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基于螯合水解增强机制的荧光探针用于可视化帕金森病模型中的 Zn。

A fluorogenic probe based on chelation-hydrolysis-enhancement mechanism for visualizing Zn in Parkinson's disease models.

机构信息

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, 211816, P. R. China.

出版信息

J Mater Chem B. 2019 Apr 14;7(14):2252-2260. doi: 10.1039/c8tb03343a. Epub 2019 Feb 5.

Abstract

Developing efficient methods for the real-time detection of Zn levels in biological systems is highly relevant to improving our understanding of the role of Zn in the progression of Parkinson's disease (PD). In this work, a novel Schiff base based Zn fluorescent probe (ZP) was designed, synthesized and systematically investigated. A significant turn-on effect on ZP upon the addition of Zn was observed, accompanied by a blue-shift of the fluorescence spectra. ZP is sensitive to Zn and has excellent selectivity against various biologically relevant cations, anions and amino acids. The sensing mechanism of ZP was studied by H NMR, MS, single crystal X-ray diffraction and theoretical calculations. The results showed that the response of ZP to Zn was based on the chelation-hydrolysis-enhancement process. Upon bonding, Zn hydrolyzes the Schiff base to an aldehyde precursor, the resulting aldehyde further coordinates to Zn to form a more stable heterobimetallic complex leading to the emission enhancement and blue-shift. ZP was applied to imaging exogenous/endogenous Zn in live HeLa cells. Furthermore, we successfully measured the Zn levels using in vitro PD models, which provided a visualization method to better understand the relationship between Zn levels and PD development.

摘要

开发用于实时检测生物体系中锌水平的有效方法,对于深入了解锌在帕金森病(PD)进展中的作用至关重要。在这项工作中,设计、合成并系统研究了一种新型基于席夫碱的锌荧光探针(ZP)。当加入锌时,ZP 表现出显著的开环效应,同时荧光光谱发生蓝移。ZP 对锌具有灵敏度和对各种生物相关阳离子、阴离子和氨基酸的优异选择性。通过 1H NMR、MS、单晶 X 射线衍射和理论计算研究了 ZP 的传感机制。结果表明,ZP 对锌的响应基于螯合-水解增强过程。在结合时,锌将席夫碱水解成醛前体,所得醛进一步与锌配位形成更稳定的杂金属配合物,导致发射增强和蓝移。ZP 被用于在活 HeLa 细胞中外源/内源性 Zn 的成像。此外,我们成功地使用体外 PD 模型测量了 Zn 水平,为更好地理解 Zn 水平与 PD 发展之间的关系提供了一种可视化方法。

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