Conversion of Methane to Methanol at the Mononuclear and Dinuclear Copper Sites of Particulate Methane Monooxygenase (pMMO):  A DFT and QM/MM Study

Abstract

Methane hydroxylation at the mononuclear and dinuclear copper sites of pMMO is discussed using quantum mechanical and QM/MM calculations. Possible mechanisms are proposed with respect to the formation of reactive copper−oxo and how they activate methane. Dioxygen is incorporated into the CuI species to give a CuII−superoxo species, followed by an H-atom transfer from a tyrosine residue near the monocopper active site. A resultant CuII−hydroperoxo species is next transformed into a CuIII−oxo species and a water molecule by the abstraction of an H-atom from another tyrosine residue. This process is accessible in energy under physiological conditions. Dioxygen is also incorporated into the dicopper site to form a (μ-η2:η2-peroxo)dicopper species, which is then transformed into a bis(μ-oxo)dicopper species. The formation of this species is more favorable in energy than that of the monocopper−oxo species. The reactivity of the CuIII−oxo species is sufficient for the conversion of methane to methanol if it is formed in the protein environment. Since the σ* orbital localized in the Cu−O bond region is singly occupied in the triplet state, this orbital plays a role in the homolytic cleavage of a C−H bond of methane. The reactivity of the bis(μ-oxo)dicopper species is also sufficient for the conversion of methane to methanol. The mixed-valent bis(μ-oxo)CuIICuIII species is reactive to methane because the amplitude of the σ* singly occupied MO localized on the bridging oxo moieties plays an essential role in C−H activation