Para obtener asistencia financiera agradecemos el EPSRC (Career Fellowship Aceleración de JAB; EP/J001538/1), el Ramsay Memorial Trust (Beca de Investigación 2009-2011 para JAB), y el Imperial College de Londres. Gracias al Prof. Alan Armstrong por el generoso apoyo y asesoramiento.

1. Preparación de Iodoaziridines con Diiodomethyllithium <ol><li> Llama seque un matraz de fondo redondo de 100 ml que contenía una barra de agitación y equipado con un tabique, bajo una corriente de argón, a continuación, dejar enfriar a temperatura ambiente bajo una atmósfera de argón. NOTA: Material de vidrio se secó en un horno durante la noche (125 ° C) y se enfrió a temperatura ambiente en una forma análoga también es apropiado. </li><li> Al matraz, añadir 5,7 ml de THF anhidro y 2,7 ml de Et2O anhidro mediante una jeringa, y hexametildisilazano recién destilado (1,50 mmol, 315 l) a través de una microjeringa. </li><li> Se agita la solución resultante y se enfría a -78 ° C en un baño de hielo seco / acetona en un Dewar de tamaño adecuado para permitir que el matraz esté bien sumergido. Cubrir el Dewar con papel de aluminio, para reducir al mínimo la exposición del recipiente de reacción a la luz. </li><li> Añadir n BuLi (1,50 mmol, 0,60 ml, 2,5 M en hexanos) gota a gota mediante una jeringa durante 2-3 minutos a la solución a -78 ° C.Dejar que la mezcla en agitación a -78 ° C durante un 30 min más para formar una solución 0,17 M de LiHMDS. PRECAUCIÓN: solución de n BuLi es inflamable, corrosiva para la piel y pirofórico. El exceso de reactivo en la jeringa debe ser apagado en consecuencia. </li><li> Después de 30 min, se añade 1 ml de THF anhidro a un matraz secado a la llama de fondo redondo de 10 ml con una jeringa, seguido de diyodometano (1,70 mmol, 135 l) a través de una microjeringa y asegurarse de que estén bien mezclados. </li><li> Añadir la solución gota a gota diyodometano durante 2 min a la solución de hexametildisilazano de litio a -78 ° C. Deje esta solución durante 20 minutos a -78 ° C. </li><li> Durante este tiempo, pesar N - [(E)-4-methylphenylmethylidene]-4-metilbencenosulfonamida (137 mg, 0,50 mmoles) en otro secado a la llama 10 ml matraz de fondo redondo y se disuelven en 2,0 ml de THF anhidro. </li><li> Después del tiempo de desprotonación 20 min, se añade gota a gota la solución de imina a la solución diiodomethyllithium más de 5 min a -78 &amp; #176; C. </li><li> Inmediatamente después de la adición gota a gota se ha completado, levante el recipiente de reacción del baño de hielo seco, y transferir a un baño de hielo / agua a 0 ° C. Vuelva a cubrir con papel de aluminio y dejar actuar durante 15 minutos a 0 º C. NOTA: La solución debe ser de color naranja. </li><li> Después de 15 min a 0 ° C, enfriar rápidamente la reacción por la adición de 30 ml de solución de bicarbonato de sodio acuosa saturada. Transfiera la mezcla a un embudo de separación y añadir 30 ml de CH 2 Cl 2. Agitar la mezcla y remover el CH 2 Cl 2 capa inferior. Repita este procedimiento de extracción dos veces más, y combinar los CH 2 Cl 2 capas. </li><li> Añadir sulfato sódico a las capas orgánicas para eliminar cualquier agua presente en la solución, a continuación, se separa por filtración el sulfato de sodio y se recoge el filtrado en un 250 ml de matraz de fondo redondo. </li><li> Eliminar el disolvente bajo presión reducida en un evaporador rotatorio para dar una muestra impura del producto deseado iodoaziridine. </li></ol> 2. Evaluación de la estabilidad del producto a las Fases estacionarias para cromatografía <ol><li> Disolver la muestra aziridina crudo en CH 2 Cl 2 (16 ml) y añadir 1,3,5-trimetoxibenceno (28,0 mg, 0,167 mmol) como un estándar interno, asegurarse de que este se disuelve completamente. Tomar una alícuota (2 ml) de esta mezcla, se elimina el disolvente a presión reducida y analizar esta muestra por espectroscopía de RMN 1 H. </li><li> Abra el registrado espectro de RMN 1 H utilizando el software estándar de procesamiento de RMN. En Mestrenova, haga clic derecho en el espectro y optó por la &quot;integración&quot;, y luego &quot;manual&quot; para proporcionar la herramienta de integración. Haga clic y arrastre para