Financial support provided by National Science Foundation (CAREER award CHE-0847262. We thank Vapourtec Ltd and Enwave Optronics for equipment support, and Daniel Daleb of the University of Connecticut for his assistance in construction of the flow cell apparatus.

1. Busque señales adecuadas para el Monitoreo de Reacción <ol><li> Obtener espectros Raman para todos los materiales de partida y el producto. </li><li> Superposición de los espectros e identificar una banda intensa que es única para el producto. </li><li> Utilice esta banda Raman para monitorizar el progreso de la reacción. Una banda a 1.608 cm-1 fue seleccionado en este caso. </li></ol> 2. Configure la celda de flujo <ol><li> Obtener una celda de flujo adecuado. Aquí utilizar uno con las siguientes dimensiones: ancho de 6,5 mm, altura de 20 mm, y una longitud de trayectoria de 5 mm (Figura 2A). </li><li> Coloque la celda de flujo en un contenedor que ofrece un ambiente libre de la luz ambiente. </li><li> Conectar los tubos a la entrada y la salida de la celda de flujo (en este caso 1 mm tubo de ID PFA). </li></ol> 3. Interfaz del Espectrómetro Raman con la celda de flujo <ol><li> Obtener un espectrómetro Raman adecuado con un conjunto óptico flexible que se puede colocar en cperder proximidad a la celda de flujo. </li><li> Coloque el conjunto óptico a través de una abertura de tamaño adecuado en la caja que contiene el conjunto de celda de flujo (Figura 2B). </li><li> Deslice el conjunto óptico hasta que toque la celda de flujo y tire de ella hacia atrás dejando un espacio de ~ 2 mm. </li><li> Llenar la celda de flujo con 100% de acetona. </li><li> Encienda el espectrómetro Raman y adquirir espectros en modo de escaneo continuo. </li><li> Enfoque el láser moviendo suavemente el tubo de luz de una fracción a la vez. Manténgase en movimiento el tubo de luz hasta que la señal se encuentra en su mayor intensidad y los picos son nítidas y bien definidas. </li></ol><img alt="Figura 2" src="/files/ftp_upload/52393/52393fig2.jpg" /> Figura 2. (A) de flujo de células y la interfaz (B) Raman utilizado. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig2large.jpg" target="_blank">Haga clic aquí para ver una grande ve</a>rsión de esta figura. 4. Preparar el reactivo y soluciones solventes <ol><li> Añadir salicilaldehído (6,106 g, 50 mmol, 1 equiv) y acetoacetato de etilo (6,507 g, 50 mmol, 1 equiv) a un matraz aforado de 50 ml. </li><li> Añadir acetato de etilo hasta un volumen total de 50 ml y luego mezclar completamente los contenidos. </li><li> Transferir una alícuota de 10 ml de la solución madre a un vial de vidrio de 20 ml que contenía una barra de agitación magnética. Etiquetar este &quot;reactivo&quot;. Vial </li><li> En una botella de 100 ml lugar 90 ml de acetato de etilo. Etiquetar esta botella &quot;solvente&quot;. En una botella de 100 ml lugar 90 ml de acetona. Etiquetar esta botella &quot;interceptar solvente&quot;. </li></ol> 5. Prepare el aparato de flujo <ol><li> Asegúrese de que la unidad de flujo tiene al menos dos bombas y etiquetarlos &quot;P1&quot; y &quot;P2&quot;. Identificar líneas de entrada de disolventes y reactivos para cada bomba. Coloque las líneas de salida de los y las líneas de &quot;cobrar&quot;, &quot;residuos&quot; en dos ibotellas ndividual 100 ml etiquetados como &quot;producto&quot; y &quot;residuos&quot;, respectivamente. </li><li> Como reactor, utilice una capacidad de bobina de 10 ml PFA capaz de ser calentado. </li><li> Conectar el tubo que sale de P1 a la entrada de la bobina reactor PFA. </li><li> Instale una de tres puertos poliéter éter cetona (PEEK) tee-mezclador después de la bobina del reactor. </li><li> Conecte el tubo de salida de P2 a la T-mezclador, 180 ° de la tubería de salida de la bobina del reactor. Conecte un trozo de tubo al tercer puerto del Tee-mezclador. En el otro extremo de este tubo colocar un regulador de contrapresión. </li><li> Conectar una línea desde la salida del regulador de presión de retorno a la entrada de la celda de flujo. Conecte una línea desde la salida de la celda de flujo a la &quot;recoger / residuos&quot; interruptor. </li><li> Primer las líneas disolvente tanto P1 y P2, así como la línea de reactivo para P1 