Oxidized metabolites from cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs). A DFT model study of their carbocations formed by epoxide ring opening.

BOROSKY, GABRIELA L.; LAALI, KENNETH K.

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY

JOHN WILEY & SONS LTD

Año: 2010

0894-3230

A density functional theory (DFT) study aimed at understanding structure-reactivity relationships in the oxidized metabolites of cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) is reported.  Epoxidation at various  positions was examined in order to identify the most stable epoxide in each class of CP-PAHs. Relative energies of the carbocations resulting from O-protonation and epoxide ring opening were analyzed and compared, taking into account the available biological activity data on these compounds. Geometrical, electronic and conformational issues were considered. Charge delocalization modes in the resulting carbocations were deduced via the natural population analysis (NPA)-derived changes in charges. Computational results pointed to the importance of the unsaturated cyclopenta ring on the reactivity of these compounds. The reported bioactivity of this highly mutagenic/carcinogenic family of PAHs was observed to parallel their relative carbocation stabilities. A different behaviour was observed in crowded nonplanar structures possessing a distorted aromatic system. A covalent adduct formed between a CP-PAH epoxide and a purine base was computed inside a DNA fragment employing the ONIOM method.