posted on 2024-03-01, 22:03authored byVyshnavi Vennelakanti, Mugyeom Jeon, Heather J. Kulik
We
study active-site models of nonheme iron hydroxylases and their
vanadium-based mimics using density functional theory to determine
if vanadyl is a faithful structural mimic. We identify crucial structural
and energetic differences between ferryl and vanadyl isomers owing
to the differences in their ground electronic states, i.e., high spin
(HS) for Fe and low spin (LS) for V. For the succinate cofactor bound
to the ferryl intermediate, we predict facile interconversion between
monodentate and bidentate coordination isomers for ferryl species
but difficult rearrangement for vanadyl mimics. We study isomerization
of the oxo intermediate between axial and equatorial positions and
find the ferryl potential energy surface to be characterized by a
large barrier of ca. 10 kcal/mol that is completely absent for the
vanadyl mimic. This analysis reveals even starker contrasts between
Fe and V in hydroxylases than those observed for this metal substitution
in nonheme halogenases. Analysis of the relative bond strengths of
coordinating carboxylate ligands for Fe and V reveals that all of
the ligands show stronger binding to V than Fe owing to the LS ground
state of V in contrast to the HS ground state of Fe, highlighting
the limitations of vanadyl mimics of native nonheme iron hydroxylases.