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1.
Angew Chem Int Ed Engl ; 58(23): 7611-7614, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-30791180

RESUMO

A fluorescent sensor for catecholamines, NS510, is presented. The sensor is based on a quinolone fluorophore incorporating a boronic acid recognition element that gives it high affinity for catecholamines and a turn-on response to norepinephrine. The sensor results in punctate staining of norepinephrine-enriched chromaffin cells visualized using confocal microscopy indicating that it stains the norepinephrine in secretory vesicles. Amperometry in conjunction with total internal reflection fluorescence (TIRF) microscopy demonstrates that the sensor can be used to observe destaining of individual chromaffin granules upon exocytosis. NS510 is the highest affinity fluorescent norepinephrine sensor currently available and can be used for measuring catecholamines in live-cell assays.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 214: 355-359, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798218

RESUMO

Endogenous H2S, considered to be involved in many physiological processes, has attracted more attention in fluorescence detection and bioimaging. Therefore, it is necessary to design probes with good biocompatibility and high bioavailability. In this study, a novel fluorescent probe, QN-1, based on azide group and quinoline derivatives was developed for detecting H2S. QN-1 can detect H2S specifically in aqueous phase, which indicated QN-1 has excellent water solubility. Besides, QN-1 shows excellent properties of higher selectivity and 11-fold fluorescence enhancement at 533 nm. Therefore, QN-1 with excellent properties can be used for cell imaging.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio/metabolismo , Quinolinas , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células Hep G2 , Humanos , Sulfeto de Hidrogênio/química , Microscopia de Fluorescência , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologia , Solubilidade , Água/química , Água/metabolismo
3.
Anal Chem ; 91(4): 3110-3117, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30669835

RESUMO

An optical molecular imaging contrast agent that is tailored toward lymphatic mapping techniques implementing near-infrared (NIR) fluorescence image-guided navigation in the planning and surgical treatment of cancers would significantly aid in enabling the real-time visualization of the potential metastatic tumor-draining lymph node(s) for their needed surgical biopsy and/or removal, thereby ensuring unmissed disease to prevent recurrence and improve patient survival rates. Here, the development of the first NIR fluorescent rosol dye (THQ-Rosol) tailored to overcome the limitations arising from the suboptimal properties of the generic molecular fluorescent dyes commonly used for such applications is described. In developing THQ-Rosol, we prepared a progressive series of torsionally restrictive N-substituted non-NIR fluorescent rosol dyes based on density functional theory (DFT) calculations, wherein we discerned high correlations amongst their calculated energetics, modeled N-C3' torsion angles, and evaluated properties. We leveraged these strong relationships to rationally design THQ-Rosol, wherein DFT calculations inspired an innovative approach and synthetic strategy to afford an uncharged xanthene core-based scaffold/molecular platform with an aptly elevated p Ka value alongside NIR fluorescence emission (ca.700-900 nm). THQ-Rosol exhibited 710 nm NIR fluorescence emission, a 160 nm Stokes shift, robust photostability, and an aptly elevated p Ka value (5.85) for affording pH-insensitivity and optimal contrast upon designed use. We demonstrated the efficacy of THQ-Rosol for lymphatic mapping with in vitro and in vivo studies, wherein it revealed timely tumor drainage and afforded definitive lymph node visualization upon its administration and accumulation. THQ-Rosol serves as a proof-of-concept for the effective tailoring of an uncharged xanthene core-based scaffold/molecular platform toward a specific imaging application using rational design.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30384021

RESUMO

A new near-infrared ratiometric type fluorescent probe was prepared. 3-formyl BODIPY derivatives without substituent group in the 2, 6-position was obtained through DDQ oxidation reaction. Furthermore, it reacted with indole salt to produce probe. This probe bears indolium group as the recognition site and the 3-formyl-BODIPY as fluorophore. The specific detection of cyanide was conducted the nucleophilic attack of cyanide toward the indolium group of the probe, breaking the intramolecular charge transfer (ICT) effect and generating a ratio change in the fluorescence signal. The probe has high selectivity and sensitivity for cyanide. Moreover, cell experiments indicated this probe was benign to HepG-2 cells, and has the potential application in imaging CN- in living HepG-2 cells.


