Monitoring acetylcholinesterase level changes under oxidative stress through ESIPT-ICT-based near-infrared fluorescent probe

Oxidative stress plays an important role in pathology, and contributes to a variety of diseases, including inflammation, neurodegenerative diseases, and cancer. Research studies have shown that acetylcholinesterase (AChE) plays a key role in regulating oxidative stress. However, an effective analytical method for real-time monitoring of AChE under oxidative stress is still lacking. Currently, fluorescent probes based on dual sensing mechanisms have attracted great attention by combining and amplifying the advantages of both mechanisms. In this work, two NIR fluorescent probes (SNCN-AE and SNC-AE) that combined ESIPT and ICT processes were designed and synthesized for accurate detection of AChE activity. After the probes reacted with AChE, the strong electron push-pull effect enhanced the ICT process, which further synergized with the ESIPT effect, resulting in a distinct NIR fluorescence signal accompanied by a large Stokes shift. In particular, SNCN-AE showed better detection performance of fast response, good photostability and low cytotoxicity, which was highly suitable for imaging of endogenous AChE in living system. Importantly, SNCN-AE had been successfully applied for monitoring AChE under oxidative stress in PC12 cells and zebrafish model. These excellent properties made probes the promising tools for studying oxidative stress and related diseases. [Display omitted] •NIR fluorescent probes that combined ESIPT and ICT processes were designed for accurate detection of AChE.•Probes showed high sensitivity and good selectivity toward AChE accompanied by a large Stokes shift.•Probe SNCN-AE with good photostability and low cytotoxicity has been applied for imaging of endogenous AChE.•Probe SNCN-AE could monitor AChE levels under oxidative stress in cells and zebrafish model.