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. Trovare Segnali adatto per il monitoraggio di reazione <ol><li> Ottenere spettri Raman per tutte le materie prime e il prodotto. </li><li> Sovrapposizione spettri e identificare una banda di intenso che è unico per il prodotto. </li><li> Utilizzare questa band Raman per monitorare l&#39;andamento della reazione. Una banda a 1.608 cm -1 è stato selezionato in questo caso. </li></ol> 2. Impostare la cella di flusso <ol><li> Ottenere una cella di flusso adatto. Qui usare uno con le seguenti dimensioni: larghezza di 6,5 mm, altezza di 20 mm e una lunghezza di percorso di 5 mm (Figura 2A). </li><li> Posizionare la cella di flusso in un contenitore che fornisce un ambiente privo di luce ambientale. </li><li> Collegare il tubo di ingresso e uscita della cella di flusso (in questo caso la tubazione ID PFA 1 mm). </li></ol> 3. Interfaccia Raman spettrometro con la cella di flusso <ol><li> Ottenere uno spettrometro Raman adeguato con un gruppo ottico flessibile, che può essere posizionato in cperdere vicinanza alla cella di flusso. </li><li> Posizionare il gruppo ottico attraverso un&#39;apertura di dimensioni adeguate nella scatola contenente il gruppo della cella di flusso (Figura 2B). </li><li> Far scorrere il gruppo ottico fino a toccare la cella di flusso e poi tirare indietro lasciando uno spazio di ~ 2 mm. </li><li> Riempire la cella di flusso con il 100% di acetone. </li><li> Accendere il spettrometro Raman e acquisire spettri in modo continuo a scansione. </li><li> Mettere a fuoco il laser muovendo delicatamente il tubo di luce una frazione alla volta. Continuate a muovervi il tubo di luce fino a quando il segnale è al suo massimo di intensità e le cime sono nitide e ben definite. </li></ol><img alt="Figura 2" src="/files/ftp_upload/52393/52393fig2.jpg" /> Figura 2. (A) Portata cellulare e l&#39;interfaccia (B) Raman usato. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig2large.jpg" target="_blank">Cliccate qui per vedere una più grande ve</a>rsion di questa figura. 4. Preparare reagente e solventi Soluzioni <ol><li> Aggiungere salicilaldeide (6,106 g, 50 mmol, 1 equiv) e acetoacetato di etile (6,507 g, 50 mmol, 1 equiv) in un pallone tarato da 50 ml. </li><li> Aggiungere acetato di etile per un volume totale di 50 ml e poi mescolare il contenuto. </li><li> Trasferire un&#39;aliquota da 10 ml della soluzione madre di un flaconcino di vetro da 20 ml contenente una ancoretta magnetica. Etichettare questa fiala &quot;reagente&quot;. </li><li> In un flacone 100 ml posto 90 ml di acetato di etile. Etichettare questa bottiglia &quot;solvente&quot;. In un flacone 100 ml posto 90 ml di acetone. Etichettare questa bottiglia &quot;intercettare solvente&quot;. </li></ol> 5. Preparare il flusso di apparecchi <ol><li> Assicurarsi che l&#39;unità di flusso ha almeno due pompe e li etichetta &quot;P1&quot; e &quot;P2&quot;. Identificare solventi e reagenti linee di ingresso per ogni pompa. Posizionare le linee di uscita dalle linee e &quot;Collect&quot;, &quot;rifiuti&quot; in due individual 100 ml bottiglie etichettate &quot;prodotto&quot; e &quot;rifiuto&quot;, rispettivamente. </li><li> Come un reattore, utilizzare 10 ml PFA bobina poter essere riscaldato. </li><li> Collegare il tubo uscita P1 all&#39;ingresso della bobina reattore PFA. </li><li> Installare una tre porte chetone polietere etere (PEEK) tee-mixer dopo la bobina del reattore. </li><li> Collegare il tubo di uscita P2 al tee-mixer, a 180 ° dal tubo di uscita della bobina del reattore. Collegare un pezzo di tubo alla terza porta del Tee-mixer. Sull&#39;altra estremità di questo tubo inserire un regolatore di contropressione. </li><li> Collegare una linea dall&#39;uscita del regolatore di contropressione all&#39;ingresso della cella di flusso. Collegare una linea dall&#39;uscita della cella di flusso allo switch &quot;rifiuti / raccogliere&quot;. </li><li> Prime le linee del solvente