Oxygen-18 Labeling Defines a Ferric Peroxide (Compound 0) Mechanism in the Oxidative Deformylation of Aldehydes by Cytochrome P450 2B4
Year: 2024
Type: article
Abstract: Most cytochrome P450 (P450) oxidations are considered to occur with the active oxidant being a perferryl oxygen (FeO 3+, Compound I). However, a ferric peroxide (FeO 2 ̅, 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 18 O labeling. The formic acid product contained one 18 O derived from 18 O 2, which is indicative of a dominant Compound 0 mechanism. The formic acid also contained only one 18 O derived from H 2 18 O, 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.
Source: ACS Catalysis
Institution: Vanderbilt University
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4391383010