con disolvente. Mueva la línea de reactivo para P1 de la botella de disolvente a la botella de reactivo. </li><li> Usando P1, pasar acetato de etilo a través del reactorbobina a 2 ml min hasta que se llena /. Pasar a través de P2 acetona a una velocidad de flujo de 2 ml / min durante 2 min. </li><li> Ajuste las tasas de flujo de disolvente tanto para P1 y P2 a 1 ml / min. Ajuste el regulador de presión de retorno a una presión de 7 bar. Ajuste la temperatura de la bobina del reactor a la temperatura deseada. </li><li> Haga doble comprobar el equipo está configurado como se muestra en el esquema de la Figura 3. </li><li> Una vez que el sistema alcanza la temperatura y la presión constante, revise si hay fugas y vuelva a ejecutar la reacción. </li></ol><img alt="Figura 3" src="/files/ftp_upload/52393/52393fig3.jpg" /> Figura 3. Esquema de la configuración de los equipos utilizados para los experimentos de seguimiento de reacción. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig3large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a> 6. Supervisar la Reacción <ol><li> Takea exploración de fondo del sistema disolvente de acetato de etilo / acetona, ya que pasa a través de la celda de flujo. Esto se restará automáticamente de todos los análisis posteriores. </li><li> Configurar el espectrómetro de tomar las exploraciones cada 15 segundos (en este caso el espectrómetro Raman se establece en un tiempo de integración de 10 segundos, furgón = 3, y Media = 1). </li><li> Inyectar piperidina (0,05 ml, 0,05 mmol, 0,1 equiv) de una vez en el vial de vidrio con la etiqueta &quot;reactivo&quot;. </li><li> Después de mezclar a fondo, cambiar P1 de &quot;solvente&quot; para &quot;reactivo&quot;. Ajuste la corriente de salida a &quot;recoger&quot;. </li><li> Cuando todo el material se ha cargado por completo, el interruptor P1 de &quot;reactivo&quot; de nuevo a &quot;solvente&quot;. Continúa fluyendo disolvente a través de la bobina del reactor durante otros 30 minutos. Una vez transcurrido este tiempo, apague la calefacción. </li><li> Bombas Turn P1 y P2 apaga cuando la temperatura de la bobina reactor se ha enfriado por debajo de 50 ° C. </li></ol> 7. Analizar los Datos <ol&gt; <li> Exportar los datos del espectrómetro Raman a una hoja de cálculo y la trama intensidad Raman a 1608 cm-1 vs. hora. </li><li> Para optimizar las condiciones, realizar la reacción a través de un número de velocidades de flujo y las temperaturas del reactor de manera iterativa. </li><li> Parcelas de superposición de intensidad Raman de 1608 cm-1 vs. hora. Nota: Superior intensidad Raman se correlaciona con una mayor conversión del producto. </li></ol> 8. Ejecute la reacción usando condiciones optimizadas <ol><li> Tener proyectadas varias condiciones (tasas de flujo variables / temperaturas del reactor), ejecute la reacción usando las condiciones optimizadas para proporcionar el más alto de conversión del producto. </li></ol> 9. Aislar el producto <ol><li> Tome el contenido del matraz de producto y se vierte en un vaso de precipitados que contiene 100 ml de hielo y 20 ml de HCl 2 M. </li><li> Lavar el matraz producto con una cantidad mínima de acetato de etilo (2 ml) y la transferencia al vaso de precipitados. </li><li> Revuelva la mezcla de heladohasta que todo el hielo se derrita por completo. </li><li> Establecer un sistema de filtración con un embudo Hirsch, frasco de brazo lateral, collar de goma y una longitud de tubo de vacío de goma. </li><li> Se filtra el precipitado resultante al vacío, enjuague con éter dietílico frío (10 ml) y deje que se seque bajo una lámpara de calor (2-3 horas) o O seco / N al vacío. </li><li> Confirmar la identidad del producto por 1 H resonancia magnética (RMN) nuclear usando CDCl3 como disolvente. Para un espectrómetro de RMN 500 MHz, los datos de 1H NMR de 3-acetylcoumarin es el siguiente: δ = 2,73 (s, 3 H) 7,31 - 7,40 (m, 2 H) 7,65 (ddd, J = 7,53, 4,37, 2,60 Hz , 2 H) 8,51 (s, 1 H) ppm, 13 de datos C RMN: δ = 30,84 (CH 3) 117,00 (CH) 118,56 (C) 124,86 (CH) 125,27 (CH) 130,51 (CH) 134,68 (C) 147,74 (CH) 155,64 (C) 159,52 (C) 195,77 (C) ppm. </li></ol>

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The authors have nothing to disclose.

