Mechanism of C−H Activation by Diiron Methane Monooxygenases: Quantum Chemical Studies

A variety of plausible mechanisms for methane hydroxylation in methane monooxygenases (MMO) have been tested by high-level quantum chemical methods on model systems with simple ligands chosen on the basis of the MMO crystal structure and the available biophysical data. One pathway survives the present level of tests in having intermediates with plausible energies and structures and a low-energy transition state for C−H abstraction. In this proposed pathway, the Fe2(II,II) dinuclear iron site of the reduced form of MMO reacts with O2 to give two different Fe2(III,III) peroxo species and, after O−O bond cleavage, an Fe2(IV,IV) bis-μ-oxo species probably directly analogous to “compound Q” of MMO. As a result of the large Jahn−Teller distortions in the d4 bis-μ-oxo species, the Fe−O−Fe bridges are highly asymmetric, allowing the system to open up easily to a key FeIII−O−FeVO intermediate that is shown to be capable of reacting with methane via a low-energy transition state. This intermediate is shown to be be...