Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
Chemistry. 2018 Apr 17;24(22):5779-5789. doi: 10.1002/chem.201706128. Epub 2018 Mar 2.
A series of disulfide-linked dendritic phthalocyanines were synthesized by using the Cu -catalyzed alkyne-azide cycloaddition reaction as the key step. Whereas these compounds were essentially nonaggregated in N,N-dimethylformamide, they were stacked in citrate solution (pH 7.4, with 1 % Cremophor EL), as shown by the broad appearance of their Q-band absorption. Having two-to-six zinc(II) phthalocyanine units in a molecule, these compounds were significantly self-quenched, particularly in citrate solution. Both the fluorescence intensity and singlet-oxygen generation efficiency were significantly lower than those of the monomeric counterparts, and the self-quenching efficiency increased as the number of phthalocyanine units increased. Upon interaction with 5 mm glutathione (GSH) in citrate solution, the fluorescence intensity of these compounds increased as a result of cleavage of the disulfide linkages and separation of the phthalocyanine units, which thereby reduced the self-quenching effect. The "on/off" ratios were found to be 7, 18, 23, and 21 for the dimeric (PC2), trimeric (PC3), tetrameric (PC4), and hexameric (PC6) systems, respectively. GSH also enhanced the fluorescence emission inside human colon adenocarcinoma HT29 cells and promoted the formation of singlet oxygen of these compounds. Upon irradiation, their half maximal inhibitory concentration (IC ) values were found to be in the range of 0.18 to 0.38 μm. Finally, the biodistribution and activation of PC2 and PC6 were also examined in HT29 tumor-bearing nude mice. For both compounds, the fluorescence intensity per unit area at the tumor was found to grow gradually during the first 24 h. Whereas the intensity then dropped for PC2, the intensity for PC6 remained steady over the following 6 d, which might have been a result of the enhanced permeability and retention effect arising from the larger molecular mass of the hexameric system.
一系列二硫键连接的树枝状酞菁通过铜催化的炔烃-叠氮环加成反应作为关键步骤合成。虽然这些化合物在 N,N-二甲基甲酰胺中基本上不聚集，但在柠檬酸溶液中（pH7.4，含 1% Cremophor EL），它们是堆积的，这从它们的 Q 带吸收的宽外观可以看出。这些化合物的分子中含有两个至六个锌（II）酞菁单元，因此它们的自猝灭作用显著，特别是在柠檬酸溶液中。荧光强度和单线态氧生成效率都显著低于单体类似物，而且自猝灭效率随着酞菁单元数的增加而增加。在柠檬酸溶液中与 5mm 谷胱甘肽（GSH）相互作用时，由于二硫键的断裂和酞菁单元的分离，这些化合物的荧光强度增加，从而降低了自猝灭效应。对于二聚体（PC2）、三聚体（PC3）、四聚体（PC4）和六聚体（PC6）系统，分别观察到“开/关”比值为 7、18、23 和 21。GSH 还增强了这些化合物在人结肠腺癌 HT29 细胞内的荧光发射，并促进了它们的单线态氧的形成。光照下，它们的半最大抑制浓度（IC ）值在 0.18 到 0.38μm 的范围内。最后，还在 HT29 荷瘤裸鼠中检查了 PC2 和 PC6 的生物分布和激活。对于这两种化合物，在第一个 24 小时内，肿瘤单位面积的荧光强度逐渐增加。虽然 PC2 的强度随后下降，但 PC6 的强度在接下来的 6 天内保持稳定，这可能是由于六聚体系统较大的分子量引起的增强的通透性和保留效应。
