Frontier Molecular Orbital Contributions to Chlorination versus Hydroxylation Selectivity in the Non-Heme Iron...

The ability of an Fe^IV═O intermediate in SyrB2 to perform chlorination versus hydroxylation was computationally evaluated for different substrates that had been studied experimentally. The π-trajectory for H atom abstraction (Fe^IV═O oriented perpendicular to the C-H bond of substrate) was found to lead to the S = 2 five-coordinate HO-Fe^III-Cl complex with the C^• of the substrate, π-oriented relative to both the Cl^- and the OH^- ligands. From this ferric intermediate, hydroxylation is thermodynamically favored, but chlorination is intrinsically more reactive due to the energy splitting between two key redox-active dπ* frontier molecular orbitals (FMOs). The splitting is determined by the differential ligand field effect of Cl^- versus OH^- on the Fe center. This makes chlorination effectively competitive with hydroxylation. Chlorination versus hydroxylation selectivity is then determined by the orientation of the substrate with respect to the HO-Fe-Cl plane that controls either the Cl^- or the OH^- to rebound depending on the relative π-overlap with the substrate C radical. The differential contribution of the two FMOs to chlorination versus hydroxylation selectivity in SyrB2 is related to a reaction mechanism that involves two asynchronous transfers: electron transfer from the substrate radical to the iron center followed by late ligand (Cl^- or OH^-) transfer to the substrate.