Proton assisted oxygen-oxygen bond splitting in cytochrome p450

Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound O has been investigated by density functional theory, showing a barrier for the slightly endothermic formation of the iron-oxo Compound I. The barrier and the endothermicity increase with decreasing acidity of the distal proton source. Protonation of the proximal iron heme ligand favors the O-O bond scission and provides an important regulatory component in the catalytic cycle. The Compound 0 → 1 conversion is slightly exothermic for the peroxidase and catalase models. Implications of the energetic relationship between the two reactive intermediates are discussed in terms of possible oxidative pathways. © 2007 American Chemical Society.