Recent Progress in the Rational Design of Biothiol-Responsive Fluorescent Probes

Biothiols such as cysteine, homocysteine, and glutathione play significant roles in important biological activities, and their abnormal concentrations have been found to be closely associated with certain diseases, making their detection a critical task. To this end, fluorescent probes have become increasingly popular due to their numerous advantages, including easy handling, desirable spatiotemporal resolution, high sensitivity, fast response, and favorable biocompatibility. As a result, intensive research has been conducted to create fluorescent probes for the detection and imaging of biothiols. This brief review summarizes recent advances in the field of biothiol-responsive fluorescent probes, with an emphasis on rational probe design, including the reaction mechanism, discriminating detection, reversible detection, and specific detection. Furthermore, the challenges and prospects of fluorescence probes for biothiols are also outlined.

[1]  Dokyoung Kim,et al.  All-Nontoxic Fluorescent Probe for Biothiols and Its Clinical Applications for Real-Time Glioblastoma Visualization. , 2023, ACS Sensors.

[2]  Zhihong Liu,et al.  Cysteine-Activatable Near-Infrared Fluorescent Probe for Dual-Channel Tracking Lipid Droplets and Mitochondria in Epilepsy. , 2023, Analytical chemistry.

[3]  Jianguo Fang,et al.  Naphthalimide Fluorescent Skeleton for Facile and Accurate Quantification of Glutathione. , 2023, Analytical chemistry.

[4]  T. Gunnlaugsson,et al.  Photoinduced electron transfer (PeT) based fluorescent probes for cellular imaging and disease therapy. , 2023, Chemical Society reviews.

[5]  Fang Wang,et al.  Excited-state intramolecular proton transfer (ESIPT)-based fluorescent probes for biomarker detection: design, mechanism, and application. , 2023, Chemical Communications.

[6]  M. Coen,et al.  Increased cysteine metabolism in PINK1 models of Parkinson's disease , 2023, Disease models & mechanisms.

[7]  R. Kaushik,et al.  Near-Infrared Probes for Biothiols (Cysteine, Homocysteine, and Glutathione): A Comprehensive Review , 2022, ACS omega.

[8]  Guolin Zhang,et al.  Dual-Fluorophore and Dual-Site Multifunctional Fluorescence Sensor for Visualizing the Metabolic Process of GHS to SO2 and the SO2 Toxicological Mechanism by Two-Photon Imaging. , 2022, Analytical chemistry.

[9]  Xiaoyan Cui,et al.  A Substituted-Rhodamine-Based Reversible Fluorescent Probe for In Vivo Quantification of Glutathione. , 2022, Angewandte Chemie.

[10]  Q. Tu,et al.  Dual-Site Chemosensor for Monitoring ·OH-Cysteine Redox in Cells and In Vivo. , 2022, Journal of the American Chemical Society.

[11]  Cuiling Zhang,et al.  Dual-Channel Fluorescent Probe for the Detection of Peroxynitrite and Glutathione in Mitochondria: Accurate Discrimination of Inflammatory and Progressing Tumor Cells. , 2022, Analytical chemistry.

[12]  Leyu Wang,et al.  Dual-Channel Recognition of Human Serum Albumin and Glutathione by Fluorescent Probes with Site-Dependent Responsive Features. , 2022, Analytical chemistry.

[13]  Chunyang Chen,et al.  A ratiometric fluorescent probe based on two-isophorone fluorophore for detecting cysteine. , 2022, Journal of materials chemistry. B.

[14]  Xiaohong Cen,et al.  Near-Infrared Fluorescent and Photoacoustic Dual-Mode Probe for Highly Sensitive and Selective Imaging of Cysteine In Vivo. , 2022, Analytical chemistry.

[15]  A. Moskovtsev,et al.  Determination of glutathione in blood via capillary electrophoresis with pH‐mediated stacking , 2022, Electrophoresis.

[16]  Fang Wang,et al.  A Rhodol-Derived Probe for Intracellular Biothiols Imaging and Rapid Labelling of Sulfhydryl-Containing Proteins , 2022, SSRN Electronic Journal.

