The synthesis, photophysical and photobiological properties and in vitro structure-activity relationships of a set of silicon phthalocyanine PDT photosensitizers.

Abstract

Four silicon phthalocyanine photosensitizers have been prepared and studied in an effort to learn more about the structural features that a silicon phthalocyanine must have in order to be a good photodynamic therapy (PDT) photosensitizer. The compounds that have been studied are the known phthalocyanines HOSiPcOSi(CH3)2-(CH2)3N(CH3)2, Pc 4; and SiPc[OSi(CH3)2(CH2)3N(CH3)2]2, Pc 12; and the new photosensitizers HOSiPcOSi(CH3)2- (CH2)3N(CH2CH3)(CH2)2N(CH3)2, Pc 10; and SiPc[OSi (CH3)2(CH2)3N(CH2CH3)(CH2)2N(CH3)2]2, Pc 18. The triplet lifetimes of the four photosensitizers, their singlet oxygen quantum yields, their ability to photoenhance the generation of lipid peroxidation products in human erythrocyte ghosts, their ability to partition into V79 cells and their ability to photokill V79 and L5178Y-R cells have been determined. It is concluded that the presence of a small axial ligand (e.g. an OH ligand) is not necessary for efficient photosensitization, the presence of two aminosiloxy ligands generally provides at least as good photosensitization as one such ligand, and the presence of an elongated diaminosiloxy axial ligand rather than a short aminosiloxy ligand is less desirable. Further, it is concluded that the presence of structural features leading to improvement in the association between the photosensitizers and important cellular targets are more useful than those leading to improvements in their already acceptable photophysical and photochemical properties.