A highly sensitive and responsive fluorescent probe based on 6-azide-chroman dye for detection and imaging of hydrogen sulfide in cells.

Hydrogen sulfide or H2S is known as an important gasotransmitter involved in regulation of many physiological and pathological processes. Since a small amount of H2S is produced by endogenous cells in the body and microorganisms in the gastrointestinal tract (GI tract), the current detection probes are limited for their use in measurement of unpretentious change of H2S level both in vitro and in vivo. Therefore, development of a highly sensitive and responsive fluorescent probe for measurement of H2S in vivo is of great significance for investigation of H2S function and toxicity. Here, we designed a novel fluorescent probe AC-N3 through introducing azide in 6-position of chroman dye based on the hypothesis that 6-position (para-position) of chromone may be a potential trigger of fluorescent properties. The probe AC-N3 exhibits a better selectivity without interference from analytes, high sensitivity and little cytotoxicity. In addition, we confirmed that the conversion of electron-donating group in 6-position of chromone can trigger the change of fluorescence, which can be applied to design of other fluorescent probes.

[1]  C. S. Lim,et al.  A two-photon fluorescent probe for specific detection of hydrogen sulfide based on a familiar ESIPT fluorophore bearing AIE characteristics. , 2017, Chemical communications.

[2]  R. Martínez‐Máñez,et al.  A new chromo-chemodosimeter selective for sulfide anion. , 2003, Journal of the American Chemical Society.

[3]  Oh Seok Kwon,et al.  A near-infrared "turn-on" fluorescent probe with a self-immolative linker for the in vivo quantitative detection and imaging of hydrogen sulfide. , 2017, Biosensors & bioelectronics.

[4]  K. Namekata,et al.  Cystathionine β‐synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  K. Abe,et al.  The possible role of hydrogen sulfide as an endogenous neuromodulator , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  M. Stipanuk,et al.  Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. , 1982, The Biochemical journal.

[7]  Rui Wang,et al.  The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener , 2001 .

[8]  Yuan Guo,et al.  A facile fluorescent probe with a large Stokes shift for sequentially detecting copper and sulfide in 100% aqueous solution and imaging them in living cells , 2018 .

[9]  K. Moore,et al.  Making and working with hydrogen sulfide: The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: a review. , 2009, Free radical biology & medicine.

[10]  J. Cummings,et al.  A new method for the determination of sulphide in gastrointestinal contents and whole blood by microdistillation and ion chromatography. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[11]  P. Kamoun,et al.  Endogenous hydrogen sulfide overproduction in Down syndrome , 2003, American journal of medical genetics. Part A.

[12]  K. Ahn,et al.  Two-photon fluorescent probe for hydrogen sulfide based on a red-emitting benzocoumarin dye , 2018 .

[13]  S. Takashima,et al.  Cystathionine β-synthase is enriched in the brains of Down’s patients , 2005 .

[14]  I. Niki,et al.  L-cysteine inhibits insulin release from the pancreatic beta-cell: possible involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter. , 2006, Diabetes.

[15]  Ke Li,et al.  In vivo imaging of alkaline phosphatase in tumor-bearing mouse model by a promising near-infrared fluorescent probe. , 2017, Talanta.

[16]  Fernanda Borges,et al.  Chromone as a Privileged Scaffold in Drug Discovery: Recent Advances. , 2017, Journal of medicinal chemistry.

[17]  N. Matsuki,et al.  The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. , 1997, Biochemical and biophysical research communications.

[18]  J. Heptinstall,et al.  The endogenous production of hydrogen sulphide in intrauterine tissues , 2009, Reproductive biology and endocrinology : RB&E.

[19]  K. Hanaoka,et al.  Development of a highly selective fluorescence probe for hydrogen sulfide. , 2011, Journal of the American Chemical Society.

[20]  Xuming Jia,et al.  Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats , 2009, Laboratory Investigation.

