Inactivation of Cytochrome P-450 during Catalytic Oxidation of a 3-sydnone: N-Vinyl Heme Formation via Insertion into the Fe-N Bond

Article abstract of DOI:10.1021/ja00278a037

A 3-<(2-arylthio)ethyl>-4-methylsydnone has been synthesized and shown to destroy hepatic microsomal cytochrome P-450 in a time- and NADPH-dependent manner.Enzyme destruction is accompanied by the formation of pyruvic acid and a green hepatic pigment.The pigment has been purified and identified by analytical and spectroscopic methods as a mixture of the four isomers of N-vinylprotoporphyrin IX.The results indicate that enzyme-catalyzed hydroxylation of the sydnone anionic carbon fragments the heterocyclic ring into pyruvic acid and a 2-(arylthio)ethyl diazonium species that reacts with the prosthetic heme group.Internal elimination of the arylthio moiety from a bridged Fe-CHR-N adduct rationalizes the formation of N-vinylprotoporphyrin IX.The results provide strong support for the biological formation of bridged Fe-C-N species and an explanation for some of the biological activities of the sydnones.