In-situ construction of fluorescent probes for hydrogen peroxide detection in mitochondria and lysosomes with on-demand modular assembling and double turn-on features

• Published in: Bioorganic chemistry 2023-01, Vol.130, p.106199, Article 106199
• Main Authors: Feng, Gang, Zhai, Peng, Li, Zhengzheng, Fan, Miaozhuang, Jiang, Yihang, Qiao, Nan, Chen, Ribao, Tang, Shuo, Xu, Zhourui, Wang, Xiaomei, Lin, Guimiao, Yang, Chengbin, Ying, Ming, Dong, Biqin, Shao, Yonghong, Xu, Gaixia
• Format: Article
• Language: English
• Subjects: Click reaction; Hydrogen peroxide detection; Lysosomes; Mitochondria; Probe in-situ construction
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.106199

The on-demand modular assembling strategy to construct fluorescent probes for H2O2 detection in mitochondria and lysosomes. [Display omitted] •On-demand strategy to prepare fluorescent probes for H2O2 intracellular detection at desired organelles.•The double turn-on mechanism enhanced the anti-interference performance.•High biocompatibility for intracellular construction of fluorescent probes. Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.