Computational studies of the coordination stereochemistry, bonding, and metal selectivity of mercury.

Knowledge of the bonding and selectivity of organic mercury, [H3C-Hg]+ (MeHg+), and inorganic Hg2+ for protein and DNA functional groups is important for understanding the mechanism of heavy metal poisoning. Herein, we elucidate (1) the differences between inorganic Hg2+ and organic MeHg+ in their interactions with different ligands of biological interest, (2) the protein and DNA functional groups that Hg2+ and MeHg+ target in aqueous solution, and (3) the likelihood of "soft" Hg2+ displacing the "borderline" Zn2+ bound to "harder" nitrogen/oxygen-containing side chains such as His and Asp/Glu. The results reveal that, relative to Hg2+, the lower positive charge on MeHg+ results in a longer and weaker bond with a given ligand, in accord with the observed kinetic lability of MeHg+ complexes. They also indicate that negatively charged or polar amino acid side chains containing S-/O-/S/N donors could coordinate to both organic MeHg+ and inorganic Hg2+. In addition, Gua and Cyt could also coordinate to MeHg+ and disrupt Gua...Cyt base pairing. A key novel finding is that Hg2+ is a far better electron acceptor than Zn2+, and can thus accept more negative charge from the Zn ligands than the native Zn2+, thus enhancing Hg-ligand interactions and enabling Hg2+ to displace the native cofactor from zinc essential enzymes and "structural" Zn proteins. The results herein support several possible mechanisms for Hg poisoning. Ways that mercury poisoning could be prevented in cells are discussed.