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Fluorogenic Probe Using a Mislow-Evans Rearrangement for Real-Time Imaging of Hydrogen Peroxide

preprint
revised on 23.06.2020 and posted on 25.06.2020 by Dianne Pham, Upamanyu Basu, Ivanna Pohorilets, Claudette M. St Croix, Simon Watkins, Kazunori Koide

Hydrogen peroxide (H2O2) is a second messenger that mediates the biology of wound healing, apoptosis, inflammation, aging, neurodegenerative diseases, and more. Its presence has been fluorometrically imaged with protein- or small molecule-based sensors. However, only protein-based sensors have afforded temporal insights with the resolution of seconds. Small molecule-based fluorogenic probes are preferred for various reasons; however, current electrophilic chemosensors react with H2O2 slowly, requiring >20 minutes for a sufficient response. Here, we report a fluorogenic probe that selectively reacts with H2O2 and undergoes a [2,3]-sigmatropic rearrangement (seleno-Mislow-Evans rearrangement) followed by an acetal hydrolysis to produce a green fluorescent molecule in seconds. The mode of reaction is based on the umpolung of previously developed sensors; the probe acts as a nucleophile rather than an electrophile. The fast kinetics outcompete the reaction between thiols and H2O2, enabling real-time imaging of H2O2 produced inside the subcellular compartments of cells in 8 seconds. Further, the probe was able to recapitulate data previously observed only with a genetically encoded protein-based sensor. The present probe design provides a platform that can match the temporal resolution of protein-based H2O2 detection.

Funding

NSF CHE-0911092 and CHE-1506942

History

Email Address of Submitting Author

koide@pitt.edu

Institution

University of Pittsburgh

Country

United States

ORCID For Submitting Author

0000-0001-8894-8485

Declaration of Conflict of Interest

no conflict of interest

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Read the published paper

in Angewandte Chemie International Edition

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