Studies On The DNA-binding Properties Of The Metal Complexes With Schiff Base Ligands Derive From Cinchophen Drug

New chemical group introduction, reconstruction and decoration of drugs have drawn lots of attention in medicine chemistry recently. The cinchophen drug was reconstructed and decorated in this thesis, acylhydrazone groups was introduced to this drug and their metal complex was synthesized, DNA-binding properties was studied to provide important information for discussing structure-activity relationship and probing interaction of metal and target molecules, and to exhibit the important theoretical guidance in new pharmic properties discovery and drugs merit improvement.DNA is the primary target molecule for most of anticancer therapies according to the cell biology. Studies on the interaction between small molecules and DNA have become the main research topic of chemistry and biology. In this thesis, the development in the studies of the DNA and small molecules, as well as the basic composition of DNA, the interaction mode and influence factors, research methods and techniques are reviewed, and the important theoretical and practical significance of this research work in the pharmic filtration and biochemistry are also discussed herein.Schiff bases play an important role in bioinorganic chemistry as they exhibit remarkable biological activity. The acid hydrazides R-CO-NH-NH2, a class of Schiff base, their corresponding aroylhydrazones, R-CO-NH-N=CH-R', and the dependence of their mode of chelation with transition metal ions present in the living system have been of significant interest. The coordination compounds of aroylhydrazones have been reported to act as enzyme inhibitors and are useful due to their pharmacological applications. In this thesis, we synthesized and characterized 33 metal complexes with 6 ligands derive from 2-phenylquinoline-4-carboylhydrazone and different aldehyde andβ-diketone by elemental analysis, molar conductivity, IR spectra, X-ray diffraction methods. The complexes are more soluble compare with the corresponding ligand. It is noted that the pharmacentical phase properties of drugs can be influenced remarkably due to the introduction of metal to ligands.The DNA-binding mechanism was studied by UV, CD, fluorescence spectra, viscometric titration and voltametric studies. The results show:1. R' group play an important role in the interaction between complexes and DNA. The H₂L¹ and its complexes have higher affinity when take the mode of intercalation, the H₃L² and its complexes have stronger interaction with DNA when take the groove binding, because the steric interference and one more -OH group which can bond to DNA through H-bonding. The ligands (HL³, HL⁴) and their complexes can intercalate more deeply into the DNA base pairs compare with H₂L¹ and H₃L², when the R' (benzene) was substituted by five-member furan and thiophen ring and is unbranched-chain.These results can help us to understand the structure-activity relationship more deeply and provide important information for new drugs design.2. Ligands and complexes can bond to DNA, and the complexes have more higher affinity compare with the ligands, so can have better pharmacological and biological activity compare with ligands, increase the pharmacodynemic phase activity of the drugs.3. The studies on the DNA-binding of complexes derive fromβ-diketone show that the binding mode of complexes with H₂L⁵ is groove binding due to the -OH groups in the complexes which can form H-bonding with base pairs, and the complexes with H₂L⁶ take the mode of intercalation when bond to DNA. And the complexes have higher affinity compare with the ligands.4. The fluorescence intensity enhanced remarkably with the increasing DNA concentrations when take the mode of intercalation. Especially for HL3, the fluorescence can not exhibit when in the absence of DNA and intensity can enhance observably when in the presence of DNA, so can be applied in optical switch.