Effect of the axial ligand on substrate sulfoxidation mediated by iron(IV)-oxo porphyrin cation radical oxidants

Cytochromes P450 catalyze a range of different oxygen-transfer processes including aliphatic and aromatic hydroxylation, epoxidation, and sulfoxidation reactions. Herein, we have investigated substrate sulfoxidation mediated by models of P450 enzymes as well as by biomimetic oxidants using density functional-theory methods and we have rationalized the sulfoxidation reaction barriers and rate constants. We carried out two sets of calculations: first, we calculated the sulfoxidation by an iron(IV)-oxo porphyrin cation radical oxidant Fe(IV)=O(Por(+.))SH] that mimics the active site of cytochrome P450 enzymes with a range of different substrates, and second, we studied one substrate (dimethyl sulfide) with a selection of different iron(IV)-oxo porphyrin cation radical oxidants Fe(IV)=O(Por(+.))L] with varying axial ligands L. The study presented herein shows that the barrier height for substrate sulfoxidation correlates linearly with the ionization potential of the substrate, thus reflecting the electron-transfer processes in the rate-determining step of the reaction. Furthermore, the axial ligand of the oxidant influences the pK(a) value of the iron(IV)-oxo group, and, as a consequence, the bond dissociation energy (BDE(OH) value correlates with the barrier height for the reverse sulfoxidation reaction. These studies have generalized substrate-sulfoxidation reactions and have shown how they fundamentally compare with substrate hydroxylation and epoxidation reactions.