Solution structure of iron(III)-anthracycline complexes

The interaction of Fe3+ with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, Mossbauer, and EPR spectroscopy. The formation of two major Fe3+-Ida complexes, labeled I and II, was observed. In complex I, Fe3+ ion was bound to anthracycline at the {C(12)=O; C(11)-O-} coordination site. In complex II, two Fe3+ ions were bound at sites {C(5)=O; C(6)-O-} and {C(12)=O; C(11)-O-}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe3+:Ida stoichiometry (beta(1) = 4.8 x 10(11) M-1), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe3+:Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M-2). Alternatively, complex II may be oligomeric with Fe3+:Ida = 1:1 and with each Fe3+ bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe3+-Ida system, we suggest that the formal 1:3 Fe3+:anthrracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.