Theoretical studies on ortho-oxidation of phenols with dioxygen mediated by dicopper complex: Hints for a catalyst with the phenolase activity of tyrosinase

Theoretical studies on the chemo- and regioselective. ortho-oxidation reaction of phenols mediated by a biomimetic (μ-η²: ²peroxo)dicopper(II) complex were performed using unrestricted hybrid density functional theory (UB3LYP) calculations, with the aim of providing a guide for the development of new bio-inspired catalysts with the phenolase activity of tyrosinase. Energetic, structural, and electronic analyses suggested the involvement of a side-on (μ-²:²)-Cu ₂O₂ complex as an active intermediate, and a single electron transfer (SET)-induced electrophilic aromatic substitution mechanism is proposed for the rate-determining C-O bond forming process; this is consistent with experimental observations. Moreover, the inherent roles of, and requirement for, two copper ions in this reaction have been elucidated.