SPECTROSCOPY AND KINETICS OF THE INTERACTION OF ELLIPTICINIUM DERIVATIVES WITH LIPOSOMES - INFLUENCE OF THE ALIPHATIC SIDE-CHAIN ON THE BINDING MECHANISM

Spectroscopic (absorption and fluorescence) and kinetic (T-jump) methods have been used to study the binding equilibria between a series of cationic alkyl-oxazolopyridocarbazole drugs with increasing side-chain length (alkyl-OPC), derived from the ellipticine family and membrane models (liposomes). From the spectral changes it was possible to estimate all the binding parameters, i.e., association constants and the number of ligands complexed per phospholipidic unit, and to characterize the influence on the binding mechanism of the side chain length of drugs and of the nature of the polar heads of liposomes. T-jump experiments show that the binding process is satisfactorily described by the reversible addition of drugs onto the liposomes, as previously proposed for the binding of a cyanine dye (Merocyanine 540) to micelles, liposomes, and mitochondrial membranes. The kinetic data suggest that the binding reaction is essentially diffusion controlled and show that the residence time of the drugs on or within the liposomes increases with the length of their side chain. All these results clearly indicate that the aliphatic tails borne by the ellipticinium chromophore play a major role in the binding mechanism and suggest the existence for the long-tail derivatives (propyl-, butyl-, and pentyl-OPC) of additional binding sites in membranes, located in electrically neutral areas. © 1990 American Chemical Society.