Orbital Analysis Captures the Existence of a Mixed‐Valent CuIII−O−CuII 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 CuIII−O−CuII 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 CuIII−O−CuII core with the removal of a water molecule. The orbital and spin density analyses unravel the mixed‐valent nature of CuIII−O−CuII. We further investigated the reactivity of this mixed‐valent core for aliphatic C−H hydroxylation. Our study unveiled that mixed‐valent CuIII−O−CuII 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 CuIII−O−CuII core, we investigated aliphatic C−H activation by a symmetrical CuII−O−CuII core. DFT results show that the mixed‐valent CuIII−O−CuII core is more reactive toward the C−H bond than the symmetrical CuII−O−CuII core. [ABSTRACT FROM AUTHOR]