Para apoio financeiro que agradecem o EPSRC (Carreira Aceleração Fellowship para JAB; EP/J001538/1), a Ramsay Memorial Trust (Bolsa de Investigação para 2009-2011 JAB) e Imperial College London. Obrigado ao Prof Alan Armstrong para generoso apoio e conselhos.

1. Preparação de Iodoaziridines com Diiodomethyllithium <ol><li> Chama seco num balão de fundo redondo de 100 ml contendo uma barra de agitação e equipado com um septo, sob uma corrente de árgon, em seguida, deixa-se arrefecer até à temperatura ambiente, sob uma atmosfera de árgon. NOTA: material de vidro seco em um forno durante a noite (125 ° C) e arrefeceu-se até à temperatura ambiente de uma maneira análoga é também adequado. </li><li> Ao balão, adicionar 5,7 ml de THF anidro e 2,7 ml de Et2O anidro através de uma seringa, e hexametildisilazano recentemente destilado (1,50 mmol, 315 uL) através de uma microsseringa. </li><li> Agita-se a solução resultante e arrefece-se até -78 ° C num banho de gelo seco / acetona em um vaso Dewar de tamanho adequado para permitir que o balão seja bem submersa. Cobrir o Dewar com uma folha de alumínio, para minimizar a exposição do recipiente de reacção à luz. </li><li> Adicionar nBuLi (1,50 mmol, 0,60 mL, 2,5 M em hexanos) gota a gota através de uma seringa ao longo de 2-3 min a uma solução a -78 ° C.Deixar a mistura a agitar a -78 ° C durante mais 30 minutos para formar uma solução de 0,17 M de LiHMDS. CUIDADO: solução n BuLi é inflamável, corrosivo para a pele e pirofórico. O reagente em excesso na seringa deve ser extinta em conformidade. </li><li> Após 30 minutos, adicionar 1 ml de THF anidro a um balão de fundo redondo de 10 mL seco à chama, através de uma seringa, seguido por di-iodometano (1,70 mmol, 135 uL) através de uma micro-seringa e assegurar que eles são bem misturados. </li><li> Adicionar a solução de di-iodometano gota a gota ao longo de 2 min para a solução de hexametildissilazano de lítio, a -78 ° C. Deixar a solução durante 20 min a -78 ° C. </li><li> Durante este tempo, pesam-se N - [(E)-4-methylphenylmethylidene]-4-metilbenzenossulfonamida (137 mg, 0,50 mmol) em uma outra seco de chama 10 ml balão de fundo redondo e dissolve-se em 2,0 ml de THF anidro. </li><li> Após o tempo de desprotonação de 20 minutos, adiciona-se gota a gota a solução de imina e a solução diiodomethyllithium longo de 5 min a -78 &amp; #176; C. </li><li> Imediatamente após a adição gota a gota fica completa, levantar o recipiente de reacção do banho de gelo seco, e transferir para um banho de gelo / água a 0 ° C. Re-cover com papel alumínio e deixe por 15 min a 0 ° C. NOTA: A solução deve ser de cor laranja. </li><li> Após 15 min a 0 ° C, extingue-se a reacção pela adição de 30 ml de solução de bicarbonato de sódio aquoso saturado. Transferir a mistura para um funil de separação e adicionar 30 ml de CH 2 Cl 2. Agitar a mistura e remover o menor CH 2 Cl 2 camada. Repita este procedimento de extração mais duas vezes, e combinar os CH 2 Cl 2 camadas. </li><li> Adicionar sulfato de sódio para as camadas orgânicas para remover qualquer água presente na solução, em seguida, filtrou-se o sulfato de sódio e recolher o filtrado num frasco de 250 ml de fundo redondo. </li><li> Remover o solvente sob pressão reduzida num evaporador rotativo para se obter uma amostra impura do produto desejado iodoaziridine. </li></ol> 2. Avaliação da Estabilidade do produto para Fases Estacionárias para Cromatografia <ol><li> Dissolve-se a amostra de aziridina em bruto em CH 2 Cl 2 (16 ml) e adicionar 1,3,5-trimetoxibenzeno (28,0 mg, 0,167 mmol) como um padrão interno, assegurando este está completamente dissolvido. Tomar uma aliquota (2 ml) a partir desta mistura, remover o solvente sob pressão reduzida e analisar esta amostra por espectroscopia de RMN 1H. </li><li> Abra o gravado um espectro de RMN H utilizando software de processamento de RMN padrão. Em Mestrenova, clique direito do espectro e escolheu &quot;integração&quot;, depois em &quot;manual&quot; para fornecer a ferramenta de integração. Clique e arraste