DNA-Topo Inhibition And T-RNA Stability Regulation By Ruthenium(Ⅱ) Complexes

The thesis consists of four chapters.The first chapter: An introduction was concentrated on the basic knowledge ofnucleic acids (DNA/RNA) and DNA topoisomeras, and the research methods of DNAbinding and topoisomerase inhibition and the related current situation.The second chapter: four new and differenr ruthenium complexes weresynthesized and charactarized by1HNMR and Elemental analysis. The properties ofDNA binding with Ru(Ⅱ) complexes have been studied by UV-Vis, emission spectraand viscosity measurements. The results reveal that these four complexes bind toCT-DNA by classic intercalation mode, and the complexes of [Ru(phen)2(tcpb)]2+and[Ru(phen)2(tcpb-2Br)]2+interact with DNA more stronger compared to the two othercomplexes.The third chapter: The DNA photocleavage activity and DNA photocleavagemechanism of two ruthenium(Ⅱ) complexes [Ru(phen)2(tcpb)]2+and[Ru(phen)2(tcpb-2Br)]2+were emphatically explored, the results suggest that bothcomplexes have positive DNA photocleavage efficiency, and that their photocleavagemechanism may be that the OH as an active agent in the cleavage reaction, whichenhances the photocleavage efficiency of DNA. The DNA Topoisomerase inhibitionof these two Ru(Ⅱ) complexes has been researched by relaxation assay and strandpassage assay. The results indicate that [Ru(phen)2(tcpbp)]2+and[Ru(phen)2(tcpb-2Br)]2+can inhibit the activities of Topo I and Topo Ⅱ effecintly.Both of them are proved to be a dual Topo I/Ⅱ inhibitor,which is meaningful the studyof anti-cancer drug.The fourth chapter, the interaction of the four ruthenium(Ⅱ) complexes andtriplex RNA has been studied. The experiment results suggest that, the fourcomplexes may bind with triplex RNA via intercalation mode by UV-Vis,luminescence titration and thermal denaturation experiments, and they can affect thestability of the triple RNA’s structure. We also find that when complexes under certainconcentration can improve the unwinding temperature of triple RNA’s Hoogsteen andWatson-Crick hydrogen bond. These studies are innovatory and meaningful for thedevolopment of inorganic chemistry.