Department of Chemistry and Center of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Chemistry. 2010 Apr 26;16(16):4777-83. doi: 10.1002/chem.200903580.
A series of aryl hydroxyamines prepared by reductive amination were treated with silicon(IV) phthalocyanine dichloride in the presence of pyridine to give the diaxially substituted phthalocyanine-polyamine conjugates 1-5. The electronic absorption, fluorescence emission, and efficiency at generating reactive oxygen species of these compounds were all sensitive to the pH environment. Under acidic conditions, the fluorescence quantum yields and the singlet oxygen quantum yields of these compounds were greatly enhanced in DMF as a result of protonation of the amino moieties, which inhibited the photoinduced electron-transfer deactivation pathway. The Q band was diminished and broadened, and the fluorescence intensity decreased as the pH increased in citrate buffer solutions. The rate of superoxide radical formation was also reduced in a higher pH environment. Compound 3, containing a terminal 4-chlorophenyl group at the axial substituent, showed the most desirable pH-responsive properties, which makes it a promising tumor-selective fluorescence probe and photosensitizer for photodynamic therapy. All of the phthalocyanines 1-5 were highly photocytotoxic against HT29 and HepG2 cells with IC(50) values as low as 0.03 microM. Compound 3 was highly selective toward lysosomes, but not mitochondria of HT29 cells.
一系列通过还原胺化制备的芳基羟胺在吡啶存在下与硅（IV）酞菁二氯化物反应，得到轴向取代的酞菁-多胺缀合物 1-5。这些化合物的电子吸收、荧光发射和生成活性氧的效率都对 pH 环境敏感。在酸性条件下，由于氨基部分的质子化，这些化合物在 DMF 中的荧光量子产率和单线态氧量子产率大大提高，抑制了光诱导电子转移失活途径。在柠檬酸盐缓冲溶液中，随着 pH 值的升高，Q 带减弱且变宽，荧光强度降低。在较高 pH 环境下，超氧自由基的形成速率也降低。含有轴向取代基末端 4-氯苯基的化合物 3 表现出最理想的 pH 响应特性，使其成为一种有前途的肿瘤选择性荧光探针和光动力治疗光敏剂。所有的酞菁 1-5 对 HT29 和 HepG2 细胞都具有高的光细胞毒性，IC（50）值低至 0.03 microM。化合物 3 对 HT29 细胞的溶酶体具有高度选择性，但对线粒体没有选择性。
