Studies of the mechanisms of adduction of 2 '-deoxyadenosine with styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides

The mechanism of adduction of 2'-deoxyadenosine by styrene oxide and polycy clic aromatic hydrocarbon dihydrodiol epoxides has been explored using N-15 (6)-labeled adenine nucleosides. The extent of reaction at N1 versus N-6 wa s evaluated by H-1 NMR of the N-6 adducts after allowing Dimroth rearrangem ent to occur. Products arising from attack at N1 followed by Dimroth rearra ngement exhibited a small two-bond H-1-N-15 coupling constant (N1-H2 J simi lar to 13 Hz); products from direct attack exhibited a much larger one-bond H-1-N-15 coupling constant (J similar to 90 Hz). In the case of styrene ox ide, all of the N-6 beta adduct arose by initial attack at N1, whereas the majority (70-80%) of the N-6 alpha adducts came from direct attack. The sty rene oxide reaction was also studied with a self-complementary oligodeoxynu cleotide (24-mer) containing nine N-15(G)-labeled adenine residues. NMR exa mination of the N-6 alpha- and beta-styrene oxide adducts isolated after en zymatic degradation of the 24-mer gave very similar results, indicating tha t N1 attack can occur readily even with a duplexed oligonucleotide. With th e PAH dihydrodiol epoxides, only naphthalene dihydrodiol epoxide exhibited significant initial reaction at N1 (50%). No detectable rearranged product was seen in reactions with benzo[a]pyrene dihydrodiol epoxide or non-bay or bay region benz[a]anthracene dihydrodiol epoxide; interestingly, a small a mount of N1 attack (5-7%) was seen in the case of benzo[c]phenanthrene dihy drodiol epoxide. It appears that initial attack at N1 is only a significant reaction pathway for epoxides attached to a single aromatic ring.