Large scale ab initio quantum chemical calculation of the intermediates inthe soluble methane monooxygenase catalytic cycle

Ab initio DFT quantum chemical methods are applied to study intermediates i n the catalytic cycle of soluble methane monooxygenase hydroxylase (MMOH), a dinuclear iron-containing enzyme that converts methane and dioxygen selec tively to methanol and water. The quantum chemical models reproduce reliabl y the X-ray crystallographic coordinates of the active site for the oxidize d diiron(III) and reduced diiron(II) states to a high degree of structural precision. The results inspired a reexamination of the X-ray structure of r educed MMOH and revealed previously unassigned electron density now attribu ted to a key structural water molecule. The quantum chemical calculations r equired construction of a model containing about 100 atoms, which preserved key hydrogen bonding patterns necessary for structural integrity. Smaller models were unstable for the reduced form of the enzyme, an observation wit h significant mechanistic implications. The large model was then used to in vestigate the catalytic intermediates H-peroxo. formed upon the addition of dioxygen, and Q, the active species that reacts with methane. The structur es, which differ significantly from alternatives proposed in the literature , are consistent with the experimentally available information concerning t he spin states, geometries, and thermodynamics of formation of these interm ediates. Other models that have been proposed, particularly in the case of Q, are ruled out in our calculations by energetic considerations, which hav e a simple physical interpretation. A bound water molecule is critical in a ssembling the catalytically active species Q.