Co-reporter:Caixia Yin, Fangjun Huo, Ming Xu, Charles L. Barnes, Timothy E. Glass
Sensors and Actuators B: Chemical 2017 Volume 252(Volume 252) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.snb.2017.06.044
•A novel NIR fluorescent material was prepared firstly and characterized fully.•The material can specially recognize HS−/CN− as a colorimetric and fluorescent probe.•The NIR fluorescent material was successfully used to detect endogenous H2S in A549 cells under SNP induced.A novel NIR fluorescent material, which is constructed with interweaved quinline and benzimidazole as the fluorophore system, indolium as a dye and reactive site under connected double bond conjugation. The sensor mechanism relied on strong nucleophilic attack of only HS−/CN− which shortened the conjugated system resulting in the fluorescent spectral changes as well as a change in color. Other nucleophilic reagents such as thiols and bisulfate did not undergo the reaction and therefore did not induce color and fluorescence changes. The pretty 1H NMR titration results strongly proved the nucleophilic mechanism. The fluorescent material was successfully used to detect endogenous H2S in A549 cells using S-Nitroso-N-acetyl-DL- penicillamine (SNP), a commercial NO donor to stimulate production of H2S and exogenous H2S.A novel NIR fluorescent material was constructed. Only strong nucleophiles such as HS−/CN− could attack and shorten the conjugated system resulting in the color and fluorescence change, thiols and bisulfate did not undergo the reaction. The material was showed a success application by A549 cell imaging under SNP stimulation.Download high-res image (73KB)Download full-size image
Co-reporter:Yutao Yang, Fangjun Huo, Caixia Yin, Ming Xu, Ying Hu, Jianbin Chao, Yongbin Zhang, Timothy E. Glass and Juyoung Yoon
Journal of Materials Chemistry A 2016 vol. 4(Issue 30) pp:5101-5104
Publication Date(Web):05 Jul 2016
DOI:10.1039/C6TB01392A
The reaction of salicylhydroxamic acid with hypochlorite produces 1,2-benzisoxazoline-3-one, a heterocycle that contains a fluorophore. As a result, this reaction was used as the basis for a new, selective and sensitive fluorescence system for the recognition of hypochlorite. The effectiveness of the method was demonstrated by its use to detect hypochlorite in a disinfectant solution as well as to image hypochlorite in cells.
Co-reporter:Kenneth S. Hettie and Timothy E. Glass
ACS Chemical Neuroscience 2016 Volume 7(Issue 1) pp:21
Publication Date(Web):October 31, 2015
DOI:10.1021/acschemneuro.5b00235
A molecular imaging tool that provides for the direct visualization of serotonin would significantly aid in the investigation of neuropsychiatric disorders that are attributed to its neuronal dysregulation. Here, the design, synthesis, and evaluation of NeuroSensor 715 (NS715) is presented. NS715 is the first molecular sensor that exhibits a turn-on near-infrared fluorescence response toward serotonin. Density functional theory calculations facilitated the design of a fluorophore based on a coumarin-3-aldehyde scaffold that derives from an electron-rich 1,2,3,4-tetrahydroquinoxaline framework, which provides appropriate energetics to prevent the hydroxyindole moiety of serotonin from quenching its fluorescence emission. Spectroscopic studies revealed that NS715 produces an 8-fold fluorescence enhancement toward serotonin with an emission maximum at 715 nm. Accompanying binding studies indicated NS715 displays a 19-fold selective affinity for serotonin and a modest affinity for catecholamines over other primary-amine neurotransmitters. The utility of NS715 toward neuroimaging applications was validated by selectively labeling and directly imaging norepinephrine within secretory vesicles using live chromaffin cells, which serve as a model system for specialized neurons that synthesize, package, and release only a single, unique type of neurotransmitter. In addition, NS715 effectively differentiated between cell populations that express distinct neurotransmitter phenotypes.Keywords: fluorescent sensor; live cell imaging; molecular imaging; near-infrared; neurotransmitter; serotonin
Co-reporter:Tam Minh Tran, Yuksel Alan and Timothy Edward Glass
Chemical Communications 2015 vol. 51(Issue 37) pp:7915-7918
Publication Date(Web):01 Apr 2015
DOI:10.1039/C5CC00415B
A new fluorescent chemical sensor for glucosamine is reported. The sensor is based on a boronic acid-containing coumarin aldehyde and shows excellent selectivity for glucosamine by forming a boronic ester with the sugar diol as well as an iminium ion with the amine group of glucosamine. The sensor successfully discriminates glucosamine over other similar biomolecules in terms of both fluorescence intensity and binding affinity. This method provides a new concept for the design and synthesis of very selective turn-on optical sensors for selective detection of multi-functional biomolecules.
