Study On The Coordination Modes Between β-Amyloid Peptide And Copper (Ⅱ) Or Zinc (Ⅱ) Ion With The Method Of Model Compounds

Alzheimer's disease is the most common form of dementia in the elderly, and is characterized by the senile plaques (SPs) in the extracellular of patients' brains. The SPs are neurotoxic and their extensive depositions would cause atrophy and death of neurons. Many studies have revealed that SPs are formed for the aggregation, fibrosis and codeposition of amyloidβ-peptides(Ap) with other numerous associated proteins and nonprotein components. As the main factors of inducing the aggregation of Aβ, enrichment of the Zn(Ⅱ) and Cu(Ⅱ) ions has the direct relationship with Aβpeptide and AD. So it is very necessary for us to understand the mechanism of AD and develop new therapeutic agents. However, since the Aβpeptide possesses the big molecular weight and numbers of bonding sets, the exact binding modes between these metal ions and Aβpeptide are still unclear. In this paper, we have studied the binding modes between copper ion, zinc ion and Aβpeptide by synthesizing model complexes. The main results include:1. Six ligands containing imidazole moiety had been synthesized follow the literature method, including bis(2-benzimidazoly)ethane(bbime), 2-(Aminomethyl)-benzimidazoledihydrohloride(ambmz·2HCl), N-salicylidi-ne-2-aminomethylbenzimidazole(Hsal-ambmz),1,3-bis(ben-zimidazol-2-yl)-propylamine(bbimpa),1-(2-hydroxyphenyl)-2-aza-3,5-bis(benzimidazol-2-yl)pentane(Hhbbimp),2-(2'-hydroxyphenyl)benzimidazole (Hhpbim). 2. ligands containing imidazole that have been synthesized were reacted with copper ion and Zinc ion, five complexes of copper, four complexes of zinc had been synthesized and characterized by elemental analysis, IR spectra and UV-Visible spectra, the obtained compounds are Cu(bbime)(NO3)2, Cu(ambmz)2Cl2·H2O, Cu(sal-ambmz)Cl, Cu(bbimpa)(OAC)·4H2O, Cu2(hbbimp)2(OAC)2, Zn(bbime)(OAC)2, [Zn(ambmz)2·H2O]Cl2·2H2O, Zn(bbimpa)(OAC)·3H2O, Zn(hpbim)2·C2H5OH. All of them haven't been reported except the complexes [Zn(ambmz)2·H2O]Cl2·2H2O and Zn(hpbim)2·C2H5OH.In comparison with the electronic spectra of synthesized model complexes and Cu-Aβ, we conclude that under physiological conditions the possibility of Cu coordinating to Aβpeptide in 2N2O mode is rather low.