The mechanism of action of the selenenamide 1 as a mimic of the
glutathione peroxidase (GPx) was investigated by the density functional theory. The
solvent-assisted
proton exchange procedure was applied to model the catalytic behavior and
antioxidant activity of this mimic. To have an insight into the charge transfer effect, different aromatic
thiols, including electron donating substituents on the phenyl ring were considered. The catalytic behavior of the selenenamide was modeled in a four-step mechanism, described by the oxidation of the mimic, the reduction of the obtained product,
selenoxide, the reduction of the selenenylsulfide and
dehydration of selenenic
acid. On the basis of the activation parameters, the final step of the proposed mechanism is the rate determining states of the catalytic cycle. Turnover frequency (TOF) analysis showed that the electron donating groups at the para-position of the phenyl ring of the PhSH do not affect the catalytic activity of the selenenamide in contrast to p-methyl
thiophenol which indicates the highest nucleophilicity. The evaluation of the electronic contribution of the various donating groups on the phenyl ring of the aromatic
thiols shows that the
antioxidant activity of the selenenamide sufficiently increases in the presence of the electron-donating substitutions. Finally, the charge transfer process at the rate-determining state was investigated based on the natural bond orbital analysis.