Chemical reactivity of protonated aziridine with nucleophilic centers of DNA bases.

Abstract

AbstractA series of molecular orbital calculations, using MINDO/3 and CNDO/2L methods, have been used to characterize the chemical reaction of protonated aziridine with DNA nucleophilic base sites. The N‐7 atom of guanine is found to be the preferred alkylation site only when the O‐6 atom of guanine is involved in base‐pair hydrogen bonding. Otherwise O‐6 is the predicted major site of alkylation. This indirectly suggests that protonated aziridine alkylation processes involve base‐paired DNA structures, since N‐7 guanine is the observed major site of alkylation. Alkylation of N‐3 adenine is predicted to be more favorable than chemical attack of the N‐7 adenine position. Both of these sites, however, are predicted to be less reactive than N‐7 of guanine. These chemical reactivity studies resolve alkylation specifically not achieved in the DNA–alkylator physical association calculations reported in the preceding paper.