Aqueous Red‐Emissive Probe for the Selective Fluorescent Detection of Cysteine by Deprotection/Cyclization Cascade Resulting in Large Stokes’ Shift

Abstract

Cysteine plays a crucial role in cellular functions and in human pathologies. However, the development of cysteine probes with extremely accurate detection is still a key challenge for the field. Herein, we have fully characterized and developed a novel selective fluorescent probe: red emission, aqueous detection and large Stokes' shift for cysteine (Reals-C). Key in the probe synthesis is a Michael addition onto an acroylate group and subsequent intramolecular cyclization. The probe exhibits analyte detection via an intricate role set up by the leaving groups so to discriminate and form the red-emissive analyte sensing platform (λ =471 nm, λ =637 nm) through a chemical cascade pathway. Furthermore, the sensing ability of the probe was demonstrated by both in vitro and in vivo assays. This probe enables for successfully endogenous cysteine sensing in HaCaT human keratinocytes through comparison with a commercial thiol-sensitive probe; Reals-C shows excellent in vivo cysteine detection in a drug-induced animal liver injury model.

Development of Lysosome‐Targeted Fluorescent Probes for Cys by Regulating the Boron‐dipyrromethene (BODIPY) Molecular Structure

“…Increased reactivity towards Cys was observed along with increasing pH values for both probes. These observations correlated well with previous reports describing the larger concentration of thiolate species in higher pH environments . Lysosomes are spherical‐shaped, catabolic organelles with an acidic interior (pH 4.0–6.0) .…”

“…These observations correlatedw ell with previous reports describing the larger concentration of thiolates peciesi nh igher pH environments. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Lysosomes are spherical-shaped, catabolic organelles with an acidic interior (pH 4.0-6.0). [63] Although diminished reactivity towards Cys was found, both Lyso-S and Lyso-D could functionp roperly under al ysosomal pH environment.…”

“…Al arge number of innovative fluorescent probesh ave been discoveredt od istinguish and measureb iothiols [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and some impressive works have succeeded in differentiating GSH from Cys and Hcy. [19][20][21][22][23][24][25][26][27] However,i ti ss till ac hallenge to construct probesf or discriminating Cys from Hcy owing to the similar pK a and steric congestion of Cys and Hcy,which also frequently suffers from drawbacks such as unsatisfactory selectivity,l ong responset ime, and undesired spectra overlap.…”

Biosensor and Chemosensor Fluorophores that contain Chalcogenide Centers

“…Our research group has synthesized a series of molecular probes bearing organic chalcogenide sites (i.e., S, Se, and Te) [18][19][20][21]. These chalcogenide probes can indicate the presence and concentration of important analytes, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), including hydrogen peroxide (…”

A Near-Infrared Ratiometric Fluorescent Probe for Highly Selective Recognition and Bioimaging of Cysteine

“…Additionally, the ratiometric fluorescent probes could provide an inherent reliability originating from its effective self-calibration advantage by monitoring two well-resolved emissions (Kikuchi et al, 2004; Demchenko, 2010; Lee et al, 2015). Although a number of fluorescent probes for Cys detection and imaging have been reported, most of them could not discriminate Cys from Hcy/GSH due to their similar molecular structures and reactivity (Chen et al, 2017, 2018; Li et al, 2017; Liu X. et al, 2017; Nawimanage et al, 2017; Wang F. et al, 2017; Wang Q. et al, 2017, 2018a; Wu et al, 2017; Yin et al, 2017; Yue et al, 2017a,b; Zhang et al, 2017, 2018a,b; Hou et al, 2018; Kim et al, 2018; Ren et al, 2018; Song et al, 2018; Tian et al, 2018; Wang et al, 2018b; Wang J. et al, 2018; Wang L. et al, 2018; Sheng et al, 2019). Several ratiometric fluorescent probes for Cys have been developed (Lv et al, 2014; Feng et al, 2017; Liu G. et al, 2017; Wang F. et al, 2017; Wang L. et al, 2018 Wu et al, 2018; Yue et al, 2018; Zhu et al, 2018), but only a few of them showed the fluorescence emission in NIR region (Feng et al, 2017; Zhu et al, 2018).…”