Meso-tetraphenyl porphyrin derivatives : the effect of structural modifications on binding to DMPC liposomes and albumin

Three series of glycoconjugated and hydroxylated derivatives of 5,10,15,20-meso-tetraphenyl porphyrin (TPP) were studied in order to evaluate the effect of a porphyrin structure on its binding to dimyris- toylphosphatidylcholine (DMPC) liposomes and to human serum albumin (HSA). The studied derivatives have been developed as potent photosensitizers for photodynamic therapy (PDT) of cancers. Steady state and time resolved fluorescence emission spectroscopy, Stern–Volmer quenching and fluorescence anisotropy were used for this evaluation. The lipophilicity of the compounds has been deduced from their retention time in reverse phase liquid chromatography. The results demonstrated that the more polar glycoconjugated compounds presented limited aggregation in aqueous media and very rapid binding kinetics to DMPC liposomes and HSA. Derivatives having intermediate or high hydrophobicity showed extensive auto-association in aqueous media and as a consequence slow association kinetics. The strength of porphyrin binding to DMPC liposomes also depended on their lipophilicity and was lower for the polar glycoconjugated analogues. The highest affinity for liposomes was observed for hydroxylated derivatives with intermediate lipophilicity. In contrast, the highest binding constant for albumin was observed for a polar tetra-glycoconjugated analogue. The depth of penetration into the phospholipid bilayer did not appear to be directly related to the global hydrophobicity of the compounds, but depended more on the number of apolar, non-substituted phenyl groups grafted to a tetrapyrrolic macrocycle. Furthermore, liposome–albumin competition studies revealed that the porphyrins were always mainly partitioned into the phospholipid bilayer.