Co-reporter:Dr. Jessica L. Klockow;Dr. Kenneth S. Hettie;Dr. Kristen E. Secor;Dr. Dipti N. Barman ;Dr. Timothy E. Glass
Chemistry - A European Journal 2015 Volume 21( Issue 32) pp:11446-11451
Publication Date(Web):
DOI:10.1002/chem.201501379
Abstract
Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis.
Co-reporter:Kenneth S. Hettie ; Jessica L. Klockow
Journal of the American Chemical Society 2014 Volume 136(Issue 13) pp:4877-4880
Publication Date(Web):March 10, 2014
DOI:10.1021/ja501211v
Convenient methods for the direct visualization of neurotransmitter trafficking would bolster investigations into the development of neurodegenerative diseases. Here, tunable fluorescent molecular logic gates with applications to neuronal imaging have been developed. The three-input AND molecular logic gates are based on the coumarin-3-aldehyde scaffold and designed to give a turn-on fluorescence response upon the corelease of glutamate and zinc from secretory vesicles via exocytosis. Spectroscopic studies reveal an 11-fold fluorescence enhancement under conditions mimicking exocytosis. Methylation of the scaffold was used to optimize the spectral profile of the sensors toward desired excitation wavelengths. A binding study that elucidates the sensor-analyte interactions is presented. These sensors serve as a proof-of-concept toward the direct imaging of neurotransmitters released upon exocytosis using fluorescent molecular logic gates.
Co-reporter:Kenneth S. Hettie ; Timothy E. Glass
Chemistry - A European Journal 2014 Volume 20( Issue 52) pp:17488-17499
Publication Date(Web):
DOI:10.1002/chem.201403128
Abstract
NeuroSensor 521 (NS521) is a fluorescent sensor for primary-amine neurotransmitters based on a platform that consists of an aryl moiety appended to position C4 of the coumarin-3-aldehyde scaffold. We demonstrate that sensors based on this platform behave as a directly linked donor–acceptor system that operates through an intramolecular acceptor-excited photoinduced electron transfer (a-PET) mechanism. To evaluate the PET process, a series of benzene- and thiophene-substituted derivatives were prepared and the photophysical properties, binding affinities, and fluorescence responses toward glutamate, norepinephrine, and dopamine were determined. The calculated energy of the highest occupied molecular orbital (EHOMO) of the pendant aryl substituents, along with oxidation and reduction potential values derived from the calculated molecular orbital energy values of the platform components, allowed for calculation of the fluorescence properties of the benzene sensor series. Interestingly, the thiophene derivatives did not fit the typical PET model, highlighting the limitations of the method. A new sensor, NeuroSensor 539, displayed enhanced photophysical properties aptly suited for biological imaging. NeuroSensor 539 was validated by selectively labeling and imaging norepinephrine in secretory vesicles of live chromaffin cells.
Co-reporter:Jessica L. Klockow and Timothy E. Glass
Organic Letters 2013 Volume 15(Issue 2) pp:235-237
Publication Date(Web):December 24, 2012
DOI:10.1021/ol303025m
Kynurenine, a metabolite of tryptophan, is known to contribute to cancer progression when overproduced. A method for facile fluorescent sensing of kynurenine using sensor 1 has been developed. When bound at low pH, sensor 1 undergoes a very large bathochromic shift because kynurenine extends the conjugation of the fluorophore. This unusual mechanism of activation provides a 390-fold fluorescence enhancement that is very specific to kynurenine and a wavelength of fluorescence that extends into the red.
