Version 2 2024-02-05, 12:03Version 2 2024-02-05, 12:03
Version 1 2024-01-31, 18:04Version 1 2024-01-31, 18:04
journal contribution
posted on 2024-02-05, 12:03authored byYasuhiro Tateishi, Kevin D. McCarty, Martha V. Martin, F. Peter Guengerich
Most cytochrome P450
(P450) oxidations are considered to occur
with the active oxidant being a perferryl oxygen (FeO3+, Compound I). However, a ferric peroxide (FeO2̅, Compound 0) mechanism has been proposed, as well, particularly
for aldehyde substrates. We investigated three of these systems, the
oxidative deformylation of the model substrates citronellal, 2-phenylpropionaldehyde,
and 2-methyl-2-phenylpropionaldehyde by rabbit P450 2B4, using 18O labeling. The formic acid product contained one 18O derived from 18O2, which is indicative of
a dominant Compound 0 mechanism. The formic acid also contained only
one 18O derived from H218O, which
ruled out a Compound I mechanism. The possibility of a Baeyer–Villiger
reaction was examined by using synthesized possible intermediates,
but our data do not support its presence. Overall, these findings
unambiguously demonstrate the role of the Compound 0 pathway in these
aldehyde oxidative deformylation reactions.