Cytoprotective effects of imidazole-based [S1] and [S2]-donor ligands against mercury toxicity: a bioinorganic approach

Abstract

Here we report the coordination behaviour of an imidazole-based [S₁]-donor ligand, 1,3-dimethyl-imidazole-2(3H)-thione (L1), and [S₂]-donor ligand, 3,3′-methylenebis(1-methyl-imidazole-2(3H)-thione) (L2) or 4,4′-(3,3′-methylenebis-(2-thioxo-2,3-dihydro-imidazole-3,1-diyl))dibutanoic acid (L3), with HgX₂ (X = Cl, Br or I) in solution and the solid state. NMR, UV-Vis spectroscopic, and single crystal X-ray studies demonstrated that L1 or L2 coordinated rapidly and reversibly to the mercury center of HgX₂ through the thione moiety. Treatment of L2 with HgCl₂ or HgBr₂ afforded 16-membered metallacycle k¹-(L2)₂Hg₂Cl₄ or k¹-(L2)₂Hg₂Br₄ where two Cl or Br atoms are located inside the ring. In contrast, treatment of L2 with HgI₂ afforded a chain-like structure of k¹-[L2Hgl₂]_n, possibly due to the large size of the iodine atom. Interestingly, [S₁] and [S₂]-donor ligands (L1, L2, and L3) showed an excellent efficacy to protect liver cells against HgCl₂ induced toxicity and the strength of their efficacy is in the order of L3 > L2 > L1. 30% decrease of ROS production was observed when liver cells were co-treated with HgCl₂ and L1 in comparison to those cells treated with HgCl₂ only. In contrast, 45% and 60% decrease of ROS production was observed in the case of cells co-treated with HgCl₂ and thiones L2 and L3, respectively, indicating that [S₂]-donor ligands L2 and L3 have better cytoprotective effects against oxidative stress induced by HgCl₂ than [S₁]-donor ligand L1. Water-soluble ligand L3 with N-(CH₂)₃CO₂H substituents showed a better cytoprotective effect against HgCl₂ toxicity than L2 in liver cells.