Chelation of copper(II) by daunomycin and 5-iminodaunomycin and interaction of the complexes with mononucleotides: An ESR study

Coordination of copper(II) ions by daunomycin and 5-iminodaunomycin has been studied by electron spin resonance spectroscopy, at various values of pH and r, the anthracycline-to-Cu(II) molar ratio. At r = 1–5, polymeric complexes are formed in the case of daunomycin. At r = 5, a mononuclear complex is predominant and at r = 10, this is the only one formed with the 63Cu and 65Cu hyperfine interaction being clearly defined in the g∥ region (g∥ = 2.26, 63A∥ = 175; 65A∥ = 190 G). For 5-iminodaunomycin both chelation sites are involved in the coordination and a polymeric structure (in which exchange interactions between Cu(II) centers operate) is stable in the range r = 1–3. At r = 3, the triplet state of a dinuclear Cu(II) complex is observed and 5-iminodaunomycin behaves as both a bridging and a terminal ligand. For r = 5–10, the dinuclear complex coexists with the mononuclear one. In the presence of mononucleotides dGMP, dAMP, dCMP and thymidine, no ternary complex such as mononucleotide/Cu(II)/anthracycline was observed.