Synthesis And Bioactivity Studies Of Ruthenium(Ⅱ) Polypyridyl Complexes

The interactions of ruthenium(II) polypyridyl complexes with DNA have attractedconsiderable interest during recent decades. The DNA-bindig behaviors were investigatedby absorption titration, fluorescence spectra, viscosity measurements, thermal denaturationand photoocleavage. The DNA photocleavage activity was studied by agarose gelelectrophoresis. The cytotoxicity in vitro was assayed by MTT method. The apoptosis wasperformed by staining with acridine orange (AO) and ethidium bromide and the Flowcytometry. The cell cycle arrest was carried out by flow cytometry.This paper is divided into five chapters. In chapter1, the basic theory and relativeresearch methods of ruthenium(II) complexes with DNA are introduced. The appliedprospect and the meaning of this project are summarized.In chapter2, a symmetric ligand containing two bromide atoms was synthesized, andtwo relative ruthenium (II) polypyridyl complexes were prepared and characterized byelemental analysis, ES-MS,1H NMR. The DNA-binding behaviors were studied by UV/Visspectra, viscosity measurements, thermal denaturation and photocleavage. The resultsshowed these complexes interact with CT DNA by intercalative mode. The cytotoxicity invitro and morphologic apoptosis suggested these complexes possess high antitumoractivity.In chapter3, two new ligand APIP and HAPIP were prepared and eight relativeruthenium (II) complexes were synthesized. DNA-binding studies showed that these complexes bind to CT DNA through intercalation. The studies on the role of radicals in theDNA cleavage suggested that shows that the DNA cleavage of the plasmid by complexeswas not inhibited in the presence of hydroxyl radical (OH) scavengers such as mannitoland DMSO. In the presence of SOD, the effect on DNA cleavage was obviously improved.All these complexes can effectively induce apoptosis of BEL-7402cells. The cellularuptake showed these complexes can enter into the cytoplasm and accumulate in the nuclei.When ligands bond to form complexes, the antioxidant activity of ligand is obviouslyweakened.In chapter4, a ligand of dppz derivate containing an amino group and four complexeswere synthesized and characterized by elemental analysis, ES-MS and1H NMR. Thecytotoxicity in vitro, apoptosis and call cycle arrest were explored. This series of complexesshowed high cytotoxic activity against selected tumor cell lines.In chapter5, a symmetric ligand containing two amino groups and three ruthenium (II)complexes were prepared. The cytotoxicity in vitro, apoptosis and cell cycle distribution byflow cytometry were investigated.