THE SYNTHESIS, PHOTOPHYSICAL AND PHOTOBIOLOGICAL PROPERTIES AND IN-VITRO STRUCTURE-ACTIVITY-RELATIONSHIPS OF A SET OF SILICON PHTHALOCYANINE PDT PHOTOSENSITIZERS

Four silicon phthalocyanine photosensitizers have been prepared and st udied in an effort to learn more about the structural features that a silicon phthalocyanine must have in order to be a good photodynamic th erapy (PDT) photosensitizer, The compounds that have been studied are the known phthalocyanines HOSiPcOSi(CH3)(2)(CH2)(3)N(CH3)(2), Pc 4; an d SiPc[OSi(CH3)(2)(CH2)(3)N(CH3)(2)](2), Pc 12; and the new photosensi tizers SiPcOSi(CH3)(2)(CH2)(3)N(CH2CH3)(CH2)(2)N(CH3)(2), Pc 10; and S iPc[OSi (CH3)(2)(CH2)(3)N(CH2CH3)(CH2)(2)N(CH3)(2)](2), Pc 18, The tri plet lifetimes of the four photosensitizers, their singlet oxygen quan tum yields, their ability to photoenhance the generation of lipid pero xidation products in human erythrocyte ghosts, their ability to partit ion into V79 cells and their ability to photokill V79 and L5178Y-R cel ls have been determined, It is concluded that the presence of a small axial ligand (e.g. an OH ligand) is not necessary for efficient photos ensitization, the presence of two aminosiloxy ligands generally provid es at least as good photosensitization as one such ligand, and the pre sence of an elongated diaminosiloxy axial ligand rather than a short a minosiloxy ligand is less desirable. Further, it is concluded that the presence of structural features leading to improvement in the associa tion between the photosensitizers and important cellular targets are m ore useful than those leading to improvements in their already accepta ble photophysical and photochemical properties.