The Copper-zinc Superoxide Dismutase Analog Compound Design, Synthesis, Characterization And Structure-activity Relationship Study

The developing history and the catalytic mechanism of CuZn-Superoxide Dismutase have been summeU-ized. A systematic study on the crystal structure and the electron structure of native active site in CuZn-SOD have been carried out. Ligands bis (2-benzimi dazolmethyl) amine (N3), tris (2-benzimidazolmethyl) amine (NIB) and 36 transition metallic complexes of copper and zinc have been synthesized. Some mimetic complexes have been characterized by spectra analysis and structure analysis. Their biological activities have been tested. The structure and function relationship was discussed.l.A summery of history and new tendency of SOD studying.2.Outlined the structures of different sources CuZn-SOD and introduced the structure of CuZn-SOD extracted from spinach leaves, in detail. The results indicated that SOD extracted from different source are highly conserved.3 Take the active sites of SOD extracted from different sources as model, ab mitio calculations have performed using Gassian94 with B3YLPILANL2DZ basis sets. The molecular frontier orbital energies, the total atomic charge of these complexes and theiidocked into the active sites of SOD, the interactive energy was calculated using DOCK program for the spinach leave SOD.4.The catalytic mechanism of Copper Zinc-Superoxide Dismutase was summarized. CuZn-SOD has ability to eliminate Oj. because Cu2~ ion play an important role. Zn2~ ion only stabilized the whole structure.5.Synthesis and C, H, N, element analysis of the ligands (N3 and NTB) and its mono-,bis-,metallic complexes have been reported. IR and UR spectra analysis were performed on the ligand and some complexes.6.The crystal structure of a bisnuclear copper complex ligand of N3 and a mononuclear Zinc complex ligand of NIB have been investigated. In the binuclear, the 4,4'-dipy molecule bridged two copper atoms. The geometry around the copper ion is described as distorted octahedral configuration. Whereas, the 4,4'-dipy doesn't coordinated with zinc ion in the mononuclear Zinc complex ligand of NTB, only is in its solvent molecule state. Zinc ligands show trigonal dipyramid.7.The bioactivity of compounds were assaied by means of improved pyrogallol autoxidation. The active data of Cu-im-Zn and Cu-dipy-Cu are higher than others. Their 50% inhibition were respectively 5.17 and 4.30.