[21]  M. Prakriya,et al.  Depletion of H2S during obesity enhances store-operated Ca2+ entry in adipose tissue macrophages to increase cytokine production , 2015, Science Signaling.

[22]  Zheng-yin Yang,et al.  A novel chromone and rhodamine derivative as fluorescent probe for the detection of Zn(II) and Al(III) based on two different mechanisms. , 2018, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[23]  Yu Zhao,et al.  Capture and visualization of hydrogen sulfide by a fluorescent probe. , 2011, Angewandte Chemie.

[24]  Kyo Han Ahn,et al.  "Turn-on" fluorescent sensing with "reactive" probes. , 2011, Chemical communications.

[25]  J. Taylor,et al.  Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. , 1989, Biochemical pharmacology.

[26]  Lingyun Wu,et al.  H2S, Endoplasmic Reticulum Stress, and Apoptosis of Insulin-secreting Beta Cells* , 2007, Journal of Biological Chemistry.

[27]  Michael A. Peterson,et al.  Hydrogen sulfide consumption measured at low steady state concentrations using a sulfidostat. , 2004, Analytical biochemistry.

[28]  J. Bełtowski,et al.  Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists. , 2007, Pharmacological reports : PR.

[29]  Rui Wang Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. , 2012, Physiological reviews.

[30]  Yanyan Ma,et al.  A turn-on endoplasmic reticulum-targeted two-photon fluorescent probe for hydrogen sulfide and bio-imaging applications in living cells, tissues, and zebrafish , 2017, Scientific Reports.

[31]  V. Ravindranath,et al.  Inhibition of cystathionine-γ-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS , 2007, Neurochemistry International.

[32]  V. Darley-Usmar,et al.  Polarographic measurement of hydrogen sulfide production and consumption by mammalian tissues. , 2005, Analytical biochemistry.

[33]  Chao-rui Li,et al.  A Novel Chromone Schiff-Base Fluorescent Chemosensor for Cd(II) Based on C=N Isomerization , 2016, Journal of Fluorescence.

[34]  J. Gagnon,et al.  Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones , 2016, Oxidative medicine and cellular longevity.

[35]  H. Lou,et al.  Strategies to diversify natural products for drug discovery , 2018, Medicinal research reviews.

[36]  Zhihong Liu,et al.  A ratiometric two-photon fluorescent probe for imaging hydrogen sulfide in lysosomes. , 2017, Talanta.

[37]  P. Moore,et al.  Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis. , 2005, Biochemical and biophysical research communications.

[38]  Minyong Li,et al.  Coumarin-based Fluorescent Probes for H2S Detection , 2012, Journal of Fluorescence.

[39]  Zhixian Yang,et al.  Hydrogen Sulfide and Carbon Monoxide Are in Synergy with Each Other in the Pathogenesis of Recurrent Febrile Seizures , 2006, Cellular and Molecular Neurobiology.

[40]  Shuai Xu,et al.  A novel flavone-based fluorescent probe for relay recognition of HSO3(-) and Al(3+). , 2015, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[41]  Z. Zadák,et al.  A simple, optimized method for the determination of sulphide in whole blood by GC-mS as a marker of bowel fermentation processes. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[42]  Wen Sun,et al.  A two-photon fluorescent probe with near-infrared emission for hydrogen sulfide imaging in biosystems. , 2013, Chemical communications.

[43]  Pan Jia,et al.  A highly specific and ultrasensitive near-infrared fluorescent probe for imaging basal hypochlorite in the mitochondria of living cells. , 2018, Biosensors & bioelectronics.

[44]  C. Huang,et al.  Small organic molecules as fluorescent probes for nucleotides and their derivatives , 2010 .

[45]  Saran Long,et al.  Synthesis of an ultrasensitive BODIPY-derived fluorescent probe for detecting HOCl in live cells , 2018, Nature Protocols.

[46]  J. Furne,et al.  Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[47]  Xuming Jia,et al.  Activation of KATP channels by H2S in rat insulin‐secreting cells and the underlying mechanisms , 2005, The Journal of physiology.