Computational Study of Naphthalene Peri‐Diselenide as Glutathione Peroxidase Mimics: Mechanistic Insights and Substitution Effects

Abstract The full catalytic cycle of naphtho[1,8‐c,d]‐1,2‐diselenole, a potential glutathione peroxidase mimic, has been investigated using the density functional theory and the energetic span model. The effects of substitutions and solvent on the catalytic cycle have also been investigated. Among the four steps of the catalytic cycle, the step involving the regeneration of the catalyst exhibits the highest activation energy. Polar solvent (methanol) enhances the overall catalytic activity by decreasing the activation barrier for most of the steps. The ortho position (to selenium) of the naphthalene ring is found most suitable for the substitution, showing the highest turnover frequency (TOF) for both nitro and methoxy substituents. Meta substitution leads to a decline in catalytic efficiency, showing lower TOF than the unsubstituted molecule. Substitution at the para position enhances the activity for the methoxy group, while the nitro group reduces it.