Density functional theory study of the reaction mechanism and energetics of the reduction of hydrogen peroxide by ebselen, ebselen diselenide, and ebselen selenol.

Density functional theory calculations at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31G(d,p) level have been performed to elucidate the mechanism and reaction energetics for the reduction of hydrogen peroxide by ebselen, ebselen diselenide, ebselen selenol, and their sulfur analogues. The effects of solvation have been included with the CPCM model, and in the case of the selenol anion reaction, diffuse functions were used on heavy atoms for the geometry optimizations and thermochemical calculations. The topology of the electron density in each system was investigated using the quantum theory of atoms in molecules, and a detailed interpretation of the electronic charge and population data as well as the atomic energies is presented. Reaction free energy barriers for the oxidation of ebselen, ebselen diselenide, and ebselen selenol are 36.8, 38.4, and 32.5 kcal/mol, respectively, in good qualitative agreement with experiment. It is demonstrated that the oxidized selenium atom is significantly destabilized in all cases and that the exothermicity of the reactions is attributed to the peroxide oxygen atoms via reduction. The lower barrier to oxidation exhibited by the selenol is largely due to entropic effects in the reactant complex.