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 axia l ligand as well as the hydroxylation of fluorobenzene, catalyzed by porphy rin-Fe(III)-hydroperoxide with a cysteinate-type of axial ligand as catalyt ic intermediates, have been investigated by electronic structure calculatio ns in local spin-density approximation. Non-repulsive potential curves are, in contrast with porphyrin-Fe(III)-hydroperoxide, obtained only in the cas e 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 comp ared with the parallel orientation between these two planes. This orientati on differs for the case of fluorobenzene hydrolation from the corresponding one calculated by us with the ferryl-oxo-pi -cation radical complex as a c atalytic intermediate. The calculated reaction profiles show also the effec tiveness of the histidyl-type coordinated porphyrin-Fe(III)-peroxide involv ed in P450 type of hydroxylation reactions. The calculations demonstrate th e predominant role of the O-1-O-2 moiety of the porphyrin-Fe(III)-per-oxide anion in the hydroxylation process of the substrates. The results indicate that the porphyrin-Fe(III)-peroxide anion is an effective catalytic specie s in hydroxylation reactions. In all the studied cases irrespective of the substrate and the nature of the axial ligand, the potential curves reach mi nimum at approximately 130-140 pm, expressing the length of an aromatic C-O bond. (C) 2000 Elsevier Science B.V. All rights reserved.