One-Electron Oxidation of 6-Substituted Benzopyrenes by Manganic Acetate. A Model for Metabolic Activation

Article abstract of DOI:10.1021/jo00276a013

Radical cations of benzopyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3*2H2O.Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion.BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of 1,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones.In the case of 6-ClBP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP.These results indicate that nucleophilic substitution of BP-radical-cation and 6-FBP-radical-cation occurs exclusively at C-6.For 6-ClBP-radical-cation and 6-BrBP-radical-cation substitution at C-1 and C-3, which are the positions of second highest charge density in their radical cations after C-6, complete successfully for nucleophilic substitution.For 6-CH3BP-radical-cation charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack.Competitive acetoxylation of 6-CH3BP-radical-cation also occurs to a minor extent at C-1 and C-3.These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases.Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.