The peri effect in aromatic hydrocarbon carcinogenesis: An empirical force field examination

Abstract

AbstractMethyl substitutents located peri to bay‐region benzo rings of polycyclic aromatic hydrocarbons generally reduce or eliminate carcinogenic activity, most likely because such substituents force the hydroxyl groups of dihydrodiol intermediates to adopt preferentially pseudodiaxial, rather than pseudodiequatorial, conformations. Empirical force field calculations have been employed to examine the influences of peri and other positional substituents on hydroxyl conformation, taking naphthalene, anthracene, and phenanthrene as model compounds. For the unsubstituted naphthalene and anthracene dihydrodiols, the pseudodiequatorial conformation is preferred. This preference is reduced by adjacent methyl substitution and reversed by peri methyl substitution. Because of steric crowding the phenanthrene bay‐region dihydrodiol preferentially adopts a pseudodiaxial conformation. The results are discussed in relation to recent experimental evidence.