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

Alzheimer disease(AD),one of neurodegenerative disorders of the central nervous system,is affecting an important fraction of the aged population in the world.AD is characterized by the loss of cholinergic neurons and the progressive deterioration of cognitive function,memory, and self-care.A major pathological hallmark is that senile plaques(SPs) occur in the brains of patients.SPs are neurotoxic and their extensive depositions would cause neurodegeneration.Many studies have shown that amyloidβ-peptides(Aβ) aggregate and accumulate,moreover,colocalize with numerous other associated protein and nonprotein components to form SPs.Many factors may induce the aggregation of Aβpeptide,however, metal ions such as Zn(â…¡) and Cu(â…¡) play key roles in the aggregation of Aβ. Studying the interactions of these metal ions with Aβpeptide is essential for us to understand the pathogenesis of AD and develop new therapeutic agents. But the exact binding modes of these metal ions with Aβpeptide are still unclear.In this paper,we have investigated the binding modes between zinc ion and Aβpeptide by synthesizing model complexes.1.Five ligands containing more than one imidazole moiety has been synthesized,including 2-(Aminomethyl) benzimidazole dihydrochloride (ambmz·2HCl),N-salicylidine-2-aminomethylbenzimidazole(Hsal-ambmz), 2-(Aminoethyl) benzimidazole dihydrochloride(aebmz·2HCl),N-salicylidine-2-aminoethylbenzimidazole(Hsal-aebmz) and tris-(2-benz- imidazolyl methyl) amine(N4).We also synthesized the ligands of N- AcetyI-Lglutamic Acid and Imidazole Ligands.2.A novel Zn(â…¡) complex with N4-type ligand has been synthesized and characterized by elemental analysis,IR spectra,UV-visible spectra and X-ray diffraction analyses.The complex is crystallized in triclnic symmetry, P-1,with crystallographic parameters a=11.928(5)(?),b=20.130(9)(?), c=25.033(11)(?),α=66.407°,β=88.266(7)°,γ=73.103(7)°,V=5445(5)(?)³, Z=66,Dc=1.463 g/cm³.The zinc(â…¡) center in this complex is located in square pyramidal geometry and the coordination sphere is composed with one of the benzimidazole-N atoms in the axial site and two other benzimidazole-N atoms,one amine-N atom,one O atom occupied in the equatorial positions.3.Complex Zn(C₉H₁₁N₃)₂(ClO₄)₂ has been synthesized and characterized by eleme-ntal analysis,IR spectra,UV-visible spectra and molar conductivity measure-ments.A single crystal of Zn(C₉H₁₁N₃)₂(ClO₄)₂ suitable for X-ray diffraction analysis was obtained.The crystal data show that it belongs to Monoclinic,C2/c,with crystallographic parameters a=11.150(3)(?), b=15.343(3)(?),c=14.156(3)(?),α=90.00,β=93.322(4),γ=90°,V=2417.7(12)(?), Z=4,Dc=1.606 g/cm3.In Zn(C₉H₁₁N₃)2(ClO₄)2,each Zn(â…¡) ion coordinated to two imidazoles and two amine-N atoms forming distorted tetrahedral geometry.4.The complex ZnC₃₂H₂₈N₆O₂·H₂O has been synthesized and characteri zed by elemental analysis,IR spectra,UV-visible spectra and X-ray dif -fraction analyses.The complex ZnC₃₂H₂₈N₆O₂·H₂O belongs to orthorhombic symmetry,P2(1)2(1)2,with crystallographic parameters a=18.947(8) (?),b=14.675(6)(?),c=12.768(5)(?),α=β=γ=90°,V=3550(3)(?)³,Z=2,Dc=1. 606g/cm3.In this complex,Zn(â…¡) ion is coordina ted to four N atoms, two phen-olate O atoms,forming a distorted Octahedron geometry.5.Complex C₂₆H₃₆N₁₀O₁₁Zn₂ of N-AcetyI-Lglutamic Acid and Imidazole Ligands has been synthesized and characterized by elemental analysis and UV spectra.