DNA binding of metallochlorophylls with affinity to cancer cells

植物中叶绿素类金属化合物是光合作用系统中光捕获中心的模型，也是光动力治疗癌症的光敏剂。它们作为癌症治疗的光敏剂非常有效，因为它们在可见光区域有很强的吸收，而激光在可见光区域是有用的，因为激光对人体皮肤的穿透能力很高。了解水溶性金属叶绿素在细胞表面的积累特征，特别是金属叶绿素与DNA的相互作用，对于从分子水平上进行光动力学治疗具有重要意义。在本工作中，我们合成了一系列水溶性金属叶绿素作为下一代的光敏剂。通过电子吸收光谱、圆二色谱和DNA热变性温度的测定，研究了它们与DNA的相互作用。氯e_6及其衍生物与DNA的结合是静电作用，并受中心离子种类和大环结构的影响，但结合方式与金属卟啉不同。一种新型的两性(焦脱镁叶绿酸a锌)-葡萄糖胺结合物与小牛胸腺DNA有很强的相互作用，这是阳离子金属卟啉所没有观察到的。合成了e_6三甲酯或焦脱镁叶绿酸a甲酯的2a位带有三甲基氨甲基的几种阳离子金属叶绿素。它们的DNA结合几乎不受中心金属离子的种类或大环结构的影响。综上所述，本文合成的水溶性金属叶绿素已被证实能与双螺旋DNA结合。

The metallochlorophylls derived from chloropylls in plants serve as a model of the light harvesting center in photosynthetic system and as a photosensitizer of photodynamic therapy of cancer. They are very efficient as photosensitizers of cancer therapy because of their strong absorption in the visible region in which the laser light is useful due to its high penetration ability into the human skin. The accumulation characteristics of water-soluble metallochlorophylls on can er cells and particularly the interaction of metallochlorophylls with DNA should be understood to get some insights into photodynamic therapy at a molecular level. In the present work, a series of water-soluble metallochlorophylls have been synthesized as photosensitizers in the next generation. Their interaction with DNA has been studied by electronic absorption and circular dichroism spectroscopies and by measurements of thermal denaturation temperatures of DNA.The DNA binding of chlorin e_6 and its derivatives is electrostatic and influenced by the kind of the central ions and the macrocyclic structure, although the binding mode is different from that of metalloporphyrins. A new type of amphoteric (zinc(II) pyropheophorbide a)-glucosamide conjugate exhibits a strong interaction with calf thymus DNA, which has not been observed for the cationic metalloporphyrins. A few cationic metallochlorophylls with a trimethylammoniunmethyl group at the 2a position of chlorin e_6 trimethyl ester or pyropheophorbide a methyl ester have been synthesized. Their DNA binding is hardly affected by the kind of the central metal ions or the structure of the macrocycles. In conclusion, the water-soluble metallochlorophylls here synthesized have been demonstrated to outside bind to the double-helix DNA.