Elder, R. C.; Jones, B.; Webb, J. W.; Shaw, C. F. Inorg. Chem. 2010, 49, 7663–7675.
(165) Marzano, C.; Gandin, V.; Folda, A.; Scutari, G.; Bindoli, A.; Rigobello, M. P. Free Radic. Biol. Med. 2007, 42, 872–881.
(166) Mckeage, M. J.; Maharaj, L.; Berners-price, S. J. Coord. Chem. Rev. 2002, 232, 127–135.
(167) Jamieson, E. R.; Lippard, S. J. 1999.
40 (168) Metal Ions in Biological Systems; Messori, L.; Marcon, G.; Sigel, A.; Sigel, H., Eds.; New York, 2004.
(169) Pecorino, L. Molecular Biology of Cancer; Oxford: New York; pp. 42–43.
(170) Vaupel, P.; Mayer, A. Transfus. Clin. Biol. 2005, 12, 5–10.
(171) Robak, T.; Lech-Maranda, E.; Korycka, A.; Robak, E. Curr. Med. Chem. 2006, 13, 3165–3189.
(172) Larsen, A.; Kolind, K.; Pedersen, D.; Doering, P.; Pedersen, M.; Danscher, G.; Penkowa, M.; Stoltenberg, M. Histochem. Cell Biol. 2008, 130, 681–692.
(173) CRC Handbook of Chemistry and Physics; Lide, D. R., Ed.; 74th ed.; CRC Press: Boca Raton, FL.
(174) Pissuwan, D.; Valenzuela, S. M.; Cortie, M. B. Trends Biotechnol. 2006, 24, 62– 67.
41 Chapter 2 Application of Transmetalation Strategy to Synthesize Cyclometalated Iridium(III) Complexes
42 This work is published: "Room-temperature synthesis of cyclometalated iridium(III) complexes: kinetic isomers and reactive functionalities" Maity, A.; Anderson, B. L.; Deligonul, N; Gray, T. G Chemical Science 2013, 4, 1175–1181. DOI: 10.1039/C2SC21831C
2.1. Introduction
Research on luminescent transition metal complexes draws continuing interest for their versatile applications.1–5 Much effort has been concentrated on 4d6 and 5d6 metal complexes, especially on diimines (i.e. bipyridine and phenanthrolines) of Ru(II) and
Os(II) which are luminescent and photochemically active.6–12 The attraction behind d6 metal complexes is attributed to their high phosphorescence quantum yields and long excited-state lifetimes. Iridium(III) cyclometalates have drawn the most attention in the last 10 years. Since the early work by Watts and Güdel,13–16 interest was focused on developing Ir(III) cyclometalates that possess exceptional thermal stability and high emission quantum yields. When compared to Ru(II) and Os(II) diimine complexes, the
Ir(III) complexes often show longer excited state life times, typically in the order of microseconds and higher luminescence efficiencies [e.g., fac-Ir(ppy)3 (ppy = 2-
17,18 phenylpyridine), Φphos = 0.4] in fluid solutions.
Singlet-triplet intersystem crossing is efficient for complexes of iridium(III), a result
-1 19 of the metal’s spion-orbit coupling (ζIr = 3909 cm ). Low-lying triplet states become populated and phosphorescence emission at room temperature results. Density functional theory (DFT) and time-dependent DFT (TD-DFT) studies indicate the emissive triplet state to be comprised of mainly metal-to-ligand charge-transfer states (3MLCT) and ligand-centered (3LC) states or a mixture of 3MLCT/3LC.20–23 The utility of chelating cyclometalates, such as 2-phenylpyridyl and realated ligands24 is attributed to: (a)
43 aromatic chelating ligands form strong bonding interaction with transitionsmetal by occupying cis-disposed sites. (b) Strong metal-ligand covalent bonding suppresses the population in high lying d-d excited states by increasing the d-d energy gap. Nonradiative d-d quenching is inefficient. (c) Close lying ligand centered π–π∗ electronic transitions allow facile tuning of color over the spectrum by choosing correct ligand. (d) The chemical stability of the aromatic ligands and the substitutional inertness of low-spin octahedral d6 complexes allows chemical modification of the complexes.
Iridium complexes are often employed as a phosphorescent dopant in the active layers of organic light emitting diodes (OLEDs).25–30 OLEDs are poised to replace the widely used liquid crystal displays and plasma display panels.31 Phosphorescent transition-metal based OLEDs (also known as PhOLEDs) are attracting attention since they can improve electroluminescence (EL) quantum efficiencies as compared with conventional fluorescent OLEDs.31 In these devices, exciton formation leads to electron-hole recombination, and to electroluminescence (EL).
According to spin statistics, one fourth of the excitons generated from fluorescent molecules are spin-singlets; the rest are triplets that do not take part in EL. This limits the maximum internal quantum efficiency to 25%. For phosphorescent complexes, relaxed spin selection rules allow intersystem crossing. Both singlet and triplet excitons contribute to radiative decay and 100% internal quantum efficiency can be achieved.32
This process is termed triplet harvesting (Figure 2.1.1). Iridium(III) complexes are most promising dopant used in OLEDs because of their efficient luminescence, microsecond excited-state lifetimes, and color tenability over the entire visible spectrum. 33
44 e h
Electrical excitation
25% 75% S1 T 1 Fluorescence Phosphorescence
S 0
Figure 2.1.1. Energy diagram for the working principle of OLEDs.
Iridium(III) cyclometalates also have been used in light-emitting electrochemical cells (LEECs),34–38 oxygen sensing,39,40 photovoltaics,41 dye-sensitized solar cells,42,43 catalytic applications,44,45 as DNA intercalators46,47 and in biological imaging.48–53 A phosphorescent Ir(III) complex has shown promising results in optical data recording and security protection technology.54
The mechanism and scope of cyclometalation have been well documented.55–58 In a typical cyclometalation reaction a covalent metal–carbon bond is generated by chelation of a heteroatom, generally nitrogen. A five-membered metallacycle results. For example,
2-phenylpyridine (ppy), one of the most common C^N ligand, bind to a variety of second- and third-row transition-metal ions, through activation of the ortho C–H bond of the phenyl ring that is adjacent to the 2-pyridyl fragment.
45 N
N N Cl N N N Ir Ir Ir Cl AgOTf N N Ethyleneglycol N 160-190 oC
Scheme 2.1.1. Conventional synthesis of Ir(III) cyclometalates.
Robust iridium(III) cyclometalates are usually prepared under forcing conditions. The green-emitting fac-[Ir(ppy)3] was first synthesized by refluxing a mixture of Ir(acac)3, acac = acetylacetonate, and excess of ppyH in high boiling glycerol solution for an extended period of time.59 The second method uses chloride-bridged Ir(III) dimers
[(C^N)2Ir(µ-Cl)]2, which are obtained from IrCl3.nH2O and two equiv. of C^N ligand.
The dimers are then reacted with a third ligand in presence of suitable halide abstractor, silver(I), ammonium salts in similar high-boiling solvent (Scheme 2.1.1). Prolonged heating affords mononuclear facial isomers. Homoleptic complexes result if the incoming ligand is same as the ligands present in the dimer. The meridional isomers are occasionally isolated as kinetic products; heating or photolysis under UV light convert them to the more stable facial analogues.60
Homoleptic, meridional isomers are often ignored, despite emissions of that are frequently red-shifted from those of their facial counterparts. These long wavelength emitters are favored as optoelectric materials and as biological tags. Higher efficiency was reported for photovoltaic cells using long wavelength emitters.61,62 Long range emissions are also desirable for mammalian imaging.63 Therefore developing an efficient synthetic protocol that will deliver meridional isomers selectively with high degree of
46 of functional group tolerance is highly desirable.
Bernhard and co-workers64 have disclosed an efficient synthesis of bis(aquo) iridium(III) cyclometalates. We hypothesized that Ir(III) would impart acidity to the bound water ligands, and terminal hydroxide or hydroxo bridged complexes would form easily in a basic solution. Added base can also lead to form quarantined borates. Now in a basic solution either of those—(hydroxo)iridium complexes or boronate anion—may facilitate the aryl transfer to iridium from boron, namely transmetalation (Scheme 2.1.2.).
Stahl and co-workers reported a method of methoxylation of aryl boronic acids where transmetalation occurs from boronate anions to Cu(II).65 Swager and co-workers66 have reported an example of aryl transfer from a ‘click’-intermediate where transfer of aryl group takes place from Cu(I) to cyclometalated Ir(III). Amatore, Jutand, and Le Duc,67
Base Base
increased acidity of Ir(III) bound water ligand
both coluld potentially take part in transmetalation
Scheme 2.1.2. Transmetalation strategy to synthesize Ir(III) cyclometalates. and Carrow and Hartwig68 have independently shown that palladium hydroxide complexes react with boronic acids in the transmetalation step prior to cross coupling.
Chelation from the adjacent pyridyl-nitrogen would impart extra stability to the transmetalated species. These observations are encouraging for the isolation of iridium(III) organometallics by transmetalation from boron.
47 2.2. Results and Discussion
Boronated ligands were chosen so that transmetalation to Ir(III) forms a five- membered chelating ring. The ligands 1-3 were synthesized using lithiation/borylation.
The commercially available ligands 4-6 (Chart 2.1.1) were also tested for
Chart 2.1.1. Ligands and ligand precursors. transmetalation to iridium. Bis(aquo) iridium(III) complexes were prepared in a similar fashion to the synthesis employed by McDaniel et al.64
48 69 Early experiments focused on the reaction of [Ir(ppy)2(H2O)2]OTf with 1 in the presence of the base Cs2CO3 in 2-propanol at 45 °C (Table 2.1.1, entry 1), a similar condition that was previously employed for Au(I)-C bond formation.70 These reaction conditions lead to 30% product conversion after 48 h. In a separate experiment 88% yield was obtained refluxing the reaction mixture at 80 °C for 24 h.
Encouraged by these early experiments we reasoned in protic solvents, base strength
Table 2.1.1. Preliminary screening with variation of supporting base. a
Entry Base (5 eq.) Temperature (°C) Isolated Yield (%)b
1 Cs2CO3 45 30 2 CsBr 45 9 3 CsF rt 80 4 KOAc 45 0
5 K3PO4 rt 92
6 K2CO3 45 23 aReactions are performed on 0.1 mmol scale with 1 equivalent of ligand 1. bYield of isolated product after recrystallization.
might control the reaction rate. So we performed the same reaction using different bases expecting that the reaction could be done at lower temperature. Table 2.1.1 collects the results of these experiments.
The stronger base potassium phosphate gave a 92% yield after stirring at rt for 24 hours (Table 2.1.1, entry 5). Cesium fluoride gave a high yield of 80% at rt, even though
49 it is a weaker base than potassium carbonate which gave 23% yield at 45 °C. Developing at least two conditions where transmetalation proceeds to completion at room temperature after 24 h (Table 2.1.1, entry 3 and 5), we examined the effect of solvent and using KOH as the base. The results are summarized in Table 2.1.2.
Table 2.1.2. Selected conditions for base promoted transmetalation reaction.a
N N base OH2 O N N Ir B Ir O solvent OH2 N rt N
2
Entry Base Solvent Reaction Time Isolated Yield (h) (%)b i 1 K3PO4 PrOH 20 91 2 KOH iPrOH 8 89 i 3 K3PO4 1:1 PrOH:H2O 6 82 i 4 KOH 1:1 PrOH:H2O 6 84 c 5 K3PO4 H2O 6 41 c 6 KOH H2O 6 38
7 K3PO4 MeOH 24 85 8 KOH MeOH 12 77
9 K3PO4 1:1 MeOH:H2O 6 55
10 KOH 1:1 MeOH:H2O 6 34 aReactions are performed on 0.05 mmol scale with 1 equivalent of ligand 2. bYield of isolated product after recrystallization. cIn these cases, a mixture of products is detected from TLC. Yield indicates the desired product.
Use of KOH as supporting base gave a faster reaction (8h) and 89% isolated yield
(entry 2, Table 2.1.2). This significant reduction in reaction time prompted us to test the reactivity of K3PO4 and KOH base in water. Unfortunately reactions in deionized water
50 lead to mixtures of products, thus affecting the overall yield (entry 5 and 6). No significant rate enhancement was observed when the reaction was performed in 1:1 water and isopropanol mixture (Table 2.1.2, entry 3 and 4). To investigate the effect of solvent, we further tested this reaction in MeOH. The reactivities in MeOH as well as in MeOH- water mixtures were similar, as previously described for isopropanol and isopropanol- water systems, even though the yield in MeOH was less than in isopropanol. Adding water accelerates the reaction when the base is K3PO4, but not so much when KOH is the base. So the best condition for base-assisted transmetalation is to react Ir(III) substrate and the borylated precursor in presence of KOH and stirring at room temperature for 8 hours ( Table 2.1.2, entry 2).
Coordination through nitrogen: A library of iridium(III) cyclometalates was prepared following the standard protocol of reacting the bis(aquo) complex with boron reagents in presence of KOH as base in 2-propanol for 6 h at 25 °C. The cyclometalated ligands around bis(aquo) precursors as well as the boron reagents were varied to maximize the range of absorption and emission colors. Chart 2.1.1 depicts the ligands.
The transmetalation strategy tolerated a variety of cylometalating ligands around Ir(III), ranging from 2-phenylpyridine (ppy), 2-(4-methyl)-phenylpyridine (tpy), 2-(2,4- difluoropheny) pyridine (F2ppy) to bulkier phenylquinoline (pq) and benzothiophene
(btp). Boronated precursors include the known ligand 1 and 3, and the new ligand 2.
Table 2.1.3 summarizes the outcome of these reactions. 1H NMR spectra of homoleptic complexes indicate C1 symmetry, and those of known species match published spectra of the meridional isomers.60
51 Coordination through oxygen: The efficiency of the transmetalation reaction has been further demonstrated by reacting the bis-aquo complexes with carbonyl- functionalized proligands 4–6 (Chart 2.1.1) where oxygen is the binding atom in the coordinating arm. All these ligands bind iridium with subsequent loss of boron, in the presence of K3PO4. Multinuclear NMR, combustion analysis, and mass spectrometry
Table 2.1. 3. Syntheses of iridium(III) complexes.
Entry L ArBpin Product Isolated yield [%]
1 ppy 1 [Ir(ppy)3] 91
2 tpy 1 [Ir(tpy)2(ppy)] 87
3 F2ppy 1 [Ir(F2ppy)2(ppy)] 92
4 ppy 2 [Ir(ppy)2(tpy)] 88
5 tpy 2 [Ir(tpy)3] 84
6 pq 2 [Ir(pq)2(tpy)] 64
7 btp 2 [Ir(btp)2(tpy)] 58
8 ppy 3 [Ir(ppy)2(ppz)] 81
9 tpy 3 [Ir(tpy)2(ppz)] 85
10 F2ppy 3 [Ir(F2ppy)2(ppz)] 90
11 btp 3 [Ir(btp)2(ppz)] 73
verified product identities. Table 2.1.4 collects metalated products. The oxidation level of the carbonyl functionality in case of aldehyde ligand was found to depend on solvent.
For the first four entries (Table 2.1.4), the carbonyl bound intact ketone ligands found to attach Ir(III), despite a reducing solvent (2-propanol). Whereas in three cases, alcohol complexes are isolated when reactions were undertaken in 2-propanol (entries 6, 9 and
14) involving aldehydic ligand. However, corresponding intact aldehyde complexes were synthesized just by switching the solvent to toluene (Table 2.1.4, entries 5, 7, 8, 10-13,
52 Table 2.1.4. Syntheses of cyclometalated ketone, aldehyde, and alcohol complexes.
K3PO4 + [L2Ir(H2O)2] Ar!B(OH)2 [L2IrAr!] 24 h, RT
Entry L ArʹB(OH)2 Solvent Product Isolated yield (%) 1 ppy 4 i-PrOH [Ir(ppy)2(AcPh)] 86 2 tpy 4 i-PrOH [Ir(tpy)2(AcPh)] 81 3 F2ppy 4 i-PrOH [Ir(F2ppy)2(AcPh)] 82 4 btp 4 i-PrOH [Ir(btp)2(AcPh)] 72 5 ppy 5 toluene [Ir(ppy)2(FoPh)] 79 6 ppy 5 i-PrOH [Ir(ppy)2(PhMeOH)] 83 7 tpy 5 toluene [Ir(tpy)2(FoPh)] 85 8 F2ppy 5 toluene [Ir(F2ppy)2(FoPh)] 88 9 F2ppy 5 i-PrOH [Ir(F2ppy)2(PhMeOH)] 89 10 btp 5 toluene [Ir(btp)2(FoPh)] 65 11 ppy 6 toluene [Ir(ppy)2(FoTol)] 85 12 tpy 6 toluene [Ir(tpy)2(FoTol)] 70 13 F2ppy 6 toluene [Ir(F2ppy)2(FoTol)] 87 14 F2ppy 6 i-PrOH [Ir(F2ppy)2(TolMeOH)] 80 15 btp 6 toluene [Ir(btp)2(FoTol)] 61
and 15). 1H NMR spectra of reduced products (alcohol complex) show broad singlets at
δ= 3.58–4.04 ppm, whereas formyl products show sharp aldehydic resonances at δ=
9.82–9.96 ppm. The presumable reductant is the solvent. When the same reactions are
run in toluene, iridium(III) complexes of the aldehyde ligand result in undiminished
yields.
X-ray diffraction quality, red block-shaped crystals were grown for
[(F2ppy)2Ir(FoTol)] and its reduced derivative [(F2ppy)2Ir(TolMeOH)] by vapor diffusion
of hexanes into methylene chloride. The crystal structure was determined by Dr. Matthias
Zeller, Youngstown State University. Thermal ellipsoid projections of
[(F2ppy)2Ir(FoTol)] and [(F2ppy)2Ir(TolMeOH)] appear in Figure 2.1.2 and Figure 2.1.3
respectively. Pseudo-octahedral geometries about iridium are evident in both structures.
71 The pyridyl nitrogen in the F2ppy ligands are trans-disposed to each other.
53 Carbon-oxygen bond lengths are observed to be 1.247(2) Å for [(F2ppy)2Ir(FoTol)] and 1.446(3) Å for [(F2ppy)2Ir(TolMeOH)]. These bond lengths are suggestive of double and single bond character respectively, which indicates sp2 hybridization of the carbonyl
Figure 2.1.2. Crystal structure of the aldehyde complex [(F2ppy)2Ir(FoTol)] showing ellipsoids at the 50% probability level. Hydrogen atoms are omitted for clarity. Unlabeled atoms are carbon. Selected interatomic distances (Å): Ir1–C1: 2.0746(18); Ir1–C18: 2.0672(18); Ir1–C19: 1.9760(18); Ir1–N1: 2.0539(15); Ir1–N2: 2.0241(16); Ir1–O1: 2.2143(13); C3–O1: 1.247(2). Selected angles (°): C19–Ir1–N2: 80.83(7); C19–Ir1–N1: 96.60(7); N2–Ir1–N1 173.65(6); C19–Ir1–C18: 94.57(7); N2–Ir1–C18: 94.73(7); N1–Ir1– C18: 79.63(7); C19–Ir1–C1: 94.93(7); N2–Ir1–C1: 90.68(7); N1–Ir1–C1: 95.34(7); C18–Ir1– C1: 169.71(7); C19–Ir1–O1: 171.68(6); N2–Ir1–O1: 95.25(6); N1–Ir1–O1 88.03(6); C18–Ir1– O1: 93.06(6); C1–Ir1–O1: 77.72(6); O1–C3–C2: 121.44(17).
3 carbon in [(F2ppy)2Ir(FoTol)] and sp hybridization of the same in
[(F2ppy)2Ir(TolMeOH)]. This fact is further evidenced from the O–C–Caryl bond angle observed in these two complexes. The above mentioned angle in the aldehyde
[(F2ppy)2Ir(FoTol)] complex measures 121.44(17)° whereas this angle is 108.73(19)° for the alcohol complex, [(F2ppy)2Ir(TolMeOH)]. These metrics indicate that the carbonyl carbon in the aldehyde complex maintains its sp2 character where as in the alcohol complex the same carbon has reduced to alcohol, and sp3 hybridization is evident.
54 The aldehyde oxygen is a stronger trans-influencer than its alcohol counterpart, which is evident from Ir–Ctrans bond lengths; being 1.9760(18) Å for aldehyde and
Figure 2.1.3. Crystal structure of the alcohol complex [(F2ppy)2Ir(TolMeOH)] showing 50% probability ellipsoids. Hydrogen atoms and a dichloromethane of solvation are omitted for clarity; unlabeled atoms are carbon. Selected interatomic distances (Å): Ir1–C22, 1.968(2); Ir1–N2, 2.0260(19); Ir1–N1, 2.0502(18); Ir1–C11, 2.067(2); Ir1–C23, 2.088(2); Ir1–O1, 2.2176(16); C29–O1, 1.446(3). Selected interatomic angles (°): C22–Ir1–N2, 80.81(8); N1– Ir1–C11, 79.58(8); C23–Ir1–O1: 77.80(7); O1–C29–C28: 108.73(19).
1.968(2) Å for alcohol. The iridium-oxygen bond lengths in the aldehyde and alcohol complexes are not immediately different; being 2.2143(13) Å for the aldehyde and
2.2176(16) Å for the alcohol. Iridium–carbon bond lengths in the C^O ligands are also not strikingly different, 2.0746(18) Å (aldehyde) and 2.088(2) Å (alcohol).
Absorption spectra and photoluminescence spectra of oxygen-chelating complexes were collected, and results are summarized in Table 2.1.5. A combined absorption and emission spectra of [(F2ppy)2Ir(FoTol)] in deoxygenated CH2Cl2 is shown in Figure
2.1.4. Iridium complexes having three C^N chelating ligands show the optically allowed absorptions and triplet-state emission characteristic of this class of complexes.
Complexes of ketone and aldehyde ligands also emit, but relative to these, emission from
55 alcohol complexes is quenched. Luminescence spectra of aldehyde and ketone complexes show some resolvable vibronic structure at room temperature.
12000
311 nm 484 nm 10000 Absorption Emission 8000
6000
4000
2000
0 300 400 500 600 700 800
Figure 2.1.4. UV-vis absorption and emission spectra of [(F2ppy)2Ir(FoTol)] in deaerated acetonitrile.
Table 2.1.5. Photophysical properties of Ir(III) ketone, aldehyde and alcohol complexes.
–3 a c Complex Abs. λmax [nm] (ε × 10 ) λexc λem [nm] τ (RT) τ (77 [nm]b [µs]d K) [µs]e
[Ir(ppy)2(AcPh)] 272 (65.4) 273 310, 503 0.30 5.3 [Ir(tpy)2(AcPh)] 276 (82), 284 (80.6) (sh) 276 310, 501 0.40 5.1 [Ir(F2ppy)2(AcPh)] 262 (60.6) 270 312, 480 0.98 2.9 [Ir(btp)2(AcPh)] 288 (22.8), 339 (11.6), 477 320 402, 600, 644 2.1 9.0 (4.3) (sh), 712 (sh) [Ir(ppy)2(FoPh)] 266 (27.8) 344 510 0.82 5.4 [Ir(ppy)2(PhMeOH)] 274 (25.2) 330 512 0.93 4.9 [Ir(F2ppy)2(FoPh)] 262 (60.6) 344 483 0.81 3.2 [Ir(F2ppy)2(PhMeOH)] 268 (48.9) 340 486 0.94 4.3 [Ir(tpy)2(FoTol)] 274 (40.6) 320 506 0.70 3.9 [Ir(F2ppy)2(FoTol)] 311 (10.2), 346 (7.5) (sh), 320 484 0.89 4.3 388 (5.6) (sh) [Ir(F2ppy)2(TolMeOH)] 315 (6.8), 379 (4.2) (sh) 315 495 1.0 4.3 a Absorption maxima, b Excitaion wavelength for emission lifetime measurement, c Emission maxima in d e CH2Cl2, Lifetime at room temperature (298 K) in 2-MeTHF, Lifetime at 77K in 2-MeTHF.
Table 2.1.5 collects room-temperature emission maxima and lifetimes for complexes of C^O chelates. All time-resolved emission data were collected in deoxygenated 2-
56 methyltetrahydrofuran. Lifetimes are microsecond-scale at 77 K and in the hundreds of nanoseconds range at 298 K.
2.3. Conclusion
A logically simple base assisted transmetalation approach of iridium(III) diaquo complexes and boronic acids or pinacol boronate esters has been described here. The syntheses are rapid even at room temperature for these classes of complexes and yields are high. Choosing correct solvent has accommodated sensitive functional groups. Of the supporting bases screened, KOH and K3PO4 are the most effective. Reactions performed with KOH are faster, but K3PO4 has broader compatibility toward functional groups.
Among homoleptic complexes, kinetic meridional products are isolated exclusively.
Complexes bearing carbon-bound aldehyde and alcohol (not alkoxide) ligands are reported. Excited-state lifetimes at room-temperature and 77 K suggest triplet emission, in keeping with the spin-orbit coupling of iridium.19 The new results demonstrate that base-assisted transmetalation from boron is an efficient synthesis of emitting iridium(III) cyclometalates.
2.4. Experimental Section
2.4.1. Materials and Methods
All synthetic procedures involving moisture-sensitive or air-sensitive substances were performed under an inert N2 or argon atmosphere and anhydrous conditions. Anhydrous solvents were used directly from MBraun solvent purification system or were purchased from Sigma Aldrich. NMR spectra were recorded on a Varian AS-400 spectrometer.
57 High-resolution mass spectrometry was carried out on a Bruker BioTOF II or Bruker microTOFQ mass spectrometer at the University of Cincinnati.
IrCl3.H2O, palladium(II) acetate and silver(I) triflate (AgOTf) were purchased from
Strem Chemicals. The ligands 2-phenylpyridine (ppy), p-tolylpyridine (tpy) and 2- acetylphenylboronic acid (4) were purchased from Acros; 2,4-difluorophenylpyridine
(F2ppy), 2-phenylquinoline (pq), 2-(2´-benzothienyl)pyridine (btp), n-butyllithium (1.6 M in hexanes) were purchased from Sigma-Aldrich. 2-Formylphenyl boronic acid (5) and 2- formyl-5-methylphenylboronic acid (6) were purchased from Frontier Scientific.
A heavy-walled high pressure vessel (catalog no. CG-1880-05, Chemglass) was used for bromination reactions. N-bromosuccinamide (NBS) (Alfa Aesar), 2-isopropoxy-
4,4,5,5,-tetramethyl-[1,3,2]-dioxaborolane (Acros) were used as received.
Cyclometalated Ir(III) µ-chloro-bridged dimers, (C^N)2Ir(µ-Cl)2Ir(C^N)2,
(abbreviated as [{Ir(C^N)2(µ-Cl)}2]) were synthesized via the method reported by
[1] Nonoyama; IrCl3·3H2O was refluxed with 2-2.5 equiv cyclometalating ligand in a 3:1
[2] mixture of 2-ethoxyethanol (Acros) and water. Syntheses of [{Ir(ppy)2(µ-Cl)}2],
[3] [4] [5] [6] [{Ir(tpy)2(µ-Cl)}2], [{Ir(pq)2(µ-Cl)}2], [{Ir(btp)2(µ-Cl)}2], [{Ir(F2ppy)2(µ-Cl)}2], have been reported.
+ 2.4.2. Synthesis of Bis-aquo Complexes [L2Ir(H2O)2] (a-e)
General procedure: The bis(aquo) iridium(III) complexes were prepared in a similar fashion to the synthesis employed by McDaniel et al.[7] To the solid chloro-bridged dimer was added a 9:1 (v/v) mixture of ethanol and water and 2.2 equiv silver trifluoromethanesulfonate (AgOTf). The reaction mixture was then refluxed for 24 hours
58 at 100 °C. After this time period the reaction mixture was passed through Celite to remove AgCl. Solvent was removed by rotary evaporation, and the reaction mixture was dissolved in methylene chloride. After washing with water and drying over anhydrous
Na2SO4, the volume of solvent was reduced, and pentane was added with precipitation of a yellow solid. The precipitate was collected, washed with ether and pentane, and dried
[7] [8] overnight. Characterization of [Ir(ppy)2(H2O)2]OTf (a) and [Ir(pq)2(H2O)2]OTf (c) has been reported elsewhere.
1 [Ir(tpy)2(H2O)2]OTf (b): Orange-colored solid. Yield 75%. H NMR (400 MHz,
CD2Cl2), δ (ppm): 8.96 (d, 2H, J = 4.8 Hz), 7.89-7.88 (dd, 2H, J = 3.8,
1.7 Hz), 7.87 (d, 2H, J = 1.1 Hz), 7.45 (d, 2H, J = 7.9, Hz), 7.36-7.33
(m, 2H), 6.72 (d, 2H, J = 9.5 Hz), 5.92 (s, 2H), 2.05 (s, 6H). HRMS:
+ Calcd. for C24H20IrN2 [M-2H2O] : 529.1256 Found: 529.1267.
1 [Ir(F2ppy)2(H2O)2]OTf (d): Bright orange-colored solid. Yield 79%. H NMR (400
MHz, D2O), δ (ppm): 8.89 (d, 2H, J = 5.3 Hz), 8.34 (d, 2H, J = 8.2
Hz), 8.04 (t, 2H, J = 7.1 Hz), 7.51 (t, 2H, J = 7.2, Hz), 6.53 (t, 2H, J =
8.9 Hz), 5.67 (d, 2H, J = 7.9 Hz). HRMS: Calcd. for C22H12F4IrN2 [M-
+ 2H2O] : 573.0566 Found: 573.0581.
1 [Ir(btp)2(H2O)2]OTf (e): Brick red-colored solid. Yield 66%. H NMR (400 MHz,
Acetone-d6), δ (ppm): 9.33-9.02 (m, 2H), 8.23-8.14 (m, 2H), 7.90-7.85 (m, 2H), 7.75-
59 7.71 (m, 2H), 7.57-7.46 (m, 2H), 7.18-7.11 (m, 2H), 6.89-6.84 (m, 2H),
+ 6.24-6.07 (m, 2H). HRMS: Calcd. for C26H16IrN2S2 [M-2H2O] :
613.0384 Found: 613.0454.
2.4.3. Synthesis of C^N Chelating Borylated Ligands
Step 1. Bromination of free ligands. General procedure: Bromination followed the procedure of Sanford et. al.[9] To a solution of ligand (1.0 equiv), dissolved in dry
CH3CN in a high pressure tube, was added N-bromosuccinimide (NBS) (1.1 equiv) and
Pd(OAc)2 (10 mol%). The reaction vessel was evacuated and back-filled with Ar. The reaction mixture was heated to 100 °C for 24 h, after which time the mixture was cooled to room temperature and solvent was removed under vacuum. The residue was purified by chromatography. Yields, eluting solvents, and characterization data for 1Br–3Br are as follows:
2-(2-Bromophenyl)pyridine (1Br):[9] Product was purified by silica gel column
chromatography eluted with ether/hexane (1:4 v/v). A transparent liquid was
1 obtained. Yield 58%. H NMR (400 MHz, CDCl3), δ: 8.71 (d, 1H, J = 5.5
Hz), 7.76 (td, 1H, J = 7.8, 1.8 Hz), 7.67 (dd, 1H, J = 7.8, 1.2 Hz), 7.59 (d, 1H,
J = 7.8 Hz), 7.53 (dd, 1H, J = 7.6, 1.2 Hz), 7.40 (td, 1H, J = 7.4, 1.2 Hz), 7.31-7.23 (m,
+ 2H). HRMS: Calcd. for C11H9BrN [MH] : 233.9918 Found: 233.9912.
2-(2-Bromo-4-methylphenyl)pyridine (2Br):[10] Product was purified by silica gel column chromatography eluted with ether/hexane (1:5 v/v). An oily liquid was collected.
60 1 Yield 62%. H NMR (400 MHz, CDCl3), δ: 8.70 (d, 1H, J = 4.9 Hz), 7.74 (td,
1H, J = 7.8, 1.8 Hz), 7.59 (d, 1H, J = 7.8 Hz), 7.50 (s, 1H), 7.43 (d, 1H, J =
7.8 Hz), 7.29-7.27 (m, 1H), 7.21 (d, 1H, J = 7.8 Hz), 2.38 (s, 3H). HRMS:
+ Calcd. for C12H11BrN [MH] : 248.0075 Found: 248.0123.
1-(2-bromophenyl)-1H-pyrazole (3Br): Product was purified by silica gel column
chromatography eluted with ether/hexanes (1:5 v/v) to recover a liquid
1 product. Yield 40%. H NMR (400 MHz, CDCl3), δ: 7.82 (dd, 1H, J = 1.8
Hz), 7.75 (d, 1H, J = 1.7 Hz), 7.70 (m, 1H), 7.51 (m, 1H), 7.43 (m, 1H), 7.28
+ (m, 1H), 6.47 (m, 1H). HRMS: Calcd. for C9H8BrN2 [MH] : 222.9871 Found: 222.9825.
Step 2. Borylation via lithiation of brominated ligands. Synthesis of ligand precursor 1-3. General procedure: 1.6 M n-butyllithium (1.5 equiv) was slowly added to brominated ligand (1 equiv) in THF at −78 °C. The mixture was stirred for 30 min at −78 °C. 2-Isopropoxy-4,4,5,5,-tetramethyl-[1, 3, 2]-dioxaborolane (1.5 equiv) was added dropwise, and the mixture was stirred at room temperature overnight. The reaction was quenched by the addition of water, and the mixture was extracted with methylene chloride. The volume of solvent was reduced, and the crude product was purified by recrystallization from methylene chloride with pentane. In each case, an off-white solid was obtained.
61 2-[2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-pyridine (1): Yield
68%. Compound 1 has been reported elsewhere.[3]
2-[4-methyl-2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-pyridine
(2): Following the general procedure afforded 2. Yield 63%. 1H NMR
(400 MHz, CDCl3), δ: 8.61 (d, 1H, J = 5.6 Hz), 7.90 (t, 1H, J = 7.7 Hz),
7.72 (d, 1H, J = 8.9 Hz), 7.51 (t, 2H, J = 8.6 Hz), 7.29 (t, 1H, J = 7.3 Hz),
7.07 (d, 1H, J = 7.8 Hz), 2.37 (s, 3H), 1.41 (s, 12H). HRMS: Calcd. for
+ C18H22BNNaO2 [MNa] : 318.1641 Found: 318.1647.
2-[2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-pyridine (3): The
general procedure afforded the desired product as a solid. Yield 40%. This
compound has been described elsewhere.[11]
2.4.4. Base Promoted Transmetalation Reactions
2.4.4.1. Synthesis of Iridium Complexes With C^N Chelating Ligands
[Ir(ppy)3]. In 7 mL 2-propanol were suspended [Ir(ppy)2(H2O)2]OTf, a (100 mg,
0.146 mmol) and compound 1 (41 mg, 0.146 mmol). To this suspension was added KOH
62 (40.9 mg, 0.729 mmol), and the mixture was stirred at room temperature for 6 h. After 6
h the boronic ester was consumed as observed by TLC. Evaporation of
solvent under reduced pressure yielded a dark orange-colored residue
that was dissolved in 10 mL methylene chloride. The methylene chloride
layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a dark-orange solid. The precipitate was collected and dried.
1 Yield: 87 mg (91%). H NMR (400 MHz, CDCl3), δ: 8.10 (d, 1H, J = 5.5 Hz), 7.92 (d,
2H, J = 7.9 Hz), 7.79 (d, 2H, J = 8.0 Hz), 7.74 (d, 1H, J = 7.3 Hz), 7.69-7.59 (m, 4H),
7.52 (t, 1H, J = 8.0 Hz), 7.46 (t, 1H, J = 7.6 Hz), 6.97-6.92 (m, 5H), 6.88 (t, 2H, J = 7.0
Hz), 6.83 (t, 1H, J = 8.3 Hz), 6.72 (dd, 2H, J = 6.2 Hz), 6.61 (d, 1H, J = 5.9 Hz), 6.46 (d,
+ 1H, J = 9.0 Hz). HRMS: Calcd. For C33H25IrN3 [MH] : 656.1678 Found: 656.1653 Anal.
Calcd. For C33H24IrN3: C, 60.53; H, 3.69; N, 6.42. Found: C, 60.63; H, 3.98; N, 6.55.
[Ir(tpy)2ppy]. In 5 mL 2-propanol were suspended [Ir(tpy)2(H2O)2]OTf, b (91.2 mg,
0.128 mmol) and compound 1 (35.9 mg, 0.128 mmol). To this
suspension was added KOH (35.8 mg, 0.638 mmol), and the mixture was
stirred at room temperature for 6 h. Starting material was consumed after
6 h, as indicated by TLC. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in 10 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced to 0.5 mL, and sufficient pentane was added to afford a dark orange precipitate. The precipitate was collected and dried.
63 1 Yield: 76 mg (87%). H NMR (400 MHz, CD2Cl2), δ: 8.04 (d, 1H, J = 5.6 Hz), 7.95 (d,
2H, J = 7.6 Hz), 7.78 (t, 3H, J = 3.8 Hz), 7.63-7.46 (m, 5H), 6.97-6.79 (m, 6H), 6.72-6.69
(m, 3H), 6.39 (s, 1H), 6.23 (s, 1H), 2.14 (s, 3H), 2.13 (s, 3H). HRMS: Calcd. For
+ C35H29IrN3 [MH] : 684.1991 Found: 684.1988 Anal. Calcd. For C35H28IrN3: C, 61.56; H,
4.13; N, 6.15. Found: C, 61.85; H, 4.35; N, 5.90.
[Ir(F2ppy)2ppy]. In 5 mL 2-propanol were suspended [Ir(F2ppy)2(H2O)2]OTf, d (106
mg, 0.139 mmol) and compound 1 (39.3 mg, 0.139 mmol). To this
suspension was added KOH (39.2 mg, 0.699 mmol), and the mixture
was stirred at room temperature for 6 h. After 6 h the boronic ester
was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in 10 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced to 1 mL and sufficient pentane was added to precipitate an orange solid. The precipitate
1 was collected and dried. Yield: 93.6 mg (92%). H NMR (400 MHz, CD2Cl2), δ: 8.21 (d,
1H, J = 8.4 Hz), 8.08 (d, 1H, J = 5.9 Hz), 7.95 (d, 1H, J = 8.3 Hz), 7.87 (d, 1H, J = 5.5
Hz), 7.75 (d, 1H, J = 6.7 Hz), 7.67 (td, 1H, J = 8.2, 1.6 Hz), 7.59 (t, 1H, J = 7.24), 7.49 (t,
1H, J = 7.4 Hz), 7.03-6.99 (m, 3H), 6.95 (t, 1H, J = 6.0 Hz), 6.90 (d, 1H, J = 8.1 Hz),
6.75 (q, 2H, J = 5.8 Hz), 6.47-6.37 (m, 3H), 6.02 (dd, 1H, J = 7.4, 2.3 Hz), 5.82 (dd, 1H,
+ J = 9.2, 2.3 Hz). HRMS: Calcd. For C33H21F4IrN3 [MH] : 728.1301 Found: 728.1372
Anal. Calcd. For C33H20F4IrN3: C, 54.54; H, 2.77; N, 5.78. Found: C, 54.61; H, 3.06; N,
5.93.
64 [Ir(ppy)2tpy]. In 8 mL 2-propanol were suspended [Ir(ppy)2(H2O)2]OTf, a (100 mg,
0.146 mmol) and compound 2 (43.0 mg, 0.146 mmol). To this
suspension was added KOH (40.9 mg, 0.729 mmol), and the mixture
was stirred at room temperature for 6 h. After 6 h the boronic ester 2
was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in 20 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced to 0.5 mL and pentane was added to precipitate a bright orange solid. The precipitate was
1 collected and dried. Yield: 85.8 mg (88%). H NMR (400 MHz, CD2Cl2), δ: 8.12 (d, 1H,
J = 5.7 Hz), 7.89 (t, 2H, J = 8.3 Hz), 7.84 (d, 1H, J = 3.8 Hz), 7.82 (d, 1H, J = 3.6 Hz),
7.71 (d, 1H, J = 7.6 Hz), 7.67 (d, 2H, J = 7.8 Hz), 7.64-7.51 (m, 4H), 6.97-6.75 (m, 8H),
6.69 (s, 1H), 6.56 (d, 1H, J = 7.1 Hz), 6.41 (d, 1H, J = 7.4 Hz), 2.11 (s, 3H). HRMS:
+ Calcd. For C34H27IrN3 [MH] : 670.1834 Found: 670.1876 Anal. Calcd. For C34H26IrN3:
C, 61.06; H, 3.92; N, 6.28. Found: C, 61.25; H, 4.11; N, 5.98.
[Ir(tpy)3]. In 7 mL 2-propanol were suspended [Ir(tpy)2(H2O)2]OTf, b (91.2 mg,
0.128 mmol) and compound 2 (37.7 mg, 0.128 mmol). To this
suspension was added KOH (35.8 mg, 0.638 mmol), and the mixture
was stirred at room temperature for 6 h. Evaporation of solvent under
reduced pressure yielded a dark orange-colored residue that was dissolved in 10 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of
65 solvent was reduced, and pentane was added to get bright yellow precipitate. The
1 precipitate was collected and dried. Yield: 74.8 mg (84%). H NMR (400 MHz, CD2Cl2),
δ: 8.07 (d, 1H, J = 6.2 Hz), 7.90-7.88 (m, 2H), 7.79-7.76 (dd, 2H, J = 8.0, 4.2 Hz), 7.65-
7.48 (m, 8H), 6.86 (t, 1H, J = 6.3 Hz), 6.80 (t, 2H, J = 6.1 Hz), 6.72 (t, 3H, J = 6.8 Hz),
6.36 (s, 1H), 6.21 (s, 1H), 2.13 (s, 6H), 2.12 (s, 3H). HRMS: Calcd. For C36H31IrN3
+ [MH] : 698.2147 Found: 698.2144 Anal. Calcd. For C36H30IrN3: C, 62.05; H, 4.34; N,
6.03. Found: C, 62.25; H, 4.14; N, 5.88.
[Ir(pq)2tpy]. In 10 mL 2-propanol were suspended [Ir(pq)2(H2O)2]OTf, c (100 mg,
0.127 mmol) and compound 2 (37.6 mg, 0.127 mmol). To this
suspension was added KOH (35.7 mg, 0.636 mmol), and the mixture
was stirred at room temperature for 16 h. Evaporation of solvent under
reduced pressure yielded a dark orange-colored residue that was dissolved in 15 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced, and pentane was added with precipitation of a dark red solid. The precipitate was recrystallized from methylene chloride and pentane one more time to obtain, after drying, an analytically pure product. Yield: 62.6 mg (64%). 1H NMR (400
MHz, CD2Cl2), δ: 8.26 (s, 2H), 8.00 (d, 1H, J = 8.1 Hz), 7.92-7.83 (m, 3H), 7.71 (t, 2H, J
= 7.6 Hz), 7.61 (d, 1H, J = 5.4 Hz), 7.51-7.44 (m, 3H), 7.36-7.32 (m, 4H), 7.21 (t, 1H, J =
7.1 Hz), 7.02 (d, 1H, J = 7.7 Hz), 6.99-6.92 (m, 2H), 6.86 (t, 1H, J = 7.4 Hz), 6.63 (t, 1H,
J = 7.4 Hz), 6.58 (t, 2H, J = 7.2 Hz), 6.23 (d, 1H. J = 8.0 Hz), 5.99 (d, 1H, J = 7.8 Hz),
+ 5.74 (d, 1H, J = 7.8 Hz), 1.92 (s, 3H). HRMS: Calcd. For C42H31IrN3 [MH] : 770.2147
66 Found: 770.2148 Anal. Calcd. For C42H30IrN3: C, 65.60; H, 3.93; N, 5.46. Found: C,
65.81; H, 4.28; N, 5.67.
[Ir(btp)2tpy]. In 10 mL 2-propanol were suspended [Ir(btp)2(H2O)2]OTf, e (100 mg,
0.125 mmol) and compound 2 (36.9 mg, 0.125 mmol). To this
suspension was added KOH (35.0 mg, 0.626 mmol), and the mixture
was stirred at room temperature for 16 h. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in 15 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a bright red solid. The
1 precipitate was collected and dried. Yield: 56.8 mg (58%). H NMR (400 MHz, CDCl3),
δ: 9.12 (d, 1H, J = 6.0 Hz), 8.08 (d, 1H, J = 5.6 Hz), 7.81-7.65 (m, 7H), 7.59 (t, 1H, J =
7.4 Hz), 7.50 (d, 1H, J = 7.5 Hz), 7.24 (d, 1H, J = 8.2 Hz), 7.11-7.06 (m, 2H), 6.98 (t, 1H,
J = 7.1 Hz), 6.83-6.77 (m, 2H), 6.73 (t, 1H, J = 5.7 Hz), 6.59 (t, 1H, J = 6.4 Hz), 6.33 (d,
1H, J = 7.6 Hz), 6.28 (d, 1H, J = 7.9 Hz), 6.21 (s, 1H), 6.02 (d, 1H, J = 7.9 Hz), 2.02 (s,
+ 3H). HRMS: Calcd. For C38H27IrN3S2 [MH] : 782.1276 Found: 782.1263 Anal. Calcd.
For C38H26IrN3S2: C, 58.44; H, 3.36; N, 5.38. Found: C, 58.66; H, 3.29; N, 5.41.
[Ir(ppy)2ppz]. In 8 mL 2-propanol were suspended [Ir(ppy)2(H2O)2]OTf, a (100 mg,
0.146 mmol) and compound 3 (39.4 mg, 0.146 mmol). To this suspension was added
KOH (40.9 mg, 0.729 mmol), and the mixture was stirred at room temperature for 6 h.
After 6 h the boronic ester was consumed as observed by TLC. Evaporation of solvent
67 under reduced pressure yielded a dark orange-colored residue that was
dissolved in 10 mL methylene chloride. The methylene chloride layer
was washed twice with water followed by brine, and was passed through
anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a dark orange solid. The precipitate was collected and
1 dried. Yield: 76.0 mg (81%). H NMR (400 MHz, CDCl3), δ: 9.05 (d, 1H, J = 5.8 Hz),
8.01 (dd, 1H, J = 7.6, 1.1 Hz), 7.88-7.83 (m, 2H), 7.78 (t, 1H, J = 7.3 Hz), 7.52-7.43 (m,
4H), 7.37 (t, 2H, J = 6.2 Hz), 7.29 (dd, 1H, J = 7.8, 4.0 Hz), 7.12 (t, 1H, J = 7.6 Hz), 6.93
(td, 1H, J = 7.6, 1.6 Hz), 6.79-6.72 (m, 3H), 6.59 (t, 1H, J = 7.6 Hz), 6.38 (t, 1H, J = 6.0
Hz), 6.34-6.31 (m, 2H), 6.27 (t, 1H, J = 2.5 Hz), 6.01 (d, 1H, J = 7.5 Hz). HRMS: Calcd.
+ For C31H24IrN4 [MH] : 645.1630 Found: 645.1639 Anal. Calcd. For C31H23IrN4: C,
57.84; H, 3.60; N, 8.70. Found: C, 57.91; H, 3.77; N, 8.71.
[Ir(tpy)2ppz]. In 5 mL 2-propanol were suspended [Ir(tpy)2(H2O)2]OTf, b (105.6 mg,
0.148 mmol) and compound 3 (39.9 mg, 0.148 mmol). To this suspension
was added KOH (41.5 mg, 0.739 mmol), and the mixture was stirred at
room temperature for 6 h. After 6 h the boronic ester was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark orange- colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous
Na2SO4. The volume of solvent was reduced, and pentane was added. A bright yellow
1 precipitate was collected and dried. Yield: 84.5 mg (85%). H NMR (400 MHz, CDCl3),
δ: 8.95 (d, 1H, J = 5.6 Hz), 7.99 (d, 1H, J = 7.6 Hz), 7.82 (d, 1H, J = 5.5 Hz), 7.76 (t, 2H,
68 J = 8.4 Hz), 7.48 (s, 1H), 7.42-7.33 (m, 5H), 7.16 (d, 1H, J = 7.7 Hz), 7.07 (t, 1H, J = 7.6
Hz), 6.92 (t, 1H, J = 7.8 Hz), 6.58 (d, 1H, 8.6 Hz), 6.55 (d, 1H, J = 7.8 Hz), 6.32 (t, 2H, J
= 7.8 Hz), 6.26 (s, 1H), 6.11 (s, 1H), 5.81 (s, 1H), 2.07 (s, 3H), 1.92 (s, 3H). HRMS:
+ Calcd. For C33H28IrN4 [MH] : 673.1943 Found: 673.1941 Anal. Calcd. For C33H27IrN4:
C, 59.00; H, 4.05; N, 8.34. Found: C, 59.11; H, 4.13; N, 8.36.
[Ir(F2ppy)2ppz]. In 5 mL 2-propanol were suspended [Ir(F2ppy)2(H2O)2]OTf, d (120
mg, 0.158 mmol) and compound 3 (42.7 mg, 0.158 mmol). To this
suspension was added KOH (44.4 mg, 0.792 mmol), and the mixture
was stirred at room temperature for 6 h. After 6 h the boronic ester was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in 20 mL methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a bright orange solid. The precipitate was collected and dried.
1 Yield: 102.0 mg (90%). H NMR (400 MHz, CDCl3), δ: 9.05 (d, 1H, J = 6.6 Hz), 8.31 (d,
1H, J = 9.0 Hz), 8.13 (d, 1H, J = 8.5 Hz), 7.96 (d, 1H, J = 2.7 Hz), 7.94 (d, 1H, J = 5.8
Hz), 7.78 (t, 1H, J = 7.6 Hz), 7.57 (t, 1H, J = 8.3 Hz), 7.12-7.06 (m, 2H), 6.85 (td, 1H, J
= 7.1, 1.6 Hz), 6.75 (d, 1H, J = 2.3 Hz), 6.66 (t, 1H, J = 6.7 Hz), 6.54-6.47 (m, 2H), 6.43-
6.31 (m, 3H), 5.91 (dd, 1H, J = 8.5, 2.5 Hz), 5.55 (dd, 1H, J = 8.8, 2.3 Hz). HRMS:
+ Calcd. For C31H20F4IrN4 [MH] : 717.1253 Found: 717.1281 Anal. Calcd. For
C31H19F4IrN4: C, 52.02; H, 2.68; N, 7.83. Found: C, 52.39; H, 2.92; N, 8.11.
69 [Ir(btp)2ppz]. In 5 mL 2-propanol were suspended [Ir(btp)2(H2O)2]OTf, e (120 mg,
0.150 mmol) and compound 3 (40.6 mg, 0.150 mmol). To this
suspension was added KOH (42.2 mg, 0.752 mmol), and the mixture was
stirred at room temperature for 6 h. After 6 h the boronic ester was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark orange-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced to 0.5 mL and sufficient pentane was added to precipitate a dark red solid. The precipitate was collected and dried. Yield:
1 89.8 mg (79%). H NMR (400 MHz, CDCl3), δ: 9.11 (d, 1H, J = 5.5 Hz), 7.96 (d, 1H, J =
2.2 Hz), 7.93 (d, 1H, J = 5.4 Hz), 7.78-7.68 (m, 4H), 7.64 (d, 1H, J = 8.0 Hz), 7.56-7.43
(m, 2H), 7.10-7.02 (m, 2H), 6.95 (t, 1H, J = 5.8, 1.5 Hz), 6.87-6.74 (m, 4H), 6.59 (dd,
1H, J = 8.3, 1.3 Hz), 6.52-6.46 (m, 2H), 6.32 (d, 1H, J = 8.1 Hz), 6.27 (t, 1H, J = 2.5 Hz),
+ 6.10 (d, 1H, J = 8.1 Hz). HRMS: Calcd. For C35H24IrN4S2 [MH] : 757.1072 Found:
757.1097 Anal. Calcd. For C35H23IrN4S2: C, 55.61; H, 3.07; N, 7.41. Found: C, 55.83; H,
3.23; N, 7.77.
70 2.4.4.2. Synthesis of Iridium Complexes with C^O Chelating Ligands
A. Synthesis of Ir(III) acetyl and formyl complexes:
[Ir(ppy)2AcPh]. In 5 mL 2-propanol were suspended [Ir(ppy)2(H2O)2]OTf, a (100
mg, 0.146 mmol) and compound 4 (23.9 mg, 0.146 mmol). To this
suspension was added K3PO4 (154.8 mg, 0.729 mmol), and the
mixture was stirred at room temperature for 24 h. Evaporation of
solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after crystallization from methylene chloride and pentane, and
1 were dried. Yield: 77.7 mg (86%). H NMR (400 MHz, CD2Cl2), δ: 8.12 (d, 1H, J = 6.1
Hz), 7.92-7.82 (m, 4H), 7.72-7.57 (m, 5H), 7.07-6.81 (m, 7H), 6.75 (t, 1H, J = 8.3 Hz),
6.49 (d, 1H, J = 6.9 Hz), 6.38 (d, 1H, J = 7.9 Hz), 2.83 (s, 3H). IR (KBr): ῦ = 1573 (s)
-1 + cm (C O). HRMS: Calcd. For C30H24IrN2O [MH] : 620.1440 Found: 620.1445 Anal.
Calcd. For C30H23IrN2O: C, 58.14; H, 3.74; N, 4.52. Found: C, 58.44; H, 4.01; N, 4.32.
71 [Ir(tpy)2AcPh]. In 7 mL 2-propanol were suspended [Ir(tpy)2(H2O)2]OTf, b (100 mg,
0.140 mmol) and compound 4 (22.9 mg, 0.140 mmol). To this solution
was added K3PO4 (148 mg, 0.700 mmol), and the mixture was stirred
at room temperature for 22 h. After 22 h the compound 4 was consumed as observed by TLC. Evaporation of solvent under reduced pressure yielded a dark red-colored residue that was dissolved in 10 mL methylene chloride. After washing twice with water followed by brine, the resulting red liquid was passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a dark red solid. The precipitate was collected and dried. Yield: 73.5 mg (81%). 8.03 (dd, 1H, J = 5.8, 0.7 Hz), 7.78 (dd, 1H, J = 5.9, 0.9 Hz), 7.73 (dd, 2H, J =
8.0, 3.5 Hz), 7.66 (d, 1H, J = 8.0 Hz), 7.52 (d, 1H, J = 7.9 Hz), 7.51 (td, 1H, J = 7.3, 1.6
Hz), 7.42 (td, 1H, 7.4, 1.6 Hz), 7.41 (d, 1H, J = 7.8 Hz), 6.99 (td, 1H, J = 7.1, 1.2 Hz),
6.92 (dd, 1H, J = 7.3, 0.9 Hz), 6.85 (ddd, 1H, J = 7.8, 7.8, 1.4 Hz), 6.82 (ddd, 1H, J = 5.9,
5.9, 1.4 Hz), 6.66-6.64 (m, 2H), 6.59 (dd, 1H, J = 7.8, 1.3 Hz), 6.28 (s, 1H), 6.14 (s, 1H),
2.73 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H). IR (KBr): ῦ = 1589 (s) cm-1 (C O). HRMS:
+ Calcd. For C32H28IrN2O [MH] : 649.1831 Found: 649.1835 Anal. Calcd. For
C32H27IrN2O: C, 59.33; H, 4.20; N, 4.32. Found: C, 59.09; H, 4.26; N, 4.66.
[Ir(F2ppy)2AcPh]. In 10 mL 2-propanol were suspended
[Ir(F2ppy)2(H2O)2]OTf, d (100 mg, 0.132 mmol) and compound 4 (21.6
mg, 0.132 mmol). To this suspension was added K3PO4 (140 mg, 0.659
mmol), and the mixture was stirred at room temperature for 24 h. After
24 h compound 4 was consumed as observed by TLC. Solvent was evaporated under
72 reduced pressure, and the residue was dissolved in 10 mL methylene chloride which was washed twice with water followed by brine, and was passed through anhydrous Na2SO4.
The volume of solvent was reduced to 0.5 mL and sufficient pentane was added precipitate a red solid. The precipitate was collected and dried. Yield: 74.8 mg (82%). 1H
NMR (400 MHz, CDCl3), δ: 8.28 (dd, 1H, J = 8.2, 2.5 Hz), 8.18 (d, 1H, J = 8.2 Hz), 8.07
(dd, 1H, J = 5.8, 0.8 Hz), 7.85 (d, 1H, J = 5.8 Hz), 7.83 (d, 1H, J = 7.4 Hz), 7.67 (t, 1H, J
= 7.5 Hz), 7.59 (t, 1H, 7.5 Hz), 7.13 (t, 1H, J = 6.0 Hz), 7.01-6.97 (m, 3H), 6.82 (td, 1H,
J = 5.8, 1.4 Hz), 6.43-6.36 (m, 2H), 5.95 (dd, 1H, J = 7.5, 2.4 Hz), 5.78 (dd, 1H, J = 9.5,
2.3 Hz), 2.85 (s, 3H). IR (KBr): ῦ = 1589 (s) cm-1 (C O). HRMS: Calcd. For
+ C30H20F4IrN2O [MH] : 693.1141 Found: 693.1172 Anal. Calcd. For C30H19F4IrN2O: C,
52.09; H, 2.77; N, 4.05. Found: C, 52.42; H, 2.81; N, 3.88.
[Ir(btp)2AcPh]. In 5 mL 2-propanol were suspended [Ir(btp)2(H2O)2]OTf, e (50 mg,
0.063 mmol) and compound 4 (10.3 mg, 0.063 mmol). To this
suspension was added K3PO4 (66.5 mg, 0.313 mmol), and the mixture
was stirred at room temperature for 24 h. After 24 h compound 4 was
consumed as observed by TLC. Solvent was evaporated under reduced pressure, and the residue was dissolved in 15 mL methylene chloride, which was washed twice with water followed by brine, and then passed through anhydrous Na2SO4.
The volume of solvent was reduced, and pentane was added to precipitate a brick-red solid. The precipitate was collected and dried. Yield: 33.0 mg (72%). 1H NMR (400
MHz, CD2Cl2), δ: 8.26 (d, 1H, J = 5.8 Hz), 7.84 (d, 1H, J = 8.4 Hz), 7.80-7.60 (m, 6H),
7.15-7.07 (m, 3H), 7.03-7.95 (m, 2H), 6.89-6.80 (m, 3H), 6.77-6.71 (m, 2H), 6.24 (d, 1H,
73 J = 7.7 Hz), 7.19 (d, 1H, J = 7.6 Hz), 2.87 (s, 3H). IR (KBr): ῦ = 1589 (s) cm-1 (C O).
+ HRMS: Calcd. For C34H24IrN2OS2 [MH] : 733.0959 Found: 733.0949 Anal. Calcd. For
C34H23IrN2OS2: C, 55.79; H, 3.17; N, 3.83. Found: C, 55.88; H, 3.25; N, 4.01.
[Ir(ppy)2FoPh]. In 10 mL dry toluene were suspended [Ir(ppy)2(H2O)2]OTf, a (100 mg, 0.146 mmol) and compound 5 (21.8 mg, 0.146 mmol). To this suspension was added
K3PO4 (155 mg, 0.729 mmol), and the mixture was stirred at room
temperature for 24 h. After 24 h compound 5 was consumed as
observed by TLC. Solvent was evaporated under reduced pressure,
and the residue was dissolved in 10 mL methylene chloride which was washed twice with water followed by brine, and was passed through anhydrous
Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a brick-red solid. The precipitate was collected and dried. Yield: 74.8 mg
1 (79%). H NMR (400 MHz, CDCl3), δ: 9.96 (s, 1H), 8.17 (d, 1H, J = 5.3 Hz), 7.90 (dd,
1H, J = 6.2, 0.9 Hz), 7.86 (t, 2H, J = 6.4 Hz), 7.80 (d, 1H, J = 8.3 Hz), 7.71-7.68 (m, 1H),
7.64-7.59 (m, 2H), 7.54 (td, 1H, J = 7.2, 1.2 Hz), 7.09-6.93 (m, 6H), 6.86 (td, 1H, J = 7.1,
0.9 Hz), 6.81-6.76 (m, 2H), 6.57-6.55 (m, 1H), 6.46 (dd, 1H, J = 7.7, 1.1 Hz). IR (KBr): ῦ
-1 + = 1582 (s) cm (C O). HRMS: Calcd. For C29H22IrN2O [MH] : 607.1361 Found:
607.1363 Anal. Calcd. For C29H21IrN2O: C, 57.50; H, 3.49; N, 4.62. Found: C, 57.77; H,
3.61; N, 4.78.
