K-region oxides and imines derived from alkylated benz[a]anthracene congeners: synthesis, stability in aqueous media and mutagenicity.
The K-region oxides and imines of benz[a]anthracene, 1-methylbenz[a]anthracene, 7-methylbenz[a]anthracene, 7-ethylbenz[a]anthracene and 7,12-dimethylbenz[a]anthracene were synthesized and characterized (melting point, 1H-NMR and electron impact mass spectra, elemental analysis, IR spectroscopy). All 10 compounds showed high mutagenic activity in Salmonella typhimurium (reversion of his- strains TA97, TA98, TA100 and TA104). The arene imines were more potent than the corresponding arene oxides. Alkyl substitutions strongly influenced the activities. Furthermore, all compounds were more active when exposure took place in the absence of inorganic ions than when KCl (125 mM) was present. The influence of the exposure medium was more pronounced with strain TA98 than with strain TA100. The half-lives of the test compounds were determined from mutagenicity experiments in which the compound was added to the exposure medium at varying times before the bacteria. In dilute sodium phosphate buffer (10 mM, pH 7.4), the half-lives of these chemicals (or their biological activity) varied from 0.5 to 110 min. Addition of KCl (150 mM) did not measurably affect the half-lives of some test compounds and appeared to slightly shorten those of others. Therefore, it is unlikely that the strong effect of KCl on mutagenicity and the dependence of this effect on the bacterial strain used can be explained by influences of KCl on the test compounds. Rather, it appears more likely than an effect of KCl on the bacteria may be an important factor. This study provides further examples of strong influences of unobtrusive media components on mutagenicity. It also demonstrates that small structural changes (alkyl substituents at diverse positions of the aromatic system) may play an important role in chemical reactivity and biological activity.