Exploring the Bonding\nNature of Iron(IV)-Oxo Species\nthrough Valence Bond Calculations and Electron Density Analysis

Compound I (Cpd I) plays a pivotal role in substrate\ntransformations\nwithin the catalytic cycle of cytochrome P450 enzymes (P450s). A key\nconstituent of Cpd I is the iron(IV)-oxo unit, a structural motif\nalso found in other heme enzymes and nonheme enzymes. In this study,\nwe performed ab initio valence bond (VB) calculations, employing the\nvalence bond self-consistent field (VBSCF) and breathing orbital valence\nbond (BOVB) methods, to unveil the bonding nature of this vital “Fe(IV)O″\nunit in bioinorganic chemistry. Comparisons were drawn with the triplet\nO<sub>2</sub> molecule, which shares some electronic characteristics\nwith iron(IV)-oxo. Additionally, Cpd I models of horseradish peroxidase\n(HRP) and catalase (CAT) were analyzed to assess the proximal ligand\neffect on the electronic structure of iron(IV)-oxo. Our VB analysis\nunderscores the significant role of noncovalent resonance effects\nin shaping the iron(IV)-oxo bonding. The resonance stabilization within\nthe π and σ frameworks occurs to comparable degrees, with\nadditional stabilization resulting from resonance between VB structures\nfrom these frameworks. Furthermore, we elucidated the substantial\ninfluence of proximal and equatorial ligands in modulating the relative\nsignificance of different VB structures. Notably, in the presence\nof these ligands, iron(IV)-oxo is better described as iron(III)-oxyl\nor iron(II)-oxygen, displaying weak covalent character but enhanced\nby resonance effects. Although both species exhibit diradicaloid characters,\nresonance stabilization in iron(IV)-oxo is weaker than in O<sub>2</sub>. Further exploration using the Laplacian of electron density shows\nthat, unlike O<sub>2</sub>, which exhibits a charge concentration\nregion between its two oxygen atoms, iron(IV)-oxo species display\na charge depletion region.