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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
Author(s) -
Karri Ramesh,
Chalana Ashish,
Kumar Binayak,
Jayadev Sri Krishna,
Roy Gouriprasanna
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902578
Subject(s) - chemistry , glutathione , bond cleavage , mercury (programming language) , stereochemistry , antioxidant , imidazole , oxidative stress , medicinal chemistry , enzyme , biochemistry , catalysis , computer science , programming language
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 L n Se ( n =1–4, or 6), the three‐spacer L 3 Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through κ 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 (σ) parameter and the lowest HOMO(L n Se)‐LUMO(MeHgX) energy gap and, thus, L 3 Se is the most reactive among L n Se towards MeHgX (X=Cl or I). L 3 Se is highly efficient, more than L 1 Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L 3 Se relative to 50 % by L 1 Se. 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 (Δ Ψ m ) from perturbation by MeHgCl. Major Hg‐responsive genes analyses demonstrate that L 3 Se plays a significant role in MeHg + detoxification in liver cells.