Demethylation of N,N-dimethylaniline and p-Cyano-N,N-dimethylaniline and their N-oxides by cytochromes P450 sub(LM2) and P450 sub(CAM)

Cytochrome P450 catalyzes the efficient oxidation of secondary and tertiary amines, providing an important pathway of xenobiotic metabolism. The chemical mechanism of oxidative amine dealkylation has been biomimetically studied by using (mesotetraphenylporphinato)iron(III) chloride ((TPP)Fe super(III)Cl) and the exogenous oxidants N,N-dimethylaniline N-oxide (DMANO) and p-cyano-N,N-dimethylaniline N-oxide (p-CNDMANO). To help clarify the enzymatic mechanism of cytochrome P450 dependent amine dealkylation reactions, the authors have tested amine N-oxides as oxygen donors to purified rabbit liver cytochrome P450 sub(LM2) and bacterial cytochrome P450 sub(CAM). Intra- and intermolecular isotope effects on amine dealkylation were used to compare the mechanism of these exogenous oxidant supported reactions with that of the pyridine nucleotide/O sub(2) dependent ones.