para cobrir a largura dos picos a 6,08 ppm e 4,87 ppm para integrar os sinais de padrão interno e o sinal CHI aziridina respectivamente. Clique com o botão direito do mouse sobre a integral para o pico em 6,08 ppm, selecione &quot;editar integral&quot; e altere o valor &quot;normalizado&quot; para 3.0. NÃOTE: medidas similares podem ser aplicados com outros pacotes de software. </li><li> Use o valor atualizado do integrante para o sinal aziridine CHI (4,87 ppm) para determinar o rendimento do iodoaziridine, aqui usando (100/3) x (o integral do sinal CHI), o que proporciona um rendimento calculado de 59%. NOTA: Tendo em conta a quantidade conhecida de padrão interno (0,167 mmol), e o pico do produto correspondente a um protão, o rendimento de iodoaziridine é calculada pela equação seguinte: 100 x (integrante do pico do produto) × (moles de padrão interno) / moles de material de partida. </li><li> Preparar suspensões dos seguintes fases estacionárias (25 g): sílica, sílica + 1% NEt 3 (trietilamina), alumina neutra, de alumina básica (actividade I), de alumina básica (actividade IV) e Florisil, cada um em 5% de EtOAc / hexano (50 ml), em seis frascos cónicos de 250 ml separados contendo barras agitadoras. Num outro balão cónico preparar uma solução a 5% de EtOAc / hexano (50 ml), para ser usado como uma experiência de controlo. CUIDADO: silicum gel, alumina e outras fases estacionárias empregadas são perigosos se inalados, por isso deve sempre ser tratado em uma coifa eficaz. </li><li> Adicionar 2 ml de alíquotas da solução padrão iodoaziridine / interno de cada um dos frascos cónicos à TA. Agita-se as misturas de lamas durante 30 min. NOTA: esta representa a duração do composto pode ser exposta à fase estacionária durante um processo normal de cromatografia em coluna flash. </li><li> Filtrar as misturas de polpa usando um funil sinterizado, e recolher o filtrado num frasco de 250 ml de fundo redondo. Lavar o resíduo sobre o funil sinterizado com CH 2 Cl 2 (2 x 30 ml). Repita este processo de filtragem para as suspensões restantes. NOTA: É necessário compensar o início de cada fase estacionária para dar tempo para a filtração e assim manter o mesmo tempo para cada um dos materiais em fase estacionária. </li><li> Remover o solvente a partir das amostras resultantes sob pressão reduzida, e analisar por 1 H RMN spectroSCOPY para calcular a quantidade de iodoaziridine recuperado em cada caso, conforme descrito na Seção 2.2. </li><li> Comparar os rendimentos de iodoaziridine obtidos a partir de cada fase estacionária testado com a obtida na Secção 2.1. NOTA: A amostra com o rendimento mais elevado, de preferência a mesma que em 2,1, indica a fase estacionária para cromatografia óptima. Neste exemplo, alumina básica (actividade IV) foi considerado o melhor fase estacionária para purificação. </li></ol> 3. Desactivação de alumina básica e purificação do Iodoaziridine <ol><li> Repetir Secção 1 para gerar a mistura iodoaziridine bruto. </li><li> Para gerar alumina básica (actividade IV), adiciona-se 100 g de alumina básica (actividade I) a um balão de 500 ml de fundo redondo e, em seguida, adicionam-se 10 ml de água ao balão e se encaixam com uma rolha de vidro. </li><li> Agitar o frasco vigorosamente até há nódulos são visíveis, indicando ainda se espalhando água durante todo o alumina. Permitir que a alumina se arrefecer para a TA. CUIDADO: a adsorçãoção de água é exotérmica, então o balão pode ficar quente e pode resultar em um acúmulo de pressão. Solte qualquer aumento de pressão com freqüência. </li><li> Purifica-se o iodoaziridine bruto por cromatografia de coluna usando alumina básica (actividade IV) como a fase estacionária, por eluição com hexano, para classificação de 5% de EtOAc / hexano. NOTA: altas concentrações de EtOAc não deve ser utilizado com alumina básica. Nestes casos, o éter dietílico podem ser utilizados em vez disso. </li><li> Combinar o produto contendo as fracções e remover o solvente sob pressão reduzida para se obter o iodoaziridine puro. </li></ol>

