Mechanism of the microsomal N-hydroxylation of para-substituted benzamidines.

With the aid of HPLC analyses and simple Michaelis-Menten kinetics, the maximum rates of the microsomal N-oxygenation of various para-substituted benzamidines 1 to benzamidoximes 2 were determined. The presence of electron-donating substituents increased the rates whereas the presence of electron-accepting substituents decreased them. A significant correlation between the logarithm of the maximum rates with the Hammett sigma p constants was found for a reaction constant of rho = -0.88. These results support the postulated radical mechanism for the N-oxygenation by the cytochrome P-450 enzyme system.