Organoplatinum(ll) Gomplexes with Hyd rogen-Bond i ng F u nctional itY YO and Their Potential Use as Molecular Receptors for Adeni ne A Thesis Submitted for the Degree of Master of Science Michael G. Crisp B.Sc (Hons.) ADELAIDE UNIVERSITY AUSTRALIA cBucE Department of Chemistry January 2002 Errata with The titles of complexes should commence Table of contents (pages viii and ix): "trans" îot"Trans" not "ComPlexations PlaY "Complexation plays ' ' " Page 10, paragraph 1: Should read read"" to the host ,." not "...host binding' "" Page 1 l,patagraph 1: Should 'binding Page20:Theiodoligandisused.inthis'reactionas(36)ismorereactivethanthe (35) in the presence of silvel ions' corresponding chlorã complex to the term "not applicable"' Page23,Table 1: "na" and"nla" refer (50). - (53) contained more ,Iine 2:Picolinic acid complexes to their low symmetry' Lnt p.oton, than the other isomers owing rH complicated NMR spectra' Page2g,paragraph2,Iine_2:Shouldstart..Complexes(52)and(53)weretheonlytwo complexes.. '" d by "Obscu'ed by PMePh"' and not "Obscure page 34:Entry for (54) H3 should read "As for H4" not "e"' PMePhr"' Entry ror (5i) Hs should read Page39:Preparationoftheplatinum(Il)-iodocomplex(59)isshowninScheme2.6. as Nujol mulls. 1 1: The IR spectra were recofded Page 4|,Table 9 and Page 52,Tab1e "r4N" not "Nr14" Page 60, paragraph 2: Should read "possess" not "posses"' PageT2,paragraph 1, line -3: shotrld be at 600 MHz and not 300 MHz' Page73:2D NMR spectra were t'ecorded Declaration This thesis contains no material which has been accepted for the award of any other degree or I diploma in any university and, to the best of my knowledge, contains no material previously 1l published or written by another person, except where due reference is made. l I l I consent for the thesis being made available for photocopying and loan if accepted for the award ,l of this degree. I I I l Michael G. Crisp Jamary 2002 ll Acknowledgements Dr. Louis M. Rendina provided me with the opportunity to do this project. I would like to thank him for providing me with this opportunity, and for allowing me to develop my o\ün project and helping me turn my ideas for this project into reality. Thanlcyou to Dr. Edward Tiekink for his invaluable assistance with the crystallographic data. Thanks to my fellow laboratory l0 members for their support, encouragement and friendship over the course of this project, Susan Woodhouse, David Gallasch, David Clarke, Jean Todd, Doug Smyth, Ben Ellis, and DanielaCatazza. I would like to thank Sarah who married me on the 30th of September 2001. Thanþou Saratr for being so supportive during the cowse of my work. You provided me with a great motivation to finish this project and always encourage me to follow my dreams. I would like to thank my Mum and my Dad for their continued support in everything that I do. I would like to thank them for listening to my continual ranting about the ups and downs of my project. iii Abstract The preparation and characterisation of a novel series of organoplatinum(Il) complexes with hydrogen-bonding functionality are described. The mononuclear platinum(Il) complexes of the type trans-[Pt(o-aryl)L(PPh3)2]OTf (L : nicotinic acid, picolinic acid, isonicotinic acid) and the dinuclear complexes of the type trans-[Pt(o-aryl)(PPh3)(p-Y)Pt(o-aryl)(PPh3)2](OTÐz (Y : 4,4'- bipyridyl, 4,7 -phenanthroline, 4,4' -dipyrazolylmethan e, l,l'-phenyl-4 ,4'-dipyrazolylmethane) tH¡ were investigated. The complexes were primarily characterised by multinuclear 13rP, t-O and 2-D NMR spectroscopy, IR spectroscopy and, in some cases, X-ray crystallography. These platinum(I) complexes, both mono-nuclear and di-nuclear, have the potential to act as hosts for nucleobase guests such as adenine, and this was investigated also. The mono-platinum complexes were found to interact with the guest 9-sec-pentyladenine in a variety of ways in CDCb solution including, l:1, 2;l and in some cases 3: I association ratios at both the V/atson-Crick and the Hoogsteen site. The dinuclear platinum(Il) molecular "tweezers" were found to bind simultaneously to two 9-sec-pentyladenine molecules in CDCI3 solution. lv Abbreviations General: o degrees OC degrees Celsius AG change in free energy 1-D one dimensional 2-D two dimensional Å Angstrom cm centimetre DNA deoxyribonucleic acid DPZM 4,4' - dipy r azolylmethane bû gram h hou¡ K Kelvin MS mass spectomeûy mL millilitre OTf, triflate CF¡ SOE', trifluoromethanesulfonate Ph phenyl THF tetratrydrofuran Nuclear magnetic resonance spectroscopy: ô nuclear magnetic resonance chemical shift in ppm tH NMR proton nuclear magnetic resonance ttP{tH} 3rP NMR proton decoupled nuclear magnetic resonance d doublet dd doublet of doublets Hz Hertz I nuclear spin quantum number m multiplet v Ilv4Hz megahertz "Jri n bond coupling constant between nuclei i and j NMR nuclea¡ magnetic resonance ppm parts per million S singlet t triplet vt Table of Contents Declaration i Acknowledgements ii Abstract lll Abbreviations iv Table of Contents vii Chapter I Introduction I l.l Self Assembly I I .2 DNA/RNA Nucleobases l0 I .3 Platinum Complexes with Hydrogen-Bonding Functionality t4 I .4 Molecular Tweezers Containing Platinum(I I) 16 Chapter 2 Preparation and Characterization of Mononuclear Platinum(Il) Complexes with Hydrogen-Bonding Functionality 19 2.1 Synthesis and Characterisation of lodoplatinum(Il) Precursor Complexes t9 2.2 Synthesis and Characterisation of Mononuclear Platinum(Il) Complexes with Hydrogen-Bonding Functionality 27 2.3 pKaDeterminations for Complexes (43), (46), (47), (48), and (51) 44 Chapter 3 Preparation and Characterisation of Dinuclear Organoplatinum(Il) Complexes with Hydrogen-Bonding Functionality 47 Chapter 4 Molecular Recognition of Adenine by Platinum(Il) Complexes with Hydrogen-Bonding Functionality 56 4. 