Theoretical studies on the carcinogenic activity of diol epoxide derivatives of PAH: proton affinity and aromaticity as decisive descriptors.

A comparative study between bay-region and nonbay-region diol epoxide (DE) derivatives of seventeen carcinogenic polycyclic aromatic hydrocarbons (PAHs) was carried out using the B3LYP/6-31G(d,p) level of density functional theory to understand the factors responsible for the increased carcinogenic activity of bay-region derivatives. Molecular electrostatic potential analysis as well as proton affinity calculations showed that the epoxide sites of bay-region derivatives are much more reactive than the corresponding nonbay-region analogs. The charge delocalization mode in the carbocation intermediates resulting from the protonation reactions was followed through LUMO analysis. The relative aromaticity in the different rings in the arenium ions was gauged by NICS(1)(zz) computations. Both these calculations revealed that the protonated DEs (DEH(+)) are stabilized by higher aromaticity in the bay-region derivatives than the nonbay-region derivatives. Hence, a bay-region DEH(+) can be retained in the reacting medium for a longer time than compared with the DEH(+) formed from a nonbay-region DEs. Thus the high carcinogenic activity of bay-region DEs is attributed to the high reactivity of the epoxide system for protonation and the high thermodynamic stability of the resulting cation. Multiple regression analysis also confirms the above results wherein proton affinity and aromaticity significantly explain the variations in the carcinogenic activity of the molecules under study.