Substrate sulfoxidation by a biomimetic cytochrome P450 Compound I mimic: How do porphyrin and phthalocyanine equatorial ligand compare?

The cytochrome P450 enzymes are important enzymes in the liver that trigger drug metabolism reactions. In biotechnology and biomimetic chemistry, synthetic models of the active species of P450 have been developed and designed and often react differently. Here, we investigate a biomimetic P450 model complex with phthalocyanine equatorial ligand rather than heme or porphyrin and with and without four tert-butyl substituents to the periphery of the ligand. Density functional theory studies on the electronic properties of the iron(IV)-oxo ligand cation radical species and its reactivity in oxygen atom transfer were studied. The work shows that a phthalocyanine equatorial ligand rather than porphyrin leads to a dramatic effect on the orbital energy levels of the iron(IV)-oxo species and creates a species with close-lying doublet and quartet spin states with two unpaired electrons in *xz and *yz for the FeO interaction coupled to a ligand radical in an a1u-type orbital. The latter contrasts P450 Compound I that has the a1u orbital doubly occupied and a singly occupied a2u orbital instead, As a consequence, our biomimetic model gives a reduced redox potential as compared to a system with a porphyrin-based ligand. Nevertheless, the iron(IV)-oxo cation radical species with phthalocyanine ligand is shown to react with para-X-substituted thioanisole (X = CH3, Cl, CN, H, NO2, OCH3) substrates with small oxygen atom transfer barriers that align with the -Hammett parameter. The reactions are concerted with a single barrier leading to sulfoxide products.