Chemical reactivities and mutagenicities of a series of chloromethylbenzo[ a]pyrenes

Abstract

The chemical and mutagenic properties of a series of chloromethylbenzo[ a]pyrenes (chloromethyl-BaP) (chloromethyl groups in position 1-, 4-, 5-, 6-, 10-, 11- or 12-) were studied in order to address the question of the importance of arylmethyl carbocations as possible ultimate carcinogens of methylated polycyclic aromatic hydrocarbons (PAH). The rates of solvolysis of the series of chloromethyl-BaP in 50% aqueous acetone decrease in the order: 6 > 1 ⪢ 4 > 12 > 5 > 10 > 11. There is a rough correlation ( r = −0.80, P < 0.05) between rates of solvolysis and the carbon chemical shifts of the methylene carbons. There is a good correlation ( r = 0.98, P < 0.001) between the rates of solvolysis and the gas phase stabilities of the carbocations, (M + − 35), obtained from mass spectral analysis. The mutagenicities of the series of chloromethyl-BaP in the Ames assay with strains TA98 and TA100 showed strong to very strong mutagenicities for the 4-, 5-, 10-, 11- and 12-isomers and weak mutagenicities for the 1- and 6-isomers. The corresponding hydroxymethyl-BaP were not mutagenic. The mutagenicities of some of the chloromethyl-BaP are among the highest reported for direct-acting (not requiring microsomal activation) mutagens in the Ames assay.