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.