La facilidad con la que el espectrómetro Raman se puede interconectar con la unidad de flujo hace que esta técnica valiosa para la monitorización en línea de reacción. Un número de variables de reacción se puede probar de una manera acelerada, que permite al usuario llegar a condiciones de reacción optimizadas más rápido que cuando se utilizan métodos fuera de línea. La aplicación de las técnicas descritas en este documento también permite la monitorización de la formación de productos secundarios, supo...

Mediante el uso de procesamiento de flujo continuo, los químicos están descubriendo que pueden realizar una serie de reacciones químicas de manera segura, eficaz y con facilidad 1,2. Como resultado, el equipo de la química flujo se está convirtiendo en una herramienta integral para el funcionamiento de las reacciones tanto en entornos industriales, así como laboratorios de investigación en las instituciones académicas. Una amplia variedad de transformaciones de química sintética han llevado a cabo en reactores de flujo 3,4. En casos seleccionados, reacciones que no funcionan en el lote se ha demostrado que proceder sin problemas en condiciones de flujo continuo 5. Por tanto la optimización de reacción y control de calidad, la incorporación de monitoreo de reacción en línea con el procesamiento de flujo ofrece ventajas significativas. En línea monitoreo proporciona un análisis continuo con respuesta en tiempo real a las condiciones reales de la muestra. Esto es más rápido y, en algunos casos, más fiable que las técnicas comparables fuera de línea. Un número de técnicas analíticas en línea se han interconectado con fbajos reactores 7. Los ejemplos incluyen infrarrojo 8,9, UV-Visible 10,11, 12,13 RMN, espectroscopía Raman 14,15, 16,17 y espectrometría de masas. Nuestro grupo de investigación ha interconectado un espectrómetro Raman con una unidad de microondas científica 18. El uso de este, una serie de reacciones han sido controlados, tanto desde el cualitativo y cuantitativo 20 19 punto de vista. Sobre la base de este éxito, hemos interconectado recientemente nuestro espectrómetro Raman con una de nuestras unidades de flujo continuo y empleado para la vigilancia de reacción en la línea de una serie de transformaciones orgánicas clave-medicinalmente relevante. 21 En cada caso se pudo controlar la reacciones y también en un ejemplo, por medio de una curva de calibración, pudimos determinar la conversión del producto a partir de datos espectrales Raman. En Aquí se describe cómo configurar el aparato y lo utilizan para controlar las reacciones. Utilizamos la síntesis piperidina catalizado de 3-acetylcoumarin (1) a partir de salicilaldehído con acetoacetato de etilo (Figura 1) como la reacción modelo aquí. <img alt="Figura 1" src="/files/ftp_upload/52393/52393fig1.jpg" /> Figura 1. Base reacción catalizada por condensación entre salicilaldehído y acetoacetato de etilo para dar 3-acetylcoumarin (1). <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">Haga clic aquí para ver una versión más grande de esta figura.</a>

<table border="0">
	<tbody>
		<tr>
			<td>Salicylaldehyde</td>
			<td>Sigma-Aldrich</td>
			<td>S356</td>
			<td>Reagent Grade, 98%</td>
		</tr>
		<tr>
			<td>Ethyl acetoacetate</td>
			<td>Acros Organics</td>
			<td>117970010</td>
			<td>99%</td>
		</tr>
		<tr>
			<td>Piperidine</td>
			<td>Sigma-Aldrich</td>
			<td>104094</td>
			<td>Reagent Plus, 99%</td>
		</tr>
		<tr>
			<td>Hydrochloric acid</td>
			<td>Sigma-Aldrich</td>
			<td>320331</td>
			<td>ACS Reagent, 37%</td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Sigma-Aldrich</td>
			<td>34858</td>
			<td>CHROMASOLV, for HPLC, &#62;99.7%</td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>Sigma-Aldrich</td>
			<td>650501</td>
			<td>CHROMASOLV, for HPLC, &#62;99.9%</td>
		</tr>
		<tr>
			<td>Flow cell</td>
			<td>Starna Cells</td>
			<td></td>
			<td>583.65.65-Q-5/Z20</td>
		</tr>
		<tr>
			<td>Flow unit</td>
			<td>Vapourtec</td>
			<td></td>
			<td>E-series system</td>
		</tr>
		<tr>
			<td>Raman spectrometer</td>
			<td>Enwave Optronics Inc</td>
			<td></td>
			<td>Model EZRaman-L</td>
		</tr>
	</tbody>
</table>

real-time monitoring of reactions performed using continuous-flow processing: the preparation of 3-acetylcoumarin as an example

