Syntheses, Structures, Anticancer Activities And Interactions With DNA Of Novel Asymmetrical Oxamido-bridged Polynuclear Complexes

The research of the anticancer complexes was pushed forward by the discovery of the anticancer activities of cis-platin and its worldwide clinical application. The design and synthesis of novel functional coordination compounds with antitcancer activity become one of the most challenging subjects in the field of inorganic medicinal chemistry. This dissertation aims at finding anticancer complexes with broad spectrum, high activity and low toxicity. A novel dissymmetrical oxamide ligand and nine polynuclear complexes bridged by it were synthesized, and characterized by means of X-ray single crystal diffraction, elemental analysis and IR, and the influencing factors on structures of the compounds have been investigated. The actions of these compounds to DNA were also investigated by spectral and electrochemical methods. Finally, the cytotoxicity activities of 10 compounds against SMMC-7721 and A549 cell lines were studied in vitro.. This thesis consists of three sections as follows:1. One novel dissymmetrical oxamide ligand, N-(2-hydroxybenzyl)- N'-[3-dimethylamino)propyl]-oxamide (H3dmapob) (1), have been synthesized and characterized by X-ray single crystal diffraction, elemental analysis, IR, 1H NMR and MS. The diversity of complexes with different structures is carried out by successful synthetic strategy of using dmapob3- as bridging ligand, controlling species of metal ions, counter anions and solvent in the course of synthesis. Nine complexes bridged by dmapob3-: three trinuclear complexes, Cu[Cu(dmapob)(CH₃OH)]2 (2), {Co(CH₃OH)2[Cu(dmapob)(CH₃OH)]2}·4CH₃OH (3) and {[Cu(dmapob)(CH₃OH)]- Ni(CH₃OH)2[Cu(dmapob)]}·3CH₃OH (4); three tetranuclear complexes, [Cu2- (dmapob)(phen)2]2(ClO4)2·2H₂O (5), [Cu2(dmapob)(phen)2]2(NO3)2·2H₂O (6) and [Cu2(dmapob)(bpy)2]2(ClO4)2·4CH₃OH (7); two 1-D polynuclear complexes ,{Mn[Cu(dmapob)]2}n (8) and {Zn[Cu(dmapob)]2}n (9); one 2-D polynuclear complex , {Cd[Cu(dmapob)(DMSO)]2}n·nH₂O (10), have been synthesized and characterized by X-ray single crystal diffraction, elemental analysis, IR spectra.2. DNA binding studies of ten compounds with HS-DNA have been studied by the spectroscopic (absorption and emission spectra) and electrochemical measurements. The results show that all these compounds can interact with HS-DNA and the interaction mode is intercalation. The interactions of complexes (5), (6) and (7) with DNA are strongest, complexes (8), (9) and (10) are better, and ligand (1) is the worst. The interactions of metal complexes with pBR322 DNA were also studied by gel electrophoresis technique. The results show that compounds (5), (6) and (7) can cleavage pBR322 DNA directly under physiological conditions. Among them, complex (5) has the strongest effects of cleavaging pBR322 DNA to linear.3. The cytotoxicities of ligand H3dmapob (1) and its complexes (2)⁴, (6)⁸, (10) are examined in vitro by SRB assay. The results indicate that the eight compounds showed different cytotoxic activities against SMMC-7721 and A549 cell lines. Among these compounds, complexes (8) and (10) have the strongest effects on HS-DNA, with the IC50 = 10³0 ng/mL in two human tumor cell lines. The researches of the paper not only enriched the content of inorganic medicinal chemistry, but also supplied valuable information for design and synthesis of inorganic antitcancer medicinal with high activity and low toxicity.