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

Molecular rotor-based fluorophores (RBFs) have been widely used in many fields. However, the lack of control of their viscosity sensitivity limits their application. Herein, this problem is resolved by chemically installing extended pi-rich alternating carbon-carbon linkages between the rotational electron donors and acceptors of RBFs. The data reveal that the length of the linkage strongly influences the viscosity sensitivity, likely resulting from varying height of the energy barriers between the fluorescent planar and the dark twisted configurations. Three RBF derivatives that span a wide range of viscosity sensitivities were designed. These RBFs demonstrated, through a dual-color imaging strategy, that they can differentiate misfolded protein oligomers and insoluble aggregates, both in test tubes and live cells. Beyond RBFs, it is envisioned that this chemical mechanism might be generally applicable to a wide range of photoisomerizable and aggregation-induced emission fluorophores.

Automated summary

By chemically installing extended pi-rich alternating carbon-carbon linkages between the rotational electron donors and acceptors of RBFs, the lack of control of their viscosity sensitivity has been resolved. The length of the linkage strongly influences the viscosity sensitivity, providing the possibility to design RBFs with different viscosity sensitivities. RBFs can differentiate misfolded protein oligomers and insoluble aggregates in test tubes and live cells through a dual-color imaging strategy.