Assuntos
Técnicas Biossensoriais/métodos , Cianetos/análise , Fluorescência , Corantes Fluorescentes/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Células Hep G2 , Humanos , Técnicas de Sonda Molecular
5.
Angew Chem Int Ed Engl ; 57(39): 12741-12744, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30079457

RESUMO

Many biologically important compounds are amphiphilic in character. Glycolipids, for example, represent a biologically important class of amphiphiles. Receptors and sensors for such compounds must also be amphiphilic making them a challenge to prepare. Here, a cucurbit[8]uril (CB[8])-based sensor system has been prepared and tested for detection of amphiphilic compounds. This multi-component system consists: a CB[8], which acts as a hydrophobic lipid receptor, a hydrophilic pyridinium-based carbohydrate receptor, and a fluorescent indicator. The system self-assembles in aqueous solution. The pyridinium quenches the fluorescence of the indicator giving a strong turn-on response when it is displaced by the analyte. The sensor system was characterized by NMR, X-ray crystallography, and fluorescence titrations.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Glicolipídeos/análise , Imidazóis/química , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Cristalografia por Raios X , Corantes Fluorescentes/química , Glicolipídeos/química , Glicolipídeos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Imidazóis/metabolismo , Espectroscopia de Ressonância Magnética , Conformação Molecular , Compostos de Piridínio/química , Espectrometria de Fluorescência
6.
ACS Chem Neurosci ; 8(6): 1159-1162, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28257176

RESUMO

The direct visualization of neurotransmitters is a continuing problem in neuroscience; however, functional fluorescent sensors for organic analytes are still rare. Herein, we describe a fluorescent sensor for glutamate and zinc ions. The sensor acts as a fluorescent logic gate, giving a turn-off response to glutamate or zinc ion alone. The combination of analytes produces a large increase in fluorescence. This type of sensor will aid in the study of neurotransmission, in this case, for neurons that copackage high concentrations of zinc and glutamate.


Assuntos
Corantes Fluorescentes/síntese química , Ácido Glutâmico/análise , Neurotransmissores/análise , Imagem Óptica/métodos , Zinco/análise , Corantes Fluorescentes/química
7.
ACS Chem Neurosci ; 7(1): 21-5, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26521705

RESUMO

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.


Assuntos
Células Cromafins/metabolismo , Imagem Molecular , Serotonina/análise , Animais , Células Cromafins/química , Células Cromafins/citologia , Relação Dose-Resposta a Droga , Epinefrina/metabolismo , Corantes Fluorescentes/farmacocinética , Ácido Glutâmico/metabolismo , Vesículas Secretórias/efeitos dos fármacos , Vesículas Secretórias/metabolismo , Espectrometria de Fluorescência , Sulfatos/farmacologia
8.
Chemistry ; 21(32): 11446-51, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26119241

RESUMO

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.


Assuntos
Cumarínicos/química , Exocitose/efeitos dos fármacos , Corantes Fluorescentes/química , Neurônios/química , Neurotransmissores/química , Computadores Moleculares , Cumarínicos/metabolismo , Neurônios/metabolismo , Neurotransmissores/metabolismo , Imagem Óptica
9.
Chemistry ; 20(52): 17488-99, 2014 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-25346467

RESUMO

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.


Assuntos
Aldeídos/química , Células Cromafins/química , Corantes/química , Cumarínicos/química , Corantes Fluorescentes/química , Neurotransmissores/química , Norepinefrina/química , Transporte de Elétrons , Oxirredução , Tomografia por Emissão de Pósitrons , Teoria Quântica , Espectrometria de Fluorescência
10.
J Am Chem Soc ; 136(13): 4877-80, 2014 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-24611584

RESUMO

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.


Assuntos
Cumarínicos/análise , Corantes Fluorescentes/análise , Ácido Glutâmico/metabolismo , Neurotransmissores/metabolismo , Zinco/metabolismo , Computadores Moleculares , Cumarínicos/metabolismo , Exocitose , Fluorescência , Corantes Fluorescentes/metabolismo , Neurônios/metabolismo , Imagem Óptica , Vesículas Secretórias/metabolismo
11.
Org Biomol Chem ; 11(42): 7387-92, 2013 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-24065122

RESUMO

A fluorescent chemosensor for the detection of phosphoserine is reported. The ditopic sensor features a phosphate-coordinating zinc(II)-dipicolylamine (Zn(2+)-DPA) unit tethered to an amine-binding coumarin aldehyde fluorophore. With phosphoserine, the sensor demonstrates a 30-fold fluorescence enhancement under buffered aqueous conditions.


Assuntos
Técnicas de Química Analítica/instrumentação , Corantes Fluorescentes/química , Compostos Organometálicos/química , Fosfosserina/análise , Aminas/química , Fosfatos/química , Fosfosserina/química , Ácidos Picolínicos/química
12.
ACS Chem Neurosci ; 4(10): 1334-8, 2013 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23926946

RESUMO

A dual-analyte fluorescent chemosensor (ExoSensor 517) for the direct visualization of neurotransmitters released upon exocytosis is presented. The sensor exploits the high concentration of neurotransmitters (e.g., glutamate, norepinephrine, and dopamine) and the pH gradient between the vesicle and synaptic cleft. The cooperative recognition elements require both binding and a change in environmental pH to afford a fluorescence response which makes ExoSensor 517 one of the first integrated molecular logic gates to be used for biological applications.


