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Methylmercury – Chalcogenolates Ligand Exchange: Insight from DFT into A Very Fast Reaction
1 , 1 , 2 , 3 , 1 , 2 , * 1
1  Dipartimento di Scienze Chimiche Università degli Studi di Padova Via Marzolo 1 35131 Padova, Italy
2  Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria RS Brazil
3  Dipartimento di Scienze Chimiche Università degli Studi di Padova Via Marzolo 1 35131 Padova, Italy Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria RS Brazil

Published: 09 November 2020 by MDPI in 1st International Electronic Conference on Catalysis Sciences session Posters
Abstract:

Methylmercury (CH3Hg+) binding to thiol- and selenol- based enzymes is a key-element to explain its high toxicity. CH3Hg+ is not found in its free form in biological environment, but is present as a chalcogenolate complex. Thus, chalcogen-mercury bond reactivity is implicated in the distribution of this toxicant in the human body. Particularly, Hg – S and Hg – Se bond formation and disruption is responsible for glutathione depletion and CH3Hg+ delivery to target enzymes. We have investigated systematically, in silico, trends and mechanisms of nine ligand-exchange model reactions between a methylchalcogenolate and a methylmercury methylchalcogenolate complex in order to understand the role of the chalcogen (S, Se, Te) and of the environment (gas phase vs solvent).1 We discuss trends in activation and reaction energies, highlighting a change in mechanism (from a single-well to a unimodal/double-well potential energy surface) when moving from gas to condensed phase, in analogy with SN2 reactions. Further similarities with SN2 reactions are quantified by means of activation strain analysis. Reactions involving S and Se display very similar energetics and (low) activation energies. Therefore, the reasons behind the biochemically challenging detoxification of CH3Hg+ inhibited (seleno)proteins clearly emerge also from our minimal model, which paves the route to future mechanistic investigations.

  1. A. Madabeni, M. Dalla Tiezza, O. B. Folorunsho, P. A. Nogara, M. Bortoli, J. B. Rocha, L. Orian, J. Comput. Chem. 2020, 41, 2045-2059
Keywords: selenium; sulfur; methylmercury; dft;
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