[Ir(tpy)2FoPh]. In 5 mL dry toluene were suspended [Ir(tpy)2(H2O)2]OTf, b (100 mg,
0.140 mmol) and compound 5 (21 mg, 0.140 mmol). To this suspension was added
74 K3PO4 (148 mg, 0.700 mmol), and the mixture was stirred at room
temperature for 24 h. After 24 h compound 5 was consumed as
observed by TLC. Solvent was evaporated under reduced pressure, and the residue was dissolved in 10 mL methylene chloride, which was washed twice with water followed by brine, and then passed through anhydrous Na2SO4. The volume of solvent was reduced to 0.5 mL and sufficient pentane was added to precipitate a deep red solid. The precipitate was collected and dried. Yield: 75.5 mg (85%). 1H NMR (400
MHz, CDCl3), δ: 9.93 (s, 1H), 8.11 (d, 1H, J = 5.9 Hz), 7.86 (dd, 2H, J = 6.4, 6.3 Hz),
7.80 (d, 1H, J = 8.0 Hz), 7.74 (d, 1H, J = 8.4 Hz), 7.61-7.57 (m, 2H), 7.54-7.48 (m, 2H),
7.08-7.01 (m, 2H), 6.97 (td, 1H, J = 6.7, 1.4 Hz), 6.91 (td, 1H, J = 5.9, 1.4 Hz), 6.76-6.73
(m, 2H), 6.67 (dd, 1H, J = 8.1, 0.9 Hz), 6.36 (s, 1H), 6.25 (s, 1H), 2.13 (s, 3H), 2.11 (s,
-1 + 3H). IR (KBr): ῦ = 1582 (s) cm (C O). HRMS: Calcd. For C31H26IrN2O [MH] :
635.1674 Found: 635.1643 Anal. Calcd. For C31H25IrN2O: C, 58.75; H, 3.98; N, 4.42.
Found: C, 58.82; H, 4.33; N, 4.78.
[Ir(F2ppy)2FoPh]. In 7 mL dry toluene were suspended [Ir(F2ppy)2(H2O)2]OTf, d
(120 mg, 0.158 mmol) and compound 5 (23.7 mg, 0.158 mmol). To
this suspension was added K3PO4 (168 mg, 0.792 mmol), and the
mixture was stirred at room temperature for 24 h. Evaporation of
solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after crystallization from methylene chloride and pentane, and
75 1 were dried. Yield: 94.4 mg (88%). H NMR (400 MHz, CDCl3), δ: 9.96 (s, 1H), 8.28 (dd,
1H, J = 7.8, 2.4 Hz), 8.19 (d, 1H, J = 8.2 Hz), 8.09 (dd, 1H, J = 5.8, 0.8 Hz), 7.89 (dd,
1H, J = 8.1, 0.7 Hz), 7.86 (dd, 1H, J = 5.8, 2.3 Hz), 7.69 (t, 1H, 7.5 Hz), 7.61 (t, 1H, J =
7.4 Hz), 7.14 (t, 1H, J = 7.4, 1.3 Hz), 7.07-6.99 (m, 3H), 6.84 (ddd, 1H, J = 5.8, 5.8, 1.4
Hz), 6.41 (ddd, 2H, J = 11.6, 1.1 Hz), 5.96 (dd, 1H, J = 7.9, 2.4 Hz), 5.80 (dd, 1H, J =
-1 9.4, 2.4 Hz). IR (KBr): ῦ = 1585 (s) cm (C O). HRMS: Calcd. For C29H18F4IrN2O
+ [MH] : 679.0985 Found: 679.0983 Anal. Calcd. For C29H17F4IrN2O: C, 51.40; H, 2.53;
N, 4.13. Found: C, 51.71; H, 2.46; N, 4.54.
[Ir(btp)2FoPh]. In 5 mL dry toluene were suspended [Ir(btp)2(H2O)2]OTf, e (50 mg,
0.063 mmol) and compound 5 (9.4 mg, 0.063 mmol). To this suspension
was added K3PO4 (66.5 mg, 0.313 mmol), and the mixture was stirred at
room temperature for 24 h. Evaporation of solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after crystallization from methylene chloride and pentane, and were dried. Yield: 29.2 mg (65%). 1H NMR (400
MHz, CD2Cl2), δ: 9.93 (s, 1H), 8.29 (d, 1H, J = 5.9 Hz), 7.92 (dd, 1H, J = 3.4, 2.6 Hz),
7.78-7.61 (m, 6H), 7.16-7.01 (m, 5H), 6.89-6.78 (m, 5H), 6.74 (t, 1H, J = 8.2 Hz), 6.18
+ (d, 1H, J = 8.2 Hz). HRMS: Calcd. For C33H22IrN2OS2 [MH] : 719.0803 Found:
719.0815 Anal. Calcd. For C33H21IrN2OS2: C, 55.21; H, 2.95; N, 3.90. Found: C, 55.44;
H, 3.29; N, 4.13.
76 [Ir(ppy)2FoTol]. In 5 mL dry toluene were suspended [Ir(ppy)2(H2O)2]OTf, a (100
mg, 0.146 mmol) and compound 6 (23.9 mg, 0.146 mmol). To this
suspension was added K3PO4 (158 mg, 0.729 mmol), and the mixture
was stirred at room temperature for 24 h. After 24 h compound 6 was
consumed as observed by TLC. Solvent was evaporated under reduced pressure, and the residue was dissolved in 10 mL methylene chloride, which was washed twice with water followed by brine, and then passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to yield a brick red precipitate. The precipitate was collected and dried. Yield: 76.8 mg (85%). 1H NMR
(400 MHz, CDCl3), δ: 9.86 (s, 1H), 8.16 (d, 1H, J = 5.7 Hz), 7.93 (d, 1H, J = 5.8 Hz),
7.82 (dd, 2H, J = 8.0, 7.8 Hz), 7.75 (d, 1H, J = 7.8 Hz), 7.68 (dd, 1H, J = 4.0, 2.1 Hz),
7.64-7.52 (m, 3H), 6.97-6.91 (m, 3H), 6.87-6.75 (m, 5H), 6.52 (dd, 1H, J = 3.5, 2.0 Hz),
6.45 (dd, 1H, J = 7.8, 0.8 Hz), 2.20 (s, 3H). IR (KBr): ῦ = 1584 (s) cm-1 (C O). HRMS:
+ Calcd. For C30H24IrN2O [MH] : 621.1518 Found: 621.1511 Anal. Calcd. For
C30H23IrN2O: C, 58.14; H, 3.74; N, 4.52. Found: C, 58.34; H, 4.06; N, 4.67.
[Ir(tpy)2FoTol]. In 5 mL dry toluene were suspended [Ir(tpy)2(H2O)2]OTf, b (100
mg, 0.140 mmol) and compound 6 (22.9 mg, 0.140 mmol). To this
suspension was added K3PO4 (148 mg, 0.700 mmol), and the mixture
was stirred at room temperature for 24 h. Evaporation of solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after
77 crystallization from methylene chloride and pentane, and were dried. Yield: 72.0 mg
1 (70%). H NMR (400 MHz, CDCl3), δ: 9.84 (s, 1H), 8.12 (d, 1H, J = 5.3 Hz), 7.90 (d,
1H, J = 5.8 Hz), 7.79 (d, 1H, J = 8.1 Hz), 7.74 (d, 1H, J = 8.0 Hz), 7.73 (d, 1H, J = 7.7
Hz), 7.60-7.56 (m, 2H), 7.51 (t, 1H, J = 7.1 Hz), 7.49 (d, 1H, J = 7.9 Hz), 6.90 (td, 1H, J
= 6.0, 1.3 Hz), 6.84 (s, 1H), 6.80-6.73 (m, 3H), 6.66 (dd, 1H, J = 7.9, 1.3 Hz), 6.33 (s,
1H), 6.25 (s, 1H), 2.21 (s, 3H), 2.14 (s, 3H), 2.10 (s, 3H). IR (KBr): ῦ = 1583 (s) cm-1
+ (C O). HRMS: Calcd. For C32H28IrN2O [MH] : 649.1831 Found: 649.1853 Anal. Calcd.
For C32H27IrN2O: C, 59.33; H, 4.20; N, 4.32. Found: C, 59.13; H, 4.56; N, 4.38.
[Ir(F2ppy)2FoTol]. In 5 mL dry toluene were suspended [Ir(F2ppy)2(H2O)2]OTf, d
(120 mg, 0.158 mmol) and compound 6 (25.9 mg, 0.158 mmol). To this
suspension was added K3PO4 (168 mg, 0.792 mmol), and the mixture
was stirred at room temperature for 24 h. After 24 h compound 6 was consumed as observed by TLC. Solvent was evaporated under reduced pressure, and the residue was dissolved in 10 mL methylene chloride, which was washed twice with water followed by brine, and then passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to precipitate a brick-red solid. The
1 precipitate was collected and dried. Yield: 95.0 mg (87%). H NMR (400 MHz, CDCl3),
δ: 9.84 (s, 1H), 8.27 (dd, 1H, J = 7.6, 2.6 Hz), 8.20 (d, 1H, J = 8.3 Hz), 8.10 (dd, 1H, J =
5.8, 0.8 Hz), 7.89 (dd, 1H, J = 5.8, 1.0 Hz), 7.78 (d, 1H, J = 7.7 Hz), 7.68 (t, 1H, J = 8.1
Hz), 7.61 (t, 1H, J = 8.5 Hz), 7.00 (ddd, 1H, J = 5.9, 5.9, 1.4 Hz), 6.87-6.83 (m, 2H), 6.80
(s, 1H), 6.44-6.37 (m, 2H), 5.93 (dd, 1H, J = 7.5, 2.4 Hz), 5.82 (dd, 1H, J = 9.5, 2.4 Hz),
-1 2.25 (s, 3H). IR (KBr): ῦ = 1585 (s) cm (C O). HRMS: Calcd. For C30H20F4IrN2O
78 + [MH] : 693.1141 Found: 693.1157 Anal. Calcd. For C30H19F4IrN2O: C, 52.09; H, 2.77;
N, 4.05. Found: : C, 52.39; H, 3.03; N, 4.28.
[Ir(btp)2FoTol]. In 5 mL dry toluene were suspended [Ir(btp)2(H2O)2]OTf, e (50 mg,
0.063 mmol) and compound 6 (10.3 mg, 0.063 mmol). To this suspension
was added K3PO4 (66.5 mg, 0.313 mmol), and the mixture was stirred at
room temperature for 24 h. Evaporation of solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after crystallization from methylene chloride and pentane, and were dried. Yield: 28.0 mg (61%). 1H NMR (400
MHz, CDCl3), δ: 9.82 (s, 1H), 8.28 (dd, 1H, J = 6.5, 1.6 Hz), 7.84-7.60 (m, 8H), 7.13 (t,
1H, J = 7.8 Hz), 7.09 (t, 1H, J = 7.9 Hz), 6.89-6.79 (m, 4H), 6.74 (t, 1H, J = 6.9 Hz), 6.64
(s, 1H), 6.26 (d, 1H, J = 7.9 Hz), 6.16 (d, 1H, J = 8.5 Hz), 2.15 (s, 3H). HRMS: Calcd.
+ For C34H24IrN2OS2 [MH] : 733.0959 Found: 733.0961 Anal. Calcd. For C34H23IrN2OS2:
C, 55.79; H, 3.17; N, 3.83. Found: C, 55.88; H, 3.34; N, 4.14.
B. Synthesis of Ir(III) alcohol complexes:
[Ir(ppy)2PhMeOH]. In 5 mL 2-propanol were suspended
[Ir(ppy)2(H2O)2]OTf, a (100 mg, 0.146 mmol) and compound 5 (21.8
mg, 0.146 mmol). To this suspension was added K3PO4 (155 mg,
0.729 mmol), and the mixture was stirred at room temperature for 24 h. After 24 h compound 5 was consumed as observed by TLC. Solvent was evaporated
79 under reduced pressure, and the residue was dissolved in 10 mL methylene chloride, which was washed twice with water followed by brine, and then passed through anhydrous Na2SO4. The volume of solvent was reduced to 0.5 mL and sufficient pentane was added to precipitate an orange solid. The precipitate was collected and dried. Yield:
1 73.5 mg (83%). H NMR (400 MHz, CDCl3), δ: 8.64 (d, 1H, J = 5.8 Hz), 8.41 (dd, 1H, J
= 5.8, 1.2 Hz), 7.85 (d, 1H, J = 8.0 Hz), 7.80 (d, 1H, J = 8.2 Hz), 7.66 (td, 2H, J = 7.6,
1.7 Hz), 7.57 (dd, 1H, J = 7.8, 1.4 Hz), 7.51 (td, 1H, J = 7.1, 1.1 Hz), 6.98 (d, 1H, J = 7.1
Hz), 6.94-6.73 (m, 7H), 6.67 (td, 1H, J = 7.6, 1.1 Hz), 6.59 (dd, 1H, J = 6.7, 1.9 Hz), 6.52
(dd, 1H, J = 7.1, 1.4 Hz), 6.31 (dd, 1H, J = 7.8, 1.1 Hz), 5.04 (dd, 1H, J = 11.7 Hz), 4.86
(dd, 1H, J = 11.5 Hz), 3.60 (s, 1H, alcoholic broad peak). IR (KBr): ῦ = 3422 (s) cm-1 (O-
+ H br singlet). HRMS: Calcd. For C29H24IrN2O [MH] : 609.1518 Found: 609.1554 Anal.
Calcd. For C29H23IrN2O: C, 57.31; H, 3.81; N, 4.61. Found: C, 57.43; H, 4.04; N, 4.81.
[Ir(F2ppy)2PhMeOH]. In 5 mL 2-propanol were suspended [Ir(F2ppy)2(H2O)2]OTf,
d (120 mg, 0.158 mmol) and compound 5 (23.7 mg, 0.158 mmol). To
this suspension was added K3PO4 (168 mg, 0.792 mmol), and the
mixture was stirred at room temperature for 24 h. Evaporation of
solvent under reduced pressure yielded a dark red-colored residue that was dissolved in methylene chloride. The methylene chloride layer was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. Deep red crystals were collected after crystallization from methylene chloride and pentane, and
1 were dried. Yield: 96 mg (89%). H NMR (400 MHz, CDCl3), δ: 8.63 (d, 1H, J = 6.7
Hz), 8.41 (d, 1H, J = 5.8 Hz), 8.30 (d, 1H, J = 8.8 Hz), 8.21 (d, 1H, J = 6.8 Hz), 7.75 (td,
80 1H, J = 7.5, 1.5 Hz), 7.60 (td, 1H, J = 7.5, 1.5 Hz), 7.04 (d, 1H, J = 6.8 Hz), 7.01 (t, 1H, J
= 5.9 Hz), 6.94 (t, 1H, J = 5.9 Hz), 6.87 (t, 1H, J = 7.3 Hz), 6.81 (t, 1H, J = 6.6 Hz), 6.53
(d, 1H, J = 7.12), 6.40-6.34 (m, 2H), 5.98 (dd, 1H, J = 7.3, 2.4 Hz), 5.67 (dd, 1H, J = 9.6,
2.3 Hz), 5.28 (d, 1H, J = 11.3 Hz), 5.04 (d, 1H, J = 11.6 Hz), 3.58 (s, 1H, alcoholic
-1 broad). IR (KBr): ῦ = 3419 (s) cm (O-H br singlet). HRMS: Calcd. For C29H20F4IrN2O
+ [MH] : 681.1141 Found: 681.1162 Anal. Calcd. For C29H19F4IrN2O: C, 51.25; H, 2.82;
N, 4.12. Found: C, 51.30; H, 2.88; N, 4.23.
[Ir(F2ppy)2TolMeOH]. In 5 mL 2-propanol were suspended [Ir(F2ppy)2(H2O)2]OTf,
d (120 mg, 0.158 mmol) and compound 6 (25.9 mg, 0.158 mmol). To
this suspension was added K3PO4 (168 mg, 0.792 mmol), and the
mixture was stirred at room temperature for 24 h. After 24 h
compound 6 was consumed as observed by TLC. Solvent was evaporated under reduced pressure, and the residue was dissolved in 10 mL methylene chloride, which was washed twice with water followed by brine, and was passed through anhydrous Na2SO4. The volume of solvent was reduced, and sufficient pentane was added to get brick red precipitate. The precipitate was collected and dried. Yield: 88.0 mg
1 (80%). H NMR (400 MHz, CDCl3), δ: 8.60 (d, 1H, J = 5.8 Hz), 8.41 (d, 1H, J = 5.8 Hz),
8.25 (d, 1H, J = 8.9 Hz), 8.20 (d, 1H, J = 8.5 Hz), 7.72 (t, 1H, J = 8.3 Hz), 7.58 (t, 1H, J
= 7.9 Hz), 6.98 (t, 1H, J = 7.2 Hz), 6.91 (d, 2H, J = 7.9 Hz), 6.66 (d, 1H, J = 7.68 Hz),
6.34-6.30 (m, 3H), 5.94 (dd, 1H, J = 7.5, 2.4 Hz), 5.64 (dd, 1H, J = 9.7, 2.3 Hz), 5.16 (d,
1H, J = 11.5 Hz), 4.92 (d, 1H, J = 11.3 Hz), 4.04 (s, 1H, broad signal), 2.05 (s, 3H). IR
-1 + (KBr): ῦ = 3429 (s) cm (O-H br singlet). HRMS: Calcd. For C30H22F4IrN2O [MH] :
81 695.1298 Found: 695.1231 Anal. Calcd. For C30H21F4IrN2O: C, 51.94; H, 3.05; N, 4.04.
Found: C, 52.11; H, 3.19; N, 4.12.
2.4.5. Luminescence Measurements
Steady state emission spectra were recorded at room temperature on a Cary Eclipse fluorescence spectrophotometer. Time resolved phosphorescence lifetime data were collected on a nanosecond laser system. Excitation wavelengths were generated as described previously.72 The emitted light passed through a Triax 320 spectrometer, was dispersed by a blazed grating and detected with a Hamamatsu R928 photomultiplier tube
(PMT). The PMT outputs were collected and averaged with a 1 GHz oscilloscope
(LeCroy 9382CM). Samples for these measurements were prepared in a glovebox containing a dinitrogen atmosphere and housed in sealable quartz EPR tubes. For lifetime measurements at 77 K, the EPR tube was immersed in liquid nitrogen in a quartz finger dewar.
2.5. References
(1) Kalyanasundaram, K. Photochemistry of Polypyridine and Porphyrin complexes.; Academic Press, London, 1992.
(2) Balzani, V.; Scandola, F. Supramolecular Photochemistry.; Ellis Horwood, New York: New York, 1991.
(3) Balzani, V.; Venturi, M.; Credi, A. Molecular DeVices and Machines: A Journey into the Nanoworld.; Wiley-VCH: Weinheim, Germany, 2003.
(4) Holder, E.; Langeveld, B. M. W.; Schubert, U. S. Adv. Mater. 2005, 17, 1109– 1121.
(5) Coe, B. J.; Curati, N. R. M. Comments Inorg. Chem. 2004, 25, 147– 184.
82 (6) Kalyanasundaran, K. Coord. Chem. Rev. 1982, 46, 159.
(7) Tan-Sien-Hee, L.; Mesmaeker, A. K.-D. J. Chem. Soc., Dalt. Trans. 1994, 24, 3651.
(8) Kalyanasundaram, K.; Gratzel, M. M. Coord. Chem. Rev. 1998, 177, 347.
(9) Anderson, P. A.; Anderson, R. F.; Furue, M.; Junk, P. C.; Keene, F. R.; Patterson, B. T.; Yeomans, B. D. Inorg. Chem. 2000, 39.
(10) Li, C.; Hoffman, M. Z. Inorg. Chem. 1998, 37, 830.
(11) Berg-Brennan, C.; Subramanian, P.; Absi, M.; Stern, C.; Hupp, J. T. Inorg. Chem. 1996, 35, 3719.
(12) Patra, S. C.; Weyhermüller, T.; Ghosh, P. Inorg. Chem. 2014, 53, 2427–2440.
(13) G. A. Carlson, P. I. Djurovich and R. J. Watts. Inorg. Chem. 1993, 32, 4483–4484.
(14) M.G. Colombo, A. H. and H. U. G. del. Inorg. Chem. 1993, 32, 3088–3092.
(15) F. O. Garces, K. A. King and R. J. Watts. Inorg. Chem. 1988, 27, 3464–3471.
(16) K. A. King, P. J. Spellane and R. J. Watts. J. Am. Chem. Soc. 1985, 107, 1431– 1432.
(17) Sprouse, S.; King, K. A.; Spellane, P. J.; Watts, R. J. J. Am. Chem. Soc. 1984, 106, 6647.
(18) Crosby, G. A. J. Chim. Phys. 1967, 64, 160.
(19) Montalti, M.; Credi, A.; Prodi, L.; Gandolfi, M. T. Handbook of Photochemistry; CRC Press: Boca Raton, FL, 2006.
(20) Vlček, A., Jr.; Záliš, S. Coord. Chem. Rev. 2007, 251, 258−287.
(21) Ladouceur, S.; Fortin, D.; Zysman-Colman, E. Inorg. Chem. 2010, 49, 5625−5641.
(22) Valore, A.; Cariati, E.; Dragonetti, C.; Righetto, S.; Roberto, D.; Ugo, R.; De Angelis, F.; Fantacci, S.; Sgamellotti, A.; Macchioni, A.; Zuccaccia, D. Chem. Eur. J. 2010, 16, 4814−4825.
(23) Zanoni, K. P. S.; Kariyazaki, B. K.; Ito, A.; Brennaman, M. K.; Meyer, T. J.; Murakami Iha, N. Y. Inorg. Chem. 2014, 53, 4089–4099.
(24) P.-T. Chou and Y. Chi. Eur. J. Inorg. Chem. 2006, 3319.
83 (25) Ho, C.-L.; Wong, W.-Y. New J. Chem. 2013, 37, 1665−1683.
(26) Yun, C.; Chou, P.-T. Chem. Soc. Rev. 2010, 39, 638−655.
(27) Yersin, H., E. Highly Efficient OLEDs with Phosphorescent Materials; Wiley- VCH: Berlin, 2008.
(28) Seo, J. H.; Kim, Y. K.; Ha, Y. Thin Solid Films 2009, 517, 1807−1810.
(29) (2) Endo, A.; Suzuki, K.; Yoshihara, T.; Tobita, S.; Yahiro, M.; Adachi, C. Chem. Phys. Lett. 2008, 460, 155−157.
(30) Fan, C.; Zhu, L.; Liu, T.; Jiang, B.; Ma, D.; Qin, J.; Yang, C. Angew. Chem. Int. Ed. Engl. 2014, 53, 2147–2151.
(31) L. Xiao, Z. Chen, B. Qu, J. Luo, S. Kong, Q. Gong, J. K. Adv. Mater. 2011, 23, 926–952.
(32) Y. Kawamura, K. Goushi, J. Brooks, J.J. Brown, H. Sasabe, C. A. Appl. Phys. Lett. 2005, 86, 071104–1–071104–3.
(33) M.A. Baldo, M.E. Thompson, S. R. F. Nature 2000, 403, 750–753.
(34) Parker, S. T.; Slinker, J. D.; Lowry, M. S.; Cox, M. P.; Bernhard, S.; Malliaras, G. G. Chem. Mater. 17, 3187−3190.
(35) Bolink, H. J.; Cappelli, L.; Coronado, E.; Grätzel, M.; Ortí, E.; Costa, R. D.; Viruela, P. M.; Nazeeruddin, M. K. J. Am. Chem. Soc. 2006, 128, 14786−14787.
(36) Rothe, C.; Chiang, C.-J.; Jankus, V.; Abdullah, K.; Zeng, X.; Jitchati, R.; Batsanov, A. S.; Bryce, M. R.; Monkman, A. P. Adv. Funct. Mater. 2009, 19, 2038−2044.
(37) Fernández-Hernández, J. M.; Yang, C.-H.; Beltrán, J. I.; Lemaur, V.; Polo, F.; Fröhlich, R.; Cornil, J.; De Cola, L. J. Am. Chem. Soc. 2011, 133, 10543−10558.
(38) Costa, R. D.; Ortí, E.; Bolink, H. J.; Monti, F.; Accorsi, G.; Armaroli, N. Angew. Chem., Int. Ed. 2012, 51, 8178−8211.
(39) Demas, J. N.; Harris, E. W.; Flynn, C. M.; Diemente, D. J. Am. Chem. Soc. 1975, 97, 3838−3839.
(40) Gao, R.; Ho, D. G.; Hernandez, B.; Selke, M.; Murphy, D.; Djurovich, P. I.; Thompson, M. E. J. Am. Chem. Soc. 2002, 124, 14828−14829.
(41) G. L. Schulz and S. Holdcroft. Chem. Mater. 2008, 20, 5351–5355.
84 (42) Y. Shinpuku, F. Inui, M. Nakai and Y. Nakabayashi. J. Photochem. Photobiol., A, 2011, 222, 203–209.
(43) Y.-J. Yuan, J.-Y. Zhang, Z.-T. Yu, J.-Y. Feng, W.-J. Luo, J.-H. Y. and Z.-G. Z. Inorg. Chem. 2012, 51, 4123–4133.
(44) Terrett, J. a; Clift, M. D.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136, 6858–6861.
(45) Huo, H.; Fu, C.; Harms, K.; Meggers, E. J. Am. Chem. Soc. 2014, 136, 2990–2993.
(46) Shao, F.; Barton, J. K. J. Am. Chem. Soc 2007, 129, 14733− 14738.
(47) Elias, B.; Shao, F.; Barton, J. K. J. Am. Chem. Soc. 2008, 130, 1152−1153.
(48) K. K.-W. Lo, A. W.-T. C. and W. H.-T. L. Dalt. Trans. 2012, 41, 6021–6047.
(49) Q. Zhao, C. Huang and F. Li. Chem. Soc. Rev. 2011, 40, 2508– 2524.
(50) Y. You, Y. Han, Y.-M. Lee, S. Y. Park, W. N. and S. J. L. J. Am. Chem. Soc. 2011, 133, 11488–11491.
(51) Hsieh, J.-M.; Ho, M.-L.; Wu, P.-W.; Chou, P.-T.; Tsai, T.-T.; Chi, Y. Chem. Commun. 2006, 615−617.
(52) Zhang, G.; Zhang, H.; Gao, Y.; Tao, R.; Xin, L.; Yi, J.; Li, F.; Liu, W.; Qiao, J. Organometallics 2014, 33, 61–68.
(53) Chen, Y.; Qiao, L.; Ji, L.; Chao, H. Biomaterials 2014, 35, 2–13.
(54) Sun, H.; Liu, S.; Lin, W.; Zhang, K. Y.; Lv, W.; Huang, X.; Huo, F.; Yang, H.; Jenkins, G.; Zhao, Q.; Huang, W. Nat. Commun. 2014, 5, 3601.
(55) A. D. Ryabov. Chem. Rev. 1990, 90, 403.
(56) Shul’pin, A. E. S. and G. B. Chem. Rev. 1997, 97, 2879.
(57) H. Werner. Dalt. Trans 2003, 3829.
(58) I. Omae. Coord. Chem. Rev. 2004, 248, 995.
(59) K. Dedeian, P. I. Djurovich, F. O. Garces, G. C. and R. J. W. Inorg. Chem. 1991, 30, 1685.
(60) Tamayo, A. B.; Alleyne, B. D.; Djurovich, P. I.; Lamansky, S.; Tsyba, I.; Ho, N. N.; Bau, R.; Thompson, M. E. J. Am. Chem. Soc. 2003, 125, 7377–7387.
85 (61) K. W. Johnston, A. G. Pattantyus-Abraham, J. P. Clifford, S. H. Myrskog, D. D. MacNeil, L. L. and E. H. S. Appl. Phys. Lett. 2008, 92, 151115.
(62) J. Y. Kim, K. Lee, N. E. Coates, D. Moses, T. Q. Nguyen, M. D. and A. J. H. Science (80-. ). 2007, 317, 222–225.
(63) P. N. Prasad. Introduction to Biophotonics; Wiley Interscience: New York, 2003; Vol. 37, pp. 433–463.
(64) McDaniel, N. D.; Coughlin, F. J.; Tinker, L. L.; Bernhard, S. J. Am. Chem. Soc. 2008, 130, 210–217.
(65) A. E. King, B. L. Ryland, T. C. B. and S. S. S. Organometallics 2012, 31, 7948– 7957.
(66) Swager, T. M. Inorg. Chem. 2011, 50, 7598–7609.
(67) C. Amatore, A. J. and G. L. D. Chem.–Eur. J. 2011, 17, 2492–2503.
(68) B. P. Carrow and J. F. Hartwig. J. Am. Chem. Soc. 2011, 133, 2116–2119.
(69) Liu, J.; Liu, Y.; Liu, Q.; Li, C.; Sun, L.; Li, F. J. Am. Chem. Soc. 2011, 133, 15276–15279.
(70) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chem. Int. Ed. Engl. 2006, 45, 8188–8191.
(71) You, Y.; Nam, W. Chem. Soc. Rev. 2012, 41, 7061–7084.
(72) Seyedsayamdost, M. R.; Reece, S. Y.; Nocera, D. G.; Stubbe, J. J. Am. Chem. Soc. 2006, 128, 1569–1579.
86 Chapter 3 Suzuki–Miyaura Coupling of Arylboronic Acids to Gold(III)
87 This work has been submitted for publication.
3.1. Introduction
The field of gold organometallics has evolved during the past decade. Gold(I) has drawn the most attention1–3 for applications as anticancer prodrugs,4–11 as catalysts for organic transformations,1,12,13 and as luminescent compounds.14–17 Gold(I) is redox- neutral, and catalytic pathways diverge from those of other transition elements, where sequences of oxidative addition and reductive elimination predominate. Gold is sometimes called the relativistic element, and its heavy-atom character18–21 transforms the excited-state character of luminescent gold species.15–17,22–24 Relativistic effects may also modulate the thermal reactivity of gold; this remains a topic of active inquiry.25
The chemistry of gold(III) is less investigated, when compared to gold(I); and is gaining scrutiny.26–30 In recent studies, cyclometalated gold(III) species have attracted particular attention31 because of reported anticancer9,32–35 and photophysical properties.36,37 Contemporary studies indicate that gold(III) aryl complexes are luminescent, with excited states that are often ligand-localized.38 Limitations in synthesis have hindered the emergence of organogold(III) chemistry. A handful of methods available in literature to achieve Au–C σ-bonds are transmetalation reactions from
Grignard,39 organolithium,40,41 tin,42–44 or mercury(II) reagents,45 and oxidative aryl transfer from thallium(III) to gold(I).46 All of these reagents are hazardous, organolithium, and magnesium reagents being pyrophoric, and tin, mercury, thallium complexes being toxic. Substrate scopes are limited. Gold(III) is oxidizing: E°(AuIII/Au0)
= +1.51 V in aqueous acid.47 Its redox character often leads to decomposition in reactions
88 with formal carbanion sources. There is a clear need for wider-ranging nonredox transformations that yield organogold(III) species.
Our interest in a synthetic protocol that would give straightforward access to a novel class of cyclometalated gold(III) organometallics prompted us to investigate the reaction of gold(III) halides with boronic acids under catalytic conditions. Gold-carbon σ-bonds are covalent and modestly polar. The Pauling electronegativities of gold (2.5) and carbon
(2.55) are nearly equal. We therefore, hypothesized that catalytic carbon-carbon bond- forming reactions might extend to carbon-gold bond formation. Among the most powerful are cross-coupling protocols, such as the Suzuki-Miyaura coupling of organoboron species with organic halides and pseudohalides.48,49 This reaction is palladium-catalyzed, and a supporting base is normally required. A frequent challenge is the coupling of aryl chlorides.50 Cross-coupling reactions where the desired product is an organometallic complex are little explored.51,52 As reported here, this strategy has allowed us to obtain direct di-arylation of Au(III) chloride bonds in a Pd-catalysed condition. The reactions proceed at room temperature in presence of base. The resulting gold(III) complexes have been authenticated crystallographically, and the geometry of incomplete aryl transfer reaction product has led us to propose a mechanistic scheme involving two cycles of arylation process involving oxidative addition, transmetalation, aryl transfer from Pd to Au and reductive elimination.
3.2. Results and Discussion
The study of Pd-catalyzed Au(III)-Cl bond arylation was initiated with gold(III) dichloro complex 1 [(tpy)AuCl2] with p-fluorophenylboronic. [(tpy)AuCl2] was chosen
89 due to its robustness, and p-fluorophenylboronic provides a 19F NMR-spectroscopic handle to monitor the reaction.
Table 3.2.1. Optimization of reaction conditions for di-arylation of dichlorogold(III) complexes.a
Entry Catalyst Ligand (L) Base Time Yield (%)b (h) Mono Di 1 Pd(PPh3)4 None Cs2CO3 24 60 30 2 Pd(PPh3)4 None Cs2CO3 48 0 85 3 Pd(PPh3)4 None K2CO3 16 51 0 4 Pd(OAc)2 None K2CO3 16 90 0 5 Pd(OAc)2 PPh3 K2CO3 16 38 0 t 6 Pd(OAc)2 P Bu3 K2CO3 16 40 60 c 7 Pd2dba3 Xphos K2CO3 16 50 44 c 8 Pd(dppf)Cl2 dppf K2CO3 16 27 0 c 9 Pd(OAc)2 dcpe K2CO3 16 34 0 t 10 PdCl2 P Bu3 K2CO3 16 31 0 11 Pd(OAc)2 PCy3 K2CO3 16 49 0 t 12 Pd(OAc)2 P Bu3 NaOMe 16 12 47 t 13 Pd(OAc)2 P Bu3 KOH 16 25 25 t n 14 Pd(OAc)2 P Bu3 Bu4NF 16 0 0 t 15 Pd(OAc)2 P Bu3 K3PO4 16 0 88 16 Pd2dba3 PCy3 K3PO4 16 5 86 t 17 Pd(OAc)2 [HP( Bu)3]BF4 K3PO4 16 0 90 t 18 None [HP( Bu)3]BF4 K3PO4 16 0 0 aConditions: Experiments were performed with 1 (0.05 mmol), 2 (0.125 mmol), Pd catalyst (0.002 mmol), ligand (0.007 mmol), base (0.2 mmol), toluene (5 mL), rt. bYields 19 c are based on F NMR relative to C6H5F as an internal standard. Xphos = tricyclohexyl(2ʹ,4ʹ,6ʹ-triisopropyl-[1,1ʹ-biphenyl]-2-yl)-4-phosphane; dppf = 1,6-bis- (diphenylphosphino)ferrocene; dcpe = 1,2-bis(dicyclohexylphosphino)ethane.
90 No reaction occurs between 1 and boronic acids without additives. Reactions were screened with a variety of palladium sources, phosphine ligands, and supporting bases; di-aryl complexes are targeted. Table 3.2.1 summarizes outcomes. Formation of product was monitored by multinuclear NMR spectroscopy. Most indicative is the 19F NMR signal at δ = –118.4 ppm corresponding to mono and δ = –120.4 and –119.4 ppm corresponding to the bis arylated product.
All reactions proceeded at room temperature, in contrast to the high-temperature (150
°C) transmelatations of Nevado and coworkers.53 They contrast also with previously described boron transmetalation to gold(I), for which palladium additives are needless.54–
57 Reaction between 1 and p-fluorophenylboronic acid in the presence of Pd(PPh3)4 and
Cs2CO3 in toluene led, after 24 h, to a mixture of mono- (60%) and di(p-fluorophenyl)
(30%), as estimated by 19F nuclear magnetic resonance (NMR) spectroscopy, Table
3.2.1, entry 1. The diaryl is the exclusive product after 48 h, and shows 19F singlets at δ –
120.4 and –119.4 ppm, Table 3.2.1, entry 2. A similar reaction using K2CO3 as base led to 51% mono-aryl product, Table 3.2.1, entry 3. The mono-aryl product is recovered in
90% yield without added ligand, showing that L is not obligatory for the first coupling;
Table 3.2.1, entry 4. A reaction with Pd(OAc)2, tri-(t-butylphosphine), and K2CO3 gave mono- and diaryl products in 40% and 60% yields, respectively, Table 3.2.1, entry 6.
Changing the supporting base to K3PO4 afforded diaryl product in 88% yield after 16 h; no mono-aryl product was observed; Table 3.2.1, entry 15. Use of the air- and moisture-
t stable phosphonium salt [HP( Bu)3]BF4 gave the di-arylated gold(III) complex in unimpaired yields, Table 3.2.1 entry 17; and allowed reaction components to be weighed under ambient laboratory conditions. (However, reactions proceeded under an argon
91 atmosphere.) Use of the stronger bases NaOMe and KOH gave diminished yields of both products, Table 3.2.1 entries 12 and 13. No reaction was observed in the presence of
n anhydrous Bu4NF, Table 3.2.1 entry 14.
Table 3.2.2. Screening of bases and solvents for di-arylation of dichloro-gold(III) complexes.a
Entry Base Solvent Time (h) Yield (%)b Mono Di
1 K3PO4 1,4-dioxane 16 0 0
2 K3PO4 DMF 16 0 0
i 3 K3PO4 1% PrOH in toluene 16 10 70
4 K3PO4 1% EtOH in toluene 16 30 60
5 K3PO4 THF 16 50 50
6 Li3PO4 Toluene 16 0 0
7 KOH Toluene 16 30 10
8 K2CO3 10% H2O in THF 16 0 0
i 9 K3PO4 1:1 toluene/ PrOH 4 0 82
i 10 K2CO3 1:1 toluene/ PrOH 10 0 85 aConditions: Experiments were performed with 1 (0.05 mmol), 2 (0.125 mmol), t Pd(OAc)2 (0.002 mmol), [HP( Bu)3]BF4 (0.007 mmol), base (0.2 mmol), indicated b 19 solvent/solvent mixture (5 mL), rt. Yields are based on F NMR relative to C6H5F as internal standard.
The reaction accelerated with addition of 2-propanol. Adding 1% of 2-prpanol in toluene led to 70% di-arylated product along with 10% mono-arylated product after 16 h,
Table 3.2.2 entry 3. In 1:1 mixture of 2-propanol and toluene with K2CO3 as supporting
92 base, the reaction was complete in 10 h, Table 3.2.2 entry 10. With K3PO4 as base, the reaction was completed in 4 h, Table 3.2.2, entry 9. However, when the reaction was performed in toluene, DMF or 1,4-dioxane, only the starting materials were isolated,
Table 3.2.2 entry 1, 2 and 6. The reaction conditions described in Table 3.2.2, entry 10, involving K2CO3 were chosen for subsequent work for its higher yield across a variety of boronic acid substrates.
The standardized protocol was applied to the synthesis of a range of gold(III) aryls,
Table 3.2.3. Aryl groups with electron-withdrawing such as fluorine or nitro groups (3a–
3f), electron-neutral such as aryl groups (3g–3l) and electron- releasing substituents such as p- methoxy, -isopropoxy groups (3m–3o) were bound to gold. Isolated yields range from 42%–78%. Efficiencies are comparable for boronic acids with electron- withdrawing or releasing substituents. Sensitive functional groups such as 4- acetylphenyl, ester groups, which often react with lithium reagents, are tolerated.
Organogold complexes are readily prepared having oxidized substituents that, like gold(III) itself, degrade on treatment with lithium reagents or other formal carbanion sources. The products are purified by column chromatography on basic alumina, and are stable as solids to air and water.
The reaction is specifically arylates in exchange of boron. Complexes 3a, 3c, 3d, 3j,
3l, and 3n were characterized by X-ray diffraction crystallography. They are shown in
Figure 3.2.1 to Figure 3.2.3. In each structure, p-tolylpyridyl ligand acts as a bidentate spectator ligand. Geometric parameters about the metal are within ranges typical of
Au(III).58 Trans-influences of carbon and nitrogen are evident in gold–aryl carbon bond distances. In all instances, the Au–C bond trans to carbon is significantly longer59 than
93 that trans to nitrogen.
Table 3.2.3. Gold(III) products and isolated yields. Carbon-gold bonds formed are indicated in red. Et = ethyl; Ph = phenyl.
94 a)
b) c)
Figure 3.2.1. a) Crystal structure of 3a, b) Crystal structure of 3c, c) Crystal structure of 3d. All are showing 50% probability ellipsoids and hydrogen atoms are omitted for clarity. Crystal structures were collected by Dr. M. Zeller, Yougstown State University.
While surveying reaction parameters for diarylation, mono-arylated products were isolated. Complexes 4a and 4b were isolated as products of incomplete aryl transfer.
95 a)
b)
Figure 3.2.2. a) Crystal structure of disordered 3j, b) Crystal structure of 3l. Both are showing 50% probability ellipsoids and hydrogen atoms are omitted for clarity. Crystal structures were collected by Dr. M. Zeller, Yougstown State University.
1H NMR experiments show that both products form as a single isomer, arylation has
occurred trans to pyridyl-nitrogen. The crystal structure of 4a appears as Figure 3.2.3.
(b) and that of 4b as Figure 3.2.3. (c). The p-fluorophenyl ligand binds trans to the
pyridyl nitrogen despite the kinetic trans effect. Nevertheless, the observed structure of
96 a)
b) c)
Figure 3.2.3. a) Crystal structure of 3n, b) Crystal structure of 4a. Unlabeled atoms are carbon. Selected interatomic distances (Å): C11–Au, 2.023(4); Au–N, 2.116(3); C13–Au, 2.018(4); Au– Cl, 2.3707(9). Selected angles (°): N–Au–C11, 81.05(14); C13–Au–Cl: 91.07(10). c) Crystal structure of 4b. All are showing 50% probability ellipsoids and hydrogen atoms are omitted for clarity. Crystal structures were collected by Dr. M. Zeller, Yougstown State University.
4a is expected to be more stable than its diastereomer where p-fluorophenyl binds opposite carbon.
The stereochemistry of 4a and 4b is surprising in that square-planar d8 complexes tend not to rearrange. If arylation proceeds in a single step, then the shorter Au–Cl bond
97 ostensibly breaks first. Attempts to grow single crystals of 1 failed. However, the
structure of the related complex dichloro(2-(4-fluorophenyl)pyridine)gold(III) was
obtained. This complex differs from 1 in that fluorine substitutes for methyl in the C^N
ligand. The structure (Figure 3.2.4) shows a longer Au–Cl bond trans to carbon.
Pertinent interatomic distances are 2.3750(15) Å for Au–Cl trans to C and 2.2721(17) Å
for Au–Cl trans to N. Thus, the shorter Au–Cl bond opposite nitrogen is sacrificed in the
first arylation. The aryl ligands in 4a and 4b are opposite nitrogen. We propose
transmetalation by an associative or associative interchange mechanism, possibly
Figure 3.2.4. Crystal structure of dichloro(2-(4-fluorophenyl)pyridine)gold(III) (1a) showing 50% probability ellipsoids. Hydrogen atoms are omitted for clarity.
mediated by palladium, that avoids mutually trans carbon atoms and leads to the
thermodynamic isomers 4a and 4b.
Reactions under standard conditions of 1 with (2-acetylphenyl)boronic acid yielded
the singly arylated 4c. 1H and 13C NMR experiment indicate a single species in solution,
not a mixture, suggesting that the reaction is specific for 4c. This complex is a C-bound
enolate stabilized by chelation of the benzene ring. The pKa of acetophenone is 24.7 in
dimethyl sulfoxide.60 Deprotonation of the α-carbon atom may simply result from the
98 action of base. Vapor diffusion of pentane into dichloromethane solution afforded diffraction-quality crystals. The structure of 4c appears in Figure 3.2.5. The sp3- hybridized carbon atom lies trans to the pyridyl nitrogen of the tpy ligand. A ν(CO) stretching frequency at 1666 cm–1 and a 13C{1H} NMR resonance at δ 209 ppm both indicate retention of the C-bound enolate geometry. It is noteworthy that gold(III) binds to the softer carbon, rather than oxygen, as is common for oxidized metals of the earlier d-block.61,62
Figure 3.2.5. Crystal structure of 4c showing 50% probability ellipsoids. Hydrogen atoms are omitted for clarity. Unlabeled atoms are carbon. Selected interatomic distances (Å): C11–Au, 2.058(5); Au–N, 2.134(4); C13–Au, 2.080(5); C20–Au, 2.041(6). Selected angles (°): N–Au– C11, 79.62(18); C13–Au–C20, 80.8(2).
A potential mechanism for the formation of 3a–o appears in Scheme 3.2.1. Oxidative addition of 1 to palladium(0) occurs at the longer Au–Cl bond trans to carbon (right cycle). Formation of a palladium alkoxide or hydroxide intermediate occurs before transmetalation from boron, in keeping with results from Hartwig, Amatore, Jutand, and their respective co-workers.63–65 Aryl migration66 from palladium to gold follows.
Scheme 3.2.1 shows a chloro ligand transferring to palladium, but this is speculative; chloride may remain outer-sphere. Reductive elimination yields monosubstituted
99 products with the stereochemistry established for 4a and 4b. Singly arylated products can then re-enter the catalytic process (left cycle), undergo transmetalation and reductive elimination, and emerge as di-aryls. Experiments that test this hypothesis are underway.
Scheme 3.2.1. Proposed mechanism of gold(III) monoarylation (right cycle) and subsequent di- arylation (left cycle).
3.3. Conclusion
We report catalytic arylation of gold(III) through Suzuki-Miyaura couplings at room- temperature. The reaction is palladium-mediated and requires an assisting base; the electrophilic reacting partner is a cyclometalated gold(III) dichloro complex. Screening experiments show that palladium(II) acetate is an effective catalyst precursor when combined with potassium phosphate and tri-(t-butylphosphine). The phosphine is conveniently delivered as an air- and moisture-stable phosphonium tetrafluoroborate salt.
Variously substituted arylboronic acids couple to gold in similar yields. An ortho- substituted enolizable ketone leads to a C-bound enolate, without continuing to form a
100 diaryl. Spectroscopic characterization of the enolate complex indicates that a single product forms. Crystal-structure determination shows that the sp3-hybridized carbon binds opposite the pyridyl nitrogen, and a phenyl carbon binds trans to the tolyl carbon of the C^N ligand.
Compounds 4a and 4b are singly arylated products that were characterized structurally. Spectral data indicate a single isomer of each in solution. Both crystal structures show aryl substitution trans to the C^N nitrogen atom. This stereospecificity is counterintuitive given the trans-influence of carbon: the shorter Au–Cl bond disappears first. We propose that oxidative addition of an Au–Cl bond to palladium happens trans to the tolyl carbon of the C^N ligand. Aryl migration from palladium to gold displaces a chloro ligand and forms a gold-carbon bond trans to nitrogen. Reductive elimination generates monoaryls of the observed stereochemistry and liberates palladium.
The monoaryl product, if not isolated, can then re-enter the catalytic sequence to yield diaryls.
In conclusion, the results described herein demonstrate that cyclometalated gold(III) dichloride can undergo a Suzuki-Miyaura type arylation with a variety of boronic acids under palladium catalysis. Presence of palladium and base are essential. Presence of alcoholic solvent reduces the reaction time to 6 h. To the best of our knowledge such Pd- catalyzed Au(III)-Cl bond activation is the first example of metal-carbon bond formation by Pd-catalysis. The photophysical properties of gold(III) aryls are being investigated.
Future work will also seek to extend this protocol to other metals.
101 3.4. Experimental Section
3.4.1. Materials and Methods
All experimental procedures involving air- or moisture-sensitive substances were performed under argon using Schlenk line techniques or in a nitrogen-filled MBraun drybox. The toluene used for the arylation reactions was degassed by purging with argon for 45 min and then dried with a MBraun solvent purification system comprising column containing activated alumina. Other anhydrous solvents were purchased from Sigma-
Aldrich. TLC plates were visualized by ultraviolet light and cerium molybdate staining solution. Analytical thin layer chromatography was carried out using glass bedded
Whatman silica gel UV254, 0.25 mm plates. Column chromatography was performed using activated basic alumina, ∼150 mesh, 58 Å (Aldrich).
1H NMR experiments are performed on a Varian-400 FT NMR spectrometer operating at 399.7 MHz. 1H chemical shifts are reported in parts per million (δ) with integration and multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, dt = doublet of triplets, td = triplet of doublets, ddd = doublet of doublets of doublets and m = multiplet), measured from tetramethylsilane (0 ppm) and are referenced
13 1 to residual solvent in CDCl3 (7.26 ppm), C6D6 (7.15) or CD2Cl2 (5.32 ppm). C{ H}
NMR spectra were recorded on a Varian INOVA AS-600 spectrometer operating at 150.0
MHz. 13C NMR chemical shifts are reported in parts per million (δ), measured from tetramethylsilane (0 ppm) and are referenced to solvent residuals in CDCl3 (77.00 ppm).
19F NMR spectra were recorded on a Varian INOVA AS-400 spectrometer operating at
376.1 MHz. 19F NMR chemical shifts are reported in parts per million (δ) and measured from CFCl3 (0.00 ppm) or C6H5F (–113.15 ppm) as reference. Solvents were degassed by
102 bubbling argon for 20 min prior to use for UV/Vis and luminescence measurements.
UV/Vis and luminescence data were recorded using a Cary 5G UV/Vis/NIR spectrometer and a Cary Eclipse spectrometer, respectively. Elemental analyses were carried out by
Robertson Microlit Laboratories, Ledgewood, NJ. Caution: Safety precautions, including use of a blast shield, are recommended for reactions run under pressure.
All reagents were purchased from commercial sources and used without further purification. HAuCl4·H2O was purchased from Strem Chemicals; 2-(p-tolyl)pyridine was purchased from Sigma-Aldrich; all boronic acids were purchased from Sigma-Aldrich,
Acros Organics, Oakwood Chemicals and Frontier Scientific. Pd-catalysts and phosphine ligands were purchased from Strem Chemicals and Sigma-Aldrich; and were used as received. K2CO3 was purchased from Sigma-Aldrich and K3PO4 from Strem Chemicals.
3.4.2. Synthesis of [(C^N)AuCl2]
Synthesis of [(tpy)AuCl2] (tpy = 2-(p-tolyl)pyridine), 1: (tpy)AuCl2 was synthesized with a slight modification of literature procedure.67 A high-pressure flask was used in place of microwave heating. Into a high-pressure reaction flask, equipped with a stir bar, was added HAuCl4·H2O (1.015 g, 2.990 mmol) followed by 10 mL deionized water. To this was added a solution of 2-(p-tolyl)pyridine (tpy) (0.57 mL, 3.330 mmol) in
2 mL acetonitrile. A yellow precipitate formed immediately. The reaction mixture was warmed at 60 °C for 30 min. After cooling, the yellow precipitate was collected by filtration and was washed thoroughly with water. The crude product was again loaded back into the high-pressure reaction flask followed by 10 mL of 1:1 (v/v) acetonitrile and water. After securely closing the cap of the vessel, the reaction mixture was heated at 180
103 °C for 12 h. After cooling down to room temperature, the precipitate was collected as off- white solid by filtration. The precipitate was washed with methanol and diethyl ether.
Drying under vacuum yielded analytically pure product. Yield: 0.88 g (68%). 1H NMR is
67 reported elsewhere; analysis (calcd., found for C12H10AuCl2N): C (33.05, 33.34), H
(2.31, 2.59), N (3.21, 3.47).
Synthesis of [(Fppy)AuCl2] (Fppy = 2-(4-fluorophenyl)pyridine), 1a: (Fppy)AuCl2 was synthesized following the procedure described above. A high-pressure flask was used in place of microwave heating. Into a high-pressure reaction flask, equipped with a stir bar, was added HAuCl4·H2O (974 mg, 2.866 mmol) followed by 10 mL deionized water. To this was added a solution of 2-(4-fluorophenyl)pyridine (Fppy) (546 mg, 3.153 mmol) in 2 mL acetonitrile. A yellow precipitate formed immediately. The reaction mixture was warmed at 60 °C for 30 min. After cooling, the yellow precipitate was collected by filtration and was washed thoroughly with water. The crude product was again loaded back into the high-pressure reaction flask followed by 10 mL of 1:1 (v/v) acetonitrile and water. After securely closing the cap of the vessel, the reaction mixture was heated at 180 °C for 12 h. After cooling down to room temperature, the precipitate was collected as off-white solid by filtration. The precipitate was washed with methanol and diethyl ether. Drying under vacuum yielded analytically pure product. Yield: 656 mg
(52%); 1H NMR (400 MHz, DMSO): δ 9.47 (d, J = 5.9 Hz, 1H), 8.40-8.38 (m, 2H), 8.15
(t, J = 5.9, 1H), 7.76 (t, J = 5.3 Hz, 1H), 7.57 (dd, J = 5.3, 1.8 Hz, 1H), 7.42 (td, J = 8.0,
2.1 Hz, 1H); 19F NMR (376.1 MHz, DMSO): δ –103.8 (m, 1F); analysis (calcd., found for C11H7AuCl2FN): C (30.02, 30.21), H (1.60, 1.94), N (3.18, 3.34).
104 3.4.3. Synthesis of [(tpy)Au(aryl)2]
[(tpy)Au(p-C6H5F)2], 3a: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in 10 mL dry toluene under argon. To this was added [HP(t-
Bu)3]BF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol). A pale yellow solution resulted, which was stirred for 5 min at room temperature under argon. To the flask was added (tpy)AuCl2 (100 mg, 0.229 mmol) followed by 4-fluorophenylboronic acid (80.2 mg, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of
Celite. The volume of solvent was reduced and the mixture was passed through a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether
(1:3, v/v). The desired product eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 96 mg
1 (76%); TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.68; H NMR (400 MHz, CD2Cl2):
δ 8.06 (dt, J = 5.9, 1.0 Hz, 1H), 7.95 (d, J = 4.7 Hz, 2H), 7.71 (d, J = 8.1 Hz, 1H), 7.45
(d, J = 6.7 Hz, 1H), 7.43 (d, J = 6.5 Hz, 1H), 7.40 (d, J = 6.1 Hz, 1H), 7.37 (d, J = 6.1 Hz,
1H), 7.18 (q, J = 2.6 Hz, 1H), 7.09 (dd, J = 8.1, 1.2 Hz, 1H), 7.02–6.90 (m, 4H), 6.78 (d,
19 J = 1.1 Hz, 1H), 2.22 (s, 3H); F NMR (376.1 MHz, CDCl3): δ –119.4 (m, 1F), –120.4
-1 -1 (m, 1F); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 272 (sh, 31000), 329
(12000); emission (methylene chloride): λex, nm (Int.) 467 (170), 494 (199); analysis
(calcd., found for C24H18AuF2N): C (51.90, 52.21), H (3.27, 3.31), N (2.52, 2.88).
105 [(tpy)Au(2,4-difluorophenyl)2], 3b: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon.
(tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture, followed by
2,4-difluorophenylboronic acid (90.5 mg, 0.573 mmol) and 2-propanol (10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. Upon completion, as indicated by TLC, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear yellow solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 76 mg (56%); TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.70;
1 H NMR (400 MHz, CD2Cl2): δ 8.13–8.06 (m, 1H), 8.00–7.93 (m, 2H), 7.69 (d, J = 8.25
Hz, 1H), 7.49–7.32 (m, 2H), 7.22–7.18 (m, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.86–6.71 (m,
19 4H), 6.68–6.65 (m, 1H), 2.21 (s, 3H); F NMR (376.1 MHz, CD2Cl2): δ –93.52 (s, 1F), –
95.97 (s, 1F), –117.51 (s, 1F), –118.55 (s, 1F); UV/Vis (methylene chloride): λmax, nm (ε,
-1 -1 M cm ) 270 (sh, 42000), 330 (14000); emission (methylene chloride): λex, nm (Int.) 468
(149), 495 (172); analysis (calcd., found for C24H16AuF4N): C (48.75, 48.94), H (2.73,
2.80), N (2.37, 2.61).
106 [(tpy)Au(4-(trifluoromethyl)phenyl)2], 3c: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (15 mL) inside a 100-mL argon-filled Schlenk flask. To this was
t added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon. (tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture, followed by 4-(trifluoromethyl)phenylboronic acid (109 mg, 0.573 mmol) and 2-propanol
(10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. After the completion of the reaction, as indicated by TLC, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear solution. Removal of solvent under reduced pressure rendered an off-white solid which was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 112 mg (75%); TLC (hexanes:diethyl ether,
1 40:60 v/v): Rf = 0.65; H NMR (400 MHz, CD2Cl2): δ 8.00 (d, J = 5.5 Hz, 1H), 7.98–
7.96 (m, 2H), 7.71 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 7.7 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H),
7.48 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.22–7.18 (m, 1H), 7.10 (d, J = 8.1 Hz,
19 1H), 6.72 (s, 1H), 2.21 (s, 3H); F NMR (376.1 MHz, CD2Cl2): δ –63.01 (s, 3F), –63.05
-1 -1 (s, 3F); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 272 (sh, 22000), 329 (8000); emission (methylene chloride): λex, nm (Int.) 466 (182), 495 (210); analysis (calcd., found for C26H18AuF6N): C (47.65, 47.71), H (2.77, 2.85), N (2.14, 2.27).
107 [(tpy)Au(3-nitrophenyl)2], 3d: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011
t mmol) was dissolved in 12 mL dry toluene under argon. To this was added P Bu3·HBF4
(9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added (tpy)AuCl2 (100 mg, 0.229 mmol), followed by 3-nitrophenylboronic acid (95.7 mg, 0.573 mmol) and 12 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 20 mL methylene chloride and passed through a plug of Celite. The volume of the solvent was reduced and finally purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:3, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 103 mg (74%); TLC
1 (hexanes:diethyl ether, 40:60 v/v): Rf = 0.40; H NMR (400 MHz, CD2Cl2): δ 8.35 (dd, J
= 2.5, 0.9 Hz, 1H), 8.29 (dd, J = 1.3, 1.0 Hz, 1H), 7.99–7.98 (m, 3H), 7.92 (t, J = 8.5 Hz,
2H), 7.86 (dt, J = 7.5, 1.0 Hz, 1H), 7.81 (dt, J = 7.4, 1.0 Hz, 1H), 7.71 (d, J = 8.2 Hz,
1H), 7.42 (t, J = 7.5 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.21–7.18 (m, 1H), 7.11 (d, J = 7.5
-1 -1 Hz, 1H), 6.65 (s, 1H), 2.19 (s, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M cm )
272 (31000), 324 (13000); emission (methylene chloride): λex, nm (Int.) 486 (73); analysis (calcd., found for C24H18AuN3O4): C (47.30, 47.55), H (2.98, 3.11), N (6.90,
7.29).
108 [(tpy)Au(3-ethoxycarbonylphenyl)2], 3e: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was
t added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon. (tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture followed by 3-ethoxycarbonylphenylboronic acid (111 mg, 0.573 mmol) and 2-propanol
(10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. After the completion of the reaction, as indicated by TLC, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear yellow solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 117 mg (77%); TLC (hexanes:diethyl ether,
1 40:60 v/v): Rf = 0.41; H NMR (400 MHz, CD2Cl2): δ 8.18 (t, J = 1.2 Hz, 1H), 8.11 (t, J
= 1.6 Hz, 1H), 8.01 (dt, J = 5.4, 1.1 Hz, 1H), 7.96 (d, J = 1.3 Hz, 1H), 7.95 (t, J = 1.2 Hz,
1H), 7.74–7.70 (m, 4H), 7.66 (dt, J = 7.7, 1.4 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.24 (t, J
= 7.7 Hz, 1H), 7.16 (q, J = 4.4 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 6.71 (s, 1H), 4.32 (q, J
= 3.9 Hz, 2H), 4.29 (q, J = 3.2 Hz, 2H), 2.19 (s, 3H), 1.35 (t, J = 7.0 Hz, 3H), 1.34 (t, J =
-1 -1 7.1 Hz, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 273 (22000), 330
(10000); emission (methylene chloride): λex, nm (Int.) 466 (136), 495 (162); analysis
(calcd., found for C30H28AuNO4): C (54.31, 54.59), H (4.25, 4.33), N (2.11, 2.38).
109 [(tpy)Au(4-acetylphenyl)2], 3f: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (15 mL) inside a 100-mL argon-filled Schlenk flask. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon.
(tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture followed by
4-acetylphenylboronic acid (94 mg, 0.573 mmol) and 2-propanol (10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. After completion of the reaction, as indicated by TLC, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 20 mL of methylene chloride and filtered through Celite to obtain a clear solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:9, v/v). The desired product was eluted using hexanes/diethyl ether (1:9, v/v).
Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield:
1 78 mg (57%); TLC (hexanes:diethyl ether, 10:90 v/v): Rf = 0.55; H NMR (400 MHz,
CD2Cl2): δ 8.02 (br s, 1H), 7.98–7.96 (m, 2H), 7.80 (d, J = 8.1 Hz, 2H), 7.73 (t, J = 6.4
Hz, 3H), 7.64 (d, J = 6.4 Hz, 2H), 7.59 (d, J = 6.4 Hz, 2H), 7.18 (t, J = 5 Hz, 1H), 7.10
(d, J = 7.4 Hz, 1H), 6.74 (s, 1H), 2.53 (s, 3H), 2.52 (s, 3H), 2.20 (s, 3H); UV/Vis
-1 -1 (methylene chloride): λmax, nm (ε, M cm ) 329 (8000); emission (methylene chloride):
λex, nm (Int.) 465 (141), 494 (167); analysis (calcd., found for C28H24AuNO2): C (55.73,
55.84), H (4.01, 4.29), N (2.32, 2.53).
110 [(tpy)Au(phenyl)2], 3g: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011 mmol)
t was dissolved in 10 mL of dry toluene under argon. To this was added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added
(tpy)AuCl2 (100 mg, 0.229 mmol) followed by phenylboronic acid (70 mg, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 8 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced and finally purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 78 mg (66%); TLC (hexanes:diethyl ether,
1 40:60 v/v): Rf = 0.42; H NMR (400 MHz, CD2Cl2): δ 8.09 (dt, J = 5.6, 1.3 Hz, 1H),
7.94–7.92 (m, 2H), 7.70 (d, J = 8.1 Hz, 1H), 7.48 (d, 7.7 Hz, 2H), 7.43 (d, J = 8.2 Hz,
2H), 7.22 (t, J = 7.41 Hz, 2H), 7.18–713 (m, 3H), 7.05 (q, J = 6.9 Hz, 3H), 6.81 (s, 1H),
-1 -1 2.21 (s, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 328 (17000); emission
(methylene chloride): λex, nm (Int.) 464 (82), 493 (97); analysis (calcd., found for
C24H20AuN): C (55.50, 55.73), H (3.88, 4.19), N (2.70, 2.92).
[(tpy)Au(2-naphthyl)2], 3h: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was added
111 t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon.
(tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture followed by
2-naphthylboronic acid (98.6 mg, 0.573 mmol) and 2-propanol (10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. After the completion of the reaction, as indicated by TLC, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in
10 mL methylene chloride and filtered through Celite to obtain a clear yellow solution.
Removal of solvent under reduced pressure rendered an off-white solid which was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 103 mg (73%); TLC (hexanes:diethyl ether, 40:60
1 v/v): Rf = 0.64; H NMR (400 MHz, CD2Cl2): δ 8.11 (d, J = 5.7 Hz, 1H), 8.00–7.91 (m,
4H), 7.75–7.67 (m, 8H), 7.61 (d, J = 8.4 Hz, 1H), 7.40–7.31 (m, 4H), 712–7.07 (m, 2H),
6.85 (s, 1H), 2.14 (s, 3H); analysis (calcd., found for C32H24AuN): C (62.04, 62.18), H
-1 -1 (3.90, 4.15), N (2.26, 2.35); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 273 (sh,
70000), 323 (22000); emission (methylene chloride): λex, nm (Int.) 369 (771).
[(tpy)Au(2-anthracenyl)2], 3i: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011
t mmol) was dissolved in 15 mL dry toluene under argon. To this was added P Bu3·HBF4
(9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was
112 added (tpy)AuCl2 (100 mg, 0.229 mmol), followed by 2-anthraceneboronic acid (127 mg,
0.573 mmol) and 15 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 24 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced. The product was purified on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a yellow solid, which was dried under vacuum for 6 h. Yield: 69 mg (42%);
1 TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.53; H NMR (400 MHz, C6D6): δ 8.44 (s,
1H), 8.31 (s, 1H), 8.26 (s, 1H), 8.19–8.18 (m, 2H), 8.11 (s, 1H), 8.09 (d, J = 5.6 Hz, 1H),
7.99 (d, J = 8.8 Hz, 1H), 7.88 (d, J = 4.5 Hz, 2H), 7.85–7.72 (m, 2H), 7.52 (s, 1H), 7.40
(d, J = 7.9 Hz, 1H), 7.35 (s, 2H), 7.23–7.20 (m, 3H), 7.10–7.05 (m, 2H), 6.98–6.95 (m,
2H), 6.74 (t, J = 8.4 Hz, 1H), 5.95 (t, J = 6.8 Hz, 1H), 1.94 (s, 3H); UV/Vis (methylene
-1 -1 chloride): λmax, nm (ε, M cm ) 298 (64000), 315 (52000), 367 (19000), 387 (15000); emission (methylene chloride): λex, nm (Int.) 433 (457), 459 (527); analysis (calcd., found for C40H28AuN): C (66.76, 66.91), H (3.92, 4.18), N (1.95, 2.30).
[(tpy)Au(benzo[b]thien-2-yl)2], 3j: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg,
0.011 mmol) was dissolved in 10 mL of dry toluene under argon. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this
113 flask was added (tpy)AuCl2 (0.100 g, 0.229 mmol) followed by benzo[b]thien-2- ylboronic acid (102 mg, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure.
The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced and finally purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted with hexanes/diethyl ether (1:2, v/v).
Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield:
1 98 mg (68%); TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.44; H NMR (400 MHz,
CD2Cl2) δ 8.36 (d, J = 5.8 Hz, 1H), 8.01–7.94 (m, 2H), 7.78–7.70 (m, 5H), 7.29 (s, 1H),
7.26–7.19 (m, 4H), 7.15 (t, J = 8.0 Hz, 3H), 7.04 (s, 1H), 2.21 (s, 3H). UV/Vis
-1 -1 (methylene chloride): λmax, nm (ε, M cm ) 333 (22000); emission (methylene chloride):
λex, nm (Int.) 378 (405), 462 (48); analysis (calcd., found for C28H20AuNS2): C (53.25,
53.41), H (3.19, 3.30), N (2.22, 2.37).
[(tpy)Au(m-tolyl)2], 3k: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011 mmol)
t was dissolved in 10 mL of dry toluene under argon. To this was added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added
(tpy)AuCl2 (100 mg, 0.229 mmol) followed by m-tolylboronic acid (78 mg, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive
114 freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced and finally purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 90 mg (72%); TLC (hexanes:diethyl ether,
1 40:60 v/v): Rf = 0.78; H NMR (400 MHz, CD2Cl2): δ 8.06 (dt, J = 5.4, 1.3 Hz, 1H), 7.93
(d, J = 1.3 Hz, 1H), 7.93–7.92 (m, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.32–7.26 (m, 3H), 7.22
(d, J = 7.4 Hz, 1H), 7.18–7.02 (m, 4H), 6.87 (d, J = 7.6 Hz, 2H), 6.82 (s, 1H), 2.31 (s,
-1 -1 3H), 2.29 (s, 3H), 2.21 (s, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 330
(18000); emission (methylene chloride): λex, nm (Int.) 464 (95), 491 (112); analysis
(calcd., found for C26H24AuN.CH2Cl2): C (51.28, 51.39), H (4.14, 4.35), N (2.21, 2.46).
[(tpy)Au(o-tolyl)2], 3l: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene
t (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon. (tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture, followed by o-tolylboronic acid (78 mg, 0.573 mmol) and 2-propanol (10 mL). The reaction mixture was degassed with three successive freeze-pump-thaw cycles and stirred at room temperature for 24 h.
After completion of the reaction, as indicated by TLC, the solvent was evaporated under
115 reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear yellow solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 76 mg
1 (61%); TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.75; H NMR (400 MHz, CD2Cl2):
δ 7.94 (m, 3H), 7.71 (dd, J = 7.91, 1.9 Hz, 1H), 7.51 (d, J = 5.9 Hz, 1H), 7.43–7.27 (m,
1H), 7.15–6.90 (m, 8H), 6.63 (d, J = 5.9 Hz, 1H), 2.50 (s, 3H), 2.40 (s, 3H), 2.17 (s, 3H);
-1 -1 UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 329 (17000); emission (methylene chloride): λex, nm (Int.) 463 (96), 491 (109); analysis (calcd., found for C26H24AuN): C
(57.04, 57.26), H (4.42, 4.38), N (2.56, 2.80).
[(tpy)Au(4-methoxyphenyl)2], 3m: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg,
0.011 mmol) was dissolved in 10 mL dry toluene under argon. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added (tpy)AuCl2 (100 mg, 0.229 mmol) followed by 4-methoxyphenylboronic acid (87.1 mg, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of
116 Celite. The volume of solvent was reduced. The crude product was purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether
(1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 99 mg
1 (75%); TLC (hexanes:diethyl ether, 40:60 v/v): Rf = 0.65; H NMR (400 MHz, CD2Cl2):
δ 8.11 (dt, J = 5.3, 1.4 Hz, 1H), 7.92 (d, J = 1.1 Hz, 1H), 7.91 (m, 1H), 7.69 (d, J = 7.9
Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H), 7.17–7.14 (m, 1H), 7.05 (d, J
= 7.8 Hz, 1H), 6.86 (s, 1H), 6.83 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 3.75 (s,
-1 -1 3H), 3.74 (s, 3H), 2.21 (s, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 328
(19000); emission (methylene chloride): λex, nm (Int.) 493 (133); analysis (calcd., found for C26H24AuNO2): C (53.89, 54.18), H (4.17, 4.24), N (2.42, 2.71).
[(tpy)Au(4-isopropoxyphenyl)2], 3n: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg,
0.011 mmol) was dissolved in 10 mL dry toluene under argon. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added (tpy)AuCl2 (100 mg, 0.229 mmol) followed by 4- isopropoxyphenylboronic acid (0.103 g, 0.573 mmol) and 10 mL dry 2-propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 10 h at room temperature. Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced. The
117 crude product purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted using hexanes/diethyl ether (1:2, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 97 mg (67%); TLC (hexanes:diethyl ether, 40:60 v/v):
1 Rf = 0.70; H NMR (400 MHz, C6D6): δ 8.13 (dd, J = 5.5, 1.2 Hz, 1H), 7.63 (d, J = 8.9
Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.51 (s, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.05 (d, J = 8.2
Hz, 1H), 7.02 (d, J = 8.5 Hz, 2H), 6.95 (dd, J = 7.9, 1.2 Hz, 1H), 6.91 (d, J = 8.6 Hz, 2H),
6.75 (td, J = 7.4, 1.2 Hz, 1H), 6.04 (td, J = 7.1, 1.2 Hz, 1H), 4.25 (sep, J = 5.8 Hz, 1H),
4.19 (sep, J = 5.8 Hz, 1H), 2.06 (s, 3H), 1.14 (d, J = 5.8 Hz, 6H), 1.11 (d, J = 5.8 Hz,
-1 -1 6H); UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 328 (29000); emission
(methylene chloride): λex, nm (Int.) 492 (112); analysis (calcd., found for
C30H32AuNO2.CH2Cl2): C (51.68, 51.80), H (4.76, 4.93), N (1.94, 2.29).
[(tpy)Au(4-(benzyloxy)phenyl)2], 3o: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) followed by K2CO3 (128 mg, 0.917 mmol). The resultant yellow reaction mixture was stirred for 5 min under argon. (tpy)AuCl2 (100 mg,
0.229 mmol) was added to the stirred reaction mixture followed by 4-
(benzyloxy)phenylboronic acid (130.7 mg, 0.573 mmol) and 2-propanol (10 mL). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 10 h. Progress of the reaction was monitored by TLC. Upon completion, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear
118 yellow solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:1, v/v). The desired product was eluted using hexanes/diethyl ether (1:1, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 130 mg (78%); TLC (hexanes:diethyl ether,
1 40:60 v/v): Rf = 0.68; H NMR (400 MHz, CD2Cl2): δ 8.12 (d, J = 4.9 Hz, 1H), 7.93–
7.91 (m, 2H), 7.70 (d, J = 7.7 Hz, 1H), 7.50–7.30 (m, 14H), 7.18–7.15 (m, 1H), 7.07 (d, J
= 7.5 Hz, 1H), 7.02 (d, J = 7.7 Hz, 1H), 6.91 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H),
-1 5.02 (s, 2H), 5.01 (s, 2H), 2.22 (s, 3H); UV/Vis (methylene chloride): λmax, nm (ε, M
-1 cm ) 328 (16000); emission (methylene chloride): λex, nm (Int.) 467 (88), 493 (105); analysis (calcd., found for C38H32AuNO2): C (62.38, 62.39), H (4.41, 4.78), N (1.91,
2.22).
3.4.4. Synthesis of monoarylated products
[(tpy)Au(Cl)( 4-fluorophenyl)], 4a: In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg,
0.011 mmol) was dissolved in 10 mL of dry toluene under argon. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added (tpy)AuCl2 (100 mg, 0.229 mmol) followed by 4-fluorophenylboronic acid (80.2 mg, 0.573 mmol). The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 12 h at room temperature. Progress of the reaction was monitored by TLC. After 12 h, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10
119 mL methylene chloride and passed through a plug of Celite. The volume of solvent was reduced. The crude product was purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted as the second fraction using hexanes/diethyl ether (1:3, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 73 mg (65%); TLC
1 (hexanes:diethyl ether, 40:60 v/v): Rf = 0.30; H NMR (400 MHz, CDCl3): δ 9.44 (d, J =
5.8 Hz, 1H), 8.02 (t, J = 7.5 Hz, 1H), 7.91 (t, J = 7.8 Hz, 1H), 7.60 (d, J = 7.7 Hz, 1H),
7.55–7.45 (m, 4H), 7.12 (d, J = 7.7 Hz, 1H), 7.02 (t, J = 8.8 Hz, 1H), 6.65 (s, 1H), 2.22
(s, 3H); analysis (calcd., found for C18H14AuClFN): C (43.61, 43.53), H (2.85, 2.76), N
(2.83, 3.19).
[(tpy)Au(Cl)(1-naphthyl)], 4b: Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in dry toluene (10 mL) inside a 100-mL argon-filled Schlenk flask. To this was added
t P Bu3·HBF4 (9.9 mg, 0.034 mmol) and K2CO3 (128 mg, 0.917 mmol) resulting in a light yellow reaction mixture, which was stirred for 5 min at room temperature under argon.
(tpy)AuCl2 (100 mg, 0.229 mmol) was added to the stirred reaction mixture followed by
1-naphthylboronic acid (98.6 mg, 0.573 mmol). The reaction mixture was degassed by three successive freeze-pump-thaw cycles and stirred at room temperature for 12 h. After the time period, the solvent was evaporated under reduced pressure. The resultant mixture was suspended in 10 mL methylene chloride and filtered through Celite to obtain a clear yellow solution. Removal of solvent under reduced pressure rendered an off-white solid that was chromatographed on a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:3, v/v). The desired product was eluted as
120 second fraction using hexanes/diethyl ether (1:3, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 49 mg (41%); TLC
1 (hexanes:diethyl ether, 40:60 v/v): Rf = 0.25; H NMR (400 MHz, CD2Cl2): δ 9.45 (d, J =
5.1 Hz, 1H), 8.15 (d, J = 7.9 Hz, 1H), 8.08 (td, J = 7.4, 1.8 Hz, 1H), 7.97 (d, J = 7.9 Hz,
1H), 7.86 (d, J = 8.07 Hz, 1H), 7.77 (d, J = 8.3 Hz, 1H), 7.66–7.63 (m, 2H), 7.55 (t, J =
6.1 Hz, 1H), 7.45–7.37 (m, 3H), 7.08 (d, J = 8.1 Hz, 1H), 6.28 (s, 1H), 1.98 (s, 3H);
-1 -1 UV/Vis (methylene chloride): λmax, nm (ε, M cm ) 283 (63000), 326 (22000); emission
(methylene chloride): λex, nm (Int.) 485 (147); analysis (calcd., found for C22H17AuClN):
C (50.06, 50.37), H (3.25, 3.55), N (2.65, 2.90).
4c.
In a 100-mL Schlenk flask, Pd(OAc)2 (2.6 mg, 0.011 mmol) was dissolved in 10 mL
t of dry toluene under argon. To this was added P Bu3·HBF4 (9.9 mg, 0.034 mmol) and
K2CO3 (128 mg, 0.917 mmol) resulting in a pale yellow solution, which was stirred for 5 min at room temperature under argon. To this flask was added (tpy)AuCl2 (100 mg, 0.229 mmol) followed by 2-acetylphenylboronic acid (94 mg, 0.573 mmol) and 10 mL dry 2- propanol. The reaction mixture was degassed by three successive freeze-pump-thaw cycles. Finally the reaction mixture was sealed and stirred for 24 h at room temperature.
Progress of the reaction was monitored by TLC. Upon completion, volatiles were removed under reduced pressure. The resulting crude product was suspended in 10 mL
121 methylene chloride and passed through a plug of Celite. The volume of solvent was reduced and finally purified by a short basic alumina column using variant polarity between hexanes and hexanes/diethyl ether (1:9, v/v). The desired product was eluted using hexanes/diethyl ether (1:9, v/v). Removal of solvent rendered a white solid, which was dried under vacuum for 6 h. Yield: 88 mg (80%); TLC (hexanes:diethyl ether, 10:90
1 v/v): Rf = 0.75; H NMR (400 MHz, CD2Cl2): δ 9.14 (d, J = 6.5 Hz, 1H), 8.07–8.00 (m,
3H), 7.78 (d, J = 7.7 Hz, 1H), 7.72 (dd, J = 7.7, 1.1 Hz, 1H), 7.59 (td, J = 7.7, 1.6 Hz,
1H), 7.55 (s, 1H), 7.49 (t, J = 6.4 Hz, 1H), 7.33 (td, J = 7.5, 0.9 Hz, 1H), 7.15 (d, J = 7.8
13 Hz, 1H), 3.57 (s, 2H), 2.40 (s, 3H); C NMR (150 MHz, CDCl3): δ 209.3, 168.6, 167.1,
166.2, 148.9, 145.2, 143.7, 141.6, 140.6, 135.3, 132.5, 131.9, 127.6, 127.2, 126.8, 125.1,
-1 122.9, 120.5, 45.3, 22.1; IR (KBr): 1666.4 cm ; UV/Vis (methylene chloride): λmax, nm
-1 -1 (ε, M cm ) 302 (10000), 321 (11000); emission (methylene chloride): λex, nm (Int.) 492
(74); analysis (calcd., found for C20H16AuNO): C (49.70, 49.85), H (3.34, 3.48), N (2.90,
3.13).
3.5. References
(1) Hashmi, A. S. K.; Toste, F. D. Modern Gold Catalyzed Synthesis; Hashmi, A. S. K.; Toste, F. D., Ed.; Wiley-VCH: Weinheim, Germany, 2012.
(2) Schmidbaur, H.; Schier, A. Organometallics 2009, 29, 2–23.
(3) Schmidbaur, H.; Schier, A. In ; Crabtree, R. H.; Mingos, D. M. P., E. Comprehensive Organometallic Chemistry III Volume 2, Section 2.05.; Elsevier, 2006.
(4) Craig, S.; Gao, L.; Lee, I.; Gray, T.; Berdis, A. J. J. Med. Chem. 2012, 55, 2437– 2451.
(5) Sun, R. W.-Y.; Che, C.-M. Coord. Chem. Rev. 2009, 253, 1682–1691.
122 (6) Kean, W. F.; Kean, I. R. L. Inflammopharmacology 2008, 16, 112–125.
(7) Urig, S.; Fritz-Wolf, K.; Réau, R.; Herold-Mende, C.; Tóth, K.; Davioud-Charvet, E.; Becker, K. Angew. Chem. Int. Ed. Engl. 2006, 45, 1881–1886.
(8) Yan, K.; Lok, C.-N.; Bierla, K.; Che, C.-M. Chem. Commun. (Camb). 2010, 46, 7691–7693.
(9) Cinellu, M. a.; Maiore, L.; Manassero, M.; Casini, A.; Arca, M.; Fiebig, H.-H.; Kelter, G.; Michelucci, E.; Pieraccini, G.; Gabbiani, C.; Messori, L. ACS Med. Chem. Lett. 2010, 1, 336–339.
(10) Rigobello, M. P.; Scutari, G.; Folda, A.; Bindoli, A. Biochem. Pharmacol. 2004, 67, 689–696.
(11) Shaw, C. F. I. Chem. Rev. 1999, 99, 2589–2600.
(12) Rudolph, M.; Hashmi, A. S. K. Chem. Soc. Rev. 2012, 41, 2448–2462.
(13) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chemie Int. Ed. 2006, 45, 7896–7936.
(14) Partyka, D. V; Teets, T. S.; Zeller, M.; Updegraff, J. B.; Hunter, A. D.; Gray, T. G. Chemistry 2012, 18, 2100–2112.
(15) Partyka, D. V; Esswein, A. J.; Zeller, M.; Hunter, A. D.; Gray, T. G. Organometallics 2007, 26, 3279–3282.
(16) Vogt, R. A.; Gray, T. G.; Crespo-Hernández, C. E. J. Am. Chem. Soc. 2012, 134, 14808–14817.
(17) Gao, L.; Peay, M. A.; Partyka, D. V; Updegraff, J. B.; Teets, T. S.; Esswein, A. J.; Zeller, M.; Hunter, A. D.; Gray, T. G. Organometallics 2009, 28, 5669–5681.
(18) Pyykkö, P. Inorganica Chim. Acta 2005, 358, 4113–4130.
(19) Pyykkö, P. Angew. Chem. Int. Ed. Engl. 2004, 43, 4412–4456.
(20) Schwerdtfeger, P.; Boyd, P. D. W.; Brienne, S.; Burrell, A. K. Inorg. Chem. 1992, 31, 3411–3422.
(21) Kaltsoyannis, N. J. Chem. Soc., Dalt. Trans. 1996, 1–11.
(22) Vogt, R. A.; Peay, M. A.; Gray, T. G.; Crespo-Hernández, C. E. J. Phys. Chem. Lett. 2010, 1, 1205–1211.
(23) Yam, V. W.-W.; Cheng, E. C.-C. Chem. Soc. Rev. 2008, 37, 1806–1813.
123 (24) Yang, C.; Messerschmidt, M.; Coppens, P.; Omary, M. A. Inorg. Chem. 2006, 45, 6592–6594.
(25) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403.
(26) Teets, T. S.; Nocera, D. G. J. Am. Chem. Soc. 2009, 131, 7411–7420.
(27) Tkatchouk, E.; Mankad, N. P.; Benitez, D.; Goddard, W. A.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 14293–14300.
(28) Ghidiu, M. J.; Pistner, A. J.; Yap, G. P. A.; Lutterman, D. A.; Rosenthal, J. Organometallics 2013, 32, 5026–5029.
(29) Guenther, J.; Mallet-Ladeira, S.; Estevez, L.; Miqueu, K.; Amgoune, A.; Bourissou, D. J. Am. Chem. Soc. 2014, 136, 1778–1781.
(30) Winston, M. S.; Wolf, W. J.; Toste, F. D. J. Am. Chem. Soc. 2014, 136, 7777– 7782.
(31) Kilpin, K. J.; Henderson, W.; Nicholson, B. K. Polyhedron 2007, 26, 434–447.
(32) Akerman, K. J.; Fagenson, A. M.; Cyril, V.; Taylor, M.; Muller, M. T.; Akerman, M. P.; Munro, O. Q. J. Am. Chem. Soc. 2014.
(33) Wilson, C. R.; Fagenson, A. M.; Ruangpradit, W.; Muller, M. T.; Munro, O. Q. Inorg. Chem. 2013, 52, 7889–7906.
(34) Casini, A.; Hartinger, C.; Gabbiani, C.; Mini, E.; Dyson, P. J.; Keppler, B. K.; Messori, L. J. Inorg. Biochem. 2008, 102, 564–575.
(35) Sun, R. W.-Y.; Li, C. K.-L.; Ma, D.-L.; Yan, J. J.; Lok, C.-N.; Leung, C.-H.; Zhu, N.; Che, C.-M. Chemistry 2010, 16, 3097–3113.
(36) Yam, V. W.-W.; Wong, K. M.-C.; Hung, L.-L.; Zhu, N. Angew. Chemie Int. Ed. 2005, 44, 3107–3110.
(37) Wang, J.-B.; Wu, Q.-Q.; Min, Y.-Z.; Liu, Y.-Z.; Song, Q.-H. Chem. Commun. 2012, 48, 744–746.
(38) Bronner, C.; Wenger, O. S. Dalt. Trans. 2011, 40, 12409–12420.
(39) Komiya, S.; Shibue, A. Organometallics 1985, 4, 684–687.
(40) Szentkuti, A.; Bachmann, M.; Garg, J. A.; Blacque, O.; Venkatesan, K. Chem. – A Eur. J. 2014, 20, 2585–2596.
124 (41) Garg, J. A.; Blacque, O.; Fox, T.; Venkatesan, K. Inorg. Chem. 2010, 49, 11463– 11472.
(42) Usón, R.; Vicente, J.; Cirac, J. A.; Chicote, M. T. J. Organomet. Chem. 1980, 198, 105–112.
(43) David, B.; Monkowius, U.; Rust, J.; Lehmann, C. W.; Hyzak, L.; Mohr, F. Dalt. Trans. 2014, 10.1039/C4DT00778F.
(44) Zehnder, T. N., Blacque, O., Venkatesan, K. . Dalt. Trans. 10.1039/C4DT01187B.
(45) Rosca, D.-A.; Smith, D. A.; Bochmann, M. Chem. Commun. 2012, 48, 7247–7249.
(46) Uson, R.; Laguna, A.; Laguna, M.; Fernandez, E.; Jones, P. G.; Sheldrick, G. M. J. Chem. Soc., Dalt. Trans. 1982, 1971–1976.
(47) Kovala-Demertzi, D.; Tauridou, P.; Russo, U.; Gielen, M. Inorganica Chim. Acta 1995, 239, 177–183.
(48) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
(49) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
(50) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685–4696.
(51) Shi, Y.; Ramgren, S. D.; Blum, S. A. Organometallics 2009, 28, 1275–1277.
(52) Hashmi, A. S. K.; Lothschütz, C.; Döpp, R.; Rudolph, M.; Ramamurthi, T. D.; Rominger, F. Angew. Chemie Int. Ed. 2009, 48, 8243–8246.
(53) Hofer, M.; Gomez-Bengoa, E.; Nevado, C. Organometallics 2014, 33, 1328–1332.
(54) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chemie Int. Ed. 2006, 45, 8188–8191.
(55) Heckler, J. E.; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chemie Int. Ed. 2012, 51, 5924–5928.
(56) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Inorg. Chem. 2012, 51, 8394–8401.
(57) Lenker, H. K.; Gray, T. G.; Stockland, R. A. Dalt. Trans. 2012, 41, 13274–13276.
125 (58) Schmidbaur, H., Grohmann, A., Olmos, M. E. In Organogold Chemistry. In Gold: Progress in Chemistry, Biochemistry and Technology; Schmidbaur, H., Ed.; Wiley: Chichester, 1999; pp. 647–746.
(59) Stout, G. H.; Jensen, L. H. X-ray Structure Determination: A Practical Guide, 2d Ed; Wiley Interscience, 1989; pp. 404–405.
(60) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456–463.
(61) Cámpora, J.; Maya, C. M.; Palma, P.; Carmona, E.; Gutiérrez-Puebla, E.; Ruiz, C. J. Am. Chem. Soc. 2003, 125, 1482, and references therein.
(62) Soo, H. S.; Diaconescu, P. L.; Cummins, C. C. Organometallics 2004, 23, 498– 503.
(63) Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 2116–2119.
(64) Amatore, C.; Jutand, A.; Le Duc, G. Chem. – A Eur. J. 2011, 17, 2492–2503.
(65) Amatore, C.; Le Duc, G.; Jutand, A. Chem. – A Eur. J. 2013, 19, 10082–10093.
(66) Campo, M. A.; Zhang, H.; Yao, T.; Ibdah, A.; McCulla, R. D.; Huang, Q.; Zhao, J.; Jenks, W. S.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, 6298–6307.
(67) Shaw, A. P.; Tilset, M.; Heyn, R. H.; Jakobsen, S. J. Coord. Chem. 2011, 64, 38– 47.
126 Chapter 4 Cyclometalated Iridium(III) Complexes with Deoxyribose Substituents
127 This work is published: "Cyclometalated Iridium(III) Complexes with Deoxyribose Substituents " Maity, A.; Choi, J.-S.; Teets, T.-S.; Deligonul, N.; Berdis, A. J.; Gray, T. G. Chem. Eur. J. 2013, 19, 15924–15932. DOI: 10.1039/C2SC21831C
4.1. Introduction
Fluorescent molecular probes have become powerful tools for chemists and biologists for monitoring ions,1,2 small molecules3–6 and bio-macromolecules7–10 inside living cells. Several benefits of using fluorescent probes remain, such as high spatiotemporal resolution with at minimal doses and versatile synthetic tuning. Despite the advantages of fluorescent probes, organic luminophores exhibit drawbacks such as interference from background fluorescence,11,12 short excitation wavelengths13 and low photostability.14
In comparison to organic dyes, metal-based emissive dyes are encouraging alternatives because they display many superior physico-chemical properties for bio- imaging. These include: large Stokes shifts (hundreds of nm), long luminescence lifetimes (100 ns to ms), and enhanced photostabilities (lower photobleaching).15 Among the transition metal complexes, phosphorescent iridium(III) cyclometalates have emerged as promising candidates with applications in sensing metal ions,16–21 oxygen,22–24 anions,25 and bio-logical molecules, such as DNA,26 amino acids,27–30 and glucose;31 live cell compartmentalization staining including nuclei,7,32 mitochondria,33 lysosomes,34 endoplasmic reticuli,35,36 plasma membranes,34,37 and cytoplasms.32,34,38,39 More details on phosphorescence bioimaging including cellular staining using cyclometalated iridium(III) complexes can be found in recent reviews.15,40,41
Coordinatively saturated, cyclometalated complexes of iridium(III) are 18- electron closed shell species that withstand the inhospitable settings of living cells.42–52
128 These complexes have high phosphorescence quantum yields and the emission wavelengths are subject to rational tuning by selective choice of cyclometalating ligand.53–58 Triplet luminescence arises from either a metal-to-ligand charge-transfer
(MLCT) state or a ligand-centered excited state.59–67
Iridium(III) complexes are used extensively in bioconjugation reactons.68 Complexes have been appended to biotin for binding and crosslinking streptavidin.69,70 Lo and co- workers reported that estradiol tethered emission of two distinct iridium complexes intensifies upon binding to the receptor ERa.71 Iridium(III) complexes have also been attached to steroids, such as estradiol.72 Sugars have been conjugated to iridium complexes indirectly through tethers that end in amino-oxy moieties.73 These functional groups undergo bioconjugation reactions with the carbonyl groups of reducing sugars.
The resulting complexes enter HeLa cells, and perinuclear staining occurs. Internalization is rapid for the glucose conjugate and less so for those of galactose, lactose, or maltose.
In a recent article it has been shown that few anionic iridium(III) cyclometalates have shown better performance when compare with the regular mitochondrial tracking compounds currently present in merket.74
Nucleoside transporters are integral membrane glycoproteins.75 These proteins regulate cellular proliferation, neurotransmission, and cardiovascular activity by membrane translocation of natural and synthetic nucleosides in mammalian cells. They are imperfectly understood, despite being essential to cell survival and proliferation. In cells actively dividing, de novo nucleoside synthesis predominates. In other cells, nucleosides are recycled, and nucleoside transporters enable salvaging. There are two broad classes of transporters: equilibrative nucleoside transporters (ENT) and
129 concentrative nucleoside transporters (CNT). The equilibrative transporters move nucleosides into or out of the cell, along a concentration gradient. Concentrative nucleoside transporters ferry nucleosides inwards, against the gradient. For most CNTs, nucleoside transport is coupled to Na+ transport, and these proteins are sodium– nucleoside symporters. Another isoform, designated CNT3, utilizes Na+ and/or H+ to facilitate nucleoside transport.76
Many chemotherapeutic drugs are nucleoside analogues,77–85 and their effectiveness depends on nucleoside transporters for cellular uptake. Mechanistic understanding of these glycoproteins is sparse, mainly because of limited structural information on such dynamic biomolecules. To date, there is a single report of a crystal structure of a CNT from the bacterium Vibrio cholera.86 Although more structures are likely to emerge, there is a clear need for probes that accurately report on the activity of transporters in cells and live animals.
This work reports optical markers for the facilitated diffusion of nucleosides.
Nucleoside transporters recognize the sugar moiety; the nucleobase is secondary. We describe iridium(III)-based emitters bound covalently to deoxyribose sugars through β- glycoside linkages. These non-natural nucleosides assemble in copper-catalyzed [3+2] cycloaddition reactions of azides with terminal alkyne precursors. Metalation follows in thermal reactions with iridium(III) dimers.87 Instead of a purine or pyrimidine nucleobase, the deoxyribose sugar supports cyclometalated iridium(III) at the 1ʹ-position.
The new probes are visible-light emitters. Their syntheses and optical properties are disclosed, along with crystallographic findings of a representative complex.
130 4.2. Results and Discussion
Synthesis: Synthesis of a chelating deoxyribose ligand proceeded as in Scheme 4.2.1.
Concentrated hydrochloric acid (1.5 equiv) was treated with 2-deoxy-d-ribose in methanol. The methyl-protected product 2 was treated with para-toluoyl chloride in pyridine to protect the 3´- and 5´-hydroxyls.
HO HO pyridine O OH HCl O OMe MeOH TolCl HO HO O 2 1 TolCl = Cl
TolO TolO NaN O OMe HCl O 3 AcOH DMF, RT Cl TolO TolO 3 4
TolO TolO N 1. Anomeric separation 3 2. NaOMe O + O N MeOH TolO 3 TolO 5α 5β
N HO N3 N N O HO N N CuI, N(i-Pr)2Et HO O 6 Toluene / THF HO 7
Scheme 4.2.1. Synthesis of nucleoside 7.
131 Compound 3 was converted to chloro-Hoffer sugar 4 with an HCl solution in glacial acetic acid generated by adding acetyl chloride to an aqueous solution of acetic acid. The chloro sugar dissolved in N,N-dimethylformamide was treated with sodium azide to yield the two anomers, α and β of protected azido sugar 5. The resulting diastereomeric mixture was separated by silica gel column chromatography. Deprotection with sodium methoxide in dry methanol afforded azidodeoxyribose 6. Copper-catalyzed [3+2] cycloaddition with 2-ethynylpyridine produced 7 after purification by silica gel column chromatography. Ligand 7 recurs in all complexes in this work.88–91
Chart 4.2.1. Cyclometalating ligands
Scheme 4.2.2. Synthesis of typical metallonucleoside.
Metallonucleosides were prepared by the treatment of slight excess of 7 with known, chloro-bridged iridium(III) dimers in presence of NH4PF6. The products were isolated as
132 the cationic complex of hexafluorophosphate salt. An example appears in Scheme 4.2.2.
Ambient workup and precipitation yielded the products as analytically pure solids in isolated yields ranging from 62–79%. Chart 4.2.1. enumerates the non-nucleoside ligands.
Crystallography: Vapor diffusion of pentane into a chloroform solution afforded diffraction quality single crystals of [Ir(ppy)2(7)](PF6). The crystal was grown by Dr.
Figure 4.2.1. Thermal ellipsoid representation (50% probability) of the cation of [Ir(ppy)2(7)](PF6) along c. Hydrogen atoms and counterion are omitted for clarity. A partial atom labeling scheme is indicated. Selected interatomic distances (Å): Ir1–C34, 2.017(4); Ir1–C23, 2.019(7); Ir1–N6, 2.047(5); Ir1–N5, 2.048(6); Ir1–N1, 2.141(4); Ir1– N4, 2.163(5). Selected angles (°): N1–Ir1–N4, 76.7(3); C23–Ir1–N5, 80.2(3).
Nihal Deligonul and structure was determined by Dr. Matthias Zeller, Youngstown State
University. A thermal ellipsoid depiction appears in Figure 4.2.1. Iridium–carbon bond lengths are 2.017(4) and 2.019(7) Å; the nucleoside pyridyl and triazolyl nitrogen donors exert similar trans influences. Iridium–pyridyl nitrogen bond lengths are 2.047(5) and
133 2.048(6) Å for the 2-phenylpyridine ligands, and 2.163(5) Å for the nucleoside. The Ir–
Ntriazolyl distance is 2.141(4) Å, also reflecting a trans disposition to carbon. Counterion
and intraligand metrics, including those of the sugar, are unexceptional.
Luminescence: New complexes were characterized by UV−vis absorption and
photoluminescence (PL) spectra obtained in degassed acetonitrile solutions at room
temperature. Absorption features appear in the visible region from about 250–435 nm
(Figure 4.2.1. (a)), with more intense bands in the ultraviolet region. The weaker low-
energy absorption bands could be assigned to spin-allowed and spin-forbidden metal-to-
ligand charge transfer (1MLCT and 3MLCT) [π*(N^N and N^C)←dπ(Ir)] transitions,92
and the more intense high-energy bands to spin-allowed intraligand (1IL) π*←π
transitions. Such absorption features are commonplace among C^N chelated complexes
of iridium(III).93 Photoexcitation at the MLCT transition bands provokes strong room
temperature phosphorescence emission.
(a) (b)
200 [Ir(ppy) (N^N)]PF 30000 2 6 [Ir(ppy)2(N^N)]PF6 [Ir(tpy)2(N^N)]PF6 [Ir(tpy)2(N^N)]PF6 ) [Ir(bzq) (N^N)]PF -1 150 2 6 [Ir(bzq)2(N^N)]PF6 [Ir(pq) (N^N)]PF Cm [Ir(pq) (N^N)]PF 2 6 -1 2 6 20000 [Ir(btp) (N^N)]PF [Ir(btp)2(N^N)]PF6 2 6 100
10000 50 Emission Intensity (a.u.) Intensity Emission Molar Absorptivity (M Absorptivity Molar
0 0 300 400 500 600 400 600 800 Wavelength (nm) Wavelength (nm)
Figure 4.2.1. (a) Absorption spectra of metallonucleosides collected in acetonitrile solvent at 298K; (b) Normalized emission spectra (298 K) of new complexes in 2- methyltetrahydrofuran.
134 Photoexcitation of the complexes resulted in intense and long-lived green to yellow emission in fluid solutions under ambient conditions and in low-temperature 2- methyltetrahydrofuran glass (Figure 4.2.1. (b)). The C^N ligand variations produce color-tuned phosphorescence over a wide spectral range of 475−592 nm. The phosphorescence quantum yields range from 2.6% to 15% in degassed 2-
[Ir(ppy) (7)]+ 2 [Ir(tpy) (7)]+ 2 [Ir(bzq) (7)]+ 2 [Ir(btp) (7)]+ 2 [Ir(pq) (7)]+ 2
Normalized emission / 77 K
450 500 550 600 650 700 Wavelength / nm
Figure 4.2.3. Normalized emission spectra (77 K) of new complexes in 2- methyltetrahydrofuran glass. methyltetrahydrofuran solutions. Results are summarized in Table 4.2.1. The new complexes emit in fluid solution and in low-temperature glasses. Normalized emission spectra at 77 K appear in Figure 4.2.3. The cyclometalating ligands modulate the luminescence; emission colors span the visible spectrum. Vibronically structured emission is pronounced. Their microsecond-scale emission lifetimes indicate phosphorescence. The highest triplet state life time was observed for [Ir(bzq)2(7)]PF6 complex which probably explain the lowest quantum yield, 2.6% for the compound.
135 Table 4.2.1. Emission wavelengths λem, lifetimes τ, and quantum yields φem of – iridium(III) complexes as PF6 salts at 295 K and 77 K in 2-methyltetrahydrofuran.
Sample 295 K 77 K a λem (nm) τ (µs) φem λem (nm) τ (µs) + [Ir(ppy)2(7)] 475 1.5 0.15 475 4.4 + [Ir(tpy)2(7)] 475 1.6 0.13 475 5.8 + [Ir(bzq)2(7)] 520 6.8 0.026 500 62 + [Ir(btp)2(7)] 592 7.2 0.044 582 13 + [Ir(pq)2(7)] 565 1.2 0.064 542 4.6 a ±10%; absorbance of solutions was ≤0.1.
Taken together, the spectra indicate emitting states of considerable ligand character, with origins that range from 3MLCT to ligand-centered. The sugar pendants did not significantly perturb the photophysical properties of the complexes.
4.3. Conclusion
Described herein is a synthetic strategy with which deoxyribose sugars are linked to chelating pyridyl-triazoles. An efficient method has been developed that attaches these sugar-bearing ligands to cyclometalated iridium(III). The resulting assemblies are luminescent. Choice of the cyclometalating C^N ligand controls emission colors, and lumophores of many hues can be prepared. Membrane-bound enzymes translocate nucleosides from extracellular space into the cytosol in the first step of nucleoside metabolism. Most nucleoside transport enzymes support sweeping variations in the nucleobase. The pendant (deoxy)sugar is the recognition site of nucleoside substrates.
Chemical tags that monitor nucleoside transport are few, and studies of transport in vivo are hindered. The conjugates herein join an emissive complex to a deoxyribose sugar.
They are potential photoactive surrogates of natural nucleosides; their biodisposition can be tracked optically. These studies are in progress.
136 4.4. Experimental Section
4.4.1. Materials and Methods
Experimental procedures involving air- or moisture sensitive substances were performed under argon using either Schlenk line techniques or in a nitrogen-filled
MBraun drybox. Anhydrous solvents were used directly from an MBraun solvent purification system or were purchased from Sigma-Aldrich. 1H NMR experiments were performed on a Varian-400 FT NMR spectrometer operating at 399.7 MHz. Chemical shifts are reported in parts per million (δ), measured from tetramethylsilane (0 ppm) and are referenced to the solvent CDCl3 (7.26 ppm), acetone-d6 (2.05 ppm), DMSO-d6 (2.49
1 ppm), D2O (4.79 ppm), CD2Cl2 (5.32 ppm) or MeOH-d4 (3.31 ppm) for H NMR.
13C{1H} NMR spectra were recorded on a Varian INOVA AS-600 spectrometer operating at 150.0 Hz. 13C NMR chemical shifts are reported in parts per million (δ), measured from tetramethylsilane (0 ppm) and are referenced to the solvent CDCl3 (77.00 ppm) or CD2Cl2 (54.00 ppm). High-resolution electrospray ionization mass spectrometry
(Hi-Res ESI-MS) experiments were performed on an IonSpec HiRes ESI-FTICRMS at the University of Cincinnati Mass Spectrometry facility. Acetonitrile was degassed prior to use for UV-Vis and luminescence measurements. UV-Vis and luminescence data were recorded using a Cary 5G UV-Vis-NIR spectrometer and a Cary Eclipse spectrometer, respectively. Thin layer chromatography (TLC) was carried out using Whatman Silica
Gel UV254 plates. Column chromatography was performed using Fisher Scientific Silica
Gel, sizes 32–63. Elemental analyses were carried out by Robertson Microlit
Laboratories, Ledgewood, NJ.
137 Chemicals from commercial sources were used as received. 2-Deoxy-D-ribose, pyridine, p-toluoyl chloride, acetyl chloride, 2-ethoxyethanol, and sodium methoxide
(NaOMe) were purchased from Acros Organics. Sodium azide (NaN3), N,N- diisopropylethylamine (DIPEA) and copper(I) iodide (CuI) were purchased from Sigma-
Aldrich; iridium(III) chloride (IrCl3·3H2O) and ammonium hexafluorophosphate
(NH4PF6) were purchased from Strem Chemicals.
Hoffer’s α-chlorosugar (1-α-chloro-3,5-di-(O-p-toluoyl)-2-deoxy-D-ribose) was synthesized with a slight modification of the first step of an established procedure94 where an equivalent amount of concentrated hydrochloric acid was used in place of dissolving hydrogen chloride gas in methanol. Cyclometalated Ir(III) µ-chloro-bridged dimers, (C^N)2Ir(µ-Cl)2Ir(C^N)2, (abbreviated as [{Ir(C^N)2(µ-Cl)}2]) were synthesized
95 via the method reported by Nonoyama; IrCl3.3H2O was refluxed with 2-2.5 equiv cyclometalating ligand in a 3:1 mixture of 2-ethoxyethanol and water. Synthesis and
96 97 98 characterization of [{Ir(ppy)2(µ-Cl)}2], [{Ir(tpy)2(µ-Cl)}2], [{Ir(bzq)2(µ-Cl)}2],
99 100 [{Ir(pq)2(µ-Cl)}2], and [{Ir(btp)2(µ-Cl)}2], were reported previously.
4.4.2. Synthesis of ligandoside
1-β-azido-3,5-di-(O-p-toluoyl)-2-deoxy-D-ribose (5β): To a mixture of α-
TolO chlorosugar 4 (1.5 g, 3.85 mmol) in dry DMF (50 mL), stirred at rt for N3 O 30 min, was added NaN3 (390 mg, 5.99 mmol). The mixture was TolO 5β vigorously stirred at rt for 2 h in an inert atmosphere as the reaction was tracked by TLC. After completion of the reaction, EtOAc (100 mL) was added to the reaction mixture to form a uniform organic layer. The organic layer was washed with
138 water (2 x100 mL), followed by brine (150 mL) and dried (over anhydrous Na2SO4).
Evaporation under reduced pressure afforded the crude product mixture (1.4 g, 92%, β:α
≈ 1:1), which was resolved by chromatography using ether/hexanes (1:9 v/v) mixture.
Compound 5β was eluted as the first fraction. Yield: 0.823 g (54%). Rf = β: 0.55 (diethyl
1 ether/hexanes = 30/70). H NMR (400 MHz, CDCl3), δ (ppm): 7.97 (d, 2H. J = 8.1 Hz),
7.89 (d, 2H, J = 8.2 Hz), 7.24-7.21 (m, 4H), 5.70 (t, 1H, J = 5.2 Hz), 5.56 (td, 1H, J = 2.4,
5.5 Hz), 4.59-4.50 (m, 3H), 2.42-2.39 (m, 8H). HRMS: Calcd. For C21H21N3NaO5
[M+Na]+: 418.1379 Found: 418.1376.
1-α-azido-3,5-di-(O-p-toluoyl)-2-deoxy-D-ribose (5α): Collected as the second
TolO fraction from the column. Yield: 0.7 g (46%). Rf = α: 0.48 (diethyl O 1 ether/hexanes = 30/70). H NMR (400 MHz, CDCl3), δ (ppm): 7.96 (d, N TolO 3 5 α 2H. J = 8.3 Hz), 7.91 (d, 2H, J = 8.2 Hz), 7.27-7.23 (m, 4H), 5.71 (d,
1H, J = 5.6 Hz), 5.51-5.48 (m, 1H), 4.72 (q, 1H, J = 3.8 Hz), 4.63-4.50 (m, 2H), 2.58-
2.52 (m, 1H), 2.42 (s, 3H), 2.41 (s, 3H), 2.25-2.21 (m, 1H). HRMS: Calcd. For
+ C21H21N3NaO5 [M+Na] : 418.1379 Found: 418.1366.
1-β-azido-2-deoxy-D-ribose (6): Into a dry round bottom flask, loaded with 5β (950
mg, 2.4 mmol), was added 50 mL of dry MeOH followed by sodium
methoxide (410 mg, 7.58 mmol). The reaction mixture was stirred under
inert atmosphere at rt for 24 h and monitored by TLC. After this time, the solvent was removed under vacuum. The residue was loaded on a silica gel column, and the desired product 6 was isolated when eluted with 5% MeOH in ether. Yield: 0.310
139 1 g (81%). Rf = 0.60 (methanol/diethyl ether = 5/95). H NMR (400 MHz, CDCl3), δ
(ppm): 5.55 (t, 1H, J = 4.0 Hz), 4.39 (d, 1H, J = 4.8 Hz), 3.95-3.92 (m, 1H), 3.75-3.66
+ (m, 2H), 2.15-2.11 (m, 2H). HRMS: Calcd. For C5H9N3NaO3 [M+Na] : 182.0542 Found:
182.0545.
1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-(2-pyridinyl))-1,2,3-triazole (7):
Compound 6 (0.540 g, 3.39 mmol) was dissolved in a mixture of
THF (10 mL) and toluene (40 ml). To the reaction mixture was
added 2-ethynylpyridine (0.54 mL, 5.35 mmol), DIPEA (2.7 mL,
15.5 mmol), and CuI (0.646 g, 3.39 mmol). The solution was heated to reflux. The reaction was complete after 24 h. The solvent was removed by rotary evaporation. The crude reaction mixture was loaded on a silica gel column packed with 1:1 v/v ether:hexanes. The desired product 7 was isolated when the eluant polarity was increased to 1:9 v/v MeOH:ether. Yield: 0.665 g (75%). Rf = 0.20 (methanol/diethyl
1 ether = 5/95). H NMR (400 MHz, CDCl3), δ (ppm): 8.49 (d, 1H, J = 4.0 Hz), 8.46 (s,
1H), 8.09 (d, 1H, J = 8.3 Hz), 7.77 (td, 1H, J = 6.0, 1.6 Hz), 7.24-7.21 (m, 1H), 6.42 (tapp, characteristic peak for β-anomer, 1H, J = 6.7 Hz), 4.77 (d, 1H, J = 4.8 Hz), 4.13 (d, 1H, J
= 3.9 Hz), 3.88-3.72 (m, 2H), 2.89-2.83 (m, 1H), 2.63-2.57 (m, 1H). 13C NMR (150
MHz, CDCl3), δ (ppm): 149.72, 149.23, 148.03, 137.24, 123.14, 121.53, 120.43, 88.96,
+ 88.39, 71.69, 62.61, 41.67. HRMS: Calcd. For C12H14N4NaO3 [M+Na] : 285.0964
Found: 285.0974. Anal. Calcd. For C12H14N4O3: C, 54.96; H, 5.38; N, 21.36. Found: C,
55.12; H, 5.42; N, 21.34.
140 4.4.3. Synthesis of metallonucleosides
[Ir(ppy)2(7)]PF6: In 20 mL dry acetonitrile was suspended [{Ir(ppy)2(µ-Cl)}2] (0.040
g, 0.037 mmol). To this was added a 10-mL THF
solution of compound of 7 (0.024 g, 0.092 mmol)
followed by NH4PF6 (0.0125 g, 0.076 mmol). After
purging with argon, the reaction mixture was heated
to 45 ºC and left stirring for 12 h. The reaction was complete after this time period as indicated by TLC. The solvent was removed under reduced pressure to render a dark orange residue. The crude reaction mixture was washed with THF, water and ice-cold acetone followed by ether and pentane. The product was vacuum-dried to give analytically pure compound. Yield: 0.053 g (75%). 1H NMR (400
MHz, CD2Cl2), δ (ppm): 9.23 (d, 1H, J = 3.2 Hz), 8.25 (dd, 1H, J = 4.2, 5.0 Hz), 8.01 (t,
1H, J = 7.8 Hz), 7.95-7.92 (m, 2H), 7.83 (d, 1H, J = 5.4 Hz), 7.81-7.76 (m, 2H), 7.72-
7.68 (m, 3H), 7.50 (dd, 1H, J = 6.3, 5.3 Hz), 7.29 (t, 1H, J = 7.3 Hz), 7.10-6.96 (m, 4H),
6.92 (t, 1H, J = 7.1 Hz), 6.86 (t, 1H, J = 7.6 Hz), 6.50-6.41 (m, 1H), 6.31-6.28 (m, 2H),
4.73-4.62 (m, 1H), 4.12-4.08 (m, 1H), 3.96-3.80 (m, 2H), 2.76-2.53 (m, 2H). 13C NMR
(150 MHz, CD2Cl2), δ (ppm): 168.59, 167.95, 150.83, 150.04, 149.94, 149.82, 149.22,
149.07, 146.68, 144.56, 140.18, 138.71, 138.64, 132.50, 132.07, 131.12, 130.43, 127.13,
125.32, 124.92, 124.46, 124.36, 124.13, 124.00, 123.79, 123.69, 123.31, 122.86, 120.19,
-1 -1 91.88, 89.11, 70.97, 62.04, 42.82. UV/Vis (acetonitrile): λmax, nm (ε, M cm ) 249
(27000), 380 (4000). Emission (acetonitrile): λex, nm (Int.) 478 (190), 506 (178). HRMS:
+ Calcd. for C34H30IrN6O3 [M-PF6] : 763.2003 Found: 763.2004 Anal. Calcd. For
C34H30F6IrN6O3P: C, 44.98; H, 3.33; N, 9.26. Found: C, 45.21; H, 3.52; N, 9.35.
141 [Ir(tpy)2(7)]PF6: In 25 mL dry acetonitrile was suspended [{Ir(tpy)2(µ-Cl)}2] (0.046
g, 0.041 mmol). To this was added a solution of
compound 7 (0.026 g, 0.099 mmol) dissolved in 10 mL
dry THF, followed by NH4PF6 (0.014 g, 0.086 mmol).
After purging with argon, the reaction mixture was
sealed and heated to 45 ºC. The reaction was complete
after 12 h as indicated by TLC. The solvent was removed under reduced pressure to render a dark orange residue. The crude reaction mixture was washed with THF, water and ice cold acetone, followed by ether and pentane. The remaining product was dried under vacuum to give analytically pure
1 compound. Yield: 0.047 g (62%). H NMR (400 MHz, acetone-d6), δ (ppm): 9.43 (d, 1H,
J = 5.9 Hz), 8.40 (dd, 1H, J = 5.3, 3.2 Hz), 8.19 (t, 1H, J = 7.8 Hz), 8.14 (d, 2H, J = 8.3
Hz), 7.95-7.85 (m, 4H), 7.78-7.69 (m, 3H), 7.55 (t, 1H, J = 5.6 Hz), 7.13-7.05 (m, 2H),
6.86 (d, 1H, J = 7.4 Hz), 6.78 (d, 1H, J = 7.5 Hz), 6.46 (q, 1H, J = 8.8 Hz), 6.17-6.14 (m,
2H), 4.63-4.48 (m, 1H), 4.07-4.08 (m, 1H), 3.76-3.62 (m, 2H), 2.64-2.53 (m, 2H), 2.08
13 (s, 3H), 2.05 (s, 3H). C NMR (150 MHz, CD2Cl2), δ (ppm): 168.56, 167.97, 150.83,
150.03, 149.92, 149.85, 149.19, 148.89, 146.81, 141.91, 141.84, 141.48, 140.69, 140.03,
138.51, 138.45, 133.19, 132.75, 127.03, 125.21, 124.82, 124.36, 124.29, 123.85, 123.67,
123.52, 123.39, 123.10, 119.79, 91.76, 89.10, 70.78, 61.92, 42.78, 22.05 (2 CH3-C).
-1 -1 UV/Vis (acetonitrile): λmax, nm (ε, M cm ) 249 (15000), 267 (sh, 14000), 378 (3000).
Emission (acetonitrile): λex, nm (Int.) 480 (160), 508 (147). HRMS: Calcd. for
+ C36H34IrN6O3 [M-PF6] : 791.2316 Found: 791.2320 Anal. Calcd. For C36H34F6IrN6O3P:
C, 46.20; H, 3.66; N, 8.98. Found: C, 46.51; H, 3.85; N, 9.21.
142 [Ir(bzq)2(7)]PF6: In 20 mL dry acetonitrile was suspended [{Ir(bzq)2(µ-Cl)}2] (0.045
g, 0.038 mmol). To this was added a 10-mL THF solution
of compound 7 (0.025 g, 0.096 mmol) followed by NH4PF6
(0.016 g, 0.096 mmol). The reaction mixture was purged
with argon, heated to 45 ºC, and left stirring for 12 h. The
reaction was complete after this time period as indicated by
TLC. The solvent was removed under reduced pressure to render a dark orange residue. The crude reaction mixture was washed with THF, water and ice-chilled methanol, followed by ether and pentane. The product was vacuum dried
1 to give analytically pure compound. Yield: 0.058 g (79%). H NMR (400 MHz, CD2Cl2),
δ (ppm): 9.48 (d, 1H, J = 13.7 Hz), 8.31-8.29 (m, 3H), 8.06 (q, 1H, J = 5.3, 1.2 Hz), 7.91-
7.85 (m, 4H), 7.78 (t, 1H, J = 6.5 Hz), 7.72-7.68 (m, 2H), 7.51 (d, 1H, J = 7.6 Hz), 7.47-
7.37 (m, 3H), 7.18-7.12 (m, 2H), 7.10 (td, 1H, J = 7.2, 1.4 Hz), 6.40-6.24 (m, 3H), 4.79-
4.62 (m, 1H), 3.98-3.94 (m, 1H), 3.85-3.82 (m, 2H), 2.70-2.36 (m, 2H). 13C NMR (150
MHz, CD2Cl2), δ (ppm): 158.10, 157.52, 151.21, 150.41, 149.44, 149.06, 148.37, 148.13,
146.42, 143.19, 141.57, 141.32, 140.15, 137.70, 134.86, 134.56, 130.50, 130.39, 130.29,
129.83, 129.74, 129.41, 127.79, 126.92, 124.88, 124.44, 124.10, 123.85, 122.95, 122.74,
122.37, 121.30, 120.80, 91.60, 88.92, 69.79, 61.11, 42.43. UV/Vis (acetonitrile): λmax,
-1 -1 nm (ε, M cm ) 242 (14000), 315 (8000). Emission (acetonitrile): λex, nm (Int.) 516
+ (176), 540 (sh, 150). HRMS: Calcd. for C38H30IrN6O3 [M-PF6] : 811.2003 Found:
811.2004 Anal. Calcd. For C38H30F6IrN6O3P: C, 47.75; H, 3.16; N, 8.79. Found: C,
47.86; H, 3.36; N, 9.11.
143 [Ir(btp)2(7)]PF6: In 25 mL dry acetonitrile was suspended [{Ir(btp)2(µ-Cl)}2] (0.050
g, 0.038 mmol). To this was added a solution of compound
7 (0.026 g, 0.098 mmol) in 10 mL dry THF, followed by
NH4PF6 (0.014 g, 0.086 mmol). After purging with argon,
the reaction mixture was sealed and heated to 45 ºC. The reaction was complete after 12 h as indicated by TLC. The solvent was removed under reduced pressure to render a brick-red residue. The crude reaction mixture was washed with THF, water and ice cold methanol, followed by ether and pentane. The remaining product was dried under vacuum to give analytically pure compound. Yield: 0.061 g
1 (78%). H NMR (400 MHz, acetone-d6), δ (ppm): 9.48 (d, 1H, J = 9.0 Hz), 8.47 (d, 1H, J
= 5.6 Hz), 8.27 (d, 1H, J = 6.3 Hz), 8.07-7.98 (m, 2H), 7.94-7.80 (m, 3H), 7.65-7.30 (m,
5H), 7.20 (dd, 2H, J = 8.9, 6.3 Hz), 7.10 (t, 2H, J = 6.4 Hz), 6.89 (dd, 2H, J = 7.6, 6.1
Hz), 6.45-6.40 (m, 1H), 6.19-6.09 (m, 2H), 4.70-4.39 (m, 1H), 4.21-3.92 (m, 1H), 3.76-
-1 -1 3.52 (m, 2H), 2.74-2.52 (m, 2H). UV/Vis (acetonitrile): λmax, nm (ε, M cm ) 283
(31000), 325 (20000), 435 (7500). Emission (acetonitrile): λex, nm (Int.) 593 (180), 637
+ (126). HRMS: Calcd. for C38H30IrN6O3S2 [M-PF6] : 875.1445 Found: 875.1437 Anal.
Calcd. For C38H30F6IrN6O3PS2: C, 44.75; H, 2.96; N, 8.24. Found: C, 44.88; H, 3.19; N,
8.27.
[Ir(pq)2(7)]PF6: Chloro-bridged dimer, [{Ir(pq)2(µ-Cl)}2] (0.040 g, 0.031 mmol) was suspended in 20 ml of dry acetonitrile. To this was added a 10-mL THF solution of compound of 7 (0.021 g, 0.078 mmol) followed by NH4PF6 (0.013 g, 0.078 mmol). After purging with argon, the reaction mixture was heated to 45 ºC and left stirring for 16 h.
