Mechanism of the methane → methanol conversion reaction catalyzed by methane monooxygenase: A density functional study

The hybrid density functional (DFT) method B3LYP was used to study the mechanism of the methane hydroxylation reaction catalyzed by a non-heme diiron enzyme, methane monooxygenase (MMO). The key reactive compound Q of MMO was modeled by (NH₂)(H₂O)Fe(m-O)₂(η²-HCOO)₂Fe(NH₂)(H₂O), I. The reaction is shown to take place via a bound-radical mechanism and an intricate change of the electronic structure of the Fe core is associated with the reaction process. Starting with I, which has a diamond-core structure with two Fe(IV) atoms, L₄F(IV)(μ-O)2Fe(IV)L₄, the reaction with methane goes over the rate-determining H-abstraction transition state III to reach a bound-radical intermediate IV, L₄Fe(IV)(μ-O)(μ-OH(· · · CH₃))Fe(III)L₄, which has a bridged hydroxyl ligand interacting weakly with a methyl radical and is in an Fe(III)-Fe(IV) mixed valence state. This short- lived intermediate IV easily rearranges intramolecularly through a low barrier at transition state V for addition of the methyl radical to the hydroxyl ligand to give the methanol complex VI, L₄Fe(III)(OHCH₃)(μ- O)Fe(III)L₄, which has an Fe(III)-Fe(III) core. The barrier of the rate- determining step, methane H-abstraction, was calculated to be 19 kcal/mol. The overall CH₄ oxidation reaction to form the methanol complex, I + CH₄ → VI, was found to be exothermic by 39 kcal/mol.