SUBSTRATE-DEPENDENT CHANGES OF THE OXIDATIVE O-DEALKYLATION MECHANISMOF SEVERAL CHEMICAL AND BIOLOGICAL OXIDIZING SYSTEMS

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