DNA cleavage by Di- and trihydroxyalkylbenzenes. Characterization of products and the roles of O2, Cu(II), and alkali

Article abstract of DOI:10.1021/ja00156a005

Several 5-alkyl-1,3-dihydroxybenzene (5-alkylresorcinol, 1) and 6-alkyl-1,2,4-trihydroxybenzene (2) derivatives were prepared and used to study the mechanism by which such compounds effect Cu(II)-dependent DNA strand scission. Comparison of the methyl, n-pentyl, n-undecyl, and n-hexadecyl derivatives in each structural series indicated that the efficiency of DNA cleavage increased with increasing length of the alkyl substituent. DNA cleavage by the 5-alkylresorcinols appears to involve initial oxygenation of the benzene nucleus, a process that occurs readily at alkaline pH in the presence of Cu²⁺ and O₂. The resulting trihydroxylated benzenes mediate DNA cleavage in a reaction dependent on the presence of both Cu²⁺ and O₂. The mechanism appears to involve reduction of Cu²⁺ by the trihydroxybenzene moiety in 2, with subsequent formation of reactive oxygen species. The ability of catalase and dimethyl sulfoxide to suppress DNA strand scission is consistent with the intermediacy of H₂O₂ and ^?OH in the DNA strand scission process.