Frontier Molecular Orbital Contributions to Chlorination versus Hydroxylation Selectivity in the Non-Heme Iron Halogenase SyrB2

This is the authors' abstract. We don't add key points for this paper.

The ability of an FeIV═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 (FeIV═O oriented perpendicular to the C-H bond of substrate) was found to lead to the S = 2 five-coordinate HO-FeIII-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.