144 The reaction was complete after this time period as
indicated by TLC. The solvent was removed under
reduced pressure to render a dark orange residue. The
crude reaction mixture was washed with THF, water
and ice-cold acetone followed by ether and pentane. The
product was vacuum-dried to give analytically pure
1 compound. Yield: 0.048 g (76%). H NMR (400 MHz, CD2Cl2), δ (ppm): 8.90 (m, 1H),
8.28-8.13 (m, 4H), 8.08-8.05 (m, 2H), 7.95 (dd, 1H, J = 5.8, 4.7 Hz), 7.77-7.69 (m, 4H),
7.60 (dd, 1H, J = 9.3, 9.1 Hz), 7.39-7.11 (m, 7H), 6.93 (dd, 1H, J = 8.2 Hz), 6.86 (dd, 1H,
J = 7.4 Hz ), 6.79-6.75 (m, 1H), 6.69 (d, 1H, J = 7.6 Hz), 6.52 (dd, 1H, J = 8.5, 6.7 Hz),
6.30-6.26 (m, 1H), 4.60-4.27 (m, 1H), 3.96-3.95 (m, 1H), 3.71-3.63 (m, 2H), 2.57-2.22
13 (m, 2H). C NMR (150 MHz, CD2Cl2), δ (ppm): 171.10, 170.21, 151.59, 149.67, 148.51,
148.31, 148.08, 147.21, 146.88, 146.41, 140.43, 140.19, 139.85, 135.77, 134.94, 131.99,
131.76, 131.09, 130.59, 129.67, 129.32, 128.30, 128.03, 127.51, 127.37, 127.08, 126.97,
126.64, 126.03, 125.79, 125.25, 123.68, 123.57, 123.26, 123.05, 117.88, 117.80, 91.31,
-1 -1 89.11, 69.81, 61.48, 41.99. UV/Vis (acetonitrile): λmax, nm (ε, M cm ) 234 (8,200), 264
(7,600), 332 (4000). Emission (acetonitrile): λex, nm (Int.) 567 (245). HRMS: Calcd. for
+ C42H34IrN6O3 [M-PF6] : 863.2322 Found: 863.2328 Anal. Calcd. For C42H34F6IrN6O3P:
C, 50.05; H, 3.40; N, 8.34. Found: C, 50.15; H, 3.77; N, 8.60.
4.4.4. Luminescence Measurements
Steady-state luminescence spectra were recorded by Dr. T. S. Teets at room temperature on a Cary Eclipse fluorescence spectrophotometer, or on an automated
145 Photon Technology International (PTI) QM 4 fluorimeter equipped with a 150-W Xe arc lamp and a Hamamatsu R928 photomultiplier tube at Massachusetts Institute of
Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge,
Massachusetts 02139 (USA). Excitation light was excluded with suitable glass filters.
Sample solutions were added to a quartz ESR tube equipped with a Teflon valve, freeze- pump-thaw degassed (four cycles, 1 × 10–5 Torr) and sealed. Low temperature emission spectra were recorded in rigid solvent glass at 77 K by immersion of the sealed ESR tubes into a liquid nitrogen-filled dewar. Time-resolved phosphorescence lifetime data were recorded on a nanosecond laser system described previously.101
Emission quantum yields (23 ± 2 °C) were measured102 in deoxygenated 2- methyltetrahydrofuran by referencing sample luminescence intensities to those of
103 optically dilute standards of 9,10-diphenylanthracene (φem = 0.9) in cyclohexane.
Quantum yields φ were computed by:
⎛⎞ADη2 φ=φ rs s sr⎜⎟AD2 ⎝⎠srη r where r and s indicate reference and sample, respectively, A is the absorbance at wavelength λexc, η is the refractive index of the solvent, and D is the integrated area beneath the absorption spectrum.
4.5. References
(1) Kim, M. K.; Lim, C. S.; Hong, J. T.; Han, J. H.; Jang, H.-Y.; Kim, H. M.; Cho, B. R. Angew. Chemie Int. Ed. 2010, 49, 364–367.
(2) Hirayama, T.; Okuda, K.; Nagasawa, H. Chem. Sci. 2013, 4, 1250–1256.
146 (3) Lippert, A. R.; New, E. J.; Chang, C. J. J. Am. Chem. Soc. 2011, 133, 10078– 10080.
(4) Qian, Y.; Karpus, J.; Kabil, O.; Zhang, S.-Y.; Zhu, H.-L.; Banerjee, R.; Zhao, J.; He, C. Nat Commun 2011, 2, 495.
(5) Guo, Z.; Nam, S.; Park, S.; Yoon, J. Chem. Sci. 2012, 3, 2760–2765.
(6) Wang, J.; Karpus, J.; Zhao, B. S.; Luo, Z.; Chen, P. R.; He, C. Angew. Chemie Int. Ed. 2012, 51, 9652–9656.
(7) Li, F. J. Am. Chem. Soc. 2011, 133, 11231–11239.
(8) Peng, X.; Wu, T.; Fan, J.; Wang, J.; Zhang, S.; Song, F.; Sun, S. Angew. Chemie Int. Ed. 2011, 50, 4180–4183.
(9) Gill, M. R.; Garcia-Lara, J.; Foster, S. J.; Smythe, C.; Battaglia, G.; Thomas, J. A. Nat Chem 2009, 1, 662–667.
(10) Li, G.; Chen, Y.; Wang, J.; Lin, Q.; Zhao, J.; Ji, L.; Chao, H. Chem. Sci. 2013, 4, 4426–4433.
(11) Montgomery, C. P.; Murray, B. S.; New, E. J.; Pal, R.; Parker, D. Acc. Chem. Res. 2009, 42, 925–937.
(12) Mohandessi, S.; Rajendran, M.; Magda, D.; Miller, L. W. Chem. – A Eur. J. 2012, 18, 10825–10829.
(13) Lee, K.-S.; Kim, T.-K.; Lee, J. H.; Kim, H.-J.; Hong, J.-I. Chem. Commun. 2008, 6173–6175.
(14) Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 2nd ed.; Kluwer Academic/Plenum Publisher: New York, 1999.
(15) Fernandez-Moreira, V.; Thorp-Greenwood, F. L.; Coogan, M. P. Chem. Commun. 2010, 46, 186–202.
(16) Wu, Y.; Jing, H.; Dong, Z.; Zhao, Q.; Wu, H.; Li, F. Inorg. Chem. 2011, 50, 7412– 7420.
(17) Zhao, Q.; Liu, S.; Li, F.; Yi, T.; Huang, C. Dalt. Trans. 2008, 3836–3840.
(18) Han, Y.; You, Y.; Lee, Y.-M.; Nam, W. Adv. Mater. 2012, 24, 2748–2754.
(19) You, Y.; Han, Y.; Lee, Y.-M.; Park, S. Y.; Nam, W.; Lippard, S. J. J. Am. Chem. Soc. 2011, 133, 11488–11491.
147 (20) You, Y.; Lee, S.; Kim, T.; Ohkubo, K.; Chae, W.-S.; Fukuzumi, S.; Jhon, G.-J.; Nam, W.; Lippard, S. J. J. Am. Chem. Soc. 2011, 133, 18328–18342.
(21) Lee, P.-K.; Law, W. H.-T.; Liu, H.-W.; Lo, K. K.-W. Inorg. Chem. 2011, 50, 8570–8579.
(22) Koren, K.; Dmitriev, R. I.; Borisov, S. M.; Papkovsky, D. B.; Klimant, I. ChemBioChem 2012, 13, 1184–1190.
(23) Zhang, S.; Hosaka, M.; Yoshihara, T.; Negishi, K.; Iida, Y.; Tobita, S.; Takeuchi, T. Cancer Res. 2010, 70, 4490–4498.
(24) Yoshihara, T.; Yamaguchi, Y.; Hosaka, M.; Takeuchi, T.; Tobita, S. Angew. Chemie Int. Ed. 2012, 51, 4148–4151.
(25) Reddy G., U.; Das, P.; Saha, S.; Baidya, M.; Ghosh, S. K.; Das, A. Chem. Commun. 2013, 49, 255–257.
(26) Li, C.; Lin, J.; Guo, Y.; Zhang, S. Chem. Commun. 2011, 47, 4442–4444.
(27) Wong, K.-Y. Angew. Chem. Int. Ed. Engl. 2008, 47, 3735–3739.
(28) Wang, X.; Jia, J.; Huang, Z.; Zhou, M.; Fei, H. Chem. – A Eur. J. 2011, 17, 8028– 8032.
(29) Xiong, L.; Zhao, Q.; Chen, H.; Wu, Y.; Dong, Z.; Zhou, Z.; Li, F. Inorg. Chem. 2010, 49, 6402–6408.
(30) Liu, X.; Xi, N.; Liu, S.; Ma, Y.; Yang, H.; Li, H.; He, J.; Zhao, Q.; Li, F.; Huang, W. J. Mater. Chem. 2012, 22, 7894–7901.
(31) Zhou, C.; Shi, Y.; Ding, X.; Li, M.; Luo, J.; Lu, Z.; Xiao, D. Anal. Chem. 2012, 85, 1171–1176.
(32) Zhang, K. Y.; Li, S. P.-Y.; Zhu, N.; Or, I. W.-S.; Cheung, M. S.-H.; Lam, Y.-W.; Lo, K. K.-W. Inorg. Chem. 2010, 49, 2530–2540.
(33) Li, S. P.-Y.; Tang, T. S.-M.; Yiu, K. S.-M.; Lo, K. K.-W. Chemistry 2012, 18, 13342–13354.
(34) Moromizato, S.; Hisamatsu, Y.; Suzuki, T.; Matsuo, Y.; Abe, R.; Aoki, S. Inorg. Chem. 2012, 51, 12697–12706.
(35) Lo, K. K.-W.; Leung, S.-K.; Pan, C.-Y. Inorganica Chim. Acta 2012, 380, 343– 349.
148 (36) Lee, P.-K.; Liu, H.-W.; Yiu, S.-M.; Louie, M.-W.; Lo, K. K.-W. Dalt. Trans. 2011, 40, 2180–2189.
(37) Shi, H.; Sun, H.; Yang, H.; Liu, S.; Jenkins, G.; Feng, W.; Li, F.; Zhao, Q.; Liu, B.; Huang, W. Adv. Funct. Mater. 2013, 23, 3268–3276.
(38) Yang, H.; Li, L.; Wan, L.; Zhou, Z.; Yang, S. Inorg. Chem. Commun. 2010, 13, 1387–1390.
(39) Jiang, W.; Gao, Y.; Sun, Y.; Ding, F.; Xu, Y.; Bian, Z.; Li, F.; Bian, J.; Huang, C. Inorg. Chem. 2010, 49, 3252–3260.
(40) Baggaley, E.; Weinstein, J. A.; Williams, J. A. G. Coord. Chem. Rev. 2012, 256, 1762–1785.
(41) Lo, K. K.-W.; Li, S. P.-Y.; Zhang, K. Y. New J. Chem. 2011, 35, 265–287.
(42) Haas, K. L.; Franz, K. J. Chem. Rev. 2009, 109, 4921–4960.
(43) Yang, Y.; Zhao, Q.; Feng, W.; Li, F. Chem. Rev. 2013, 113, 192–270.
(44) Thorpe-Greenwood, F. L. Organometallics 2012, 31, 5686–5692.
(45) Patra, M.; Gasser, G. ChemBioChem 2012, 13, 1232–1252.
(46) Baggaley, E.; Weinstein, J. A. ; Williams, J. A. G. Coord. Chem. Rev. 2012, 256, 1762–1785.
(47) Thorp-Greenwood, F. L.; Balasingham, R. G. . C.; M. P. J. Organomet. Chem. 2012, 714, 12–21.
(48) Lo, K. K. -W.; Choi, A. W. -T.; Law, W. H.-T. Dalton. Trans. 2012, 41, 6021– 6047.
(49) Zhao, Q.; Huang, C.; Li, F. Chem. Soc. Rev. 2011, 40, 2508–2524.
(50) Lo, K. K. -W.; Li, S. P. -Y.; Zhang, K. Y. New J. Chem. 2011, 35, 265–287.
(51) Lo, K. K.-W.; Zhang, K. Y.; Li, S. P.-Y. Pure. Appl. Chem. 2011, 83, 823−840.
(52) Ruggi, A.; Reinhoudt, D. N.; Velders, A. H. In In Bioinorganic Medicinal Chemistry; Wiley: New York, 2011; p. 397−421.
(53) Shavaleev, N. M.; Monti, F.; Scopelliti, R.; Baschieri, A.; Sambri, L.; Armaroli, N.; Gratzel, M.; Nazeeruddin, M. K. Organometallics 2013, 32, 460–467.
149 (54) Shavaleev, N. M.; Monti, F.; Costa, R. D.; Scopelliti, R.; Bolink, H. J.; Ortí, E.; Accorsi, G.; Armaroli, N.; Baranoff, E.; Grätzel, M.; Nazeeruddin, M. K. Inorg. Chem. 2012, 51, 2263–2271.
(55) Rausch, A. F.; Thompson, M. E.; Yersin, H. J. Phys. Chem. A 2009, 113, 5927−5932.
(56) Stagni, S.; Colella, S.; Palazzi, A.; Valenti, G.; Zacchini, S.; Paolucci, F.; Marcaccio, M.; Albuquerque, R. Q.; De Cola, L. Inorg. Chem. 2008, 47, 10509– 10521.
(57) Tamayo, A. B.; Garon, S.; Sajoto, T.; Djurovich, P. I.; Tsyba, I. M.; Bau, R.; Thompson, M. E. Inorg. Chem. 2005, 44, 8723–8732.
(58) Neve, F.; Crispini, A.; Campagna, S.; Serroni, S. Inorg. Chem. 1999, 38, 2250−2258.
(59) Yersin, H.; Finkenzeller, W. J. Highly Efficient OLEDs with Phosphorescent Materials; H. Yersin.; Wiley-VCH: Weinheim, Germany, 2008; pp. 1–97.
(60) Ulbricht, C.; Beyer, B.; Friebe, C.; Winter, A.; Schubert, U. S. Adv. Mater. 2009, 21, 4418−4441.
(61) Wilde, A. P.; King, K. A.; Watts, R. J. J. Phys. Chem. 1991, 95, 629– 634.
(62) Dedeian, K.; Djurovich, P. I.; Garces, F. O.; Carlson, G.; Watts, R. J. Inorg. Chem. 1991, 30, 1685–1687.
(63) Garces, F. O.; Watts, R. J. Inorg. Chem. 1990, 29, 582–584.
(64) Garces, F. O.; King, J. A.; Watts, R. J. Inorg. Chem. 1988, 27, 3464–3471.
(65) Ohsawa, Y.; Sprouse, S.; King, K. A.; DeArmond, M. K. .; Hanck, K. W.; Watts, R. J. J. Phys. Chem. 1987, 91, 1047–1054.
(66) King, K. A.; Spellane, P. J.; Watts, R. J. J. Am. Chem. Soc. 1985, 107, 1431–1432.
(67) Sprouse, S.; King, K. A.; Spellane, P. J.; Watts, R. J. J. Am. Chem. Soc. 1984, 106, 6647–6653.
(68) Zhao, Q.; M. Yu,; Shi, L.; Liu, S.; Li, C.; Shi, M.; Zhou, Z.; Huang, C.; Li, F. . Organometallics 2010, 29, 1085–1091.
(69) Lo, K. K. W.; Lau, J. S. Y. Inorg. Chem. 2007, 46, 700–709.
(70) Lo, K. K.; Chan, J. S.; Chung, C.; Lui, L. Organometallics 2004, 23, 3108–3116.
150 (71) Lo, K. K.-W.; Zhang, K. Y.; Chung, C.-K.; Kwok, K. Y. Chem. Eur. J. 2007, 13, 7110−7120.
(72) Lo, K. K.-W.; Zhang, K. Y.; Leung, S.-K.; Tang, M.-C. Angew. Chem. Int. Ed. 2008, 47, 2213–2216.
(73) Liu, H.-W.; Zhang, K. Y.; Law, W. H.-T.; Lo, K. K.-W. Organometallics 2010, 29, 3474−3476.
(74) Chen, Y.; Qiao, L.; Ji, L.; Chao, H. Biomaterials 2014, 35, 2–13.
(75) Choi, J. S.; Berdis, A. J. Futur. Med. Chem. 2012, 4, 1461–1478.
(76) Smith, K.M.; Slugoski, M.D.; Loewen, S.K.; Ng, A.M.L.; Yao, S.Y.M.; Chen, X.Z.; Karpinski, E.; Cass; C. E.; Baldwin, S. A.; Young, J. D. J. Biol. Chem. 2005, 280:, 25436–25449.
(77) Robak, T.; Robak, P. Curr. Pharm. Des. 2012, 18, 3373–3388.
(78) Koczor, C. A.; Torres, R. A.; Lewis, W. Expert Opin. Drug Metab. Toxicol. 2012, 8, 665–676.
(79) Marks, P. W. Expert Rev. Anticancer Ther. 2012, 12, 299–305.
(80) Gesto, D. S.; Cerqueira, N. M. F. S. A.; Fernandes, P. A. and Ramos, M. J. Curr. Med. Chem. 2012, 19, 1076–1087.
(81) Gandhi V, P. W. Curr. Opin. Oncol. 2006, 18, 584–590.
(82) Parker, W.B.; Secrist III, J.A.; Waud, W. R. Curr. Opin. Investig. Drugs 2004, 5, 592–596.
(83) Gandhi, V.; Plunkett, W. Clin Pharmacokinet. 2002, 41, 93–103.
(84) Plunkett W, G. V. Hematol Cell Ther. 1996, 38, S67–74.
(85) Berdis, A. J. Biochemistry 2008, 47.
(86) Johnson, Z. L.; Cheong, C. G.; Lee, S. Y. . Nature 2012, 483, 489–493.
(87) Maity, A.; Anderson, B. L.; Deligonul, N; Gray, T. G. Chem. Sci. 2013, 4, 1175– 1181.
(88) Liu, S.; Müller, P. Takase, M. K.; Swager, T. M. Inorg. Chem. 2011, 50, 7598– 7609.
151 (89) Zanarini, S.; Felici, M.; Valenti, G.; Marcaccio, M.; Prodi, L.; Bonacchi, S.; Contreras-Carballada, P.; Williams, R. M.; Feiters, M. C.; Nolte, R. J. M.; De Cola, L.; Paolucci, F. Chem. – A Eur. J. 2011, 17, 4640–4647.
(90) Swanick, K. N.; Ladouceur, S.; Zysman-Colman, E.; Ding, Z. Chem. Commun. (Camb). 2012, 48, 3179–3181.
(91) Fernández-Hernández, J. M.; Beltrán, J. I.; Lemaur, V.; Gálvez-López, M.-D.; Chien, C.-H.; Polo, F.; Orselli, E.; Fröhlich, R.; Cornil, J.; De Cola, L. Inorg. Chem. 2013, 52, 1812–1824.
(92) Tamayo, A. B.; Alleyne, B. D.; Djurovich, P. I.; Lamansky, S.; Tsyba, I.; Ho, N. N.; Bau, R.; Thompson, M. E. J. Am. Chem. Soc. 2003, 125, 7377–7387.
(93) You, Y.; Nam, W. Chem. Soc. Rev. 2012, 41, 7061–7084.
(94) Rolland, V.; Kotera, M.; Lhomme, J. Synth. Commun. 1997, 27, 3505–3511.
(95) Nonoyama. Bull. Chem. Soc. Jpn. 1974, 47, 767–768.
(96) E. Baranoff, B. F. E. Curchod, J. Frey, R. Scopelliti, F. Kessler, I. Tavernelli, U. Rothlisberger, M. Graetzel, M. K. N. Inorg. Chem. 2012, 215–224.
(97) Shin, I.; Yoon, S.; Kim, J. I.; Lee, J.; Kim, T. H.; Kim, H. Electrochim. Acta 2011, 56, 6219–6223.
(98) T. Peng, Y. Yang, Y. Liu, D. Ma, Z. Houc, Y. W. Chem. Commun. 2011, 47, 150– 3152.
(99) M. Schmittel, S. Q. Chem. Commun. 2012, 48,, 2707–2709.
(100) S. Lamansky, P. Djurovich, D. Murphy, F. Abdel-Razzaq, H. Lee, C. Adachi, P. E. Burrows, S. R. Forrest, M. E. T. J. Am. Chem. Soc. 2001, 123, 4304–4312.
(101) E. J. McLaurin, A. B. Greytak, M. G. Bawendi, D. G. Nocera. J. Am. Chem. Soc. 2009, 131, 12994–13001.
(102) Demas, J. N.; Crosby, G. A. J. Phys. Chem. 1971, 75, 991–1024.
(103) S. Hamai, F. Hirayama. J. Phys. Chem. 1983, 87, 83–89.
152 Chapter 5 Synthesis and Reactivity of Bridging and Terminal Fluoride Complexes of Bis(cyclometalated) Iridium(III)
153 This work has been submitted for publication.
5.1. Introduction
There are relatively few literature reports on fluorides complexes of late transition metals in contrast to the large number of known inorganic Lewis acids binding to chlorides, bromides or iodides.1,2 It is known that late d-block metals with higher electron count, are more compatible with functional groups and less oxophilic than early transition metals. Fluoro complexes of late transition metals are currently under investigation.
Fluoride is compact, hard, and minimally polarizable. In accordance with hard-soft acid- base theory, the hard fluoride ligand is with large and soft late transition metals.3
Fluoride complexes of the late transition metals are relatively labile owing to d-p π- antibonding interactions between lone pairs on fluorine and metal d-electrons,4–6.
Sadighi and co-workers were reported the first terminal fluoride of gold.7 This complex inserts inactivated alkynes in a 1,2-fluoroauration reaction. The same authors demonstrated gold-catalyzed 1,2-hydrofluorination of alkynes from (carbene)gold(I) chlorides and mild F– sources. The olefinic products are primarily E-isomers.8 Afterward, the groups of Fackler9 and Toste10,11 described fluoride complexes of gold(II) and gold(III) respectively. Holland and collaborators12 have disclosed iron(II) fluorides, both bridging and terminal. These complexes react with main-group electrophiles. Catalytic hydrodefluorination of fluorocarbons was achieved, albeit with low turnovers. Recent findings of Beller and co-workers have shown that a terminal iron(II) fluoride complex catalyzes the hydrogenation of CO2 and bicarbonate. These few examples illustrate the useful reactivity of late metal fluorides.13–24
154 Cyclometalated iridium(III) complexes are pervasive organometallics of the late d- block. Octahedral bis- and tris(cyclometalated) Ir(III) complexes are triplet-state emitters.25,26 Excited-state lifetimes are on the scale of microseconds at room temperature. Double-digit emission quantum yields are common. The prototype is fac-
[Ir(ppy)3], where ppy = 2-phenylpyridine. This complex emits green phosphorescence,
27 λem = 508 nm in 2-methyltetrahydrofuran at room temperature. Iridium(III) is substitutionally inert,28 and its cyclometalates are stable on the open bench top and in electronic devices. Iridium(III) cyclometalates are lumophores known for light-emitting diodes,29,30 light-emitting electrochemical cells,31–34 and biological tags.35–40
41 Bis(cyclometalates) are (pre)catalysts for water oxidation and sensitizers for CO2
42 43 reduction and H2 evolution.
Cyclometalated Ir(III) complexes of fluoride are attractive as synthons, as catalysts, and as emitters in their own right. Bergman and co-workers have investigated piano- stool complexes of (fluoro)iridium(III).44 The fluoride ligand is weakly bound, even in nonpolar solvents. Both fluoride and triflate have similar labilities in this family of complexes. Thermodynamic affinities of F– for Ir(III) are as anticipated by hard-soft acid-base theory: phosphine > pyridine > water. The bound fluoride reacts with main- group electrophiles, and iridium(III) with nucleophiles. More recently, Kläring and
45,46 Braun have documented the insertion of CS2 into the Ir(III)–F bond of a five- coordinate complex. Density-functional theory (DFT) calculations suggest a synchronous mechanism, where C–F bond making coincides with Ir–F bond breaking. These results show that iridium(III) fluoride complexes are isolable and reactive.
155 For the first time we report the synthesis of bis-cyclometalated iridium(III) fluorides.
Both bridging and terminal fluorides are described. Terminal fluoride ligands are stabilized by hydrogen-bond donors in the metal’s coordination sphere, and possibly by nearby C–H bonds. They react with carbon- and silicon-based electrophiles. Dimeric and monomeric fluoride complexes are phosphorescent.
5.2. Results and Discussion
Reaction of the dimer [(bt)2Ir(µ-Cl)]2 with 2.5 eq AgF in methanol yielded fluoro- bridged dimer 1a at room temperature, Scheme 5.2.1.
Scheme 5.2.1. Syntheses of cyclometalated iridium(III) fluoride complexes.
156 An analogous synthesis delivers fluoro-bridged dimer 1b where the cyclometalating ligand on iridium is 2-(2,4-difluorophenyl)pyridine (F2ppy). The bridged products are isolated by filtration of methanol solutions followed by precipitation with diethyl ether.
Vapor diffusion of pentane into THF/benzene solution of 1a produced diffraction- quality crystals. A thermal ellipsoid depiction appears as Figure 5.2.1. The Ir–F bond distance is 2.172(2) Å, and the Ir···Ir distance is 3.454 Å; there is no suggestion of direct metal-metal bonding.
Figure 5.2.1. Crystal structure of the iridium(III) dimer [(bt)2Ir(µ-F)]2 (50%) (1a) showing ellipsoids at the 50% probability level. Unlabeled atoms are carbon. Selected interatomic distances (Å): Ir1–F1: 2.172(2); Ir1–Ir1ʹ: 3.454; Ir1–N1 2.045(4). This crystal structure was collected by Dr. C. E. Moore and Prof. A. Rheingold, University of California at San Diego.
157 Reaction of red 1a with 3,5-dimethylpyrazole in dry chloroform proceeded for 6 h at
19 55 °C without color change. F NMR experiments indicate loss of the (µ-F)2 dimer with formation of a new fluorine-containing species, δ –260 ppm. The 1H NMR spectrum shows two singlets at δ 2.3 and 3.4 ppm corresponding to the methyl groups of 3,5- dimethylpyrazole; methyl groups of the free ligand resonate at δ 2.28 ppm. Workup in air, followed by precipitation with pentane and washing with ether affords terminal fluoride 2a in 84% isolated yield as a red solid. A similar synthesis yielded a terminal fluoride complex with the cyclometalating ligand F2ppy, Scheme 5.2.1. In this complex,
19F resonances integrate in the expected 4:1 (ligand : terminal fluoro) ratio.
Figure 5.2.2. Crystal structure of 2a (50% probability). Hydrogen atoms are omitted for clarity. A partial atom labelling scheme is indicated; unlabelled atoms are carbon. Selected interatomic distances (Å): Ir1–C13, 1.997(9); Ir1–C26, 2.004(9); Ir1–N1, 2.040(8); Ir1–N2, 2.059(8); Ir1–F1, 2.168(5); Ir1–N3, 2.172(7). Selected angle (°): C13–Ir1–F1, 178.4(3). This crystal structure was collected by Dr. M. Zeller, Youngstown State University.
In complex 2a, a pyrazole nitrogen is poised to donate a hydrogen bond to fluoride.
No reaction is observed between 1a and 1,3,5-trimethylimidazole, Scheme 5.2.1.
Attempts to synthesize a terminal fluoro complex from (µ-F)2 dimers with trimethylphosphine, trimethylphosphine, tricyclohexylphosphine, pyridine, 3,5-
158 difluoropyridine, acetonitrile, and tert-butylisonitrile led to recovery of starting material.
However, reaction of 1a with 2-aminopyridine at 55 °C for 12 h in CHCl3 yielded the corresponding fluoride complex ligated by 2-aminopyridine. This complex was isolated similarly, as an air-stable red solid.
The crystal structure of 2a appears as Figure 5.2.2. Both enantiomers are present in the unit cell. Fluoride and 3,5-dimethylpyhrazole are trans to carbon atoms. Pyrazole nitrogen and fluoride are similar trans influencers. The Ir–C bond length opposite F is
1.997(9); that trans to N is 2.004(9), and the difference between them is not statistically significant.47 The Ir–F bond distance is 2.168(5) Å. The Ir–F bond distance in dimer 1a is 2.176(2), also not significantly different from that of 2a. For comparison, the Ir–F
Et 44 bond length in Bergman’s Cp Ir(PMe3)(Ph)F is 2.069(4) Å, and those in Braun’s iridium(III) fluoro hydride complexes are 2.039(2) and 2.0508(17).45 All three are significantly shorter than either Ir–F bond encountered here. The bond between Ir and the dimethylpyrazole nitrogen is longer than the iridium-cyclometalating nitrogen bonds:
2.172(7) Å, vs. 2.040(8) and 2.059(8) Å, respectively. Other metrics involving 3,5- dimethylpyrazole and the cyclometalating ligands are unexceptional.
A hydrogen bond exists between 3,5-dimethylpyrazole and fluoride. The distance between F and N4 in 2a (Figure 5.2.2) is 2.536 Å. This separation is consistent with an
NH···F hydrogen bond, as suggested by Wallwork.48
Complex 2a was selected for reactivity studies. The complex reacts in high yields with a range of organosilicon compounds, Scheme 5.2.2. Reaction with silyl chloride and bromide reagents yields halide complexes with loss of fluoride. Phenolato and thiophenolato ligands are installed by treatment with the corresponding trimethylsilyl
159 – – reagents. The pseudohalides N3 and NCS are also bound to Ir(III) by displacement with silicon species. Crystal structures have been obtained for 3a, 5a, and 8a. Thermal ellipsoid depictions appear in Figure 5.2.3. The structure of chloro complex 3a indicates a pyrazole NH···Cl hydrogen bond similar to that of 2a.
a) b)
c)
Figure 5.2.3. a) Crystal structure of 3a (50% probability). b) Crystal structure of 5a (50% probability). c) Crystal structure of 7a (50% probability). Hydrogen atoms are omitted for clarity. A partial atom labelling scheme is indicated; unlabelled atoms are carbon. This crystal structure was collected by Dr. M. Zeller, Youngstown State University.
160
Scheme 5.2.2. Reactions of terminal fluoride complex 2a with organosilanes. A numbering system and isolated yields are indicated.
161 Reaction of 2a with sulfur- and carbon-based electrophiles yielded sulfonyl and acyl fluorides, Scheme 5.2.3. Tosyl chloride reacts with 2a to yield tosyl fluoride in 95% spectroscopic yield. Acyl chlorides react to form aryl fluorides in yields better than 90%, whereas a chloromethyl functionality survives. The longer reaction times and generally harsher conditions here indicate that the terminal F– of 2a is less labile than those described earlier43 in substituted cyclopentadienyl complexes.
O O O O S S Cl 2a F 95% THF 45 °C, 12 h
O O Cl 2a F 99% THF rt, 6 h
O O 2a Cl 91% Cl Cl F THF rt, 6 h
Scheme 5.2.3. Reactions of 2a with sulphur- and carbon-based electrophiles. Yields were determined by 19F NMR integration relative to an internal standard.
Both terminal and bridging fluoride complexes are luminescent. Figure 5.2.3 shows absorption and emission spectra of 1a and 2a at 298 K in 2-methyltetrahydrofuran.
Emission is quenched on exposure to air, and vibronic structure is evident. Table 5.2.1 collects photophysical properties of fluoride complexes and terminal chloride (3a) and bromide (4a) analogues. Emission lifetimes are microsecond-scale at 298 K and 77 K.
162
Figure 5.2.4. Normalized, room-temperature emission spectra of 1a (solid) and 2a (dashed) in 2- methyltetrahydrofuran. The excitation wavelength is 355 nm.
Table 5.2.1. Emission wavelengths (Eem), quantum yields (φem) and lifetimes (τ) of bridging and terminal fluoride complexes at 298 and 77 K in 2-methyltetrahydrofuran.
[a] Compound Eem (nm) φem τ (µs), 298 K τ (µs), 77 K 1a 566, 610 0.32 1.6 6.4 2a 556, 592 0.073 1.3 3.4 3a 551, 591 0.18 1.2 2.6 4a 551, 591 0.28 0.85 3.5 1b 526 0.033 0.66 3.4 2c 557, 591 (sh) 0.050 1.2 3.3
[a] Error in quantum yield is ± 10%; absorbance of solutions was ≤ 0.1. Standard deviations in lifetime measurements are within 4% of stated value.
The emission quantum yields were collected by Mr. Robert Stanek. Compound 1a has a notable quantum yield of 26%. Quantum yields of terminal fluoride complexes are less.
Luminescence from 1a is red-shifted from that of terminal fluoride 2a.
Emission maxima of mononuclear halide complexes are insensitive to the identity of the halogen. This, combined with the vibronic structure of the emission spectra, indicates
163 excited states resident mainly on the organic ligands. The long lifetimes and O2 quenching suggests triplet-state emission, as is usual for cyclometalates of Ir(III).25,26,30
5.3. Conclusion
To summarize, we report the first fluoride complexes of cyclometalated iridium(III).
Fluoro-bridged dimers form upon treatment of the corresponding µ2-Cl2 complexes with
AgF. Reaction with hydrogen-bond donating ligands affords terminal fluorides. The crystal structure of one complex indicates that fluoride engages in a second-sphere hydrogen bond to a pyrazole proton. The new fluoride complexes are phosphorescent; the emission quantum yield of the dimer is 26% at room temperature. However, a terminal fluoride complex emits in lower yield than the corresponding complexes of the higher halides. Terminal fluoride complex 2a reacts with carbon and silicon electrophiles. Late d-block fluorides are emergent synthons in organometallic chemistry.
The new complexes broaden the range of late-metal fluorides to cyclometalated Ir(III).
Consequences for reactivity and materials synthesis are being pursued.
5.4. Experimental Section
5.4.1. Materials and Methods
All experiments involving fluoride-bridged complexes or terminal-fluoride complexes were conducted under argon using standard Schlenk line techniques or inside a nitrogen-filled MBraun glove box. Anhydrous solvents were used for all experiments unless mentioned otherwise. Anhydrous chloroform was passed through activated basic alumina before it was used for synthesizing 2a. 1H NMR experiments were performed on
164 a Varian INOVA AS-400 NMR spectrometer operating at 399.7 MHz. Chemical shifts are reported in parts per million (δ) with integration and multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, dt = doublet of triplets, td = triplet of doublets and m = multiplet), measured from tetramethylsilane (0 ppm) and are
19 referenced to the solvent CDCl3 (7.26 ppm) and C6D6 (7.15 ppm). F NMR spectra were recorded on a Varian INOVA AS-400 spectrometer operating at 376.1 MHz; chemical shifts are reported in parts per million (δ) and measured from CFCl3 (0.00 ppm).
Anhydrous 2-methyltetrahydrofuran was purchased from Sigma-Aldrich and was degassed for at least 20 minutes prior to use for UV-vis and luminescence measurements.
UV-vis and luminescence data were recorded using a Cary 5G UV-vis-NIR spectrometer and a Cary Eclipse spectrometer, respectively. Elemental analyses were carried out by
Midwest Microlab, LLC, Indianapolis, IN.
Anhydrous solvents were obtained from MBraun solvent purification system or were purchased from Sigma-Aldrich and Acros Organics. Chemicals from commercial sources were used as received. IrCl3·3H2O and silver(I) fluoride (AgF) were purchased from
Strem Chemicals. 2-phenylbenzothiazole (bt), 2-(2,4-difluorophenyl)pyridine (F2ppy), triisopropylsilyl chloride, bromotrimethylsilane, trimethyl(phenylthio)silane, trimethyl(phenoxy)silane and (trimethylsilyl)isothiocyanate were purchased from Sigma-
Aldrich. Azidotrimethylsilane, p-tolylsulfonyl chloride and chloroacetyl chloride were purchased from Acros Organics.
Cyclometalated Ir(III) µ-chloro-bridged dimers, (C^N)2Ir(µ-Cl)2Ir(C^N)2 were
49 synthesized via the method reported by Nonoyama; IrCl3·3H2O was refluxed with 2–2.5 equiv cyclometalating ligand in a 2:1 mixture of 2-ethoxyethanol and water. Synthesis
165 50 51 and characterization of [(bt)2Ir(µ-Cl)2Ir(bt)2] and [(F2ppy)2Ir(µ-Cl)2Ir(F2ppy)2] were reported previously.
5.4.2. Synthesis of Fluoride Bridged Ir(III) Cyclometalates
[{Ir(bt)2(µ-F)}2] (1a): A 100-mL round bottom flask was loaded with [{Ir(bt)2(µ-
Cl)}2] (0.500 g, 0.386 mmol) under argon. To this was added 20 mL anhydrous methanol followed by AgF (0.122 g, 0.964 mmol). The reaction mixture was stirred vigorously for
6 h under argon at room temperature. After this time, the crude reaction mixture was passed through a bed of celite to remove silver chloride and excess silver fluoride resulting in a clear orange filtrate. Solvent was removed under vacuum rendering a red residue, which was re-dissolved into toluene. The volume of toluene was reduced to a minimum, and addition of excess pentane led to precipitation of the desired fluoro- bridged product as a red solid. The solid was collected by filtration and washed with pentane and diethyl ether. Drying under vacuum for 6 h yielded analytically pure product
1 as a red fluffy solid. Yield: 0.365 g (75%). H NMR (400 MHz, C6D6), δ: 9.00 (d, 4H, J =
7.3 Hz), 7.49 (d, 4H, J = 7.3 Hz), 6.85 (d, 4H, J = 7.4 Hz), 6.72–6.62 (m, 12H), 6.32–
19 6.27 (m, 8H). F NMR (376.1 MHz, C6D6), δ: –350.3 (s, 2F). UV/Vis (2-
-1 -1 methyltetrahydrofuran): λmax, nm (ε, M cm ) 329 (41400), 365 (13600), 410 (10500),
453 (9400), 492 (sh, 7200). Emission (2-methyltetrahydrofuran): λex, nm (Int.) 566 (205),
610 (133). Anal. Calcd. For C52H32F2Ir2N4S4·C6H6: C, 51.92; H, 2.86; N, 4.18. Found: C,
52.22; H, 3.10; N, 4.29.
[{Ir(F2ppy)2(µ-F)}2] (1b): A 100-mL round bottom flask was loaded with
[{Ir(F2ppy)2(µ-Cl)}2] (0.500 g, 0.411 mmol) under argon. To this was added 20 mL anhydrous methanol followed by AgF (0.130 g, 1.028 mmol). The reaction mixture was
166 stirred vigorously for 6 h under argon at room temperature. After this time period the crude reaction mixture was passed through a bed of celite to remove silver chloride and excess silver fluoride resulting a clear yellow filtrate. The solvent was removed under vacuum, rendering a red-colored residue, which was re-dissolved in toluene. The volume of toluene was reduced to a minimum and excess pentane was added to precipitate the desired fluoro-bridged product as a yellow solid. The solid was collected by filtration and washed with pentane. Drying under vacuum for 6 h yielded analytically pure product.
1 Yield: 0.330 g (68%). H NMR (400 MHz, C6D6), δ: 8.43 (d, 4H, J = 4.9 Hz), 7.90 (d,
4H, J = 8.2 Hz), 6.61 (t, 4H, J = 7.8 Hz), 6.33 (t, 4H, J = 9.9 Hz), 5.68 (d, 4H, J = 8.7
19 Hz), 5.57 (t, 4H, J = 5.4 Hz). F NMR (376.1 MHz, C6D6), δ: –108.3 (m, 4F), –111.0 (m,
4F), –332.3 (s, 2F). Anal. Calcd. For C44H24F10Ir2N4: C, 44.67; H, 2.04; N, 4.74. Found:
C, 44.49; H, 2.31; N, 5.02.
5.4.3. Synthesis of Terminal Fluoride Complexes of Ir(III) Cyclometalates
[Ir(bt)2(F)(3,5-dimethylpyrazole)] (2a): Inside a 100-mL round bottom flask,
[{Ir(bt)2(µ-F)}2] (0.250 g, 0.198 mmol) was dissolved in 20 mL of dry chloroform under argon. To this was added 3,5-dimethylpyrazole (0.057 g, 0.593 mmol). The reaction flask was flushed with argon, sealed and left stirring at 55 °C for 6 h. After completion of the reaction as indicated by 19F NMR, the solvent was removed by rotary evaporation, resulting in a red-colored residue. The crude product was re-dissolved in a minimum amount of methylene chloride. Addition of pentane led to precipitation of the desired product as a red solid that was collected by filtration and washed with diethyl ether and pentane. Drying under vacuum for 4 h resulted in analytically pure product as a red
1 powder. Yield: 0.242 g (84%). H NMR (400 MHz, CDCl3), δ: 9.26 (t, 1H, J = 7.4 Hz),
167 7.87 (t, 2H, J = 6.6 Hz), 7.63 (d, 1H, J = 8.6 Hz), 7.60 (d, 1H, J = 8.9 Hz), 7.51 (t, 1H, J
= 8.2 Hz), 7.42 (t, 1H, J = 7.4 Hz), 7.35 (t, 1H, J = 8.2 Hz), 7.19 (t, 1H, J = 7.9 Hz),
6.86–6.79 (m, 2H), 6.67 (t, 1H, J = 7.1 Hz), 6.59–6.52 (m, 3H), 6.21 (d, 1H, J = 7.4 Hz),
5.79 (s, 1H), 2.18 (s, 3H), 1.36 (s, 3H). The 3,5-dimethylpyrazole N–H proton was not
19 observed in CDCl3. F NMR (376.1 MHz, C6D6), δ: –260.2 (s, 1F). UV/Vis (2-
-1 -1 methyltetrahydrofuran): λmax, nm (ε, M cm ) 326 (23000), 359 (sh, 8300), 439 (4400).
Emission (2-methyltetrahydrofuran): λex, nm (Int.) 556 (70), 592 (44). Anal. Calcd. For
C31H24FIrN4S2: C, 51.15; H, 3.32; N, 7.70. Found: C, 51.36; H, 3.45; N, 7.82.
[Ir(F2ppy)2(F)(3,5-dimethylpyrazole)] (2b): Inside a 100-mL round bottom flask,
[{Ir(F2ppy)2(µ-F)}2] (0.250 g, 0.211 mmol) was dissolved in 20 mL of dry chloroform under argon. To this was added 3,5-dimethylpyrazole (0.060 g, 0.634 mmol). The reaction flask was flushed with argon, sealed and left stirring at 55 °C for 6 h. After this time period the solvent was removed by rotary evaporation, resulting in a red-colored residue. The crude product was re-dissolved in a minimal amount of methylene chloride.
Pentane was added to precipitate a red-colored solid, which was collected by filtration.
The product was washed with pentane, followed by diethyl ether, and dried under
1 vacuum for 4 h. Yield: 0.212 g (75%). H NMR (400 MHz, CDCl3), δ: 9.20 (d, 1H, J =
5.8 Hz), 8.26 (d, 1H, J = 9.1 Hz), 8.19 (d, 1H, J = 8.6 Hz), 7.85 (d, 1H, J = 5.4 Hz), 7.76
(t, 2H, J = 7.7 Hz), 7.23 (t, 1H, J = 6.6 Hz), 7.06 (t, 1H, J = 6.2 Hz), 6.38–6.31 (m, 2H),
5.79 (s, 1H), 5.76 (dd, 1H, J = 9.0, 2.1 Hz), 5.52 (dd, 1H, J = 9.0, 2.9 Hz), 2.26 (s, 3H),
19 1.42 (s, 3H). The 3,5-dimethylpyrazole N–H proton was not observed in CDCl3. F
NMR (376.1 MHz, C6D6), δ: –108.9 (m, 2F), –111.5 (m, 2F), –256.6 (s, 1F). Anal. Calcd.
For C27H20F5IrN4: C, 47.16; H, 2.93; N, 8.15. Found: C, 47.39; H, 2.84; N, 8.26.
168 [Ir(bt)2(F)(2-aminopyridine)] (2c): Inside a 100-mL round bottom flask, [{Ir(bt)2(µ-
F)}2] (0.250 g, 0.211 mmol) was dissolved in 20 mL of dry chloroform under argon. To this was added 2-aminopyridine (0.061 g, 0.633 mmol). The reaction flask was flushed with argon, sealed and left stirring at 55 °C for 6 h. After this time period the solvent was removed by rotary evaporation, resulting in a red-colored residue. The crude product was re-dissolved in a minimal amount of methylene chloride. Pentane was added to precipitate a red-colored solid, which was collected by filtration. The product was washed with pentane, followed by diethyl ether, and dried under vacuum for 4 h. Yield 0.209 g
1 (73%). H NMR (400 MHz, CDCl3), δ: 9.26 (t, 1H, J = 7.2 Hz), 7.89 (d, 1H, J = 8.4 Hz),
7.86 (d, 1H, J = 8.0 Hz), 7.67 (d, 1H, J = 7.6 Hz), 7.61 (d, 1H, J = 8.0 Hz), 7.50 (t, 1H, J
= 7.2 Hz), 7.43 (t, 1H, J = 8.0 Hz), 7.34 (t, 1H, J = 7.6 Hz), 7.22–7.18 (m, 2H), 7.12 (d,
1H, J = 8.8 Hz), 7.11 (d, 1H, J = 6.0 Hz), 6.84 (q, 2H, J = 7.6 Hz), 6.66 (t, 1H, J = 7.2
Hz), 6.62 (t, 1H, J = 6.8 Hz), 6.48 (d, 1H, J = 6.8 Hz), 6.26 (d, 1H, J = 8.4 Hz), 6.14 (d,
19 1H, J = 7.6 Hz), 6.07 (t, 1H, J = 6.8 Hz). No amino protons were observed in CDCl3. F
NMR (376.1 MHz, CDCl3), δ: –270.0 ppm (s, 1F). UV/Vis (2-methyltetrahydrofuran):
-1 -1 λmax, nm (ε, M cm ) 324 (36000), 360 (sh, 13500). Emission (2-methyltetrahydrofuran):
λex, nm (Int.) 557 (390), 591 (285). Anal. Calcd. For C32H22FIrN3S2: C, 53.10; H, 3.06;
N, 5.80. Found: C, 53.22; H, 3.15; N, 5.71.
5.4.4. Reactivity of [Ir(bt)2(F)(3,5-dimethylpyrazole)] (2a) with Silylated Reagents
[Ir(bt)2(Cl)(3,5-dimethylpyrazole)] (3a): In a 100-mL round bottom flask, 2a (0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution was added triisopropylsilyl chloride (0.044 mL, 0.206 mmol) dropwise. An orange-
169 yellow precipitate formed in 1 h. The reaction was monitored by 19F NMR. After 12 h stirring at room temperature, the solvent was removed under vacuum to obtain a orange yellow solid. The solid was collected and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded analytically pure product. Yield: 0.083 g (81%). 1H NMR
(400 MHz, CDCl3), δ: 13.12 (br s, 1H), 9.80 (d, 1H, J = 8.0 Hz), 7.90 (d, 1H, J =7.8 Hz),
7.86 (d, 1H, J = 8.4 Hz), 7.64 (dd, 1H, J = 6.8, 1.4 Hz), 7.60–7.55 (m, 2H), 7.45 (t, 1H, J
= 7.3 Hz), 7.39 (t, 1H, J = 7.1 Hz), 7.22 (t, 1H, J = 7.7 Hz), 6.87–6.83 (m, 2H), 6.71 (td,
1H, J = 6.8, 1.4 Hz), 6.66–6.62 (m, 2H), 6.39 (d, 1H, J = 7.86 Hz), 6.29 (d, 1H, J = 6.7
Hz), 5.74 (s, 1H), 2.18 (s, 3H), 1.29 (s, 3H). UV/Vis (2-methyltetrahydrofuran): λmax, nm
-1 -1 (ε, M cm ) 326 (31000), 358 (sh, 12000). Emission (2-methyltetrahydrofuran): λex, nm
(Int.) 552 (74), 591 (51). Anal. Calcd. For C31H24ClIrN4S2: C, 50.02; H, 3.25; N, 7.53.
Found: C, 50.37; H, 3.19; N, 7.72.
[Ir(bt)2(Br)(3,5-dimethylpyrazole)] (4a): In a 100-mL round bottom flask, 2a
(0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution bromotrimethylsilane (0.027 mL, 0.206 mmol) was added dropwise. The reaction was monitored by 19F NMR. After stirring for 12 h at 45 °C, orange yellow precipitate was observed. After this time period, the solvent was removed under vacuum to obtain an orange-yellow solid. The solid was collected and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded analytically pure product. Yield:
1 0.096 g (89%). H NMR (400 MHz, CDCl3), δ: 12.79 (br s, 1H), 9.89 (d, 1H, J = 9.2 Hz),
7.89 (d, 1H, J = 7.6 Hz), 7.84 (d, 1H, J = 7.6 Hz), 7.62 (d, 1H, J = 7.6 Hz), 7.58–7.54 (m,
2H), 7.43 (t, 1H, J = 6.8 Hz), 7.38 (t, 1H, J = 6.8 Hz), 7.22 (t, 1H, J = 6.8 Hz), 6.86–6.79
(m, 2H), 6.75 (d, 1H, J = 8.4 Hz), 6.70 (t, 1H, J = 6.8 Hz), 6.63 (t, 1H, J = 8.2 Hz), 6.31
170 (t, 2H, J = 8.4 Hz), 5.70 (s, 1H), 2.18 (s, 3H), 1.27 (s, 3H). UV/Vis (2-
-1 -1 methyltetrahydrofuran): λmax, nm (ε, M cm ) 326 (36500), 358 (sh, 12000). Emission
(2-methyltetrahydrofuran): λex, nm (Int.) 551 (193), 591 (138). Anal. Calcd. For
C31H24BrIrN4S2: C, 47.20; H, 3.07; N, 7.10. Found: C, 47.55; H, 3.29; N, 7.34.
[Ir(bt)2(SPh)(3,5-dimethylpyrazole)] (5a): In a 100-mL round bottom flask, 2a
(0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution, trimethyl(phenylthio)silane (0.039 mL, 0.206 mmol) was added dropwise. The mixture underwent a color change to deep red and was left stirring for 6 h at room temperature. The reaction was monitored by 19F NMR. The solvent was then removed under vacuum to obtain a red-colored solid. The crude product was dissolved in 1 mL of methylene chloride. Addition of pentane led to precipitation of the desired product, which was collected by filtration and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded analytically pure product. Yield: 0.082 g (73%). 1H NMR (400
MHz, C6D6), δ: 9.77 (d, 1H, J = 8.7 Hz), 7.45 (d, 1H, 6.9 Hz), 7.41 (d, 1H, J = 8.6 Hz),
7.26 (t, 1H, J = 7.8 Hz), 7.11 (d, 2H, J = 8.6 Hz), 6.95 (t, 2H, J = 6.1 Hz), 6.90–6.83 (m,
5H), 6.71–6.59 (m, 4H), 6.52–6.42 (m, 4H), 5.38 (s, 1H), 1.69 (s, 3H), 1.45 (s, 3H). The
3,5-dimethylpyrazole N–H proton was not observed in CDCl3. Anal. Calcd. For
C37H29IrN4S3: C, 54.32; H, 3.57; N, 6.85. Found: C, 54.65; H, 3.62; N, 7.21.
[Ir(bt)2(OPh)(3,5-dimethylpyrazole)] (6a): In a 100-mL round bottom flask, 2a
(0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution, trimethyl(phenoxy)silane (0.038 mL, 0.206 mmol) was added dropwise. The reaction mixture was left stirring for 12 h at 45 °C. The reaction was monitored by 19F
NMR. After this time period, the solvent was removed under vacuum to obtain a red
171 solid. The crude product was dissolved in 1 mL of methylene chloride. Addition of pentane led to precipitation of the desired product, which was collected by filtration and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded
1 analytically pure compound. Yield: 0.089 g (81%). H NMR (400 MHz, C6D6), δ: 10.29
(d, 1H, J = 8.0 Hz), 7.51 (d, 1H, J = 7.0 Hz), 7.32 (d, 1H, J = 6.1 Hz), 7.25–7.17 (m, 3H),
7.07–6.84 (m, 5H), 6.81–6.63 (m, 5H), 6.60 (t, 1H, J = 7.0 Hz), 6.54 (t, 1H, J = 6.4 Hz),
6.43 (t, 1H, J = 8.0 Hz), 6.26 (d, 2H, J = 8.0 Hz), 5.42 (s, 1H), 1.65 (s, 3H), 1.53 (s, 3H).
The 3,5-dimethylpyrazole N–H proton was not observed in CDCl3. Anal. Calcd. For
C37H29IrN4OS2: C, 55.41; H, 3.64; N, 6.99. Found: C, 55.78; H, 3.96; N, 7.28.
[Ir(bt)2(N3)(3,5-dimethylpyrazole)] (7a): In a 100-mL round bottom flask, 2a (0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution, azidotrimethylsilane (0.027 mL, 0.206 mmol) was added dropwise. The reaction mixture was left stirring for 6 h at room temperature. The reaction was monitored by 19F NMR.
After this time period, the solvent was removed under vacuum to obtain a red-colored solid. The crude product was dissolved in 1 mL of methylene chloride. Addition of pentane led to precipitation of the desired product, which was collected by filtration and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded
1 analytically pure product. Yield: 0.065 g (63%). H NMR (400 MHz, C6D6), δ: 13.27 (br s, 1H), 9.69 (d, 1H, J = 8.7 Hz), 7.68 (d, 1H, J = 7.4 Hz), 7.49 (d, 1H, J = 7.4 Hz), 7.23
(d, 1H, J = 8.0 Hz), 7.19–7.11 (m, 2H), 7.04–7.00 (m, 2H), 6.97–6.87 (m, 3H), 6.72 (td,
1H, J = 7.7, 1.1 Hz), 6.69–6.64 (m, 2H), 6.58 (td, 1H, J = 7.6, 1.4 Hz), 6.46 (td, 1H, J =
7.0, 1.1 Hz), 5.26 (d, 1H, J = 2.1 Hz), 1.41 (s, 3H), 1.36 (s, 3H). Anal. Calcd. For
C31H24IrN7S2: C, 49.58; H, 3.22; N, 13.06. Found: C, 49.74; H, 3.34; N, 13.28.
172 [Ir(bt)2(NCS)(3,5-dimethylpyrazole)] (8a): In a 100-mL round bottom flask, 2a (0.100 g, 0.137 mmol) was dissolved in 2 mL dry THF under argon. To the clear red solution, (trimethylsilyl)isothiocyanate (0.029 mL, 0.206 mmol) was added dropwise. The reaction mixture was left stirring for 2 h at room temperature. The reaction was monitored by 19F NMR. After this time period, the solvent was removed under vacuum to obtain a red-colored solid. The crude product was dissolved in 1 mL of methylene chloride. Addition of pentane led to precipitation of the desired product, which was collected by filtration and washed with diethyl ether and pentane. Drying under vacuum for 4 h afforded analytically pure product. Yield: 0.069 g (66%). 1H NMR (400 MHz,
CDCl3), δ: 11.15 (s, 1H), 8.89 (d, 1H, J = 8.8 Hz), 7.94 (d, 1H, J = 7.9 Hz), 7.89 (d, 1H, J = 7.4 Hz), 7.66 (t, 2H, J = 7.4 Hz), 7.60 (d, 1H, J = 7.4 Hz), 7.49 (t, 1H, J = 7.4 Hz), 7.42 (t, 1H, J = 7.8 Hz), 7.25–7.21 (m, 1H), 6.87 (q, 2H, J = 7.4 Hz), 6.70 (t, 1H, J = 7.4 Hz), 6.65 (t, 1H, J = 8.1 Hz), 6.57 (d, 1H, J = 7.9 Hz), 6.40 (d, 1H, J = 7.4 Hz), 6.18 (d, 1H, J
= 7.5 Hz), 5.75 (s, 1H), 2.24 (s, 3H), 1.25 (s, 3H). Anal. Calcd. For C32H24IrN5S3: C, 50.11; H, 3.15; N, 9.13. Found: C, 50.36; H, 3.23; N, 9.47.
5.4.5. Fluorine Transfer Reaction with Carbon and Sulfur Based Electrophile General procedure: A Schlenk tube was loaded with 2a (0.027 mmol) under argon.
To this was added 2 mL of C6D6 containing 5 mol% of fluorobenzene (internal standard) and the electrophile (0.027 mmol). The reaction progress was monitored by 19F NMR spectroscopy. p-Toluoyl fluoride: The general procedure for fluorine transfer reactions was followed using p-toluoyl chloride reagent. The fluorine resonance of p-toluoyl fluoride in 19F NMR is 16.8 ppm.52 After 6 h stirring at room temperature 95% conversion to product was calculated. p-Toluenesulfonyl fluoride: The general procedure for fluorine transfer reactions was followed using p-toluenesulfonyl chloride reagent. The fluorine resonance appears
173 at 64.7 ppm in the 19F NMR spectrum of p-toluenesulfonyl fluoride.53 After 12 h of stirring at 45 °C, 99% conversion to product was calculated. Chloroacetyl fluoride: The general procedure for fluorine transfer reactions was followed using chloroacetyl chloride reagent. The fluorine resonance appears at 34.4 ppm in the 19F NMR spectrum of 3-chloroacetyl fluoride.54 After 6 h of stirring at room temperature, 91% conversion to product was calculated. 5.4.6. X-ray Crystallography The crystal structure was determined by Dr. Curtis Moore, Dr. Arnold L. Rheingold at UCSD and Dr. Matthias Zeller, Dr. Allen D. Hunter at Youngstown State University.
Crystallographic data were collected on either a Bruker AXS SMART APEXII CCD diffractometer or a Bruker AXS Quest diffractometer using monochromatic Mo Kα radiation with omega and/or phi scan techniques. The unit cells were retrieved using the
APEX2 Crystallographic Suite. Structures were solved by direct methods and refined by full matrix least squares against F2 with all reflections using SHELXL2013 and
SHELXLE. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were placed in calculated positions and were refined with an isotropic displacement parameter
1.5 (CH3) or 1.2 (all others) times that of the adjacent carbon atom.
5.4.7. Luminescence Measurements
Steady-state luminescence spectra were recorded by Mr. Bryce L. Anderson at room temperature on a Cary Eclipse fluorescence spectrophotometer, or on an automated
Photon Technology International (PTI) QM 4 fluorimeter equipped with a 150-W Xe arc lamp and a Hamamatsu R928 photomultiplier tube at Massachusetts Institute of
Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge,
Massachusetts 02139 (USA). Excitation light was excluded with suitable glass filters.
174 Sample solutions were added to a quartz ESR tube equipped with a Teflon valve, freeze- pump-thaw degassed (four cycles, 1 × 10–5 Torr) and sealed. Low temperature emission spectra were recorded in rigid solvent glass at 77 K by immersion of the sealed ESR tubes into a liquid nitrogen-filled dewar. Time-resolved phosphorescence lifetime data were recorded on a nanosecond laser system described previously.55
Emission quantum yields (23 ± 2 °C) were measured56 in deoxygenated 2- methyltetrahydrofuran by referencing sample luminescence intensities to those of
57 optically dilute standards of 9,10-diphenylanthracene (φem = 0.9) in cyclohexane.
Quantum yields φ were computed by:
⎛⎞ADη2 φ=φ rs s sr⎜⎟AD2 ⎝⎠srη r where r and s indicate reference and sample, respectively, A is the absorbance at wavelength λexc, η is the refractive index of the solvent, and D is the integrated area beneath the absorption spectrum.
5.5. References
(1) Wilkinson, G.; Gillard, R. D.; McCleverty, J. A. Comprehensive Coordination Chemistry; Pergamon, Oxford, 1987.
(2) McCleverty, J. A.; Meyer, T. J. No TitleComprehensive Coordination Chemistry II; Elsevier: Oxford, 2004.
(3) Pearson, R. G. J. Am. Chem. Soc. 1963, 85, 3533–3539.
(4) Poulton, J. T.; Sigalas, M. P.; Folting, K.; Streib, W. E.; Eisenstein, O.; Caulton, K. G. Inorg. Chem. 1994, 33, 1476–1485.
(5) Caulton, K. G. New J. Chem. 1994, 18, 25.
175 (6) Mayer, J. M. Comments Inorg. Chem. 1988, 8, 125–135.
(7) Laitar, D. S.; Müller, P.; Gray, T. G.; Sadighi, J. P. Organometallics 2005, 24, 4503–4505.
(8) Akana, J. A.; Bhattacharyya, K. X.; Müller, P.; Sadighi, J. P. J. Am. Chem. Soc. 2007, 129, 7736–7737.