cubrir la anchura de los picos a 6,08 ppm y 4,87 ppm en la integración de las señales de la norma interna y la señal CHI aziridina respectivamente. Haga clic derecho en la integral para el pico a 6,08 ppm, seleccione &quot;editar integral&quot; y cambie el valor &quot;normalizado&quot; a 3,0. NOTE: Pasos similares se pueden aplicar a otros paquetes de software. </li><li> Utilice el valor actualizado de la integral de la señal de CHI aziridina (4,87 ppm) para determinar el rendimiento de la iodoaziridine, aquí el uso de (100/3) × (la integral de la señal de CHI), que ofrece un rendimiento calculado de 59%. NOTA: Dada la cantidad conocida de estándar interno (0,167 mmoles), y el pico de producto correspondiente a 1 protón, el rendimiento de iodoaziridine se calcula por la siguiente ecuación: 100 × (integral de pico del producto) x (moles de patrón interno) / moles de material de partida. </li><li> Preparar suspensiones de las siguientes fases estacionarias (25 g): sílice, sílice + 1% NEt3 (trietilamina), alúmina neutra, de alúmina básica (actividad de E), de alúmina básica (actividad IV) y Florisil, cada uno en 5% de EtOAc / hexano (50 ml), en seis matraces cónicos de 250 ml separados que contienen barras de agitación. En otro matraz cónico de preparar una solución de 5% de EtOAc / hexano (50 ml), para ser utilizado como un experimento de control. PRECAUCIÓN: silicun gel, alúmina y otras fases estacionarias empleadas son peligrosos si se inhalan, por tanto, siempre debe ser manejado en una campana de extracción eficaz. </li><li> Añadir 2 ml de alícuotas de la solución estándar iodoaziridine / interno a cada uno de los matraces cónicos a TA. Agitar las mezclas de lechada durante 30 min. NOTA: esto representa la duración, el compuesto puede ser expuesto a la fase estacionaria durante un procedimiento normal de cromatografía en columna flash. </li><li> Filtrar las mezclas de suspensión usando un embudo sinterizado, y recoger el filtrado en un 250 ml de matraz de fondo redondo. Lavar el residuo en el embudo sinterizado con CH 2 Cl 2 (2 × 30 ml). Repita este proceso de filtrado de las suspensiones restantes. NOTA: Es adecuado que contrarreste al comienzo de cada fase estacionaria para dar tiempo a la filtración y así mantener el mismo tiempo para cada uno de los materiales de la fase estacionaria. </li><li> Eliminar el disolvente de las muestras resultantes a presión reducida, y analizar por 1 H RMN SpectroSCOPY para calcular la cantidad de iodoaziridine recuperados en cada caso, como se describe en la Sección 2.2. </li><li> Comparar los rendimientos de iodoaziridine obtenidos de cada fase estacionaria probado con la obtenida en la Sección 2.1. NOTA: La muestra que proporcione el rendimiento más alto, idealmente el mismo que en 2.1, indica la fase estacionaria óptima para la cromatografía. En este ejemplo, alúmina básica (actividad IV) se consideró la mejor fase estacionaria para la purificación. </li></ol> 3. Desactivación de alúmina básica y purificación de la Iodoaziridine <ol><li> Repita la Sección 1 para generar la mezcla iodoaziridine crudo. </li><li> Para generar alúmina básica (actividad IV), añadir 100 g de alúmina básica (actividad de I) a un 500 ml de matraz de fondo redondo y a continuación, añadir 10 ml de agua al matraz y encajar con un tapón de vidrio. </li><li> Agitar el frasco enérgicamente hasta que no haya grumos son visibles, indicando incluso la difusión de agua a través de la alúmina. Dejar que la alúmina se enfríe a temperatura ambiente. PRECAUCIÓN: la adsorciónción del agua es exotérmica, por lo que el frasco se puede calentar y puede dar lugar a una acumulación de presión. Liberar cualquier presión acumulada con frecuencia. </li><li> Se purifica el iodoaziridine bruto por cromatografía en columna usando la alúmina básica (actividad IV) como la fase estacionaria, eluyendo con hexano, la clasificación a 5% de EtOAc / hexano. NOTA: altas concentraciones de EtOAc no deben utilizarse con alúmina básica. En estos casos, dietil éter se puede utilizar en su lugar. </li><li> Combinar el producto que contiene fracciones y eliminar el disolvente a presión reducida para obtener el iodoaziridine pura. </li></ol>

