The DNA/Triplex-helix RNA-binding Mechanism Studies Of Ruthenium(Ⅱ) Polypyridyl Complexes

The biological macromolecules nucleic acid contains a wealth of geneticinformation, usually binding with protein in vivo to become nucleic acid protein. As akind of Lewis base, it can bind with metal ion through a various of ways. Therefore,the metal ion exhibit many kinds of physiological functions in vivo. At present, theinteraction of ions and their complexes with DNA is a vibrant area of research.Ruthenium(Ⅱ) polypyridyl complexes with its abundant physicochemical properties,low toxicity and easy to be absorbed in the body, caused the widespread attentionfrom scientific research scholars. By modifying ligand can be targeted in the designand control the properties of the ruthenium complexes, therefore, rutheniumcomplexes in the inorganic medicines application value is very prospect.This paper designed and synthesized four ruthenium complexes, three of whichthe introduction of the carbazole group, and the other containing an intramolecularhydrogen bond. Based on these four complexes, Its interaction with CT-DNA, triplehelix RNA and topoisomerases was studied using spectroscopy, fluidics,thermodynamics and gel electrophoresis. We hope that this study can provide someideas for the synthesis of inorganic drugs. Specific work are as follows:In chapter1, the course of development of the bio-inorganic chemistry, thenucleic acids, the nucleic acid triple helix, the topoisomerase, the research methodsof interaction between ruthehium(Ⅱ) complexes and nucleic acid, The significance ofthe thesis were introduced.In chapter2, Three novel intercalative ligands cpipH, Bcpcc, Dcpcc whichcontaining Carbazolyl group and its complexes [Ru(phen)2(cpipH)]2+(1),[Ru(phen)2(Bcpcc)]2+(2)，[Ru(phen)2(Dcpcc)]2+(3) have been designed, synthesizedand characterized by1H NMR and ES-MS. The DNA-binding properties of the threecomplexes were studied using UV-spectral titration, fluorescence spectral titration,photoactivated cleavage of DNA, viscosity measurements. The results suggest that allthe complexes bind to DNA by an intercalative mode, and the binding ability followsthe order of1>2>3.In chapter3, based on the former chapter, with the aid of fluorescence spectraltitration and UV-spectral titration, the intercalative triple helix RNA binding mode ofthe synthesized complexes has been concluded. Three complexes can increase themelting temperature of the triple helix RNA (Hoogsteen and Watson-Crick hydrogen bonds) and improve the stability of the triple helix RNA structure.In chapter4, with the aid of gel electrophoresis, the Topo Ⅰ/Ⅱ inhibition activiesand mechanisms of Ru(Ⅱ) complexes has been studied. The results suggest that thecomplex1was proved to be dual Topo Ⅰ/Ⅱ inhibitors, and the complex2have noinhibion activities on Topo Ⅰ.In chapter5, a novel intercalative ligand HPIP which containing anintramolecular hydrogen bond and ancillary ligands IP and its complexes[Ru(IP)2(HPIP)]2+(4), have been designed, synthesized and characterized by1H NMRand ES-MS. The results suggest that the complexes bind to DNA and RNA by anintercalative mode and the complexes can improve the stability of the triple-helixRNA structure; as to Topo inhibition, the complexs was proved to be dual Topo Ⅰ/Ⅱinhibitors.