(9) Melgarejo, D. Y.; Chiarella, G. M.; Fackler, J. P.; Perez, L. M.; Rodrigue-Witchel, A.; Reber, C. Inorg. Chem. 2011, 50, 4238–4240.
(10) Mankad, N. P.; Toste, F. D. J. Am. Chem. Soc. 2010, 132, 12859–12861.
(11) Mankad, N. P.; Toste, F. D. Chem. Sci. 2012, 3, 72–76.
(12) Vela, J.; Smith, J. M.; Yu, Y.; Ketterer, N. A.; Flaschenriem, C. J.; Lachicotte, R. J.; Holland, P. L. J. Am. Chem. Soc. 2005, 127, 7857–7870.
(13) Campbell, M. G.; Ritter, T. Org. Process Res. Dev. 2014, 18, 474–480.
(14) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chemie Int. Ed. 2013, 52, 8214– 8264.
(15) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470–477.
(16) Hollingworth, C.; Gouverneur, V. In C–H and C–X Bond Functionalization: Transition Metal Mediation; Ribas, X., Ed.; RSC Catalysis Series No. 11; Royal Society of Chemistry, 2013; pp. 193–261.
(17) Lee, H. G.; Milner, P. J.; Buchwald, S. L. J. Am. Chem. Soc. 2014, 136, 3792– 3795.
(18) Fier, P. S.; Hartwig, J. F. Science. 2013, 342 , 956–960.
(19) Ye, Y.; Schimler, S. D.; Hanley, P. S.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 16292–16295.
(20) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160–171.
(21) Furuya, T.; Benitez, D.; Tkatchouk, E.; Strom, A. E.; Tang, P.; Goddard, W. A.; Ritter, T. J. Am. Chem. Soc. 2010, 132, 3793–3807.
(22) Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang, Y.; García-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science. 2009, 325 , 1661–1664.
(23) Murphy, E. F.; Murugavel, R.; Roesky, H. W. Chem. Rev. 1997, 97, 3425–3468.
176 (24) Doherty, N. M.; Hoffmann, N. W. Chem. Rev. 1991, 91, 553–573.
(25) K. A. King, P. J. Spellane and R. J. Watts. J. Am. Chem. Soc. 1985, 107, 1431– 1432.
(26) Maity, A.; Anderson, B. L.; Deligonul, N.; Gray, T. G. Chem. Sci. 2013, 4, 1175.
(27) Sajoto, T.; Djurovich, P. I.; Tamayo, A. B.; Oxgaard, J.; Goddard, W. A.; Thompson, M. E. J. Am. Chem. Soc. 2009, 131, 9813–9822.
(28) Cusanelli, A.; Frey, U.; Richens, D. T.; Merbach, A. E. J. Am. Chem. Soc. 1996, 118, 5267–5271.
(29) Lamansky, S.; Djurovich, P.; Murphy, D.; Abdel-Razzaq, F.; Lee, H.-E.; Adachi, C.; Burrows, P. E.; Forrest, S. R.; Thompson, M. E. J. Am. Chem. Soc. 2001, 123, 4304–4312.
(30) Nazeeruddin, M. K.; Klein, C.; Grätzel, M.; Zuppiroli, L.; Berner, D. Highly Efficient OLEDs with Phosphorescent Materials; Yersin, H., Ed.; Wiley-VCH, Weinheim, 2008; pp. 363–390.
(31) Chen, H.-F.; Wu, C.; Kuo, M.-C.; Thompson, M. E.; Wong, K.-T. J. Mater. Chem. 2012, 22, 9556–9561.
(32) Bolink, H. J.; Cappelli, L.; Coronado, E.; Grätzel, M.; Ortí, E.; Costa, R. D.; Viruela, P. M.; Nazeeruddin, M. K. J. Am. Chem. Soc. 2006, 128, 14786–14787.
(33) Costa, R. D.; Ortí, E.; Bolink, H. J.; Monti, F.; Accorsi, G.; Armaroli, N. Angew. Chemie Int. Ed. 2012, 51, 8178–8211.
(34) Lowry, M. S.; Bernhard, S. Chem. – A Eur. J. 2006, 12, 7970–7977.
(35) Zhang, G.; Zhang, H.; Gao, Y.; Tao, R.; Xin, L.; Yi, J.; Li, F.; Liu, W.; Qiao, J. Organometallics 2013, 33, 61–68.
(36) Maity, A.; Choi, J.-S.; Teets, T. S.; Deligonul, N.; Berdis, A. J.; Gray, T. G. Chem. – A Eur. J. 2013, 19, 15924–15932.
(37) Q. Zhao, C. Huang and F. Li. Chem. Soc. Rev. 2011, 40, 2508– 2524.
(38) Lo, K. K. -W.; Choi, A. W. -T.; Law, W. H.-T. Dalton. Trans. 2012, 41, 6021– 6047.
(39) Li, C.; Yu, M.; Sun, Y.; Wu, Y.; Huang, C.; Li, F. J. Am. Chem. Soc. 2011, 133, 11231−11239.
177 (40) You, Y.; Lee, S.; Kim, T.; Ohkubo, K.; Chae, W.-S.; Fukuzumi, S.; Jhon, G.-J.; Nam, W.; Lippard, S. J. J. Am. Chem. Soc. 2011, 133, 18328–18342.
(41) McDaniel, N. D.; Coughlin, F. J.; Tinker, L. L.; Bernhard, S. J. Am. Chem. Soc. 2008, 130, 210–217.
(42) Yuan, Y.-J.; Yu, Z.-T.; Chen, X.-Y.; Zhang, J.-Y.; Zou, Z.-G. Chem. – A Eur. J. 2011, 17, 12891–12895.
(43) Y.-J. Yuan, J.-Y. Zhang, Z.-T. Yu, J.-Y. Feng, W.-J. Luo, J.-H. Y. and Z.-G. Z. Inorg. Chem. 2012, 51, 4123–4133.
(44) Veltheer, J. E.; Burger, P.; Bergman, R. G. J. Am. Chem. Soc. 1995, 117, 12478– 12488.
(45) Kläring, P.; Jungton, A.-K.; Braun, T.; Müller, C. Eur. J. Inorg. Chem. 2012, 2012, 1430–1436.
(46) Kläring, P.; Braun, T. Angew. Chemie Int. Ed. 2013, 52, 11096–11101.
(47) Stout, G. H.; Jensen, L. H. X-ray Structure Determination: A Practical Guide; 2d Ed.; Wiley Interscience, 1989; pp. 404–405.
(48) Wallwork, S. C. Acta Crystallogr. 1962, 15, 758–759.
(49) Nonoyama. Bull. Chem. Soc. Jpn. 1974, 47, 767–768.
(50) Laskar, I. R.; Chen, T.-M. Chem. Mater. 2004, 16, 111–117.
(51) You, Y.; Park, S. Y. J. Am. Chem. Soc. 2005, 127, 12438–12439.
(52) Brownlee, R. T. C.; Craik, D. J. Org. Magn. Reson. 1980, 14, 186–191.
(53) Ung, G.; Bertrand, G. Chemistry 2012, 18, 12955–12957.
(54) Schaumburg, K. J. Magn. Reson. 1972, 183, 177–183.
(55) E. J. McLaurin, A. B. Greytak, M. G. Bawendi, D. G. Nocera. J. Am. Chem. Soc. 2009, 131, 12994–13001.
(56) Demas, J. N.; Crosby, G. A. J. Phys. Chem. 1971, 75, 991–1024.
(57) S. Hamai, F. Hirayama. J. Phys. Chem. 1983, 87, 83–89.
178 Chapter 6 Synthesis and Cytotoxicity Studies of a Non-natural Nucleoside Bearing (triphenylphosphine)gold(I)
179 Manuscript under preparation for publication.
6.1. Introduction
Much research has sought analogues of naturally occurring nucleosides having a spectrum of biological activities.1 Purine and pyrimidine antimetabolites hold of 20% anticancer drug market today.2 FDA approval of four new non-natural nucleoside drugs since 2004 and also many in clinical trial reinforce the importance of these classes of pharmaceuticals.
Many nucleosides are cytotoxic. Once nucleosides diffuse into the cell through nucleoside transporters,3 they compete with natural nucleosides for incorporation into
DNA.4 Incorporation of non-natural nucleotides causes steric hindrance and stalls the replication fork. Cells activate S-phase DNA damage checkpoint, stops further replication and activate DNA repair mechanisms. But severe effect leads to apoptosis.
Purine analogues established their activity against B-cell malignancies with the emergence of gemcitabine. Thiopurines are antimetabolites used for the treatment of acute lymphocytic leukemia. We hypothesized that attaching 2-deoxy-ribose moiety to 6- mercaptopurine (MP) would facilitate incorporation of this nucleoside into DNA as well as enhance cellular uptake hence higher potency of the final drug.
The idea of medicinal gold chemistry is an old one. Gold compounds have been applied as remedies for a variety of diseases, sometimes with little basis in evidence. In modern times, gold compounds have been used to treat rheumatoid arthritis
(chrysotherapy), bronchial asthma, tuberculosis, and malaria.5–10 Gold based anti-arthritic compounds (gold(I) thiomalate, gold(I) thiopropanol sulfinate, gold(I) thioglucose; as
180 shown in Figure 6.1.1) are considered as prodrug and effectively deliver gold to the site of inflammation.9
OH
NaO2C O HO S Au HO Au S CO2Na n S SO Na HO n Au 3 n gold(I) thioglucose (Solganol) aurothiomalate (Myocrisin) aurothiopropanol sulfonate (Allocrysin)
OAc
AcO O Na [O S–S–Au–S–SO ] S 3 3 3 AcO Au OAc P
aurothiosulfate (Sanocrysin) Auranofin
Figure 6.1.1. Clinically established gold(I) anti-arthritic drugs.
Gold(I) is a soft metal, and it usually interacts with cysteine (Cys) and selenocystein
(Sec) containing proteins and enzymes, and in some cases histidine residues.11 Gold(I) inhibits the mammalian enzyme mitochondrial thioredoxin reductase, which supports redox homeostasis inside the cell.12,13 Auranofin has been shown to have in vivo antitumor effect against P388 murine leukemia and in vitro cytotoxicity against B16 melanoma.14 A different mode of action of auranofin was attributed when it overcome the cisplatin resistance in human ovarian cancer cells and it was found that auranofin causes production of hydrogen peroxide, hence creating suitable conditions for apoptosis.
Gold(I) complexes of chelating bidentate phosphine ligands15 and N-heterocyclic carbenes16 have also demonstrated activity against cancer cell lines; evidence for mitochondrial thioredoxin reductase inhibition was presented.
181 PPh3 Au S
N N
N N O HO
HO
8a
Figure 6.1.2. Designing of gold(I) containing nucleoside.
Figure 6.1.2 depicts a gold-bearing MP derivative that has been evaluated in vitro against human cancer cell lines (this work). Synthesis, chemical and structural characterization, and cell-culture studies of three such complexes are summarized here.
All compounds were interrogated by 1H NMR, 31P{1H} spectroscopy and one of such compounds, 8b has been X-ray crystallographically authenticated. The purity of the samples were tested by high resolution mass spectrometry and elemental analysis The efficacy of compound 8a was tested against various human cancer cell lines.
In the quest of further development in the evolution of non-natural nucleoside drugs we disclose here the synthesis and characterization of three unique Au(I) containing metallonuceosides 8a-c (Scheme 6.2.1).
6.2. Results and Discussion
6.2.1. Synthesis
182 Scheme 6.2.1 represents the stepwise synthesis of target compound 8a used in the present study. In the preparation of the Chloro Hoffer’s sugar, 4 (Scheme 6.2.1) we used
O O O OH MeOH / HCl O Pyridine OMe HCl / AcOH HO HO OMe TolO TolO Cl 92 % p-Toluoyl chloride 69 % HO HO TolO TolO 82 % 3 4 1 2
SH Cl Cl SH N N N N N N N N N N N N O N NH O N O N O NaHS / MeOH MeOH / NH3 TolO TolO TolO HO Cl 74 % 73 % TolO NaH / CH CN HO 3 TolO TolO 7 4 5 6 61 %
L Au SH S
N N N N
N N N N O LAuCl / Cs CO O HO 2 3 HO rt, 4 h HO HO 7
8a, 83 %, L = PPh3, 8b, 77 %, L = PCy3 8c, 75 %, L = 1,3-diisopropylimidazol-2-ylidene
Scheme 6.2.1. Synthesis of gold(I) nucleosides. the same reactions as those reported by Fieser and Fieser,17 with slight simplification of first step where we used equivalent amount of concentrated hydrochloric acid in place of generating hydrogen chloride gas in situ. The resulting mixture of the methylfuranoside anomers 2 was acylated by treatment with p-toluoyl chloride in pyridine to give 3.
Compound 3 was converted to compound 4 with a solution of HCl in acetic acid prepared as follows: HCl was generated in situ by adding 16.3 mL acetyl chloride to a solution of
81 mL acetic acid and 4 mL water.
The sodium salt of commercially available 6-chloropurine, generated in situ by the treatment of sodium hydride in acetonitrile, was reacted with 1-chloro-2-deoxy-3,5-di-O- p-toluoyl-α-D-erythro-pentafuranose (4) at ambient temperature under nitrogen
183 atmosphere. Two nucleosidic isomers, N-9 and N-7 were formed. After silica gel column chromatography required N-9 isomer, 6-chloro-9-(2-deoxy-3,5-di-O-p-toluoyl-β-D- erythro-pentofuranosyl)purine (5) was isolated in 60% yield, while 20% of N-7 glycosyl isomer was collected as well. No α-anomer was detected by TLC, in agreement with published literature. 15,18 When 5 was treated with 2 equiv of NaHS in methanol, nucleophilic displacement of chlorine group occurred to give 9-(2-deoxy-3,5-di-O-p- toluoyl-β-D-erythro-pentofuranosyl)purine-6-thione (6). Deprotection of the carbohydrate moiety was accomplished by treating 6 with methanolic ammonia to give 7 at 73% yield. The Desired Au–S bond was formed when compound 7 was reacted with
31 1 (PPh3)AuCl in presence of excess amount of base to yield 8a. The characteristic P{ H} resonance shifts δ= 2.5 ppm downfield in 8a when compared to that of (PPh3)AuCl, δ=
34.1 ppm. The presence of an apparent triplet (tapp) peak at δ= 6.3–6.5 ppm with J = ~7
Hz, for the C-bound proton in the C–N glycosidic bond in 1H NMR spectrum of all three complexes 8a–c (as shown in Figure 6.2.1) are characteristics for the β-anomer of N- nucleosides.19 The final compound was purified by silica-gel column chromatography and recrystallized from hot methanol.
N PPh Au 3 PCy Au N S Au 3 S S N N N N N N N N N N O N N O HO O HO HO HO HO HO 8c 8a 8b
Figure 6.2.1. Synthesized gold(I) containing nucleosides.
184
Figure 6.2.2. Crystal structure of the complex 8b showing ellipsoids at the 50% probability level. Hydrogen atoms are omitted for clarity. Unlabeled atoms are carbon. Selected interatomic distances (Å): Au1–S1: 2.3095(19); Au1–P1: 2.2719(18); C6–N3: 1.457(10). Selected angles (°): S1–Au1–P1: 179.16(7); O1–C6–N3: 108.8(8).
A suitable crystal for X-ray crystallography was grown by vapor diffusion of diethyl
ether into a concentrated methanol solution of 8b. Figure 6.2.2 shows the crystal
structure of compound 8b in 50% probability. The bond angle S1–Au1–P1 is 179.16° in
keeping with the near-linear geometry of most gold(I) complexes.20–25 The Au1–S1
distance is 2.3095 Å and Au1–P1 bond distance is 2.2719; both are unexceptional.24–27
Thus a simple high yield methodology provided the biologically active new gold
containing nucleosides 8a–c.
6.2.2. Cytotoxicity Studies
185 The in vitro cytotoxicity of compound 8a was evaluated against four different human cancer cell lines, Leukemia (Molt 4 and CCRF CEM-7), breast (MCF-7) and cervical
(HeLa) cancer. The effectiveness in potency upon Au(I) binding was demonstrated by testing the free ligand 7. Also as a phosphine containing reference, PPh3AuCl was tested alongside.
Figure 6.2.3. CCRF CEM-7 cell proliferation after different concentration of drug treatment
over 48 h. Compound 7 is represented as dR-MP and compound 8a as dR-MP-AuPPh3.
Figure 6.2.4. Drug sensitivity profile of CCRF CEM-7 cells treated with 7 and 8a for 48 h.
Compound 7 is represented as dR-MP and compound 8a as dR-MP-AuPPh3.
The dose dependency of these compounds against adherent cell lines were tested by measuring cell viability using PrestoBlue cell viability protocol. In a regular experiment, cells are normally exposed to variable concentrations (0.001 – 100 µM) of drugs for up to
186 48 h and then cell viability was assessed. Each individual experiment represents an average of at least three independent experiments each of which was done in duplicate.
Representative data appear in Figure 6.2.3 to Figure 6.2.5, which indicate the dose
Figure 6.2.5. Cytotoxicity of 8a on Molt 4 cells after 48 h. Compound 8a as dr-MP-AuPPh3. dependency of 7 and 8a on systemic cell lines. The data show that the total cell count
(Figure 6.2.3) and the cell viability (Figure 6.2.4) decrease as the concentration of 7 or
8a increases. A fit of the data to equation 1 (described in Experimental Section) provides
IC50 values: 17.93 ± 1.5 µM (7) and 0.03 ± 0.008 µM (8a) for CCRF CEM-7 cells
(Figure 6.2.3). Therefore, the potency of compound 7 had increased significantly upon
Au(I) binding.
Similar experiments have been done with all three compounds on four different human cancer cell lines and the IC50 and LD50 values are summarized in Table 6.2.1.
These data indicate compound 8a is cytotoxic to all tested cancer cell lines, with LD50 values ranging from µM to nM. Comparing the LD50 values, compound 8a is clearly more effective against systemic cell lines than adherent cell lines. The highest potency is
187 observed against CCRF CEM-7 cells having IC50 value in nano molar range (IC50 = 30 nM, LD50 = 60 nM). It is evident that upon gold binding the LD50 of 7 decreases 19-fold
(from 11.25 ± 0.82 µM for compound 7 to 0.59 ± 0.07 µM for compound 8a) in case of
Molt 4 cells and more than 400-fold (from 27.01 ± 2 µM for compound 7 to 0.06 ± 0.008
µM for compound 8a) for CCRF CEM-7 cell line. The IC50 values for compound 8a against adherent cell lines are in the micromolar range (MCF-7, 6.34 ± 0.55 µM; HeLa,
1.65 ± 0.04 µM), while free nucleoside 7 does not show cytotoxicity when tested up to
500 µM concentration.
Table 6.2.1. Summary of in vitro cytotoxicity in terms of LD50 and IC50 values for compounds 7, b 8a and AuPPh3Cl against selected adherent and systemic cancer cell lines.
7 AuPPh3Cl 8a
a Molt 4 LD50 (µM) 11.25 ± 0.82 1.92 ± 0.06 0.59 ± 0.07
IC50 (µM) 6.15 ± 0.13 0.71 ± 0.07 0.30 ± 0.02
a CEM CCRF -7 LD50 (µM) 27.01 ± 2 0.15 ± 0.04 0.06 ± 0.008
IC50 (µM) 17.93 ± 1.5 0.05 ± 0.003 0.03 ± 0.008
a MCF 7 IC50 (µM) >500 11.4 ± 0.82 6.34 ± 0.55
a HeLa IC50 (µM) >500 6.46 ± 0.53 1.65 ± 0.04 b Assays were performed as described in methods and materials. LD50 is the concentration of the drug which reduces the cell viability to 50% of the untreated control cells. Whereas IC50 is the concentration of the drug which inhibits the cell to grow by 50% of the untreated control cells. [a] Molt 4, CCRF CEM-7 = human acute lymphoblastic leukemia cell line , MCF-7 = human breast adenocarcinoma cell line, HeLa = human cervical adenocarcinoma cell line.
188 The above findings indicate attachment of Au(I) to the nucleoside analog is a suitable strategy to obtain bioactive compounds. AuPPh3Cl treatment data shows that replacing a chloride ligand on gold by mercaptopurine nucleoside has a significant effect on the potency of the compound. Comparing the data of the reference gold ligand and compound 8a it is evident that efficacy of AuPPh3Cl has been increased by almost 2-fold in case of CCRF CEM-7 (AuPPh3Cl, 0.15 ± 0.04 µM; compound 8a, 0.06 ± 0.008 µM) and MCF-7 cell line (AuPPh3Cl, 11.4 ± 0.82 µM; compound 8a, 6.34 ± 0.55 µM) while the same effect is observed as 4 fold in case of Molt 4 (AuPPh3Cl, 1.92 ± 0.06 µM; compound 8a, 0.59 ± 0.07 µM) and HeLa (AuPPh3Cl, 6.46 ± 0.53 µM; compound 8a,
1.65 ± 0.04 µM) cells.
6.2.3. Flow-cytometric Analysis
In this study, a cell-cycle analysis was performed to examine if 8a would affect DNA synthesis of highly proliferative Molt 4 cancer cells. Fluorescence Activated Cell Sorting
(FACS) analysis was done to assess DNA content of the cancer cells after 24 hr of drug treatment followed by staining with propidium iodide. The cells were treated with LD50 of compound 8a, IC50 of compound 7 as positive control, and untreated DMSO as negative control. After 24 hour of drug treatment it was evident from Figure 6.2.6 that the percentage of cells in S phase increases from 44.9% (DMSO control) to 54.5% in case of compound 8a. However this S-phase block is not as pronounced as that of compound 7 (68.2%), which is a known antileukemic agent. This effect is particularly interesting keeping in the mind that the LD50 value of compound 8a is 20 times lower than that of compound 7. Possibly 8a targets the kinase involved in S-phase, as well as it
189 could interact with another biological target to exert its cytotoxicity, as manifested by a low-micromolar LD50.
Figure 6.2.6. Induction of cell cycle arrest in the Molt 4 cancer cells after treatment with compound 7 and compound 8a. Data were collected after 24 hr of incubation. G1 = G1-phase cells, G2/M= G2/M phase cells, S = S phase cells, subG1 = subG1 DNA content cells. Compound 7 is represented as dR-MP and compound 8a as dR-MP-AuPPh3.
190 Also comparing the structural analogy between 7 and 8a, it is plausible that compound 7 might incorporate into DNA of the highly proliferative cancer cells but once incorporated, blocks replication. That might explain the blockage of S phase. But in case of compound 8a, the presence of a bulky capping triphenylphosphine ligand on gold makes it unlikely to incorporate in DNA. Lack of subG1 DNA after 24 hour of drug treatment, in both the compound suggests that the compounds exert cytostatic effect after
24 hour with the experimental concentration of drug.
6.2.4. Apoptosis Measurement
Apoptosis is a regulated physiological process leading to cell death. Necrosis is a nonprogrammed death of cells leading inflammatory issues in cells. Thus, it is desirable to exert the cytotoxicity of a drug by apoptosis rather than necrosis. Molt 4 cells were treated with compound 8a with concentration of 1 µM for 48 h and the annexin/PI dual staining data reveals that compound 8a induces apoptosis in Molt 4 cancer cells (Figure
Figure 6.2.7. Annexin-PI staining of Molt 4 cells treated with compound 8a for 48 hr.
191 6.2.7). Comparing the quadrant 1 which is annexin negative and PI negative, (Q1) of
DMSO control cells and the drug-treated cells it is clear that around 40% of cells viable after drug treatment. A Q2 (Annexin positive and PI negative) comparison suggests that after the current condition of drug treatment the number of cells in early apoptotic stage has increased significantly, but the cells in Q2 are still viable as membrane integrity is not lost. Figure 3 indicates a large fraction of cells are late apoptotic (Q3 which is Annexin positive and PI positive) as they are stained by both annexin and PI. However, 48 hour of drug treatment fails to show a significant increase in the number of cells in Q4 (Annexin negative and PI positive) suggesting induction of apoptosis rather than necrosis by compound 8a.
6.2.5. Mitochondrial Permeability Transition
Collapse in mitochondrial membrane potential is an early event in apoptosis. Changes in mitochondrial membrane potential (ΔΨm) initiate the introduction of proapoptotic proteins inside the mitochondria and possible oligomerization of BID, BAK, BAX, BAD,
a) DMSO Control after 48 hr, Formation b) 7 µM of 8a (Monomeric dye lights of J-Complex inside healthy up green color). Mitochondria creats red dots.
Figure 6.2.8. Mitochondrial permeability transition assay performed with HeLa cells.
192 and other proteins that destroy the membrane potential and release cytochrome c into the cytoplasm.28
In our work collapse of mitochondrial membrane potential, indicative of apoptosis, has been detected using a unique fluorescent cationic dye, 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ- tetraethylbenzamidazolocarbocyanin iodide, commonly known as JC-1. The mitochondrial depolarization event was detected using fluorescence microscope. Having a delocalized positive charge, lipophilic JC-1 dye enters the healthy negatively charged mitochondria of non-apoptotic cells where it aggregates and fluoresces red. Due to destruction of mitochondrial ΔΨm in apoptotic cells, the dye exits the mitochondria and disperses through cell in its monomeric form, where it fluoresces green.
Data are shown in Figure 9. HeLa cells were treated with 8a at a concentration of 7
µM for 48 h with a DMSO control experiment alongside. In the DMSO, control (healthy cells) the dye aggregates within mitochondria and appears as red dots inside the cells
(Figure 6.2.8 (a)). After the high amount of drug treatment the shape of the cells changes from normal long shape to a round shape and there are no red dots inside the cells
(Figure 6.2.8 (b)). This suggest that the dye no longer aggregates inside the mitochondria; instead, it disperses over cytoplasm and the whole cell appears green.
6.2.6. Inhibition of Thioredoxin Reductase (TrxR)
The inhibition of both cytosolic and mitochondrial thioredoxin reductase enzyme has been observed by a number of gold(I) drugs. So the inhibitory potential of compound 8 was studied using rate lever TrxR by the DTNB reduction assay. This assay works in the
193 way that TrxR reduces the disulfide bonds of DTNB with the formation of 5- thionitrobenzoic acid whose formation can be detected photometrically.
As it is evident from the Figure 6.2.9, the effect of compound 8a is linear over the time. Considering the TrxR+DTNB as 100% of enzyme present in the system, the inhibitory effect of different concentration of compound 8a was calculated from the slope of each straight line. It was found that treatment of 1 µM 8a with TrxR (approximately
0.06 units of TrxR were present in each reaction medium) inhibits the activity of TrxR by
80% whereas 0.1 µM of compound 8a inhibited the thioredoxin reductase enzyme by
33% confirming TrxR as possible biological target.
Inhibition of TrxR 0.2 DTNB Control 0.1 uM dR-MPAuPPh3 DTNB+TrxR 1 uM dR-MPAuPPh3
0.15
0.1
0.05 Absorbance at 412 nm 412 at Absorbance
0 0 20 40 60 80 100 120 140 160 Time (Second)
Figure 6.2.9. The time course vs absorbance plot for thioredoxin reductase inhibition assay when treated with two different concentratopn of compound 8a along with positive (marked as DTNB+TrXR in the graph) and negative control (marked as DTNB control). A detail of this experiment has been described in materials and methods section. Compound 8a as is
represented as dR-MP-AuPPh3.
194 6.3. Conclusion
In this chapter we have disclosed a method to synthesize gold(I) containing nucleosides. The synthesis described here is high-yielding and simple. Gold(I) contining metallonucleosides are air and moisture stable. One of the complex has been crystallographically characterized. Crystal structure reveals that linear geometry of two coordinated gold(I) has been maintained. Compond 8a was chosen for biological study.
The compound 8a is most potent against CCRF CEM-7 cells having IC50 value in nano molar range (IC50 = 30 nM, LD50 = 60 nM). Annexin/PI dual staining data reveals that compound 8a induces apoptosis in Molt 4 cancer cell. Mitochondrial permeability transition assay and TrxR assay predicts mitochondrial TrxR as possible biological target to be the target. The above findings indicate attachment of Au(I) to the nucleoside analog is a suitable strategy to obtain bioactive compound.
6.4. Experimental Section
6.4.1. Materials and Methods
Experimental procedures involving air- or moisture sensitive substances were performed under argon using either Schlenk line techniques or in a nitrogen-filled
MBraun drybox. Anhydrous solvents were used directly from an MBraun solvent purification system or were purchased from Sigma-Aldrich. NMR spectra (1H and
31P{1H}) were recorded on a Varian AS-400 spectrometer operating at 399.7 and 161.8
MHz, respectively. Chemical shifts are reported in parts per million (δ), measured from tetramethylsilane (0 ppm) and are referenced to the solvent CDCl3 (7.26 ppm) or MeOH-
1 31 1 d4 (3.31 ppm) for H NMR. For P{ H} NMR spectra, chemicals shifts were determined
195 relative to 85% aqueous H3PO4. High-resolution electrospray ionization mass spectrometry (Hi-Res ESI-MS) experiments were performed on an IonSpec HiRes ESI-
FTICRMS at the University of Cincinnati Mass Spectrometry facility. Acetonitrile was degassed prior to use for UV-Vis and luminescence measurements. UV-Vis and luminescence data were recorded using a Cary 5G UV-Vis-NIR spectrometer and a Cary
Eclipse spectrometer, respectively. Thin layer chromatography (TLC) was carried out using Whatman Silica Gel UV254 plates. Column chromatography was performed using
Fisher Scientific Silica Gel, sizes 32–63. Elemental analyses were carried out by
Robertson Microlit Laboratories, Ledgewood, NJ.
All chemicals were purchased from Sigma-Aldrich or Acros as highest purity grade and used without further purification. Bovine serum albumin was obtained from Sigma-
Aldrich. Presto-Blue reagent, apoptosis Kit #2, thioredoxin reductase was purchased from
Invitrogen. Cell-titer blue reagent was purchased from Promega. Purity of all biologically active compounds was >95% as judged by micro-combustion analyses (C, H, and N) performed by Robertson Microlit Laboratories (Ledgewood, NJ).
Ph3PAuCl was synthesized by a slight modification of the literature procedures (using toluene and Au(THT)Cl).29 Similarly compound 4 was synthesized according to the published procedure.30
6.4.2. Synthesis of gold(I) nucleosides
6-Chloro-9-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)purine, (5).
A mixture of 6-chloropurine (1.790 g, 11.581 mmol) and anhydrous sodium hydride
(0.305 g, 12.74 mmol) taken in anhydrous acetonitrile (80 ml) was stirred at ambient
196 temperature for 30 minutes inside a glove box. Dry, powdered 1-chloro-2-deoxy-3,5-di-
O-p-toluoyl-α-D-erythro-pentafuranose, 4 (4.954 g, 12.74 mmol) was added by portions over a period of 20 minutes and stirring was continued for further 18 h at rt. After completion of the reaction any small amount of insoluble material present in the reaction was removed by filtration. Evaporation of the solvent resulted an oily residue, which was further purified by column chromatography using silica gel. The desired N-9 isomer was isolated as the first major fraction by eluting a mixture of hexanes and diethyl ether
(60:40, v/v). Evaporation of the solvent under reduced pressure and drying under vacuum for 4 h yielded analytically pure product as white solid. Yield: 3.58 g, 61%. 1H NMR
(400 MHz, CDCl3), δ: 8.67 (s, 1H), 8.29 (s, 1H), 7.97 (d, 2H, J = 8.0 Hz), 7.86 (d, 2H, J
= 8.4 Hz), 7.29 (d, 2H, J = 8.8 Hz), 7.21 (d, 2H, J = 8 Hz), 6.57 (tapp. 1H, J = 5.6 Hz),
5.84–5.82 (m, 1H), 4.80 (d, 1H, J = 10 Hz), 4.68–4.63 (m, 2H), 3.17–3.13 (m, 1H), 2.92–
+ 2.89 (m, 1H), 2.44 (s, 3H), 2.40 (s, 3H). HRMS: Calcd. for C26H24ClN4O5 [M+H] :
507.1435 Found: 507.1423 Anal. Calcd. For C26H23ClN4O5: C, 61.60; H, 4.57; N, 11.05.
Found: C, 61.86; H, 4.81; N, 11.34.
9-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)purine-6-thione, (6).
Compound 5 (1.210 g, 2.390 mmol) was suspended in 40 mL anhydrous methanol with continuous stirring under argon. To this was added solution of NaHS (0.268 g, 4.781 mmol) in 10 mL anhydrous methanol. The reaction was then left stirring at rt for 8 h.
Solvent was removed under vacuum and yellowish residue was purified by silica gel column chromatography. The product was collected by eluting a solvent mixture of diethyl ether and methanol (90:10, v/v). Yield: 0.892 g, 74 %. 1H NMR (400 MHz,
197 CDCl3), δ: 8.24 (s, 1H), 8.11 (s, 1H), 7.94 (d, 2H, J = 8.1 Hz), 7.87 (d, 2H, J = 7.9 Hz),
7.26 (d, 2H, J = 7.7 Hz), 7.21 (d, 2H, J = 7.8 Hz), 6.45 (tapp, 1H, J = 7.1 Hz), 5.78 (d, 1H,
J = 6.7 Hz), 4.76–4.71 (m, 1H), 4.67–4.61 (m, 2H), 3.10–3.02 (m, 1H), 2.80 (ddd, 1H, J
= 14.4, 6.4, 2.1 Hz), 2.42 (s, 3H), 2.38 (s, 3H). HRMS: Calcd. for C26H24N4NaO5S
+ [M+Na] : 527.1365 Found: 527.1361. Anal. Calcd. For C26H24N4O5S: C, 61.89; H, 4.79;
N, 11.10. Found: C, 62.21; H, 4.67; N, 10.82.
9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-thione (7).
A solution of 6 (0.850, 1.684 mmol) in methanolic ammonia (saturated by passing ammonia gas for 15 min at 0 °C, 40 mL) was allowed to stir at room temperature for 20 h. After that, the solvent was removed to dryness and the residue was purified by column chromatography using silica gel. The desired product was collected as the major fraction when eluted with a mixture of diethyl ether and methanol (80:20, v/v). Solvent was removed under reduced pressure and the desired product was collected as white powder.
1 Yield: 0.330 g, 73%. H NMR (400 MHz, CD3OD), δ: 8.44 (s, 1H), 8.12 (s, 1H), 6.43
(tapp, 1H, J = 7.0 Hz), 4.54 (quin, 1H, J = 3.0 Hz), 4.02 (q, 1H, J = 3.5 Hz), 3.75 (ddd,
2H, J = 15.2, 11.6, 3.5 Hz), 2.70 (quin, 1H, J = 7.5 Hz), 2. ). HRMS: Calcd. for
+ C10H13N4O3S [M+Na] : 269.0708 Found: 269.0704. Anal. Calcd. For C10H12N4O3S: C,
44.77; H, 4.51; N, 20.88. Found: C, 44.86; H, 4.73; N, 20.83.
(9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-thio)(triphenylphosphine)gold-
(I) (8a).
198 Compound 7 (0.070 g, 0.261 mmol) and Cs2CO3 (0.170 g, 0.522 mmol) were suspended in 2-propanol under argon. A solution of (PPh3)AuCl (0.130 g, 0.261 mmol) in dry acetone was added drop wise into the stirred mixture. The reaction flask was sealed and left stirring at rom temperature for 4 h. After completion of the reaction, solvent was removed under reduced pressure. The white residue was purified by a small silica gel column by eluting a mixture of diethyl ether and methanol (80:20, v/v). Desired product was collected as major fraction. After removal of solvent and drying in vacuum for 6 h
1 gave analytically pure product. Yield: 0.157 g, 83 %. H NMR (400 Hz, CD3OD), δ:
8.39 (s, 1H), 8.31 (s, 1H), 7.68–7.63 (m, 6H), 7.58–7.50 (m, 9H), 6.45 (tapp, 1H, J = 6.5
Hz), 4.58 (q, 1H, J = 2.7 Hz), 4.06–4.04 (m, 1H), 3.79 (ddd, 2H, J = 17.2, 5.4, 3.6 Hz),
31 1 2.83–2.77 (m, 1H), 2.46 (ddd , 1H, J = 13.3, 5.9, 3.1 Hz). P{ H} NMR (CD3OD), δ:
+ 37.5. HRMS: Calcd. for C28H27AuN4O3PS [M+H] : 727.1207 Found: 727.1228 Anal.
Calcd. For C28H26AuN4O3PS: C, 46.29; H, 3.61; N, 7.71. Found: C, 46.51; H, 3.93; N,
8.03.
(9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-thio)(tricyclohexylphosphine) -
-gold- (I) (8b).
Compound 7 (0.070 g, 0.261 mmol) and Cs2CO3 (0.170 g, 0.522 mmol) were suspended in 2-propanol under argon. A solution of (PCy3)AuCl (0.134 g, 0.261 mmol) in dry acetone was added drop wise into the stirred mixture. The reaction flask was sealed and left stirring at rom temperature for 4 h. After completion of the reaction, solvent was removed under reduced pressure. The white residue was purified by a small silica gel column by eluting a mixture of diethyl ether and methanol (80:20, v/v). Desired product
199 was collected as major fraction. After removal of solvent and drying in vacuum for 6 h
1 gave analytically pure product. Yield: 0.150 g, 77%. H NMR (400 Hz, CDCl3), δ: 8.42
(s, 1H), 7.83 (s, 1H), 6.33 (tapp, 1H, J = 6.5 Hz), 4.11 (q, 1H, J = 7.2 Hz), 3.98–3.77 (m,
2H), 3.10–3.03 (m, 1H), 2.83–2.77 (m, 1H), 2.30 (dd , 1H, J = 13.7, 5.3 Hz), 2.07–2.03
(m, 6H), 1.87–1.84 (m, 6H), 1.74–1.72 (m, 3H), 1.56–1.53 (m, 6H), 1.35–1.22 (m, 12H).
31 1 + P{ H} NMR (CDCl3), δ: 57.6. HRMS: Calcd. for C28H45AuN4O3PS [M+H] : 745.2616
Found: 745.2603 Anal. Calcd. For C28H44AuN4O3PS: C, 45.16; H, 5.96; N, 7.52. Found:
C, 45.27; H, 5.77; N, 7.27.
(9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-thio)(1,3-diisopropylimidazol-
2-ylidene)gold(I) (8c).
Compound 7 (0.070 g, 0.261 mmol) and Cs2CO3 (0.170 g, 0.522 mmol) were suspended in isopropanol under argon. A solution of (1,3-diisopropylimidazol-2-ylidene)gold(I) chloride (0.101 g, 0.261 mmol) in dry acetone was added drop wise into the stirred mixture. The reaction flask was sealed and left stirring at room temperature for 4 h. After completion of the reaction, solvent was removed under reduced pressure. The white residue was purified by a small silica gel column by eluting a mixture of diethyl ether and methanol (80:20, v/v). Desired product was collected as major fraction. After removal of solvent and drying in vacuum for 6 h gave analytically pure product. Yield: 121 g, 75%.
1 H NMR (400 Hz, CD3OD), δ: 8.43 (s, 1H), 8.35 (s, 1H), 7.40 (s, 2H), 6.46 (tapp, 1H, J =
6.9 Hz), 5.26 (sep, 2H, J = 7.1 Hz), 4.59 (m, 1H), 4.07–4.05 (m, 1H), 3.87–3.71 (m, 2H),
2.86–2.79 (m, 1H), 2.46 (ddd , 1H, J = 12.6, 6.2, 2.9 Hz), 1.53 (d, 12H, J = 7.2 Hz).
200 + HRMS: Calcd. for C19H29AuN6O3S [M+H] : 618.1687 Found: 618.1691 Anal. Calcd. For
C19H28AuN6O3S: C, 36.96; H, 4.57; N, 13.61. Found: C, 37.30; H, 4.79; N, 13.82.
6.4.3. General Cell Culture Procedures
HeLa, MCF-7, Molt 4 and CEM-C7 were obtained from the American Type Culture
Collection (Manassas, VA, USA). All adherent cell lines were maintained in Dulbecco’s modified Eagle’s medium (Mediatech) with 100 U/mLpenicillin (Invitrogen), 100
µg/mLstreptomycin (Invitrogen), 0.25 µg/mLamphotericin B (Invitrogen), and 10% fetal bovine serum(USA Scientific) and incubated at 37°C with 5% CO2. CEM and Molt 4 cells were maintained in RPMI-1640 media supplemented with 100 U/mLpenicillin, 100
µg/mLstreptomycin, 0.25 µ g/mLamphotericin B, and 10% fetal bovine serum and incubated at 37°C with 5% CO2. Compounds were freshly dissolved as stock solutions in
DMSO prior to the experiments. Unless stated otherwise, the final concentration of the
DMSO vehicle was 0.1% (V/V).
6.4.4. Cell Proliferation Assays
Cells were plated at a density of 7,000-13,000/well in 100 µL of media overnight in a
96-well plate. Each drug was added to wells in a dose-dependent manner (0.01-100 µM).
Cells were treated with compounds for variable time periods (8-48 h). With adherent cell lines, medium was removed from the wells and then 90 µL of fresh medium was added into each well followed by the addition of 10µL of PrestoBlue Cell Viability Reagent
(invitrogen). Cells were incubated with reagent for 20-60 minutes and the optical density of samples was read at 595 nm using a microplate reader. The background absorbance of
201 dye with media was subtracted from each sample. Cell viability was then normalized against cells treated with DMSO. IC50 values were obtained using a fit of the data to
Equation 1
Y = 100% / [1 + (IC50/Inhibitor)] (1) where y is the fraction of viable cells, IC50 is described as the concentration reducing proliferation of untreated control cells by 50% and Inhibitor is the concentration of compound tested.
6.4.5. Measurements of Apoptosis
Cells were plated at 250,000/mL, different analogs were added in a dose-dependent fashion for 12-48 hr. Cells were trypsinized and then washed with cold PBS. After discarding the supernatant, a 100 µL solution containing 1X annexin-binding buffer, 5 µL of Alexafluor 488 Annexin V and 1 µg/mL of PI solution was added to each sample. The cells were incubated at room temperature for 15 min. After this incubation period, an additional 400 µL of 1X annexin-binding buffer was added. Cells were analyzed using bandpass filters with wavelengths of 525/40 nm and 620/30 nm with a Beckman Coulter
XL flow cytometer.
6.4.6. Cell Cycle Analyses
Cells were plated at a density of 200,000/mL. The compounds were then added in a dose-dependent manner for time periods varying from 1 to 3 days. Cells were treated with 0.25% trypsin and harvested by centrifugation. The supernatant was removed and then washed with PBS. After aspiration of PBS, 500 µL of 70% ethanol was added and
202 cells were incubated on ice for 15 minutes followed by centrifugation and the removal of ethanol. One mL of PI staining solution [(10 mL of 0.1 Triton X-100/PBS, 0.4 mL of 500
µg/mL of PI, and 2 mg/mL of DNase-free RNase)] was added to the cell suspension, placed on ice for 30 minutes, and then analyzed using a Beckman Coulter XL flow cytometer with a red filter. Data were analyzed with ModFit software.
6.4.7. Assessment of the Mitochondrial Membrane Potential
Cells were cultured on 12 well plate at a cell density optimal for apoptosis induction and minimizing any cell sloughing. After incubation of 24-48 h with different concentrations of compound 8, around 1-2 million of suspension cells were centrifuged and washed with PBS. For adherent cell lines, cells were plated at density of 2000/mL in
12 well plate. After 48 hour of drug treatment the supernatant was removed. The cells were then suspended with 0.5 mL1X MitoPT JC-1 solution (MitoPTTM -JC1 Assay Kit,
Immuno Chemistry Technologies, LLC). The cells were incubated for 20 minutes at 37 oC. Control cells were likewise incubated with JC1 dye. The suspension cells were centrifuged and washed several times with the assay buffer. A monolayer of cells was formed and covered with a sterile cover slip. In case of adherent cells the monolayer was washed with 1-2 mL of assay buffer and one drop of assay buffer was placed and covered with sterile coverslip. The integrity of mitochondrial membrane potential was assessed by an optical microscope.
203 6.4.8. Thioredoxin Reductase Inhibition
Commercially available rat liver TrxR (Sigma) was used to determine the inhibitory effect of the gold drugs towards TrxR. The assay was performed following the manufacturer’s instruction (Sigma product information sheet T 9698). Before each experiment, 10 µL of supplied rat liver TrxR was diluted to give 100 µL TrxR solution in potassium phosphate buffer. 10 µL of this aliquot (containing approximately 0.06 unit of
TrxR) was placed in a 0.5 mLcuvette along with 10 µL of required gold drug with increasing concentration, 80 µL distilled water and 500 µL reaction mixture (10 mL of reaction mixture consisted of 1.0 mL of 1.0 M potassium phosphate buffer, pH 7.0, 0.20 mL of 500 mM EDTA solution pH 7.5, 0.80 mL of 63 mM DTNB in ethanol, 0.10 mL of
20 mg/mLbovine serum albumin, 0.05 mL of 48 mM NADPH and 7.85 mL of water).
After mixing, the formation of 5-thionitrobenzol was monitored by measuring the absorbance at 412 nm using BioRad SmartSpecTM 3000 spectrophotometer over 3 min in
10s intervals. The increase in 5-thionitrobenzol over time followed a linear trend
(r2≥0.99) and the enzymatic activities were calculated as the slopes (increase in absorbance per second) thereof.
6.5. References
(1) Gandhi, B. V.; Plunkett, W.; Weller, S.; Du, M.; Ayres, M.; Rodriguez, C. O.; Ramakrishna, P.; Rosner, G. L.; Hodge, J. P.; Brien, S. O.; Keating, M. J. J. Clin. Oncol. 2001, 19, 2142–2152.
(2) Parker, W. B. Chem. Rev. 2009, 109, 2880–2893.
(3) Zhang, J.; Visser, F.; King, K. M.; Baldwin, S. a; Young, J. D.; Cass, C. E. Cancer Metastasis Rev. 2007, 26, 85–110.
204 (4) Huang, P.; Chubb, S.; Hertel, L. W.; Grindey, G. B.; Plunkett, W. Cancer Res. 1991, 51, 6110–6117.
(5) Sadler, P. J. Gold Bull. 1976, 9, 110–118.
(6) Dive, D.; Biot, C. ChemMedChem 2008, 3, 383–391.
(7) Shaw, C. F. I. Chem. Rev. 1999, 99, 2589–2600.
(8) Barnard, P. J.; Berners-Price, S. J. Coord. Chem. Rev. 2007, 251, 1889–1902.
(9) Berners-Price, S. J.; Filipovska, A. Metallomics 2011, 3, 863–873.
(10) Berners-Price, S. J. In Bioinorganic Medicinal Chemistry, ed. E. Alessio, Wiley- VCH, Weinheim; 2011; pp. 197–221.
(11) Zou, J.; Taylor, P.; Dornan, J.; Robinson, S.; Walkinshaw, M.; Sadler, P. Angew. Chem. Int. Ed. Engl. 2000, 39, 2931–2934.
(12) Bindoli, A.; Rigobello, M. P.; Scutari, G.; Gabbiani, C.; Casini, A.; Messori, L. Coord. Chem. Rev. 2009, 253, 1692–1707.
(13) Go, Y.-M.; Jones, D. P. Antioxid. Redox Signal. 2010, 13, 489–509.
(14) Marzano, C.; Gandin, V.; Folda, A.; Scutari, G.; Bindoli, A.; Rigobello, M. P. Free Radic. Biol. Med. 2007, 42, 872–881.
(15) Rackham, O.; Nichols, S. J.; Leedman, P. J.; Berners-Price, S. J.; Filipovska, A. Biochem. Pharmacol. 2007, 74, 992–1002.
(16) Hickey, J. L.; Ruhayel, R. a; Barnard, P. J.; Baker, M. V; Berners-Price, S. J.; Filipovska, A. J. Am. Chem. Soc. 2008, 130, 12570–12571.
(17) Fieser, L. F.; Fieser, M. Reagents Org. Synth. Louis F. Fieser Mary Fieser. Wiley, New York 1968, 668.
(18) Hanna, N. B.; Ramasamy, K.; Robins, R. K.; Revankar, G. R. J. Heterocycl. Chem. 1988, 25, 1899–1903.
(19) Ren, R. X.-F.; Chaudhuri, N. C.; Paris, P. L.; Rumney; Kool, E. T. J. Am. Chem. Soc. 1996, 118, 7671–7678.
(20) Gao, L.; Niedzwiecki, D. S.; Deligonul, N.; Zeller, M.; Hunter, A. D.; Gray, T. G. Chem. – A Eur. J. 2012, 18, 6316–6327.
205 (21) Gao, L.; Peay, M. A.; Partyka, D. V; Updegraff, J. B.; Teets, T. S.; Esswein, A. J.; Zeller, M.; Hunter, A. D.; Gray, T. G. Organometallics 2009, 28, 5669–5681.
(22) Partyka, D. V; Robilotto, T. J.; Zeller, M.; Hunter, A. D.; Gray, T. G. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 14293–14297.
(23) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chemie Int. Ed. 2006, 45, 8188–8191.
(24) Heckler, J. E.; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chemie Int. Ed. 2012, 51, 5924–5928.
(25) Partyka, D. V; Teets, T. S.; Zeller, M.; Updegraff, J. B.; Hunter, A. D.; Gray, T. G. Chemistry 2012, 18, 2100–2112.
(26) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Angew. Chem. Int. Ed. Engl. 2006, 45, 8188–8191.
(27) Partyka, D. V; Zeller, M.; Hunter, A. D.; Gray, T. G. Inorg. Chem. 2012, 51, 8394–8401.
(28) Basanez, G.; Nechushtan, A.; Drozhinin, O.; Chanturiya, A.; E, C.; S, T.; A, W. K.; T, H. Y.; J, Z.; J, Y. R. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 5492–5497.
(29) Mann, F. G.; Wells, A. F.; Purdie, D. J. Chem. Soc. 1937, 1828–1836.
(30) Maity, A.; Choi, J.-S.; Teets, T. S.; Deligonul, N.; Berdis, A. J.; Gray, T. G. Chem. – A Eur. J. 2013, 19, 15924–15932.
206 Chapter 7
Conclusion And Future Direction
207 Conclusion And Future Direction
Attaching heavy transition element to organic moiety has several benefits. The resulting compounds are often triplet state emitters, and applications range from catalysis to material science, optoelectronics to biosensors. The expansion of this field has been limited by synthesis. Moreover, due to the unreactive nature of C–H bonds, harsh reaction conditions (temperature often exceeds 150 °C) and use of toxic metals such as mercury, and cadmium are commonplace.
Described herein are two distinct methodologies that will open the direct access to a library of organo-gold and -iridium species. The first method, which relies on transmetalation from boronic acid/ester precursors, delivers robust iridium cyclometalates in high yield under mild conditions. A supporting base is necessary and reactions are performed at 23 °C. Products can be purified in open air. A broad range of functional groups are accommodated. Thus, fine tuning of cyclometalating ligand surrounding the metal resulted phosphorescent materials with varied light absorption and emission profile.
On a different account, a palladium-catalyzed cross coupling reaction that has revolutionized organic chemistry, has been applied to metal halide coupling partners for the first time. Gold(III) dichlorides were reacted with boronic acids to deliver diarylated products with high fidelity. Both base and Pd catalyst was necessary. Reactions are rapid and proceed at room temperature (Scheme 7.1). Incomplete aryl transfer leads to apparently counterintuitive mono arylated products where shorter gold(III)–chloride breaks first.
208
OH Pd(OAc)2 (5 mol%) t B [HP Bu3][BF4] (15 mol%) N OH Au O K2CO3 (4 eq) Cl Cl toluene : iPrOH (2:1, v/v)
Scheme 7.1. Developed synthetic protocol for Au(III)–Cl arylation.
Synthesizing organo-iridium(III) and -gold(III) compounds of different photophysical properties by varying cyclometalated ligands, shown in Figure 7.1 are of immediate priorities.
N N N O N
S
F3C CF3 3-CF3-ppy 4-CF3-ppy thp bon
S N O N O N O O N O
NEt2 bo op dpo C6
S N S N S N
S
αbsn btth βbsn
Figure 7.1. Various cyclometalating ligand that are available.
209 Ligands will be brominated followed by borylation reaction then will be reacted with iridium-oxo species, as shown in Scheme 7.2.
N N OH base N S 2 S N Ir Ir O 2-propanol OH 2 B 6 h, rt N O N
Scheme 7.2. Proposed reaction for iridium cyclometalation.
Detailed mechanistic investigation of gold(III)–Cl diarylation are underway. s19F
NMR handle will be used extensively to characterize the in situ formed species.
Expanding the protocol shown in Scheme 7.1. will be applied to arylate other M–Cl bonds, where M will be varied over a range of transition metals.
We have reported the first fluoride complexes of cyclometalated iridium(III)—both bridging and terminal. The new fluoride complexes are phosphorescent; the emission quantum yield of fluorobridged dimer exceeds 20% at room temperature. The new complexes broaden understanding of late-metal fluorides. Experiments on reactivity and materials design are under investigation.
Emissive iridium(III) cyclometalates have been attached to a deoxyribose sugar. They are potential photoactive surrogates of natural nucleosides; their biodisposition can be tracked optically.
Gold(I) containing metallonucleosides have been synthesized and one of them has induced cytotoxicity by targeting mitochondrial TrxR. These findings indicate attachment of Au(I) to the nucleoside analog is a suitable strategy to obtain bioactive compounds.