sia per P1 e P2 e la linea del reagente per P1 con solvente. Spostare la linea del reagente per P1 dalla bottiglia di solvente nel flacone. </li><li> Utilizzando P1, passare acetato di etile attraverso il reattorecoil a 2 ml / min fino a riempirlo. Passare acetone attraverso P2 ad un flusso di 2 ml / min per 2 min. </li><li> Regolare le portate solvente sia per P1 e P2 di 1 ml / min. Impostare il regolatore di contropressione per una pressione di 7 bar. Impostare la temperatura della bobina del reattore alla temperatura desiderata. </li><li> Doppio controllare l&#39;apparecchio è configurato come mostrato nello schema di figura 3. </li><li> Una volta che il sistema raggiunge temperatura e pressione costante, controllare eventuali perdite e quindi eseguire la reazione. </li></ol><img alt="Figura 3" src="/files/ftp_upload/52393/52393fig3.jpg" /> Figura 3. Schema della configurazione attrezzature utilizzate per gli esperimenti di controllo reazione. <a href="https://www.jove.com/files/ftp_upload/52393/52393fig3large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> 6. Monitorare la reazione <ol><li> Taksfondo ea scansione del sistema solvente acetato di etile / acetone come è passato attraverso la cella di flusso. Questo sarà automaticamente sottratto da tutte le scansioni successive. </li><li> Configurare lo spettrometro di prendere scansioni ogni 15 secondi (in questo caso lo spettrometro Raman stato impostato un tempo di integrazione 10 sec, vagone = 3, e media = 1). </li><li> Iniettare piperidina (0,05 ml, 0,05 mmol, 0,1 equiv) tutti in una volta nel flacone di vetro con l&#39;etichetta &quot;reagente&quot;. </li><li> Dopo aver accuratamente la miscelazione, interruttore P1 da &quot;solvente&quot; a &quot;reagente&quot;. Impostare il flusso di uscita di &quot;raccogliere&quot;. </li><li> Quando tutto il materiale è completamente caricata, passare da P1 &quot;reagente&quot; torna a &quot;solvente.&quot; Continua scorre solvente attraverso la bobina reattore per altri 30 minuti. Una volta trascorso questo tempo, spegnere il riscaldamento. </li><li> Pompe turno P1 e P2 quando la temperatura della batteria del reattore è raffreddato al di sotto di 50 ° C. </li></ol> 7. Analizzare i dati <ol&gt; <li> Esportare i dati dello spettrometro Raman a un foglio di calcolo e la trama intensità Raman a 1.608 centimetri -1 vs. orario. </li><li> Per ottimizzare le condizioni, effettuare la reazione in una serie di portate e temperature del reattore in modo iterativo. </li><li> Trame sovrapposizione di intensità Raman a 1.608 centimetri -1 vs. orario. Nota: Più alta intensità Raman correla con la conversione del prodotto superiore. </li></ol> 8. Eseguire la reazione Usando condizioni ottimizzate <ol><li> Avere varie condizioni schermati (diverse le portate / temperature del reattore), eseguire la reazione utilizzando le condizioni ottimali per permettere la conversione del prodotto più alto. </li></ol> 9. Isolare il prodotto <ol><li> Prendere il contenuto del pallone prodotto e versarlo in un becker contenente 100 ml di ghiaccio e 20 ml di 2 M HCl. </li><li> Risciacquare la beuta prodotto con una quantità minima di acetato di etile (2 ml) e trasferimento al becher. </li><li> Mescolate il composto di ghiacciofino a quando tutto il ghiaccio è completamente sciolto. </li><li> Impostare un sistema di filtrazione con un imbuto Hirsch, beuta braccio laterale, guarnizione di gomma e una lunghezza di tubo a vuoto in gomma. </li><li> Filtrare il precipitato sotto vuoto, lavare con etere etilico freddo (10 ml) e lasciarlo asciugare sotto una lampada di calore (2-3 ore) e O secco / N sotto vuoto. </li><li> Confermare l&#39;identità del prodotto da 1 H risonanza magnetica (NMR) nucleare usando CDCl 3 come solvente. Per un 500 MHz spettrometro NMR, i 1 dati H NMR di 3 acetylcoumarin è il seguente: 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 C NMR dati: 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>

