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The DNA/RNA-Binding Mechanism And Cell Activity Studies Of Functional Metal Complexes

Posted on:2012-12-11Degree:MasterType:Thesis
Country:ChinaCandidate:X L LiangFull Text:PDF
GTID:2214330338471953Subject:Inorganic Chemistry
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Nucleic acid is one of the main composition of the life, therefore, understanding the interactions and mechanism of metal complexes binding with nucleic acid (DNA/Yeast tRNA) may be a more complete finding out of the origin of life on a molecular level, which have important theoretical significance and potential applied values in biological science.Ruthenium(II) polypyridine complexes play a significant role in the fields of photochemistry, photophysies, a molecular assembling, electrochemistry, etc. In particular, a considerable attention have been attracted in their extensive potentials as DNA molecule structure recognition, DNA footprinting, DNA mediated electron transfer, anticaner drugs, sequence-specific cleaving agents, and so on. Therefore, during the past decades, strong interest have been caused to the interactions of Ruthenium(II) polypyridine complexes with DNA. The main works are to plan and synthesis complexes with bigger binding strengths and antitumor activity in this paper. The major contents as follows:In chapter 2, three new water-soluble Ruthenium(II) complexes with monodentate co-ligands [Ru(MeIm)4L]2+(L = phen, ip, pip) (MeIm = 1-methylimidazole, phen = 1,10-phenanthroline, ip = imidazo[4,5-f][1,10]phenanthroline, pip = 2-phenylimidazo -[4,5-f][1,10]phenanthroline), have been synthesized and characterized. The results suggest that the three complexes bind to DNA in an intercalative mode, but with different binding strengths. The complex 3 containing the intercalative ligand pip with the larger planar area and a more extendedπsystem can intercalate more deeply into adjacent DNA.In chapter 3, two heterodinuclear(Ru, Co) metal polypyridyl complexes [(phen)2Ru (bpibH2)Co(phen)2]5+ {phen = 1,10-phenanthroline, bpibH2 = 1,4-bis([1,10]-phebanth -roline-[5,6-d]imidazol-2-yl)-benzene} and [(phen)2Ru(btbtp)Co(phen)2]5+ {btbtp = [11,12']bi[4,5,9,14-tetraaza-benzo[b]triphenylenyl} have been designed and synthesized. The comparative study on the interaction of the Ru(II)-Co(III) complex with calf thymus DNA (CT-DNA) and yeast tRNA have been investigated by UV-vis spectroscopy, fluorescence spectroscopy, viscosity, as well as equilibrium dialysis and circular dichroism (CD). The antitumor activities of the complexes have been evaluated by MTT{3-(4,5-dimethylthiazol-2-yl)-2,5-dipheny-ltetrazolium bromide} method and Giemsa staining experiment. These results indicate that the structures of nucleic acids have significant effects on the binding behaviors of metal complexes. Furthermore, the complex demonstrates different antitumor activity against selected tumor cell lines in vitro, and can make the cell languish.In chapter 4, a polypyridyl ligand PTBM(phenyl-(4,5,9,14-tetraaza-benzo[b] Triphenylen1,1-yl)-methanone) which containing carbonyl group and its complex [Cr(PTBM)2Cl2](ClO4) have been designed, synthesized and characterized by elemental analysis and IR spectroscopy. The nucleic acid-binding properties of the complex was investigated by luminescence titration and quenching, UV-Vis, viscosity measurements. The results indicate that complex binds to nucleic acid via an intercalative mode and the RNA-binding affinity is greater than the DNA-binding. The results suggest that nucleic acid structure has significant effect on the binding strengths.In chapter 5, two ruthenium(II) complexes [Ru(bpy)2(btbtp)](ClO4)2·2H2O and [Ru(dmb)2(btbtp)](ClO4)2·2H2O have been synthesized and characterized. The binding of the two complexes with nucleic acid have been investigated by steady-state luminescence, absorption, viscosity measurements. The results suggest the group of ancillary have significant effect on the complexes binding with nucleic acid.
Keywords/Search Tags:Metal complex, DNA, RNA, Nucleic acid-binding, Cytotoxicity
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