Modeling the chelation of As(III) in lewisite by dithiols using density functional theory and solvent-assisted proton exchange.

Modeling the chelation of As(III) in lewisite by dithiols using density functional theory and solvent-assisted proton exchange.
J Inorg Biochem. 2015 Oct 9;153:60-67
Authors: Harper LK, Bayse CA
Abstract
Dithiols such as British anti-lewisite (BAL, rac-2,3-dimercaptopropanol) are an important class of antidotes for the blister agent lewisite (trans-2-chlorovinyldichloroarsine) and, more generally, are chelating agents for arsenic and other toxic metals. The reaction of the vicinal thiols of BAL with lewisite through the chelation of the As(III) center has been modeled using density functional theory (DFT) and solvent-assisted proton exchange (SAPE), a microsolvation method that uses a network of water molecules to mimic the role of bulk solvent in models of aqueous phase chemical reactions. The small activation barriers for the stepwise SN2-type nucleophilic attack of BAL on lewisite (0.7-4.9kcal/mol) are consistent with the favorable leaving group properties of the chloride and the affinity of As(III) for soft sulfur nucleophiles. Small, but insignificant, differences in activation barriers were found for the initial attack of the primary versus secondary thiol of BAL and the R vs S enantiomer. An examination of the relative stability of various dithiol-lewisite complexes shows that ethanedithiols like BAL form the most favorable chelation complexes because the angles formed in five-membered ring are most consistent with the hybridi...

Source: Journal of Inorganic Biochemistry - October 9, 2015 Category: Biochemistry Authors: Harper LK, Bayse CA Tags: J Inorg Biochem Source Type: research