The binding of copper ions to daunomycin and adriamycin

Using visible absorption, CD, ¹H nmr, and epr spectroscopy, the Cu(II) binging properties of daunomycin, adriamycin, and N-trifluoroacetyl daunomycin in water and ethanol have been explored. The drugs form two water soluble complexes having Cu-drug stoichiometries of 1:1 and 1:2, and with apparent pK_as of formation of 5.6 and 6.5, respectively. At pH values above ～8, the drugs form insoluble polymeric complexes with Cu(II). Similar species are also observed in ethanol. The structure of the compounds have been interpreted in terms of binding of the deprotonated hydroxyquinone portion of the drug to the copper ion. No evidence for the binding of the amino group on daunosamine was found.