Substrate-dependent changes of the oxidative O-dealkylation mechanism of several chemical and biological oxidizing systems

The O-dealkylation mechanisms of a series of alkyl aryl ethers, mediated by several chemical and biological oxidizing systems, i.e. Cu2+-ascorbic acid-O-2, gamma-radiolysis and rat liver microsomes-NADPH/O-2, were examined, In every oxidizing system, the O-dealkylation mechanisms changed dramatically depending on the nature of the substrates, In the Cu2+-ascorbic acid-O-2 system and gamma-radiolysis, electron density at the ipso-position and the ease of H atom abstraction from the alkyl moiety of the substrates were critical to determine the O-dealkylation mechanism, In the cytochrome P450-dependent monooxygenases, the determinant was whether or not the substrate has a phenolic hydroxy group at an ortho- or para-position relative to the alkoxy group, The results have led us to propose a new O-dealkylation mechanism involving the initial formation of a phenoxyl radical.