Covalent binding of aromatic hydrocarbons to cellular macromolecules, the first probable step in the tumor-initiating process, requires metabolic activation by monooxygenase enzyme systems. Acid-catalyzed proton-deuterium exchange was used as a model to simulate the electrophilic oxygen atom activated by such enzymes. Kinetics of exchange with deuterium ion for a series of carcinogenic and noncarcinogenic methylbenzanthracenes were studied by NMR in two sets of conditions, i.e., CCl4-CF3COOD (85:15 v/v and 50:50 v/v). Deuteration of the potent carcinogen 7,12-dimethylbenz[a]anthracene at the most basic position C-12 generated a carbonium ion with charge localized at the complementary 7 position, resulting in the specific deuteration of the attached methyl group. Similarly, selective attack of deuterium ion on C-6 in 3-methylcholanthrene produced a carbonium ion with a high degree of charge localization at C-12b and, consequently, specific deuteration at the adjacent methylene group. This study has revealed that charge localization in the carbonium ion renders this intermediate chemically reactive; such a distinctive property might play a role in the bioactivation of these compounds.
ASJC Scopus subject areas
- Organic Chemistry