Co-reporter:Kenneth S. Hettie, Xin Liu, Kevin D. Gillis, and Timothy E. Glass
ACS Chemical Neuroscience 2013 Volume 4(Issue 6) pp:918
Publication Date(Web):March 25, 2013
DOI:10.1021/cn300227m
A method for the selective labeling and imaging of catecholamines in live and fixed secretory cells is reported. The method integrates a tailored approach using a novel fluorescence-based turn-on molecular sensor (NeuroSensor 521) that can exploit the high concentration of neurotransmitters and acidic environment within secretory vesicles for the selective recognition of norepinephrine and dopamine. The utility of the method was demonstrated by selectively labeling and imaging norepinephrine in secretory vesicles such that discrimination between norepinephrine- and epinephrine-enriched populations of chromaffin cells was observed. This method was validated in fixed cells by co-staining with an anti-PNMT antibody.Keywords: catecholamine; cell imaging; chromaffin; Fluorescent sensor; norepinephrine
Co-reporter:Chad M. Cooley, Kenneth S. Hettie, Jessica L. Klockow, Shana Garrison and Timothy E. Glass
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 42) pp:7387-7392
Publication Date(Web):19 Sep 2013
DOI:10.1039/C3OB41677A
A fluorescent chemosensor for the detection of phosphoserine is reported. The ditopic sensor features a phosphate-coordinating zinc(II)–dipicolylamine (Zn2+–DPA) unit tethered to an amine-binding coumarin aldehyde fluorophore. With phosphoserine, the sensor demonstrates a 30-fold fluorescence enhancement under buffered aqueous conditions.
Co-reporter:Wanjun Zhu, James L. Zajicek, Donald E. Tillitt and Timothy E. Glass
Analytical Methods 2013 vol. 5(Issue 2) pp:446-448
Publication Date(Web):13 Dec 2012
DOI:10.1039/C2AY26047F
A fluorogenic thiamine analogue is presented as a fluorescent probe for thiaminase activity. The emission of the fluorophore is quenched by photoinduced electron transfer (PET) to the N-substituted pyridinium portion of the probe. Action of the enzyme releases the free pyridine group causing a substantial increase in fluorescence.
Co-reporter:Christopher T. Avetta, Berkeley J. Shorthill, Chun Ren, and Timothy E. Glass
The Journal of Organic Chemistry 2012 Volume 77(Issue 2) pp:851-857
Publication Date(Web):January 10, 2012
DOI:10.1021/jo201791a
Two fluorescent sensors for lipids have been prepared and tested for detection of a number of hydrophobic compounds of varying shape and size. The data suggest that the two sensors have a different mode of fluorescent response. Yet, the two sensors are only different in the bridging group—one having a flexible amide and one having a rigid allyl bridge. The fluorescence data are explained based on a difference in conformation of the two sensors in aqueous solution.
Co-reporter:Shaohui Zhang, Timothy E. Glass
Tetrahedron Letters 2010 Volume 51(Issue 1) pp:112-114
Publication Date(Web):6 January 2010
DOI:10.1016/j.tetlet.2009.10.097
A multifunctional metallo-receptor was designed with both metal and boronic acid binding groups. A sensor ensemble was prepared using the metallo-receptor and the fluorescent dye ARS. The dye produced two distinct fluorescent bands from interaction with the boronic acid and the metal, respectively. Partial displacement of the dye by simple analytes led to different fluorescent signatures than full displacement. This differential response provided easy discrimination of the individual analytes.
Co-reporter:Scott J. Dalgarno, Karla M. Claudio-Bosque, John E. Warren, Timothy E. Glass and Jerry L. Atwood
Chemical Communications 2008 (Issue 12) pp:1410-1412
Publication Date(Web):19 Feb 2008
DOI:10.1039/B716777F
Reaction of p-carboxylatocalix[4]arene-O-methyl ether with either rubidium or caesium hydroxide results in the formation of interpenetrated nano-capsule networks with the calixarene in the 1,3-alternate conformation.
Co-reporter:Scott J. Dalgarno, John E. Warren, Jochen Antesberger, Timothy E. Glass and Jerry L. Atwood
New Journal of Chemistry 2007 vol. 31(Issue 11) pp:1891-1894
Publication Date(Web):05 Oct 2007
DOI:10.1039/B712800B
Non-covalent nanotubular assemblies with large core diameters are rare. Here we show that simple crystallisation of para-carboxylatocalix[4]arene from pyridine results in the formation of one such assembly, facilitated by back-to-back packing of calixarenes and the well known pyridine–carboxylic acid interaction.
