Synthesis, Structures And Anti-tumor Activities Of 1,10-Phenanthroline-5,6-dione Dinuclear Cu(Ⅱ), Ni(Ⅱ) Complexes Bridged By N,N’-bis(Substituted)Oxamides

The inorganic pharmaceuticals have reveived more and more attention since the development and clinical using of cisplatin as anti-cancer drugs. As the foundation of further researching and the requirement of rational drug design, increasingly importance has been attached to the investigation of interaction between inorganic small molecules with various targets of anti-cancer drugs, especially, with DNA and proteins. 1,10-phenanthroline-5,6-dione complexes have good bioactivies and oxamide compounds are versatile bridging ligand. From this consideration, we have decided to aim our studies on a series of binuclear complexes constructed by the two kinds of ligands, having high antitumor activity and lower toxicity. Five binuclear copper(II), nickel(II) complexes have been synthesized and characterized. The investigations have been carried out of the interaction of the metal complexes with DNA and BSA at molecular level by ultraviolet spectroscopy, fluorescence spectroscopy, electrochemical method and viscosity method;and antitumor activities at cellular level by SRB assay. The influences of the molecular structures on the activities are also discussed preliminarily. This thesis covers the following four aspects:1. Synthesis and structures of the 1,10-phenanthroline-5,6-dione dinuclear complexes bridged by oxamido ligands:Two dinuclear complexes:Five dinuclear complexes 1-5 bridged by H3dmpb and H3pdpo have been synthesized. In which, two complexes of [Cu2(dmpb)(phendione)(H2O)]ClO4·H2O (1) and [Cu2(pdpo)(phendione)(H2O)]ClO4·H2O (4) have been characterized through X-ray single crystal diffraction. The other three complexes have been proved the similar structures by elemental analyses, IR spectra studies, et. al. The influence factors of the crystal structures of these complexes were also discussed.2. Interactions of complexes with DNA:DNA-binding properties of the five complexes have been studied by the electronic spectra, fluorescence spectra, viscosity measurement and electrochemical method. All of the five complexes interacted HS-DNA by intercalation manner. According to the different metal ions and terminal ligands, the bonding strength of these complexes with HS-DNA is distinct.3. Interactions of complexes with BSA:The protein binding ability has been monitored by electronic spectra and tryptophan fluorescence quenching experiment in the presence of the five compounds using bovine serum albumin (BSA) as model protein. The results indicate that the complexes 1-5 interact with BSA by static quenching, and the binding site of these compounds with BSA maybe the Trp-134 residue on the surface.4. Antitumor activity of complexes:The in vitro cytotoxicity activities of five compounds against two cancer cell lines:human hepatocellular carcinoma cell line (SMMC-7721) and human lung adenocarcinoma cell line (A549) were tested by SRB method. The results indicate that five compounds have certain cytotoxicities against these cancer cell lines.The above workes not only enrich the content of oxamide-bridged complexes and supply the chemical basis to explore novel bridging polynuclear complexes with high antitumor activities and low toxicities, but also make contributions to the study on the structure-activity relationship of such complexes.