The DNA/RNA-binding Mechanism And Anticancer Activity Studies Of Ruthenium(Ⅱ) Complexes

DNA is the main composition of the chromosome, the main material basis of gene stroage, copy, expression. The double-stranded structure of DNA directly affects the stability of gene and accuracy of reproduction, It is also relative to pathological changes. RNA is also the important component material of biology. It takes part in the biosynthesis of protein and plays a significant role in regulation of gene expression. It is also relative to diagnosis and therapy of some diseases.In recent years, studies of interaction of ruthenium(II) polypyridyl complexes with DNA have aroused intense interest because of their rich photophysical, photochemical and electrochemical properties. These studies about the binding mechanisms of these complexes with calf thymus DNA/RNA are very important to screen out the diagnosis reagent and chemical therapy medicine of some diseases related to gene and virus in clinic medicine. This thesis consists of five chapters.In chapter 1,The theoretical foundation, the current situation, the research methods of interaction between ruthehium(Ⅱ) polypyridine complexes and DNA were introduced. The research significance of this thesis was summarized.In chapter 2,A novel polypyridyl ligand PTBM(phenyl-(4,5,9,14-tetraaza-benzo[b] Triphenylenl,1-yl)-methanone) which containing carbonyl group and its complexes [Ru(phen)2(PTBM)]2+(1)and [Ru(bpy)2(PTBM)]2+(2)have been designed, synthesized and characterized by elemental analysis,H NMR and mass spectroscopy. The DNA-binding properties of the two complexes were investigated by UV-Vis, luminescence titration and quenching, viscosity measurements, CD spectra and photoactivated cleavage of DNA. The results indicate that both complexes bind to DNA via an intercalative mode and the DNA-binding affinity of 1 is greater than that of 2;the two complexes can interact with DNA enantioselectively; The result suggest that the ancillary and carbonyl group have significant effect on the complexes.In chapter 3,A new polypyridyl ligand BTCP(2-benzo[b]thiophen-3-yl-1H-1,3,7,8-tetraa-zacyclopenta[1]phenanthrene) and its Ru complexes [Ru(bpy)2(BTCP)]2+(1), [Ru(phen)2(BTCP)]2+(2), and [Ru(dmb)2(BTCP)]2+(3)(dmb=4,4'-dimethyl-2,2'-bipyridine) have been designed, synthesized and characterized. The DNA binding properties of the three complexes were investigated by spectroscopic methods,viscosity measurements, thermal denaturation study and CD spectra. The results indicate that complexes 1,2 and 3 bind to DNA by an intercalative mode; The three complexes interact enantioselectively with DNA; The thermal denaturation study indicate that the process of complexes bind to DNA is the decrease ofΔGTθ,ΔAHθandΔSθ,it drived by enthalpy; When irradiated, they can cleave DNA effectively.In chapter 4, two new polypyridyl ligands stcp and ptcp(where stcp=2-Styryl-lH-1,3,7,8-tetraaza-cyclopenta[/]phenanthrene, ptcp=2-Phenethyl-1H-1,3,7,8-tetraazacyclop-enta[/]phenanthrene) and its five Ru complexes have been designed, synthesized and characterized. The interactions of metal complexes with yeast tRNA and DNA have been investigated comparatively by spectroscopic and viscosity measurements. The results indicate that 1 can intercalate to local formation of double strand tRNA, Which is similar to the role of DNA; These complexes contain stcp bind to DNA via intercalative mode; However, those complexes contain ptcp bind to DNA via electrostatic mode; Taken together, these results indicate that the structures of nucleic acids and the difference of ancillary ligands have significant effects on the binding behaviors of metal complexes. A small difference in the structure leads a significant difference in the function. These fundamental results may be useful and serve as database for the development of futuristic tRNA based small molecule therapeutics.In chapter 5,the complexes we synthesized have been subjected to anti-cancer test in vitro by MTT method. Preliminary results indicate that some of the complexes show high activity against HepG2 and HL-60.In order to describe visually the decease of the cell after drug added, Wrights-Giemsa coloration experiment was also carried.we can see the typical apoptotic bodies of HepG2 cell in presence of complexes and cisplatin. More experiences and studies on mechanism can help pick out the efficient anticaner medicines.