Reaction mechanism for the methane-methanol conversion by soluble methane monooxygenase

Mechanisms of methane C-H bond activation by soluble methane monooxygenase (sMMO) are discussed. Widely-believed oxygen rebound mechanism for alkane hydroxylation by sMMO is critically reexamined. We suggest a two-step concerted mechanism for the hydroxylation of methane on the basis of our theoretical studies by means of a hybrid density-functional method. The activation of methane C-H bond by intermediate Q of sMMO which is suggested to involve a high valent Fe₂(μ-O)₂ diamond core is found to occur through the formation of the Q(CH₄) complex with an Fe-C bond and Fe-H bonds, followed by a concerted H atom abstraction via a four-centered transition state. Methyl migration via a three-centered transition state successively occurs within the complex leading to the formation of product methanol. Our proposed mechanism for the conversion of methane to methanol is able to explain the important experimental results of kinetic isotope effect and inversion of stereochemistry. The two-step concerted mechanism sheds new light on recent experimental results which are inconsistent with the widely-accepted radical mechanism.