Methane hydroxylation is a thermochemically difficult process due to the strength of the C-H bond that needs to be broken in the process. In Nature only the methane monoxygenases have a catalytic center that is active enough to perform this task. Other metalloenzymes, such as, mononuclear iron monoxygenases and dioxygenases, including the cytochromes P450, are not known to catalyze methane hydroxylation. The cytochromes P450 contain an iron heme group that in a catalytic cycle is converted into an iron(IV)-oxo heme cation radical (Compound I). To gain insight into the features that affect methane hydroxylation by Compound I and synthetic model complexes, we have done a detailed computational study. Thus, we investigated the chemical properties of iron(IV)-oxo porphyrins with varying axial ligands, including SH<sup>−</sup>, F<sup>−</sup>, OH<sup>−</sup>, CN<sup>−</sup>, CF<sub>3</sub>COO<sup>−</sup> and CH<sub>3</sub>COO<sup>−</sup>. In addition, we calculated the methane hydroxylation pathways for a selection of these oxidants and rationalize the obtained trends with thermochemical cycles and valence bond schemes. In general, the rate determining hydrogen atom abstraction barrier is dependent on the π<sub>xz</sub>/π*<sub>xz</sub> energy splitting along the Fe−O bond, the excitation energy from π<sub>xz</sub> to a<sub>2u</sub>, as well as the bond dissociation energies of the methane C−H bond and the newly formed O−H bond. Our studies predict that iron(IV)-oxo porphyrin cation radical models with hydroxide as axial ligand should be efficient oxidants of substrate hydroxylation reactions and able to activate methane at room temperature. However, changing the axial ligand to a weaker electron donating group decreases its activity and raises the hydrogen atom abstraction barriers dramatically. These studies show that subtle modifications to the oxidant can have a great impact on the catalytic ability of the active center.
A comprehensive test set of epoxidation rate constants for iron(iv)–oxo porphyrin cation radical complexes
