【摘要】 大脑中淀粉样Cross-β纤维沉淀是老年痴呆症(AD)的一个关键性病理特征.X射线分析显示有大量Cu2+和Zn2+集中到患者的大脑中,暗示了这些失调的离子与AD疾病有关.实验发现,在适度酸性pH值下,Cu2+与组氨酸咪唑环上的Nt配位可诱导Aβ多肽聚合成沉淀,而在中性pH值下,Cu2+与组氨酸咪唑环上的Np及主链上的去质子N或O配位生成可溶的配位化合物.本文应用密度泛函理论(B3LYP)方法,研究了Cu2+与Aβ多肽中的四肽(HHQK)形成可溶性配合物的结构,结果得到N(3)O(1)及N(4)O(1)两类配位方式,其中以N(3)O(1)配位形成变形的平面正方形配位结构,而以N(4)O(1)配位形成变形的四方锥结构.由于分子内氢键的形成,优化得到了6个不同的结构,通过能量对比找到了最稳定的结构,并深入探讨了最稳定结构的原子电荷布居规律、一些前沿分子轨道以及配合物的振动光谱,在振动光谱方面,理论与实验符合得很好.更多还原

【Abstract】 Producing amyloid cross-β fibrils are one of crucial pathological signs of Alzheimer’s disease(AD)in cerebra.X-ray analysis has shown that copper ion and zinc ion are significantly concentrated in the neurophil of AD patients,which suggests that imbalances of metal ions may be related to the pathogenesis of AD.The Nt-metal ligation occurs in Cu(II)-induced Aβ aggregation at mildly acidic pH.At neutral pH,however,copper ion binds to Np,the nitrogen of the histidine imidazole ring,and to deprotonated amide ni-trogens or oxygen of the peptide main chain.The chelation of Cu(II)by histidine and main-chain amide groups results in soluble complexes.All geometry optimizations have been carried out by density functional theory(B3LYP)methods to study the soluble coordination complexes which contain copper ion and tetrapeptide(HHQK)of Aβ.Two coordination patterns are provided.One is N(3)O(1)which can form dis-torted plane square,the other is N(4)O(1)which can form distorted square prick.Six structures have been gained when hydrogen bond in molecule is considered.The populations of the atomic net charges,some frontier molecular orbitals and vibration spectrum of complexes have been investigated for the most stable structure.It is very important that the theory can agree with the experiment very well for vibration spectrum.更多还原