<ol>
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The authors declare that they have no competing financial interests.

Un procedimiento para la preparación diastereoselectiva de cis - N-TS-iodoaziridines se describe, junto con un protocolo de estudio de estabilidad para indicar cuantitativamente la mejor fase estacionaria para la purificación de compuestos potencialmente inestables por cromatografía en columna ultrarrápida. Se prevé que el acceso a iodoaziridines a través de este enfoque permitirá a los métodos para acceder a una amplia gama de aziridinas a ser desarrollado, por derivatización del anillo intac...

El objetivo de este método es para preparar iodoaziridines que ofrecen un potencial para funcionalización adicional a los derivados de aziridina. El método incorpora un protocolo para la selección cuantitativa de la fase estacionaria óptima para la cromatografía. Aziridinas, como ciclos de tres miembros, poseen tensión del anillo inherente que hace que sean elementos importantes en la química orgánica 1. En ellas se muestran una amplia gama de reactividad a menudo con apertura del anillo de aziridina 2,3, particularmente como intermedios en la síntesis de aminas funcionalizadas 4,5, o la formación de otros heterociclos de nitrógeno que contiene 6,7. La síntesis de una serie de derivados de aziridina por funcionalización de un precursor que contiene un anillo de aziridina intacto ha surgido como una estrategia viable 8. Tipo de grupo funcional-de metal, para generar un anión aziridinilo, y reacción con electrófilos se ha demostrado ser eficaz <sup&gt; 9,10,11, y recientemente desprotonación regio-y estereoselectiva de aziridinas N-protegidos también se ha logrado 12-15. Muy recientemente, catalizada por paladio métodos de acoplamiento cruzado para formar aziridinas a partir de precursores de aziridina arilo funcionalizados ha sido desarrollado por Vedejs 16,17, y nosotros mismos 18. La química de heteroátomos sustituido aziridinas abre preguntas fascinantes de la reactividad y la estabilidad 19. Hemos estado interesados ​​en la preparación de iodoaziridines como un grupo funcional novela que ofrece el potencial de proporcionar precursores a una amplia gama de derivados con la reactividad complementaria para reacciones de funcionalización aziridina existentes. En 2012 se informó de la primera preparación de aril N-Boc-iodoaziridines 20, y muy recientemente informó de la preparación de arilo y alquilo N-TS-21 iodoaziridines sustituido. El método para acceiodoaziridines ss utiliza diiodomethyllithium, un reactivo que recientemente también ha sido empleado en la preparación de diiodoalkanes 22,23, 22,24 diiodomethylsilanes y yoduros vinílicos 25-27. La naturaleza carbenoide similar de este reactivo requiere preparación y el uso a bajas temperaturas 22,28. A continuación se describen las técnicas y las condiciones utilizadas para la generación de diiodomethyllithium en la preparación de iodoaziridines. Mientras que la sílice se ha convertido en el material de elección para cromatografía de 29 años, que resultó no ser adecuado para la purificación de los N-TS-iodoaziridines. El gel de sílice es generalmente el primer y único material sólido fase empleado en cromatografía flash en química orgánica debido a la disponibilidad y eficaces separaciones. Sin embargo, la naturaleza ácida de gel de sílice puede causar la descomposición de sustratos sensibles durante la purificación, la prevención de aislamiento del material deseado. Mientras que otra víafases acionario o geles de sílice modificados están disponibles para la cromatografía de 30, no había manera de evaluar la compatibilidad de la molécula diana para estas diferentes materiales. Debido a la naturaleza sensible de los iodoaziridines, establecimos un protocolo para evaluar la estabilidad de un compuesto de una serie de fases estacionarias 21, lo que se demuestra aquí. Esto tiene potencial para su aplicación en la síntesis de una amplia gama de compuestos con grupos funcionales sensibles. El siguiente protocolo proporciona un acceso eficiente a iodoaziridines N-Ts, lo que permite la síntesis diastereoselectiva de ambos alquilo y aromáticos cis-iodoaziridines con un alto rendimiento.