[17]  Ke-Zheng Chen,et al.  A photocontrollable thermosensitive chemical spatiotemporally destabilizes mitochondrial membranes for cell fate manipulation. , 2022, Biomaterials Science.

[18]  Lidai Wang,et al.  Photoacoustic/Fluorescence Dual-Modality Probe for Biothiol Discrimination and Tumor Diagnosis in Cells and Mice. , 2022, ACS sensors.

[19]  Z. Geng,et al.  Red and Near-Infrared Fluorescent Probe for Distinguishing Cysteine and Homocysteine through Single-Wavelength Excitation with Distinctly Dual Emissions. , 2022, Analytical chemistry.

[20]  Weiying Lin,et al.  Research on mitochondrial oxidative stress accompanying the diabetic process under airborne particulate matter pollution by NIR fluorescence imaging of cysteine , 2022, Chemical Engineering Journal.

[21]  C. Fan,et al.  Recent Research Progress of Red-Emitting/Near-Infrared Fluorescent Probes for Biothiols , 2022, New Journal of Chemistry.

[22]  Sushil Ranjan Bhatta,et al.  A detailed insight into anion sensing based on intramolecular charge transfer (ICT) mechanism: A comprehensive review of the years 2016 to 2021 , 2021 .

[23]  S. Samuel,et al.  Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person , 2021, EPMA Journal.

[24]  I. Fülöp,et al.  Profiling the Concentration of Reduced and Oxidized Glutathione in Rat Brain Using HPLC/DAD Chromatographic System , 2021, Molecules.

[25]  Jun Feng Zhang,et al.  A review on recognition of tri-/tetra-analyte by using simple organic colorimetric and fluorometric probes , 2021 .

[26]  Qinglong Qiao,et al.  Twisted intramolecular charge transfer (TICT) and twists beyond TICT: from mechanisms to rational designs of bright and sensitive fluorophores. , 2021, Chemical Society reviews.

[27]  Guoqiang Feng,et al.  Smart dual-response probe reveals an increase of GSH level and viscosity in Cisplatin-induced apoptosis and provides dual-channel imaging for tumor , 2021, Sensors and Actuators B: Chemical.

[28]  Junling Yin,et al.  Small molecule based fluorescent chemosensors for imaging the microenvironment within specific cellular regions. , 2021, Chemical Society reviews.

[29]  Qin-Hua Song,et al.  An 8-arylselenium BODIPY fluorescent probe for rapid and sensitive discrimination of biothiols in living cells. , 2021, Chemical communications.

[30]  C. Yin,et al.  Molecular-Dimension-Dependent ESIPT Break for Specific Reversible Response to GSH and Its Real-Time Bioimaging. , 2021, Analytical chemistry.

[31]  Ruo-Jun Man,et al.  A novel selective probe for detecting glutathione from other biothiols based on the concept of Fluorescence Fusion. , 2021, Analytica Chimica Acta.

[32]  Yong Ye,et al.  Visualization of biothiols and HClO in cancer therapy via a multi-responsive fluorescent probe , 2021 .

[33]  Guo-jiang Mao,et al.  A near-infrared fluorescent probe with large Stokes shift for imaging Cys in tumor mice. , 2021, Analytica chimica acta.

[34]  Xiangzhi Song,et al.  A Ratiometric, Fast-Responsive, and Single-Wavelength Excited Fluorescent Probe for the Discrimination of Cys and Hcy. , 2021, Analytical chemistry.

[35]  Yanyan Song,et al.  Mitochondria-targeted fluorescent probe for rapid detection of thiols and its application in bioimaging , 2021, Dyes and Pigments.

[36]  Bin Liu,et al.  A fluorescent probe with dual acrylate sites for discrimination of different concentration ranges of cysteine in living cells. , 2021, Analytica chimica acta.

[37]  Liancheng Zhao,et al.  Lysosome-targeted near-infrared fluorescent dye and its application in designing of probe for sensitive detection of cysteine in living cells , 2021, Dyes and Pigments.