Mediante el uso de monitoreo en línea, es posible optimizar reacciones realizadas mediante el procesamiento de flujo continuo de una manera simple y rápida. También es posible para garantizar la calidad del producto consistente en el tiempo utilizando esta técnica. Aquí mostramos cómo conectar una unidad de flujo disponible comercialmente con un espectrómetro Raman. La celda de flujo Raman se coloca después del regulador de contrapresión, lo que significa que puede ser operado a presión atmosférica. Además, el hecho de que la corriente de producto pasa a través de un tramo de tubo antes de entrar en la celda de flujo significa que el material es a TA. Es importante que los espectros se adquirió en condiciones isotérmicas desde intensidad de la señal Raman es dependiente de la temperatura. Después de haber montado el aparato, que a continuación mostramos cómo monitorizar una reacción química, la síntesis catalizada de piperidina 3-acetylcoumarin de salicilaldehído y acetoacetato de etilo se utiliza como un ejemplo. La reacción puede llevarse a cabo en un rango de caudales de unatemperaturas d, la herramienta de monitoreo in situ que se utilizan para optimizar las condiciones de manera sencilla.

La preparación de flujo continuo de 3-acetylcoumarin fue elegido como una reacción representante para la monitorización en línea. En lotes, la reacción procede bien cuando usando acetato de etilo como disolvente. Sin embargo, el producto (1) no es completamente soluble a temperatura ambiente. Para evitar la obstrucción del potencial regulador de contrapresión, así como mitigar el riesgo de tener partículas sólidas en la celda de flujo que perturbar adquisición de la señal, se utilizó una t?...

Watch this Scientific Journal Video about Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example at JoVE.com

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

Monitoreo en tiempo real permite la optimización rápida de las reacciones realizadas utilizando el procesamiento de flujo continuo. Aquí la preparación de 3-acetylcoumarin se utiliza como un ejemplo. El aparato para realizar in situ monitoreo Raman se describe, al igual que los pasos necesarios para optimizar la reacción.

Monitoreo en tiempo real de reacciones realizadas Utilizando Procesamiento de flujo continuo: La Preparación de 3-Acetylcoumarin como ejemplo

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible ...

real-time-monitoring-reactions-performed-using-continuous-flow

Research

JoVE Journal

Chemistry

9.6K vistas.  University of Connecticut.  Monitoreo en tiempo real permite la optimización rápida de las reacciones realizadas utilizando el procesamiento de flujo continuo. Aquí la preparación de 3-acetylcoumarin se utiliza como un ejemplo. El aparato para realizar in situ monitoreo Raman se describe, al igual que los pasos necesarios para optimizar la reacción. 

Video: Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

A method for species identification of botanical material by direct analysis in real time-high resolution mass spectrometry and multivariate statistical analysis is presented.

Rápida de alto rendimiento Identificación de Especies de material botánico Uso del análisis directo en tiempo real de alta resolución Espectrometría de Masas

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, ...

Investigación

Química

Capillary Electrophoresis to Monitor Peptide Grafting onto Chitosan Films in Real Time

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. Compared to other analytical separation techniques, such as chromatography, CE is cheap, robust and effectively requires no sample preparation (for a number of complex natural matrices or polymeric samples). CE is fast and can be used to follow the evolution of mixtures in real time (e.g., chemical reaction kinetics), as the signals observed for the separated compounds are directly proportional to their quantity in solution.
Here, the efficiency of CE is demonstrated for monitoring the covalent grafting of peptides onto chitosan films for subsequent biomedical applications. Chitosan&#39;s antimicrobial and biocompatible properties make it an attractive material for biomedical applications such as cell growth substrates. Covalently grafting the peptide RGDS (arginine - glycine - aspartic acid - serine) onto the surface of chitosan films aims at improving cell attachment. Historically, chromatography and amino acid analysis have been used to provide a direct measurement of the amount of grafted peptide. However, the fast separation and absence of sample preparation provided by CE enables equally accurate yet real-time monitoring of the peptide grafting process. CE is able to separate and quantify the different components of the reaction mixture: the (non-grafted) peptide and the chemical coupling agents. In this way the use of CE results in improved films for downstream applications.
The chitosan films were characterized through solid-state NMR (nuclear magnetic resonance) spectroscopy. This technique is more time-consuming and cannot be applied in real time, but yields a direct measurement of the peptide and thus validates the CE technique.