<table border="0" cellpadding="0" cellspacing="0" width="871">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">Hexamethyldisilazane</td>
			<td style="width:273px;">999-97-3</td>
			<td style="width:197px;">Alfa Aesar</td>
			<td style="width:192px;">Distill from KOH under argon prior to use.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">n-Butyllithium</td>
			<td style="width:273px;">109-72-8</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;">2.5 M in hexanes, titrate prior to use.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">Diiodomethane</td>
			<td style="width:273px;">75-11-6</td>
			<td style="width:197px;">Alfa Aesar</td>
			<td style="width:192px;">Contains copper as a stabilizer.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">1,3,5-Trimethoxybenzene</td>
			<td style="width:273px;">621-23-8</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Silica</td>
			<td style="width:273px;">112945-52-5</td>
			<td style="width:197px;">Merck</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Basic alumina</td>
			<td style="width:273px;">1344-28-1</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Neutral alumina</td>
			<td style="width:273px;">1344-28-1</td>
			<td style="width:197px;">Merck</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Florisil</td>
			<td style="width:273px;">1343-88-0</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:23px;width:209px;">THF</td>
			<td colspan="3" rowspan="3" style="width:663px;">All anhydrous solvents were dried through activated alumina purification columns.&#160;</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:209px;">Et2O</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:209px;">CH2Cl2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">NMR spectrometer</td>
			<td>Bruker AV 400&#160;</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">NMR processing software</td>
			<td>MestReNova&#160;</td>
			<td>7.0.2-8636</td>
			<td></td>
		</tr>
	</tbody>
</table>

synthesis and purification of iodoaziridines involving quantitative selection of the optimal stationary phase for chromatography

