The Effect of Temperature on the Stereochemistry of Adducts and Hydrolysis Products Derived from anti-Benzo[a]pyrene Diol Epoxide in the Presence and Absence of Halide Ions

The activation of benzo[a]pyrene involves the formation of bay region diol epoxides, which can directly alkylate DNA. The products of this reaction are primarily trans exocyclic amino group adducts. Halide-catalyzed alkylation by an S N 2 mechanism also occurs and at the same sites in DNA but, in this reaction, the major products are cis adducts. At 0 °C and in the absence of halide ion, 19% of the adducts formed by alkylation of dAMP are cis. This value increases to 43% and 84% in the presence of 100 mM chloride and iodide, respectively. In general, increasing temperature also increases the fraction of cis products in the alkylation and hydrolysis reactions. These effects are reduced in the presence of halide ions. The temperature effect on stereochemistry is probably due to the higher energy of activation required for the formation of cis versus trans adducts.