Oxidized metabolites from benzo[a]pyrene, benzo[e]pyrene, and aza-benzo[a]pyrenes. A computational study of their carbocations formed by epoxide ring opening reactions.

BOROSKY, GABRIELA L.; LAALI, KENNETH K.

Organic & Biomolecular Chemistry

The Royal Society of Chemistry

Año: 2007 vol. 5 p. 2234 - 2242

1477-0520

A DFT study aimed at understanding structure-reactivity relationships and fluorine substitution effects on carbocation stability in benzo[a]pyrene (BaP),  benzo[e]pyrene (BeP), and aza-benzo[a]pyrenes (aza-BaPs) derivatives are reported. Relative energies of the resulting carbocations were examined and compared, taking into account the available biological activity data on these compounds. O-protonation of the epoxides and diol epoxides leads to carbocation formation by barrierless processes. Charge delocalization modes in the resulting carbocations were deduced via NPA-derived changes in charges, and fluorine substitution effects were analyzed on the basis of charge density at different carbocation positions. Thus, fluorine substitution at sites bearing negative charge generated inductive destabilization of the carbocation , whereas a fluorine atom at a ring position which presented significant positive charge density produced a less pronounced destabilization due to fluorine p-p back-bonding. Protonation reactions were also studied for the azaBaPs. In selected cases, the covalent adducts generated via bond formation with the exocyclic nitrogen of cytosine were computed and relative energies and geometries of the resulting adducts were examined.