[38]  S. Yao,et al.  Au/Metal–Organic Framework Nanocapsules for Electrochemical Determination of Glutathione , 2021 .

[39]  Mengmeng Guo,et al.  Design and synthesis of a novel "turn-on" long range measuring fluorescent probe for monitoring endogenous cysteine in living cells and Caenorhabditis elegans. , 2021, Analytica chimica acta.

[40]  Xi Li,et al.  Selective and discriminative fluorescence sensing of Cys, Hcy, GSH and H2S with concise and distinct signals , 2021 .

[41]  Minhuan Lan,et al.  Advances and perspectives in carbon dot-based fluorescent probes: Mechanism, and application , 2021 .

[42]  M. Cagna,et al.  Changes in Glutathione Content in Liver Diseases: An Update , 2021, Antioxidants.

[43]  Li-Ya Niu,et al.  Visualizing the Underlying Signaling Pathway Related to Nitric Oxide and Glutathione in Cardiovascular Disease Therapy by a Sequentially Activated Fluorescent Probe. , 2021, Analytical chemistry.

[44]  B. Tang,et al.  AIE-based luminescence probes for metal ion detection , 2021 .

[45]  Juanjuan Chen,et al.  Changes in Biothiol Levels Are Closely Associated with Alzheimer's Disease. , 2021, Journal of Alzheimer's disease : JAD.

[46]  Junbo Li,et al.  Recent Advances in Fluorescent Probes for Biothiols , 2021, Youji huaxue.

[47]  C. Yin,et al.  The chronological evolution of small organic molecular fluorescent probes for thiols , 2020, Chemical science.

[48]  M. Brimble,et al.  Fluorescent probes for bioimaging of potential biomarkers in Parkinson's disease. , 2020, Chemical Society reviews.

[49]  Jianbin Chao,et al.  Thiol "Click" Chromene Ring Opening and Subsequent Cascade Nucleophilic Cyclization NIR Fluorescence Imaging Reveal High Levels of Thiol in Drug-Resistant Cells. , 2020, Analytical chemistry.

[50]  J. B. Vicente,et al.  Cysteine metabolic circuitries: druggable targets in cancer , 2020, British Journal of Cancer.

[51]  Lijuan Jiao,et al.  Direct sulfonylation of BODIPY dyes with sodium sulfinates through oxidative radical hydrogen substitution at the α-position. , 2020, Chemical communications.

[52]  Weisheng Liu,et al.  Hydro-soluble NIR fluorescent probe with multiple sites and multiple excitations for distinguishing visualization of endogenous Cys/Hcy, and GSH , 2020 .

[53]  Hongwei Zhou,et al.  A FRET-based near-infrared ratiometric fluorescent probe for detection of mitochondria biothiol. , 2020, Talanta.

[54]  Zhaochao Xu,et al.  Fluorescent probes for biothiols based on metal complex , 2020 .

[55]  Rui Ren,et al.  A 2, 7-naphthyridine-based fluorescent turn-on probe for detection of biothiols in vitro and in vivo , 2020 .

[56]  F. Jiang,et al.  On the Route to Quantitative Detection and Real-Time Monitoring of Glutathione in Living Cells by Reversible Fluorescent Probes. , 2020, Analytical chemistry.

[57]  F. Cheng,et al.  A New Strategy: Distinguishable Multi-substance Detection, Multiple Pathway Tracing Based on a New Site Constructed by the Reaction Process and Its Tumor Targeting. , 2020, Journal of the American Chemical Society.

[58]  Shengxiang Zhang,et al.  Cooperation of ESIPT and ICT Processes in the Designed 2-(2'-Hydroxyphenyl)benzothiazole Derivative: A Near-Infrared Two-Photon Fluorescent Probe with a Large Stokes Shift for the Detection of Cysteine and Its Application in Biological Environments. , 2020, Analytical chemistry.

[59]  X. Lou,et al.  Enzyme-Responsive Peptide-Based AIE Bioprobes , 2020, Topics in Current Chemistry.