Co-reporter:Kristen Secor, Jeffrey Plante, Christopher Avetta and Timothy Glass
Journal of Materials Chemistry A 2005 vol. 15(Issue 37) pp:4073-4077
Publication Date(Web):12 Aug 2005
DOI:10.1039/B503269E
A series of seven diamine sensors was prepared using dimers of a quinolone aldehyde chromophore. Binding to six different diamine guests was explored by a combination of NMR, absorption and fluorescence spectroscopy. It was shown that the dimeric sensors bound the diamine guests by formation of a bis-iminium ion which produced large changes in the fluorescence of the quinolone core. Issues of selectivity between guests are discussed.
Co-reporter:Yutao Yang, Fangjun Huo, Caixia Yin, Ming Xu, Ying Hu, Jianbin Chao, Yongbin Zhang, Timothy E. Glass and Juyoung Yoon
Journal of Materials Chemistry A 2016 - vol. 4(Issue 30) pp:NaN5104-5104
Publication Date(Web):2016/07/05
DOI:10.1039/C6TB01392A
The reaction of salicylhydroxamic acid with hypochlorite produces 1,2-benzisoxazoline-3-one, a heterocycle that contains a fluorophore. As a result, this reaction was used as the basis for a new, selective and sensitive fluorescence system for the recognition of hypochlorite. The effectiveness of the method was demonstrated by its use to detect hypochlorite in a disinfectant solution as well as to image hypochlorite in cells.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 2) pp:
Publication Date(Web):
DOI:10.1039/C2AY26047F
A fluorogenic thiamine analogue is presented as a fluorescent probe for thiaminase activity. The emission of the fluorophore is quenched by photoinduced electron transfer (PET) to the N-substituted pyridinium portion of the probe. Action of the enzyme releases the free pyridine group causing a substantial increase in fluorescence.
Co-reporter:Tam Minh Tran, Yuksel Alan and Timothy Edward Glass
Chemical Communications 2015 - vol. 51(Issue 37) pp:NaN7918-7918
Publication Date(Web):2015/04/01
DOI:10.1039/C5CC00415B
A new fluorescent chemical sensor for glucosamine is reported. The sensor is based on a boronic acid-containing coumarin aldehyde and shows excellent selectivity for glucosamine by forming a boronic ester with the sugar diol as well as an iminium ion with the amine group of glucosamine. The sensor successfully discriminates glucosamine over other similar biomolecules in terms of both fluorescence intensity and binding affinity. This method provides a new concept for the design and synthesis of very selective turn-on optical sensors for selective detection of multi-functional biomolecules.
Co-reporter:Scott J. Dalgarno, Karla M. Claudio-Bosque, John E. Warren, Timothy E. Glass and Jerry L. Atwood
Chemical Communications 2008(Issue 12) pp:NaN1412-1412
Publication Date(Web):2008/02/19
DOI:10.1039/B716777F
Reaction of p-carboxylatocalix[4]arene-O-methyl ether with either rubidium or caesium hydroxide results in the formation of interpenetrated nano-capsule networks with the calixarene in the 1,3-alternate conformation.
Co-reporter:Chad M. Cooley, Kenneth S. Hettie, Jessica L. Klockow, Shana Garrison and Timothy E. Glass
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 42) pp:NaN7392-7392
Publication Date(Web):2013/09/19
DOI:10.1039/C3OB41677A
A fluorescent chemosensor for the detection of phosphoserine is reported. The ditopic sensor features a phosphate-coordinating zinc(II)–dipicolylamine (Zn2+–DPA) unit tethered to an amine-binding coumarin aldehyde fluorophore. With phosphoserine, the sensor demonstrates a 30-fold fluorescence enhancement under buffered aqueous conditions.
![[2,2'-Bipyridine]-6-carboxaldehyde](/data/chemimg/481100/134296-07-4.png)
![[2,2'-Bipyridine]-6-carboxaldehyde](/data/chemimg/481100/134296-07-4_b.png)
