Insights into Cytochrome P450 Enzyme Catalyzed Defluorination of Aromatic Fluorides
Yi Zhang, Thirakorn Mokkawes, Sam P. de Visser
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.
Topics & Concepts
FluorineChemistryProtonCatalysisCytochrome P450EpoxideElectrophileElectrophilic fluorinationDensity functional theoryComputational chemistryEnzymeStereochemistryCombinatorial chemistryOrganic chemistryPhysicsQuantum mechanicsMetal-Catalyzed Oxygenation MechanismsPharmacogenetics and Drug MetabolismFluorine in Organic Chemistry