Interaction of copper(II) ions with the daunomycin-calf thymus DNA complex

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Abstract
The interaction of Cu(II) with the native and heat-denatured DNA complexes of [the antineoplastic drugs] daunomycin and N-(trifluoroacetyl)daunomycin was examined by using absorption and circular dichroism spectroscopies. At low rt, where rt is the input molar ratio of drug to DNA phosphate, Cu(II) interacts with the native and heat-denatured calf thymus DNA complex of daunomycin to form a ternary complex involving the aglycon portion of the antibiotic, Cu(II) and DNA. A Job plot of the titration involving Cu(II) and heat-denatured DNA shows that the Cu(II)-drug stoichiometry in the ternary complex is .ltoreq. 1. Although the N-(trifluoroacetyl)daunomycin-native DNA complex does not form a ternary complex, the denatured DNA complex with the antibiotic does. Copper (II) titrations of the daunomycin-native DNA complex, at high rt, where both strongly and weakly bound antibiotic molecules are very likely present in solution, result in the formation of both the ternary species and binary complex involving only the metal ion and the antibiotic. The spectroscopic results indicate that in the ternary complex the Cu(II) ion is bound to the unintercalated aglycon portion of the antibiotic and probably also to the heterocyclic bases of DNA.