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

Um processo para a preparação de cis diastereosselectiva - N-Ts-iodoaziridines é descrito, juntamente com um protocolo de estudo de estabilidade para indicar quantitativamente a melhor fase estacionária para purificação de compostos potencialmente instáveis ​​por cromatografia em coluna flash. Prevê-se que o acesso aos iodoaziridines através desta abordagem permitirá métodos para aceder a uma vasta gama de aziridinas a ser desenvolvido, por derivatização do anel intacto. <p class="...

O objectivo deste método é a de preparar iodoaziridines que oferecem potencial para posterior funcionalização de derivados de aziridina. O método incorpora um protocolo para a selecção quantitativa da fase estacionária para cromatografia óptima. Aziridinas, como anéis de três membros, possuem inerente tensão anel que os torna importantes blocos de construção em química orgânica 1. Eles exibem uma vasta gama de reactividade muitas vezes envolvendo a abertura do anel da aziridina de 2,3, em particular como intermediários na síntese de aminas funcionalizadas 4,5, ou a formação de outras azoto contendo heterociclos 6,7. A síntese de uma série de derivados de aziridina de funcionalização de um precursor contendo um anel de aziridina intacto tem emergido como uma estratégia viável 8. Funcional troca grupo-metal, para gerar um anião aziridinilo, e da reacção com electró tem demonstrado ser eficaz <sup&gt; 9,10,11, e recentemente desprotonação régio-e estereo-selectiva de aziridinas protegidos em N foi também conseguida 12-15. Muito recentemente, catalisado por paládio métodos de acoplamento cruzado para formar aziridinas a partir de precursores de arilo aziridina funcionalizadas foi desenvolvido por Vedejs 16,17, e nos 18. A química de heteroátomos substituído aziridinas abre questões fascinantes de reatividade e estabilidade 19. Nós estávamos interessados ​​na preparação de iodoaziridines como um grupo funcional romance que oferece o potencial para fornecer precursores para uma ampla gama de derivados com reatividade complementar a reações aziridina de funcionalização existentes. Em 2012, relatou a primeira preparação de aril N-Boc-iodoaziridines 20, e muito recentemente relatou a preparação de aril e alquil N-Ts-21 iodoaziridines substituído. O método para aceiodoaziridines ss usa diiodomethyllithium, um reagente que também foi recentemente utilizada na preparação de diiodoalkanes 22,23, 22,24 diiodomethylsilanes, e iodetos de vinilo 25-27. A natureza carbenoid-like deste reagente requer preparação e utilização em baixas temperaturas 22,28. As técnicas e as condições utilizadas para a geração de diiodomethyllithium na preparação de iodoaziridines são descritos abaixo. Enquanto sílica emergiu como o material de escolha para a cromatografia de 29, provou ser inadequado para a purificação das N-Ts-iodoaziridines. A sílica gel é geralmente o primeiro e único material sólido fase utilizada em cromatografia flash em química orgânica, devido à disponibilidade e eficazes separações. No entanto, a natureza ácida do gel de sílica pode provocar a decomposição de substratos sensíveis durante a purificação, impedindo o isolamento do material desejado. Enquanto outra ruafases ationary ou géis de sílica modificados estão disponíveis para a cromatografia de 30, não havia maneira de avaliar a compatibilidade de uma molécula alvo para estes diferentes materiais. Devido à natureza sensível das iodoaziridines, estabelecemos um protocolo para avaliar a estabilidade de um composto de uma série de fases estacionárias 21, o que é demonstrado aqui. Este tem o potencial para aplicação na síntese de uma vasta gama de compostos com grupos funcionais sensíveis. O protocolo a seguir fornece acesso eficiente a iodoaziridines N-Ts, permitindo a síntese diastereosseletivo de ambos alquilo e aromáticos cis-iodoaziridines em alto rendimento.

