Reaction-Based Fluorescent Probes for the Imaging of Nitroxyl (HNO) in Biological Systems

Abstract

Nitroxyl (HNO) has been identified as an important signaling molecule in biological systems and plays critical roles in many physiological processes. Fluorescence imaging could provide a robust approach to explore the biological formation of HNO and its physiological functions. Herein, we summarize the organic reaction types for constructing HNO probes and specifically focus on review of the recent advances in the development of the reaction-based HNO probes and their imaging applications in living systems.

A Chemiluminescent Probe for HNO Quantification and Real‐Time Monitoring in Living Cells

“…Thiol trapping of HNO allows monitoring of cellular delivery using capillary electrophoresis and, recently, a fluorescent probe based on the reaction of HNO with a sterically hindered thiol has been reported . Despite progress, quantification and real‐time monitoring of HNO dynamics using reaction‐based probes remain an unsolved problem …”

Imaging of anti-inflammatory effects of HNO via a near-infrared fluorescent probe in cells and in rat gouty arthritis model

“…As far as we know, there is a lack of fluorescent probes for the mitochondrial localization of HNO, because HNO is mainly produced in mitochondria. 54 It is unfortunate that only one probe has been reported for imaging HNO that is derived from the reaction between NO and H 2 S. 55 However, nearly all the probes that have been developed focus on the visual inspection of HNO in cells and tissues, instead of the in situ real-time detection of HNO in mitochondria and animals. 54 Nearinfrared (NIR) fluorescence can deeply penetrate tissue and effectively avoid background noise.…”

“…54 It is unfortunate that only one probe has been reported for imaging HNO that is derived from the reaction between NO and H 2 S. 55 However, nearly all the probes that have been developed focus on the visual inspection of HNO in cells and tissues, instead of the in situ real-time detection of HNO in mitochondria and animals. 54 Nearinfrared (NIR) fluorescence can deeply penetrate tissue and effectively avoid background noise. 51 Therefore, the imaging of HNO in mitochondria and animals using a desirable mitochondriatargeting NIR probe is another considerable issue that must be addressed.…”

A Chemiluminescent Probe for HNO Quantification and Real‐Time Monitoring in Living Cells

“…[21] HNO-selective electrodes based on immobilization of metalloporphyrins that bind to HNO offer the distinct advantage of real-time detection [22] but are unable to operate inside of living cells.This challenge is being addressed by the development of small-molecule copperbased, [23] phosphine-based, [24][25][26] and TEMPO-based fluorescent probes. [30] Chemiluminescence offers dramatic increases in signal-tonoise ratios and sensitivity over fluorescence techniques. [29] Despite progress,q uantification and real-time monitoring of HNO dynamics using reaction-based probes remain an unsolved problem.…”

“…[29] Despite progress,q uantification and real-time monitoring of HNO dynamics using reaction-based probes remain an unsolved problem. [30] Chemiluminescence offers dramatic increases in signal-tonoise ratios and sensitivity over fluorescence techniques. [31,32] In particular, sterically stabilized 1,2-dioxetanes,s uch as Schaapsd ioxetane [33] enable reaction-based triggering of chemiluminescence emission using ac hemically initiated electron exchange luminescence (CIEEL) mechanism.…”