Theoretical Study Related to the Carcinogenic Activity of Polycyclic Aromatic Hydrocarbon Derivatives

Ab initio, density functional, and semiempirical calculations concerning the reactivity of polycyclic aromatic hydrocarbons (PAHs) were performed. The reactions considered were those related to the carcinogenic activity of PAHs. The increased reactivity of the diol epoxide derivatives is explained by the greater propensity of benzene diol epoxide to undergo acid-catalyzed opening of the epoxide ring, as well as its thermodynamic tendency to react with nucleophiles in substitution reactions. However, rearrangement to phenol was the favored path for benzene oxide. Bay-region compounds were found to open spontaneously upon protonation, thus revealing a greater reactivity in the rate-determining step of the mechanism of carcinogenesis. A correlation was observed between the exothermicity of the process and the charge delocalization in the resulting carbocation. The enhanced activity of bay-region methyl-substituted compounds was attributed to the instability of the closed structures due to steric interactions rather than stabilization of the carbocations by hyperconjugation.