| A group of phthalocyanines was prepared as a part of a study of photosensitizers for photodynamic therapy, PDT. Four metal-free phthalocyanines of the types of H2Pc[CH2(CH2)3NR2] 2 and H2Pc[CH2(CH2)3NR 2]8 were prepared from o-xylene by a seven-step procedure, involving aromatic bromination, side-chain bromination, alcoholysis, cyanization, mesylation, amination, and cyclization. Thirty-five alkoxy, phenoxy and siloxy silicon phthalocyanines of the types (R2O) 2SiPc[CH2(CH2)3NR1 2]8, (ArO)2SiPc[CH2(CH2) 3NR2]8, (R23SiO) 2SiPc[CH2(CH2)3NR1 2]8 and (R23SiO)2SiPc[CH 2(CH2)3NR12]2 were prepared from these metal-free phthalocyanines by a two- or three-step procedure, involving silicon insertion with trichlorosilane, hydrolysis in the case of siloxy compounds, and ligand exchange to alkoxy, phenoxy and siloxy groups using alcohols, phenols, silanols and N,O-bis(trimethylsilyl)acetamide.; Twenty-eight non-ring substituted silicon phthalocyanines of the types SiPc[OSiMe2(CH2)nR]2 and SiPc[OSiR 1R2R3][OSiMe2(CH2) nR4] were prepared from SiPc(OH)2 by a single-step procedure involving ligand exchange to siloxy groups using specially designed and prepared alkoxysilanes and chlorosilanes, or by a two-step procedure involving ligand exchange to siloxy groups using specially designed and prepared alkoxysilanes and chlorosilanes, and then functionality transformation effected by condensation, nucelophilic substitution or hydrolysis.; Four phospholipid-phthalocyanine conjugates, SiPc[OSiMe2(CH 2)5OPO3CH2CH(O2CR)CH 2(O2CR)]2·2HNEt3, HOSiPc[OSiMe 2(CH2)5OPO3CH2CH(O 2CR)CH2(O2CR)]·HNEt3, SiPc[OSiMe 2(CH2)3NMe2][OSiMe 2(CH2)5OPO3CH2CH(O 2CR)CH2(O2CR)]·HNEt3, and SiPc[OSiMe 2(CH2)3NHMe2][OSiMe2(CH 2)5OPO3CH2CH(O2CR)CH 2(O2CR)], were prepared by coupling their respective hydroxy intermediates with dipalmitoyl phosphatidic acid.; Photophysical, biological and photobiological data gathered by co-workers on these compounds were used in PDT structure-activity relationship studies. This work showed that the ring-substituted phthalocyanines were generally PDT inactive, and that the non-ring substituted phthalocyanines were active when the ligands carried an amino or a uramido functionality. It also showed that the length of the linker-chain of the ligands in the phthalocyanines influenced their PDT activity. Finally, it showed that 69, SiPc[OSiMe 2(CH2)3NHCON(CH3)2] 2, is of particular interest as a new, potential PDT drug. |