210 Appendix I. Crystallographic Data of Synthesized New Compound
Table AI.1. X-ray crystallographic data for (9-(2-deoxy-β-D-erythro- pentofuranosyl)purine-6-thio)(tricyclohexylphosphine) -gold- (I) (8b)
AI.1a. Crystal data AI.1b. Data collection
Chemical C32H49AuN4O4PS Diffractometer Bruker AXS APEX II formula CCD area detector diffractometer Mr 813.75 Absorption Multi-scan Crystal Monoclinic, P21 correction AXscale in APEX II system, space (Bruker 2004) group Tmin, Tmax 0.450, 0.826 Temperature 170 (K) No. of measured, 42824, 16455, 11970 independent and a, b, c (Å) 19.2228 (12), 7.8174 observed [I > (5), 23.5392 (14) 2σ(I)] reflections
β (°) 103.312 (1) Rint 0.044
3 −1 V (Å ) 3442.2 (4) (sin θ/λ)max (Å ) 0.670
Z 4
Radiation type Mo Kα
µ (mm−1) 4.42
Crystal size 0.22 × 0.11 × 0.05 (mm)
211 AI.1c. Refinement AI.1d. Crystal Structure R[F2 > 0.039, 0.103, 1 2σ(F2)], wR(F2 .03 ), S
No. of 16455 reflections
No. of 787 parameters
No. of 1 restraints
H-atom H-atom treatment parameters constrained
(Δ/σ)max 1.045
Δρmax, Δρmin (e 1.29, −0.87 Å−3)
Absolute Flack H D structure (1983), Acta Cryst. A39, 876-881
Absolute −0.003 (6) structure parameter
AI.1e. Bonds (Å) AI.1f. Angles (˚) Au1—P1 2.2719(18) P1—Au1—S1 179.16(7) Au1—S1 2.3095(19) P2—Au2—S2 177.47(8) Au2—P2 2.260(2) C11—P1—C17 107.7(3) Au2—S2 2.3049(19) C11—P1—C23 108.9(4) P1—C11 1.821(7) C17—P1—C23 105.8(4) P1—C17 1.831(7) C11—P1—Au1 112.9(3) P1—C23 1.847(8) C17—P1—Au1 110.2(2) S1—C1 1.741(8) C23—P1—Au1 111.0(3) P2—C51 1.839(9) C1—S1—Au1 104.0(3) P2—C45 1.838(7) C51—P2—C45 105.0(4) P2—C39 1.854(10) C51—P2—C39 111.7(6) S2—C29 1.766(9) C45—P2—C39 105.8(4) N2—C2 1.323(13) C51—P2—Au2 106.7(3) N2—C3 1.349(10) C45—P2—Au2 115.0(3)
212 N3—C3 1.359(9) C39—P2—Au2 112.5(3) N3—C4 1.377(10) C29—S2—Au2 103.1(3) N3—C6 1.457(10) C2—N2—C3 110.3(7) C1—N1 1.368(11) C3—N3—C4 104.7(7) C1—C5 1.376(11) C3—N3—C6 129.8(7) C5—C3 1.377(11) C4—N3—C6 124.9(7) C5—N4 1.385(9) N1—C1—C5 117.5(8) N1—C2 1.339(12) N1—C1—S1 115.1(6) C18—C19 1.526(10) C5—C1—S1 127.4(7) C18—C17 1.549(12) C1—C5—C3 119.1(8) C18—H18A 0.99 C1—C5—N4 131.1(9) C18—H18B 0.99 C3—C5—N4 109.5(7) C17—C22 1.519(10) N2—C3—N3 127.1(7) C17—H17 1 N2—C3—C5 125.2(7) N4—C4 1.309(10) N3—C3—C5 107.7(7) C19—C20 1.519(11) C2—N1—C1 116.6(8) C19—H19A 0.99 C19—C18—C17 109.9(6) C19—H19B 0.99 C19—C18—H18A 109.7 C30—N6 1.322(12) C17—C18—H18A 109.7 C30—N5 1.407(12) C19—C18—H18B 109.7 C30—H30 0.95 C17—C18—H18B 109.7 N7—C32 1.296(11) H18A—C18— 108.2 N7—C31 1.313(11) H18B 111.2(6) N7—C34 1.497(11) C22—C17—C18 111.4(5) C31—N6 1.261(11) C22—C17—P1 115.2(5) C31—C33 1.459(13) C18—C17—P1 106.1 C12—C11 1.531(11) C22—C17—H17 106.1 C12—C13 1.532(10) C18—C17—H17 106.1 C12—H12A 0.99 P1—C17—H17 104.2(6) C12—H12B 0.99 C4—N4—C5 112.3(6) C16—C15 1.516(11) C20—C19—C18 109.2 C16—C11 1.532(10) C20—C19—H19A 109.2 C16—H16A 0.99 C18—C19—H19A 109.1 C16—H16B 0.99 C20—C19—H19B 109.1 C11—H11 1 C18—C19—H19B 107.9 C50—C49 1.514(10) H19A—C19— 124.6(9) C50—C45 1.549(9) H19B 117.7 C50—H50A 0.99 N6—C30—N5 117.7 C50—H50B 0.99 N6—C30—H30 111.1(8) C45—C46 1.540(10) N5—C30—H30 123.5(8) C45—H45 1 C32—N7—C31 125.1(8) C21—C20 1.519(11) C32—N7—C34 136.8(11) C21—C22 1.534(10) C31—N7—C34 120.1(9) C21—H21A 0.99 N6—C31—N7 103.1(8) C21—H21B 0.99 N6—C31—C33 120.9(10) C20—H20A 0.99 N7—C31—C33 112.2(6)
213 C20—H20B 0.99 C31—N6—C30 109.2 C29—N5 1.379(11) C11—C12—C13 109.2 C29—C33 1.414(11) C11—C12—H12A 109.1 C28—C27 1.509(12) C13—C12—H12A 109.2 C28—C23 1.535(11) C11—C12—H12B 107.9 C28—H28A 0.99 C13—C12—H12B 112.8(6) C28—H28B 0.99 H12A—C12— 109.1 C23—C24 1.505(11) H12B 109 C23—H23 1 C15—C16—C11 109 C22—H22A 0.99 C15—C16—H16A 109 C22—H22B 0.99 C11—C16—H16A 107.8 C51—C56 1.526(12) C15—C16—H16B 109.7(7) C51—C52 1.558(11) C11—C16—H16B 110.6(5) C51—H51 1 H16A—C16— 111.1(5) N8—C32 1.311(11) H16B 108.5 N8—C33 1.356(11) C12—C11—C16 108.5 C32—H32 0.95 C12—C11—P1 108.5 C24—C25 1.550(12) C16—C11—P1 111.1(6) C24—H24A 0.99 C12—C11—H11 109.4 C24—H24B 0.99 C16—C11—H11 109.4 C4—H4 0.95 P1—C11—H11 109.4 C48—C47 1.517(11) C49—C50—C45 109.4 C48—C49 1.523(10) C49—C50—H50A 108 C48—H48A 0.99 C45—C50—H50A 110.3(6) C48—H48B 0.99 C49—C50—H50B 110.3(5) C46—C47 1.547(11) C45—C50—H50B 111.2(5) C46—H46A 0.99 H50A—C50— 108.3 C46—H46B 0.99 H50B 108.3 C49—H49A 0.99 C46—C45—C50 108.3 C49—H49B 0.99 C46—C45—P2 111.2(6) C47—H47A 0.99 C50—C45—P2 109.4 C47—H47B 0.99 C46—C45—H45 109.4 C53—C54 1.481(15) C50—C45—H45 109.4 C53—C52 1.525(13) P2—C45—H45 109.4 C53—H53A 0.99 C20—C21—C22 108 C53—H53B 0.99 C20—C21—H21A 111.8(7) C52—H52A 0.99 C22—C21—H21A 109.3 C52—H52B 0.99 C20—C21—H21B 109.3 C56—C55 1.498(13) C22—C21—H21B 109.3 C56—H56A 0.99 H21A—C21— 109.3 C56—H56B 0.99 H21B 107.9 C26—C27 1.483(13) C19—C20—C21 117.3(9) C26—C25 1.512(12) C19—C20—H20A 117.7(7) C26—H26A 0.99 C21—C20—H20A 125.0(7) C26—H26B 0.99 C19—C20—H20B 112.7(7) C15—C14 1.496(14) C21—C20—H20B 109
214 C15—H15A 0.99 H20A—C20— 109.1 C15—H15B 0.99 H20B 109 C25—H25A 0.99 N5—C29—C33 109 C25—H25B 0.99 N5—C29—S2 107.8 C13—C14 1.565(12) C33—C29—S2 111.3(7) C13—H13A 0.99 C27—C28—C23 113.2(6) C13—H13B 0.99 C27—C28—H28A 118.1(6) C14—H14A 0.99 C23—C28—H28A 104.2 C14—H14B 0.99 C27—C28—H28B 104.1 C44—C39 1.497(13) C23—C28—H28B 104.1 C44—C43 1.507(15) H28A—C28— 111.2(7) C44—H44A 0.99 H28B 109.4 C44—H44B 0.99 C24—C23—C28 109.4 C39—C40 1.382(16) C24—C23—P1 109.4 C39—H39 1 C28—C23—P1 109.4 C54—C55 1.531(14) C24—C23—H23 108 C54—H54A 0.99 C28—C23—H23 109.3(7) C54—H54B 0.99 P1—C23—H23 114.2(7) C55—H55A 0.99 C17—C22—C21 117.9(6) C55—H55B 0.99 C17—C22—H22A 104.6 C34—O4 1.418(13) C21—C22—H22A 104.6 C34—C35 1.541(15) C17—C22—H22B 104.6 C34—H34 1 C21—C22—H22B 105.4(8) O4—C37 1.420(12) H22A—C22— 112.7(8) C2—H2 0.95 H22B 123.7 C27—H27A 0.99 C56—C51—C52 123.7 C27—H27B 0.99 C56—C51—P2 109.5(7) C43—C42 1.317(19) C52—C51—P2 109.8 C43—H43 0.95 C56—C51—H51 109.8 C40—C41 1.545(15) C52—C51—H51 109.8 C40—H40 0.95 P2—C51—H51 109.8 C6—O1 1.423(11) C32—N8—C33 108.2 C6—C7 1.468(16) N7—C32—N8 113.9(7) C6—H6 1 N7—C32—H32 123 C41—C42 1.518(15) N8—C32—H32 123 C41—H41A 0.99 C23—C24—C25 110.8(6) C41—H41B 0.99 C23—C24—H24A 109.5 C36—O6 1.454(15) C25—C24—H24A 109.5 C36—C37 1.477(17) C23—C24—H24B 109.5 C36—C35 1.510(16) C25—C24—H24B 109.5 C36—H36 1 H24A—C24— 108.1 C35—H35A 0.99 H24B 111.6(6) C35—H35B 0.99 N4—C4—N3 109.3 C37—C38 1.430(19) N4—C4—H4 109.3 C37—H37 1 N3—C4—H4 109.3 O1—C9 1.417(9) C47—C48—C49 109.3
215 C9—C10 1.488(13) C47—C48—H48A 108 C9—C8 1.507(15) C49—C48—H48A 112.8(7) C9—H9 1 C47—C48—H48B 109 C42—H42 0.95 C49—C48—H48B 109 O6—H6A 0.8401 H48A—C48— 109 C38—O5 1.67(2) H48B 109 C38—H38A 0.99 C45—C46—C47 107.8 C38—H38B 0.99 C45—C46—H46A 112.3(6) O5—H5 0.84 C47—C46—H46A 109.1 C10—O3 1.406(12) C45—C46—H46B 109.1 C10—H10A 0.99 C47—C46—H46B 109.1 C10—H10B 0.99 H46A—C46— 109.1 O2—C8 1.684(19) H46B 107.9 O3—H3 0.8417 C50—C49—C48 114.5(11) C7—C8 1.389(17) C50—C49—H49A 108.6 C7—H7 0.95 C48—C49—H49A 108.6 O8—C64 1.41(3) C50—C49—H49B 108.6 O8—C61 1.71(4) C48—C49—H49B 108.6 C64—C63 1.39(2) H49A—C49— 107.6 C64—H64A 0.99 H49B 108.7(8) C64—H64B 0.99 C48—C47—C46 110 C59—C60 1.31(2) C48—C47—H47A 110 C59—C58 1.42(2) C46—C47—H47A 110 C59—H59A 0.99 C48—C47—H47B 110 C59—H59B 0.99 C46—C47—H47B 108.3 C60—O7 1.34(2) H47A—C47— 112.2(9) C60—H60A 0.99 H47B 109.2 C60—H60B 0.99 C54—C53—C52 109.2 C57—C58 1.31(2) C54—C53—H53A 109.2 C57—O7 1.46(3) C52—C53—H53A 109.2 C57—H57A 0.99 C54—C53—H53B 107.9 C57—H57B 0.99 C52—C53—H53B 117.3(9) C58—H58A 0.99 H53A—C53— 112.6(8) C58—H58B 0.99 H53B 109.1 C8—O2A 1.137(18) C53—C52—C51 109.1 C62—C63 1.39(2) C53—C52—H52A 109.1 C62—C61 1.44(4) C51—C52—H52A 109.1 C62—H62A 0.99 C53—C52—H52B 107.8 C62—H62B 0.99 C51—C52—H52B 111.0(8) C63—H63A 0.99 H52A—C52— 109.4 C63—H63B 0.99 H52B 109.4 C61—H61A 0.99 C55—C56—C51 109.4 C61—H61B 0.99 C55—C56—H56A 109.5 C51—C56—H56A 108 C55—C56—H56B 111.9(7) C51—C56—H56B 109.2
216 H56A—C56— 109.2 H56B 109.3 C29—N5—C30 109.2 C27—C26—C25 107.9 C27—C26—H26A 110.8(7) C25—C26—H26A 109.5 C27—C26—H26B 109.5 C25—C26—H26B 109.5 H26A—C26— 109.5 H26B 108.1 C14—C15—C16 109.1(8) C14—C15—H15A 109.9 C16—C15—H15A 109.9 C14—C15—H15B 109.9 C16—C15—H15B 109.9 H15A—C15— 108.3 H15B 113.3(9) C26—C25—C24 108.9 C26—C25—H25A 108.9 C24—C25—H25A 108.9 C26—C25—H25B 108.9 C24—C25—H25B 107.7 H25A—C25— 118.7(11) H25B 117.8(10) C12—C13—C14 117.9(7) C12—C13—H13A 97.9 C14—C13—H13A 97.9 C12—C13—H13B 97.9 C14—C13—H13B 111.1(8) H13A—C13— 109.4 H13B 109.4 C15—C14—C13 109.4 C15—C14—H14A 109.4 C13—C14—H14A 108 C15—C14—H14B 111.9(8) C13—C14—H14B 109.2 H14A—C14— 109.2 H14B 109.2 C39—C44—C43 109.2 C39—C44—H44A 107.9 C43—C44—H44A 107.4(9) C39—C44—H44B 105.0(8) C43—C44—H44B 114.0(9) H44A—C44— 110.1 H44B 110.1 C40—C39—C44 110.1
217 C40—C39—P2 107.0(9) C44—C39—P2 130.9(9) C40—C39—H39 114.5 C44—C39—H39 114.5 P2—C39—H39 112.1(8) C53—C54—C55 109.2 C53—C54—H54A 109.2 C55—C54—H54A 109.2 C53—C54—H54B 109.2 C55—C54—H54B 107.9 H54A—C54— 126.5(11) H54B 116.8 C56—C55—C54 116.8 C56—C55—H55A 116.7(12) C54—C55—H55A 121.7 C56—C55—H55B 121.7 C54—C55—H55B 132.5(8) H55A—C55— 107.7(8) H55B 119.7(9) O4—C34—N7 108.8(8) O4—C34—C35 107.5(8) N7—C34—C35 115.4(10) O4—C34—H34 108.3 N7—C34—H34 108.3 C35—C34—H34 108.3 C34—O4—C37 115.2(10) N2—C2—N1 108.5 N2—C2—H2 108.5 N1—C2—H2 108.5 C26—C27—C28 108.5 C26—C27—H27A 107.5 C28—C27—H27A 101.2(14) C26—C27—H27B 112.1(10) C28—C27—H27B 102.5(9) H27A—C27— 113.3 H27B 113.3 C42—C43—C44 113.3 C42—C43—H43 100.3(11) C44—C43—H43 111.7 C39—C40—C41 111.7 C39—C40—H40 111.8 C41—C40—H40 111.8 N8—C33—C29 109.5 N8—C33—C31 110.8(14) C29—C33—C31 110.0(9) O1—C6—N3 114.8(11)
218 O1—C6—C7 106.9 N3—C6—C7 106.9 O1—C6—H6 106.9 N3—C6—H6 107.5(7) C7—C6—H6 107.1(7) C42—C41—C40 107.5(8) C42—C41—H41A 115.9(9) C40—C41—H41A 108.7 C42—C41—H41B 108.7 C40—C41—H41B 108.6 H41A—C41— 117.1(12) H41B 121.5 O6—C36—C37 121.4 O6—C36—C35 109.5 C37—C36—C35 107.2(11) O6—C36—H36 110.3 C37—C36—H36 110.3 C35—C36—H36 110.2 C36—C35—C34 110.2 C36—C35—H35A 108.5 C34—C35—H35A 109.4 C36—C35—H35B 114.9(8) C34—C35—H35B 108.7 H35A—C35— 108.5 H35B 108.4 O4—C37—C38 108.5 O4—C37—C36 107.5 C38—C37—C36 109.8 O4—C37—H37 108.3(10) C38—C37—H37 125.8 C36—C37—H37 125.9 C9—O1—C6 114(2) O1—C9—C10 103(2) O1—C9—C8 111.1 C10—C9—C8 111.1 O1—C9—H9 111.1 C10—C9—H9 111.1 C8—C9—H9 109 C43—C42—C41 95.8(17) C43—C42—H42 112.5 C41—C42—H42 112.6 C36—O6—H6A 112.7 C37—C38—O5 112.6 C37—C38—H38A 110.1 O5—C38—H38A 108(2) C37—C38—H38B 110.1
219 O5—C38—H38B 110 H38A—C38— 110.3 H38B 110.3 C38—O5—H5 108.5 O3—C10—C9 97(2) O3—C10—H10A 112.4 C9—C10—H10A 112.5 O3—C10—H10B 112.3 C9—C10—H10B 112.3 H10A—C10— 110 H10B 116(2) C10—O3—H3 108.3 C8—C7—C6 108.2 C8—C7—H7 108.2 C6—C7—H7 108.2 C64—O8—C61 107.3 C63—C64—O8 100.7(19) C63—C64—H64A 126.0(15) O8—C64—H64A 123.4(15) C63—C64—H64B 106.6(11) O8—C64—H64B 61.8(14) H64A—C64— 93.1(13) H64B 99.5(10) C60—C59—C58 120(3) C60—C59—H59A 107.3 C58—C59—H59A 107.3 C60—C59—H59B 107.2 C58—C59—H59B 107.2 H59A—C59— 106.9 H59B 111(2) C59—C60—O7 109.4 C59—C60—H60A 109.3 O7—C60—H60A 109.3 C59—C60—H60B 109.3 O7—C60—H60B 108 H60A—C60— 89.4(19) H60B 113.7 C58—C57—O7 113.8 C58—C57—H57A 113.8 O7—C57—H57A 113.8 C58—C57—H57B 111 O7—C57—H57B H57A—C57— H57B C57—C58—C59 C57—C58—H58A
220 C59—C58—H58A C57—C58—H58B C59—C58—H58B H58A—C58— H58B C60—O7—C57 O2A—C8—C7 O2A—C8—C9 C7—C8—C9 O2A—C8—O2 C7—C8—O2 C9—C8—O2 C63—C62—C61 C63—C62—H62A C61—C62—H62A C63—C62—H62B C61—C62—H62B H62A—C62— H62B C62—C63—C64 C62—C63—H63A C64—C63—H63A C62—C63—H63B C64—C63—H63B H63A—C63— H63B C62—C61—O8 C62—C61—H61A O8—C61—H61A C62—C61—H61B O8—C61—H61B H61A—C61— H61B
221 Table AI.2. X-ray crystallographic data for [(Fppy)AuCl2]
AI.2a. Crystal data AI.2b. Data collection
Chemical C11H7AuCl2FN Diffractometer Bruker formula AXS SMART APEX CCD diffractometer Mr 440.04 Absorption Multi-scan Crystal Monoclinic, P21/c correction Apex2 v2013.4-1 (Bruker, system, space 2012) group Tmin, Tmax 0.317, 0.746 Temperature 100 (K) No. of 10696, 3310, 2710 measured, a, b, c (Å) 9.1445 (19), 7.8648 independent and (16), 15.710 (3) observed [I > 2σ(I)] β (°) 106.294 (5) reflections V (Å3) 1084.5 (4) Rint 0.048
Z 4 −1 (sin θ/λ)max (Å ) 0.728 Radiation Mo Kα type
µ (mm−1) 14.04
Crystal size 0.30 × 0.18 × 0.04 (mm)
222 AI.2c. Refinement AI.2d. Crystal Structure R[F2 > 0.036, 0.103, 1. 2σ(F2)], wR(F2) 09 , S
No. of 3310 reflections
No. of 145 parameters
H-atom H-atom treatment parameters constrained
Δρmax, Δρmin (e 3.63, −2.61 Å−3)
AI.2e. Bonds (Å) AI.2f. Angles (˚) Au1—C11 2.026(5) C11—Au1—N1 81.7(2) Au1—N1 2.033(5) C11—Au1—Cl5 93.22(18) Au1—Cl5 2.2721(17) N1—Au1—Cl5 174.65(14) Au1—Cl4 2.3750(15) C11—Au1—Cl4 176.33(17) N1—C1 1.344(8) N1—Au1—Cl4 95.04(15) N1—C5 1.376(7) Cl5—Au1—Cl4 90.03(6) C1—C2 1.369(9) C1—N1—C5 120.1(5) C1—H1 0.95 C1—N1—Au1 124.7(4) F1—C9 1.355(8) C5—N1—Au1 115.1(4) C4—C5 1.375(8) N1—C1—C2 121.5(5) C4—C3 1.396(9) N1—C1—H1 119.3 C4—H4 0.95 C2—C1—H1 119.3 C3—C2 1.389(9) C5—C4—C3 119.3(5) C3—H3 0.95 C5—C4—H4 120.4 C2—H2 0.95 C3—C4—H4 120.4 C6—C7 1.407(7) C2—C3—C4 119.3(6) C6—C11 1.411(8) C2—C3—H3 120.3 C6—C5 1.459(8) C4—C3—H3 120.3 C7—C8 1.382(9) C1—C2—C3 119.4(6) C7—H7 0.95 C1—C2—H2 120.3 C8—C9 1.372(9) C3—C2—H2 120.3 C8—H8 0.95 C7—C6—C11 119.2(6) C9—C10 1.392(8) C7—C6—C5 123.9(5) C10—C11 1.383(9) C11—C6—C5 116.9(5) C10—H10 0.95 C8—C7—C6 120.1(6) C8—C7—H7 120
223 C6—C7—H7 120 C9—C8—C7 118.5(5) C9—C8—H8 120.8 C7—C8—H8 120.8 F1—C9—C8 118.2(5) F1—C9—C10 117.5(6) C8—C9—C10 124.2(6) C11—C10—C9 116.8(6) C11—C10—H10 121.6 C9—C10—H10 121.6 C10—C11—C6 121.2(5) C10—C11—Au1 126.5(4) C6—C11—Au1 112.3(4) C4—C5—N1 120.4(6) C4—C5—C6 125.8(5) N1—C5—C6 113.9(5)
224 Table AI.3. X-ray crystallographic data for [(tpy)AuI2]
AI.3a. Crystal data AI.3b. Data collection
Chemical C12H10AuI2N Diffractometer Bruker AXS D8 formula Quest CMOS diffractometer Mr 618.98 Absorption Multi-scan Crystal system, Monoclinic, C2/c correction Apex2 v2014.1-1 space group (Bruker, 2014)
Temperature 100 Tmin, Tmax 0.345, 0.746 (K) No. of measured, 14887, 3924, 3469 a, b, c (Å) 21.5351 (6), 6.9464 independent and (2), 19.7130 (6) observed [I > 2σ(I)] reflections β (°) 118.1728 (8) R 0.028 V (Å3) 2599.53 (13) int −1 (sin θ/λ)max (Å ) 0.714
Z 8
Radiation type Mo Kα
µ (mm−1) 16.04
Crystal size 0.42 × 0.08 × 0.04 (mm)
AI.3c. Refinement AI.3d. Crystal Structure R[F2 > 0.021, 0.041, 1. 2σ(F2)], wR(F2) 08 , S
No. of 3924 reflections
No. of 146 parameters
H-atom H-atom treatment parameters constrained
2 2 w = 1/[σ (Fo ) 2 + (0.0111P) + 10.7266P]
225 where P = 2 2 (Fo + 2Fc )/3
Δρmax, Δρmin (e 1.08, −1.51 Å−3)
AI.3e. Bonds (Å) AI.3f. Angles (˚) C1—N1 1.345(4) N1—C1—C2 121.3(3) C1—C2 1.383(4) N1—C1—H1 119.3 C1—H1 0.95 C2—C1—H1 119.3 C2—C3 1.384(5) C1—C2—C3 119.0(3) C2—H2 0.95 C1—C2—H2 120.5 C3—C4 1.385(5) C3—C2—H2 120.5 C3—H3 0.95 C2—C3—C4 119.8(3) C4—C5 1.397(4) C2—C3—H3 120.1 C4—H4 0.95 C4—C3—H3 120.1 C5—N1 1.359(4) C3—C4—C5 119.2(3) C5—C6 1.463(5) C3—C4—H4 120.4 C6—C7 1.390(5) C5—C4—H4 120.4 C6—C11 1.405(4) N1—C5—C4 120.2(3) C7—C8 1.392(5) N1—C5—C6 115.0(3) C7—H7 0.95 C4—C5—C6 124.8(3) C8—C9 1.398(5) C7—C6—C11 119.5(3) C8—H8 0.95 C7—C6—C5 122.9(3) C9—C10 1.401(5) C11—C6—C5 117.6(3) C9—C12 1.506(5) C6—C7—C8 120.4(3) C10—C11 1.390(5) C6—C7—H7 119.8 C10—H10 0.95 C8—C7—H7 119.8 C11—Au1 2.058(3) C7—C8—C9 120.8(3) C12—H12A 0.98 C7—C8—H8 119.6 C12—H12B 0.98 C9—C8—H8 119.6 C12—H12C 0.98 C8—C9—C10 118.4(3) N1—Au1 2.100(3) C8—C9—C12 120.9(3) I1—Au1 2.5741(2) C10—C9—C12 120.6(3) I2—Au1 2.6783(3) C11—C10—C9 121.2(3) C11—C10—H10 119.4 C9—C10—H10 119.4 C10—C11—C6 119.6(3) C10—C11—Au1 127.9(2) C6—C11—Au1 112.4(2) C9—C12—H12A 109.5 C9—C12—H12B 109.5 H12A—C12— 109.5 H12B 109.5 C9—C12—H12C 109.5 H12A—C12— 109.5
226 H12C 120.4(3) H12B—C12— 125.3(2) H12C 114.2(2) C1—N1—C5 80.64(12) C1—N1—Au1 93.75(9) C5—N1—Au1 173.63(8) C11—Au1—N1 176.66(9) C11—Au1—I1 96.48(8) N1—Au1—I1 89.214(8) C11—Au1—I2 N1—Au1—I2 I1—Au1—I2
227 Table AI.4. X-ray crystallographic data for [(tpy)Au(4-isopropoxyphenyl)2]
AI.4a. Crystal data AI.4b. Data collection Crystal data Diffractometer Bruker AXS D8 Quest CMOS Chemical C30H32AuNO2 diffractometer formula Absorption Multi-scan Mr 635.53 correction Apex2 v2014.1-1 (Bruker, 2014) Crystal system, Monoclinic, C2/c
space group Tmin, Tmax 0.415, 0.746 Temperature 100 No. of measured, 26992, 8316, 7095 (K) independent and observed [I > a, b, c (Å) 19.4071 (9), 15.6565 2σ(I)] reflections (7), 19.6251 (9) R 0.031 β (°) 112.078 (1) int −1 3 (sin θ/λ)max (Å ) 0.715
V (Å ) 5525.8 (4)
Z 8
Radiation type Mo Kα
µ (mm−1) 5.35
Crystal size 0.24 × 0.18 × 0.10 (mm)
AI.4c. Refinement AI.4d. Crystal Structure R[F2 > 0.038, 0.084, 1.10 2σ(F2)], wR(F2), S
No. of reflections 8316
No. of parameters 312
H-atom treatment H-atom parameters constrained
2 2 w = 1/[σ (Fo ) + (0.0196P)2 + 51.1794P] 2 where P = (Fo + 2 2Fc )/3
228 Δρmax, Δρmin (e 3.57, −1.02 Å−3)
AI.4e. Bonds (Å) AI.4f. Angles (˚) C1—N1 1.335(6) N1—C1—C2 122.5(5) C1—C2 1.374(7) N1—C1—H1 118.7 C1—H1 0.95 C2—C1—H1 118.7 C2—C3 1.382(8) C1—C2—C3 118.6(5) C2—H2 0.95 C1—C2—H2 120.7 C3—C4 1.384(8) C3—C2—H2 120.7 C3—H3 0.95 C2—C3—C4 119.7(5) C4—C5 1.396(6) C2—C3—H3 120.2 C4—H4 0.95 C4—C3—H3 120.2 C5—N1 1.361(5) C3—C4—C5 119.3(5) C5—C6 1.473(6) C3—C4—H4 120.3 C6—C7 1.391(6) C5—C4—H4 120.3 C6—C11 1.415(6) N1—C5—C4 119.9(4) C7—C8 1.383(8) N1—C5—C6 115.3(4) C7—H7 0.95 C4—C5—C6 124.8(4) C8—C9 1.390(8) C7—C6—C11 120.4(4) C8—H8 0.95 C7—C6—C5 123.3(4) C9—C10 1.392(6) C11—C6—C5 116.4(4) C9—C12 1.511(7) C8—C7—C6 119.8(5) C10—C11 1.393(6) C8—C7—H7 120.1 C10—H10 0.95 C6—C7—H7 120.1 C11—Au1 2.064(4) C7—C8—C9 121.5(5) C12—H12A 0.98 C7—C8—H8 119.3 C12—H12B 0.98 C9—C8—H8 119.3 C12—H12C 0.98 C8—C9—C10 118.1(5) C13—C14 1.390(6) C8—C9—C12 121.2(5) C13—C18 1.398(6) C10—C9—C12 120.6(5) C13—Au1 2.073(4) C9—C10—C11 122.4(4) C14—C15 1.393(6) C9—C10—H10 118.8 C14—H14 0.95 C11—C10—H10 118.8 C15—C16 1.388(6) C10—C11—C6 117.8(4) C15—H15 0.95 C10—C11—Au1 128.4(3) C16—C17 1.374(7) C6—C11—Au1 113.5(3) C16—O1 1.390(5) C9—C12—H12A 109.5 C17—C18 1.396(6) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—H18 0.95 H12B 109.5 C19—O1 1.457(6) C9—C12—H12C 109.5 C19—C21 1.498(7) H12A—C12— 109.5 C19—C20 1.514(7) H12C 116.4(4) C19—H19 1 H12B—C12— 122.3(3)
229 C20—H20A 0.98 H12C 121.3(3) C20—H20B 0.98 C14—C13—C18 122.4(4) C20—H20C 0.98 C14—C13—Au1 118.8 C21—H21A 0.98 C18—C13—Au1 118.8 C21—H21B 0.98 C13—C14—C15 119.4(4) C21—H21C 0.98 C13—C14—H14 120.3 C22—C23 1.382(6) C15—C14—H14 120.3 C22—C27 1.401(6) C16—C15—C14 120.1(4) C22—Au1 1.999(4) C16—C15—H15 118.0(4) C23—C24 1.393(6) C14—C15—H15 121.7(4) C23—H23 0.95 C17—C16—C15 119.5(4) C24—C25 1.377(6) C17—C16—O1 120.3 C24—H24 0.95 C15—C16—O1 120.3 C25—C26 1.378(6) C16—C17—C18 122.3(4) C25—O2 1.385(5) C16—C17—H17 118.9 C26—C27 1.389(6) C18—C17—H17 118.9 C26—H26 0.95 C17—C18—C13 111.3(5) C27—H27 0.95 C17—C18—H18 106.3(4) C28—O2 1.430(5) C13—C18—H18 112.5(5) C28—C30 1.506(7) O1—C19—C21 108.9 C28—C29 1.516(7) O1—C19—C20 108.9 C28—H28 1 C21—C19—C20 108.9 C29—H29A 0.98 O1—C19—H19 109.5 C29—H29B 0.98 C21—C19—H19 109.5 C29—H29C 0.98 C20—C19—H19 109.5 C30—H30A 0.98 C19—C20—H20A 109.5 C30—H30B 0.98 C19—C20—H20B 109.5 C30—H30C 0.98 H20A—C20— 109.5 N1—Au1 2.115(3) H20B 109.5 C19—C20—H20C 109.5 H20A—C20— 109.5 H20C 109.5 H20B—C20— 109.5 H20C 109.5 C19—C21—H21A 117.7(4) C19—C21—H21B 122.0(3) H21A—C21— 120.1(3) H21B 121.5(4) C19—C21—H21C 119.3 H21A—C21— 119.3 H21C 120.1(4) H21B—C21— 119.9 H21C 119.9 C23—C22—C27 119.4(4) C23—C22—Au1 124.0(4) C27—C22—Au1 116.4(4)
230 C22—C23—C24 120.6(4) C22—C23—H23 119.7 C24—C23—H23 119.7 C25—C24—C23 120.7(4) C25—C24—H24 119.7 C23—C24—H24 119.7 C24—C25—C26 109.5(4) C24—C25—O2 106.4(4) C26—C25—O2 112.1(4) C25—C26—C27 109.6 C25—C26—H26 109.6 C27—C26—H26 109.6 C26—C27—C22 109.5 C26—C27—H27 109.5 C22—C27—H27 109.5 O2—C28—C30 109.5 O2—C28—C29 109.5 C30—C28—C29 109.5 O2—C28—H28 109.5 C30—C28—H28 109.5 C29—C28—H28 109.5 C28—C29—H29A 109.5 C28—C29—H29B 109.5 H29A—C29— 109.5 H29B 120.0(4) C28—C29—H29C 125.3(3) H29A—C29— 114.6(3) H29C 116.3(4) H29B—C29— 119.7(3) H29C 94.69(16) C28—C30—H30A 88.24(16) C28—C30—H30B 176.06(16) H30A—C30— 174.24(15) H30B 79.97(15) C28—C30—H30C 97.19(15) H30A—C30— H30C H30B—C30— H30C C1—N1—C5 C1—N1—Au1 C5—N1—Au1 C16—O1—C19 C25—O2—C28 C22—Au1—C11 C22—Au1—C13
231 C11—Au1—C13 C22—Au1—N1 C11—Au1—N1 C13—Au1—N1
232 Table AI.5. X-ray crystallographic data for [(tpy)Au(2-acetylphenylato)]
AI.5a. Crystal data AI.5b. Data collection Crystal data Diffractometer Bruker AXS D8 Quest CMOS Chemical C20H16AuNO·0.62(CH2Cl2) diffractometer formula Absorption Multi-scan Mr 535.71 correction Apex2 v2014.1-1 (Bruker, 2014) Crystal Orthorhombic, Pca21
system, Tmin, Tmax 0.490, 0.747 space group No. of measured, 15815, 5456, 4977 Temperature 100 independent and (K) observed [I > 2σ(I)] reflections a, b, c (Å) 22.3204 (12), 11.4097
(5), 7.0554 (3) Rint 0.029
3 −1 V (Å ) 1796.79 (15) (sin θ/λ)max (Å ) 0.746
Z 4
Radiation Mo Kα type
µ (mm−1) 8.38
Crystal size 0.11 × 0.10 × 0.02 (mm)
233 AI.5c. Refinement AI.5d. Crystal Structure R[F2 > 0.028, 0.066, 1.05 2σ(F2)], wR(F2), S
No. of reflections 5456
No. of parameters 266
No. of restraints 104
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e 1.47, −1.79 Å−3)
Absolute structure Refined as an inversion twin.
Absolute structure 0.224 (16) parameter
AI.5e. Bonds (Å) AI.5f. Angles (˚) C1—N1 1.338(7) N1—C1—C2 122.0(5) C1—C2 1.387(8) N1—C1—H1 119 C1—H1 0.95 C2—C1—H1 119 C2—C3 1.379(8) C3—C2—C1 119.0(6) C2—H2 0.95 C3—C2—H2 120.5 C3—C4 1.403(8) C1—C2—H2 120.5 C3—H3 0.95 C2—C3—C4 118.9(5) C4—C5 1.385(7) C2—C3—H3 120.5 C4—H4 0.95 C4—C3—H3 120.5 C5—N1 1.369(7) C5—C4—C3 120.1(5) C5—C6 1.462(8) C5—C4—H4 119.9 C6—C7 1.397(9) C3—C4—H4 119.9 C6—C11 1.408(8) N1—C5—C4 119.6(5) C7—C8 1.389(11) N1—C5—C6 115.4(5) C7—H7 0.95 C4—C5—C6 125.0(5) C8—C9 1.395(10) C7—C6—C11 120.5(6) C8—H8 0.95 C7—C6—C5 122.8(6) C9—C10 1.396(9) C11—C6—C5 116.7(5) C9—C12 1.513(10) C8—C7—C6 120.0(6) C10—C11 1.397(8) C8—C7—H7 120 C10—H10 0.95 C6—C7—H7 120 C11—Au2 2.058(5) C7—C8—C9 120.8(6) C12—H12A 0.98 C7—C8—H8 119.6
234 C12—H12B 0.98 C9—C8—H8 119.6 C12—H12C 0.98 C8—C9—C10 118.5(6) C13—C14 1.394(10) C8—C9—C12 120.9(7) C13—C18 1.421(10) C10—C9—C12 120.5(7) C13—Au2 2.080(5) C9—C10—C11 122.2(6) C14—C15 1.388(9) C9—C10—H10 118.9 C14—H14 0.95 C11—C10—H10 118.9 C15—C16 1.390(10) C10—C11—C6 117.9(5) C15—H15 0.95 C10—C11—Au2 127.8(4) C16—C17 1.390(11) C6—C11—Au2 114.1(4) C16—H16 0.95 C9—C12—H12A 109.5 C17—C18 1.399(10) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—C19 1.476(9) H12B 109.5 C19—O1 1.228(8) C9—C12—H12C 109.5 C19—C20 1.497(9) H12A—C12— 109.5 C20—Au2 2.041(6) H12C 116.1(5) C20—H20A 0.99 H12B—C12— 131.1(5) C20—H20B 0.99 H12C 112.7(5) C21—Cl2 1.67(2) C14—C13—C18 121.4(7) C21—Cl1 1.67(2) C14—C13—Au2 119.3 C21—H21A 0.99 C18—C13—Au2 119.3 C21—H21B 0.99 C15—C14—C13 121.1(7) C21B—Cl1B 1.665(18) C15—C14—H14 119.5 C21B—Cl2B 1.68(2) C13—C14—H14 119.5 C21B—H21C 0.99 C14—C15—C16 120.0(6) C21B—H21D 0.99 C14—C15—H15 120 Au2—N1 2.134(4) C16—C15—H15 120 C15—C16—C17 118.0(7) C15—C16—H16 121 C17—C16—H16 121 C16—C17—C18 123.2(6) C16—C17—H17 121.9(6) C18—C17—H17 114.8(5) C17—C18—C13 124.5(6) C17—C18—C19 122.3(6) C13—C18—C19 113.1(5) O1—C19—C18 110.3(4) O1—C19—C20 109.6 C18—C19—C20 109.6 C19—C20—Au2 109.6 C19—C20—H20A 109.6 Au2—C20—H20A 108.1 C19—C20—H20B 119(2) Au2—C20—H20B 107.5 H20A—C20— 107.5
235 H20B 107.5 Cl2—C21—Cl1 107.5 Cl2—C21—H21A 107 Cl1—C21—H21A 116.1(17) Cl2—C21—H21B 108.3 Cl1—C21—H21B 108.3 H21A—C21— 108.3 H21B 108.3 Cl1B—C21B— 107.4 Cl2B 96.2(2) Cl1B—C21B— 80.8(2) H21C 175.1(4) Cl2B—C21B— 173.1(4) H21C 79.62(18) Cl1B—C21B— 103.67(16) H21D 120.3(5) Cl2B—C21B— 125.7(4) H21D 113.9(3) H21C—C21B— H21D C20—Au2—C11 C20—Au2—C13 C11—Au2—C13 C20—Au2—N1 C11—Au2—N1 C13—Au2—N1 C1—N1—C5 C1—N1—Au2 C5—N1—Au2
236 Table AI.6. X-ray crystallographic data for [(tpy)Au(4-(trifluoromethyl)phenyl)2]
AI.6a. Crystal data AI.6b. Data collection
Chemical C26H18AuF6N·CH2Cl2 Diffractometer Bruker AXS D8 formula Quest CMOS diffractometer Mr 740.31 Absorption Multi-scan Crystal Triclinic, P1 correction Apex2 v2014.1-1 system, space (Bruker, 2014) group Tmin, Tmax 0.366, 0.746 Temperature 100 (K) No. of measured, 20316, 20316, 18797 independent and a, b, c (Å) 9.3340 (11), 11.4331 observed [I > (13), 12.8416 (17) 2σ(I)] reflections
α, β, γ (°) 73.407 (4), 81.938 Rint 0.078 (4), 73.869 (3) (sin θ/λ) (Å−1) 0.725 3 max V (Å ) 1258.9 (3)
Z 2
Radiation Mo Kα type
µ (mm−1) 6.12
Crystal size 0.21 × 0.18 × 0.03 (mm)
237 AI.6c. Refinement AI.6d. Crystal Structure R[F2 > 0.067, 0.175, 1. 2σ(F2)], wR(F2), 08 S
No. of 20316 reflections
No. of 336 parameters
H-atom H-atom treatment parameters constrained
2 2 w = 1/[σ (Fo ) + 38.3672P] where P = 2 2 (Fo + 2Fc )/3
Δρmax, Δρmin (e 9.46, −4.27 Å−3)
AI.6e. Bonds (Å) AI.6f. Angles (˚) C1—N1 1.354(13) N1—C1—C2 121.4(12) C1—C2 1.374(16) N1—C1—H1 119.3 C1—H1 0.95 C2—C1—H1 119.3 C2—C3 1.42(2) C1—C2—C3 119.9(11) C2—H2 0.95 C1—C2—H2 120.1 C3—C4 1.384(18) C3—C2—H2 120.1 C3—H3 0.95 C4—C3—C2 118.4(12) C4—C5 1.409(15) C4—C3—H3 120.8 C4—H4 0.95 C2—C3—H3 120.8 C5—N1 1.350(14) C3—C4—C5 119.0(13) C5—C6 1.486(14) C3—C4—H4 120.5 C6—C7 1.402(15) C5—C4—H4 120.5 C6—C11 1.415(14) N1—C5—C4 121.4(10) C7—C8 1.378(16) N1—C5—C6 114.8(9) C7—H7 0.95 C4—C5—C6 123.7(10) C8—C9 1.379(17) C7—C6—C11 120.6(9) C8—H8 0.95 C7—C6—C5 123.3(10) C9—C10 1.395(15) C11—C6—C5 116.0(9) C9—C12 1.520(14) C8—C7—C6 120.4(11) C10—C11 1.406(13) C8—C7—H7 119.8 C10—H10 0.95 C6—C7—H7 119.8 C11—Au1 2.053(10) C7—C8—C9 120.7(11) C12—H12A 0.98 C7—C8—H8 119.6
238 C12—H12B 0.98 C9—C8—H8 119.6 C12—H12C 0.98 C8—C9—C10 119.0(10) C13—C18 1.383(13) C8—C9—C12 120.1(10) C13—C14 1.403(14) C10—C9—C12 120.8(10) C13—Au1 2.071(10) C9—C10—C11 122.5(10) C14—C15 1.388(16) C9—C10—H10 118.7 C14—H14 0.95 C11—C10—H10 118.7 C15—C16 1.385(15) C10—C11—C6 116.7(10) C15—H15 0.95 C10—C11—Au1 129.3(8) C16—C17 1.380(15) C6—C11—Au1 114.0(7) C16—C19 1.507(16) C9—C12—H12A 109.5 C17—C18 1.406(15) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—H18 0.95 H12B 109.5 C19—F1 1.331(14) C9—C12—H12C 109.5 C19—F3 1.335(15) H12A—C12— 109.5 C19—F2 1.341(15) H12C 117.2(9) C20—C25 1.416(13) H12B—C12— 120.8(8) C20—C21 1.436(13) H12C 121.8(7) C20—Au1 1.976(9) C18—C13—C14 122.3(10) C21—C22 1.373(16) C18—C13—Au1 118.9 C21—H21 0.95 C14—C13—Au1 118.9 C22—C23 1.391(16) C15—C14—C13 118.9(10) C22—H22 0.95 C15—C14—H14 120.5 C23—C24 1.375(16) C13—C14—H14 120.5 C23—C26 1.501(16) C16—C15—C14 120.6(10) C24—C25 1.377(15) C16—C15—H15 119.1(10) C24—H24 0.95 C14—C15—H15 120.3(10) C25—H25 0.95 C17—C16—C15 119.5(10) C26—F4 1.333(15) C17—C16—C19 120.2 C26—F5 1.337(15) C15—C16—C19 120.2 C26—F6 1.348(16) C16—C17—C18 121.4(10) C27—Cl2 1.739(18) C16—C17—H17 119.3 C27—Cl1 1.770(16) C18—C17—H17 119.3 C27—H27A 0.99 C13—C18—C17 105.6(10) C27—H27B 0.99 C13—C18—H18 104.7(11) Au1—N1 2.112(9) C17—C18—H18 107.1(11) F1—C19—F3 112.8(11) F1—C19—F2 113.5(10) F3—C19—F2 112.4(10) F1—C19—C16 116.0(9) F3—C19—C16 123.7(7) F2—C19—C16 120.3(7) C25—C20—C21 120.6(10) C25—C20—Au1 119.7 C21—C20—Au1 119.7
239 C22—C21—C20 121.2(11) C22—C21—H21 119.4 C20—C21—H21 119.4 C21—C22—C23 119.6(11) C21—C22—H22 121.7(11) C23—C22—H22 118.7(11) C24—C23—C22 120.3(10) C24—C23—C26 119.8 C22—C23—C26 119.8 C23—C24—C25 122.2(10) C23—C24—H24 118.9 C25—C24—H24 118.9 C24—C25—C20 106.4(10) C24—C25—H25 105.2(11) C20—C25—H25 106.0(12) F4—C26—F5 113.8(11) F4—C26—F6 112.4(10) F5—C26—F6 112.3(10) F4—C26—C23 113.1(9) F5—C26—C23 109 F6—C26—C23 109 Cl2—C27—Cl1 109 Cl2—C27—H27A 109 Cl1—C27—H27A 107.8 Cl2—C27—H27B 95.8(4) Cl1—C27—H27B 86.3(4) H27A—C27— 177.9(4) H27B 175.6(3) C20—Au1—C11 79.9(4) C20—Au1—C13 98.1(3) C11—Au1—C13 119.9(10) C20—Au1—N1 115.3(7) C11—Au1—N1 124.9(8) C13—Au1—N1 C5—N1—C1 C5—N1—Au1 C1—N1—Au1
240 Table AI.7. X-ray crystallographic data for [(tpy)Au(3-nitrophenyl)2]
AI.7a. Crystal data AI.7b. Data collection
Chemical C24H18AuN3O4 Diffractometer Bruker AXS D8 formula Quest CMOS diffractometer Mr 609.38 Absorption Multi-scan Crystal Orthorhombic, Pbcn correction Apex2 v2014.1-1 system, space (Bruker, 2014) group Tmin, Tmax 0.587, 0.746 Temperature 100 (K) No. of measured, 23940, 5103, 4447 independent and a, b, c (Å) 11.1263 (3), 14.1527 observed [I > (4), 26.2319 (7) 2σ(I)] reflections 3 V (Å ) 4130.7 (2) Rint 0.031
−1 Z 8 (sin θ/λ)max (Å ) 0.667
Radiation type Mo Kα
µ (mm−1) 7.16
Crystal size 0.16 × 0.16 × 0.12 (mm)
AI.7c. Refinement AI.7d. Crystal Structure R[F2 > 0.030, 0.060, 1.0 2σ(F2)], wR(F2), 7 S
No. of reflections 5103
No. of parameters 290
H-atom treatment H-atom parameters constrained
2 2 w = 1/[σ (Fo ) + (0.0059P)2 + 28.2499P] 2 where P = (Fo + 2 2Fc )/3
241 Δρmax, Δρmin (e 3.26, −1.35 Å−3)
AI.7e. Bonds (Å) AI.7f. Angles (˚) C1—N1 1.332(6) N1—C1—C2 123.0(4) C1—C2 1.384(6) N1—C1—H1 118.5 C1—H1 0.95 C2—C1—H1 118.5 C2—C3 1.375(6) C3—C2—C1 118.2(4) C2—H2 0.95 C3—C2—H2 120.9 C3—C4 1.374(7) C1—C2—H2 120.9 C3—H3 0.95 C4—C3—C2 119.6(4) C4—C5 1.400(6) C4—C3—H3 120.2 C4—H4 0.95 C2—C3—H3 120.2 C5—N1 1.366(5) C3—C4—C5 120.5(4) C5—C6 1.460(6) C3—C4—H4 119.7 C6—C7 1.403(6) C5—C4—H4 119.7 C6—C11 1.411(5) N1—C5—C4 118.9(4) C7—C8 1.381(7) N1—C5—C6 114.9(3) C7—H7 0.95 C4—C5—C6 126.2(4) C8—C9 1.391(6) C7—C6—C11 119.8(4) C8—H8 0.95 C7—C6—C5 122.5(4) C9—C10 1.396(6) C11—C6—C5 117.7(4) C9—C12 1.499(6) C8—C7—C6 119.7(4) C10—C11 1.387(6) C8—C7—H7 120.1 C10—H10 0.95 C6—C7—H7 120.1 C11—Au1 2.056(4) C7—C8—C9 121.4(4) C12—H12A 0.98 C7—C8—H8 119.3 C12—H12B 0.98 C9—C8—H8 119.3 C12—H12C 0.98 C8—C9—C10 118.4(4) C13—C18 1.381(6) C8—C9—C12 121.6(4) C13—C14 1.384(6) C10—C9—C12 120.0(4) C13—Au1 2.024(4) C11—C10—C9 121.8(4) C14—C15 1.400(7) C11—C10—H10 119.1 C14—H14 0.95 C9—C10—H10 119.1 C15—C16 1.383(7) C10—C11—C6 118.8(4) C15—H15 0.95 C10—C11—Au1 128.5(3) C16—C17 1.380(6) C6—C11—Au1 112.6(3) C16—H16 0.95 C9—C12—H12A 109.5 C17—C18 1.390(6) C9—C12—H12B 109.5 C17—N2 1.475(6) H12A—C12— 109.5 C18—H18 0.95 H12B 109.5 C19—C24 1.386(6) C9—C12—H12C 109.5 C19—C20 1.406(6) H12A—C12— 109.5 C19—Au1 2.076(4) H12C 119.3(4) C20—C21 1.391(7) H12B—C12— 119.6(3)
242 C20—H20 0.95 H12C 120.8(3) C21—C22 1.383(7) C18—C13—C14 121.0(4) C21—H21 0.95 C18—C13—Au1 119.5 C22—C23 1.384(6) C14—C13—Au1 119.5 C22—H22 0.95 C13—C14—C15 120.0(4) C23—C24 1.388(6) C13—C14—H14 120 C23—N3 1.474(6) C15—C14—H14 120 C24—H24 0.95 C16—C15—C14 118.0(4) N1—Au1 2.112(3) C16—C15—H15 121 N2—O2 1.226(5) C14—C15—H15 121 N2—O1 1.237(5) C17—C16—C15 122.7(4) N3—O4 1.221(6) C17—C16—H16 118.7(4) N3—O3 1.228(5) C15—C16—H16 118.6(4) C16—C17—C18 119.0(4) C16—C17—N2 120.5 C18—C17—N2 120.5 C13—C18—C17 117.2(4) C13—C18—H18 120.6(3) C17—C18—H18 122.2(3) C24—C19—C20 121.8(4) C24—C19—Au1 119.1 C20—C19—Au1 119.1 C21—C20—C19 120.5(4) C21—C20—H20 119.8 C19—C20—H20 119.8 C22—C21—C20 117.5(4) C22—C21—H21 121.2 C20—C21—H21 121.2 C21—C22—C23 122.7(4) C21—C22—H22 119.4(4) C23—C22—H22 117.9(4) C22—C23—C24 120.3(4) C22—C23—N3 119.9 C24—C23—N3 119.9 C19—C24—C23 119.8(4) C19—C24—H24 126.1(3) C23—C24—H24 114.0(3) C1—N1—C5 123.4(4) C1—N1—Au1 118.5(4) C5—N1—Au1 118.1(4) O2—N2—O1 122.9(5) O2—N2—C17 118.5(4) O1—N2—C17 118.6(4) O4—N3—O3 92.87(15) O4—N3—C23 89.38(15) O3—N3—C23 177.22(15)
243 C13—Au1—C11 173.22(14) C13—Au1—C19 80.41(15) C11—Au1—C19 97.32(14) C13—Au1—N1 C11—Au1—N1 C19—Au1—N1
244 Table AI.8. X-ray crystallographic data for [(tpy)Au(benzo[b]thien-2-yl)2]
AI.8a. Crystal data AI.8b. Data collection
Chemical C28H20AuNS2 Diffractometer Bruker AXS D8 formula Quest CMOS diffractometer Mr 631.54 Absorption Multi-scan Crystal system, Tetragonal, I41/a correction Apex2 v2014.1-1 space group (Bruker, 2014)
Temperature (K) 100 Tmin, Tmax 0.398, 0.751 a, c (Å) 35.5669 (9), 7.2973 No. of measured, 83233, 7052, 6761 (2) independent and observed [I > V (Å3) 9231.1 (5) 2σ(I)] reflections Z 16 Rint 0.039
Radiation type Mo Kα −1 (sin θ/λ)max (Å ) 0.714 µ (mm−1) 6.57
Crystal size (mm) 0.25 × 0.19 × 0.17
AI.8c. Refinement AI.8d. Crystal Structure R[F2 > 0.033, 0.065, 1.40 2σ(F2)], wR(F2), S
No. of reflections 7052
No. of parameters 699
No. of restraints 881
H-atom treatment H-atom parameters constrained
2 2 w = 1/[σ (Fo ) + 59.5458P] 2 where P = (Fo + 2 2Fc )/3
Δρmax, Δρmin (e 1.00, −0.99 Å−3)
245 AI.8e. Bonds (Å) AI.8f. Angles (˚) N1—C1 1.349(5) C1—N1—C5 120.3(3) N1—C5 1.361(5) C1—N1—Au1 125.5(3) N1—Au1 2.089(3) C5—N1—Au1 114.2(3) C1—C2 1.376(6) N1—C1—C2 121.9(4) C1—H1 0.95 N1—C1—H1 119 C2—C3 1.377(6) C2—C1—H1 119 C2—H2 0.95 C1—C2—C3 118.8(4) C3—C4 1.389(6) C1—C2—H2 120.6 C3—H3 0.95 C3—C2—H2 120.6 C4—C5 1.390(5) C2—C3—C4 119.5(4) C4—H4 0.95 C2—C3—H3 120.3 C5—C6 1.467(5) C4—C3—H3 120.3 C6—C11 1.405(5) C3—C4—C5 120.0(4) C6—C7 1.405(5) C3—C4—H4 120 C7—C8 1.395(6) C5—C4—H4 120 C7—H7 0.95 N1—C5—C4 119.5(4) C8—C9 1.384(6) N1—C5—C6 115.2(3) C8—H8 0.95 C4—C5—C6 125.3(4) C9—C10 1.405(5) C11—C6—C7 119.7(3) C9—C12 1.502(6) C11—C6—C5 117.2(3) C10—C11 1.393(5) C7—C6—C5 123.1(3) C10—H10 0.95 C8—C7—C6 119.9(4) C11—Au1 2.057(4) C8—C7—H7 120 C12—H12A 0.98 C6—C7—H7 120 C12—H12B 0.98 C9—C8—C7 121.2(4) C12—H12C 0.98 C9—C8—H8 119.4 Au1—C21 1.992(4) C7—C8—H8 119.4 Au1—C13 2.073(4) C8—C9—C10 118.5(4) C13—C14 1.399(14) C8—C9—C12 120.8(4) C13—S1 1.683(6) C10—C9—C12 120.6(4) S1—C15 1.758(12) C11—C10—C9 121.6(4) C14—C20 1.435(16) C11—C10—H10 119.2 C14—H14 0.95 C9—C10—H10 119.2 C15—C20 1.410(12) C10—C11—C6 119.0(3) C15—C16 1.423(13) C10—C11—Au1 128.3(3) C16—C17 1.367(13) C6—C11—Au1 112.5(3) C16—H16 0.95 C9—C12—H12A 109.5 C17—C18 1.385(14) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—C19 1.369(11) H12B 109.5 C18—H18 0.95 C9—C12—H12C 109.5 C19—C20 1.400(13) H12A—C12— 109.5 C19—H19 0.95 H12C 80.84(14) C21—C22 1.373(11) H12B—C12— 112.3(7) C21—S2 1.717(4) H12C 91.7(6)
246 S2—C23 1.757(8) C11—Au1—N1 114.4(12) C22—C28 1.441(12) C14—C13—S1 122.8 C22—H22 0.95 C13—S1—C15 122.8 C23—C24 1.404(8) C13—C14—C20 119.9(11) C23—C28 1.406(8) C13—C14—H14 112.6(10) C24—C25 1.369(11) C20—C14—H14 127.3(10) C24—H24 0.95 C20—C15—C16 118.9(11) C25—C26 1.401(11) C20—C15—S1 120.5 C25—H25 0.95 C16—C15—S1 120.5 C26—C27 1.383(8) C17—C16—C15 120.7(10) C26—H26 0.95 C17—C16—H16 119.7 C27—C28 1.403(8) C15—C16—H16 119.7 C27—H27 0.95 C16—C17—C18 121.6(10) S1B—C15B 1.746(12) C16—C17—H17 119.2 C14B—C20B 1.446(17) C18—C17—H17 119.2 C14B—H14B 0.95 C19—C18—C17 119.7(11) C15B—C20B 1.413(12) C19—C18—H18 120.2 C15B—C16B 1.416(13) C17—C18—H18 120.2 C16B—C17B 1.372(12) C18—C19—C20 119.0(11) C16B—H16B 0.95 C18—C19—H19 132.0(12) C17B—C18B 1.390(13) C20—C19—H19 108.8(12) C17B—H17B 0.95 C19—C20—C15 111.2(5) C18B—C19B 1.375(12) C19—C20—C14 92.5(3) C18B—H18B 0.95 C15—C20—C14 114.9(9) C19B—C20B 1.411(13) C22—C21—S2 122.6 C19B—H19B 0.95 C21—S2—C23 122.6 Au1C—C13C 2.02(3) C21—C22—C28 120.7(7) Au1C—C21C 2.06(3) C21—C22—H22 128.1(6) Au1C—C11C 2.066(18) C28—C22—H22 111.1(5) Au1C—N1C 2.090(18) C24—C23—C28 119.3(7) C13C—C14C 1.398(18) C24—C23—S2 120.3 C13C—S1C 1.690(16) C28—C23—S2 120.3 S1C—C15C 1.744(17) C25—C24—C23 120.7(6) C14C—C20C 1.440(19) C25—C24—H24 119.7 C14C—H14C 0.95 C23—C24—H24 119.7 C15C—C16C 1.412(17) C24—C25—C26 120.5(7) C15C—C20C 1.415(16) C24—C25—H25 119.7 C16C—C17C 1.366(17) C26—C25—H25 119.7 C16C—H16C 0.95 C27—C26—C25 119.8(7) C17C—C18C 1.393(18) C27—C26—H26 120.1 C17C—H17C 0.95 C25—C26—H26 120.1 C18C—C19C 1.373(17) C26—C27—C28 118.9(6) C18C—H18C 0.95 C26—C27—H27 130.7(7) C19C—C20C 1.401(17) C28—C27—H27 110.3(7) C19C—H19C 0.95 C27—C28—C23 122.4 C21C—C22C 1.393(18) C27—C28—C22 120.5(11)
247 C21C—S2C 1.691(16) C23—C28—C22 112.2(10) S2C—C23C 1.743(16) C20B—C14B— 127.0(10) C22C—C28C 1.435(19) H14B 118.9(10) C22C—H22C 0.95 C20B—C15B— 120.6 C23C—C24C 1.411(17) C16B 120.6 C23C—C28C 1.422(16) C20B—C15B— 120.2(10) C24C—C25C 1.368(17) S1B 119.9 C24C—H24C 0.95 C16B—C15B— 119.9 C25C—C26C 1.393(18) S1B 122.5(10) C25C—H25C 0.95 C17B—C16B— 118.7 C26C—C27C 1.371(17) C15B 118.7 C26C—H26C 0.95 C17B—C16B— 118.6(11) C27C—C28C 1.400(17) H16B 120.7 C27C—H27C 0.95 C15B—C16B— 120.7 N1C—C1C 1.348(19) H16B 119.0(11) N1C—C5C 1.353(18) C16B—C17B— 132.1(13) C1C—C2C 1.38(2) C18B 108.5(12) C1C—H1C 0.95 C16B—C17B— 91(2) C2C—C3C 1.37(2) H17B 90.4(19) C2C—H2C 0.95 C18B—C17B— 173.2(16) C3C—C4C 1.39(2) H17B 170.4(19) C3C—H3C 0.95 C19B—C18B— 98.4(18) C4C—C5C 1.398(19) C17B 80.1(10) C4C—H4C 0.95 C19B—C18B— 110.7(15) C5C—C6C 1.466(18) H18B 123(2) C6C—C7C 1.401(18) C17B—C18B— 125.2(19) C6C—C11C 1.417(18) H18B 93.1(11) C7C—C8C 1.40(2) C18B—C19B— 114.8(18) C7C—H7C 0.95 C20B 122.6 C8C—C9C 1.377(19) C18B—C19B— 122.6 C8C—H8C 0.95 H19B 121.0(18) C9C—C10C 1.401(19) C20B—C19B— 127.0(19) C9C—C12C 1.495(19) H19B 111.7(15) C10C—C11C 1.385(19) C19B—C20B— 119(2) C10C—H10C 0.95 C15B 120.3 C12C—H12D 0.98 C19B—C20B— 120.3 C12C—H12E 0.98 C14B 120(2) C12C—H12F 0.98 C15B—C20B— 120.2 S2B—C23B 1.754(16) C14B 120.2 C22B—C28B 1.440(18) C13C—Au1C— 122(2) C22B—H22A 0.95 C21C 119.1 C23B—C24B 1.414(16) C13C—Au1C— 119.1 C23B—C28B 1.414(15) C11C 120(2) C24B—C25B 1.368(17) C21C—Au1C— 120 C24B—H24B 0.95 C11C 120 C25B—C26B 1.398(18) C13C—Au1C— 117.7(18)
248 C25B—H25B 0.95 N1C 133(2) C26B—C27B 1.376(16) C21C—Au1C— 108.9(17) C26B—H26B 0.95 N1C 111.1(15) C27B—C28B 1.405(16) C11C—Au1C— 123.3(16) C27B—H27B 0.95 N1C 125.4(15) C14C—C13C— 92.6(11) S1C 114.6(18) C14C—C13C— 122.7 Au1C 122.7 S1C—C13C— 118.6(18) Au1C 129.0(17) C13C—S1C— 111.7(14) C15C 120(2) C13C—C14C— 119.8 C20C 119.8 C13C—C14C— 118(2) H14C 120.8 C20C—C14C— 120.8 H14C 121(2) C16C—C15C— 119.5 C20C 119.5 C16C—C15C— 120(2) S1C 120 C20C—C15C— 120 S1C 117.8(18) C17C—C16C— 132(2) C15C 109.1(16) C17C—C16C— 123(2) H16C 122(2) C15C—C16C— 114.7(16) H16C 120(2) C16C—C17C— 120.1 C18C 120.1 C16C—C17C— 119(2) H17C 120.7 C18C—C17C— 120.7 H17C 122(2) C19C—C18C— 119.1 C17C 119.1 C19C—C18C— 118(2) H18C 121.2 C17C—C18C— 121.2 H18C 119.0(19) C18C—C19C— 116.1(19) C20C 125(2) C18C—C19C— 120.1(18)
249 H19C 124(2) C20C—C19C— 115.5(18) H19C 120(2) C19C—C20C— 119.9 C15C 119.9 C19C—C20C— 120(2) C14C 120.1 C15C—C20C— 120.1 C14C 119(2) C22C—C21C— 121(2) S2C 120(2) C22C—C21C— 122(2) Au1C 118.8 S2C—C21C— 118.8 Au1C 117.4(18) C21C—S2C— 129.1(19) C23C 113.4(15) C21C—C22C— 109.5 C28C 109.5 C21C—C22C— 109.5 H22C 109.5 C28C—C22C— 109.5 H22C 109.5 C24C—C23C— 123.7 C28C 122.5(15) C24C—C23C— 125.1(15) S2C 112.2(13) C28C—C23C— 118.4(18) S2C 120.8 C25C—C24C— 120.8 C23C 117.5(18) C25C—C24C— 121.2 H24C 121.2 C23C—C24C— 122.8(19) H24C 118.6 C24C—C25C— 118.6 C26C 118.7(18) C24C—C25C— 120.7 H25C 120.7 C26C—C25C— 116.8(15) H25C 134.4(17) C27C—C26C— 108.8(15) C25C C27C—C26C— H26C C25C—C26C—
250 H26C C26C—C27C— C28C C26C—C27C— H27C C28C—C27C— H27C C27C—C28C— C23C C27C—C28C— C22C C23C—C28C— C22C C1C—N1C—C5C C1C—N1C—Au1C C5C—N1C—Au1C N1C—C1C—C2C N1C—C1C—H1C C2C—C1C—H1C C3C—C2C—C1C C3C—C2C—H2C C1C—C2C—H2C C2C—C3C—C4C C2C—C3C—H3C C4C—C3C—H3C C3C—C4C—C5C C3C—C4C—H4C C5C—C4C—H4C N1C—C5C—C4C N1C—C5C—C6C C4C—C5C—C6C C7C—C6C—C11C C7C—C6C—C5C C11C—C6C—C5C C8C—C7C—C6C C8C—C7C—H7C C6C—C7C—H7C C9C—C8C—C7C C9C—C8C—H8C C7C—C8C—H8C C8C—C9C—C10C C8C—C9C—C12C C10C—C9C— C12C C11C—C10C— C9C
251 C11C—C10C— H10C C9C—C10C— H10C C10C—C11C— C6C C10C—C11C— Au1C C6C—C11C— Au1C C9C—C12C— H12D C9C—C12C— H12E H12D—C12C— H12E C9C—C12C— H12F H12D—C12C— H12F H12E—C12C— H12F C28B—C22B— H22A C24B—C23B— C28B C24B—C23B— S2B C28B—C23B— S2B C25B—C24B— C23B C25B—C24B— H24B C23B—C24B— H24B C24B—C25B— C26B C24B—C25B— H25B C26B—C25B— H25B C27B—C26B— C25B C27B—C26B— H26B
252 C25B—C26B— H26B C26B—C27B— C28B C26B—C27B— H27B C28B—C27B— H27B C27B—C28B— C23B C27B—C28B— C22B C23B—C28B— C22B
253 Table AI.9. X-ray crystallographic data for [(tpy)Au(o-tolyl)2]
AI.9a. Crystal data AI.9b. Data collection Crystal data Diffractometer Bruker AXS D8 Quest CMOS Chemical C26H24AuN diffractometer formula Absorption Multi-scan Mr 547.43 correction Apex2 v2014.1-1 (Bruker, 2014) Crystal Monoclinic, P21/n
system, space Tmin, Tmax 0.420, 0.746 group No. of measured, 16310, 16310, 13718 Temperature 100 independent and (K) observed [I > 2σ(I)] reflections a, b, c (Å) 7.5722 (7), 16.2301
(14), 16.7076 (18) Rint ?
