Synthesis, Characturization And Interaction With DNA/Serum-Albumin Of Novel Complexes

Many studies on the molecular structure of metal complexes and their biological activity caused much interest in the field of inorganic chemistry. DNA binding studies are very important for the development of new therapeutic reagents and DNA probes. Furthermore, human serum albumin (HSA) is the most abundant protein in the blood plasma, and has very important physiological functions, such as transportation, buffering, nutrition, etc. These inspire considerable interest in the study of the biochemical behavior of these complexes including their interactions with DNA and serum proteins, which are primary target molecules, when metal compound is administered intravenously.This dissertation consists of four chapters:Chapter 1: The structure, function and properties of DNA and protein were introduced, the methods for the analysis of the interaction of drugs with DNA, protein and research progress in preparation, bioactivities and application of complexes were summarized.Chapter 2: Four sulfur-containing D(+)-glucosamine metal complexes have been synthesized (M-GLUS, M = Co, Cu, Ni, Zn) and characterized by elementary analysis, molar conductance, and proton nuclear magnetic resonance. The yields of all these complexes were about 70%, they dissolved easily in water. The ligand coordinate metal ions mainly between sulphur and metalions, the coordination molar ratio of the ligand to metalion was 2:1, the molar conductivity indicated that all the complexes are nonelectrolyte. The mechanism of the interaction between metal complexes and calf thymus (ct) DNA has also been studied by ultraviolet absorption and fluorescence spectroscopy in Tris buffer (pH=7.08). The results from varied experiments show that the intensity of the maximal absorption peaks increased with gradual addition of metal complexes, but the metal ions can decrease the maximal absorption and the ligand has no effect on it. Meanwhile, metal complexes could remarkably quench the emission intensity of the DNA-EB system, the metal complexes could be bound to ct DNA. The quenching mechanism was discussed by Stern-Volmer's equation, the figure showed that it is influenced by static quenching and dynamic quenching, so the partial interaction of the complexes and ct DNA was the major mode. Under physiological pH condition, this study was designed to examine the effect of complexes on human serum albumin and bovine serum albumin by fluorescence, the complexes can decrease the intensity. The binding constants and sites of the interaction with serum albumin were analyzed by the Scatchard's equation, the results indicated that there was a strong interaction between the four metal complexes and serum albumin, the binding force was Co-GLUS > Zn-GLUS > Cu-GLUS＞Cu-GLUS, and the binding site is only one.Chapter 3: A new ligand, V,V'-dibenzylethane-l,2-diamine (L) and its four transition metal(â…¡) complexes, ML₂(OAc)₂·2H₂O (M = Cu, Ni, Zn, Co), have been synthesized and characterized by elemental analysis, mass spectra, molar conductivity, NMR and IR. Moreover, the crystals structure of Cu(â…¡) and Ni(â…¡) complexes characterized by single crystal X-ray diffraction showed that the complexes have a similar molecular structure. Ni(â…¡) has an regular octahedral coordination environment complexes, but typical Jahn Teller effect influenced Cu(â…¡) in an elongated octahedral environment. The interaction between complexes and calf thymus DNA were studied by UV and fluorescence spectra measure, which showed that the binding mode of complexes with DNA is intercalation. Under physiological pH condition, the effects of Cu(OAc)₂L₂·2H₂O and Ni(OAc)₂L₂·2H₂O on human serum albumin were examined by fluorescence. The results of spectroscopic measurements suggested that the hydrophobic interaction is the predominant intermolecular force. The enthalpy changeâ–³H⁰ and the entropy changeâ–³S⁰ of Cu(OAc)₂L₂·2H₂O and Ni(OAc)₂L₂·2H₂O were calculated to be -11.533 kJ·mol^-1 and 46.339 J·mol^-1·K^-1, -11.026 kJ·mol^-1 and 46.396 J·mol^-1·K^-1 respectively, according to the Scatchard's equation. The quenching mechanism and the number of binding site (n≈l) were also obtained from fluorescence titration data.Chapter 4: A new ligand, N-benzyl-N'-[2-(benzylamino)ethyl]ethane-l,2-diamine, is a KBH₄ reduction product of the Schiff base derived from the condensation reaction of A-(2-aminoethyl)ethane-l,2-diamine with 2 equiv of benzaldehyde. Its complexes with transition metal chlorides were synthesized. These complexes with the general formula of M₂L₂Cl₃ (M=Cu, Ni, Zn, Co) were characterized by molar conductivity, elemental analysis, IR spectra. And the crystal structure of Ni (II) complex determined by single crystal X-ray diffraction show that there was a chlorine atom as bridge. The interaction of complexes with calf thymus DNA was investigated by ultraviolet spectroscope and fluorescent spectroscopy, which showed that the mode of complexes binding to DNA was electrostatic binding, and the binding affinity with DNA was Cu(â…¡) complex＞Zn(â…¡) complex＞Ni(â…¡) complex＞Co(â…¡) complex. The binding constants and sites of the interaction with human serum albumin were analyzed by the Scatchard' equation, the results indicated that there was a strong interaction between the metal complexes and HSA. As indication by thermodynamic analyses, the binding was mainly based on hydrophobic interaction.