Exploiting the κ 2 -Fashioned Coordination of [Se 2 ]-Donor Ligand L 3 Se for Facile Hg-C Bond Cleavage of Mercury Alkyls and Cytoprotection against Methylmercury-Induced Toxicity.

The Hg-C bond of MeHgCl, a ubiquitous environmental toxicant, is notoriously inert and exceedingly difficult to cleave. The cleavage of the Hg-C bond of MeHgCl at low temperature, therefore, is of significant importance for human health. Among various bis(imidazole)-2-selones LnSe (n=1-4, or 6), the three-spacer L3Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through kappa(2)-fashion, in which both the Se atoms simultaneously attack the Hg center of mercury alkyls for facile Hg-C bond cleavage. It has the highest softness (sigma) parameter and the lowest HOMO(LnSe)-LUMO(MeHgX) energy gap and, thus, L3Se is the most reactive among LnSe towards MeHgX (X=Cl or I). L3Se is highly efficient, more than L1Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L3Se relative to 50 % by L1Se. It shows an excellent cytoprotective effect in liver cells against MeHgCl-induced oxidative stress by protecting vital antioxidant enzymes from inhibition caused by MeHgCl and, thus, does not allow to increase the intracellular reactive oxygen species (ROS) levels. Furthermore, it protects the mitochondrial membrane potential (Delta psi(m)) from perturbation by MeHgCl. Major Hg-responsive genes analyses demonstrate that L3Se plays a significant role in MeHg+ detoxification in liver cells.