DNA binding of metallochlorophylls with affinity to cancer cells

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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.