Synthesis and testing of selective ‘pyrrophen’ systems for visual uranyl detection Madeleine G. Forbes, Julie E. Niklas, Jacob T. Mayhugh, John D. Gorden, Anne E. V. Gorden Department of Chemistry and Biochemistry Auburn University, Auburn, AL Background Synthesis Discussion Industrial applications include the development of colorimetric sensors Much of actinide chemistry highlights ligands with hard-donor for radioactive aqueous environments. Enhanced uranyl detection heteroatoms to coordinate uranyl (O=U=O2+). methods contribute to recent demands for nuclear remediation. These ligands are of interest to sense uranyl in aqueous environments for nuclear waste remediation. Challenges in pyrrophen’s development include binding competition among transition metals and matching the efficiency of current Scheme 1. Synthesis of Benzyl 4-ethyl-5-formyl-3-methyl-1H-pyrrole-2-carboxylate. Reagents and conditions: a) NaNO (aq), HOAc, rt to 0 ⁰C; b) Recent developments have focused on salophen models as they are 2 instrumental methods. Considering these constraints, the sensors must Acetylacetone, HOAc, excess Zn; c) NaBH , BF ·Et O, THF, rt; d) CAN. easy to prepare. Softer-ligands such as macrocyclic expanded 4 3 2 also meet the following criteria: rapid detection, selective binding, porphyrins are also of interest, yet they are synthetically demanding inexpensive production, and binary results. and have unfavourable binding kinetics. The designed supramolecular ligand systems also provide insight on the “Pyrrophen” is a new framework featuring a hexadentate, pyrrole- fundamental properties of uranyl complexes. Pyrrophen’s coordination containing, macro-acyclic ligand that combines features from offers distinct uranyl and transition metal binding motifs. The inclusion of salophens and expanded porphyrins, which can be used for softer donor atoms and stable planar geometry increases selectivity for molecular recognition of uranyl. 2+ UO2 over usually-competitive transition metals. Electrochemical data highlights more positive uranyl redox potentials in comparison to salophen complexes, demonstrating pyrrophen’s advantageous “softer” binding. Figure 2. Left: 50 μM (bottom) and salophen isoamethyrin alaskaphyrin 500 μM (top) solutions of L1 and Figure 1. Structural representations of ligand frameworks that inspired metal complexes in 9:1 THF:MeOH. pyrrophen’s design. Right: Uranyl and zinc complexes of Scheme 2. Synthesis of pyrrophen (L1), dimethylpyrrophen (L2), and the corresponding metal complexes (UO L1, UO L2, Zn L1 and Cu L1 ). 2+ Zn2+ 2 2 2 2 2 2 UO2 L1, 500 μM in ACN. Results Crystallography Average θ: 60.15(5)o Spectroscopy Electrochemistry o Sum θ: 360.80 -0.045 -0.200 70000 1 a a Pyrrophen Pyr a b -0.150 UO2 5 min 60000 Uranyl-Pyr -0.025 -0.100 UO2 10 min * 0.8 * Copper-Pyr UO2 15 min * -0.050 50000 UO2 20 min Zinc-Pyr -0.005 2+/+ 2+/+ UO2 UO2 25 min UO2 0.000 Cobalt-Pyr 0.6 UO2 30 min 40000 0.050 1) - Nickel-Pyr I (mA) UO2 35 min 0.015 I (mA) Abs UO2 40 min 0.100 1cm 30000 - 0.4 2- 2- UO2 45 min L12/L12 L22/L22 (M 0.150 ε 0.035 20000 2+ + 0.200 0.2 Zn2 /Zn2 Average θ: 60.79(5)o 10000 0.055 0.250 o 0.300 Sum θ: 360.13 0 0 -1 -2 -3 -0.5 -1 -1.5 -2 -2.5 -3 275 375 475 575 675 275 375 475 575 675 b b E (V vs Fc+/0) Wavelength (nm) Wavelength (nm) E (V vs Fc+/0) Figure 10. Cyclic voltammograms of a) UO L1 and Zn L1 and b) UO L2 and L2 (500uM in ACN Figure 6. Pyrrophen (L1) and complexes (20 Figure 7. Addition of 2.5 equivalent UO 2+ 2 2 2 2 2 0.1M TBAPF (scan rates in b normalized at 0.01 V/s – 0.05 V/s. (A / v1/2)*1000 ; I = current (A), v = μM in 9:1 THF:MeOH). pyrrophen (L1, 20 μM in 9:1 THF:MeOH). 6 scan rate (V/s). Pyrrophen Dimethylpyrrophen 2+ 2+ Replacement of Zn by UO2 2+/+ 6+/5+ 2+/+ 6+/5+ . The UO2 (U ) redox couple . The UO2 (U ) redox couple is 1.0 1 1 is observed at E1/2 = -1.27 V (ΔE observed at E1/2 = -1.28 V (ΔE = 90 Zn2L12Zn2L12 Zn-pyrrophen Zn2L12 ZnZn-Pyrrophen2L12 a 5+UO min2 5 min b + UO2 30s c = 85 mV, QR). mV, QR). Figure 3. Asymmetric unit of a) L1 (top) and b) L2 Figure 4. Asymmetric unit of a) UO2L1 (top) and b) UO2L2 0.9 0.9 +UO2 30s 0.9 +UO+UO22 30m30 min 30+UO min2 30 min ++UO UO2 2020m min (bottom). (bottom). 