Exploring Bonding in Bioinorganic Chemistry: Ab Initio Valence Bond Calculations of Iron(II)‐CO and Iron(IV)‐Oxo Units in Cytochrome P450 under Oriented External Electric Fields

Abstract

AbstractWe performed ab initio valence bond (VB) calculations under oriented external electric fields (OEEFs) to explore the bonding nature of iron(II)‐CO and iron(IV)‐oxo units in cytochrome P450 enzymes (P450s). By utilizing ligand‐free models and analyzing changes in electronic structures under OEEFs, we gained insights into how ligands influence the iron center in realistic environments. Our findings revealed that ligand effects in P450s, exerted by the proximal and equatorial ligands, align with an electric field of approximately −0.125 to −0.100 au along the bond axis (Fz). Additionally, the proximal thiolate ligand alone corresponds to a weaker field, with Fz values around −0.060 to −0.050 au. Negative Fz values enhanced π backdonation while suppressing σ donation in iron(II)‐CO, whereas positive Fz values exhibited the opposite trend. Furthermore, negative Fz values significantly stabilized VB structures with higher oxidation states of Fe in iron(IV)‐oxo. In the absence of OEEFs, the oxidation state of Fe in iron(IV)‐oxo is predominantly Fe(II). However, under negative Fz values, VB structures with Fe(III) character become considerably more stable. These findings underscore the significant influence of external electric fields – and by extension, ligands – on the electronic properties of metal‐containing bioinorganic systems.