Spectroscopic studies on iron complexes of different anthracyclines in aprotic solvent systems

Iron complexes of daunorubicin, idarubicin, pirarubicin, and doxorubicin in anhydrous DMF were studied by UV/vis, CD, fluorescence, Mossbauer, and EPR spectroscopy. Titration studies of the metal-free anthracyclines showed on e (UV-detectable) deprotonation step requiring 2 equiv of base, compared to 1 equiv for quinizarine. Metal complexation was studied at three different metal/ligand ratios, and with increasing amounts of base. The results obta ined from optical spectroscopy show the existence of two different complex species and give clear indications for the requirements of metal complexati on. Complex species I, formed at a low iron-to-ligand ratio, is less depend ent on base addition than complex species II formed with equimolar ferric i on. EPR and Mossbauer experiments provide further insight into the structur es of both complex species. Lack of spin density of the Mossbauer samples i n EPR indicates spin coupling between the metal centers. Mossbauer spectra consist of single quadrupole doublets with values typical for high-spin fer ric ion in an octahedral arrangement. The Mossbauer spectroscopic features at 7 T exclude the presence of S = 0 dimers. Complex I represents a monomer ic ferric iron complex whereas complex H is consistent with a more or less aggregrated oligomeric Fe-anthracycline system.