Transition-state alkylation geometries of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene enantiomeric isomers with nucleic acid dimers.
The steric contact spaces associated with the reaction of the enantiomeric isomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (I) with the exocyclic amino group of guanine of dinucleoside dimer structures were examined for a fixed transition-state geometry. This reaction is sterically prohibited for the B form DNA conformation. If, however, the nucleic acid structure is deformed, such that the distance between two adjacent base pairs (one containing guanine and cytosine) is maximized, sterically allowed transition-state geometries can be identified. It was not possible to uniquely identify the preferred transition-state complex with respect to nucleic acid structure or isomer of I. However, two types of general transition-state geometries were observed. In one, I was located "outside" the nucleic acid structure; in the other geometry, I was intercalated between adjacent base pairs in the transition state. The intercalation process might serve as a physical catalyst for the alkylation of NH2-guanine by I.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000478:Alkylation; D001580:Benzopyrenes / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D013237:Stereoisomerism
D001580:Benzopyrenes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA