Lo Pui-Chi, Fong Wing-Ping, Ng Dennis K P
Department of Chemistry and Centre of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
ChemMedChem. 2008 Jul;3(7):1110-7. doi: 10.1002/cmdc.200800042.
A series of silicon(IV) phthalocyanines with two axial isopropylidene-protected galactose moieties and one, two, or eight chloro group(s) on the periphery of the macrocycle have been synthesised and spectroscopically characterised. The photophysical properties and in vitro photodynamic activities of these compounds have been studied and compared with those of the nonchlorinated analogue. All the compounds, with the exception of the octachlorinated counterpart which has a limited solubility, are essentially nonaggregated in N,N-dimethylformamide. The fluorescence quantum yield decreases and the singlet oxygen quantum yield increases as the number of chloro substituent increases, which is in accord with the heavy-atom effect. The non-, mono-, and dichlorinated phthalocyanines formulated with Cremophor EL are all photodynamically active against HT29 human colon adenocarcinoma and HepG2 human hepatocarcinoma cells with IC(50) values ranging from 0.03 to 1.05 microM. The photocytotoxicity as well as the efficiency to generate intracellular reactive oxygen species decrease along this series because of the increase in aggregation tendency upon chloro substitution. The nonchlorinated analogue exhibits the highest potency and can target the lysosomes of HT29 cells, whereas the monochlorinated counterpart is not localised in the lysosomes.
已合成了一系列在大环外围带有两个轴向异亚丙基保护的半乳糖部分以及一个、两个或八个氯原子的硅（IV）酞菁，并对其进行了光谱表征。研究了这些化合物的光物理性质和体外光动力活性，并与未氯化类似物的性质进行了比较。除溶解度有限的八氯化类似物外，所有化合物在N，N-二甲基甲酰胺中基本不聚集。随着氯取代基数量的增加，荧光量子产率降低，单线态氧量子产率增加，这与重原子效应一致。用聚氧乙烯蓖麻油（Cremophor EL）配制的未氯化、一氯化和二氯化酞菁对HT29人结肠腺癌和HepG2人肝癌细胞均具有光动力活性，IC（50）值范围为0.03至1.05 microM。由于氯取代后聚集趋势增加，该系列化合物的光细胞毒性以及产生细胞内活性氧的效率均降低。未氯化类似物表现出最高的效力，并且可以靶向HT29细胞的溶酶体，而一氯化类似物则不定位在溶酶体中。
