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Synthesis And Bioactivity Studies Of Ruthenium(II) Polypyridyl Complexes

Posted on:2011-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:C H CengFull Text:PDF
GTID:2121330338475518Subject:Drug analysis
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The current situation, the theoretical foundation and research methods of ruthehium polypyridine complexes with DNA were summarized. Five series of novel ligands and their ruthenium(II) complexes were synthesized and characterized. The effect of different complexes on DNA-binding properties was investigated by electronic absorption titration, viscosity measurements, DNA thermal denaturation and photoactivated cleavage experiment. The in vitro cytotoxic activity and the values of IC50 of some complexes were eluvateded by the method of MTT. Besides, the apoptosis activity and hydroxyl radical scavenging activity of ligand and their complexes were investigated. This dissertation concretely consists of the following five chapters.In chapter 1, the structural character of ruthenium polypyridyl complexes, the interaction modes, study methods and current study situations were summarized. The trend of the research in this field and the significance of these researches dissertation were put forward.In chapter 2, a ligand, Fpp (2-(3',3'-difluoro-3,4-methylenedioxyphenyl)imidazo [4,5-f][1,10]phenanthroline) which contains elements of fluorin and oxygen and its ruthenium(II) polypyridyl complexes [Ru(dmb)2(Fpp)]2+ and [Ru(bpy)2(Fpp)]2+ were synthesized and characterized by elemental analysis, ES-MS and 1H NMR and 13C NMR, their electrochemical behaviors were studied by cyclic voltammetry. DNA-binding properties were investigated by electronic absorption titration, viscosity measurements, DNA thermal denaturation and photoactivated cleavage experiment. The results show that the two complexes combine with DNA in the mode of intercalation, the DNA-binding affinity of the two complexes is [Ru(bpy)2(Fpp)]2+ > [Ru(dmb)2(Fpp)]2+, which implies the effect of the ancillary ligand has an on going trend from dmb→bpy. This may be due to他the difference in hydrophobicity of these ancillary ligands. And the electrochemical behaviors of these complexes were analyzed.In chapter 3, two new ligands maip (2-(3-nitrophenyl)imidazo[4,5-f][1,10] phenanthroline) and paip (2-(4-nitrophenyl)imidazo[4,5-f][1,10] phenanthroline) containing amino and their ruthenium(II) polypyridyl complexes ([Ru(bpy)2(maip)]2+, [Ru(bpy)2(paip)]2+, [Ru(dmb)2(maip)]2+, [Ru(dmb)2(paip)]2+, [Ru(dmp)2(maip)]2+, [Ru(dmp)2(paip)]2+, [Ru(phen)2(maip)]2+ and [Ru(phen)2(paip)]2+) were synthesized and characterized by elemental analysis, ES-MS and 1H NMR. The interaction of these complexes with DNA was investigated by electronic absorption titration, viscosity measurements, DNA thermal denaturation and photoactivated cleavage experiment. Results show that intercalative ligand paip has larger DNA binding affinity than maip, this may ascribe to that paip has richer electron than maip. The cell viability of these complexes was investigated by the method of MTT. The hydroxyl radical scavenging activity was also studied.In chapter 4, a novel symmetric ligand DBHIP (2-(3,5-dibromo-4-hydroxyphenyl) imidazo[4,5-f][1,10]phenanthroline) and its ruthenium(II) polypyridyl complexes ([Ru(bpy)2DBHIP](ClO4)2 and [Ru(phen)2DBHIP](ClO4)2) were synthesized and characterized by elemental analysis, ES-MS, 1HNMR and 13C NMR. The DNA-binding properties were studied by electronic absorption titration, viscosity measurements, DNA thermal denaturation and photoactivated cleavage. The results show complex [Ru(phen)2(DBHIP)]2+ has larger DNA affinity than complex [Ru(bpy)2(DBHIP)]2+. Their electrochemical behaviors were also studied by cyclic voltammetry. The cytotoxicity in vitro and the values of IC50 of these complexes were obtained by the MTT method. The cytotoxicity of ligand was slightly weakened when the ligand bonded to the metal atom Ru to form complexes. The antioxidant activity of ligang and its complexes against hydroxyl radical scavenging activity was also explored.In chapter 5, Ru (II) polypyridyl complex [Ru(dmb)2ITAP](ClO4)2 (ITAP = isatino [1,2-b]-1,4,8,9-tetraazatriphenylene, dmb = 4,4'-dimethyl-2,2'-bipyridine) was synthesized and characterized by elemental analysis, ES-MS and 1H NMR. The electrochemical behaviors of this complex were studied by cyclic voltammetry. The DNA-binding properties were studied by electronic absorption titration, viscosity measurements, DNA thermal denaturation and photoactivated cleavage experiment. The results indicate that [Ru(dmb)2ITAP](ClO4)2 interacts with DNA through intercalation mode.
Keywords/Search Tags:ruthenium(Ⅱ) polypyridyl complex, bioactivity, studies
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