Synthesis, DNA binding mode, singlet oxygen photogeneration and DNA photocleavage activity of ruthenium compounds with porphyrin-imidazo[4,5-f] phenanthroline conjugated ligand

Using 1,10-phenanothroline-5,6-dione and 10,20-bis(4-methylphenyl)porphyrin copper as starting materials, a conjugated porphyrin-imidazo[4,5-f]-1,10-phenanothroline ligand (Por 1) was prepared. Subsequently, the copper complex of Por 1 was reacted with Ru(1,10-phenanothroline)(2)Cl-2 to yield ruthenium compound Por 2. After removal of copper metal under acid condition, the free base porphyrin of Por 2 (Por 3) was prepared. The structure of these compounds was confirmed using UV-visible, H-1 NMR, mass and infrared spectroscopies and elemental analysis. Through UV-visible, fluorescence and circular dichroism analyses, the interaction modes between Por 1-3 and calf thymus DNA were investigated. Por 1 interacted with DNA via outside groove face, but Por 2 and Por 3 showed intercalative interaction with DNA. Binding constants between Por 1-3 and DNA were 7.79 x 10 (5), 1.29 x 10(6) and 1.32 x 10(6) M-1, respectively. With 5,10,15,20-tetraphenylporphyrin (H2TPP) as a control, the singlet oxygen ( O-1(2)) generation of Por 1-3 was measured using the 1,3-diphenylisobenzofuran method. The O-1(2) generation rate of Por 1-3 followed the order: Por 3 >Por 1 >H2TPPP >Por 2. Por 1 and Por 3 showed better O-1(2) quantum yields than Por 2, which were almost threefold higher than that of H2TPP. The DNA cleavage ability of Por 1-3 was analyzed using gel electrophoresis. Por 3 showed higher DNA photocleavage activity, with more than 50% photocleavage rate at 20 mu M. These results suggest that amphipathic (hydrophilic/lipophilic) Por 3 with conjugated Por 1 ligand is a potential photosensitizer in cancer therapy.