Syntheses And Structures Of Polycopper(Ⅱ) Complexes Bridged By N,N’-bis(Substituted)oxamides: Antitumor Activity, DNA-and BSA-binding Studies

The interactions of small organic molecules, in particular transition metalcomplexes with biological macromolecules, have been an active field of coordinationchemistry and medicinal chemistry. DNA and BSA are not only important biologicalmolecules, but also many of the targets of the drug in vivo. Investigation of theinteraction between metal complexes and DNA and BSA play an important role inexploring the structure and function of DNA and BSA, understanding the mechanismof anticancer drug, design and synthesis metal complexes with DNA andBSA-bonding function.With the aim of finding broad-spectrum, more-efficacious and less-toxicanti-cancer metal complexes, in this paper, we chose two kinds ofN,N’-bis(substituted)oxamide as bridging ligand, to design and synthesis a series ofpolycopper(II) complexes with different terminal ligands. Their structures have beencharacterized by single-crystal X-ray diffraction. Furthermore, the DNA-andBSA-binding ability has been monitored by using UV absorption and fluorescencespectrum experiment, and the cytotoxic activity was determined in vitro. The detailcontents mainly include the following three parts:1. Synthesis and structures of free ligand and polycopper complexes: onetetracopper(II) complex [Cu4(bhyox)2(phen)2(H2O)2](pic)2(1) bridged byN-benzoate-N′-[2-(2-hydroxyethylamino)ethyl]oxamide (H3bhyox) was synthesized,and one new asymmetrical N,N’-bis(substituted)oxamide ligand, N-benzoate-N′-[3-(diethylamino)propyl]oxamide (H3bdpox)(2) and its one one-dimensionalpolymeric copper(II) complex {[Cu2(bdpox)(dabt)]NO3·H2O}n(3) and twotetracopper(II) complexes [Cu4(bdpox)2(phen)2](NO3)2·2H2O (4) and [Cu4(bdpox)2-(Me2bpy)2](ClO4)2·2C2H5OH (5) with different terminal ligands, have beensynthesized and characterized by single-crystal X-ray diffraction. We also discussedthe influence of hydrogen bonds and π-π stacking interactions on the supramolecularstructures of these compounds.2. Interactions of compounds with DNA and BSA: To investigate the interaction of five compounds with DNA, electronic and fluorescence spectra andviscosity measurements have been used. Furthermore, the bovine serum albumin(BSA) binding ability with the five compounds have been monitored by using UVabsorption and tryptophan fluorescence quenching experiment. The results ofDNA-binding experiment showed that the free ligand interacts with DNA via thegroove binding mode, while the four polycopper complexes interact with DNA in themode of intercalation. Besides, influenced by the terminal ligands, the bondingstrength follows the order:(4)>(5)>(3)>(2). And the BSA binding experimentshowed that the five compounds can interact with BSA via changing its proteinconformation.3. Antitumor activity of compounds: We also tested in vitro cytotoxic activitiesof compounds (1)-(5) against human hepatocellular carcinoma line (SMMC-7721)and human lung adenocarcinoma cell line (A549) by SRB assays, and the resultsshow that all of the five compounds have different levels of cytotoxic activities, andthe four polycopper complexes are superior to the free ligands.On the basis of previous laboratory research work, the researches of thisdissertation enrich the research contents of oxamide-bridged complexes. These studiescould supply some valuable information for understanding the influence of thestructure-activity relationship of complexes with the bonding strength and activity ofDNA and BSA, and provide instructional information for the design and synthesis ofhigh efficiency, low toxicity, broad-spectrum complexes.