Synthesis, Structures And Bioactivities Of Bridging Polynuclear Transition Metal Complexes

Inorganic or metal-containing medicinal compounds have been attracting considerable attentions due to their possible application in the treatment of cancer. The design and synthesis of novel functional coordination compounds with antitumor activity remain an elusive scientific challenge in the fields of coordination chemistry and medicinal chemistry. In this dissertation, the synthesis, crystal structure, DNA binding activities, SH-SY5Y protective effects and antitumor activities targeted to topoisomerase I of oxamido-bridged polynuclear transition metal complexes and decavanadates have been studied systematically. This dissertation consists of two sections as follows:1. Two symmetrical oxamide ligands, H2heap and H2heae, and two dissymmetrical oxamide ligands, H3oxbe and H3oxbme have been synthesized and characterized by elemental analysis, IR and MS. Fifteen oxamido-bridged compounds (H4heap)(ClO4)2 (1), [Cu2(heap)](ClO4)2·2H2O (2), Cu2(heap)(NO3)2 (3), Cu2(heap)Cl2 (4), Cu4(heap)2(SO4)2(CH3OH)2 (5), [Ni2(heap)(H2O)4]Cl2 (6), [Cu2(heae)(bpy)2](ClO4)2 (7), [Cu2(heae)(phen)2](ClO4)2 (8), Cu[Cu(oxbe)(H2O)2]2 (9), Zn(CH3OH)(H2O)[Cu(oxbe)]2·H2O (10), Mn(H2O)2[Cu(oxbe)]2·2H2O (11), Mn(H2O)2[Cu(oxbme)]2·2H2O (12), {Cu[Cu(oxbme)(H2O)]2}n (13), [Cu(oxbe) Cu(dmen)]n·(ClO4)n (14), [Cu(oxbme)Cu(tmen)(H2O)]4V4O12·16H2O (15), and five decavanadate compounds (H2tmen)3V10O28·6H2O (16), (H2dmen)3V10O28·5H2O (17), (H2en)3V10O28·2H2O (18), (H2dmpn)3V10O28·6H2O (19), (H2pn)3V10O28·5.5H2O (20), have been synthesized and characterized by elemental analysis, IR spectra and X-ray single crystal diffraction. The function of the supramolecular interactions such as hydrogen bonds,π?πinteractions has been preliminarily discussed.2. The bioactivities concerning DNA binding activities, nerve protection and antitumor activities targeted to topoisomerase I have been studied:(1) The interactions of complexes (2)-(15) with HS-DNA have been studied by UV absorption titrations, ethidium bromide fluorescence displacement experiments, electrochemical techniques and viscosity measurements. The results suggest that these complexes can interact with HS-DNA via electrostatic, intercalative or groove binding mode.(2) Decavanadate compounds (16)-(20) have been evaluated for their effects on the human neuroblastoma cell line SH-SY5Y. Compound (20) can protect the SH-SY5Y from the damnification of KCl.(3) DNA relaxation assay has been used to detect the activities of compounds (2)-(20) on topoisomerase I (Topo I). The results indicate that compounds (2), (4), (7), (8), (10), (15) and (18) can inhibit Topo I notablely. The IC50 of compound (2) is 8.6±1.2μM, lower than that of hydroxycamptothecin (OPT).(4) Antitumour activities of these compounds have been tested by MTT and SRB methods. Compounds (7)-(12) exhibit good activities against MCF-7, SF-268, NCI- H460, SMMC-7721 and A549.The researches here not only enrich the content of oxamido-bridged complexes and decavanadates, but also can be the references for designing and synthesizing new non-platinum complexes with antitumor activity, studying their relationship between structure and activity.