High-valent oxygen intermediates of mononuclear non-heme iron enzymes [electronic resource] : geometric/electronic structure and reactivity

Mononuclear non-heme iron (NHFe) enzymes catalyze a wide variety of biologically-important reactions such as hydroxylation, halogenation, desaturation, ring closure, and electrophilic aromatic substitution. The key intermediate in the catalytic cycle is the S = 2 Fe(IV)=O species, capable of abstracting an H-atom from inert C--H bonds as strong as 106 kcal/mol. The Fe(IV)=O intermediate in enzymes is transient and difficult to trap; as such, stable synthetic analogs have proven invaluable for spectroscopic elucidation of the geometric/electronic structure of the Fe(IV)=O unit and how it is activated for reactivity. Such biomimetic Fe(IV)=O model complexes can be either intermediate-spin (S = 1) or high-spin (S = 2) in contrast to the S = 2 ground state of enzyme intermediates. For an S = 1 Fe(IV)=O species, the Fe--oxo [beta] [pi]*-frontier molecular orbital (FMO) [from the combination of Fe d(xz/yz) and oxo p(x/y)] is involved in H-atom abstraction, and this FMO requires a side-on approach ([pi]-attack) to achieve maximum overlap with the substrate C--H bond. Through magnetic circular dichroism (MCD) and nuclear vibrational resonance spectroscopy (NRVS) studies, the reactivity of the S = 1 Fe(IV)=O unit has been shown to be affected by the oxo contribution in the [pi]*-FMO, where a larger oxo contribution results in greater orbital overlap (with the substrate C--H) and higher reactivity; also, the [pi]-attack pathway results in steric clashes between substrate and ligand, giving a significant steric contribution to the energy of the reaction barrier. For an S = 2 Fe(IV)=O species, the Fe--oxo [alpha] [sigma]*-FMO [Fe d(z2) and oxo p(z)] is spin-polarized (exchange-stabilized) to an energy level comparable with its [pi]*-FMO, making it accessible as a second pathway ([sigma]-attack) for reactivity. In the S = 2 Fe(IV)=O model complex ligated by TMG3tren, this [sigma]*-FMO is active but is axially hindered by the ligand, again giving a large steric contribution to the reaction barrier; however, the intrinsic electronic reaction barriers of the S = 2 [sigma]*-FMO and the S = 1 [pi]*-FMO are comparable, suggesting they are similarly active in H-atom abstraction. Furthermore, MCD excited-state spectroscopy in combination with multiconfigurational calculations on the S = 2 model reveal two different [pi]-pathways for reactivity involving Fe(III)—oxyl[p(x), [pi]] character, in addition to the [sigma]-pathway involving Fe(III)—oxyl[p(z), [sigma]] character, showing that the S = 2 Fe(IV)=O unit is activated for both [pi] and [sigma] H-atom abstraction reactivities. Finally, the S = 2 enzyme intermediate for the halogenase SyrB2 was trapped and structurally characterized by NRVS, revealing two possible 5-coordinate trigonal bipyramidal candidates with the Fe--oxo vector oriented either perpendicular or parallel to the substrate C--H bond. Importantly, this difference in orientation leads to Fe(III)—OH products oriented efficiently for different rebound reactivities -- native halogenation in the case of perpendicular orientation and non-native hydroxylation in the case of parallel orientation.

Keywords: Chemistry
Advisor: Solomon Edward I. primary advisor. Thesis advisor
Hedman B. (Britt)
Hodgson Keith