Interaction of glycosylated tetraphenyl porphyrins with model lipid membranes of different compositions

Porphyrin derivatives are one of the major groups of compounds applied in p hotodynamic therapy. Their effect and interaction with different cell organ elles and macromolecules is dependent on their chemical structure. We have examined the effect of the molecular structure of porphyrin derivatives on binding to liposomes without net charge and with negative charge. In this s tudy a series of substituted tetraphenyl porphyrins (TPPs) has been used. T wo of them, TP(4-OGluOH)(4)P and TP( 4-OXylOH)(4)P, are symmetrically subst ituted derivatives having four carbohydrate - glucose or xylose - moieties linked to the macrocycle. The other two derivatives, TP(4-OGluOH)(3)P and T PF5(4-OGalOH)(3)P, were selected as asymmetrically substituted amphiphilic molecules with slightly different hydrophobic character due to the differen t ligand moieties. Association constants (K-L) of derivatives to liposomes and rare constants of liposome binding have been determined and also the ge l-to-liquid-crystalline phase-transition parameters have been monitored in order to determine the type and strength of interaction. According to our m easurements, the K-L values follow the order TP(4-OGluOH)(3)P > TPF5 (4-OGa lOH)(3)P > TP(4-OXylOH)(4)P for both types of liposomes. TP(4-OGluOH)(4)P i s able to bind only to vesicles holding negative charges on their surface. At 18 degrees C, the measured data are best fitted by two exponentials for three TPP derivatives. The binding of TP(4-OGluOH)(4)P follows single-expon ential kinetics. At 37 degrees C, TP( 4-OGluOH)(3)P binds to DMPC Liposomes according to biexponential kinetics, but all the other binding processes f ollow monoexponential kinetics under similar conditions. The strongest effe ct on phase-transition parameters is caused by TP(4-OGluOH)(3)P. From the r esults it can be concluded, that the binding process of TPPs, especially th at of the symmetrically substituted derivatives, is drastically influenced by the surface charges of the model membranes. According to present data, t he negative surface charges of DMPC/DMPG liposomes can facilitate the assoc iation of the symmetrically substituted hydrophilic porphyrins to the lipos omes. However, the asymmetrically substituted derivative TP( 4-OGluOH)(3)P, which is the most lipophilic compound in the present investigation, still has the largest association constant to both neutral and negatively charged liposomes. In general, in both types of liposomes the order of the associa tion constant follows the order of the lipophilicity of the porphyrin deriv atives. (C) 1999 Elsevier Science S.A. All rights reserved.