Fluorescence umpolung enables light-up sensing of N-acetyltransferases and nerve agents

Intramolecular charge transfer (ICT) is a fundamental mechanism that enables the development of numerous fluorophores and probes for bioimaging and sensing. However, the electron-withdrawing targets (EWTs)-induced fluorescence quenching is a long-standing and unsolved issue in ICT fluorophores, and significantly limits the widespread applicability. Here we report a simple and generalizable structural-modification for completely overturning the intramolecular rotation driving energy, and thus fully reversing the ICT fluorophores' quenching mode into light-up mode. Specifically, the insertion of an indazole unit into ICT scaffold can fully amplify the intramolecular rotation in donor-indazole--acceptor fluorophores (fluorescence OFF), whereas efficiently suppressing the rotation in their EWT-substituted system (fluorescence ON). This molecular strategy is generalizable, yielding a palette of chromophores with fluorescence umpolung that spans visible and near-infrared range. This strategy expands the bio-analytical toolboxes and allows exploiting ICT fluorophores for light-up sensing of EWTs including N-acetyltransferases and nerve agents. The electron-withdrawing target (EWT)-induced fluorescence quenching is an unsolved issue in intramolecular charge transfer (ICT) fluorophores that limits their applicability. Here, the authors report a simple and generalizable strategy to reverse the EWT-induced quenching mode into light-up mode, by introducing an indazole building block between the pi -bridge and the donor in the ICT scaffold.

Automated summary

This study presents a simple and generalizable strategy to reverse the electron-withdrawing target (EWT)-induced quenching mode in intramolecular charge transfer (ICT) fluorophores into a light-up mode by introducing an indazole building block into the ICT scaffold.