Intercalation of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene enantiomeric isomers with dinucleoside dimers: a basis for alkylation of the 2-amino group in guanine

The minimum-energy intercalation-complex geometries of the (+/-)enantiomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzoa]pyrene (I) with two dinucleoside dimers were determined. The purpose of these calculations was to see if I could intercalate into DNA in such a way that the observed alkylation of the 2-amino group of guanine could occur subsequent to intercalation. For both dinucleoside dimer sequences, it was found that the (+)-(9 alpha, 10 alpha) isomer could form a stable intercalation complex in which the orientation and distance of the epoxide of I to the 2-amino group of guanine was close to the calculated critical transition-state geometry for the alkylation reaction. The (-)enantiomers can intercalate, but not in a manner close to the transition-state geometry necessary for the alkylation of the 2-amino group of guanine.