A theoretical study of electronic factors affecting hydroxylation by modelferryl complexes of cytochrome P-450 and horseradish peroxidase

Density functional theory (DFT) is used to study model ferryl species of cy tochrome P-450 and horseradish peroxidase (HRP), as well as of the product complex due to oxidation of H-2 by the P-450 species (1-4 and 7). The ferry l species studied include neutral and cation radical states of the porphyri n, as well as high- and low-spin situations. A few issues are addressed con cerning the mechanism of alkane hydroxylation, and theoretical support is p rovided for: (i) the contention that spin inversion occurs along the reacti on path, (ii) that the cation radical state of the porphyrin is an essentia l feature required to accommodate an excess electron from the ferryl moiety and thereby stabilize the ground state of the hydroxylation product, and ( iii) that the donor property of the proximal ligand has a significant influ ence on the energy of the ferryl-to-ring charge-transfer states which are e ssential to convert the reactant state to the hydroxylation product state. In this sense, our study sheds some light on the difference between the oxi dized and reduced HRP forms, HRP(I) and HRP(II),and suggests that the combi nation of a cation radical porphyrin state and a good pi-donor proximal lig and like thiolate, could be the underlying reason for the potent hydroxylat ion ability of the P-450 ferryl-complex.