THE INTERACTIONS OF FE3-57 MOSSBAUER AND ELECTRONIC SPECTROSCOPIES( IONS WITH ADRIAMYCIN STUDIED BY FE)

Tbe interactions between ferric ions and the anticancer antibiotic adr iamycin have been investigated by Fe-57 Mossbauer and electronic spect roscopies. The Mossbauer parameters are markedly dependent on the prep aration procedure, the equilibration time, the metal-to-ligand ratio, and the concentration of the drag. At millimolar drag concentration, t he 4.2 K Mossbauer spectra exhibit a broad Fe(III) magnetic sextet att ributed to polynuclear aggregates of high magnetic anisotropy, and a q uadrupole split Fe(III) doublet attributed to a species of lower magne tic anisotropy, which exhibits superparamagnetic behavior. The two spe cies are in equilibrium, as indicated by the time evolution of both Mo ssbauer and electronic spectra. At 3.0 10(-5) M drag concentration, wh en 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 wh ose relative area increases with aging. The species responsible for th is sextet should be some polymerizable hydrolysis product of the Fe(II I) ions present in the dilate solation. In addition, the presence of a transient Fe(II) quadrupole doublet, both in this preparation and whe n the [Fe]/[ADR] ratio is 1:5 at millimolar drag concentration, is exp lained with the known intramolecular one-electron redox reaction which ferric-adriamycin undergoes under anaerobic conditions. The present r esults confirm that adriamycin is markedly more reactive than daunomyc in due to its hydroxymethyl side-chain, and suggest that the stacking of the drug molecules plays a role in the observed cooperative phenome na. (C) 1997 Elsevier Science Inc.