<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>
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		<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

A preparação altamente diastereosseletivo de cis - N-Ts-iodoaziridines através da reação de diiodomethyllithium com N-Ts aldiminas é descrito. Diiodomethyllithium é preparado por desprotonação de diiodometano com LiHMDS, em uma mistura de éter de THF / éter dietílico, a -78 ° C no escuro. Estas condições são essenciais para a estabilidade do reagente LICHI 2 gerado. A adição gota a gota subsequente de N-Ts aldiminas à solução diiodomethyllithium pré-formado oferece uma amino-di-iodeto intermediário, o qual não é isolado. Aquecimento rápido da mistura de reacção para 0 ° C promove a ciclização para se obter iodoaziridines exclusiva com cis-diastereosselectividade. As fases de adição e ciclização da reacção é mediada em um frasco de reacção através de um cuidadoso controlo da temperatura. Devido à sensibilidade dos iodoaziridines a purificação, a avaliação de métodos adequados de purification é necessária. Um protocolo para avaliar a estabilidade de compostos sensíveis à fase estacionária para a cromatografia de coluna é descrita. Este método é adequado para aplicar novas iodoaziridines, ou outros novos compostos potencialmente sensíveis. Consequentemente, este método pode encontrar aplicação no conjunto de projetos sintéticos. O processo envolve em primeiro lugar a avaliação do rendimento da reacção, antes da purificação, por espectroscopia de RMN 1 H a comparação com um padrão interno. As porções de mistura de produto impuro são então expostas a suspensões de várias fases estacionárias adequadas para cromatografia, num sistema solvente adequado, como o eluente em cromatografia flash. Depois de se agitar durante 30 min a imitam cromatografia, seguido por filtragem, as amostras são analisadas por espectroscopia de RMN de 1H. Os rendimentos calculados para cada fase estacionária são então comparados para que inicialmente obtido a partir da mistura de reacção em bruto. Os resultados obtidos fornecem uma avaliação quantitativa da tque a estabilidade do composto para as diferentes fases estacionárias; daí o óptimo pode ser seleccionado. A escolha de alumina básica, modificado para a actividade IV, como uma fase estacionária adequada, permitiu o isolamento de determinados iodoaziridines em excelente rendimento e pureza.

O procedimento descrito proporciona cis - (±)-2-iodo-3-(4-tolil) -1 - (4-tolilsulfonil) aziridina como um único diastereoisómero e com uma pureza excelente (Figura 1). Antes da purificação, com um rendimento de 59% do produto iodoaziridine foi calculado por espectroscopia de RMN 1H. No entanto, este iodoaziridine foi particularmente difícil de purificar e foi submetido a decomposição significativa em sílica. A purificação sobre alumina básica (actividade IV), tal como det...

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

Um protocolo para o diastereosseletivo preparação de um pote de cis - N-Ts-iodoaziridines é descrito. A geração de diiodomethyllithium, além de N-Ts aldiminas e ciclização do amino-gem-di-iodeto intermediário para iodoaziridines é demonstrada. Também está incluído um protocolo para avaliar rapidamente e quantitativamente a fase estacionária mais adequada para a purificação por cromatografia.

Síntese e Purificação de Iodoaziridines Envolvendo Quantitative Seleção do Optimal fase estacionária para cromatografia

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

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12.4K visualizações.  Imperial College London.  Um protocolo para o diastereosseletivo preparação de um pote de cis - N-Ts-iodoaziridines é descrito. A geração de diiodomethyllithium, além de N-Ts aldiminas e ciclização do amino-gem-di-iodeto intermediário para iodoaziridines é demonstrada. Também está incluído um protocolo para avaliar rapidamente e quantitativamente a fase estacionária mais adequada para a purificação por cromatografia. 

Vídeo: 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.

Determinação da acidez em fase gasosa de Oligopeptídeos

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

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.

Split-and-piscina Síntese e Caracterização de Peptídeos Terciário Amide 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.

Detecção quantitativa de rastreamento vapores explosivos por temperatura programada Desorption Gas Chromatography-Electron Captura Detector

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.

Processamento de nitrogênio supercrítico para a purificação de Reativos Porous Materials

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.

A Quantitative Glycomics e Proteomics Combinada estratégia de purificação

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 a Síntese de Derivados de Anilina Orto-trifluorometoxilados

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.

Síntese de Bioconjugados de proteínas<em&gt; via</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.

Síntese Facile de micelas Worm-like por luz visível Mediated Dispersão Polimerização Usando Photoredox Catalisador

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 síntese de fase sólida de oligómeros de ARN contendo um 2&#39;-<em&gt; O</em&gt; -tiofenilmetilo Modificação e Caracterização através do 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.

Síntese e análise de espectrometria de massa de Oligo-peptoids

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