Assuntos
Benzimidazóis/química , Dopamina/química , Exocitose/fisiologia , Sistemas Neurossecretores/química , Neurotransmissores/química , Neurotransmissores/metabolismo , Norepinefrina/química , Piperidinas/química , Benzimidazóis/metabolismo , Catecolaminas/metabolismo , Dopamina/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Glutamatos/metabolismo , Concentração de Íons de Hidrogênio , Sistemas Neurossecretores/metabolismo , Norepinefrina/metabolismo , Piperidinas/metabolismo , Ligação Proteica/fisiologia , Vesículas Secretórias/química , Vesículas Secretórias/metabolismo
13.
ACS Chem Neurosci ; 4(6): 918-23, 2013 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-23527575

RESUMO

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.


Assuntos
Células Cromafins/química , Corantes Fluorescentes/análise , Corantes Fluorescentes/química , Norepinefrina/análise , Animais , Sítios de Ligação/fisiologia , Catecolaminas/análise , Bovinos , Células Cultivadas
14.
Org Lett ; 15(2): 235-7, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23265271

RESUMO

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.


Assuntos
Corantes Fluorescentes/síntese química , Cinurenina/análise , Triptofano/metabolismo , Cromatografia Líquida de Alta Pressão , Fluorescência , Corantes Fluorescentes/química , Humanos , Cinurenina/química , Cinurenina/farmacologia , Estrutura Molecular
15.
J Org Chem ; 77(2): 851-7, 2012 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-22263717

RESUMO

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.


Assuntos
Lipídeos/análise , Sondas Moleculares , Amidas/química , Fluorescência , Corantes Fluorescentes/química , Isomerismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Soluções/química
16.
Tetrahedron Lett ; 51(1): 112-114, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-20161524

RESUMO

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.

17.
Chem Commun (Camb) ; (12): 1410-2, 2008 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-18338039

RESUMO

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.


Assuntos
Calixarenos/química , Metais Alcalinos/química , Nanoestruturas/química , Compostos Organometálicos/química , Cristalografia por Raios X , Hidróxidos/química , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química
18.
Org Lett ; 8(10): 2163-6, 2006 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-16671807

RESUMO

[reaction: see text] A fluorescent sensing ensemble for pyridine-derived compounds is described. The receptor portion of the ensemble is prepared from a bisimidazole pyridine which coordinates copper to form a well-defined cavity. Small heteroaromatic guests such as adenine bind strongly in the cavity. The fluorescent response is provided by a dye which is coordinated to the receptor and quenched by the metal ion. The dye is released upon guest binding providing up to 25-fold fluorescence increases.


Assuntos
Corantes Fluorescentes/química , Metais/química , Modelos Moleculares , Piridinas/química , Cristalografia por Raios X , Ligantes , Conformação Molecular , Estrutura Molecular , Água/química
19.
J Am Chem Soc ; 126(40): 12732-3, 2004 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-15469241

RESUMO

The design, synthesis, and recognition properties of two isomeric calixnaphthalene-type molecular tubes is described. The anti isomer showed strong fluorescence quenching upon titration with various simple lipid guests in water, in which the more hydrophobic guests associated with higher affinity. The syn isomer bound long straight-chain guests tightly with a similar fluorescence-quenching response. However, the syn isomer was more selective, giving an increase in fluorescence upon titration of guests which could not thread through the tube. Thus, the syn isomer is a selective fluorescent sensor for long straight-chain lipids.


Assuntos
Corantes Fluorescentes/química , Lipídeos/análise , Naftalenos/química , Amidas/química , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Conformação Molecular , Soluções , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Água/química
20.
Org Lett ; 6(21): 3727-30, 2004 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-15469334

RESUMO

[reaction: see text] A boronic acid-containing coumarin aldehyde was designed and synthesized. The sensor binds to catecholamines such as dopamine and norepinephrine by forming an iminium ion with the amine as well as a boronate ester with the catechol. An internal hydrogen bond produces a colorimetric response to these analytes with good selectivity for catecholamines over simple amines. The fluorescence of the sensor is quenched by the catechol.


Assuntos
Dopamina/análise , Norepinefrina/análise , Dopamina/química , Norepinefrina/química , Espectrofotometria Ultravioleta
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