Substituent effect studies on aza-PAH carbocations; fluorinated and methylated carbocations from oxidized metabolites of dibenz[a,h]acridine, benz[a]acridine, and benz[c]acridine; a DFT study.

BOROSKY, GABRIELA L.; LAALI, KENNETH K.

Honolulu, Hawaii, USA

Congreso; International Chemical Congress of Pacific Basin Societies, Pacifichem 2005; 2005

American Chemical Society (ACS), the Canadian Society for Chemistry (CSC), the Chemical Society of Japan (CSJ), the New Zealand Institute of Chemistry (NZIC), the Royal Australian Chemical Institute (RACI), and the Korean Chemical Society (KCS)

Metabolic activation of PAHs and aza-PAHs involves formation of their bay-region diol epoxides. The benzylic carbocations generated from these electrophilic diol epoxides by opening of the O-protonated epoxide ring are capable of forming covalent adducts with the nucleophilic sites in DNA and RNA, leading to alteration of genetic material. Experimental data revealed that the position of the nitrogen heteroatom in the aza-PAHs could have a significant effect on the carcinogenic potencies of their metabolites. Structure/activity relationships have played an important role towards understanding the mechanism of activation of PAHs. It has been established that adequate substitution has a major impact on tumorigenic activity. The relationship between site of methylation and/or fluorination and biological activity is a topic of continuing interest.                        In continuation of our previous work (Borosky, G. L., Laali, K. K., Org. Biomol. Chem. 2005, 3, 1180) we have studied the carbocations derived from the bay-region epoxides and diol epoxides of a series of methylated and fluorinated aza-PAHs. Relative carbocation stabilities (in gas phase and in water), GIAO-NMR chemical shifts (13C and 19F), and NPA charges were used to gauge substituent effects. Whenever possible the results are compared with the available biological data on various isomers.