Effects of peripheral chloro substitution on the photophysical properties and in vitro photodynamic activities of galactose-conjugated silicon(IV) phthalocyanines
Effects of peripheral chloro substitution on the photophysical properties and in vitro photodynamic activities of galactose-conjugated silicon(IV) phthalocyanines
复制标题
DOI：
10.1002/cmdc.200800042
复制
发表时间：
2008-07-01
期刊：
影响因子：
3.4
通讯作者：
Ng, Dennis K. P.
中科院分区：
文献类型：
--
作者：
Lo, Pui-Chi;Fong, Wing-Ping;Ng, Dennis K. P.
合成了一系列具有两个轴向异丙基保护的半乳糖基团和一个、两个或八个氯基团的硅酞菁，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学活性，并与未氯化的类似物进行了比较。除了具有有限溶解度的八氯化对应物外，所有化合物基本上都不聚集在N，N-二甲基甲酰胺中。随着氯取代基数目的增加，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。与Cremophor EL配制的非氯、单氯和二氯酞菁对HT29人结肠癌腺癌和HepG2人肝癌细胞均具有光动力学活性，IC50值在0.03 ~ 1.05 μ m之间。由于氯取代后聚集倾向增加，该系列酞菁的光毒性和细胞内活性氧的生成效率下降。非氯化类似物表现出最高的效力，可以靶向HT29细胞的溶酶体，而单氯化类似物不局限于溶酶体。
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 octa-chlorinated 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 IC50 values ranging from 0.03 to 1.05 mu m. 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.