Theoretical (DFT) study on the hydroxylation mechanism of Sn(IV)porphyrin: How does Sn(IV)porphyrin inhibit heme oxygenase catalysis function

Abstract

We have performed quantum mechanics (QM) calculation on the mechanism of the tin porphyrin hydroxylation, analogous process to the first step of heme degradation. We investigated a concerted mechanism, whereby the distal oxygen of hydroperoxo ligand (O2, Scheme 2a) of [SnIVporphyrin(OOH)]+ complex attacks directly to porphyrin α‑meso carbon, followed by the OOH bond cleavage and the formation of a hydroxyled porphyrin macrocycle. The first and rate-determining step of the process involves the distortion of macrocycle. We have also investigated an alternative stepwise mechanism involving hydrogen bonding interaction between hyrdoperoxo group and one water molecule, of water cluster; in which dioxygen bond of heydroperoxo breaks homolyticly. The concerted, direct attack pathway, is computed to have a higher energy barrier compared with OO homolytic cleavage mechanism. Furthermore, calculations reveal that in comparison to heme degradation process, hydroxylation of porphyrin α‑meso carbon in SnIVporphyrin complexes is a much higher-energy pathway. Therefore, according to this study, it could be concluded that in the enzymatic environment Sn complexes bounded to HO enzyme remain un-degraded.