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Nucleic Acid And Avidin-binding Behaviors Of Ruthenium(Ⅱ) Polypyridyl Complexes

Posted on:2013-12-08Degree:MasterType:Thesis
Country:ChinaCandidate:J LiuFull Text:PDF
GTID:2251330401950788Subject:Inorganic Chemistry
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Nucleic acid not only plays an important role in the growth, heredity andvariation of organism, but also closely related to the occurrence of certain diseases. Sopeople usually use it as molecular target of study. After the discovery of cisplatin asanticancer drug having various side effects, the search for alternative metal complexdrug has been an important area of interest for researchers. Among the several metalcomplex, Ruthenium(II) polypyridyl complexes occupies a prominent position.Furthermore, the design and development of new cancer drugs are also an importantpart of the bio-inorganic chemistry.We select Ruthenium(II) polypyridyl complexes as the main object of study,using a variety of spectroscopic and cell biology methods to explore the interactionsbetween the ruthenium complexes and CT-DNA, yeast tRNA, poly(U)·poly(A)*poly(U) and avidin. These researches are helpful for people to reveal the formationmechanism of some genetic diseases, and it provides a train of thought to establish anew treatment method. The main contents of this thesis can be described as follows:1. The ruthenium (II) polypyridyl complex [Ru(bpy)2(H2IIP)](ClO4)2·2H2Owhich contain indole and imidazole functional groups have been designed,synthesized and characterized. The interaction between the complexes with CT-DNAand yeast tRNA have been studied by UV-Vis, fluorescence spectroscopy titration andCD spectra; At the same time we took advantage of the pH titration to explore itspotential as a pH sensor; Furthermore, we used MTT and Giemsa staining to explorethe anti-tumor activity of the complexes. The results show that the complexes bind tothe nucleic acids (DNA and RNA) by an intercalative mode and the yeasttRNA-binding affinity is greater than that of DNA; the complexes also can inhibit thegrowth and reproduction of tumor cell and cause the apoptosis of cancer cells.2. Mononuclear Ru(II) complex [Ru(phen)2(tcbc)]2+and dinuclear complex[Ru(phen)2(bbpibH2)]4+ have been designed and synthesized. We study expansivelythe interaction between the two complexes with the triplex RNA and cyclodextrin.The results suggest that, after the interaction of the two complexes with triplex RNA,all the spectroscopy experiments have significant change and the effect ofmononuclear is better. These studies pave the way for the next chapter in which wewill inquire the interaction between complexes and triplex RNA in depth; Moreover,we also find that only mononuclear complex can cause the change of cyclodextrin’spectroscopy, and the effect for cyclodextrin and DNA to mononuclear complex is just the opposite.3. We focus on the interaction of the complexes [Ru(phen)2(mdpz)]2+ and triplexRNA. The experiment results reveal that, the complexes not only can act as the firstmolecular light switch of the triplex RNA, but also exert a thermally stabilizinginfluence on both Hoogsteen and Watson-Crick hydrogen bonds; So far, in possessionof these efficacy of the drug molecular has not been reported yet. This content is alsothe innovation and highlights of this paper.4. Through selecting different activation reagents, we connect rutheniumcomplex and biotin tactfully and get/obtain two biotinylated ruthenium complexes.We also explore their potential as an avidin fluorescent probe; Meanwhile theluminescence property of these two complexes are different from the majorityruthenium complexes, the addition of water molecular in their organic solvents canresult in fluorescence enhancement; In addition, we also initially related to the studyof these two biotinylated ruthenium complexes in cytotoxic. We hope the aboveresearches can be helpful to the treatment of genetic diseases.
Keywords/Search Tags:Ruthenium(II) polypyridyl complex, Nucleic Acid, Triplex RNA, Avidin
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