Nickel Superoxide Dismutase Model Compound Design, Synthesis, Characterization And Structure-activity Relationship Studies

The studies on Superoxide Dismutase (simplified as SOD) and its mimic complexes are of great significance to chemistry, biology and medicine, so the study on SOD have always been a hot topic. As the work of this thesis, the species, function and the developing history of SOD have been generally stated. After that, a novel member of SOD family, Nickel-containing Superoxide Dismutase (simplified as Ni-SOD) was introduced. The discovery of Ni-SOD not only pours fresh blood into SOD family, but also is benefit to understanding the function of Nickel element in biological system. Then the study progress of SOD mimics was sutnmerized. According to the limited information on properties and structure of Ni-SOD, and the high conservative nature of evolution on SOD enzyme, the active site structure of Ni-SOD and its catalytic mechanism to superoxide radical (O2--) were initially explored. A series of Ni-SOD mimics were synthesized, all the mimics and related ligands were characterized by elemental and spectral analysis. In addition, two mimics' crystal structure were determined by X-ray diffraction method and quantum chemistry calculation were performed to them. The bioligical activities of all mimics have been assayed and the relationship between structure and activity has been discussed. The major work on this thesis are as following:1. The produce, reaction activity of superoxide radical (O2-·) and its harm to the organism were stated. The species, function and developing history of SOD were summerized. Following this, a novel Ni-SOD was introduced as the subject and the study progress on SOD mimics were simply referred.2. The biological significance of Nickel element was summerized.3. The source, nomenclature, properties and the newest information on the structure of Ni-SOD were introduced. The active site structure of Ni-SOD and its catalytic mechanism to superoxide radical (O2-@) were initially explored.4. The active sites of reduced and oxided Ni-SOD, which were attained by replacing the site Iron ion of Fe-SOD as Nickel ion, have been performed quantum chemistry calculation using Gaussian 98 program pack with LANL2DZ basis sets. The molecular frontier orbital energies, the charge distribution and frontier orbital contribution of these two kinds of Ni-SODs were discussed respectively and compared with each other.5. A series of ligands containing imidazol were disigned and synthesized. Selecting dipyridine and o-phenanthroline as the assistant ligands, we have synthesized a series of mono- and dinuclear complexes with Nickel perchlorate hexahydrate and all the complexes were characterized by elemental analysis and IR, UV spectrum.6. The crystal structure of Ni-SOD mimics with synthesized ligands EDTB and tbpOH were determined by X-ray method, their crystal structure were analyzed, quantum chemistry calculation were carried out and the relationship between structure and activity were discussed.7. The biological activities of synthesized Ni-SOD mimics were tested by means of improved pyrogallol autoxidation method.