1 Síntesis de la N, N &#39;-. (, N-alcano-diilo 1) diisonicotinamide <ol><li> Secar un solo cuello o matraz de fondo redondo de tres bocas en un horno (100 º C, 1 h) para asegurar que se elimina toda la humedad. </li><li> Añadir ácido isonicotínico sólido, o su derivado, en el matraz junto con una barra de agitación magnética. Si el ligando (s) diaminoalcano son sólidos a temperatura ambiente, a continuación, 0,5 mol (a los moles número de ácido isonicotínico) se añadió al matraz en esta etapa. </li><li> Se tapa el cuello (s) del matraz con tabiques de caucho y reemplazar el aire en el matraz con nitrógeno, ya sea a través de una corriente continua de nitrógeno o mediante el uso de globos lleno de nitrógeno. </li><li> Utilice una aguja hipodérmica y una jeringa para añadir dimetilformamida o dimetilsulfóxido anhidro (4 ml por 500 mg de ácido isonicotínico o ácido 2-metil-isonicotínico) para disolver el sólido. Si los sólidos no se disuelven fácilmente, a continuación, calentar la solución suavemente. </li><li> Añadir 7 equivalentes molares (a la unamonte de ácido isonicotínico utilizado) de trietilamina (base débil) y 0,5 equivalentes molares del diaminoalcano. Si la solución es un líquido a temperatura ambiente, a continuación, añadir 1,5 equivalentes molares. </li><li> Añadir un equivalente molar de anhídrido 1-propilfosfónico (agente de acoplamiento) con agitación continua y permita que la reacción se complete durante 5-12 horas. </li></ol> 2. La purificación de los ligandos <ol><li> Para bispiridina ligandos hechas usando ligandos diaminoalcano con 10 o más grupos metileno, esperar a que los productos a precipitar de la solución a medida que avanza la reacción. </li><li> Para bispiridina ligandos hechas usando diaminooctano, precipitar el producto mediante la adición de ~ 40 ml de agua. </li><li> Para bispiridina hizo usando diaminoalcanos de cinco y cincuenta y ocho grupos metileno, añadir ~ 40 ml de agua y permite que los compuestos se cristalizan a más de 1-3 días. </li><li> Recoger cada ligando bispiridina por filtración a vacío y se recristaliza a partir de aproximadamente 400-500 ml de agua hirviendo por 200mg de ligando. Nota: Se necesita más agua para los ligandos ya bispiridina debido a su reducida solubilidad en agua. </li><li> Añadir NaOH y KOH (pH 9) a la solución para asegurar que los compuestos son bases libres mediante recristalización. </li></ol> 3. Síntesis y purificación de los dinucleares de platino Complejos <ol><li> Disolver completamente trans-diamminodichloridoplatinum (II), transplatin, en (70-80 º C) agua caliente (150 ml por 200 mg de transplatin) para producir una solución de color amarillo claro con fuerza. </li><li> Añadir un 0,5 equivalente molar del ligando bispiridina y se agita la solución a temperatura hasta que se disuelva ligando (solución clara). Espere a que la solución para convertir casi incoloro, se apaga el fuego, y se agita a temperatura ambiente durante un par de horas adicionales. </li><li> Eliminar el disolvente por evaporación rotatoria, que dar un polvo de color amarillo. </li><li> Purifica, el complejo de platino (es) por disolución en una cantidad mínima de agua caliente (~ 50 y# 186; C). Si los sólidos restantes de color amarillo o blanco están presentes, después se filtra fuera de estos. </li><li> Añadir acetona a la solución hasta que se forma un precipitado blanco que parece ser una forma polimérica de los complejos metálicos y representa hasta el 10% del producto de reacción. Continuar la adición de acetona (~ extras 20-30 ml) hasta que no aparezca más precipitado. Nota: este precipitado blanco es una impureza. </li><li> Eliminar este precipitado por filtración de los contenidos a través de papel de filtro de nylon (0,2 m de tamaño de poro) y rotatorio evaporación de la solución restante a sequedad, lo que dió un producto puro. Nota: Si es necesario, etapas de precipitación en acetona y luego adicionales se pueden realizar hasta el complejo es puro. </li></ol>

