Density functional theory applied to a difference in pathways taken by the enzymes cytochrome P450 and superoxide reductase: spin States of ferric hydroperoxo intermediates and hydrogen bonds from water.

Cytochrome P450 monooxygenase and superoxide reductase (SOR) have the same first atom coordination shell at their iron active sites: an Fe[N4S] center in a square-pyramidal geometry with the sixth coordinate site open for the catalytic reaction. Furthermore, both pass through ferric hydroperoxo intermediates. Despite these similarities, the next step in their catalytic cycle is very different: distal oxygen protonation and O−O cleavage (P450) versus proximal oxygen protonation and H2O2 release (SOR). One of the factors leading to this difference is the spin state of the intermediates. Density functional theory (DFT) applied to models for the ferric hydroperoxo, (SCH3)(L)FeIII−OOH (L = porphyrin for P450 and four imidazoles for SOR), gives different ground spin states; the P450 model with the porphyrin, which contrains the Fe−N distances, prefers a low-spin ground state, whereas the SOR model with four histidines, in which Fe−N bonds are extendable, prefers a high-spin ground state. Their ground spin state...