Electronic Structure of the Ferryl Intermediate in the α‑Ketoglutarate Dependent Non-Heme Iron Halogenase SyrB2: Contributions to H Atom Abstraction Reactivity

Low temperature magnetic circular dichroism (LT MCD) spectroscopy in combination with quantum-chemical calculations are used to define the electronic structure associated with the geometric structure of the FeIVO intermediate in SyrB2 that was previously determined by nuclear resonance vibrational spectroscopy. These studies elucidate key frontier molecular orbitals (FMOs) and their contribution to H atom abstraction reactivity. The VT MCD spectra of the enzymatic S = 2 FeIVO intermediate with Br ligation contain information-rich features that largely parallel the corresponding spectra of the S = 2 model complex (TMG3tren)­FeIVO (Srnec, M.; Wong, S. D.; England, J.; Que, L. Jr.; Solomon, E. I. Proc. Natl. Acad. Sci. USA 2012, 109, 14326–14331). However, quantitative differences are observed that correlate with π-anisotropy and oxo donor strength that perturb FMOs and affect reactivity. Due to π-anisotropy, the FeIVO active site exhibits enhanced reactivity in the direction of the substrate cavity that proceeds through a π-channel that is controlled by perpendicular orientation of the substrate C–H bond relative to the halide–FeIVO plane. Also, the increased intrinsic reactivity of the SyrB2 intermediate relative to the ferryl model complex is correlated to a higher oxyl character of the FeIVO at the transition states resulting from the weaker ligand field of the halogenase.