1 Association Studies of Mononuclear Platinum(I) Complexes with 9-sec-pentyladenine 65 4.2 Association Studies of Dinuclear vll Platinum(Il) Complexes (67) and (68) with 9-sec-pentyladenrne 7T Chapter 5 Conclusion 74 Chapter 6 Experimental 75 trans-iodophenyl-bis(triphenylphosphine)platinum(II) (3 7) 76 trans-iodo-bis(metþldiphenylphosphine)phenylplatinum(Il) (38) 76 trans-iodophenylbis(triethylphosphine)platinum(Il) (39) 76 trans-iodophenyl-bis(tricyclohexylpho sphine)platinum(Il) (40) 76 Tr an s - (nrcotinic acid)phenyl bis(triphenylphosphine)platinum(Il) trifl ate (42) 77 Tr an s - (ricotinic aci d)pheny I bis(methyldiphenylphosphine)platinum(Il) triflate (43) 77 Trans-(nrcotinic acid)phenylbis(trietþlphosphine)platinum(Il) triflate (44) 77 Tr an s - (rucotinic acid)phenyl bis(tricyclohexylphosphine)platinum(Il) trifl ate (45) 78 Tr an s - (isontcotini c acid)phenyl bis(triphenylphosphine)platinum(Il) trifl ate (46) 78 Tr an s - (isonicotinic acid)phenyl bis(methyldiphenylphosphine)platinum(Il) tnflate (47) 78 Tr an s - (isonicotinic ac id)phenyl bis(trietþlphosphine)platinum(Il) trifl ate (48) 79 vlll Tr ans - (isonicotinic acid)phenyl bis(tricyclohexylphosphine)platinum(Il) trifl ate (49) 79 Tr an s - (çicolinic acid)PhenYl 79 bis(triphenylphosphine)platinum(Il) trifl ate (50) Tr an s -(picotinic acid)PhenYl 79 bis(methyldiphenylphosphine)platinum(Il) trifl ate (5 1) Tr an s - (pic olinic acid)PhenYl 80 bis(triethylphosphine)platinum(Il) trifl ate (52) Tr an s -(pic ol inic aci d)PhenYl 80 bis(tricyclohexylphosphine)platinum(Il) triflate (53) Trans-(isonrcotinamide)phenyl 80 bis(methyldiphenylphosphine)platinum(Il) trifl ate (54) Tr an s - (rucotinamide)PhenYl 81 bis(metþldiphenylphosphine)platinum(Il) trifl ate (55) 81 Trans-iodoQ.{-metþlbenzamide)bis(triphenylphosphine)platinum(Il) (59) Tr ans -¡t-4,4' -bipyridinebis [(N-metþlbenzamide) 81 bis(triphenylphosphine)platinum(Il)l bis(trifl ate) (65) Tr ans -¡t-4,7-phenanthrolinebi s fN-metþlbenzamide] 82 bis(triphenylphosphine)ptatinum(Il)l bis(triflate) (66) Tr ans -¡t-4,4' -dipyrazolylmethanebis [(N-metþlbenzamide) 82 bis(triphenylphosphine)platinum(Il)l bis(triflate) (67) Tr ans -¡t-1,1' -phenyl-4,4' -dipyrazolylmethanebis [(N-metþlbenzamide) lx bis(triphenylphosphine)platinum(Il)l bis(trifl ate) (68) 82 Preparation of Samples for Job Plots 83 Determination of pKa values 84 References 85 x Chapter 1. lntroduction The hydrogen bond has long been known to play a pivotal role in the areas of molecular recognition and supramolecular chemistry. Many natural and synthetic supramolecular systems owe their organisation to the presence of hydrogen-bonding functionalities. Hydrogen-bonding can control the organization of molecules in the solid state, and it has been used extensively in crystal engineeringl'2 and supramolecular synthesis3-5. In contrast, only more recently have major advances been made in the use of the coordinate-covalent bond for the assembly of discrete molecular arays6. A large volume of information is at our disposal that can be used in the design of supramolecular systems containing transition metals. The coordination numbers and geometries of most transition metals are well established. This information can be drawn upon to determine what size a metal-based supramolecular complex will be, or what angles are involvedT. There are numerous papers describing the various combinations of metal atoms with diftèrent organic "building blocks" to form a variety of discrete supramolecular structuress-Io. Combining the hydrogen-bonding and coordinate-covalent motifs greatly expands the utility of metal complexes as molecular receptors. The hydrogen-bonding surface of carboxylic acids, and derivatives of carboxylic acids, are often used in the design of such receptors. In particular it has been used for the molecular recognition of nucleobases such as adenine, which is an important target in studies of molecular recognition. 1 .1 Self-Assembly Self-assembly has rapidly become a convenient means for obtaining large macrocycles and molecular polygons of predetermined shape, size and functionalityll-13. Contemporary supramolecular chemistry has its roots in classical covalent macrocycles such as crown ethers, cyclophanes, cyclodextrins, calixarerenes, cryptands, and spherands to name a few.