Cooperativity in bimetallic glutathione complexes

Abstract Glutathione interacting with Au + , Ag + , and [HgMe] + metal ions is investigated using density functional theory. An extensive conformational search shows that the sulfhydryl group of cysteine is the predominant binding motif for Au + , Ag + , and [HgMe] + . The order of binding affinities and binding free energies for the metal:ligand complexes are calculated at the B3LYP-D3(BJ)/def2-TZVP level of theory. Analysis of the gas-phase optimized structures has shown that the increase in the number of metal ions (1:1 → 2:1) during the complex formation with a single glutathione leads to a strong cooperative behavior. Conversely, anti-cooperativity is demonstrated in implicit solvation corrections as well as in explicit solvent corrections to the energies in the explicitly solvated-phase structures optimized using a density-based adaptive QM/MM methodology.