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

Journal Article · · Chemical Research in Toxicology; (USA)
DOI:https://doi.org/10.1021/tx00014a007· OSTI ID:6363465
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 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.
OSTI ID:
6363465
Journal Information:
Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 3:2; ISSN 0893-228X; ISSN CRTOE
Country of Publication:
United States
Language:
English