title: Frontier Molecular Orbital Contributions to Chlorination versus Hydroxylation Selectivity in the Non-Heme Iron Halogenase SyrB2.
abstract: 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.
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, The Czech Academy of Sciences , Dolejškova 2155/3, 182 23 Prague 8, Czech Republic.
authors.forename: Martin
authors.identifier: 0000-0001-5118-141X
authors.initials: M
authors.lastname: Srnec
authors.affiliation: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors.forename: Edward I
authors.initials: EI
authors.lastname: Solomon
mesh_terms: D054879:Halogenation; D006900:Hydroxylation; D008968:Molecular Conformation; D019159:Nonheme Iron Proteins / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D019159:Nonheme Iron Proteins