Effect of micro and bulk solvation on the mechanism of nucleophilic substitution at sulfur in disulfides

Abstract

Computational studies of the solution-phase mechanism of nucleophilic substitution at sulfur in disulfides with explicit water representation indicate that the pathway is dependent on the substituent on the sulfur under attack. B3LYP/6-1+G* optimizations for prototype thiolate-disulffide exchange reactions were performed including one to four explicit water molecules, followed by single-point free energy calculations with B3LYP/6-31+G* and the polarized continuum model (PCM). The solution-phase mechanism is the addition-elimination mechanism when the sulfur under attack bears a hydrogen, while the SN2 mechanism is predicted when the sulfur substituent is a methyl group.