Insights into Cytochrome P450 Enzyme Catalyzed Defluorination of Aromatic Fluorides

Yi Zhang; Thirakorn Mokkawes; Sam P de Visser

doi:10.1002/anie.202310785

Insights into Cytochrome P450 Enzyme Catalyzed Defluorination of Aromatic Fluorides

Angew Chem Int Ed Engl. 2023 Oct 16;62(42):e202310785. doi: 10.1002/anie.202310785. Epub 2023 Sep 8.

Authors

Yi Zhang^{1

2}, Thirakorn Mokkawes^{1

2}, Sam P de Visser^{1

2}

Affiliations

¹ Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M17DN, UK.
² Department of Chemical Engineering, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

PMID: 37641517
DOI: 10.1002/anie.202310785

Abstract

Density functional calculations establish a novel mechanism of aromatic defluorination by P450 Compound I. This is achieved via either an initial epoxide intermediate or through a 1,2-fluorine shift in an electrophilic intermediate, which highlights that the P450s can defluorinate fluoroarenes. However, in the absence of a proton donor a strong Fe-F bond can be obtained as shown from the calculations.

Keywords: Biocatalysis; Density Functional Theory; Enzyme Catalysis; Hydroxylation; Inorganic Reaction Mechanisms.