钴取代的链状Strandberg结构磷钼酸盐的合成及其对Aβ错误折叠聚集过程的调节  

Synthesis of a Linear Cobalt-Substituted Strandberg-Type Polyphospolybdate with Ability in Modulating Conformation of Aβ-Peptide Misfolding Aggregation

作　　者：滑继爱 卫雪曼 张娜 陈鹏举 马翔 HUA Ji-Ai;WEI Xue-Man;ZHANG Na;CHEN Peng-Ju;MA Xiang(Chemistry and Chemical Engineering Department,Taiyuan Institute of Technology,Taiyuan 030008,China;Department of Geriatrics,First affiliated Hospital of Naval Medical University,Shanghai 200081,China;Laboratory of Biochemistry and Pharmacy,Taiyuan Institute of Technology,Taiyuan 030008,China;State Key Laboratory of Coordination Chemistry,Nanjing University,Nanjing 210023,China)

机构地区：[1]太原工业学院化学与化工系,太原030008 [2]海军军医大学第一附属医院老年病科,上海200081 [3]太原工业学院生化药学实验室,太原030008 [4]南京大学配位化学国家重点实验室,南京210023

出　　处：《无机化学学报》2022年第10期1908-1918,共11页Chinese Journal of Inorganic Chemistry

基　　金：山西省“1331”工程;山西省基础研究计划项目(No.201901D211453,20210302124333);山西省高等学校科技创新项目(No.STIP2020L0644);配位化学国家重点实验室开放课题项目(No.SKLCC202204)资助。

摘　　要：设计并合成了一例钴取代的Strandberg结构的磷钼酸盐(H_(2)en)_(6){[Co(H_(2)O)_(4)](P_(2)Mo_(5)O_(23))}_(3)·11H_(2)O(简称CoPM,en=乙二胺),其结构通过元素分析、红外光谱、热重分析以及X射线单晶衍射进行了表征。结果显示,CoPM是由磷钼氧簇[P_(2)Mo_(5)O_(23)]^(6-)和钴配合物[Co(H_(2)O)_(4)]^(2+)交替连接而形成链状结构,其中每个循环单元包含3个{[Co(H_(2)O)_(4)](P_(2)Mo_(5)O_(23))}^(4-)结构单位,它们各自的延展方向与配位环境均不相同。利用硫黄素T荧光法、比浊法、圆二色谱、NMR等研究了CoPM对淀粉样蛋白(Aβ)错误折叠过程的干预,发现CoPM能够通过调节β错误构象,从而减少有害聚集体的形成。2',7'⁃二氯荧光素(DCF)荧光及细胞毒性实验表明CoPM还可以消除由Cu^(2+)⁃Aβ所产生的活性氧物种(ROS),进而保护PC12细胞及其突触免受Aβ错误折叠聚集体及氧化应激的损害。A linear Co-substituted Strandberg-type polyphosphomolybdate(H_(2)en)_(6){[Co(H_(2)O)_(4)](P_(2)Mo_(5)O_(23))}_(3)·11H_(2)O(abbreviated as CoPM,en=ethylenediamine)has been synthesized and structurally characterized by elemental analyses,IR spectrum,thermogravimetric analysis,and single-crystal X-ray diffraction.Structural analysis reveals that the molecular structural unit of CoPM consists of[P_(2)Mo_(5)O_(23)]^(6-)cluster,and Co-complex[Co(H_(2)O)_(4)]^(2+),and they join alternately to form the 1D infinite extension skeleton of CoPM.Furthermore,each cyclic unit of the CoPM chain contains three{[Co(H_(2)O)_(4)](P_(2)Mo_(5)O_(23))}^(4-)units in solid states based on bond valence sums(BVS)calculation.The intervention of CoPM on the misfolding process of amyloidβ-protein(Aβ)was studied by the thioflavin T fluorescence method,turbidimetric method,circular dichroism,and NMR.The results indicate that CoPM can modulate theβ-sheet-rich conformation of Aβaggregates,and thus reduce the formation of toxic species.Moreover,2’,7’-dichlorofluorescein(DCF)fluorescence and cytotoxicity experiments showed that CoPM could also eliminate reactive oxygen species(ROS)produced by Cu^(2+)-Aβaggregates.It can inhibit the cytotoxicity of β-sheet-rich species and protect synapses of PC12 cells.CCDC:1944799.

关 键 词：多聚磷钼酸盐 抗氧化 构象调节 蛋白错误折叠疾病 淀粉样蛋白 

分 类 号：O614.812[理学—无机化学] O613.62[理学—化学] O614.612