[60]  Weisheng Liu,et al.  A TAT peptide-based ratiometric two-photon fluorescent probe for detecting biothiols and sequentially distinguishing GSH in mitochondria. , 2020, Talanta.

[61]  Zhen Shen,et al.  Reversible Reaction‐Based Fluorescent Probes for Dynamic Sensing and Bioimaging , 2020 .

[62]  M. Maalej,et al.  Predictive value of oxidative stress biomarkers in drug‑free patients with schizophrenia and schizo-affective disorder , 2020, Psychiatry Research.

[63]  Yongbin Zhang,et al.  An NIR ESIPT-based fluorescent probe with large stokes shift for specific detection of Cys and its bioimaging in cells and mice , 2020 .

[64]  Jingshan Shi,et al.  Abnormal Homocysteine Metabolism: An Insight of Alzheimer's Disease from DNA Methylation , 2020, Behavioural neurology.

[65]  Weiying Lin,et al.  Through bond energy transfer (TBET)-based fluorescent chemosensors , 2020 .

[66]  Pengcheng Zhou,et al.  Measuring the distribution and concentration of cysteine by fluorescent sensor for the visual study of paracetamol-induced pro-sarcopenic effect , 2020 .

[67]  Rana Muhammad Aadil,et al.  Cysteine and homocysteine as biomarker of various diseases , 2020, Food science & nutrition.

[68]  Shaomei Xu,et al.  A novel fluorescent probe for the localization of nucleoli developed via a chain reaction of endogenous cysteine in cells. , 2020, Journal of materials chemistry. B.

[69]  Zijian Guo,et al.  A ratiometric fluorescent probe for real-time monitoring of intracellular glutathione fluctuations in response to cisplatin† , 2020, Chemical science.

[70]  H. Tian,et al.  Förster resonance energy transfer (FRET)-based small-molecule sensors and imaging agents. , 2020, Chemical Society reviews.

[71]  E. Petersson,et al.  Rational design of small molecule fluorescent probes for biological applications. , 2020, Organic & biomolecular chemistry.

[72]  Arup Podder,et al.  Highly Chemoselective Self-calibrated Fluorescent Probe Monitors Glutathione Dynamics in Nucleolus in Live Cells. , 2020, Analytical chemistry.

[73]  S. Feng,et al.  A Mitochondria-Immobilized Unimolecular Fluorescent Probe for Multiplexing Imaging of Living Cancer Cells. , 2020, Analytical chemistry.

[74]  Chao Wang,et al.  An ESIPT coupled AIE fluorescent probe for biothiols detection and imaging based on a chalcone fluorophore , 2020 .

[75]  Xingguo Chen,et al.  A novel AIEgen-based probe for detecting cysteine in lipid droplets. , 2020, Analytica chimica acta.

[76]  Huan He,et al.  Real-time Imaging of Intracellular Glutathione Levels Based on a Ratiometric Fluorescent Probe with Extremely Fast Response. , 2020, Analytical chemistry.

[77]  Shelly C. Lu.  Dysregulation of glutathione synthesis in liver disease , 2020, Liver Research.

[78]  Yongqian Fu,et al.  Recent progress in the development of fluorescent probes for detection of biothiols , 2020 .

[79]  Dongsheng Cao,et al.  A Substrate-Photocaged Enzymatic Fluorogenic Probe Enabling Sequential Activation for Light-Controllably Monitoring Intracellular Tyrosinase Activity. , 2020, Analytical chemistry.

[80]  C. Yin,et al.  Fluorescent Imaging of Resveratrol Induced Subcellular Cysteine Up-regulation. , 2020, Analytical chemistry.

[81]  Z. Xu,et al.  Recent advances in the development of responsive probes for selective detection of cysteine , 2020 .

[82]  Bin Liu,et al.  Aggregation-Induced Emission: Recent Advances in Materials and Biomedical Applications. , 2020, Angewandte Chemie.

[83]  H. Qiu,et al.  A novel off-on fluorescent probe for specific detection and imaging of cysteine in live cells and in vivo , 2020 .

