Synthesis, Characterization And Biolgical Activities Of Superoxide Dismutase And Peroxidase Model Complexes

Superoxide radical anon ^.O₂^- is an active species generated during biological oxidation utilizing molecular oxygen.It is involved in several important biological processes.High level of ^.O₂^- may cause cell damage leading to the appearance of several diseases.Superoxide dismutase(SOD) is a metal enzme found in animals,plants and microorganisms.SOD catalyzes the conversion of superoxide radical anion to hydrogen peroxide and oxygen, thus reducing its body content.Commercial SOD and MnCat products come from animal blood or microorganisms extracts and are expensive due to the high cost related to tedious extraction and preparation.Its widespread application is further limited by its poor cell permeability due to the large size of SOD.In addition its lifetime in human body is only a few hours.Therefore, chemical synthesis of SOD and MnCat mimics has attracted the attention of many chemists.SOD and MnCat mimics hold great potential as pharmaceutical agents for the treatment of many diseases.We have been involved in the synthesis and metal coordination chemistry of TACN and benzimidazole.These molecules are screened as potential model compounds of SOD and peroxidase.The structure characteristic of these complexes and its superoxide dismutase and peroxidase activity were studied.The following research was presented in this thesis:1,Derivatives from TACN were prepared by reacting with 2-chloromethylbenzimdazole,chloroacetic acid and p-tolylsulfonyl chloride, respectively.Three ligands containing different pendant arms and four structure-distinctive complexes were prepared for the first time,which were described in the second chapter.Two cyclic triamine rings are fused via ethane bridge.Binuclear Cu(Ⅱ) and Mn(Ⅱ) complexes based on the bis(pentadentate) ligand,which has been prepared by the addition of four 2-methylbenzimdazole or acetic acid pendant arms to the bis(tacn) ligand, were obtained.Those ligands and metal complexes were characterized by element analysis,IR,ESI-MS,crystal structure analysis,the electro-chemistry characterization and magnetism interactions between metal ions were studied.2,2-Benzimidazol phenolate was synthesized from o-phenylenediamine and salicylic acid,N-(benzimidazolyl-2-methyl)-methylamine was prepared from o-phenylenediamine,chloroacetic acid and methylamine.Two binuclear Cu(Ⅱ) complexes[Cu(C₁₃H₉N₂O)Cl]₂·(CH₃CN)₂,[Cu(C₉H₁₁N₃)Cl₂]2 have been prepared,and their crystal structure were determined by X-ray analysis.3,The SOD activities were assayed by photoreduction of riboflavin. Considerable data have been presented to show that the binuclear Cu(Ⅱ) complex is excellent model complex for SOD and its SOD activity are higher compared with the reported mononuclear analogue[CuLMeCN](ClO₄)₂·H₂O (L=1,4-bis(benzimidazole-2-ylmethyl)-1,4,7-triazacyclonone).The MnCAT activities were determined through catalytic disproportionation of H₂O₂ by the binuclear Mn(Ⅱ) complex.The results showed that the complex has Superoxide Dismutase activity as well as peroxidase activity.