La preparación altamente diastereoselectiva de cis - N-TS-iodoaziridines través de la reacción de diiodomethyllithium con N-Ts aldiminas se describe. Diiodomethyllithium se prepara por la desprotonación de diyodometano con LiHMDS, en una mezcla de éter de THF / dietil, a -78 ° C en la oscuridad. Estas condiciones son esenciales para la estabilidad del reactivo de lichi 2 generado. La posterior adición gota a gota de N-TS aldiminas a la solución diiodomethyllithium preformado ofrece un amino-diyoduro intermedia, que no se aísla. El calentamiento rápido de la mezcla de reacción a 0 ° C promueve la ciclación para dar iodoaziridines con exclusiva cis-diastereoselectividad. Las etapas de adición y ciclación de la reacción están mediados en un matraz de reacción mediante el control cuidadoso de la temperatura. Debido a la sensibilidad de los iodoaziridines a la purificación, la evaluación de los métodos adecuados de la PUSe requiere rificación. Un protocolo para evaluar la estabilidad de compuestos sensibles a fases estacionarias para cromatografía en columna se describe. Este método es adecuado para aplicar a nuevos iodoaziridines, u otros nuevos compuestos potencialmente sensibles. En consecuencia, este método puede encontrar aplicación en serie de proyectos sintéticos. El procedimiento implica en primer lugar la evaluación del rendimiento de la reacción, antes de la purificación, por 1 H espectroscopía de RMN con respecto a un patrón interno. Las porciones de la mezcla de producto impuro se exponen entonces a suspensiones de diversas fases estacionarias adecuadas para la cromatografía, en un sistema disolvente adecuado como el eluyente en la cromatografía de flash. Después de agitar durante 30 min para imitar la cromatografía, seguido de filtración, las muestras se analizaron por espectroscopía de 1H RMN. Los rendimientos calculados para cada fase estacionaria se comparan entonces con la obtenida inicialmente con la mezcla de reacción en bruto. Los resultados obtenidos proporcionan una evaluación cuantitativa de tque la estabilidad del compuesto para las diferentes fases estacionarias; de ahí la óptima se puede seleccionar. La elección de alúmina básica, modificado para actividad IV, como una fase estacionaria adecuada ha permitido el aislamiento de ciertos iodoaziridines en excelente rendimiento y pureza.

El procedimiento descrito permite cis - (±)-2-yodo-3-(4-tolil) -1 - (4-tolilsulfonil) aziridina como un solo diastereoisómero y con excelente pureza (Figura 1). Antes de la purificación, un rendimiento de 59% del producto iodoaziridine se calculó por espectroscopía de RMN 1 H. Sin embargo, esta iodoaziridine fue especialmente difícil para purificar y se sometió a una descomposición significativa sobre sílice. La purificación sobre alúmina básica (actividad IV) tal como se...

Watch this Scientific Journal Video about Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography at JoVE.com

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

Un protocolo para la preparación de un solo recipiente diastereoselectiva de cis - N-TS-iodoaziridines se describe. La generación de diiodomethyllithium, además de la N-Ts aldiminas y ciclación de la gema diyoduro intermedio a iodoaziridines amino se demuestra. También se incluye un protocolo para evaluar rápidamente y cuantitativamente la fase estacionaria más apropiado para la purificación por cromatografía.

Síntesis y purificación de Iodoaziridines Involucrar cuantitativa Selección de la fase estacionaria óptima para cromatografía

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. ...

synthesis-purification-iodoaziridines-involving-quantitative

Research

JoVE Journal

Chemistry

12.4K vistas.  Imperial College London.  Un protocolo para la preparación de un solo recipiente diastereoselectiva de cis - N-TS-iodoaziridines se describe. La generación de diiodomethyllithium, además de la N-Ts aldiminas y ciclación de la gema diyoduro intermedio a iodoaziridines amino se demuestra. También se incluye un protocolo para evaluar rápidamente y cuantitativamente la fase estacionaria más apropiado para la purificación por cromatografía. 

