Porphyrin-Fe(III)-hydroperoxide and porphyrin-Fe(III)-peroxide anion as catalytic intermediates in cytochrome P450-catalyzed hydroxylation reactions: a molecular orbital study

The hydroxylation of fluorobenzene and aniline, catalyzed by the porphyrin-Fe(III)-peroxide anion with either a cysteinate- or a histidyl-type of axial ligand as well as the hydroxylation of fluorobenzene, catalyzed by porphyrin-Fe(III)-hydroperoxide with a cysteinate-type of axial ligand as catalytic intermediates, have been investigated by electronic structure calculations in local spin-density approximation. Non-repulsive potential curves are, in contrast with porphyrin-Fe(III)-hydroperoxide, obtained only in the case of porphyrin-Fe(III)-peroxide anion as catalytic intermediate. The mutual substrate-porphyrin orientation with a dihedral angle between the plane of the substrate and the porphyrin plane of 45 degrees is more favorable compared with the parallel orientation between these two planes. This orientation differs for the case of fluorobenzene hydroxylation from the corresponding one calculated by us with the ferryl-oxo-pi-cation radical complex as a catalytic intermediate. The calculated reaction profiles show also the effectiveness of the histidyl-type coordinated porphyrin-Fe(III)-peroxide involved in P450 type of hydroxylation reactions. The calculations demonstrate the predominant role of the O1-O2 moiety of the porphyrin-Fe(III)-peroxide anion in the hydroxylation process of the substrates. The results indicate that the porphyrin-Fe(III)-peroxide anion is an effective catalytic species in hydroxylation reactions. In all the studied cases irrespective of the substrate and the nature of the axial ligand, the potential curves reach minimum at approximately 130-140 pm, expressing the length of an aromatic C-O bond.