A General Strategy to Control Viscosity Sensitivity of Molecular Rotor-Based Fluorophores.

A General Strategy to Control Viscosity Sensitivity of Molecular Rotor-Based Fluorophores.
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DOI:
10.1002/anie.202011108
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发表时间:
2021-01-18
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
--
通讯作者:
Zhang X
Zhang X
中科院分区:
其他
文献类型:
--
作者:
Ye S;Zhang H;Fei J;Wolstenholme CH;Zhang X

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基于分子转子的荧光团(RBFs)在许多领域有着广泛的应用。然而,如何合理控制其粘敏性仍是一个谜,从而限制了其应用。在此,我们通过在RBF的旋转电子给体和受体之间化学地安装扩展的富π交替碳-碳键来解决这个问题。我们的数据表明,富π键的长度强烈影响粘度灵敏度,可能是由于荧光平面和暗扭曲配置之间的能量势垒的高度变化。该机制允许设计跨越广泛的粘度敏感性的RBF衍生物的三个支架。双色成像策略证明了这些RBF的应用,该策略可以区分试管和活细胞中错误折叠的蛋白质低聚物和不溶性聚集体。除了RBFs,我们设想这种化学机制可能普遍适用于广泛的光致异构和聚集诱导的发射荧光团。在这项工作中,我们报道了一种新的方法来合理地控制分子转子基荧光团(RBFs)的粘度灵敏度,通过安装富π键电子供体和受体的RBFs。这项工作的结果产生了RBFs,跨越广泛的粘度敏感性,并允许检测蛋白质聚集与不同的紧凑性在体外和活细胞。
Molecular rotor-based fluorophores (RBFs) have been widely used in many fields. However, it remained enigmatic how to rationally control their viscosity sensitivity, thus limiting their application. Herein, we resolve this problem by chemically installing extended π-rich alternating carbon-carbon linkage between the rotational electron donor and acceptor of RBFs. Our data reveal that the length of π-rich linkage strongly influences the viscosity sensitivity, likely resulted from varying height of the energy barriers between the fluorescent planar and the dark twisted configurations. This mechanism allows for the design of three scaffolds of RBF derivatives that span a wide range of viscosity sensitivities. Application of these RBFs is demonstrated by a dual-color imaging strategy that can differentiate misfolded protein oligomers and insoluble aggregates both in test tubes and live cells. Beyond RBFs, we envision that this chemical mechanism might be generally applicable to a wide range of photoisomerizable and aggregation-induced emission fluorophores. In this work, we reported a novel method to rationally control the viscosity sensitivity of molecular rotor-based fluorophores (RBFs) by installing π-rich linkage between the electron donor and acceptor of RBFs. The outcome of this work generates RBFs that span a wide range of viscosity sensitivity and allow detection of protein aggregation with different compactness both in vitro and in live cells.
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