DECIPHERING THE FLUORESCENCE SIGNATURE OF DAUNOMYCIN AND DOXORUBICIN

The fluorescence characteristics of daunomycin (DNM), doxorubicin (DXR ), and other anthracycline drugs are often used to monitor localizatio n of the drug within lipid bilayers and liposomal delivery systems and to assess interaction of the drug with DNA and other macromolecules. However, the binding of DNM and DXR to proteins and membrane systems h as been observed to exhibit variable effects on the anthracycline's fl uorescence. We have delineated the spectroscopic response of DXR and D NM to their surroundings in several systems, including solvents of dif fering dielectric constant, aqueous solutions of varying pH or fluorop hore concentration, and the reverse micellar system of AOT/heptane/wat er with a range of doxorubicin concentrations. We have observed that t he ratio of fluorescence intensities at the two principal lambda(max) values shows a parabolic dependence on solvent dielectric constant, i. e. inverted solvatochromism. This behavior has been overlooked by prev ious investigators and, together with the appearance of a long-wavelen gth band near 630 nm in solvents of low dielectric strength (also prev iously not reported), is key to understanding the partitioning of anth racyclines in membrane systems as well as resolving the conflicting in terpretation of data in the literature. (C) 1998 Elsevier Science B.V. All rights reserved.