Multireference Ab Initio Quantum Mechanics/Molecular Mechanics Study on Intermediates in the Catalytic Cycle of Cytochrome P450_cam

We have investigated the elusive reactive species of cytochrome P450cam (Compound I), the hydroxo complex formed during camphor hydroxylation, and the ferric hydroperoxo complex (Compound 0) by combined quantum mechanical/molecular mechanical (QM/MM) calculations, employing both density functional theory (DFT) and correlated ab initio methods. The first two intermediates appear multiconfigurational in character, especially in the doublet state and less so in the quartet state. DFT(B3LYP)/MM calculations reproduce the relative energies from correlated ab initio QM/MM treatments quite well, except for the splitting of the lowest A1u−A2u radical states. The inclusion of dynamic correlation is crucial for the proper ab initio treatment of these intermediates.