Video: Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

Determination of the Gas-phase Acidities of Oligopeptides

Amino acid residues located at different positions in folded proteins often exhibit different degrees of acidities. For example, a cysteine residue located at or near the N-terminus of a helix is often more acidic than that at or near the C-terminus 1-6. Although extensive experimental studies on the acid-base properties of peptides have been carried out in the condensed phase, in particular in aqueous solutions 6-8, the results are often complicated by solvent effects 7. In fact, most of the active sites in proteins are located near the interior region where solvent effects have been minimized 9,10. In order to understand intrinsic acid-base properties of peptides and proteins, it is important to perform the studies in a solvent-free environment.
We present a method to measure the acidities of oligopeptides in the gas-phase. We use a cysteine-containing oligopeptide, Ala3CysNH2 (A3CH), as the model compound. The measurements are based on the well-established extended Cooks kinetic method (Figure 1) 11-16. The experiments are carried out using a triple-quadrupole mass spectrometer interfaced with an electrospray ionization (ESI) ion source (Figure 2). For each peptide sample, several reference acids are selected. The reference acids are structurally similar organic compounds with known gas-phase acidities. A solution of the mixture of the peptide and a reference acid is introduced into the mass spectrometer, and a gas-phase proton-bound anionic cluster of peptide-reference acid is formed. The proton-bound cluster is mass isolated and subsequently fragmented via collision-induced dissociation (CID) experiments. The resulting fragment ion abundances are analyzed using a relationship between the acidities and the cluster ion dissociation kinetics. The gas-phase acidity of the peptide is then obtained by linear regression of the thermo-kinetic plots 17,18.
The method can be applied to a variety of molecular systems, including organic compounds, amino acids and their derivatives, oligonucleotides, and oligopeptides. By comparing the gas-phase acidities measured experimentally with those values calculated for different conformers, conformational effects on the acidities can be evaluated.

The determination of the gas-phase acidities of cysteine-containing oligopeptides is described. The experiments are performed using a triple quadrupole mass spectrometer. The relative acidities of the peptides are measured using collision-induced dissociation experiments, and the quantitative acidities are determined using the extended Cooks kinetic method.

Determinación de la acidez en fase gaseosa de oligopéptidos

Amino acid residues located at different positions in folded proteins often exhibit different degrees of acidities. For example, a cysteine residue ...

Investigación

Química

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

Síntesis Split-y-piscina y caracterización del péptido Terciario Amida Biblioteca

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

Quantitative Detection of Trace Explosive Vapors by Programmed Temperature Desorption Gas Chromatography-Electron Capture Detector

The direct liquid deposition of solution standards onto sorbent-filled thermal desorption tubes is used for the quantitative analysis of trace explosive vapor samples. The direct liquid deposition method yields a higher fidelity between the analysis of vapor samples and the analysis of solution standards than using separate injection methods for vapors and solutions, i.e., samples collected on vapor collection tubes and standards prepared in solution vials. Additionally, the method can account for instrumentation losses, which makes it ideal for minimizing variability and quantitative trace chemical detection. Gas chromatography with an electron capture detector is an instrumentation configuration sensitive to nitro-energetics, such as TNT and RDX, due to their relatively high electron affinity. However, vapor quantitation of these compounds is difficult without viable vapor standards. Thus, we eliminate the requirement for vapor standards by combining the sensitivity of the instrumentation with a direct liquid deposition protocol to analyze trace explosive vapor samples.

Trace explosive vapors of TNT and RDX collected on sorbent-filled thermal desorption tubes were analyzed using a programmed temperature desorption system coupled to GC with an electron capture detector. The instrumental analysis is combined with direct liquid deposition method to reduce sample variability and account for instrumentation drift and losses.

Detección Cuantitativa de la traza vapores explosivos por desorción a temperatura programada Gas Detector de Captura de Electrones Cromatografía

The direct liquid deposition of solution standards onto sorbent-filled thermal desorption tubes is used for the quantitative analysis of trace explosive ...

Supercritical Nitrogen Processing for the Purification of Reactive Porous Materials

Supercritical fluid extraction and drying methods are well established in numerous applications for the synthesis and processing of porous materials. Herein, nitrogen is presented as a novel supercritical drying fluid for specialized applications such as in the processing of reactive porous materials, where carbon dioxide and other fluids are not appropriate due to their higher chemical reactivity. Nitrogen exhibits similar physical properties in the near-critical region of its phase diagram as compared to carbon dioxide: a widely tunable density up to ~1 g ml-1, modest critical pressure (3.4 MPa), and small molecular diameter of ~3.6 &#197;. The key to achieving a high solvation power of nitrogen is to apply a processing temperature in the range of 80-150 K, where the density of nitrogen is an order of magnitude higher than at similar pressures near ambient temperature. The detailed solvation properties of nitrogen, and especially its selectivity, across a wide range of common target species of extraction still require further investigation. Herein we describe a protocol for the supercritical nitrogen processing of porous magnesium borohydride.

