CP-arene oxides: the ultimate, active mutagenic forms of cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs)

Abstract

The bacterial mutagenic response (Ames-assay, Salmonella typhimurium strain TA98 ± S9-mix) of a series of monocyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) identified in combustion exhausts, viz. cyclopenta[ cd]pyrene ( 1), acephenanthrylene ( 2), aceanthrylene ( 3) and cyclopenta[ hi]chrysene ( 4), is re-evaluated. The mutagenic effects are compared with those exerted by the corresponding partially hydrogenated derivatives, 3,4-dihydrocyclopenta[ cd]pyrene ( 5), 4,5-dihydroacephenanthrylene ( 6), 1,2-dihydroaceanthrylene ( 7) and 4,5-dihydrocyclopenta[ hi]chrysene ( 8). It is shown that the olefinic bond of the externally fused five-membered ring of 1, 3 and 4 is of importance for a positive mutagenic response. In contrast, whilst CP-PAH 2 is found inactive, its dihydro analogue ( 6) shows a weak metabolism-dependent response. The importance of epoxide formation at the external olefinic bond in the five-membered ring is substantiated by the bacterial mutagenic response of independently synthesized cyclopenta[ cd]pyrene-3,4-epoxide ( 9), acephenanthrylene-4,5-epoxide ( 10), aceanthrylene-1,2-epoxide ( 11) and cyclopenta[ hi]chrysene-4,5-epoxide ( 12). Their role as ultimate, active mutagenic forms, when CP-PAHs 1, 3 and 4 exhibit a positive mutagenic response, is confirmed. Semi-empirical Austin Model 1 (AM1) calculations on the formation of the CP-arene oxides ( 9– 12) and their conversion into the monohydroxy-carbocations ( 9a– 12a and 9b– 12b) via epoxide-ring opening support our results. For 2 and 4, which also possess a bay-region besides an annelated cyclopenta moiety, the calculations rationalize that epoxidation at the olefinic bond of the cyclopenta moiety is favoured.