Free solution capillary electrophoresis is a fast, cheap and robust analytical method that enables the quantitative monitoring of chemical reactions in real time. Its utility for rapid, convenient and precise analysis is demonstrated here through analysis of covalent peptide grafting onto chitosan films for improved cell adhesion.

La electroforesis capilar para supervisar Péptido injerto sobre quitosano películas en tiempo real

Free-solution capillary electrophoresis (CE) separates analytes, generally charged compounds in solution through the application of an electric field. ...

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.

The safe and proper use of organolithium reagents is described.

Un protocolo para las reacciones de litiación segura usando reactivos orgánicos de litio

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

Monitoring the Effects of Illumination on the Structure of Conjugated Polymer Gels Using Neutron Scattering

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and absence of white light exposure. By instituting a controlled temperature ramp, the gelation of these materials can be precisely monitored as they proceed through this structural evolution, which effectively mirrors the conditions experienced during the solution deposition phase of organic electronic device fabrication. Using small angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) along with appropriate fitting protocols we quantify the evolution of select structural parameters throughout this process. Thorough analysis indicates that continued light exposure throughout the gelation process significantly alters the structure of the ultimately formed gel. Specifically, the aggregation process of poly(3-hexylthiophene-2,5-diyl) (P3HT) nano-scale aggregates is negatively affected by the presence of illumination, ultimately resulting in the retardation of growth in conjugated polymer microstructures and the formation of smaller scale macro-aggregate clusters.

A protocol for the analysis of gels formed from the optoelectronic conjugated polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) using small and ultra-small angle neutron scattering in both the presence and absence of illumination is presented.

Supervisar los efectos de iluminación en la estructura de los geles de polímero conjugado mediante dispersión de neutrones

We demonstrate a protocol to effectively monitor the gelation process of a high concentration solution of conjugated polymer both in the presence and ...

Measurements of Long-range Electronic Correlations During Femtosecond Diffraction Experiments Performed on Nanocrystals of Buckminsterfullerene

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the results of femtosecond X-ray free electron laser (XFEL) experiments. An increasing number of experimental observations have shown that although nuclear motion can be negligible, given a short enough incident pulse duration, electronic motion cannot be ignored. The current and widely accepted models assume that although electrons undergo dynamics driven by interaction with the pulse, their motion could largely be considered &#39;random&#39;. This would then allow the supposedly incoherent contribution from the electronic motion to be treated as a continuous background signal and thus ignored. The original aim of our experiment was to precisely measure the change in intensity of individual Bragg peaks, due to X-ray induced electronic damage in a model system, crystalline C60. Contrary to this expectation, we observed that at the highest X-ray intensities, the electron dynamics in C60 were in fact highly correlated, and over sufficiently long distances that the positions of the Bragg reflections are significantly altered. This paper describes in detail the methods and protocols used for these experiments, which were conducted both at the Linac Coherent Light Source (LCLS) and the Australian Synchrotron (AS) as well as the crystallographic approaches used to analyse the data.

We describe an experiment designed to probe the electronic damage induced in nanocrystals of Buckminsterfullerene (C60) by intense, femtosecond pulses of X-rays. The experiment found that, surprisingly, rather than being stochastic, the X-ray induced electron dynamics in C60 are highly correlated, extending over hundreds of unit cells within the crystals1.

Medidas de largo alcance correlaciones electrónicas durante los experimentos de difracción de femtosegundo realizadas en nanocristales de buckminsterfullereno

The precise details of the interaction of intense X-ray pulses with matter are a topic of intense interest to researchers attempting to interpret the ...

Real-time Breath Analysis by Using Secondary Nanoelectrospray Ionization Coupled to High Resolution Mass Spectrometry

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental exposure in a non-invasive manner. In this work, we present a protocol to characterize the exhaled VOCs in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS). The homemade Sec-nanoESI source was readily set up based on a commercial nanoESI source. Hundreds of peaks were observed in the background-subtracted mass spectra of exhaled breath, and the mass accuracy values are -4.0-13.5 ppm and -20.3-1.3 ppm in the positive and negative ion detection modes, respectively. The peaks were assigned with accurate elemental composition according to the accurate mass and isotopic pattern. Less than 30 s is used for one exhalation measurement, and it takes approximately 7 min for six replicated measurements.

