Ru~? Complexes Containing Different N^N Bidentate Ligands:Design,Synthesis And Interaction With DNA

In recent years,novel metal antineoplastic drugs designed by inorganic metal chemistry are developing.Based on metal selectivity,oxidation state,type and number of ligands,configuration of complexes,metal drugs have a unique mechanism for drug action.Although platinum anticancer drugs are very successful,other drugs need to be sought because of the side effects of platinum complexes in clinical use.In addition to platinum complexes,the anticancer activity of Ru complexes has been extensively studied.Ru???complexes contain many valence states.Because of the theory of"reduction activation",Ru???complexes with many advantages has been studied widely.In this paper,two kinds of Ru???complexes:arene-Ru???complexes and Ru???polypyridyl complexes are mainly involved.In this paper,Ru???complexes with different N^N bidentate ligand have been synthesized,and their interaction with DNA has been explored.The main research contents are as follows:1.Arene-Ru???complexes with N^N bidentate ligand bind to different leaving groups?Cl^-,Br^-,I^-?were synthesized.The UV spectra of three complexes hydrolyzed with time were evaluated.The hydrolysis rate of the complexes with I^-as the leaving group was the slowest.The gel electrophoresis experiment showed that the order of hydrolysis of DNA of the three complexes was Cl^-?Br^->I^-,which was consistent with the UV experiment.Experiments show that the ability of leaving group is closely related to the activity of DNA hydrolysis,and this activity can be inhibited by Cl^-in buffer.MTT revealed that antiproliferative activity of the complex with I^-was higher than the complexes with Cl^-,Br^-towards HepG2,A2780.The hydrolysis rate of the complexes with I^-took advantage to perform antiproliferative activity.2.Methylated polypyridine ligand and its complexes were synthesized,and their crystal structures were analyzed by X-ray diffraction.This was the first time that in situ solvothermal method was used for the methylation of polypyridyl compound without stirring,pale yellow crystals were obtained.The ligand and complex had good affinity to CT DNA.The complex had the activity of DNA photocleavage,mainly through the production of ¹O₂,a small amount of O₂^-and carbon free radicals to achieve the effect of photocleavage DNA.DPPH free radical scavenging assay revealed the compound was an effective antioxidant agent.MTT assay showed that the ligand and the compound had good antiproliferative activity.The complex showed better antiproliferative activity than the ligand and obvious effect towards human liver carcinoma cells comparable to cisplatin.The complex has potential to be a photosensitizer.3.Two arene-Ru???complexes with methylated polypyridine as ligand:the complex with ?⁶-benzene and the complex with ?⁶-p-cymene were synthesized.Among them,the complex with ?⁶-p-cymene has resolved the crystal structure by X-diffraction.However,the activity with DNA of the complex was not found in gel electrophoresis experiments.And the complex with ?⁶-benzene could break DNA by producing ¹O₂ and metal ions.The two complexes showed obvious effect towards human liver carcinoma cells comparable to that of cisplatin.The antiproliferative activity of complex with ?⁶-benzene a little bit better than that of cisplatin.The complex with ?⁶-benzene has potential to be a photosensitizer.4.Arene-Ru???complexes with thiabendazole and its derivatives as ligands were synthesized.Both complexes can hydrolyze DNA,and the complex containing thiabendazole derivatives had better activity than that containing thiabendazole,which could also be inhibited by Cl^-in buffer.The complex containing thiabendazole had little effect on the activity of topoisomerase?.The complex containing thiabendazole derivatives showed a little bit better antiproliferative activity than cisplatin.The structure modification of thiabendazole brings better antitumor activity.