Issue 15, 2021

Superoxide-responsive fluorogenic molecular probes for optical bioimaging of neurodegenerative events in Alzheimer's disease

Abstract

Since oxidative stress has been recognized as a major factor contributing to the progression of several neurodegenerative disorders, reactive oxygen species (ROS) including superoxide have received great attention as a representative molecular marker for the diagnosis of Alzheimer's disease (AD). Here, superoxide-sensitive fluorogenic molecular probes, benzenesulfonylated resorufin derivatives (BSRs), were newly devised for optical bioimaging of oxidative events in neurodegenerative processes. BSRs, fluorescence-quenched benzenesulfonylated derivatives of resorufin, were designed to recover their fluorescence upon exposure to superoxide through a selective nucleophilic uncaging reaction of the benzenesulfonyl cage. Among BSRs, BSR6 presented the best sensitivity and selectivity to superoxide likely due to the optimal reactivity matching between the nucleophilicity of superoxide and its electrophilicity ascribed to the highly electron-withdrawing pentafluoro-substitution on the benzenesulfonyl cage. Fluorescence imaging of inflammatory cells and animal models presented the potential of BSR6 for optical sensing of superoxide in vitro and in vivo. Furthermore, microglial cell (Bv2) imaging with BSR6 enabled the optical monitoring of intracellular oxidative events upon treatment with an oxidative stimulus (amyloid beta, Aβ) or the byproduct of oxidative stress (4-hydroxynonenal, HNE).

Graphical abstract: Superoxide-responsive fluorogenic molecular probes for optical bioimaging of neurodegenerative events in Alzheimer's disease

Supplementary files

Article information

Article type
Paper
Submitted
21 Apr 2021
Accepted
08 Jun 2021
First published
12 Jun 2021

Analyst, 2021,146, 4748-4755

Superoxide-responsive fluorogenic molecular probes for optical bioimaging of neurodegenerative events in Alzheimer's disease

J. Shin, D. M. Kang, J. Yoo, J. Heo, K. Jeong, J. H. Chung, Y. S. Han and S. Kim, Analyst, 2021, 146, 4748 DOI: 10.1039/D1AN00692D

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