−1 β (°) 93.349 (4) (sin θ/λ)max (Å ) 0.739
V (Å3) 2049.8 (3)
Z 4
Radiation type Mo Kα
µ (mm−1) 7.19
Crystal size 0.20 × 0.05 × 0.04 (mm)
254 AI.9c. Refinement AI.9d. Crystal Structure R[F2 > 0.069, 0.175, 1.0 2σ(F2)], wR(F2), 9 S
No. of reflections 16310
No. of parameters 257
H-atom treatment H-atom parameters constrained
2 2 w = 1/[σ (Fo ) + 90.5211P] 2 where P = (Fo + 2 2Fc )/3
Δρmax, Δρmin (e 4.58, −4.13 −3 Å )
AI.9e. Bonds (Å) AI.9f. Angles (˚) C1—N1 1.339(15) N1—C1—C2 122.1(11) C1—C2 1.405(19) N1—C1—H1 119 C1—H1 0.95 C2—C1—H1 119 C2—C3 1.383(19) C3—C2—C1 118.2(12) C2—H2 0.95 C3—C2—H2 120.9 C3—C4 1.368(18) C1—C2—H2 120.9 C3—H3 0.95 C4—C3—C2 119.9(13) C4—C5 1.413(17) C4—C3—H3 120.1 C4—H4 0.95 C2—C3—H3 120.1 C5—N1 1.362(14) C3—C4—C5 120.3(12) C5—C6 1.454(17) C3—C4—H4 119.9 C6—C7 1.410(15) C5—C4—H4 119.9 C6—C11 1.411(17) N1—C5—C4 119.4(11) C7—C8 1.380(18) N1—C5—C6 115.0(10) C7—H7 0.95 C4—C5—C6 125.6(10) C8—C9 1.386(19) C7—C6—C11 118.6(11) C8—H8 0.95 C7—C6—C5 123.2(11) C9—C10 1.396(17) C11—C6—C5 118.2(10) C9—C12 1.501(18) C8—C7—C6 120.4(12) C10—C11 1.374(16) C8—C7—H7 119.8 C10—H10 0.95 C6—C7—H7 119.8 C11—Au1 2.078(10) C7—C8—C9 121.0(11) C12—H12A 0.98 C7—C8—H8 119.5 C12—H12B 0.98 C9—C8—H8 119.5 C12—H12C 0.98 C8—C9—C10 118.5(12)
255 C13—C18 1.400(19) C8—C9—C12 122.0(12) C13—C14 1.405(17) C10—C9—C12 119.5(13) C13—Au1 2.083(10) C11—C10—C9 121.9(12) C14—C15 1.387(17) C11—C10—H10 119.1 C14—H14 0.95 C9—C10—H10 119.1 C15—C16 1.39(2) C10—C11—C6 119.5(10) C15—H15 0.95 C10—C11—Au1 128.5(9) C16—C17 1.360(19) C6—C11—Au1 112.0(8) C16—H16 0.95 C9—C12—H12A 109.5 C17—C18 1.407(17) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—C19 1.503(19) H12B 109.5 C19—H19A 0.98 C9—C12—H12C 109.5 C19—H19B 0.98 H12A—C12— 109.5 C19—H19C 0.98 H12C 117.8(10) C20—C21 1.37(2) H12B—C12— 121.2(9) C20—C25 1.404(18) H12C 120.7(9) C20—Au1 2.048(12) C18—C13—C14 122.1(12) C21—C22 1.41(2) C18—C13—Au1 119 C21—H21 0.95 C14—C13—Au1 119 C22—C23 1.39(2) C15—C14—C13 119.3(13) C22—H22 0.95 C15—C14—H14 120.4 C23—C24 1.39(2) C13—C14—H14 120.4 C23—H23 0.95 C14—C15—C16 119.6(12) C24—C25 1.42(2) C14—C15—H15 120.2 C24—H24 0.95 C16—C15—H15 120.2 C25—C26 1.46(2) C17—C16—C15 122.1(13) C26—H26A 0.98 C17—C16—H16 119 C26—H26B 0.98 C15—C16—H16 119 C26—H26C 0.98 C16—C17—C18 119.3(12) N1—Au1 2.112(9) C16—C17—H17 121.2(11) C18—C17—H17 119.5(12) C13—C18—C17 109.5 C13—C18—C19 109.5 C17—C18—C19 109.5 C18—C19—H19A 109.5 C18—C19—H19B 109.5 H19A—C19— 109.5 H19B 120.6(12) C18—C19—H19C 120.1(10) H19A—C19— 119.2(11) H19C 121.1(14) H19B—C19— 119.5 H19C 119.5 C21—C20—C25 120.3(15) C21—C20—Au1 119.8
256 C25—C20—Au1 119.8 C20—C21—C22 117.8(14) C20—C21—H21 121.1 C22—C21—H21 121.1 C23—C22—C21 122.7(14) C23—C22—H22 118.7 C21—C22—H22 118.7 C24—C23—C22 117.3(13) C24—C23—H23 123.7(13) C22—C23—H23 118.9(13) C23—C24—C25 109.5 C23—C24—H24 109.5 C25—C24—H24 109.5 C20—C25—C24 109.5 C20—C25—C26 109.5 C24—C25—C26 109.5 C25—C26—H26A 120.1(10) C25—C26—H26B 125.3(8) H26A—C26— 114.5(8) H26B 93.3(5) C25—C26—H26C 91.3(5) H26A—C26— 175.2(5) H26C 173.3(4) H26B—C26— 80.1(4) H26C 95.2(5) C1—N1—C5 C1—N1—Au1 C5—N1—Au1 C20—Au1—C11 C20—Au1—C13 C11—Au1—C13 C20—Au1—N1 C11—Au1—N1 C13—Au1—N1
257 Table AI.10. X-ray crystallographic data for [(tpy)Au(p-C6H5F)2]
AI.10a. Crystal data AI.10b. Data collection Crystal data Diffractometer Bruker AXS SMART APEX CCD Chemical C24H18AuF2N diffractometer formula Absorption Multi-scan Mr 555.36 correction Apex2 v2013.4-1 (Bruker, 2013) Crystal Triclinic, P1
system, space Tmin, Tmax 0.487, 0.746 group No. of 69608, 15989, 13562 Temperature 100 measured, (K) independent and observed [I > a, b, c (Å) 14.8527 2σ(I)] (13), 16.3867 reflections (14), 17.6200 (15) R 0.043 α, β, γ (°) 90.156 (1), 91.414 int −1 (1), 114.256 (1) (sin θ/λ)max (Å ) 0.625
V (Å3) 3908.3 (6)
Z 8
Radiation Mo Kα type
µ (mm−1) 7.56
Crystal size 0.15 × 0.09 × 0.06 (mm)
258 AI.10c. Refinement AI.10d. Crystal Structure R[F2 > 0.031, 0.079, 1. 2σ(F2)], wR(F2) 03 , S
No. of 15989 reflections
No. of 1014 parameters
H-atom H-atom treatment parameters constrained
2 2 w = 1/[σ (Fo ) + (0.0398P)2 + 11.0694P] where P = 2 2 (Fo + 2Fc )/3
Δρmax, Δρmin (e 5.08, −1.54 Å−3)
AI.10e. Bonds (Å) AI.10f. Angles (˚) C1—N1 1.328(7) N1—C1—C2 122.1(5) C1—C2 1.392(8) N1—C1—H1 119 C1—H1 0.95 C2—C1—H1 119 C2—C3 1.373(9) C3—C2—C1 118.2(6) C2—H2 0.95 C3—C2—H2 120.9 C3—C4 1.383(8) C1—C2—H2 120.9 C3—H3 0.95 C2—C3—C4 120.0(5) C4—C5 1.400(8) C2—C3—H3 120 C4—H4 0.95 C4—C3—H3 120 C5—N1 1.353(7) C3—C4—C5 119.6(6) C5—C6 1.461(8) C3—C4—H4 120.2 C6—C7 1.400(8) C5—C4—H4 120.2 C6—C11 1.416(7) N1—C5—C4 119.4(5) C7—C8 1.380(8) N1—C5—C6 115.7(5) C7—H7 0.95 C4—C5—C6 124.9(5) C8—C9 1.396(8) C7—C6—C11 119.7(5) C8—H8 0.95 C7—C6—C5 122.8(5) C9—C10 1.399(8) C11—C6—C5 117.4(5) C9—C12 1.503(9) C8—C7—C6 120.6(5) C10—C11 1.385(8) C8—C7—H7 119.7 C10—H10 0.95 C6—C7—H7 119.7 C11—Au1 2.052(5) C7—C8—C9 121.2(5)
259 C12—H12A 0.98 C7—C8—H8 119.4 C12—H12B 0.98 C9—C8—H8 119.4 C12—H12C 0.98 C8—C9—C10 117.3(6) C13—C14 1.387(8) C8—C9—C12 121.7(5) C13—C18 1.412(8) C10—C9—C12 121.1(6) C13—Au1 2.004(5) C11—C10—C9 123.5(5) C14—C15 1.389(8) C11—C10—H10 118.2 C14—H14 0.95 C9—C10—H10 118.2 C15—C16 1.364(9) C10—C11—C6 117.6(5) C15—H15 0.95 C10—C11—Au1 129.7(4) C16—F1 1.360(7) C6—C11—Au1 112.7(4) C16—C17 1.379(9) C9—C12—H12A 109.5 C17—C18 1.376(8) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—H18 0.95 H12B 109.5 C19—C20 1.395(7) C9—C12—H12C 109.5 C19—C24 1.400(7) H12A—C12— 109.5 C19—Au1 2.063(5) H12C 117.4(5) C20—C21 1.381(8) H12B—C12— 122.4(4) C20—H20 0.95 H12C 120.2(4) C21—C22 1.374(8) C14—C13—C18 121.6(6) C21—H21 0.95 C14—C13—Au1 119.2 C22—C23 1.363(8) C18—C13—Au1 119.2 C22—F2 1.364(6) C13—C14—C15 118.7(6) C23—C24 1.390(8) C13—C14—H14 120.6 C23—H23 0.95 C15—C14—H14 120.6 C24—H24 0.95 C16—C15—C14 118.9(6) C25—N2 1.346(7) C16—C15—H15 122.3(6) C25—C26 1.380(8) C14—C15—H15 118.8(6) C25—H25 0.95 C15—C16—F1 118.5(6) C26—C27 1.371(8) C15—C16—C17 120.8 C26—H26 0.95 F1—C16—C17 120.8 C27—C28 1.381(8) C18—C17—C16 121.5(6) C27—H27 0.95 C18—C17—H17 119.3 C28—C29 1.396(8) C16—C17—H17 119.3 C28—H28 0.95 C17—C18—C13 116.0(5) C29—N2 1.360(7) C17—C18—H18 124.8(4) C29—C30 1.465(7) C13—C18—H18 119.1(4) C30—C31 1.400(7) C20—C19—C24 122.1(5) C30—C35 1.408(7) C20—C19—Au1 118.9 C31—C32 1.395(8) C24—C19—Au1 118.9 C31—H31 0.95 C21—C20—C19 119.0(5) C32—C33 1.386(8) C21—C20—H20 120.5 C32—H32 0.95 C19—C20—H20 120.5 C33—C34 1.394(7) C22—C21—C20 119.2(5) C33—C36 1.509(8) C22—C21—H21 122.0(5)
260 C34—C35 1.391(7) C20—C21—H21 118.8(5) C34—H34 0.95 C23—C22—F2 118.0(5) C35—Au2 2.065(5) C23—C22—C21 121 C36—H36A 0.98 F2—C22—C21 121 C36—H36B 0.98 C22—C23—C24 122.8(5) C36—H36C 0.98 C22—C23—H23 118.6 C37—C38 1.382(8) C24—C23—H23 118.6 C37—C42 1.393(7) C23—C24—C19 122.2(5) C37—Au2 2.006(5) C23—C24—H24 118.9 C38—C39 1.404(8) C19—C24—H24 118.9 C38—H38 0.95 N2—C25—C26 118.3(5) C39—C40 1.358(9) N2—C25—H25 120.9 C39—H39 0.95 C26—C25—H25 120.9 C40—C41 1.361(9) C27—C26—C25 120.1(5) C40—F3 1.377(6) C27—C26—H26 119.9 C41—C42 1.401(8) C25—C26—H26 119.9 C41—H41 0.95 C26—C27—C28 120.0(5) C42—H42 0.95 C26—C27—H27 120 C43—C44 1.396(8) C28—C27—H27 120 C43—C48 1.401(8) C27—C28—C29 119.1(5) C43—Au2 2.067(5) C27—C28—H28 115.6(5) C44—C45 1.400(8) C29—C28—H28 125.4(5) C44—H44 0.95 N2—C29—C28 120.2(5) C45—C46 1.372(9) N2—C29—C30 122.7(5) C45—H45 0.95 C28—C29—C30 117.1(5) C46—C47 1.360(9) C31—C30—C35 120.1(5) C46—F4 1.367(6) C31—C30—C29 120 C47—C48 1.390(8) C35—C30—C29 120 C47—H47 0.95 C32—C31—C30 120.6(5) C48—H48 0.95 C32—C31—H31 119.7 C49—N3 1.330(7) C30—C31—H31 119.7 C49—C50 1.376(8) C33—C32—C31 118.6(5) C49—H49 0.95 C33—C32—H32 120.4(5) C50—C51 1.377(8) C31—C32—H32 121.0(5) C50—H50 0.95 C32—C33—C34 122.5(5) C51—C52 1.377(8) C32—C33—C36 118.7 C51—H51 0.95 C34—C33—C36 118.7 C52—C53 1.388(8) C35—C34—C33 118.0(5) C52—H52 0.95 C35—C34—H34 129.0(4) C53—N3 1.366(7) C33—C34—H34 113.0(4) C53—C54 1.467(8) C34—C35—C30 109.5 C54—C55 1.400(7) C34—C35—Au2 109.5 C54—C59 1.407(7) C30—C35—Au2 109.5 C55—C56 1.386(8) C33—C36—H36A 109.5 C55—H55 0.95 C33—C36—H36B 109.5 C56—C57 1.379(8) H36A—C36— 109.5
261 C56—H56 0.95 H36B 118.4(5) C57—C58 1.411(8) C33—C36—H36C 122.1(4) C57—C60 1.508(8) H36A—C36— 119.5(4) C58—C59 1.383(8) H36C 121.5(5) C58—H58 0.95 H36B—C36— 119.2 C59—Au3 2.069(5) H36C 119.2 C60—H60A 0.98 C38—C37—C42 117.6(6) C60—H60B 0.98 C38—C37—Au2 121.2 C60—H60C 0.98 C42—C37—Au2 121.2 C61—C66 1.382(8) C37—C38—C39 123.6(5) C61—C62 1.394(8) C37—C38—H38 118.4(5) C61—Au3 2.012(5) C39—C38—H38 118.0(6) C62—C63 1.379(9) C40—C39—C38 118.2(5) C62—H62 0.95 C40—C39—H39 120.9 C63—C64 1.367(9) C38—C39—H39 120.9 C63—H63 0.95 C41—C40—C39 120.7(5) C64—F5 1.360(7) C41—C40—F3 119.6 C64—C65 1.371(9) C39—C40—F3 119.6 C65—C66 1.389(8) C40—C41—C42 115.7(5) C65—H65 0.95 C40—C41—H41 124.5(4) C66—H66 0.95 C42—C41—H41 119.8(4) C67—C72 1.393(8) C37—C42—C41 123.0(5) C67—C68 1.398(8) C37—C42—H42 118.5 C67—Au3 2.062(5) C41—C42—H42 118.5 C68—C69 1.384(8) C44—C43—C48 117.2(5) C68—H68 0.95 C44—C43—Au2 121.4 C69—C70 1.365(8) C48—C43—Au2 121.4 C69—H69 0.95 C43—C44—C45 118.9(5) C70—F6 1.361(6) C43—C44—H44 123.1(5) C70—C71 1.382(8) C45—C44—H44 118.0(6) C71—C72 1.397(8) C46—C45—C44 118.3(5) C71—H71 0.95 C46—C45—H45 120.9 C72—H72 0.95 C44—C45—H45 120.9 C73—N4 1.345(7) C47—C46—F4 122.6(5) C73—C74 1.390(8) C47—C46—C45 118.7 C73—H73 0.95 F4—C46—C45 118.7 C74—C75 1.387(9) C46—C47—C48 122.5(5) C74—H74 0.95 C46—C47—H47 118.8 C75—C76 1.379(9) C48—C47—H47 118.8 C75—H75 0.95 C47—C48—C43 118.6(5) C76—C77 1.388(8) C47—C48—H48 120.7 C76—H76 0.95 C43—C48—H48 120.7 C77—N4 1.361(7) N3—C49—C50 119.2(5) C77—C78 1.462(8) N3—C49—H49 120.4 C78—C79 1.393(8) C50—C49—H49 120.4 C78—C83 1.403(8) C49—C50—C51 120.4(5)
262 C79—C80 1.380(9) C49—C50—H50 119.8 C79—H79 0.95 C51—C50—H50 119.8 C80—C81 1.389(10) C50—C51—C52 119.2(5) C80—H80 0.95 C50—C51—H51 115.3(5) C81—C82 1.400(8) C52—C51—H51 125.4(5) C81—C84 1.491(9) C51—C52—C53 120.0(5) C82—C83 1.397(8) C51—C52—H52 122.7(5) C82—H82 0.95 C53—C52—H52 117.2(5) C83—Au4 2.069(5) N3—C53—C52 120.2(5) C84—H84A 0.98 N3—C53—C54 119.9 C84—H84B 0.98 C52—C53—C54 119.9 C84—H84C 0.98 C55—C54—C59 121.3(5) C85—C90 1.390(8) C55—C54—C53 119.4 C85—C86 1.394(8) C59—C54—C53 119.4 C85—Au4 2.002(5) C56—C55—C54 117.7(5) C86—C87 1.383(8) C56—C55—H55 120.4(5) C86—H86 0.95 C54—C55—H55 121.8(5) C87—C88 1.361(9) C57—C56—C55 122.8(5) C87—H87 0.95 C57—C56—H56 118.6 C88—F7 1.362(7) C55—C56—H56 118.6 C88—C89 1.378(9) C56—C57—C58 117.9(5) C89—C90 1.385(8) C56—C57—C60 128.6(4) C89—H89 0.95 C58—C57—C60 113.0(4) C90—H90 0.95 C59—C58—C57 109.5 C91—C92 1.391(8) C59—C58—H58 109.5 C91—C96 1.397(7) C57—C58—H58 109.5 C91—Au4 2.070(5) C58—C59—C54 109.5 C92—C93 1.389(8) C58—C59—Au3 109.5 C92—H92 0.95 C54—C59—Au3 109.5 C93—C94 1.371(8) C57—C60—H60A 118.6(5) C93—H93 0.95 C57—C60—H60B 119.7(4) C94—F8 1.368(6) H60A—C60— 121.7(4) C94—C95 1.371(8) H60B 120.6(6) C95—C96 1.392(8) C57—C60—H60C 119.7 C95—H95 0.95 H60A—C60— 119.7 C96—H96 0.95 H60C 119.3(6) N1—Au1 2.124(4) H60B—C60— 120.4 N2—Au2 2.114(4) H60C 120.4 N3—Au3 2.112(4) C66—C61—C62 119.8(6) N4—Au4 2.114(4) C66—C61—Au3 118.2(6) C62—C61—Au3 122.0(5) C63—C62—C61 118.4(6) C63—C62—H62 120.8 C61—C62—H62 120.8 C64—C63—C62 121.1(6) C64—C63—H63 119.4
263 C62—C63—H63 119.4 F5—C64—C63 117.2(5) F5—C64—C65 120.2(4) C63—C64—C65 122.4(4) C64—C65—C66 121.7(5) C64—C65—H65 119.1 C66—C65—H65 119.1 C61—C66—C65 118.9(5) C61—C66—H66 120.5 C65—C66—H66 120.5 C72—C67—C68 119.1(5) C72—C67—Au3 118.7(5) C68—C67—Au3 122.2(5) C69—C68—C67 118.0(5) C69—C68—H68 121 C67—C68—H68 121 C70—C69—C68 121.8(5) C70—C69—H69 119.1 C68—C69—H69 119.1 F6—C70—C69 122.1(6) F6—C70—C71 118.9 C69—C70—C71 118.9 C70—C71—C72 118.0(6) C70—C71—H71 121 C72—C71—H71 121 C67—C72—C71 119.2(6) C67—C72—H72 120.4 C71—C72—H72 120.4 N4—C73—C74 121.4(6) N4—C73—H73 119.3 C74—C73—H73 119.3 C75—C74—C73 118.5(5) C75—C74—H74 115.2(5) C73—C74—H74 126.3(5) C76—C75—C74 119.7(6) C76—C75—H75 123.0(6) C74—C75—H75 117.4(5) C75—C76—C77 120.6(6) C75—C76—H76 119.7 C77—C76—H76 119.7 N4—C77—C76 121.2(6) N4—C77—C78 119.4 C76—C77—C78 119.4 C79—C78—C83 117.9(6) C79—C78—C77 120.5(6) C83—C78—C77 121.7(7)
264 C80—C79—C78 122.0(6) C80—C79—H79 119 C78—C79—H79 119 C79—C80—C81 118.6(5) C79—C80—H80 128.3(5) C81—C80—H80 112.9(4) C80—C81—C82 109.5 C80—C81—C84 109.5 C82—C81—C84 109.5 C81—C82—C83 109.5 C81—C82—H82 109.5 C83—C82—H82 109.5 C82—C83—C78 118.5(5) C82—C83—Au4 119.7(4) C78—C83—Au4 121.8(4) C81—C84—H84A 120.8(5) C81—C84—H84B 119.6 H84A—C84— 119.6 H84B 119.1(6) C81—C84—H84C 120.4 H84A—C84— 120.4 H84C 119.7(6) H84B—C84— 122.1(6) H84C 118.3(6) C90—C85—C86 118.7(6) C90—C85—Au4 120.7 C86—C85—Au4 120.7 C87—C86—C85 120.8(5) C87—C86—H86 119.6 C85—C86—H86 119.6 C88—C87—C86 117.6(5) C88—C87—H87 121.7(4) C86—C87—H87 120.6(4) C87—C88—F7 121.7(5) C87—C88—C89 119.1 F7—C88—C89 119.1 C88—C89—C90 118.4(5) C88—C89—H89 120.8 C90—C89—H89 120.8 C89—C90—C85 118.4(5) C89—C90—H90 119.2(5) C85—C90—H90 122.4(5) C92—C91—C96 118.5(5) C92—C91—Au4 120.7 C96—C91—Au4 120.7 C93—C92—C91 121.3(5)
265 C93—C92—H92 119.4 C91—C92—H92 119.4 C94—C93—C92 120.8(5) C94—C93—H93 125.6(4) C92—C93—H93 113.6(4) F8—C94—C95 120.3(5) F8—C94—C93 125.6(4) C95—C94—C93 114.1(3) C94—C95—C96 120.0(5) C94—C95—H95 125.5(4) C96—C95—H95 114.1(4) C95—C96—C91 120.7(5) C95—C96—H96 125.0(4) C91—C96—H96 114.2(4) C1—N1—C5 94.4(2) C1—N1—Au1 89.4(2) C5—N1—Au1 176.1(2) C25—N2—C29 174.7(2) C25—N2—Au2 80.6(2) C29—N2—Au2 95.59(19) C49—N3—C53 94.1(2) C49—N3—Au3 88.6(2) C53—N3—Au3 176.7(2) C73—N4—C77 174.15(19) C73—N4—Au4 80.28(19) C77—N4—Au4 96.95(18) C13—Au1—C11 87.4(2) C13—Au1—C19 97.4(2) C11—Au1—C19 173.4(2) C13—Au1—N1 177.3(2) C11—Au1—N1 94.85(19) C19—Au1—N1 80.2(2) C37—Au2—C35 95.5(2) C37—Au2—C43 87.6(2) C35—Au2—C43 176.5(2) C37—Au2—N2 175.20(19) C35—Au2—N2 79.9(2) C43—Au2—N2 96.97(19) C61—Au3—C67 C61—Au3—C59 C67—Au3—C59 C61—Au3—N3 C67—Au3—N3 C59—Au3—N3 C85—Au4—C83 C85—Au4—C91
266 C83—Au4—C91 C85—Au4—N4 C83—Au4—N4 C91—Au4—N4
267 Table AI.11. X-ray crystallographic data for [(tpy)Au(Cl)(1-naphthyl)]
AI.11a. Crystal data AI.11b. Data collection
Chemical C22H17AuClN Diffractometer Bruker formula AXS SMART APEX CCD diffractometer Mr 527.78 Absorption Multi-scan Crystal Monoclinic, P21/c correction Apex2 v2013.4-1 (Bruker, system, space 2013) group Tmin, Tmax 0.383, 0.746 Temperature 100 (K) No. of 19661, 4345, 3597 measured, a, b, c (Å) 10.340 (2), 18.881 independent and (4), 9.579 (2) observed [I > 2σ(I)] β (°) 110.408 (3) reflections V (Å3) 1752.7 (7) Rint 0.052
Z 4 −1 (sin θ/λ)max (Å ) 0.667 Radiation Mo Kα type
µ (mm−1) 8.55
Crystal size 0.37 × 0.07 × 0.06 (mm)
AI.11c. Refinement AI.11d. Crystal Structure R[F2 > 0.031, 0.081, 1. 2σ(F2)], wR(F2), 04 S
No. of 4345 reflections
No. of 227 parameters
H-atom H-atom treatment parameters constrained
Δρ , Δρ (e 3.61, −3.32 max min
268 Å−3)
AI.11e. Bonds (Å) AI.11f. Angles (˚) C1—N24 1.340(6) N24—C1—C2 122.1(5) C1—C2 1.374(7) N24—C1—H1 119 C1—H1 0.95 C2—C1—H1 119 C2—C3 1.385(7) C1—C2—C3 118.8(5) C2—H2 0.95 C1—C2—H2 120.6 C3—C4 1.378(7) C3—C2—H2 120.6 C3—H3 0.95 C4—C3—C2 120.1(5) C4—C5 1.396(7) C4—C3—H3 120 C4—H4 0.95 C2—C3—H3 120 C5—N24 1.368(6) C3—C4—C5 119.1(5) C5—C6 1.456(7) C3—C4—H4 120.4 C6—C7 1.402(6) C5—C4—H4 120.4 C6—C11 1.418(6) N24—C5—C4 120.1(5) C7—C8 1.358(7) N24—C5—C6 113.8(4) C7—H7 0.95 C4—C5—C6 126.1(4) C8—C9 1.389(7) C7—C6—C11 118.2(4) C8—H8 0.95 C7—C6—C5 123.1(4) C9—C10 1.405(6) C11—C6—C5 118.7(4) C9—C12 1.500(8) C8—C7—C6 120.9(4) C10—C11 1.383(7) C8—C7—H7 119.6 C10—H10 0.95 C6—C7—H7 119.6 C11—Au1 2.023(4) C7—C8—C9 122.0(4) C12—H12A 0.98 C7—C8—H8 119 C12—H12B 0.98 C9—C8—H8 119 C12—H12C 0.98 C8—C9—C10 117.8(5) C13—C14 1.371(6) C8—C9—C12 120.6(4) C13—C22 1.431(6) C10—C9—C12 121.6(4) C13—Au1 2.021(4) C11—C10—C9 121.2(4) C14—C15 1.410(7) C11—C10—H10 119.4 C14—H14 0.95 C9—C10—H10 119.4 C15—C16 1.349(7) C10—C11—C6 119.8(4) C15—H15 0.95 C10—C11—Au1 128.0(3) C16—C17 1.425(6) C6—C11—Au1 112.2(3) C16—H16 0.95 C9—C12—H12A 109.5 C17—C18 1.417(7) C9—C12—H12B 109.5 C17—C22 1.420(6) H12A—C12— 109.5 C18—C19 1.357(7) H12B 109.5 C18—H18 0.95 C9—C12—H12C 109.5 C19—C20 1.417(7) H12A—C12— 109.5 C19—H19 0.95 H12C 119.4(4) C20—C21 1.359(7) H12B—C12— 118.7(3)
269 C20—H20 0.95 H12C 121.9(3) C21—C22 1.417(6) C14—C13—C22 121.2(5) C21—H21 0.95 C14—C13—Au1 119.4 N24—Au1 2.110(4) C22—C13—Au1 119.4 Cl4—Au1 2.3634(11) C13—C14—C15 120.8(4) C13—C14—H14 119.6 C15—C14—H14 119.6 C16—C15—C14 120.2(4) C16—C15—H15 119.9 C14—C15—H15 119.9 C15—C16—C17 119.1(4) C15—C16—H16 121.4(4) C17—C16—H16 119.6(4) C18—C17—C22 121.3(5) C18—C17—C16 119.3 C22—C17—C16 119.3 C19—C18—C17 119.7(5) C19—C18—H18 120.1 C17—C18—H18 120.1 C18—C19—C20 120.3(5) C18—C19—H19 119.9 C20—C19—H19 119.9 C21—C20—C19 121.6(5) C21—C20—H20 119.2 C19—C20—H20 119.2 C20—C21—C22 118.0(4) C20—C21—H21 123.3(4) C22—C21—H21 118.7(4) C21—C22—C17 119.9(4) C21—C22—C13 126.1(3) C17—C22—C13 113.8(3) C1—N24—C5 93.53(17) C1—N24—Au1 174.37(16) C5—N24—Au1 81.19(17) C13—Au1—C11 91.28(12) C13—Au1—N24 174.78(14) C11—Au1—N24 94.07(11) C13—Au1—Cl4 C11—Au1—Cl4 N24—Au1—Cl4
270 Table AI.12. X-ray crystallographic data for [(tpy)Au(Cl)( 4-fluorophenyl)]
AI.12a. Crystal data AI.12b. Data collection
Chemical C18H14AuClFN Diffractometer Bruker formula AXS SMART APEX CCD diffractometer Mr 495.72 Absorption Multi-scan Crystal Monoclinic, P21/c correction Apex2 v2013.4-1 (Bruker, system, space 2013) group Tmin, Tmax 0.418, 0.746 Temperature 100 (K) No. of 9244, 4645, 4016 measured, a, b, c (Å) 9.4066 independent and (10), 13.2270 observed [I > (14), 13.1786 (14) 2σ(I)] reflections β (°) 110.251 (2) R 0.027 V (Å3) 1538.3 (3) int −1 (sin θ/λ)max (Å ) 0.734
Z 4
Radiation Mo Kα type
µ (mm−1) 9.74
Crystal size 0.31 × 0.19 × 0.11 (mm)
271 AI.12c. Refinement AI.12d. Crystal Structure R[F2 > 0.030, 0.075, 1.0 2σ(F2)], wR(F2), 4 S
No. of reflections 4645
No. of 200 parameters
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e 2.97, −1.61 Å−3)
AI.12e. Bonds (Å) AI. 12f. Angles (˚) C1—N1 1.343(5) N1—C1—C2 122.0(4) C1—C2 1.375(6) N1—C1—H1 119 C1—H1 0.95 C2—C1—H1 119 C2—C3 1.384(7) C1—C2—C3 119.3(4) C2—H2 0.95 C1—C2—H2 120.3 C3—C4 1.388(6) C3—C2—H2 120.3 C3—H3 0.95 C2—C3—C4 118.9(4) C4—C5 1.391(5) C2—C3—H3 120.6 C4—H4 0.95 C4—C3—H3 120.6 C5—N1 1.361(5) C3—C4—C5 119.8(4) C5—C6 1.470(5) C3—C4—H4 120.1 C6—C7 1.399(5) C5—C4—H4 120.1 C6—C11 1.405(5) N1—C5—C4 120.2(3) C7—C8 1.380(6) N1—C5—C6 114.1(3) C7—H7 0.95 C4—C5—C6 125.7(3) C8—C9 1.398(6) C7—C6—C11 119.3(3) C8—H8 0.95 C7—C6—C5 122.6(4) C9—C10 1.385(5) C11—C6—C5 118.2(3) C9—C12 1.508(6) C8—C7—C6 120.8(4) C10—C11 1.393(5) C8—C7—H7 119.6 C10—H10 0.95 C6—C7—H7 119.6 C11—Au1 2.023(4) C7—C8—C9 120.1(4) C12—H12A 0.98 C7—C8—H8 120 C12—H12B 0.98 C9—C8—H8 120 C12—H12C 0.98 C10—C9—C8 119.3(4) C13—C14 1.394(5) C10—C9—C12 120.0(4) C13—C18 1.402(5) C8—C9—C12 120.7(4) C13—Au1 2.018(4) C9—C10—C11 121.3(4)
272 C14—C15 1.399(6) C9—C10—H10 119.3 C14—H14 0.95 C11—C10—H10 119.3 C15—C16 1.367(7) C10—C11—C6 119.2(3) C15—H15 0.95 C10—C11—Au1 128.1(3) C16—F1 1.364(5) C6—C11—Au1 112.8(3) C16—C17 1.368(7) C9—C12—H12A 109.5 C17—C18 1.383(6) C9—C12—H12B 109.5 C17—H17 0.95 H12A—C12— 109.5 C18—H18 0.95 H12B 109.5 N1—Au1 2.116(3) C9—C12—H12C 109.5 Cl1—Au1 2.3707(9) H12A—C12— 109.5 H12C 118.3(4) H12B—C12— 122.3(3) H12C 119.3(3) C14—C13—C18 120.7(4) C14—C13—Au1 119.7 C18—C13—Au1 119.7 C13—C14—C15 118.3(4) C13—C14—H14 120.8 C15—C14—H14 120.8 C16—C15—C14 118.5(4) C16—C15—H15 118.4(4) C14—C15—H15 123.1(4) F1—C16—C15 118.4(4) F1—C16—C17 120.8 C15—C16—C17 120.8 C16—C17—C18 121.2(4) C16—C17—H17 119.4 C18—C17—H17 119.4 C17—C18—C13 119.8(3) C17—C18—H18 126.2(3) C13—C18—H18 113.5(2) C1—N1—C5 93.26(15) C1—N1—Au1 171.99(14) C5—N1—Au1 81.05(14) C13—Au1—C11 91.07(10) C13—Au1—N1 175.59(11) C11—Au1—N1 94.56(9) C13—Au1—Cl1 C11—Au1—Cl1 N1—Au1—Cl1
273 Table AI.13. X-ray crystallographic data for [Ir(bt)2(F)(3,5-dimethylpyrazole)]
AI.13a. Crystal data AI.13b. Data collection
Chemical C31H24FIrN4S2 Diffractometer Bruker formula AXS SMART APEX CCD diffractometer Mr 727.86 Absorption Multi-scan Crystal Monoclinic, P21/n correction TWINABS (Sheldrick, system, space 2009) group Tmin, Tmax 0.477, 0.746 Temperature 100 (K) No. of 23629, 7203, 5256 measured, a, b, c (Å) 10.291 (3), 17.035 independent and (5), 15.064 (4) observed [I > 2σ(I)] β (°) 95.208 (4) reflections V (Å3) 2630.0 (13) Rint 0.067
Z 4 −1 (sin θ/λ)max (Å ) 0.717 Radiation Mo Kα type
µ (mm−1) 5.27
Crystal size 0.12 × 0.11 × 0.03 (mm)
AI.13c. Refinement AI.13d. Crystal Structure
274 R[F2 > 0.058, 0.150, 1.01 2σ(F2)], wR(F2), S
No. of reflections 7203
No. of parameters 355
No. of restraints 12
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e 5.95, −3.03 Å−3)
AI.13e. Bonds (Å) AI.13f. Angles (˚) Ir1—C13 1.997(9) C13—Ir1—C26 89.0(3) Ir1—C26 2.004(9) C13—Ir1—N1 80.4(4) Ir1—N1 2.040(8) C26—Ir1—N1 95.1(4) Ir1—N2 2.059(8) C13—Ir1—N2 95.7(4) Ir1—F1 2.168(5) C26—Ir1—N2 79.8(3) Ir1—N3 2.172(7) N1—Ir1—N2 173.7(3) S1—C7 1.705(10) C13—Ir1—F1 178.4(3) S1—C6 1.718(13) C26—Ir1—F1 91.3(3) S2—C20 1.720(10) N1—Ir1—F1 98.0(3) S2—C19 1.731(10) N2—Ir1—F1 85.9(3) N1—C7 1.312(13) C13—Ir1—N3 98.5(3) N1—C1 1.382(12) C26—Ir1—N3 172.5(3) N2—C20 1.297(12) N1—Ir1—N3 86.4(3) N2—C14 1.405(12) N2—Ir1—N3 99.1(3) N3—C30 1.318(12) F1—Ir1—N3 81.2(2) N3—N4 1.363(10) C7—S1—C6 88.8(5) N4—C28 1.320(12) C20—S2—C19 89.3(5) N4—H4N 0.88 C7—N1—C1 111.2(9) C1—C2 1.392(14) C7—N1—Ir1 114.9(7) C1—C6 1.408(15) C1—N1—Ir1 133.7(7) C2—C3 1.383(14) C20—N2—C14 112.8(8) C2—H2 0.95 C20—N2—Ir1 114.1(6) C3—C4 1.421(18) C14—N2—Ir1 132.4(7) C3—H3 0.95 C30—N3—N4 105.1(7) C4—C5 1.329(19) C30—N3—Ir1 142.5(6) C4—H4 0.95 N4—N3—Ir1 112.3(5) C5—C6 1.427(15) C28—N4—N3 112.2(7) C5—H5 0.95 C28—N4—H4N 123.9 C7—C8 1.452(14) N3—N4—H4N 123.9
275 C8—C13 1.414(14) N1—C1—C2 127.0(10) C8—C9 1.436(14) N1—C1—C6 112.4(9) C9—C10 1.342(15) C2—C1—C6 120.6(10) C9—H9 0.95 C3—C2—C1 119.4(12) C10—C11 1.343(16) C3—C2—H2 120.3 C10—H10 0.95 C1—C2—H2 120.3 C11—C12 1.423(14) C2—C3—C4 119.5(12) C11—H11 0.95 C2—C3—H3 120.2 C12—C13 1.398(12) C4—C3—H3 120.2 C12—H12 0.95 C5—C4—C3 122.0(12) C14—C15 1.380(13) C5—C4—H4 119 C14—C19 1.400(13) C3—C4—H4 119 C15—C16 1.380(14) C4—C5—C6 119.7(13) C15—H15 0.95 C4—C5—H5 120.2 C16—C17 1.382(15) C6—C5—H5 120.2 C16—H16 0.95 C1—C6—C5 118.8(12) C17—C18 1.386(15) C1—C6—S1 111.0(8) C17—H17 0.95 C5—C6—S1 130.1(11) C18—C19 1.401(14) N1—C7—C8 117.0(9) C18—H18 0.95 N1—C7—S1 116.4(8) C20—C21 1.446(12) C8—C7—S1 126.5(8) C21—C26 1.394(13) C13—C8—C9 121.8(10) C21—C22 1.404(12) C13—C8—C7 113.0(9) C22—C23 1.380(13) C9—C8—C7 125.1(10) C22—H22 0.95 C10—C9—C8 118.3(10) C23—C24 1.365(14) C10—C9—H9 120.9 C23—H23 0.95 C8—C9—H9 120.9 C24—C25 1.410(12) C9—C10—C11 121.9(10) C24—H24 0.95 C9—C10—H10 119 C25—C26 1.401(12) C11—C10—H10 119 C25—H25 0.95 C10—C11—C12 121.6(10) C27—C28 1.502(13) C10—C11—H11 119.2 C27—H27A 0.98 C12—C11—H11 119.2 C27—H27B 0.98 C13—C12—C11 119.6(11) C27—H27C 0.98 C13—C12—H12 120.2 C28—C29 1.361(13) C11—C12—H12 120.2 C29—C30 1.397(13) C12—C13—C8 116.7(9) C29—H29 0.95 C12—C13—Ir1 128.8(8) C30—C31 1.502(13) C8—C13—Ir1 114.5(7) C31—H31A 0.98 C15—C14—C19 118.7(9) C31—H31B 0.98 C15—C14—N2 129.8(9) C31—H31C 0.98 C19—C14—N2 111.5(8) C14—C15—C16 119.6(10) C14—C15—H15 120.2 C16—C15—H15 120.2 C15—C16—C17 121.6(9)
276 C15—C16—H16 119.2 C17—C16—H16 119.2 C16—C17—C18 120.4(10) C16—C17—H17 119.8 C18—C17—H17 119.8 C17—C18—C19 117.6(10) C17—C18—H18 121.2 C19—C18—H18 121.2 C14—C19—C18 122.1(9) C14—C19—S2 111.1(7) C18—C19—S2 126.8(8) N2—C20—C21 117.9(8) N2—C20—S2 115.1(7) C21—C20—S2 127.0(8) C26—C21—C22 123.2(8) C26—C21—C20 113.2(8) C22—C21—C20 123.6(9) C23—C22—C21 118.8(9) C23—C22—H22 120.6 C21—C22—H22 120.6 C24—C23—C22 119.5(9) C24—C23—H23 120.2 C22—C23—H23 120.2 C23—C24—C25 122.0(9) C23—C24—H24 119 C25—C24—H24 119 C26—C25—C24 119.9(10) C26—C25—H25 120 C24—C25—H25 120 C21—C26—C25 116.7(8) C21—C26—Ir1 114.7(6) C25—C26—Ir1 128.5(7) C28—C27—H27A 109.5 C28—C27—H27B 109.5 H27A—C27— 109.5 H27B 109.5 C28—C27—H27C 109.5 H27A—C27— 109.5 H27C 106.5(8) H27B—C27—H27C 122.9(9) N4—C28—C29 130.5(9) N4—C28—C27 106.2(9) C29—C28—C27 126.9 C28—C29—C30 126.9 C28—C29—H29 109.9(8) C30—C29—H29 121.5(8)
277 N3—C30—C29 128.5(9) N3—C30—C31 109.5 C29—C30—C31 109.5 C30—C31—H31A 109.5 C30—C31—H31B 109.5 H31A—C31— 109.5 H31B 109.5 C30—C31—H31C H31A—C31— H31C H31B—C31—H31C
278 Table AI.14. X-ray crystallographic data for [Ir(bt)2(Cl)(3,5-dimethylpyrazole)]
AI.14a. Crystal data AI.14b. Data collection Crystal data Diffractometer Bruker AXS APEXII CCD Chemical C31H24ClIrN4S2 diffractometer formula Absorption Multi-scan Mr 744.35 correction TWINABS (Sheldrick, 2012) Crystal system, Monoclinic, P21/n
space group Tmin, Tmax 0.484, 0.746 Temperature 100 No. of measured, 16094, 5418, 4113 (K) independent and observed [I > a, b, c (Å) 10.399 (6), 16.928 2σ(I)] reflections (9), 15.294 (8) R 0.082 β (°) 94.013 (7) int −1 3 (sin θ/λ)max (Å ) 0.625
V (Å ) 2686 (2)
Z 4
Radiation type Mo Kα
µ (mm−1) 5.26
Crystal size 0.15 × 0.07 × 0.06 (mm)
279 AI.14c. Refinement AI.14d. Crystal Structure R[F2 > 0.064, 0.163, 1. 2σ(F2)], wR(F2), 03 S
No. of 5418 reflections
No. of 355 parameters
No. of restraints 381
H-atom H-atom treatment parameters constrained
2 2 w = 1/[σ (Fo ) + (0.0692P)2 + 47.0892P] where P = 2 2 (Fo + 2Fc )/3
Δρmax, Δρmin (e 7.59, −3.09 Å−3)
AI.14e. Bonds (Å) AI.14f. Angles (˚) C1—C2 1.38(2) C2—C1—N1 126.9(14) C1—N1 1.387(18) C2—C1—C6 119.0(14) C1—C6 1.39(2) N1—C1—C6 114.1(13) C2—C3 1.42(2) C1—C2—C3 119.0(15) C2—H2 0.95 C1—C2—H2 120.5 C3—C4 1.38(2) C3—C2—H2 120.5 C3—H3 0.95 C4—C3—C2 120.9(15) C4—C5 1.38(2) C4—C3—H3 119.5 C4—H4 0.95 C2—C3—H3 119.5 C5—C6 1.40(2) C5—C4—C3 119.8(15) C5—H5 0.95 C5—C4—H4 120.1 C6—S1 1.736(16) C3—C4—H4 120.1 C7—N1 1.334(18) C4—C5—C6 119.0(14) C7—C8 1.44(2) C4—C5—H5 120.5 C7—S1 1.722(13) C6—C5—H5 120.5 C8—C9 1.41(2) C1—C6—C5 122.2(15) C8—C13 1.42(2) C1—C6—S1 110.6(11) C9—C10 1.35(2) C5—C6—S1 127.2(12) C9—H9 0.95 N1—C7—C8 118.1(12) C10—C11 1.41(2) N1—C7—S1 115.3(11)
280 C10—H10 0.95 C8—C7—S1 126.4(11) C11—C12 1.37(2) C9—C8—C13 121.5(14) C11—H11 0.95 C9—C8—C7 124.4(13) C12—C13 1.39(2) C13—C8—C7 114.1(12) C12—H12 0.95 C10—C9—C8 119.3(14) C13—Ir1 2.006(15) C10—C9—H9 120.4 C14—C19 1.36(2) C8—C9—H9 120.4 C14—N2 1.391(18) C9—C10—C11 121.0(15) C14—C15 1.44(2) C9—C10—H10 119.5 C15—C16 1.39(2) C11—C10—H10 119.5 C15—H15 0.95 C12—C11—C10 118.9(15) C16—C17 1.44(3) C12—C11—H11 120.5 C16—H16 0.95 C10—C11—H11 120.5 C17—C18 1.33(3) C11—C12—C13 123.4(15) C17—H17 0.95 C11—C12—H12 118.3 C18—C19 1.39(2) C13—C12—H12 118.3 C18—H18 0.95 C12—C13—C8 115.9(14) C19—S2 1.73(2) C12—C13—Ir1 131.1(12) C20—N2 1.291(19) C8—C13—Ir1 112.9(10) C20—C21 1.44(2) C19—C14—N2 113.5(15) C20—S2 1.719(14) C19—C14—C15 120.8(14) C21—C22 1.41(2) N2—C14—C15 125.8(14) C21—C26 1.43(2) C16—C15—C14 117.7(16) C22—C23 1.39(2) C16—C15—H15 121.1 C22—H22 0.95 C14—C15—H15 121.1 C23—C24 1.38(2) C15—C16—C17 118.7(17) C23—H23 0.95 C15—C16—H16 120.6 C24—C25 1.40(2) C17—C16—H16 120.7 C24—H24 0.95 C18—C17—C16 121.8(16) C25—C26 1.398(19) C18—C17—H17 119.1 C25—H25 0.95 C16—C17—H17 119.1 C26—Ir1 2.017(14) C17—C18—C19 119.8(18) C27—C28 1.45(2) C17—C18—H18 120.1 C27—H27A 0.98 C19—C18—H18 120.1 C27—H27B 0.98 C14—C19—C18 121.3(18) C27—H27C 0.98 C14—C19—S2 110.8(12) C28—N3 1.361(18) C18—C19—S2 127.9(15) C28—C29 1.41(2) N2—C20—C21 120.5(13) C29—C30 1.39(2) N2—C20—S2 115.1(11) C29—H29 0.95 C21—C20—S2 124.4(12) C30—N4 1.350(17) C22—C21—C26 122.5(14) C30—C31 1.496(19) C22—C21—C20 125.5(14) C31—H31A 0.98 C26—C21—C20 111.9(13) C31—H31B 0.98 C23—C22—C21 119.3(16) C31—H31C 0.98 C23—C22—H22 120.4 N1—Ir1 2.042(11) C21—C22—H22 120.4
281 N2—Ir1 2.101(12) C24—C23—C22 118.5(16) N3—N4 1.370(15) C24—C23—H23 120.8 N3—Ir1 2.170(11) C22—C23—H23 120.8 N4—H4A 0.88 C23—C24—C25 123.0(16) Cl1—Ir1 2.522(4) C23—C24—H24 118.5 C25—C24—H24 118.5 C26—C25—C24 120.1(15) C26—C25—H25 119.9 C24—C25—H25 119.9 C25—C26—C21 116.6(13) C25—C26—Ir1 128.4(11) C21—C26—Ir1 114.8(10) C28—C27—H27A 109.5 C28—C27—H27B 109.5 H27A—C27— 109.5 H27B 109.5 C28—C27—H27C 109.5 H27A—C27— 109.5 H27C 110.0(13) H27B—C27— 121.4(13) H27C 128.6(15) N3—C28—C29 106.6(14) N3—C28—C27 126.7 C29—C28—C27 126.7 C30—C29—C28 105.7(13) C30—C29—H29 119.5(13) C28—C29—H29 134.7(14) N4—C30—C29 109.5 N4—C30—C31 109.5 C29—C30—C31 109.5 C30—C31—H31A 109.5 C30—C31—H31B 109.5 H31A—C31— 109.5 H31B 110.8(12) C30—C31—H31C 113.0(9) H31A—C31— 136.0(9) H31C 111.9(12) H31B—C31— 112.6(10) H31C 135.0(11) C7—N1—C1 104.3(11) C7—N1—Ir1 138.8(9) C1—N1—Ir1 116.9(8) C20—N2—C14 113.3(11) C20—N2—Ir1 123.4 C14—N2—Ir1 123.4 C28—N3—N4 89.2(7)
282 C28—N3—Ir1 88.7(8) N4—N3—Ir1 87.8(6) C30—N4—N3 81.8(5) C30—N4—H4A 92.5(5) N3—N4—H4A 95.1(5) C7—S1—C6 79.7(5) C20—S2—C19 171.7(4) C13—Ir1—C26 172.8(5) C13—Ir1—N1 99.2(5) C26—Ir1—N1 99.3(4) C13—Ir1—N2 84.8(5) C26—Ir1—N2 85.6(4) N1—Ir1—N2 173.4(4) C13—Ir1—N3 86.1(3) C26—Ir1—N3 101.3(4) N1—Ir1—N3 87.4(3) N2—Ir1—N3 C13—Ir1—Cl1 C26—Ir1—Cl1 N1—Ir1—Cl1 N2—Ir1—Cl1 N3—Ir1—Cl1
283
Table AI.15. X-ray crystallographic data for [Ir(bt)2(SPh)(3,5-dimethylpyrazole)]
AI.15a. Crystal data AI.15b. Data collection
Chemical C37H28IrN4S3 Diffractometer Bruker AXS formula APEXII CCD diffractometer Mr 817.01 Absorption Multi-scan Crystal system, Monoclinic, P21/c correction Apex2 v2013.4-1 space group (Bruker, 2013)
Temperature 100 Tmin, Tmax 0.459, 0.746 (K) No. of measured, 44458, 6005, 5499 a, b, c (Å) 16.573 (2), 11.8257 independent and (15), 16.296 (2) observed [I > 2σ(I)] reflections β (°) 98.460 (2) R 0.047 V (Å3) 3159.2 (7) int −1 (sin θ/λ)max (Å ) 0.610
Z 4
Radiation type Mo Kα
µ (mm−1) 4.46
Crystal size 0.50 × 0.37 × 0.04 (mm)
284 AI.15c. Refinement AI.15d. Crystal Structure R[F2 > 0.039, 0.102, 1.0 2σ(F2)], wR(F2), 6 S
No. of 6005 reflections
No. of 408 parameters
H-atom H-atom treatment parameters constrained
2 2 w = 1/[σ (Fo ) + (0.054P)2 + 18.0667P] 2 where P = (Fo + 2 2Fc )/3
Δρmax, Δρmin (e 2.81, −0.98 Å−3)
AI.15e. Bonds (Å) AI.15f. Angles (˚) C1—C2 1.410(8) C2—C1—C6 116.0(5) C1—C6 1.416(8) C2—C1—Ir1 128.3(5) C1—Ir1 1.996(5) C6—C1—Ir1 115.6(4) C2—C3 1.386(9) C3—C2—C1 120.9(6) C2—H2 0.95 C3—C2—H2 119.6 C3—C4 1.381(10) C1—C2—H2 119.6 C3—H3 0.95 C4—C3—C2 121.5(6) C4—C5 1.382(10) C4—C3—H3 119.3 C4—H4 0.95 C2—C3—H3 119.3 C5—C6 1.398(8) C3—C4—C5 120.0(6) C5—H5 0.95 C3—C4—H4 120 C6—C7 1.434(8) C5—C4—H4 120 C7—N1 1.328(7) C4—C5—C6 118.6(6) C7—S1 1.736(6) C4—C5—H5 120.7 C8—C9 1.386(9) C6—C5—H5 120.7 C8—N1 1.389(7) C5—C6—C1 123.0(6) C8—C13 1.417(9) C5—C6—C7 124.7(6) C9—C10 1.378(9) C1—C6—C7 112.4(5) C9—H9 0.95 N1—C7—C6 118.0(5)
285 C10—C11 1.420(11) N1—C7—S1 114.0(4) C10—H10 0.95 C6—C7—S1 127.9(4) C11—C12 1.372(11) C9—C8—N1 127.7(5) C11—H11 0.95 C9—C8—C13 119.8(5) C12—C13 1.398(9) N1—C8—C13 112.5(5) C12—H12 0.95 C10—C9—C8 119.8(6) C13—S1 1.734(7) C10—C9—H9 120.1 C14—C15 1.408(8) C8—C9—H9 120.1 C14—C19 1.430(8) C9—C10—C11 119.6(7) C14—Ir1 2.008(6) C9—C10—H10 120.2 C15—C16 1.401(8) C11—C10—H10 120.2 C15—H15 0.95 C12—C11—C10 121.9(6) C16—C17 1.377(9) C12—C11—H11 119.1 C16—H16 0.95 C10—C11—H11 119.1 C17—C18 1.389(9) C11—C12—C13 117.9(7) C17—H17 0.95 C11—C12—H12 121 C18—C19 1.382(9) C13—C12—H12 121 C18—H18 0.95 C12—C13—C8 120.9(6) C19—C20 1.442(8) C12—C13—S1 128.5(5) C20—N2 1.318(7) C8—C13—S1 110.6(5) C20—S2 1.740(6) C15—C14—C19 114.6(5) C21—C22 1.378(8) C15—C14—Ir1 129.9(4) C21—N2 1.406(7) C19—C14—Ir1 115.5(4) C21—C26 1.412(8) C16—C15—C14 121.6(6) C22—C23 1.392(8) C16—C15—H15 119.2 C22—H22 0.95 C14—C15—H15 119.2 C23—C24 1.391(10) C17—C16—C15 121.6(6) C23—H23 0.95 C17—C16—H16 119.2 C24—C25 1.374(10) C15—C16—H16 119.2 C24—H24 0.95 C16—C17—C18 118.9(6) C25—C26 1.405(8) C16—C17—H17 120.5 C25—H25 0.95 C18—C17—H17 120.5 C26—S2 1.732(6) C19—C18—C17 119.7(6) C27—C28 1.482(9) C19—C18—H18 120.1 C27—H27A 0.98 C17—C18—H18 120.1 C27—H27B 0.98 C18—C19—C14 123.5(5) C27—H27C 0.98 C18—C19—C20 125.0(6) C28—N3 1.347(7) C14—C19—C20 111.5(5) C28—C29 1.383(9) N2—C20—C19 120.0(5) C29—C30 1.377(9) N2—C20—S2 115.7(4) C29—H29 0.95 C19—C20—S2 124.3(4) C30—N4 1.349(8) C22—C21—N2 127.1(5)
286 C30—C31 1.469(9) C22—C21—C26 119.7(5) C31—H31A 0.98 N2—C21—C26 113.1(5) C31—H31B 0.98 C21—C22—C23 118.8(6) C31—H31C 0.98 C21—C22—H22 120.6 C32—C37 1.404(10) C23—C22—H22 120.6 C32—C33 1.406(9) C24—C23—C22 121.1(6) C32—S3 1.756(7) C24—C23—H23 119.4 C33—C34 1.387(9) C22—C23—H23 119.4 C33—H33 0.95 C25—C24—C23 121.4(6) C34—C35 1.354(10) C25—C24—H24 119.3 C34—H34 0.95 C23—C24—H24 119.3 C35—C36 1.421(11) C24—C25—C26 117.5(6) C35—H35 0.95 C24—C25—H25 121.3 C36—C37 1.380(10) C26—C25—H25 121.3 C36—H36 0.95 C25—C26—C21 121.4(6) C37—H37 0.95 C25—C26—S2 127.8(5) N1—Ir1 2.054(4) C21—C26—S2 110.8(4) N2—Ir1 2.079(5) C28—C27—H27A 109.5 N3—N4 1.373(6) C28—C27—H27B 109.5 N3—Ir1 2.221(5) H27A—C27— 109.5 S3—Ir1 2.4907(13) H27B 109.5 C28—C27—H27C 109.5 H27A—C27— 109.5 H27C 109.6(5) H27B—C27—H27C 121.6(5) N3—C28—C29 128.7(5) N3—C28—C27 107.7(5) C29—C28—C27 126.2 C30—C29—C28 126.2 C30—C29—H29 105.6(5) C28—C29—H29 121.4(6) N4—C30—C29 132.9(6) N4—C30—C31 109.5 C29—C30—C31 109.5 C30—C31—H31A 109.5 C30—C31—H31B 109.5 H31A—C31— 109.5 H31B 109.5 C30—C31—H31C 117.6(6) H31A—C31— 120.8(5) H31C 121.7(5) H31B—C31—H31C 120.9(6)
287 C37—C32—C33 119.6 C37—C32—S3 119.6 C33—C32—S3 121.6(6) C34—C33—C32 119.2 C34—C33—H33 119.2 C32—C33—H33 118.7(6) C35—C34—C33 120.6 C35—C34—H34 120.6 C33—C34—H34 120.3(7) C34—C35—C36 119.8 C34—C35—H35 119.8 C36—C35—H35 120.9(7) C37—C36—C35 119.6 C37—C36—H36 119.6 C35—C36—H36 113.0(5) C36—C37—C32 114.0(4) C36—C37—H37 132.9(4) C32—C37—H37 111.2(5) C7—N1—C8 112.8(4) C7—N1—Ir1 135.9(4) C8—N1—Ir1 105.2(5) C20—N2—C21 134.7(4) C20—N2—Ir1 111.3(3) C21—N2—Ir1 111.8(5) C28—N3—N4 89.8(3) C28—N3—Ir1 89.2(3) N4—N3—Ir1 107.1(2) C30—N4—N3 90.3(2) C13—S1—C7 79.9(2) C26—S2—C20 91.2(2) C32—S3—Ir1 94.4(2) C1—Ir1—C14 80.1(2) C1—Ir1—N1 169.67(18) C14—Ir1—N1 174.5(2) C1—Ir1—N2 93.1(2) C14—Ir1—N2 104.24(18) N1—Ir1—N2 82.03(17) C1—Ir1—N3 89.06(16) C14—Ir1—N3 179.35(16) N1—Ir1—N3 88.75(13) N2—Ir1—N3 99.84(13) C1—Ir1—S3 87.48(12)
288 C14—Ir1—S3 N1—Ir1—S3 N2—Ir1—S3 N3—Ir1—S3
289 Table AI.16. X-ray crystallographic data for [{Ir(bt)2(µ-F)}2]
AI.16a. Crystal data AI.16b. Data collection
Chemical C52H32F2Ir2N4S4·2(C6H6) Diffractometer Bruker X8 APEX II formula diffractometer
Mr 1419.67 Absorption Multi-scan correction SADABS2012/1 Crystal Tetragonal, I4/m (Bruker,2012) was system, space used for absorption group correction. wR2(int) was 0.0889 before Temperature 100 and 0.0532 after (K) correction. The a, c (Å) 10.4528 (15), 24.115 (5) Ratio of minimum to maximum V (Å3) 2634.9 (9) transmission is 0.6052. The λ/2 Z 2 correction factor is 0.0015. Radiation Mo Kα
type Tmin, Tmax 0.056, 0.093 −1 µ (mm ) 5.26 No. of measured, 16869, 1399, 1327 independent and Crystal size 0.24 × 0.19 × 0.08 observed [I > (mm) 2σ(I)] reflections
Rint 0.053
−1 (sin θ/λ)max (Å ) 0.626
290 AI.16c. Refinement AI.16d. Crystal Structure R[F2 > 0.017, 0.037, 1. 2σ(F2)], wR(F2), 04 S
No. of 1399 reflections
No. of 225 parameters
No. of restraints 57
H-atom H atoms treated treatment by a mixture of independent and constrained refinement
Δρmax, Δρmin (e 0.89, −0.77 −3 Å )
AI.16e. Bonds (Å) AI.16f. Angles (˚) Ir1—F1 2.176(2) F19_666—Ir1—F13_655 50.95(9) Ir1—F19_666 2.176(2) F1—Ir1—F13_655 50.95(9) Ir1—F13_655 2.176(2) F1—Ir1—F19_666 74.93(15) Ir1—F111_566 2.176(2) F1—Ir1—F111_566 50.95(9) Ir1—N13_655 2.045(4) F19_666—Ir1—F111_566 50.95(9) Ir1—N12_665 2.045(4) F13_655—Ir1—F111_566 74.93(15) Ir1—N1 2.045(4) N13_655—Ir1—F19_666 94.40(15) Ir1—N14_565 2.045(4) N14_565—Ir1—F13_655 58.01(14) Ir1—C1 2.018(5) N1—Ir1—F13_655 94.40(15) Ir1—C1B 2.016(5) N1—Ir1—F1 132.94(14) S1—C7 1.720(10) N14_565—Ir1—F1 94.40(15) S1—C8 1.714(7) N12_665—Ir1—F19_666 132.94(14) S1B—C7B 1.728(10) N13_655—Ir1—F13_655 132.94(14) S1B—C8B 1.729(7) N12_665—Ir1—F13_655 94.29(15) F1—Ir19_666 2.176(2) N1—Ir1—F111_566 94.29(15) N1—C7 1.403(11) N1—Ir1—F19_666 58.01(14) N1—C7B 1.400(11) N14_565—Ir1—F19_666 94.29(15) N1—C9 1.334(7) N12_665—Ir1—F1 58.01(14) N1—C9B 1.347(7) N13_655—Ir1—F111_566 58.01(14) C1—N13_655 1.328(12) N14_565—Ir1—F111_566 132.94(14) C1—C6 1.39 N12_665—Ir1—F111_566 94.40(15) C1—C2 1.39 N13_655—Ir1—F1 94.29(15) C6—C5 1.39 N12_665—Ir1—N14_565 89.48(2) C6—C7 1.419(12) N13_655—Ir1—N14_565 169.0(2)
291 C5—H5 0.95 N13_655—Ir1—N12_665 89.48(2) C5—C4 1.39 N14_565—Ir1—N1 89.48(2) C4—H4 0.95 N12_665—Ir1—N1 169.0(2) C4—C3 1.39 N13_655—Ir1—N1 89.48(2) C3—H3 0.95 C1—Ir1—F111_566 96.0(4) C3—C2 1.39 C1—Ir1—F1 126.0(3) C2—N13_655 1.968(9) C1—Ir1—F19_666 120.0(3) C2—H2 0.95 C1—Ir1—F13_655 170.0(3) C1B—N14_565 1.337(12) C1—Ir1—N14_565 131.0(4) C1B—C6B 1.39 C1—Ir1—N1 82.1(2) C1B—C2B 1.39 C1—Ir1—N12_665 90.4(2) C6B—C5B 1.39 C1—Ir1—N13_655 38.2(4) C6B—C7B 1.411(12) C1B—Ir1—F13_655 96.2(3) C5B—H5B 0.95 C1B—Ir1—F19_666 120.1(3) C5B—C4B 1.39 C1B—Ir1—F1 126.3(3) C4B—H4B 0.95 C1B—Ir1—F111_566 170.2(3) C4B—C3B 1.39 C1B—Ir1—N13_655 130.7(4) C3B—H3B 0.95 C1B—Ir1—N12_665 90.4(2) C3B—C2B 1.39 C1B—Ir1—N14_565 38.4(4) C2B—N14_565 1.969(9) C1B—Ir1—N1 82.0(2) C2B—H2B 0.95 C8—S1—C7 89.2(5) C9—C8 1.39 C7B—S1B—C8B 89.9(5) C9—C10 1.39 Ir19_666—F1—Ir1 105.07(15) C8—C13 1.39 C7—N1—Ir1 110.6(5) C13—H13 0.95 C7B—N1—Ir1 110.3(5) C13—C12 1.39 C9—N1—Ir1 139.7(4) C12—H12 0.95 C9—N1—C7 109.7(6) C12—C11 1.39 C9B—N1—Ir1 139.8(4) C11—H11 0.95 C9B—N1—C7B 109.9(6) C11—C10 1.39 N13_655—C1—Ir1 72.0(3) C10—H10 0.95 N13_655—C1—C6 101.9(5) C9B—C8B 1.39 N13_655—C1—C2 92.7(6) C9B—C10B 1.39 C6—C1—Ir1 114.1(4) C8B—C13B 1.39 C6—C1—C2 120 C13B—H13B 0.95 C2—C1—Ir1 125.7(4) C13B—C12B 1.39 C1—C6—C7 114.5(6) C12B—H12B 0.95 C5—C6—C1 120 C12B—C11B 1.39 C5—C6—C7 125.5(6) C11B—H11B 0.95 C6—C5—H5 120 C11B—C10B 1.39 C6—C5—C4 120 C10B—H10B 0.95 C4—C5—H5 120 C1S—H1S 0.93(2) C5—C4—H4 120 C1S—C2S 1.325(9) C5—C4—C3 120 C2S—H2S 0.95 C3—C4—H4 120 C2S—C3S 1.384(11) C4—C3—H3 120 C3S—H3S 0.95 C2—C3—C4 120
292 C3S—C4S 1.341(8) C2—C3—H3 120 C4S—H4S 0.903(19) N13_655—C2—H2 102.3 C1—C2—N13_655 42.4(5) C1—C2—H2 120 C3—C2—N13_655 121.7(4) C3—C2—C1 120 C3—C2—H2 120 N14_565—C1B—Ir1 72.0(3) N14_565—C1B—C6B 101.8(5) N14_565—C1B—C2B 92.5(6) C6B—C1B—Ir1 114.1(4) C6B—C1B—C2B 120 C2B—C1B—Ir1 125.7(4) C1B—C6B—C7B 114.3(6) C5B—C6B—C1B 120 C5B—C6B—C7B 125.7(6) C6B—C5B—H5B 120 C6B—C5B—C4B 120 C4B—C5B—H5B 120 C5B—C4B—H4B 120 C3B—C4B—C5B 120 C3B—C4B—H4B 120 C4B—C3B—H3B 120 C4B—C3B—C2B 120 C2B—C3B—H3B 120 N14_565—C2B—H2B 102.4 C1B—C2B—N14_565 42.7(5) C1B—C2B—H2B 120 C3B—C2B—N14_565 121.4(4) C3B—C2B—C1B 120 C3B—C2B—H2B 120 N1—C7—S1 113.9(7) N1—C7—C6 118.6(8) C6—C7—S1 127.3(8) N1—C7B—S1B 113.4(7) N1—C7B—C6B 119.1(8) C6B—C7B—S1B 127.4(8) N1—C9—C8 115.7(5) N1—C9—C10 124.3(5) C8—C9—C10 120 C9—C8—S1 111.4(5) C13—C8—S1 128.6(5) C13—C8—C9 120 C8—C13—H13 120 C8—C13—C12 120 C12—C13—H13 120
293 C13—C12—H12 120 C13—C12—C11 120 C11—C12—H12 120 C12—C11—H11 120 C12—C11—C10 120 C10—C11—H11 120 C9—C10—H10 120 C11—C10—C9 120 C11—C10—H10 120 N1—C9B—C8B 116.4(5) N1—C9B—C10B 123.5(5) C8B—C9B—C10B 120 C9B—C8B—S1B 110.2(5) C9B—C8B—C13B 120 C13B—C8B—S1B 129.8(5) C8B—C13B—H13B 120 C12B—C13B—C8B 120 C12B—C13B—H13B 120 C13B—C12B—H12B 120 C11B—C12B—C13B 120 C11B—C12B—H12B 120 C12B—C11B—H11B 120 C12B—C11B—C10B 120 C10B—C11B—H11B 120 C9B—C10B—H10B 120 C11B—C10B—C9B 120 C11B—C10B—H10B 120 C2S—C1S—H1S 119.7(4) C1S—C2S—H2S 120.1 C1S—C2S—C3S 119.9(8) C3S—C2S—H2S 120.1 C2S—C3S—H3S 119.8 C4S—C3S—C2S 120.4(7) C4S—C3S—H3S 119.8 C3S—C4S—H4S 120.5(4)
294 Appendix II. NMR Spectra of Synthesized New Compounds
Figure AII.1. 1H NMR spectrum of 1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-(2- pyridinyl))-1,2,3-triazole.
