Chalcogen–mercury bond formation and disruption in model Rabenstein's reactions: A computational analysis

Abstract

Methylmercury is a highly toxic compound and human exposure is mainly related to consumption of polluted fish and seafood. The inactivation of thiol-based enzymes, promoted by the strong affinity binding of electrophilic mercuric ions to thiol and selenol groups of proteins, is likely an important factor explaining its toxicity. A key role is played by the chemistry and reactivity of the mercury-chalcogens bond, particularly Hg S and Hg Se, which is the focus of this computational work (level of theory: (COSMO)-ZORA-BLYP-D3(BJ)/TZ2P). We analyze nine ligand-exchange model reactions (the so-called Rabenstein's reactions) involving an entering ligand (methylchalcogenolate) and a substrate (methylchalcogenolatemethylmercury). Trends in reaction and activation energies are discussed and a change in mechanism is reported for all cases when going from gas phase to water, that is, from a single-well potential energy surface (PES) to a canonical S N 2-like mechanism. The reasons accounting for the biochemically challenging and desired displacement of methylmercury from a seleno/ thiol protein can be found already in these model reactions, as can be seen from the similarities of the ligand exchange reactions in solution in thermodynamics and kinetics.

Integrating Diphenyl Diselenide and Its Mehg+ Detoxificant Mechanism on a Conceptual DFT Framework

“…The frequent consumption of predatory fish can result in MeHg + intoxication [2]. The toxicity of the soft electrophilic MeHg + is mediated by inactivation of proteins containing soft nucleophilic sites (e.g., thiol-and selenol-containing proteins) [3][4][5][6][7]. MeHg + has an extremely high affinity for -SH and -SeH groups [5,8].…”

“…The toxicity of the soft electrophilic MeHg + is mediated by inactivation of proteins containing soft nucleophilic sites (e.g., thiol-and selenol-containing proteins) [3][4][5][6][7]. MeHg + has an extremely high affinity for -SH and -SeH groups [5,8]. Experimental and theoretical studies have indicated that the affinity of MeHg + for -SeH is greater than for -SH groups [5].…”

“…MeHg + has an extremely high affinity for -SH and -SeH groups [5,8]. Experimental and theoretical studies have indicated that the affinity of MeHg + for -SeH is greater than for -SH groups [5]. Selenium (Se) is an essential element for vertebrates as part of the selenol group present in the selenocysteine residues found in selenoproteins.…”

“…A decreased mercury burden in liver, kidney, cerebrum and cerebellum of mouse was reported in mice treated with (PhSe)2 [3,4,9]. We have hypothesized that (PhSe)2 could be reduced to its selenol intermediate PhSeH, which formed a complex with MeHg + (i.e., PhSeHgMe) [5,9,10]. The reduction of (PhSe)2 and its eventual reaction with methylmercury have several intricate and interesting parts, as reactions may eventually depend on the conformation assumed by (PhSe)2 in the reacting medium [11][12][13].…”

Methylmercury – Chalcogenolates Ligand Exchange: Insight from DFT into A Very Fast Reaction

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Methylmercury chalcogenolates ligand exchange: insight from DFT into a very fast reaction [1] Methylmercury (CH 3 Hg + ) binding to thiol-and selenol-based enzymes is a key-element to explain its high toxicity. CH 3 Hg + is not found in its free form in biological environment, it is present as a chalcogenolate complex.

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