Exploring the Bonding Nature of Iron(IV)-Oxo Species through Valence Bond Calculations and Electron Density Analysis

Compound I (Cpd I) plays a pivotal role in substrate transformations within the catalytic cycle of cytochrome P450 enzymes (P450s). A key constituent of Cpd I is the iron(IV)-oxo unit, a structural motif also found in other heme enzymes and nonheme enzymes. In this study, we performed ab initio valence bond (VB) calculations, employing the valence bond self-consistent field (VBSCF) and breathing orbital valence bond (BOVB) methods, to unveil the bonding nature of this vital "Fe(IV)═O″ unit in bioinorganic chemistry. Comparisons were drawn with the triplet O₂ molecule, which shares some electronic characteristics with iron(IV)-oxo. Additionally, Cpd I models of horseradish peroxidase (HRP) and catalase (CAT) were analyzed to assess the proximal ligand effect on the electronic structure of iron(IV)-oxo. Our VB analysis underscores the significant role of noncovalent resonance effects in shaping the iron(IV)-oxo bonding. The resonance stabilization within the π and σ frameworks occurs to comparable degrees, with additional stabilization resulting from resonance between VB structures from these frameworks. Furthermore, we elucidated the substantial influence of proximal and equatorial ligands in modulating the relative significance of different VB structures. Notably, in the presence of these ligands, iron(IV)-oxo is better described as iron(III)-oxyl or iron(II)-oxygen, displaying weak covalent character but enhanced by resonance effects. Although both species exhibit diradicaloid characters, resonance stabilization in iron(IV)-oxo is weaker than in O₂. Further exploration using the Laplacian of electron density shows that, unlike O₂, which exhibits a charge concentration region between its two oxygen atoms, iron(IV)-oxo species display a charge depletion region.