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

Cytochromes P 450 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 P 450 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<SUP>IV</SUP>=O(Por<SUP>+.</SUP>)SH] that mimics the active site of cytochrome P 450 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<SUP>IV</SUP>=O(Por<SUP>+.</SUP>)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<SUB>a</SUB> value of the iron(IV)–oxo group, and, as a consequence, the bond dissociation energy (BDE<SUB>OH</SUB>) 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