295
Figure AII.2. 13C NMR spectrum of 1-(1´-β-2´-deoxy-D-ribofuranosyl)-4-(5-(2- pyridinyl))-1,2,3-triazole.
296
1 Figure AII.3. H NMR spectrum of [Ir(ppy)2(7)]PF6
297
13 Figure AII.4. C NMR spectrum of [Ir(ppy)2(7)]PF6
298
1 Figure AII.5. H NMR spectrum of [Ir(tpy)2(7)]PF6
299
1 Figure AII.6. H NMR spectrum of [Ir(btp)2(7)]PF6
300
13 Figure AII.7. C NMR spectrum of [Ir(tpy)2(7)]PF6
301
1 Figure AII.8. H NMR spectrum of [Ir(bzq)2(7)]PF6
302
13 Figure AII.9. C NMR spectrum of [Ir(bzq)2(7)]PF6
303
1 Figure AII.10. H NMR spectrum of [Ir(pq)2(7)]PF6
304
13 Figure AII.11. C NMR spectrum of [Ir(pq)2(7)]PF6
305
N Au
F F
1 Figure AII.12. H NMR spectrum of [(tpy)Au(p-C6H5F)2]
306
N F F Au
F F
1 Figure AII.13. H NMR spectrum of [(tpy)Au(2,4-difluorophenyl)2]
307
N
Au
F3C CF 3
1 Figure AII.14. H NMR spectrum of [(tpy)Au(4-(trifluoromethyl)phenyl)2]
308
N Au
F3C CF3
19 Figure AII.15. F NMR spectrum of [(tpy)Au(4-(trifluoromethyl)phenyl)2]
309
N Au
O2N NO2
1 Figure AII.16. H NMR spectrum of [(tpy)Au(3-nitrophenyl)2].
310
N Au
EtO2C CO2Et
1 Figure AII.17. H NMR spectrum of [(tpy)Au(3-ethoxycarbonylphenyl))2].
311
N Au
H3COC COCH3
1 Figure AII.18. H NMR spectrum of [(tpy)Au(4-acetylphenyl))2].
312
N
Au
1 Figure AII.19. H NMR spectrum of [(tpy)Au(phenyl)2].
313
N
Au
1 Figure AII.20. H NMR spectrum of [(tpy)Au(2-naphthyl)2].
314
N Au
S S
1 Figure AII.21. H NMR spectrum of [(tpy)Au(benzo[b]thien-2-yl)2].
315
N Au
1 Figure AII.22. H NMR spectrum of [(tpy)Au(m-tolyl)2].
316
N Au
O O
1 Figure AII.23. H NMR spectrum of [(tpy)Au(4-methoxyphenyl)2].
317
1 Figure AII.24. H NMR spectrum of [{Ir(bt)2(µ-Cl)}2].
318
S S
N N F
Ir Ir F N N
S S
1 Figure AII.25. H NMR spectrum of [{Ir(bt)2(µ-F)}2].
319
S S
N N F
Ir Ir F N N
S S
19 Figure AII.26. F NMR spectrum of [{Ir(bt)2(µ-F)}2]
320
1 Figure AII.27. H NMR spectrum of [Ir(bt)2(F)(2,3-dimethylpyrazolato)].
321
F
N F F Ir H F N N N
F
19 Figure AII.28. F NMR spectrum of [Ir(bt)2(F)(2,3-dimethylpyrazolato)]
322
S
N Cl
Ir H N N N S
1 Figure AII.29. H NMR spectrum of [Ir(bt)2(Cl)(2,3-dimethylpyrazolato)]
323 Bibliography:
Abbenhuis, H. C. L., Feiken, N., Haarman, H. F., Grove, D. M., Horn, E., Kooijman, H., van Koten, G. (1991). Effect of Intramolecular Coordination on Tantalum- Alkylidene-Centered Reactions: Synthesis and Structure of a Tantalum-Olefin Adduct and a Tantalum-Zinc-Alkylidene Complex. Angewandte Chemie International Edition in English, 30(8), 996–998. doi:10.1002/anie.199109961
Amii, H., & Uneyama, K. (2009). C-F bond activation in organic synthesis. Chemical Reviews, 109(5), 2119–83. doi:10.1021/cr800388c
Andersson, P. G. (Ed.). (2011). Iridium Catalysis (Topics in Organometallic Chemistry) Vol. 34. Berlin: Springer-Verlag.
Baggaley, E., Weinstein, J. A., & Williams, J. A. G. (2012). Lighting the way to see inside the live cell with luminescent transition metal complexes. Coordination Chemistry Reviews, 256(15–16), 1762–1785. doi: shttp://dx.doi.org/10.1016/j.ccr.2012.03.018
Baldo, M. A., & Forrest, S. R. (1998). Highly efficient phosphorescent emission from organic electroluminescent devices, 395(September), 151–154.
Baldo, M. A., Lamansky, S., Burrows, P. E., Thompson, M. E., & Forrest, S. R. (1999). Very high-efficiency green organic light-emitting devices based on electrophosphorescence. Applied Physics Letters, 75, 4 – 6.
Balzani, V.; Scandola, F. (1991). Supramolecular Photochemistry. New York: Ellis Horwood, New York.
Balzani, V.; Venturi, M.; Credi, A. (2003). Molecular DeVices and Machines: A Journey into the Nanoworld. Wiley-VCH: Weinheim, Germany.
Barder, T. E., Walker, S. D., Martinelli, J. R., & Buchwald, S. L. (2005). Catalysts for Suzuki−Miyaura Coupling Processes: Scope and Studies of the Effect of Ligand Structure. Journal of the American Chemical Society, 127(13), 4685–4696. doi:10.1021/ja042491j
Barnard, P. J., & Berners-Price, S. J. (2007). Targeting the mitochondrial cell death pathway with gold compounds. Coordination Chemistry Reviews, 251(13-14), 1889–1902. doi:10.1016/j.ccr.2007.04.006
Bartlett, N. (1998). Relativistic Effects and the Chemistry of Gold *, 31(11), 22–25.
Basanez, G., Nechushtan, A., Drozhinin, O., Chanturiya, A., E, C., S, T., … J, Y. R. (1999). Bax , but not Bcl-x L , decreases the lifetime of planar phospholipid bilayer
324 membranes at subnanomolar concentrations. Proceedings of the National Academy of Sciences of the United States of America, 96(May), 5492–5497.
Bayler, A., Bowmaker, G. A., & Schmidbaur, H. (1996). Propeller Isomerism in Bis(trimesitylphosphine)gold(I), -silver(I), and -copper(I) Tetrafluoroborates. Inorganic Chemistry, 35(20), 5959–5960. doi:10.1021/ic960421a
Berners-Price, S. J. (2011). BioInorganic Medicinal Chemistry. In Bioinorganic Medicinal Chemistry, ed. E. Alessio, Wiley-VCH, Weinheim (pp. 197–221).
Brewster, T. P., Blakemore, J. D., Schley, N. D., Incarvito, C. D., Hazari, N., Brudvig, G. W., & Crabtree, R. H. (2011). An Iridium(IV) Species, [Cp*Ir(NHC)Cl]+, Related to a Water-Oxidation Catalyst. Organometallics, 30(5), 965–973. doi:10.1021/om101016s
Bronner, C., & Wenger, O. S. (2011). Luminescent cyclometalated gold(iii) complexes. Dalton Trans., 40(46), 12409–12420. doi:10.1039/C1DT10636H
Brownlee, R. T. C., & Craik, D. J. (1980). The relationship between 19F substituent chemical shifts and electron densities: meta- and para-substituted benzoyl fluorides. Organic Magnetic Resonance, 14(3), 186–191. doi:10.1002/mrc.1270140308
Bruce, D. W., Deschenaux, R., Donnio, B., & Guillon, D. (2007). ComprehensiVe Organometallic Chemistry III. (D. M. P. Mingos & R. H. Crabtree, Eds.) (p. 217). Amsterdam, The Netherlands: Elsevier.
Campbell, M. G., & Ritter, T. (2014). Late-Stage Fluorination: From Fundamentals to Application. Organic Process Research & Development, 18(4), 474–480. doi:10.1021/op400349g
Carrow, B. P., & Hartwig, J. F. (2011). Distinguishing Between Pathways for Transmetalation in Suzuki−Miyaura Reactions. Journal of the American Chemical Society, 133(7), 2116–2119. doi:10.1021/ja1108326
Carvajal, M. A., Novoa, J. J., & Alvarez, S. (2004). Choice of Coordination Number in d10 Complexes of Group 11 Metals. Journal of the American Chemical Society, 126(5), 1465–1477. doi:10.1021/ja038416a
Casini, A., Hartinger, C., Gabbiani, C., Mini, E., Dyson, P. J., Keppler, B. K., & Messori, L. (2008). Gold ( III ) compounds as anticancer agents : Relevance of gold – protein interactions for their mechanism of action. Journal of Inorganic Biochemistry, 102, 564–575. doi:10.1016/j.jinorgbio.2007.11.003
Chen, H.-F., Wu, C., Kuo, M.-C., Thompson, M. E., & Wong, K.-T. (2012). Anionic iridium complexes for solid state light-emitting electrochemical cells. J. Mater. Chem., 22(19), 9556–9561. doi:10.1039/C2JM30443K
325 Chen, Y., Qiao, L., Ji, L., & Chao, H. (2014). Phosphorescent iridium(III) complexes as multicolor probes for specific mitochondrial imaging and tracking. Biomaterials, 35(1), 2–13. doi:10.1016/j.biomaterials.2013.09.051
Chen, Z., Bian, Z., & Huang, C. (2010). Functional IrIII Complexes and Their Applications. Advanced Materials, 22(13), 1534–1539. doi:10.1002/adma.200903233
Cheng, Y., Meyers, J. D., Broome, A.-M., Kenney, M. E., Basilion, J. P., & Burda, C. (2011). Deep Penetration of a PDT Drug into Tumors by Noncovalent Drug-Gold Nanoparticle Conjugates. Journal of the American Chemical Society, 133(8), 2583– 2591. doi:10.1021/ja108846h
Chi, Y., & Chou, P.-T. (2007). Contemporary progresses on neutral{,} highly emissive Os(ii) and Ru(ii) complexes. Chem. Soc. Rev., 36(9), 1421–1431. doi:10.1039/B608951H
Chi, Y., & Chou, P.-T. (2010). Transition-metal phosphors with cyclometalating ligands: fundamentals and applications. Chemical Society Reviews, 39(2), 638–55. doi:10.1039/b916237b
Cinellu, M. a., Maiore, L., Manassero, M., Casini, A., Arca, M., Fiebig, H.-H., … Messori, L. (2010). [Au 2 (phen 2Me ) 2 (µ - O) 2 ](PF 6 ) 2 , a Novel Dinuclear Gold(III) Complex Showing Excellent Antiproliferative Properties. ACS Medicinal Chemistry Letters, 1(7), 336–339. doi:10.1021/ml100097f
Cope, A. C., & Siekman, R. W. (1965). Formation of Covalent Bonds from Platinum or Palladium to Carbon by Direct Substitution. Journal of the American Chemical Society, 87(14), 3272–3273. doi:10.1021/ja01092a063
Costa, R. D., Ortí, E., Bolink, H. J., Monti, F., Accorsi, G., & Armaroli, N. (2012). Luminescent Ionic Transition-Metal Complexes for Light-Emitting Electrochemical Cells. Angewandte Chemie International Edition, 51(33), 8178–8211. doi:10.1002/anie.201201471
Cotton, F. A., Wilkinson, G., Murillo, C. A., & Bochmann, M. (Eds.). (1998). Advanced Inorganic Chemistry (6th ed.). New York,: Wiley.
Cox, A. G., Brown, K. K., Arner, E. S. J., & Hampton, M. B. (2008). The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation. Biochemical Pharmacology, 76(9), 1097–1109. doi:http://dx.doi.org/10.1016/j.bcp.2008.08.021
Craig, S., Gao, L., Lee, I., Gray, T., & Berdis, A. J. (2012). Gold-Containing Indoles as Anticancer Agents That Potentiate the Cytotoxic Effects of Ionizing Radiation. Journal of Medicinal Chemistry, 55(5), 2437–2451. doi:10.1021/jm2005942
326 Daniel, M.-C., & Astruc, D. (2004). Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chemical Reviews, 104(1), 293–346. doi:10.1021/cr030698+
David, B., Monkowius, U., Rust, J., Lehmann, C. W., Hyzak, L., & Mohr, F. (2014). Gold(III) compounds containing a chelating{,} dicarbanionic ligand derived from 4{,}4{’}-di-tert-butylbiphenyl. Dalton Trans., 10.1039/C4DT00778F. doi:10.1039/C4DT00778F
Dive, D., & Biot, C. (2008). Ferrocene Conjugates of Chloroquine and other Antimalarials: the Development of Ferroquine, a New Antimalarial. ChemMedChem, 3(3), 383–391. doi:10.1002/cmdc.200700127
Dixon, I. M., Collin, J.-P., Sauvage, J.-P., Flamigni, L., Encinas, S., & Barigelletti, F. (2000). A family of luminescent coordination compounds: iridium() polyimine complexes. Chem. Soc. Rev., 29(6), 385–391. doi:10.1039/B000704H
Djukic, J.-P., Iali, W., Hijazi, A., & Ricard, L. (2011). Synthesis of a 2- benzocymantrenylpyridine and further mechanistic insights. Journal of Organometallic Chemistry, 696(10), 2101–2107. doi:10.1016/j.jorganchem.2010.11.012
Djukic, J.-P., Sortais, J.-B., Barloy, L., & Pfeffer, M. (2009). Cycloruthenated Compounds – Synthesis and Applications. European Journal of Inorganic Chemistry, 2009(7), 817–853. doi:10.1002/ejic.200801016
DDoherty, N. M., & Hoffmann, N. W. (1991). Transition-metal fluoro compounds containing carbonyl, phosphine, arsine, and stibine ligands. Chemical Reviews, 91(4), 553–573. doi:10.1021/cr00004a005
Duan, H., Sengupta, S., Petersen, J. L., Akhmedov, N. G., & Shi, X. (2009). Triazole−Au(I) Complexes: A New Class of Catalysts with Improved Thermal Stability and Reactivity for Intermolecular Alkyne Hydroamination. Journal of the American Chemical Society, 131(34), 12100–12102. doi:10.1021/ja9041093
Dupont, J., Consorti, C. S., & Spencer, J. (2005). The potential of palladacycles: more than just precatalysts. Chemical Reviews, 105(6), 2527–71. doi:10.1021/cr030681r
Dupont, J., & Pfeffer, M. (Eds.). (2008). Palladacycles. Weinheim, Germany: Wiley- VCH.
Eliseeva, S. V, & Bunzli, J.-C. G. (2010). Lanthanide luminescence for functional materials and bio-sciences. Chem. Soc. Rev., 39(1), 189–227. doi:10.1039/B905604C
327 Esswein, A. J., & Nocera, D. G. (2007). Hydrogen production by molecular photocatalysis. Chemical Reviews, 107(10), 4022–47. doi:10.1021/cr050193e
Fagnou, K., & Lautens, M. (2003). Rhodium-catalyzed carbon-carbon bond forming reactions of organometallic compounds. Chemical Reviews, 103(1), 169–96. doi:10.1021/cr020007u
Fan, C., Zhu, L., Liu, T., Jiang, B., Ma, D., Qin, J., & Yang, C. (2014). Using an organic molecule with low triplet energy as a host in a highly efficient blue electrophosphorescent device. Angewandte Chemie (International Ed. in English), 53(8), 2147–51. doi:10.1002/anie.201308046
Fernández-Hernández, J. M., Beltrán, J. I., Lemaur, V., Gálvez-López, M.-D., Chien, C.- H., Polo, F., … De Cola, L. (2013). Iridium(III) Emitters Based on 1,4- Disubstituted-1H-1,2,3-triazoles as Cyclometalating Ligand: Synthesis, Characterization, and Electroluminescent Devices. Inorganic Chemistry, 52(4), 1812–1824. doi:10.1021/ic3018419
Fernandez-Moreira, V., Thorp-Greenwood, F. L., & Coogan, M. P. (2010). Application of d6 transition metal complexes in fluorescence cell imaging. Chem. Commun., 46(2), 186–202. doi:10.1039/B917757D
Fier, P. S., & Hartwig, J. F. (2013). Selective C-H Fluorination of Pyridines and Diazines Inspired by a Classic Amination Reaction. Science , 342 (6161 ), 956–960. Retrieved from http://www.sciencemag.org/content/342/6161/956.abstract
Fieser, L. F., & Fieser, M. (1968). Reagents for Organic Synthesis. Louis F. Fieser and Mary Fieser. Wiley, New York, 1967. 1469 pp., illus. $27.50. Reagents for Organic Synthesis. Louis F. Fieser and Mary Fieser. Wiley, New York, 668. doi:10.1126/science.159.3810.74
Furuya, T., Benitez, D., Tkatchouk, E., Strom, A. E., Tang, P., Goddard, W. A., & Ritter, T. (2010). Mechanism of C−F Reductive Elimination from Palladium(IV) Fluorides. Journal of the American Chemical Society, 132(11), 3793–3807. doi:10.1021/ja909371t
Furuya, T., Kamlet, A. S., & Ritter, T. (2011). Catalysis for fluorination and trifluoromethylation. Nature, 473(7348), 470–477. Retrieved from http://dx.doi.org/10.1038/nature10108
Gandhi, B. V., Plunkett, W., Weller, S., Du, M., Ayres, M., Rodriguez, C. O., … Keating, M. J. (2001). Fludarabine in Leukemias : Clinical Response ,. Journal of Clinical Oncology, 19(8), 2142–2152.
Gao, L., Niedzwiecki, D. S., Deligonul, N., Zeller, M., Hunter, A. D., & Gray, T. G. (2012). Gold(I) Styrylbenzene, Distyrylbenzene, and Distyrylnaphthalene
328 Complexes: High Emission Quantum Yields at Room Temperature. Chemistry – A European Journal, 18(20), 6316–6327. doi:10.1002/chem.201102502
Gao, L., Peay, M. A., Partyka, D. V, Updegraff, J. B., Teets, T. S., Esswein, A. J., … Gray, T. G. (2009). Mono- and Di-Gold(I) Naphthalenes and Pyrenes: Syntheses, Crystal Structures, and Photophysics. Organometallics, 28(19), 5669–5681. doi:10.1021/om9005214
Garg, J. A., Blacque, O., Fox, T., & Venkatesan, K. (2010). Stable and tunable phosphorescent neutral cyclometalated Au(III) diaryl complexes. Inorganic Chemistry, 49(24), 11463–72. doi:10.1021/ic101437h
Ghidiu, M. J., Pistner, A. J., Yap, G. P. A., Lutterman, D. A., & Rosenthal, J. (2013). Thermal versus Photochemical Reductive Elimination of Aryl Chlorides from NHC–Gold Complexes. Organometallics, 32(18), 5026–5029. doi:10.1021/om400701f
Gilbert, T. M., & Bergman, R. G. (1983). Preparation and reactions of tetrahydrido(pentamethylcyclopentadienyl)iridium: a novel iridium(V) polyhydride. Organometallics, 2(10), 1458–1460. doi:10.1021/om50004a037
Gilges, H., & Schubert, U. (1998). Transition Metal Silyl Complexes. 59.1 Oxidative Addition of Nonactivated Si−C Bonds to Platinum(0) Centers. Organometallics, 17(22), 4760–4761. doi:10.1021/om9805335
Gill, M. R., Garcia-Lara, J., Foster, S. J., Smythe, C., Battaglia, G., & Thomas, J. A. (2009). A ruthenium(II) polypyridyl complex for direct imaging of DNA structure in living cells. Nat Chem, 1(8), 662–667. Retrieved from http://dx.doi.org/10.1038/nchem.406
Go, Y.-M., & Jones, D. P. (2010). Redox Control Systems in the Nucleus: Mechanisms and Functions. Antioxidants & Redox Signaling, 13, 489–509. Retrieved from http://online.liebertpub.com/doi/full/10.1089/ars.2009.3021
Goldman, A. S., & Goldberg, K. I. (2004). Chapter 1 Organometallic C-H Bond Activation : An Introduction Setting the Stage for C-H Activation ( and the Opening Acts ). ACS Symposium Series 885, 1–43.
Goldman, A. S., Roy, A. H., Huang, Z., Ahuja, R., Schinski, W., & Brookhart, M. (2006). Catalytic Alkane Metathesis by Tandem Alkane Dehydrogenation-Olefin Metathesis. Science , 312 (5771 ), 257–261. doi:10.1126/science.1123787
Gorin, D. J., & Toste, F. D. (2007). Relativistic effects in homogeneous gold catalysis. Nature, 446(7134), 395–403. Retrieved from http://dx.doi.org/10.1038/nature05592
329 Greenwood, N. N., & Earnshaw, A. (1997). Chemistry of the Elements (2nd ed.) (pp. 1113–1143). Oxford: Butterworth–Heinemann.
Guenther, J., Mallet-Ladeira, S., Estevez, L., Miqueu, K., Amgoune, A., & Bourissou, D. (2014). Activation of aryl halides at gold(I): practical synthesis of (P,C) cyclometalated gold(III) complexes. Journal of the American Chemical Society, 136(5), 1778–81. doi:10.1021/ja412432k
Guo, Z., Nam, S., Park, S., & Yoon, J. (2012). A highly selective ratiometric near- infrared fluorescent cyanine sensor for cysteine with remarkable shift and its application in bioimaging. Chem. Sci., 3(9), 2760–2765. doi:10.1039/C2SC20540H
Hashmi, A. S. K., & Hutchings, G. J. (2006). Gold Catalysis. Angewandte Chemie International Edition, 45(47), 7896–7936. doi:10.1002/anie.200602454
Heckler, J. E., Zeller, M., Hunter, A. D., & Gray, T. G. (2012). Geminally Diaurated Gold(I) Aryls from Boronic Acids. Angewandte Chemie International Edition, 51(24), 5924–5928. doi:10.1002/anie.201201744
Hirayama, T., Okuda, K., & Nagasawa, H. (2013). A highly selective turn-on fluorescent probe for iron(ii) to visualize labile iron in living cells. Chem. Sci., 4(3), 1250–1256. doi:10.1039/C2SC21649C
Hofer, M., Gomez-Bengoa, E., & Nevado, C. (2014). A Neutral Gold(III)–Boron Transmetalation. Organometallics, 33(6), 1328–1332. doi:10.1021/om400884s
Holder, E., Langeveld, B. M. W., & Schubert, U. S. (2005). New Trends in the Use of Transition Metal-Ligand Complexes for Applications in Electroluminescent Devices. Advanced Materials, 17(9), 1109–1121. doi:10.1002/adma.200400284
Hollingworth, C., & Gouverneur, V. (2013). Strategies Towards Challenging Fluorination Reactions. In X. Ribas (Ed.), C–H and C–X Bond Functionalization: Transition Metal Mediation (pp. 193–261). RSC Catalysis Series No. 11; Royal Society of Chemistry.
Huang, P., Chubb, S., Hertel, L. W., Grindey, G. B., & Plunkett, W. (1991). Action of 2 ′ , 2 ′ -Difluorodeoxycytidine on DNA Synthesis Action of 2 ’, 2 ' - Difluorodeoxycytidine on DNA Synthesis. Cancer Research, 51, 6110–6117.
Isozaki, K., Takaya, H., & Naota, T. (2007). Ultrasound-Induced Gelation of Organic Fluids with Metalated Peptides. Angewandte Chemie International Edition, 46(16), 2855–2857. doi:10.1002/anie.200605067
Jamieson, E. R., & Lippard, S. J. (1999). Structure , Recognition , and Processing of Cisplatin − DNA Adducts.
330 Jiang, W., Gao, Y., Sun, Y., Ding, F., Xu, Y., Bian, Z., … Huang, C. (2010). Zwitterionic Iridium Complexes: Synthesis, Luminescent Properties, and Their Application in Cell Imaging. Inorganic Chemistry, 49(7), 3252–3260. doi:10.1021/ic9021239
Kaltsoyannis, N. (1996). Relativistic e ff ects in inorganic and organometallic chemistry †. J. Chem. Soc., Dalton Trans., 1–11.
Kalyanasundaram, K. (1992). Photochemistry of Polypyridine and Porphyrin complexes. Academic Press, London.
Kastner, M. E., Coffey, K. F., Clarke, M. J., Edmonds, S. E., & Eriks, K. (1981). Structural correlation and metal ion movement in stable pentaammineruthenium(III)-hypoxanthine complexes. Journal of the American Chemical Society, 103(19), 5747–5752. doi:10.1021/ja00409a022
Kean, W. F., & Kean, I. R. L. (2008). Clinical pharmacology of gold. Inflammopharmacology, 16(3), 112–25. doi:10.1007/s10787-007-0021-x
Kilpin, K. J., Henderson, W., & Nicholson, B. K. (2007). Organogold(III) complexes containing chelating bis(amidate) ligands: Synthesis, characterisation and biological activity. Polyhedron, 26(2), 434–447. doi:http://dx.doi.org/10.1016/j.poly.2006.06.036
Kim, M. K., Lim, C. S., Hong, J. T., Han, J. H., Jang, H.-Y., Kim, H. M., & Cho, B. R. (2010). Sodium-Ion-Selective Two-Photon Fluorescent Probe for In Vivo Imaging. Angewandte Chemie International Edition, 49(2), 364–367. doi:10.1002/anie.200904835
Kläring, P., & Braun, T. (2013). Insertion of CS2 into Iridium–Fluorine Bonds. Angewandte Chemie International Edition, 52(42), 11096–11101. doi:10.1002/anie.201305106
Kläring, P., Jungton, A.-K., Braun, T., & Müller, C. (2012). Synthesis, Structure and Reactivity of Iridium Hydrido Fluorido Complexes. European Journal of Inorganic Chemistry, 2012(9), 1430–1436. doi:10.1002/ejic.201100917
Kobayashi, H., Ogawa, M., Alford, R., Choyke, P. L., & Urano, Y. (2009). New Strategies for Fluorescent Probe Design in Medical Diagnostic Imaging. Chemical Reviews, 110(5), 2620–2640. doi:10.1021/cr900263j
Komiya, S., & Shibue, A. (1985). Steric and electronic effects of the tertiary phosphine ligand on the dissociative reductive elimination from cis- aryldimethyl(triarylphosphine)gold(III). Organometallics, 4(4), 684–687. doi:10.1021/om00123a012
331 Kong, W., Engel, K., & Wang, J. (2004). Mammalian nucleoside transporters. Current Drug Metabolism. Current Drug Metabolism, 5, 63–84.
Koren, K., Dmitriev, R. I., Borisov, S. M., Papkovsky, D. B., & Klimant, I. (2012). Complexes of IrIII-Octaethylporphyrin with Peptides as Probes for Sensing Cellular O2. ChemBioChem, 13(8), 1184–1190. doi:10.1002/cbic.201200083
Kovala-Demertzi, D., Tauridou, P., Russo, U., & Gielen, M. (1995). Adducts of organotin(IV), tin(IV) and tin(II) halides with 1-methyl-imidazoline-2(3H)-thione (Hmimt) and imidazoline-2(1,3H)-thione (Himt). Synthesis, spectroscopic (IR, Mössbauer and 1H, 13C, 119Sn NMR) studies and in vitro antitumour activity. Inorganica Chimica Acta, 239(1–2), 177–183. doi:http://dx.doi.org/10.1016/0020- 1693(95)04725-5
Laitar, D. S., Müller, P., Gray, T. G., & Sadighi, J. P. (2005). A Carbene-Stabilized Gold(I) Fluoride: Synthesis and Theory. Organometallics, 24(19), 4503–4505. doi:10.1021/om050619f
Lee, H. G., Milner, P. J., & Buchwald, S. L. (2014). Pd-Catalyzed Nucleophilic Fluorination of Aryl Bromides. Journal of the American Chemical Society, 136(10), 3792–3795. doi:10.1021/ja5009739
Lee, K.-S., Kim, T.-K., Lee, J. H., Kim, H.-J., & Hong, J.-I. (2008). Fluorescence turn-on probe for homocysteine and cysteine in water. Chem. Commun., (46), 6173–6175. doi:10.1039/B814581D
Lee, P.-K., Law, W. H.-T., Liu, H.-W., & Lo, K. K.-W. (2011). Luminescent Cyclometalated Iridium(III) Polypyridine Di-2-picolylamine Complexes: Synthesis, Photophysics, Electrochemistry, Cation Binding, Cellular Internalization, and Cytotoxic Activity. Inorganic Chemistry, 50(17), 8570–8579. doi:10.1021/ic201153d
Lee, P.-K., Liu, H.-W., Yiu, S.-M., Louie, M.-W., & Lo, K. K.-W. (2011). Luminescent cyclometallated iridium(iii) bis(quinolylbenzaldehyde) diimine complexes- synthesis{,} photophysics{,} electrochemistry{,} protein cross-linking properties{,} cytotoxicity and cellular uptake. Dalton Trans., 40(10), 2180–2189. doi:10.1039/C0DT00501K
Lenker, H. K., Gray, T. G., & Stockland, R. A. (2012). Rapid synthesis of arylgold compounds using dielectric heating. Dalton Trans., 41(43), 13274–13276. doi:10.1039/C2DT32129G
Liang, T., Neumann, C. N., & Ritter, T. (2013). Introduction of Fluorine and Fluorine- Containing Functional Groups. Angewandte Chemie International Edition, 52(32), 8214–8264. doi:10.1002/anie.201206566
332 Lide, D. R. (Ed.). (n.d.). CRC Handbook of Chemistry and Physics (74th ed.). Boca Raton, FL: CRC Press.
Lippert, A. R., New, E. J., & Chang, C. J. (2011). Reaction-Based Fluorescent Probes for Selective Imaging of Hydrogen Sulfide in Living Cells. Journal of the American Chemical Society, 133(26), 10078–10080. doi:10.1021/ja203661j
Liu, J., Liu, Y., Liu, Q., Li, C., Sun, L., & Li, F. (2011). Iridium(III) Complex-Coated Nanosystem for Ratiometric Upconversion Luminescence Bioimaging of Cyanide Anions. Journal of the American Chemical Society, 133(39), 15276–15279. doi:10.1021/ja205907y
Liu, X., Xi, N., Liu, S., Ma, Y., Yang, H., Li, H., … Huang, W. (2012). Highly selective phosphorescent nanoprobes for sensing and bioimaging of homocysteine and cysteine. J. Mater. Chem., 22(16), 7894–7901. doi:10.1039/C2JM15946E
Lo, K. K.-W., Leung, S.-K., & Pan, C.-Y. (2012). Luminescent iridium(III) arylbenzothiazole complexes: Photophysics, electrochemistry, bioconjugation, and cellular uptake. Inorganica Chimica Acta, 380(0), 343–349. doi:http://dx.doi.org/10.1016/j.ica.2011.10.072
Lukens, W. W., Smith, M. R., & Andersen, R. A. (1996). A π-Donor Spectrochemical Series for X in (Me5C5)2TiX, and β-Agostic Interactions in X = Et and N(Me)Ph. Journal of the American Chemical Society, 118(7), 1719–1728. doi:10.1021/ja953272o
M. Jensen, C. (1999). Iridium PCP pincer complexes: highly active and robust catalysts for novel homogeneous aliphatic dehydrogenations. Chem. Commun., (24), 2443– 2449. doi:10.1039/A903573G
Maity, A., Anderson, B. L., Deligonul, N., & Gray, T. G. (2013). Room-temperature synthesis of cyclometalated iridium(iii) complexes: kinetic isomers and reactive functionalities. Chemical Science, 4(3), 1175. doi:10.1039/c2sc21831c
Maity, A., Choi, J.-S., Teets, T. S., Deligonul, N., Berdis, A. J., & Gray, T. G. (2013). Cyclometalated Iridium(III) Complexes with Deoxyribose Substituents. Chemistry – A European Journal, 19(47), 15924–15932. doi:10.1002/chem.201301776
Mak, K. H. G., Chan, P. K., Fan, W. Y., Ganguly, R., & Leong, W. K. (2013). Photochemical Reaction of Cp*Ir(CO)2 with C6F5X (X = CN, F): Formation of Diiridium(II) Complexes. Organometallics, 32(4), 1053–1059. doi:10.1021/om301055h
Mankad, N. P., & Toste, F. D. (2010). C−C Coupling Reactivity of an Alkylgold(III) Fluoride Complex with Arylboronic Acids. Journal of the American Chemical Society, 132(37), 12859–12861. doi:10.1021/ja106257n
333 Marzano, C., Gandin, V., Folda, A., Scutari, G., Bindoli, A., & Rigobello, M. P. (2007). Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin- resistant human ovarian cancer cells. Free Radical Biology & Medicine, 42(6), 872– 81. doi:10.1016/j.freeradbiomed.2006.12.021
Mayer, J. M. (1988). Why Are There No Terminal Oxo Complexes of the Late Transition Metals? or The Importance of Metal–Ligand π Antibonding Interactions. Comments on Inorganic Chemistry, 8(4), 125–135. doi:10.1080/02603598808035790
McDaniel, N. D., Coughlin, F. J., Tinker, L. L., & Bernhard, S. (2008). Cyclometalated iridium(III) Aquo complexes: efficient and tunable catalysts for the homogeneous oxidation of water. Journal of the American Chemical Society, 130(1), 210–7. doi:10.1021/ja074478f
Mckeage, M. J., Maharaj, L., & Berners-price, S. J. (2002). Mechanisms of cytotoxicity and antitumor acti v ity of gold ( I ) phosphine complexes : the possible role of mitochondria. Coordination Chemistry Reviews, 232, 127–135.
McKelvey, D. R. (1983). Relativistic effects on chemical properties. Journal of Chemical Education, 60(2), 112. doi:10.1021/ed060p112
Melgarejo, D. Y., Chiarella, G. M., Fackler, J. P., Perez, L. M., Rodrigue-Witchel, A., & Reber, C. (2011). Synthesis and Structure of a Dinuclear Gold(II) Complex with Terminal Fluoride Ligands. Inorganic Chemistry, 50(10), 4238–4240. doi:10.1021/ic200394q
Montalti, M.; Credi, A.; Prodi, L.; Gandolfi, M. T. (2006). Handbook of Photochemistry. Boca Raton, FL: CRC Press.
Montgomery, C. P., Murray, B. S., New, E. J., Pal, R., & Parker, D. (2009). Cell- Penetrating Metal Complex Optical Probes: Targeted and Responsive Systems Based on Lanthanide Luminescence. Accounts of Chemical Research, 42(7), 925– 937. doi:10.1021/ar800174z
Moore, E. G., Samuel, A. P. S., & Raymond, K. N. (2009). From Antenna to Assay: Lessons Learned in Lanthanide Luminescence. Accounts of Chemical Research, 42(4), 542–552. doi:10.1021/ar800211j
Nazeeruddin, M. K., Klein, C., Grätzel, M., Zuppiroli, L., & Berner, D. (2008). Highly Efficient OLEDs with Phosphorescent Materials. (H. Yersin, Ed.) (pp. 363–390). Wiley-VCH, Weinheim.
Negishi, E. -i. (Ed.). (2002). Organopalladium: In Handbook of Organopalladium Chemistry for Organic Synthesis (pp. 973–993). New York: John Wiley & Sons.
334 Ohki, Y., Hatanaka, T., & Tatsumi, K. (2008). C−H Bond Activation of Heteroarenes Mediated by a Half-Sandwich Iron Complex of N-Heterocyclic Carbene. Journal of the American Chemical Society, 130(50), 17174–17186. doi:10.1021/ja8063028
Omae, I. (1986). Organometallic Intramolecular Coordination Compounds. The Netherlands, Amsterdam: Elsevier.
Partyka, D. V, Robilotto, T. J., Zeller, M., Hunter, A. D., & Gray, T. G. (2008). A porphyrin complex of gold(I): (phosphine)gold(I) azides as cation precursors. Proceedings of the National Academy of Sciences of the United States of America, 105(38), 14293–7. doi:10.1073/pnas.0806520105
Pissuwan, D., Valenzuela, S. M., & Cortie, M. B. (2006). Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends in Biotechnology, 24(2), 62–67. doi:http://dx.doi.org/10.1016/j.tibtech.2005.12.004
Pitzer, K. S. (1979). Relativistic effects on chemical properties. Accounts of Chemical Research, 12(8), 271–276. doi:10.1021/ar50140a001
Poulton, J. T., Sigalas, M. P., Folting, K., Streib, W. E., Eisenstein, O., & Caulton, K. G. (1994). RuHX(CO)(PR3)2: Can .nu.CO Be a Probe for the Nature of the Ru-X Bond? Inorganic Chemistry, 33(7), 1476–1485. doi:10.1021/ic00085a043
Powers, D. C., & Ritter, T. (2009). Bimetallic Pd(III) complexes in palladium-catalysed carbon–heteroatom bond formation. Nat Chem, 1(4), 302–309. Retrieved from http://dx.doi.org/10.1038/nchem.246
Poznjak, A. L., Pawlowski, V. I., Schkolnikowa, L. M., Djatlowa, N. M., & Iljuchin, A. B. (1986). Cyclometallierende photodecarboxylierung von cobalt(III)-komplexen mit 1-diethylentriaminmono-3-propionat. Journal of Organometallic Chemistry, 314(1–2), C59 – C62. doi:http://dx.doi.org/10.1016/0022-328X(86)80384-9
Procopio, L. J., Carroll, P. J., & Berry, D. H. (1994). Agostic .beta.-silicon-hydrogen interactions in silylamido complexes of zirconocene. Journal of the American Chemical Society, 116(1), 177–185. doi:10.1021/ja00080a020
Pyykkö, P. (2004). Theoretical chemistry of gold. Angewandte Chemie (International Ed. in English), 43(34), 4412–56. doi:10.1002/anie.200300624
Pyykkö, P. (2005). Theoretical chemistry of gold. II. Inorganica Chimica Acta, 358(14), 4113–4130. doi:10.1016/j.ica.2005.06.028
Qian, Y., Karpus, J., Kabil, O., Zhang, S.-Y., Zhu, H.-L., Banerjee, R., … He, C. (2011). Selective fluorescent probes for live-cell monitoring of sulphide. Nat Commun, 2, 495. Retrieved from http://dx.doi.org/10.1038/ncomms1506
335 Rios, D., Olmstead, M. M., & Balch, A. L. (2009). Blue-, Green- and Non-luminescent Crystals from One Reaction. Isolation and Structural Characterization of a Series of Gold(I)-Siver(I) Heterometallic Complexes Utilizing a Gold Carbene Metalloligand Containing Free Amino Groups. Inorganic Chemistry, 48(12), 5279–5287. doi:10.1021/ic900243v
Robak, T., Lech-Maranda, E., Korycka, A., & Robak, E. (2006). Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity. Curr. Med. Chem., 13, 3165–3189.
Rubbiani, R., Kitanovic, I., Alborzinia, H., Can, S., Kitanovic, A., Onambele, L. a, … Ott, I. (2010). Benzimidazol-2-ylidene gold(I) complexes are thioredoxin reductase inhibitors with multiple antitumor properties. Journal of Medicinal Chemistry, 53(24), 8608–18. doi:10.1021/jm100801e
Rudolph, M., & Hashmi, A. S. K. (2012). Gold catalysis in total synthesis-an update. Chem. Soc. Rev., 41(6), 2448–2462. doi:10.1039/C1CS15279C
Ruggi, A.; Reinhoudt, D. N.; Velders, A. H. (2011). Bioinorganic Medicinal Chemistry. In In Bioinorganic Medicinal Chemistry (p. 397−421). New York: Wiley.
Ryabov, A. D. (1990). Mechanisms of intramolecular activation of carbon-hydrogen bonds in transition-metal complexes. Chemical Reviews, 90(2), 403–424. doi:10.1021/cr00100a004
Ryabov, A. D., Sukharev, V. S., Alexandrova, L., Le Lagadec, R., & Pfeffer, M. (2001). New Synthesis and New Bio-Application of Cyclometalated Ruthenium(II) Complexes for Fast Mediated Electron Transfer with Peroxidase and Glucose Oxidase. Inorganic Chemistry, 40(25), 6529–6532. doi:10.1021/ic010423h
Rybtchinski, B., & Milstein, D. (1999). Metal Insertion into C−C Bonds in Solution. Angewandte Chemie International Edition, 38(7), 870–883. doi:10.1002/(SICI)1521-3773(19990401)38:7<870::AID-ANIE870>3.0.CO;2-3
Schmidbaur, H., Grohmann, A., Olmos, M. E. (1999). Organogold chemistry. In H. Schmidbaur (Ed.), Organogold Chemistry. In Gold: Progress in Chemistry, Biochemistry and Technology (pp. 647–746). Wiley: Chichester.
Schmidbaur, H.; Schier, A. In ; Crabtree, R. H.; Mingos, D. M. P., E. (2006). Comprehensive Organometallic Chemistry III Volume 2, Section 2.05. Elsevier.
Schneider, W., Bauer, A., & Schmidbaur, H. (1996). (Isocyanide)gold(I) Thiosalicylates: Supramolecular Assembly Based on both Auriophilic and Hydrogen Bonding. Organometallics, 15(26), 5445–5446. doi:10.1021/om960682s
336 Schwerdtfeger, P., Boyd, P. D. W., Brienne, S., & Burrell, A. K. (1992). Relativistic effects in gold chemistry. 4. Gold(III) and gold(V) compounds. Inorganic Chemistry, 31(16), 3411–3422. doi:10.1021/ic00042a016
Schwerdtfeger, P., Hermann, H. L., & Schmidbaur, H. (2003). Stability of the Gold(I)−Phosphine Bond. A Comparison with Other Group 11 Elements. Inorganic Chemistry, 42(4), 1334–1342. doi:10.1021/ic026098v
Scott, J., Basuli, F., Fout, A. R., Huffman, J. C., & Mindiola, D. J. (2008). Evidence for the Existence of a Terminal Imidoscandium Compound: Intermolecular CH Activation and Complexation Reactions with the Transient Sc⎭NAr Species. Angewandte Chemie International Edition, 47(44), 8502–8505. doi:10.1002/anie.200803325
Seidel, S. W., Schrock, R. R., & Davis, W. M. (1998). Tungsten and Molybdenum Alkyl or Aryl Complexes That Contain the [(C6F5NCH2CH2)3N]3- Ligand. Organometallics, 17(6), 1058–1068. doi:10.1021/om970966s
Seo, J. H.; Kim, Y. K.; Ha, Y. (2009). Efficient Blue-Green Organic Light- Emitting Diodes Based on Heteroleptic Tris-Cyclometalated Iridium- (III) Complexes. Thin Solid Films, 517, 1807−1810.
Severin, K., Bergs, R., & Beck, W. (1998). Bioorganometallic Chemistry - Transition Metal Complexes with α-Amino Acids and Peptides. Angewandte Chemie International Edition, 37(12), 1634–1654. doi:10.1002/(SICI)1521- 3773(19980703)37:12<1634::AID-ANIE1634>3.0.CO;2-C
Seyedsayamdost, M. R., Reece, S. Y., Nocera, D. G., & Stubbe, J. (2006). Mono-, Di-, Tri-, and Tetra-Substituted Fluorotyrosines: New Probes for Enzymes That Use Tyrosyl Radicals in Catalysis†. Journal of the American Chemical Society, 128(5), 1569–1579. doi:10.1021/ja055926r
Shavaleev, N. M., Monti, F., Costa, R. D., Scopelliti, R., Bolink, H. J., Ortí, E., … Nazeeruddin, M. K. (2012). Bright Blue Phosphorescence from Cationic Bis- Cyclometalated Iridium(III) Isocyanide Complexes. Inorganic Chemistry, 51(4), 2263–2271. doi:10.1021/ic202297h
Shaw, A. P., Tilset, M., Heyn, R. H., & Jakobsen, S. (2011). Microwave methods for the synthesis of gold(III) complexes. Journal of Coordination Chemistry, 64(1), 38–47. doi:10.1080/00958972.2010.521818
Shaw, C. F. I. (1999). Gold-Based Therapeutic Agents. Chemical Reviews, 99, 2589– 2600.
Shi, H., Sun, H., Yang, H., Liu, S., Jenkins, G., Feng, W., … Huang, W. (2013). Cationic Polyfluorenes with Phosphorescent Iridium(III) Complexes for Time-Resolved
337 Luminescent Biosensing and Fluorescence Lifetime Imaging. Advanced Functional Materials, 23(26), 3268–3276. doi:10.1002/adfm.201202385
Shi, Y., Ramgren, S. D., & Blum, S. A. (2009). Palladium-Catalyzed Carboauration of Alkynes and Palladium/Gold Cross-Coupling. Organometallics, 28(5), 1275–1277. doi:10.1021/om801206g
Smith, S. E., Sasaki, J. M., Bergman, R. G., Mondloch, J. E., & Finke, R. G. (2008). Platinum-Catalyzed Phenyl and Methyl Group Transfer from Tin to Iridium: Evidence for an Autocatalytic Reaction Pathway with an Unusual Preference for Methyl Transfer. Journal of the American Chemical Society, 130(6), 1839–1841. doi:10.1021/ja710365x
Suzuki, A. (1999). Recent advances in the cross-coupling reactions of organoboron derivatives with organic electrophiles, 1995–1998. Journal of Organometallic Chemistry, 576(1-2), 147–168. doi:10.1016/S0022-328X(98)01055-9
Swager, T. M. (2011). “Click” synthesis of heteroleptic tris-cyclometalated iridium(III) complexes: Cu(I) triazolide intermediates as transmetalating reagents. Inorganic Chemistry, 50(16), 7598–609. doi:10.1021/ic2005985
The definition as applied here excludes reactions leading to complexes with chelating π- bound carbon ligands, as in (heteroatom-)function- alized Cp or arene complexes. (n.d.).
Urig, S., Fritz-Wolf, K., Réau, R., Herold-Mende, C., Tóth, K., Davioud-Charvet, E., & Becker, K. (2006). Undressing of phosphine gold(I) complexes as irreversible inhibitors of human disulfide reductases. Angewandte Chemie (International Ed. in English), 45(12), 1881–6. doi:10.1002/anie.200502756
Vaupel, P., & Mayer, A. (2005). Hypoxia and anemia: effects on tumor biology and treatment resistance. Transfusion Clinique et Biologique, 12(1), 5–10. doi:http://dx.doi.org/10.1016/j.tracli.2004.11.005
Vela, J., Smith, J. M., Yu, Y., Ketterer, N. A., Flaschenriem, C. J., Lachicotte, R. J., & Holland, P. L. (2005). Synthesis and Reactivity of Low-Coordinate Iron(II) Fluoride Complexes and Their Use in the Catalytic Hydrodefluorination of Fluorocarbons. Journal of the American Chemical Society, 127(21), 7857–7870. doi:10.1021/ja042672l
Veltheer, J. E., Burger, P., & Bergman, R. G. (1995). Synthesis and Chemistry of the Aryliridium(III) Fluorides Cp’Ir(PMe3)(Aryl)F: High Reactivity due to Surprisingly Easy Ir-F Ionization. Journal of the American Chemical Society, 117(50), 12478– 12488. doi:10.1021/ja00155a012
338 Wallwork, S. C. (1962). Hydrogen-bond radii. Acta Crystallographica, 15(8), 758–759. doi:10.1107/S0365110X6200198X
Wang, F., Banerjee, D., Liu, Y., Chen, X., & Liu, X. (2010). Upconversion nanoparticles in biological labeling{,} imaging{,} and therapy. Analyst, 135(8), 1839–1854. doi:10.1039/C0AN00144A
Wang, J., Karpus, J., Zhao, B. S., Luo, Z., Chen, P. R., & He, C. (2012). A Selective Fluorescent Probe for Carbon Monoxide Imaging in Living Cells. Angewandte Chemie International Edition, 51(38), 9652–9656. doi:10.1002/anie.201203684
Wenzel, A. G., & Grubbs, R. H. (2006). Ruthenium Metallacycles Derived from 14- Electron Complexes. New Insights into Olefin Metathesis Intermediates. Journal of the American Chemical Society, 128(50), 16048–16049. doi:10.1021/ja0666598
Wilkinson, G., Gillard, R. D., & McCleverty, J. A. (1987). Comprehensive Coordination Chemistry. Pergamon, Oxford.
Wong, K.-Y. (2008). A highly selective luminescent switch-on probe for histidine/histidine-rich proteins and its application in protein staining. Angewandte Chemie (International Ed. in English), 47(20), 3735–9. doi:10.1002/anie.200705319
Wu, C.-C. (2008). Highly efficient blue-emitting iridium(III) carbene complexes and phosphorescent OLEDs. Angewandte Chemie (International Ed. in English), 47(24), 4542–5. doi:10.1002/anie.200800748
Yan, K., Lok, C.-N., Bierla, K., & Che, C.-M. (2010). Gold(I) complex of N,N’- disubstituted cyclic thiourea with in vitro and in vivo anticancer properties-potent tight-binding inhibition of thioredoxin reductase. Chemical Communications (Cambridge, England), 46(41), 7691–3. doi:10.1039/c0cc01058h
Ye, Y., Schimler, S. D., Hanley, P. S., & Sanford, M. S. (2013). Cu(OTf)2-Mediated Fluorination of Aryltrifluoroborates with Potassium Fluoride. Journal of the American Chemical Society, 135(44), 16292–16295. doi:10.1021/ja408607r
Yersin, H.; Finkenzeller, W. J. (2008). Highly Efficient OLEDs with Phosphorescent Materials (H. Yersin., pp. 1–97). Wiley-VCH: Weinheim, Germany.
Yoshihara, T., Yamaguchi, Y., Hosaka, M., Takeuchi, T., & Tobita, S. (2012). Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells. Angewandte Chemie International Edition, 51(17), 4148–4151. doi:10.1002/anie.201107557
You, Y., & Nam, W. (2012c). Photofunctional triplet excited states of cyclometalated Ir(III) complexes: beyond electroluminescence. Chemical Society Reviews, 41(21), 7061–84. doi:10.1039/c2cs35171d
339 You, Y., & Park, S. Y. (2005). Inter-ligand energy transfer and related emission change in the cyclometalated heteroleptic iridium complex: facile and efficient color tuning over the whole visible range by the ancillary ligand structure. Journal of the American Chemical Society, 127(36), 12438–9. doi:10.1021/ja052880t
Yuan, Y.-J., Yu, Z.-T., Chen, X.-Y., Zhang, J.-Y., & Zou, Z.-G. (2011). Visible-Light- Driven H2 Generation from Water and CO2 Conversion by Using a Zwitterionic Cyclometalated Iridium(III) Complex. Chemistry – A European Journal, 17(46), 12891–12895. doi:10.1002/chem.201102147
Zhou, C., Shi, Y., Ding, X., Li, M., Luo, J., Lu, Z., & Xiao, D. (2012). Development of a Fast and Sensitive Glucose Biosensor Using Iridium Complex-Doped Electrospun Optical Fibrous Membrane. Analytical Chemistry, 85(2), 1171–1176. doi:10.1021/ac303107d
340