Mechanistic Investigations into the Selective Reduction of Oxygen by a Multicopper Oxidase T3 Site-Inspired Dicopper Complex

[Image: see text] Understanding how multicopper oxidases (MCOs) reduce oxygen in the trinuclear copper cluster (TNC) is of great importance for development of catalysts for the oxygen reduction reaction (ORR). Herein, we report a mechanistic investigation into the ORR activity of the dinuclear copper complex [Cu(2)L(μ-OH)](3+) (L = 2,7-bis[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyridine). This complex is inspired by the dinuclear T3 site found in the MCO active site and confines the Cu centers in a rigid scaffold. We show that the electrochemical reduction of [Cu(2)L(μ-OH)](3+) follows a proton-coupled electron transfer pathway and requires a larger overpotential due to the presence of the Cu-OH-Cu motif. In addition, we provide evidence that metal–metal cooperativity takes place during catalysis that is facilitated by the constraints of the rigid ligand framework, by identification of key intermediates along the catalytic cycle of [Cu(2)L(μ-OH)](3+). Electrochemical studies show that the mechanisms of the ORR and hydrogen peroxide reduction reaction found for [Cu(2)L(μ-OH)](3+) differ from the ones found for analogous mononuclear copper catalysts. In addition, the metal–metal cooperativity results in an improved selectivity for the four-electron ORR of more than 70% because reaction intermediates can be stabilized better between both copper centers. Overall, the mechanism of the [Cu(2)L(μ-OH)](3+)-catalyzed ORR in this work contributes to the understanding of how the cooperative function of multiple metals in close proximity can affect ORR activity and selectivity.