[84]  Lei Wang,et al.  Fluorescent probes with multiple channels for simultaneous detection of Cys, Hcy, GSH, and H2S , 2019 .

[85]  Yan-Fei Kang,et al.  Fluorescent probes for detection of biothiols based on “aromatic nucleophilic substitution-rearrangement” mechanism , 2019, Chinese Chemical Letters.

[86]  Jong Seung Kim,et al.  Coumarin-Based Small-Molecule Fluorescent Chemosensors. , 2019, Chemical reviews.

[87]  Youyu Zhang,et al.  A fluorescent probe for the specific detection of cysteine in human serum samples , 2019, Analytical Methods.

[88]  Xuchuan Jiang,et al.  Ultrafast deep-red emission fluorescent probe for highly selective imaging of endogenous cysteine in living cells and mice , 2019, Sensors and Actuators B: Chemical.

[89]  Xu He,et al.  A red-emitting fluorescence turn-on probe for the discrimination of cysteine from biothiols and its bioimaging applications in living cells , 2019, Sensors and Actuators B: Chemical.

[90]  Xiaobing Zhang,et al.  A long wavelength emission two-photon fluorescent probe for highly selective detection of cysteine in living cells and an inflamed mouse model , 2019, Journal of Materials Chemistry B.

[91]  Ying Qian,et al.  A highly sensitive two-photon fluorescent probe for glutathione with near-infrared emission at 719 nm and intracellular glutathione imaging. , 2019, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[92]  Jiahui Tan,et al.  Design of fluorescent probes with optimized responsiveness and selectivity to GSH , 2019, Tetrahedron Letters.

[93]  N. Zhang,et al.  Ratiometric Imaging of Cysteine Level Changes in Endoplasmic Reticulum during H2O2-Induced Redox Imbalance. , 2019, Analytical chemistry.

[94]  M. Emrullahoğlu,et al.  Fluorescein propiolate: a propiolate-decorated fluorescent probe with remarkable selectivity towards cysteine. , 2019, Chemical communications.

[95]  S. Yao,et al.  Simultaneous Visualization of Endogenous Homocysteine, Cysteine, Glutathione, and their Transformation through Different Fluorescence Channels. , 2019, Angewandte Chemie.

[96]  P. Mikuš,et al.  Ultra‐high performance hydrophilic interaction liquid chromatography – Triple quadrupole tandem mass spectrometry method for determination of cysteine, homocysteine, cysteinyl‐glycine and glutathione in rat plasma , 2019, Journal of pharmaceutical and biomedical analysis.

[97]  G. S. Sharma,et al.  Disturbed homocysteine metabolism is associated with cancer , 2019, Experimental & Molecular Medicine.

[98]  Xiangzhi Song,et al.  Simultaneous Discrimination of Cysteine, Homocysteine, Glutathione, and H2S in Living Cells through a Multisignal Combination Strategy. , 2018, Analytical chemistry.

[99]  R. Strongin,et al.  Fluorescent Probes with Multiple Binding Sites for the Discrimination of Cys, Hcy, and GSH. , 2017, Angewandte Chemie.

[100]  R. Strongin,et al.  Fluorescein Tri-Aldehyde Promotes the Selective Detection of Homocysteine , 2016, Journal of Fluorescence.

[101]  Zhiqian Guo,et al.  Selective homocysteine turn-on fluorescent probes and their bioimaging applications. , 2014, Chemical communications.

[102]  Guangdong Yang,et al.  A critical life-supporting role for cystathionine γ-lyase in the absence of dietary cysteine supply. , 2011, Free radical biology & medicine.

[103]  D. Nebert,et al.  Genetically altered mice to evaluate glutathione homeostasis in health and disease. , 2004, Free radical biology & medicine.

[104]  H S Kwok,et al.  Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. , 2001, Chemical communications.

[105]  J. Blumberg,et al.  Differential Regulation of MAP Kinase Signaling by Pro‐ and Antioxidant Biothiols , 2000, Annals of the New York Academy of Sciences.