Solvolysis of the bay region diol epoxides of 7-methylbenz[c]acridine in aqueous solution and effect of DNA

Abstract

The hydrolysis of the bay-region syn- and anti-diol epoxides of 7-methylbenz[c]acridine (7MBAC) has been studied in aqueous solution. The rates of reaction have been measured at low ionic strength in the absence and presence of DNA, as a function of pH and temperature, by spectrophotometry and high-pressure liquid chromatography. The major products are the corresponding tetrols, but the syn diastereomer also undergoes rearrangement to a keto diol. The hydrolysis reaction is catalyzed by both acid and DNA and conforms to a mechanism in which a physical association complex is formed between diol epoxide and DNA, followed by two parallel pathways in which the diol epoxide either is hydrolyzed or becomes covalently bound to the DNA. The rate constants are significantly lower than the corresponding ones for the diol epoxides of benzo[a]pyrene. However, the extent of covalent binding of 7MBAC diol epoxides to DNA was found to be 12-30%, depending on the pH of reaction, values that are 2-3 times greater than for the benzo[a]pyrene diol epoxides reacted under the same conditions of low ionic strength. The very small changes (2 nm) in spectroscopic characteristics observed for the covalently bound adduct as compared to the free tetrol suggest that the binding occurs with little intercalation of the compound between the base pairs of DNA.