Study Of Synthesis, Structure And Biological Activity Of Two Kinds Of Functional Compounds

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. Deoxyribonucleic acid (DNA) is an important genetic substance in organic chemistry. As the basis of genetic expression, it plays an important role at the process of storing, copying and transmitting germ messages. This dissertation aims at finding anticancer complexes with broad spectrum, high activity and low toxicity. Firstly, one symmetrical oxamide ligand and two novel dissymmetrical oxamide ligands and six polynuclear complexes bridged by them were synthesized. Sencondly, the research of organotin compounds were extensively studied early due to their comparabilities between tin and platin. Some of them have similar structure from cisplatin and carboplatin derivatives and were recognized to have potential antitumour activity more active than that of them. So, on the other hand, we select the aromatic sereies carboxylic acid ligands containing the N and O atoms not only relevant to the material of life, but also have complicated and variable behavior of coordination in this dissertation. A series of novel complexes have been were synthesized bridged by them. For above compounds, we characterized by means of X-ray single crystal diffraction, elemental analysis and IR, respectively, and the influencing factors on structures of the compounds have been investigated. The actions of these oxamide compounds to DNA were also investigated by spectral and electrochemical methods. Finally, the cytotoxicity activities of above compounds against SMMC-7721 and A549 cell lines were studied in vitro.1. One symmetrical N,N'-bis[(3-dimethylamino)propyl]oxamide ligand (L1) and two novel dissymmetrical N,N'-bis(substituent)oxamide ligand, N-(2-hydroxy-4-Cl-benzyl)-N'-[(3-dimethylamino)propyl]oxamide (H3dmapob) (L2) and N-(2-hydroxy-5-Cl-benzyl)-N'-[(3-dimethylamino)propyl]oxamide (H3dmapob) (L3) have been synthesized and characterized by MS,'H NMR, IR and elemental analyses. 2. Six compounds with these symmetrical and dissymmetrical N,N'-bis(substituent)oxamides as ligands,{Cu2(dmapox)(OH)2(ClO4)(H2O)·H2O}n (1), [Cu2(Pya)2(CH3OH)2]·(H2dmapox) (2), [Cu2(dmapob)(phen)]2·(ClO4)2 (4), [Cu3(dmapob)2(H2O)(CH3OH)]2·2CH3OH (5),{[Cu2(dmapob)2Mn(H2O)]2·2H2O}n (6), {Mn(phen)2[Cu(dmapob)(ClO4)]-2H2O (7) and eight compounds with aromatic sereies carboxylic acid ligands containing the N and O atoms, [Sn(aiba)Ph3] (8), [Sn4(nBu)8(aiba)O2] (9), [Sn4(nBu)8(amca)O2] (10), [nBu3Sn(apca)]n (11), {[(Ph3Sn)4(1,2,4,5-btca)]}n (12), [(Ph3Sn)4(1,2,4,5-btca)] (13), [(nBu3Sn)16(1,2,4,5-btca)6]}n (14),{[Ph3Sn(DMF)]2(1,4-atpc)} (15), have been synthesized by successful synthetic strategy of controlling species of metal ions, counter anions, inventory and solvent etc. in the course of synthesis. All them have been characterized by X-ray single crystal diffraction. The coordination environments of the metal atoms in the complexes are explored. Hydrogen bonds andπ-πstacking interactions which stabilize the crystal structure in these cplexes are also discussed.3. The DNA-binding properties of the oxamide compounds have been studied by electronic absorption, fluorescence, viscometry and electrochemical technique. The results suggest that the ligands L2-L3 and compounds (1)-(2) bind to DNA via a groove binding mode while complexes (4)-(7) bind intercalatively to DNA. The structure-activity relationship of these oxamide compounds binding to DNA has been examined.4. The cytotoxicities of oxamide ligands and compounds (1)-(15) are examined in vitro by SRB assay. The results indicate that some compounds showed different cytotoxic activities against SMMC-7721 and A549 cell lines. Among these compounds, complound (6) has the strongest effects in these oxamide compounds, with IC50 values 86 and 71 ng/mL in the two human tumor cell lines, respectively. The antitumor activity of organotin compounds (8), (9), (10), (12) and (14) is very obviously.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 antitumor medicinal with high activity and low toxicity.