<ol>
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The authors have nothing to disclose.

La facilità con cui lo spettrometro Raman può essere interfacciato con l&#39;unità di flusso rende questa tecnica in linea prezioso per il monitoraggio di reazione. Un certo numero di variabili di reazione può essere sondato in modo accelerato, permettendo all&#39;utente di arrivare a condizioni di reazione più veloce rispetto ottimizzate quando si utilizzano metodi fuori linea. Applicazione delle tecniche descritte qui anche consente il monitoraggio della formazione di prodotti collaterali, assumendo una banda ada...

Utilizzando lavorazione a flusso continuo, chimici stanno scoprendo che possono eseguire una serie di reazioni chimiche in modo sicuro, efficace, e con facilità 1,2. Come risultato, attrezzature chimica flusso sta diventando uno strumento per l&#39;esecuzione di reazioni integrante sia in ambienti industriali e laboratori di ricerca in istituti accademici. Un&#39;ampia varietà di trasformazioni chimica sintetica sono state eseguite in reattori a flusso 3,4. In casi selezionati, reazioni che non funzionano in modalità batch hanno dimostrato di procedere senza intoppi in condizioni di flusso continuo 5. Sia per l&#39;ottimizzazione di reazione e controllo di qualità, l&#39;incorporazione di monitoraggio reazione in linea con l&#39;elaborazione di flusso offre vantaggi significativi. In linea di monitoraggio fornisce un&#39;analisi continuo con risposta in tempo reale alle condizioni reali del campione. Questo è più veloce e, in alcuni casi, più affidabile rispetto ai tradizionali tecniche off-line. Un certo numero di tecniche analitiche in linea è stato interfacciato con freattori bassi 7. Esempi includono infrarossi 8,9, UV-visibile 10,11, 12,13 NMR, spettroscopia Raman 14,15, 16,17 e spettrometria di massa. Il nostro gruppo di ricerca ha interfacciato uno spettrometro Raman con un gruppo a microonde scientifica 18. Usando questo, una serie di reazioni sono state monitorate da sia qualitativa e quantitativa 20 19 punto di vista. Questo successo, abbiamo recentemente interfacciato nostro spettrometro Raman con una delle nostre unità a flusso continuo e impiegato per il monitoraggio reazione di un certo numero di importanti trasformazioni organiche medicamentoso rilevanti in linea. 21 In ogni caso è stato possibile monitorare la reazioni e anche in un esempio, per mezzo di una curva di taratura, si potrebbe determinare la conversione del prodotto da dati spettrali Raman. Nel Qui si descrive come impostare il dispositivo e utilizzarlo per monitorare le reazioni. Usiamo la sintesi piperidina-catalizzata di 3-acetylcoumarin (1) da salicylaldehyde con acetoacetato di etile (Figura 1) come la reazione del modello qui. <img alt="Figura 1" src="/files/ftp_upload/52393/52393fig1.jpg" /> Figura 1. Base catalizzata reazione di condensazione tra salicilaldeide e acetoacetato di etile per dare 3 acetylcoumarin (1). <a href="https://www.jove.com/files/ftp_upload/52393/52393fig1large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa 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

