| Nitroimidazole drugs are valuable drugs for treating infections due to anaerobic bacteria, especially metronidazole drugs have been applied in clinic extensively. As time goes on, strains of bacteria increase quickly and the side effects of drugs have been raised recently. So the structure-activity relationships of nitroimidazole drugs have been well studied, in the same time, the synthesis of novel biologically active nitroimidazole derivatives seems to be in the continuous development. The recent research results indicate the inhibitory activity of the metal complex will increase because of the cooperation between the metals and ligands. In view of this, here in, on the basis of the synthesis of a series of nitroimidazole derivatives, we selected them as ligands to synthesize their transition metal complexes, characterized their crystal structures and properties. By the ultraviolet spectrum, fluorescence spectra, viscosity methods, the interaction of nitroimidazole derivatives with DNA and the factors which effect interaction of nitroimidazole derivatives with DNA also have been studied. Meanwhile the interaction between nitroimidazole derivatives'Cu and Ag metal complexes and DNA were studied by spectroscopy and viscosity methods. In addition, their antiamoebic activity has been determined in order to achieve the purpose of directional synthesis and this work will be of certain reference to develop more effective antimicrobial drugs.The paper is composed of following parts:1. Six novel nitroimidazole derivatives, rigid4-Nitro-2,2'-biimidazole,4-Nitro-2,2'-biimidazo(L2), N,N'-Dimethyl-5-nitro-2,2'-biimidazole(L3), and flexible ligands1,2-di-[1-(2-methyl-4-nitroimidazolyl)]ethane (L4),1,3-di-[1-(2-methyl-4-nitroimi-dazolyl)]propane (L5),1,4-di-[1-(2-methyl-4-nitroimidazolyl)]butane(L6) have been synthesized and characte-rized by UV, IR, melting point determination and elemental analyses.2. Twenty-three complexes have been synthesized by reaction of above novel nitroimidazole derivatives, metronidazole with Cu(â…¡),Ag(â… ),Co(â…¡),Ni(â…¡),Zn(â…¡),Mn(â…¡) salts respectively. Moreover, reactions of H2biim, MeHbiim or L4in the presence of Cu2+or Ag+as central ion and5-sulfosalicylic acid as auxiliary ligand gave three complexes. Most of complexes have been characterized by elemental analysis, UV, IR spectroscopy, TG-DTA and molar conductivity. X-ray single crystal diffraction analysis reveal that five complexes belong to mononuclear, binuclear complex and1-D chain coordition polymer respectively.3. The interaction mode between ligands, complexes and calf thymus DNA has been investigated by means of UV, fluorescence spectra and viscosity measurements. The structure-activity relationship of these compounds binding to DNA has been examined and the results indicate that the planarity and the plane surface area of the main structure of compounds are decisive influence to DNA interaction.4. With the two-fold agar dilution method, the antiamoebic activities of five nitro-imidazole derivatives, metronidazole, their copper, silver complexes and copper, silver salts have been determined, respectively. It has been found that N,N'-Dimethyl-5-nitro-2,2'-biimidazole(L3) has better effect of antiamoebic activity than metronidazole and the L3is worth further research and development. Structure-activity relationship of these compounds reveal that there is a possible link among the nitro position, methyl groups, double heterocyclic rigid of compounds and the effect of their antiamoebic activity.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 antiamoebic drugs with high activity and low toxicity.
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