How Fe3+ binds anthracycline antitumour compounds - The myth and the reality of a chemical sphinx

The interaction of Fe3+ with several anthracycline antitumour antibiotics h as been reinvestigated. Absorption and circular dichroism (CD) measurements were carried out (i) in aqueous solution and (ii) in semi-aqueous MeOH to avoid the stacking of the anthracycline molecules. The Fe3+ binding to anth racycline was dependent on the metal-to-ligand molar ratio, antibiotic conc entration, ionic strength, and pH. The formation of two major Fe3+-anthracy cline complexes, I and II, was observed for all the drugs. These species di ffered in their coordination modes to the anthracycline ligands. Complex I was a monomeric species, where Fe3+ was bound to the anthracycline through the {C(11)-O-; C(12)=0} chelating site. In complex II, Fe3+ was also bound through the {C(5)=O; C(6)-O-} coordination site. Thus, the antibiotic ligan d was acting as a bridge between two metal ions, forming oligomeric (or pol ymeric) structures. The different degree of association of the anthracyclin es could be responsible for the reactivity of the metal ion. In fact, compl exes I and II could constitute mononuclear, binuclear or polynuclear Fe3+ s pecies depending on the competitive kinetics of both coordination and hydro lysis of the metal ion. (C) 1999 Elsevier Science Inc. All rights reserved.