An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Probe for the Sensing of Hydrogen Sulfide in Living Cells and Zebrafish

Abstract

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule in many physiological processes. Relevant investigations indicated that H2S plays a cytoprotective effect under endoplasmic reticulum stress. Currently, it is still a challenge to design effective methods for ratio detection of endoplasmic reticulum H2S. Herein we are the first to construct a ratiometric near-infrared fluorescent probe (M-H2S) for sensing H2S in the endoplasmic reticulum. M-H2S has high selectivity and sensitivity toward H2S (LOD = 39.1 nM). Additionally, M-H2S possessed an excellent endoplasmic reticulum targeting ability. Moreover, M-H2S was successfully utilized to visualize exogenous/endogenous H2S in HeLa cells and zebrafish. Particularly important, endogenously produced H2S was observed under endoplasmic reticulum stress induced by tunicamycin.

Highly Selective Fluorescent Probe Design for Visualizing Hepatic Hydrogen Sulfide in the Pathological Progression of Nonalcoholic Fatty Liver

“…Second, based on either nucleophilic addition, thiolysis, or azide reduction in the H 2 S recognition mechanism, we selected representative H 2 S recognition sites to construct a H 2 S NIR probe molecule library (Figure 2A,B), which included 2,4-dinitrophenyl, 2,4dinitrobenzenesulfonyl sulfonate, thiophene acetyl, o-aldehydic benzoyl, 7-nitrobenzofurazan, and benzyl azide. 25,44,45 Afterward, as a proof of concept, six bearing different potential protective substituents were successfully introduced onto the hydroxyl group of chromophores CSOH-Cl to afford candidates (1-CSN, 2-SO 3 N, 3-CHO, 4-Thia, 5-BN 3 , and 6-NBD in Scheme S1) as recognition sites for H 2 S. The detailed synthetic steps and characterization of these candidates (Scheme S2) and their UV absorption spectra (Figure S2) are described in the Supporting Information. With six candidates in hand, we first evaluated the reactivity of these probes toward H 2 S under physiological conditions, as shown in Figures S3 and S4.…”

Recent progress in small-molecule fluorescent probes for endoplasmic reticulum imaging in biological systems

“…16), for H 2 S was synthesized by Zhang's group. 102 This probe was constructed based on dicyanoisophorone analogues, while o-carboxybenzaldehyde was employed as the recognition receptor of H 2 S. Upon reaction with this probe, H 2 S first reacted with the aldehyde group to generate an intermediate, and then the sulfhydryl group in the intermediate could also attack the carbon atom of the CvO group, releasing the fluorophore and a side product. Due to the ICT effect, this probe displayed a ratiometric fluorescence response to H 2 S with a large Stokes shift, high sensitivity toward H 2 S (39.1 nM detection limit) and good selectivity.…”

Near-Infrared Mitochondria-Targetable Fluorescent Probe for High-Contrast Bioimaging of H2S

“…In this respect, fluorescence probes exhibited great potential due to their advantages of excellent sensitivity, simple operation, and noninvasive in situ and real-time spatial imaging. − Over the past decade, the development of fluorescent probes for H 2 S has attracted extensive attention and a huge amount of probes have been developed for the fluorescence detection of H 2 S. − Although great success has been achieved, most of them are incompetent in visualizing H 2 S in mitochondria and in vivo, mainly due to their short fluorescence wavelengths (<650 nm) and lack of mitochondrial localization performance. Currently, only a few probes are available to detect H 2 S in mitochondria. − However, they are mainly fluorescent probes with visible fluorescence changes, and many of them suffer from long response time, narrow Stokes shifts, and/or unsatisfactory water solubility (Table S1).…”