Utilizzando il monitoraggio in linea, è possibile ottimizzare le reazioni eseguite utilizzando l&#39;elaborazione a flusso continuo in modo semplice e rapido. E &#39;anche possibile per garantire la qualità del prodotto costante nel tempo utilizzando questa tecnica. Siamo qui mostriamo come interfacciare una unità di flusso disponibile in commercio con uno spettrometro Raman. La cella di flusso Raman posto dopo il regolatore di contropressione, che significa che può essere azionato a pressione atmosferica. Inoltre, il fatto che il flusso di prodotto passa attraverso un tratto di tubo prima di entrare nella cella di flusso significa che il materiale è a RT. È importante che gli spettri sono acquisiti in condizioni isoterme poiché intensità di segnale Raman dipende dalla temperatura. Dopo aver assemblato l&#39;apparato, abbiamo poi mostrato come monitorare una reazione chimica, la sintesi piperidina-catalizzata di 3 acetylcoumarin da salicilaldeide e acetoacetato di etile viene utilizzato come un esempio. La reazione può essere eseguita su una gamma di PORTATE untemperature d, lo strumento di monitoraggio in situ utilizzati per ottimizzare le condizioni in modo semplice e veloce.

La preparazione flusso continuo di 3-acetylcoumarin stato scelto come rappresentante reazione per il monitoraggio in linea. In batch, la reazione procede bene usando acetato di etile come solvente. Tuttavia, il prodotto (1) non è completamente solubile a RT. Per evitare il potenziale intasamento del regolatore di contropressione, nonché ridurre il rischio di avere particelle solide nella cella di flusso che perturbare acquisizione del segnale, abbiamo utilizzato una tecnica abbiamo sviluppato in prece...

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

Monitoraggio in tempo reale consente la rapida ottimizzazione delle reazioni eseguite utilizzando l&#39;elaborazione a flusso continuo. Qui la preparazione di 3-acetylcoumarin viene utilizzato come esempio. L&#39;apparecchiatura per l&#39;esecuzione in-situ monitoraggio Raman è descritto, come lo sono i passaggi necessari per ottimizzare la reazione.

Monitoraggio in tempo reale delle reazioni eseguita utilizzando la lavorazione a flusso continuo: La preparazione di 3-Acetylcoumarin come un esempio

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 Views.  University of Connecticut.  Monitoraggio in tempo reale consente la rapida ottimizzazione delle reazioni eseguite utilizzando l'elaborazione a flusso continuo. Qui la preparazione di 3-acetylcoumarin viene utilizzato come esempio. L'apparecchiatura per l'esecuzione in-situ monitoraggio Raman è descritto, come lo sono i passaggi necessari per ottimizzare la reazione. 

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.

Rapid high-throughput Specie Identificazione del materiale botanico Utilizzando l&#39;analisi diretta in tempo reale ad alta risoluzione Spettrometria di Massa

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

Ricerca

Chimica

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.

Elettroforesi capillare per monitorare Peptide innesto su Chitosano film in tempo reale

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 protocollo per reazioni sicuro litiazione Utilizzando organolitio Reagenti

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.

Monitoraggio degli effetti di illuminazione sulla struttura del gel di polimeri coniugati utilizzando lo Scattering di neutroni

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.

Misurazioni delle correlazioni a lungo raggio elettroniche durante gli esperimenti di diffrazione a femtosecondi eseguiti su nanocristalli di 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 ...

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.

Analisi dell'espirato in tempo reale tramite ionizzazione secondaria Nanoelectrospray accoppiata alla spettrometria di massa ad alta risoluzione

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.

Chimica di flusso continuo: Reazione di Diphenyldiazomethane con l'acido p- nitrobenzoico

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 reattore di flusso continuo fotocatalitica di precisamente controllato deposizione di nanoparticelle metalliche

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.

Aspetto tecnico della sintesi automatizzata e valutazione cinetica in tempo reale di [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.