Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA, 15260, USA.
Center for Biologic Imaging, Department of Cell Biology, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA, 15261, USA.
Angew Chem Int Ed Engl. 2020 Sep 28;59(40):17435-17441. doi: 10.1002/anie.202007104. Epub 2020 Aug 6.
Hydrogen peroxide (H O ) mediates the biology of wound healing, apoptosis, inflammation, etc. H O has been fluorometrically imaged with protein- or small-molecule-based probes. However, only protein-based probes have afforded temporal insights within seconds. Small-molecule-based electrophilic probes for H O require many minutes for a sufficient response in biological systems. Here, we report a fluorogenic probe that selectively undergoes a [2,3]-sigmatropic rearrangement (seleno-Mislow-Evans rearrangement) with H O , followed by acetal hydrolysis, to produce a green fluorescent molecule in seconds. Unlike other electrophilic probes, the current probe acts as a nucleophile. The fast kinetics enabled real-time imaging of H O produced in endothelial cells in 8 seconds (much earlier than previously shown) and H O in a zebrafish wound healing model. This work may provide a platform for endogenous H O detection in real time with chemical probes.
过氧化氢 (H₂O₂) 介导着伤口愈合、细胞凋亡、炎症等生物学过程。已有基于蛋白质或小分子的探针对 H₂O₂进行了荧光成像。然而，只有基于蛋白质的探针才能在几秒钟内提供时间上的见解。在生物系统中，基于小分子的亲电性 H₂O₂探针需要几分钟才能有足够的响应。在这里，我们报告了一种荧光探针，它与 H₂O₂选择性地经历 [2,3]-σ重排（硒-Mislow-Evans 重排），然后进行缩醛水解，在几秒钟内产生绿色荧光分子。与其他亲电性探针不同，当前探针作为亲核试剂起作用。快速的动力学使我们能够实时成像内皮细胞中产生的 H₂O₂（比之前显示的更早）和斑马鱼伤口愈合模型中的 H₂O₂。这项工作可能为使用化学探针实时检测内源性 H₂O₂提供了一个平台。