2 +UO+UO22 1h1h 2+/1+ 2+UO hrs2 2h + UO2 1.5 h . The Zn redox couple is . The 10mV cathodic shift relative to 0.8 0.8 +UO2 1.5h 0.8 +UO+UO22 2h2h 2 4+UO hrs2 4h ++UO UO2 2.52.5h h +UO+UO2 4h4h 2 2 observed at E1/2 = -1.18 V (ΔE = UO2L2 is a result of the electron 0.7 8+UO hrs2 8h Table 1. Selected Average Bond Lengths (Å) of ligands and complexes. 0.7 ++UO UO22 66h h 0.7 +UO+UO22 8h8h 12+UO hrs2 12h ++UO UO22 24h +UO+UO22 12h12h 250 mV, QR). donating methyl substituents. 0.6 24+UO hrs2 24h Avg Bond Length (Å) 0.6 0.6 +UO+UO22 24h24h Compound +UO72 hrs2 72h . The reduction of the free ligand is +UO+UO22 65h65h MeOH…Nim Npyr-H…OHMe MeO-H C=Nim Npyr-H C=O U=Oyl M-Nim M-Npy M--O +UO 120h 0.5 120 hrs2 0.5 0.5 observed at E = -1.94 V L1 2.215 1.949 0.85(2) 1.2827(18) 0.919(19) 1.2119(18) - - - - 180+UO hrs2 180h pc 0.4 Absorbance L2 2.899 2.825 0.852(16) 1.4107(13) 0.884(15) 1.2129(14) - - - - 0.4 Absorbance 0.4 Absorbance UO2L1 - - - - - 1.238(2) 1.7739(9) 2.6952(15) 2.4377(15) 2.5575(13) 0.3 0.3 0.3 UO L2 - - - - - 1.2355(3) 1.774(2) 2.665(2)2.565(2) 2.4425(2) 2.6734 (19) Uranyl redox couples of these species are significantly more positive than 2 0.2 0.2 0.2 Zn2L12 - - - - - 1.2119(18) - 2.081(19) 1.958(19) - those of salophen species and are similar to those of macrocyclic species. 0.1 0.1 0.1 Cu2L12 - - - - - 1.205(3) - 2.048(2) 1.993(2) - 0.0 0 0 300 350 400 450 500 550 300 350 400 450 500 550 300 350 400 450 500 550 The uranyl complex adopts a hexagonal bipyramidal form with an unambiguous Wavelength (nm) Wavelength (nm) Wavelength (nm) U(VI) center. The elongated ester carbonyl bond indicates a donation of electron 2+ 2+ Figure 8. Addition of 0.5 (a), 1.0(b), and 2.0(c) equivalent UO2 (per Zn ) to Zn2L12, 10 μM in 9:1 density to the metal center. THF:MeOH). Uranyl lies in the center of the L1 pocket with closest contacts to the softer pyrrole References As a visual sensor the uranyl complex is a distinct color at high enough 1. Mayhugh, J, T.; Niklas, J. E.; Gorden, J. D.; Gorden, A. E. V., Pyrrophen: a pyrrolic macroacyclic hexadentate donor atoms. U—Npyr and U—Nim bond lengths closely resemble those of expanded ligand for the molecular recognition of uranyl (UO 2+). Chem. Commun.*under revision 2+ 2 porphyrins. In the L2 pocket, uranyl is closer to the imine N donors than in L1. concentrations. Regardless of UO2 concentration, pyrrophen (L1) preferentially 2. Niklas, J. E., Forbes, M. G., Mayhugh, J. T., Gorden, A. E. V., Manuscript in preparation. coordinates to uranyl, even in competition with transition metals. Displacement of 3. Niklas, J. E.; Hardy, E. E.; Gorden, A. E. V., Solid-state structural elucidation and electrochemical analysis of Zn2+ occurs even on addition of 0.5 equivalents UO 2+. uranyl naphthylsalophen. Chem. Comm. 2018, 54 (83), 11693-11696. Transition Metals 2 4. Sessler, J. L.; Vivian, A. E.; Seidel, D.; Burrell, A. K.; Hoehner, M.; Mody, T. D.; Gebauer, A.; Weghorn, S. J.; Lynch, V., Actinide expanded porphyrin complexes. Coord. Chem. Rev. 2001, 216-217, 411-434. Upon metal addition the transition- metal helicates self-assemble and adopt pseudo-tetrahedral geometries. This binding motif is distinct from the Acknowledgements Contact This work was supported by the Department of Energy– Basic Energy Sciences: Heavy The Gorden Research Group uranyl complex (UO2L1), despite similar Elements #DE-SC0019177. radii across Cu2+, Zn2+, and UO2+ Department of Chemistry and Biochemistry 179 Chemistry Bldg, Auburn, AL (87pm, 88pm, and 87pm respectively). Figure 5. Asymmetric units of Zn L1 and Thanks to Dr. Byron Farnum and the Farnum group for their potentiostat and helpful discussions about 2 2 electrochemistry. Also thanks to Dr. John Gorden for his assistance with crystallography. Auburn University Cu2L12 helicate complexes..