Radical Rebound Hydroxylation Versus H-Atom Transfer in Non-Heme Iron(III)-Hydroxo Complexes: Reactivity and Structural Differentiation

The
characterization of high-valent iron centers in enzymes has
been aided by synthetic model systems that mimic their reactivity
or structural and spectral features. For example, the cleavage of
dioxygen often produces an iron­(IV)-oxo that has been characterized
in a number of enzymatic and synthetic systems. In non-heme 2-oxogluterate
dependent (iron-2OG) enzymes, the ferryl species abstracts an H-atom
from bound substrate to produce the proposed iron­(III)-hydroxo and
caged substrate radical. Most iron-2OG enzymes perform a radical rebound
hydroxylation at the site of the H-atom abstraction (HAA); however,
recent reports have shown that certain substrates can be desaturated
through the loss of a second H atom at a site adjacent to a heteroatom
(N or O) for most native desaturase substrates. One proposed mechanism
for the removal of the second H-atom  involves a polar-cleavage
mechanism (electron transfer-proton transfer) by the iron­(III)-hydroxo,
as opposed to a second HAA. Herein we report the synthesis and characterization
of a series of iron complexes with hydrogen bonding interactions between
bound aquo or hydroxo ligands and the secondary coordination sphere in
ferrous and ferric complexes. Interconversion among the iron species
is accomplished by stepwise proton or electron addition or subtraction,
as well as H-atom transfer (HAT). The calculated bond dissociation
free energies (BDFEs) of two ferric hydroxo complexes, differentiated
by their noncovalent interactions and reactivity, suggest that
neither complex is capable of activating even weak C–H bonds,
lending further support to the proposed mechanism for desaturation
in iron-2OG desaturase enzymes. Additionally, the ferric hydroxo species
are differentiated by their reactivity toward performing a radical
rebound hydroxylation of triphenylmethylradical. Our findings should
encourage further study of the desaturase systems that may contain
unique H-bonding motifs proximal to the active site that help bias
substrate desaturation over hydroxylation.