Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents

Abstract

To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta [cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis-and trans-stereo-isomers in a close to 1:1 ratio ( 1 H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (±S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

Electronic Structure Study of Thermal Intraconversions of Some Dicyclopenta-Fused Polycyclic Aromatic Compounds

“…The free energies of P2 and P3 are by 15.34 and 22.90 kcal/mol lower than that of P1. This finding is in accord with the experimentally observed stabilities of the three isomers …”

“…This finding is in accord with the experimentally observed stabilities of the three isomers. 1 Two mechanisms for the isomerization of P1 into P2 were found. The general outline of these mechanisms is presented in Scheme 1.…”

“…Among the variety of possible PAHs, a relatively small number of them is considered to be responsible for the genotoxicity of combustion products. In addition, this property is prescribed to their specific structure, which, in most cases, implies the presence of five-membered rings as part of PAHs. − Many thermodynamic properties of various cyclopenta-fused PAHs (CP-PAHs) have been established …”

“…In addition, this property is prescribed to their specific structure, which, in most cases, implies the presence of five-membered rings as part of PAHs. [1][2][3] Many thermodynamic properties of various cyclopenta-fused PAHs (CP-PAHs) have been established. 4 Flash vacuum pyrolisis (FVP) 5 appears to be a good method for obtaining CP-PAHs in high yields.…”