An Activity‐Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO−) in the Alzheimer's Disease Brain

Abstract Peroxynitrite (ONOO − ) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO − influx in AD brains, an activatable activity‐based fluorescence probe Rd‐DPA3 was designed by a structure‐modulated strategy. Taking advantage of ONOO − ‐initiated two‐step cascade reactions of a novel chemical trigger, Rd‐DPA3 specifically responds to ONOO − in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement ( F / F 0 =50). Moreover, with its mitochondria‐targeting ability, Rd‐DPA3 can be used to efficiently monitor the alternations of intracellular ONOO − levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood–brain barrier (BBB) crossing ability, Rd‐DPA3 is suitable for in vivo imaging of cerebral ONOO − influx and illustrating an age‐dependent accumulation of ONOO − in AD mice brains.