GLYCOSYLATED DERIVATIVES OF TETRAPHENYL PORPHYRIN - PHOTOPHYSICAL CHARACTERIZATION, SELF-AGGREGATION AND MEMBRANE-BINDING

A series of glucose- or galactose-residue-bearing tetraphenyl porphyri ns (TPPs) has recently been synthesized with the aim of studying the s tructural dependence of porphyrin cellular localization and efficiency in photodynamic therapy (PDT). For the present investigation, four de rivatives with different (spherical or planar) configurations and/or d ifferent hydrophobicity have been selected. As a first step, singlet-s tate spectroscopic properties such as spectral characteristics, lifeti me and quantum yield in different solvents are determined. It is found that besides the solvent composition, the configuration of the molecu le critically influences the singlet-state spectroscopic properties. P ossible self-aggregation processes are investigated at room temperatur e in phosphate buffer (pH=7.4). Dimerization equilibrium constants are determined. These values are found to be dependent on the chemical st ructure of substituents on the tetraphenyl groups and only slightly on the conformation of the whole molecule. The association of non-aggreg ated forms of porphyrins to unilamellar liposomes, modelling the lipid bilayer of a biological membrane, is studied by fluorescence spectros copy at neutral pH. On mixing with liposomes, amphiphilic porphyrin de rivatives exhibit an increase in their fluorescence intensity and life time. The monomer-liposome binding constants are determined for these derivatives. The localization of liposome-bound dyes is studied by flu orescence labelling of (a) the Lipid region in interaction with both l ipid chains and headgroups or (b) the carbohydrate chain region of lip ids. Alterations in fluorescence intensities of porphyrin derivatives in the presence of liposomes and changes in the Lifetime and fluoresce nce excitation anisotropy of fluorescent markers in liposomes are dete cted only for unsymmetrically substituted amphiphilic porphyrin deriva tives. Our results suggest that the presence of at least one apolar su bstituent on tetrapyrrolic ring is required for the localization in th e lipid phase. (C) 1998 Elsevier Science S.A. All rights reserved.