A protocol for characterizing chemical composition of exhaled breath in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry is demonstrated.

Análisis de la respiración en tiempo real mediante el uso de ionización secundaria Nanoelectrospray acoplada a espectrometría de masas de alta resolución

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental ...

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;. Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with &#34;mixing&#34; and &#34;linear&#34; microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology&#39;s competitiveness, sustainability, and versatility in their research.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Flow chemistry carries environmental and economic advantages by leveraging superior mixing, heat transfer and cost benefits. Herein, we provide a blueprint to transfer chemical processes from batch to flow mode. The reaction of diphenyldiazomethane (DDM) with p-nitrobenzoic acid, conducted in batch and flow, was chosen for proof of concept.

Química en flujo continuo: Reacción de Diphenyldiazomethane con p- nitrobenzoico ácido

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and ...

A Continuous-flow Photocatalytic Reactor for the Precisely Controlled Deposition of Metallic Nanoparticles

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic nanoparticles is developed. Guidelines for the replication of the reactor and its operation are provided in detail. Three different composite systems (Pt/graphene, Pt/TiO2, and Au/TiO2) with monodisperse and uniformly distributed particles are produced by this reactor, and the photodeposition mechanism, as well as the synthesis optimization strategy, are discussed. The synthesis methods and their technical aspects are described comprehensively. The role of the ultraviolet (UV) dose (in each excitation pulse) on the photodeposition process is investigated and the optimum values for each composite system are provided.

For a continuous and scalable synthesis of noble-metal-based nanocomposites, a novel photocatalytic reactor is developed and its structure, operation principles, and product quality optimization strategies are described.

Un Reactor fotocatalítico de flujo continuo para la deposición precisamente controlada de nanopartículas metálicas

In this work, a novel photocatalytic reactor for the pulsed and controlled excitation of the photocatalyst and the precise deposition of metallic ...

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands for in vivo investigations. Within this protocol, a robust and reliable remote-controlled radiosynthesis of [11C]SNAP-7941, an antagonist to the melanin-concentrating hormone receptor 1, is described. The radiosynthesis starts with cyclotron produced [11C]CO2 that is subsequently further reacted via a gas-phase transition to [11C]CH3OTf. Then, this reactive intermediate is introduced to the precursor solution and forms the respective radiotracer. Chemical as well as the radiochemical purity are determined by means of RP-HPLC, routinely implemented in the radiopharmaceutical quality control process. Additionally, the molar activity is calculated as it is a necessity for the following real-time kinetic investigations. Furthermore, [11C]SNAP-7941 is applied to MDCKII-WT and MDCKII-hMDR1 cells for evaluating the impact of P-glycoprotein (P-gp) expression on cell accumulation. For this reason, the P-gp expressing cell line (MDCKII-hMDR1) is either used without or with blocking prior to experiments by means of the P-gp substrate (&#177;)-verapamil and the results are compared to the ones observed for the wildtype cells. The overall experimental approach demonstrates the importance of a precise time-management that is essential for every preclinical and clinical study using PET tracers radiolabelled with short-lived nuclides, such as carbon-11 (half-life: 20 min).

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941

Here, we represent a protocol for the fully automated radiolabelling of [11C]SNAP-7941 and the analysis of the real-time kinetics of this PET-tracer on P-gp expressing and non-expressing cells.

Aspecto técnico de la síntesis automatizada y evaluación cinética en tiempo real de [11C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands ...

Optimization of Radiochemical Reactions using Droplet Arrays

Current automated radiosynthesizers are designed to produce large clinical batches of radiopharmaceuticals. They are not well suited for reaction optimization or novel radiopharmaceutical development since each data point involves significant reagent consumption, and contamination of the apparatus requires time for radioactive decay before the next use. To address these limitations, a platform for performing arrays of miniature droplet-based reactions in parallel, each confined within a surface-tension trap on a patterned polytetrafluoroethylene-coated silicon "chip", was developed. These chips enable rapid and convenient studies of reaction parameters including reagent concentrations, reaction solvent, reaction temperature and time. This platform permits the completion of hundreds of reactions in a few days with minimal reagent consumption, instead of taking months using a conventional radiosynthesizer.

This method describes the use of a novel high-throughput methodology, based on droplet chemical reactions, for the rapid and economical optimization of radiopharmaceuticals using nanomole amounts of reagents.