TRANSVERSE LOCATION OF ANTHRACYCLINES IN LIPID BILAYERS - PARAMAGNETIC QUENCHING STUDIES

Quenching of anthracycline fluorescence by a series of spin-labeled fatty acids was used to probe the transverse location of the drug in phosphatidylcholine bilayers in the form of small unilamellar vesicles. Stern-Volmer plots of the quenching data indicate that the fluorophore moiety of the anthracycline is intercalated into the hydrocarbon region of the bilayer,with deeper penetration observed in fluid-phase than in solid-phase vesicles. 31P-NMR parameters (T1, and nuclear Overhauser enhancement (NOE)) are unaffected by the presence of drug, consistent with a binding site removed from the interfacial region. Comparison of intensity (Fo/F) plots with lifetime (θo /θ) data shows that the predominant mechanism of anthracycline quenching by membrane-bound nitroxides is static. Since the membrane-bound drug is also accessible to quenching by I-, the binding site in the membrane must create a channel which is accessible to solvent. Two other fluorescent probes, 12-(-anthroyloxy)stearate (12-AS) and diphenylhexatriene (DPH), were employed to confirm the results obtained with the anthracyclines, giving quenching data representative of their location in the bilayer. © 1990.