Syntheses, Structures And Activities Of Dicopper(Ⅱ) And Tetracopper(Ⅱ) Complexes Based On DNA Intercalation

Studies on the design and exploitation of new metal complexes with antitumor activities werealways hot spots in the filed of inorganic medicinal chemistry, since the discovery of the anticanceractivities of cis-platin and its successful application in clinic. Investigation of the interactionbetween metal complexes and DNA could obtain important information about the novel antitumoror anticancer drugs design and the mechanism of action of drugs.In order to explore new more-efficacious, target-specific, less-toxic anticancer drugs, in thisdissertation, six polynuclear complexes with two dissymmetrical N,N′-disubstituted oxamides as theligands have been designed and synthesized, their crystal structures, DNA-binding properties andcytotoxicities also have been studied systematically. The detail contents include several aspects asfollows:1. Synthesis and structures of bridging polynuclear complexes: six polynuclear complexeshave been synthesized by choosing N-（2-aminopropyl）-N′-（2-carboxylatophenyl）oxamide （H₃oxbm）and N-（hydroxypropyl）-N′-（2-carboxylatophenyl）oxamide （H3oxbpa） as the bridging ligands,including: three dicopper（II） complexes [Cu₂（oxbm）（bpy）（H₂O）₂]·（pic）（1），[Cu₂（oxbm）（phen）（H₂O）（CH₃OH）]（pic）（2），[Cu₂（oxbpa）（bpy）（CH₃OH）]·（pic）（CH₃OH）（3） andthree tetracopper（II） complexes [Cu₄（oxbm）₂（phen）₂]（NO3）₂（H₂O）6（4）,[Cu₄（oxbpa）₂（phen）₂]（ClO4）₂（H₂O）4（5）,[Cu₄（oxbpa）₂（bpy）₂]·（NO3）₂（H₂O）4（6）. Their structureshave been characterized by elemental analyses, IR and single-crystal X-ray diffraction. Theinfluence factors of the crystal structures of these complexes, and the effects of hydrogen bonds andπ-π stacking interactions on the crystal structures and supramolecular structures of these complexeswere also discussed.2. Interactions of compounds with HS-DNA: the DNA-binding properties of the two ligandsand the six complexes have been studied by the electronic and fluorescence spectra, electrochemicalmeasurements and viscosity measurements. Besides, the influences of the types of bridging ligands,terminal ligands on the interactions between complexes with HS-DNA were also investigated. Theresults reveal that all of the six complexes interact with HS-DNA via the intercalation mode, andthe bonding strength of these complexes with HS-DNA follow the order: H3oxbpa> H₃oxbm,（2）>（3）>（1）,（5）>（4）>（6）.3. Cytotoxicities of complexes: The cytotoxicities of complexes （1）⁶ against two cancercell lines: human hepatocellular carcinoma cell line SMMC-7721and human lung adenocarcinomacell line A549were tested by SRB method, the results indicate that the six complexes have a certain cytotoxicities against SMMC-7721and A549cell lines, with IC50values less than38μg/mL,respectively. Especially, complexes （4） and （5） show the strongest cytotoxicities against the twocancer cell lines in these complexes, and the IC50values are in the ranges of23³8ng/mL.The researches of this dissertation enrich the content of oxamide-bridged polynuclearcomplexes, supply the chemical basis to explore novel bridging polynuclear complexes with highactivity, low toxicity and antitumor activities, and could be the valuable references for studying therelationship between structures and properties of complexes.