Nitrogen is an effective supercritical fluid for extraction or drying processes due to its small molecular size, high density in the near-liquid supercritical regime, and chemical inertness. We present a supercritical nitrogen drying protocol for the purification treatment of reactive, porous materials.

Procesamiento de nitrógeno supercrítico para la purificación de reactivos Materiales porosos

Supercritical fluid extraction and drying methods are well established in numerous applications for the synthesis and processing of porous materials. ...

A Quantitative Glycomics and Proteomics Combined Purification Strategy

There is a growing desire in the biological and clinical sciences to integrate and correlate multiple classes of biomolecules to unravel biology, define pathways, improve treatment, understand disease, and aid biomarker discovery. N-linked glycosylation is one of the most important and robust post-translational modifications on proteins and regulates critical cell functions such as signaling, adhesion, and enzymatic function. Analytical techniques to purify and analyze N-glycans have remained relatively static over the last decade. While accurate and effective, they commonly require significant expertise and resources. Though some high-throughput purification schemes have been developed, they have yet to find widespread adoption and often rely on the enrichment of glycopeptides. One promising method, developed by Thomas-Oates et al., filter aided N-glycan separation (FANGS), was qualitatively demonstrated on tissues. Herein, we adapted FANGS to plasma and coupled it to the individuality normalization when labeling with glycan hydrazide tags strategy in order to achieve accurate relative quantification by liquid chromatography mass spectrometry and enhanced electrospray ionization. Furthermore, we designed new functionality to the protocol by achieving tandem, shotgun proteomics and glycosylation site analysis on hen plasma. We showed that N-glycans purified on filter and derivatized by hydrophobic hydrazide tags were comparable in terms of abundance and class to those by solid phase extraction (SPE); the latter is considered a gold standard in the field. Importantly, the variability in the two protocols was not statistically different. Proteomic data that was collected in-line with glycomic data had the same depth compared to a standard trypsin digest. Peptide deamidation is minimized in the protocol, limiting non-specific deamidation detected at glycosylation motifs. This allowed for direct glycosylation site analysis, though the protocol can accommodate 18O site labeling as well. Overall, we demonstrated a new in-line high-throughput, unbiased, filter based protocol for quantitative glycomics and proteomics analysis.

A high-throughput protocol was developed for combined proteomics and glycomics purification and LC-MS/MS quantification in plasma. Deamidation analysis of N-linked glycosylation motifs was specific to deglycosylated sites. Accurate quantitation of N-glycans was achieved by coupling filter aided N-glycan separation to the individuality normalization when labeling with glycan hydrazide tags strategy.

Un Glicómica cuantitativa y Proteómica estrategia de purificación combinada

There is a growing desire in the biological and clinical sciences to integrate and correlate multiple classes of biomolecules to unravel biology, define ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Protocolo para la Síntesis de<em&gt; Ortho</em&gt; derivados de anilina -trifluoromethoxylated

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

Síntesis de Proteínas bioconjugados<em&gt; vía</em&gt; Química cisteína-maleimida

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Síntesis Facile de micelas similares a gusanos de luz visible mediada por dispersión Polimerización con catalizador Photoredox

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5&#39;-[CUA CGG AAU CAU]-3&#39; containing zero, one, or two modifications located at the C2&#39;-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2&#39;-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2&#039;-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

This article provides a detailed procedure on the solid-phase synthesis, purification, and characterization of dodecamers of RNA modified at the C2&#39;-O-position. UV-vis and circular dichroism photometric analyses are used to quantify and characterize structural aspects, i.e., single-strands or double-strands.

Protocolo para la síntesis en fase sólida de oligómeros de ARN que contiene un 2&#39;-<emO</em&gt; -tiofenilmetilo Modificación y caracterización mediante dicroísmo circular

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

Síntesis y análisis de espectrometría de masas de peptoides Oligo

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...