This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Deborah C. Bebout to use multinuclear magnetic resonance spectroscopy (NMR) and electrospray ionization mass spectrometry (ESI-MS) to investigate the exchange of Hg2+ between physiologically relevant binding environments and ligand exchange between Hg2+ and Zn2+. The viability of Hg2+-thiolate complexes as kinetically labile Hg2+ buffers in exchange processes will be investigated. Non-degenerate Hg2+ ligand exchange processes will be examined under equilibrium conditions by varying the stoichiometric ratios of thiolates and competing ligands. Detailed speciation analysis will be facilitated by the use of multidentate ligands with established coordination chemistry and simple thiols. Proton NMR chemical shifts will be analyzed for evidence of a high-coordinate intermediary Hg2+ species accumulating. ESI-MS will be used to facilitate identification of species. Additional ESI-MS studies will characterize homo- and hetero-tris-thiolato-Hg2+ complexes of endogenous thiols, which are putative intermediaries in physiological ligand-ligand exchange processes involving Hg2+. Parallel studies of exchange processes involving thiol-containing pharmacological agents will elucidate similarities and differences with endogenous thiols. In addition, Zn2+-Hg2+ ligand exchange in small coordination complexes modeling metalloproteins will be explored. The kinetics for Hg2+ substitution of Zn2+ bound to suitable multidentate chelating ligand will be studied in the absence of other chelating ligands by NMR. ESI-MS will be used to characterize anticipated ternary species in the exchange process. Metal competition for a carefully chosen multidentate ligand between the bound Zn2+ and a simple bisthiolato- Hg2+ will be investigated as a model of toxicologically plausible metal-metal exchange.
An improved understanding of the complex coordination chemistry underlying cellular Hg2+ toxicity will inform the design of more effective therapies for acute and chronic exposure. The proposed work will help sustain a culture of undergraduate research in the Chemistry Department at the College of William and Mary.
