The interactions of Fe3+ ions with adriamycin studied by 57Fe Mossbauer and electronic spectroscopies

The interactions between ferric ions and the anticancer antibiotic adriamycin have been investigated by ⁵⁷Fe Mossbauer and electronic spectroscopies. The Mossbauer parameters are markedly dependent on the preparation procedure, the equilibration time, the metal-to-ligand ratio, and the concentration of the drug. At millimolar drug concentration, the 4.2 K Mossbauer spectra exhibit a broad Fe(III) magnetic sextet attributed to polynuclear aggregates of high magnetic anisotropy, and a quadrupole split Fe(III) doublet attributed to a species of lower magnetic anisotropy, which exhibits superparamagnetic behavior. The two species are in equilibrium, as indicated by the time evolution of both Mossbauer and electronic spectra. At 3.0 10^-5 M drug concentration, when adriamycin is mainly monomeric, the 4.2 K Mossbauer spectra exhibit a quadrupole split doublet, connected with a superparamagnetic system, as for the concentrated preparations, and a broad magnetic sextet whose relative area increases with aging. The species responsible for this sextet should be some polymerizable hydrolysis product of the Fe(III) ions present in the dilute solution. In addition, the presence of a transient Fe(II) quadrupole doublet, both in this preparation and when the [Fe]/[ADR] ratio is 1:5 at millimolar drug concentration, is explained with the known intramolecular one-electron redox reaction which ferric- adriamycin undergoes under anaerobic conditions. The present results confirm that adriamycin is markedly more reactive than daunomycin due to its hydroxymethyl side-chain, and suggest that the stacking of the drug molecules plays a role in the observed cooperative phenomena.