| Triplexes have enormous potential in biological therapy.triplex has low stabilization because of charge repulsion between the three phosphate framework,which limits the development of its practical utility.Research focus on improving the stability of the triplex gain people's attention.The study of ruthenium?II?polypyridine complexes interact with triplex become more and more popular,because the trait of ruthenium?II?polypyridine complexes such as thermodynamic stability,rich optical properties,low toxicity to cell and so on.The modifications of the intercalative ligands or the ancillary ligands could significantly influence the stabilization of the third strand of triplex.Here we have synthesized six chiral ruthenium?II?polypyridine complexes,We using spectroscopy,fluidics and thermodynamic methods to explored the interaction between these complexes with the triplex,and the enantioselectivity of the enantiomers with triplex also under consideration,besides,we also explore the effect of complexes to stability of triplex.providing theoretical basis for the interaction between chiral ruthenium?II?complexes and triplex,which promote the development of ruthenium?II?complexes as anti-cancer drugs.In the first chapter,we have introduce the structure and application of triple x,and describe the application of ruthenium?II?complexes interact with triplex.In the second chapter,?-[Ru?bpy?2?m-fpip?]2+and?-[Ru?bpy?2?m-fpip?]2+to investigate the influence of acceptor group on the complexes intercalation ligand to triplex stability.The results suggest that F on the intercalation ligand improve the binding affinity,with little changes on triplex stability.In addition,there aren't have differences between the enantiomers when they binding to triplex,which means complexes don't show the enantioselectivity to triplex RNA.In the third chapter,we discussed that the influences of steric hindrance to triplex ?-[Ru?bpy?2?p-fpip?]2+and?-[Ru?bpy?2?p-fpip?]2+were synthesized.We explored the influences of steric hindrance caused by different positions of insertion ligand substituents on triplex stability.The results showed that when the substituent is in ortho position,the compounds had higher binding affinity with the triplex,which proved that steric hindrance had influence on the stability of the triplex.Thermal denaturation studies showed that?-[Ru?bpy?2?o-fpip?]2+??-[Ru?bpy?2?p-fpip?]2+and?-[Ru?bpy?2?p-fpip?]2+had a stable effect on the third strand of the triplex RNA,while they showed little influence on the double strand of the triplex RNA.In the last chapter,the?-[Ru?bpy?2mip]2+,?-[Ru?bpy?2mip]2+,?-[Ru?bpy?2bdip]2+and?-[Ru?bpy?2bdip]2+were synthesized.?-[Ru?bpy?2mip]2+had lower binding affinity with the triplex compared with?-[Ru?bpy?2mip]2+.On the contrary,?-[Ru?bpy?2bdip]2+had higher binding affinity with the triplex compared with?-[Ru?bpy?2bdip]2+.The position of methylenedioxy on the ligand,which caused different steric hindrance and ligand planarity,resulting in the difference of binding affinity with the triplex RNA.Founding that?-[Ru?bpy?2mip]2+,?-[Ru?bpy?2mip]2+and?-[Ru?bpy?2bdip]2+stabilizes the third strand of triplex RNA,they also showed no obvious effect on the double strand of triplex RNA.In addition,?-[Ru?bpy?2bdip]2+stabilizes the third strand of triplex RNA while slightly destabilizes the double strand of triplex RNA.In a word,Position of ligand methylenedioxy has important influence on the stability of triplex RNA. |
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