Orbital Analysis Captures the Existence of a Mixed-Valent Cu III -O-Cu II Active-Site and its Role in Water-Assisted Aliphatic Hydroxylation.

The Cu-O-Cu core has been proposed as a potential site for methane oxidation in particulate methane monooxygenase. In this work, we used density functional theory (DFT) to design a mixed-valent Cu III -O-Cu II species from an experimentally known peroxo-dicopper complex supported by N-donor ligands containing phenolic groups. We found that the transfer of two-protons and two-electrons from phenolic groups to peroxo-dicopper core takes place, which results to the formation of a bis-μ-hydroxo-dicopper core. The bis-μ-hydroxo-dicopper core converts to a mixed-valent Cu III -O-Cu II core with the removal of a water molecule. The orbital and spin density analyses unravel the mixed-valent nature of Cu III -O-Cu II . We further investigated the reactivity of this mixed-valent core for aliphatic C-H hydroxylation. Our study unveiled that mixed-valent Cu III -O-Cu II core follows a hydrogen atom transfer mechanism for C-H activation. An in-situ generated water molecule plays an important role in C-H hydroxylation by acting as a proton transfer bridge between carbon and oxygen. Furthermore, to assess the relevance of a mixed-valent Cu III -O-Cu II core, we investigated aliphatic C-H activation by a symmetrical Cu II -O-Cu II core. DFT results show that the mixed-valent Cu III -O-Cu II core is more reactive toward the C-H bond than the symmetrical Cu II -O-Cu II core.