<ol>
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Cancer. 43, 2631-2633 (2007).</li><li>Markman, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+features+of+hypersensitivity+reactions+to+carboplatin.">Clinical features of hypersensitivity reactions to carboplatin.</a> J Clin. Oncol. 17, 1141-1145 (1999).</li><li>Ding, D., Allman, B. 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Chem. - Anti-Cancer Agents. 5, 267-279 (2005).</li><li>Beale, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+phase+I+clinical+and+pharmacological+study+of+cis-diamminedichloro(2-methylpyridine)+platinumm+II+(AMD473).">A phase I clinical and pharmacological study of cis-diamminedichloro(2-methylpyridine) platinumm II (AMD473).</a> British journal of cancer. 88, 1128-1134 (2003).</li><li>Sessa, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+and+pharmacological+phase+I+study+with+accelerated+titration+design+of+a+daily+times+five+schedule+of+BBR3464,+a+novel+cationic+triplatinum+complex.">Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex.</a> Ann. Oncol. 11, 977-983 (2000).</li><li>Brown, S. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combining+aspects+of+the+platinum+anticancer+drugs+picoplatin+and+BBR3464+to+synthesize+a+new+family+of+sterically+hindered+dinuclear+complexes;+their+synthesis,+binding+kinetics+and+cytotoxicity.">Combining aspects of the platinum anticancer drugs picoplatin and BBR3464 to synthesize a new family of sterically hindered dinuclear complexes; their synthesis, binding kinetics and cytotoxicity.</a> Dalton Trans. 41, 11330-11339 (2012).</li><li>Still, B. M., Anil Kumar, P. G., Aldrich-Wright, J. R., Price, W. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=195Pt+NMR+-+Theory+and+application.">195Pt NMR - Theory and application.</a> Chem. Soc. Rev. 36, 665-686 (2007).</li><li>Wheate, N. 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Los autores no tienen nada que revelar.

En este trabajo complejos de platino dinucleares han sido sintetizados como agentes anticancerosos potenciales. Al hacerlo ligandos bispiridina puente se sintetizaron a través de una reacción de acoplamiento de amida usando ácido isonicotínico y diaminoalcanos de longitud variable. Anteriormente se ha informado de la síntesis de bispiridina ligandos y sus análogos de metilo con 2 a 8 grupos metileno y sus respectivos complejos de platino. En este trabajo, el método de síntesis y purificación ha sido revisada po...

Medicamentos contra el cáncer de platino siguen siendo uno de la familia más ampliamente utilizado de los agentes en el tratamiento del cáncer humano 1. A pesar de su éxito, que están limitadas en su aplicación por los efectos secundarios limitantes de la dosis graves 2-4. Las dosis limitadas que pueden ser administrados a pacientes que también significa que los tumores pueden desarrollar resistencia 5. Como tales, los nuevos medicamentos se siguen desarrollando para mejorar el perfil de efectos secundarios y superar la resistencia adquirida, como phenanthriplatin 6 y 7 phosphaplatin. A finales de 1990, un fármaco de platino trinuclear fue desarrollado, BBR3464 (Esquema 1) 8, es decir hasta 1000 veces más citotóxica in vitro de los principales fármacos de platino, cisplatino. BBR3464 también es capaz de superar la resistencia adquirida en un panel de líneas celulares de cáncer humano 9. Desafortunadamente, el aumento de la actividad de BBR3464 se corresponde con 50 - a 100 - veces mayor toxicidad, quelimita su uso 10-12. También se degrada fácilmente en el cuerpo, es decir, un poco del medicamento alcanza núcleos intactos cáncer 9. Picoplatin es un fármaco a base de platino mononucleares que contiene un ligando 2-metil-piridina (Esquema 1) 13. El grupo metilo de este fármaco protege del ataque por nucleófilos biológicos; en particular, la cisteína y la metionina que contiene péptidos / proteínas 14-16. Como tal, el fármaco es muy estable y tiene una concentración mucho más alta que llega a los núcleos de cáncer en comparación con tanto BBR3464 y cisplatino 17. Su reactividad reducida también significa picoplatin tiene una dosis máxima tolerada más alta en comparación con BBR3464 y cisplatino 10,18,19. Por tanto, este proyecto se propuso combinar las propiedades de BBR3464 y picoplatin para producir nuevos medicamentos que son capaces de superar la resistencia adquirida que se vea mejorada la estabilidad biológica y menos severa lado-efeCTS (por ejemplo, Figura 1). De este modo, una gama de complejos de platino dinucleares se prepararon con ligandos bispiridina puente 20. Los ligandos se realizan mediante reacciones de acoplamiento de amida con ácido isonicotínico, o sus derivados, como el 2-metil-isonicotínico, diaminoalcanos de longitud variable. La reacción de un equivalente molar de los ligandos con dos equivalentes molares de transplatin produce los complejos de platino deseados (Esquema 1).

<table border="0" cellpadding="0" cellspacing="0" width="782">
	<tbody>
		<tr height="24">
			<td height="24" style="height:24px;width:297px;">D2O</td>
			<td style="width:175px;">Aldrich</td>
			<td align="right" style="width:159px;">151882</td>
			<td style="width:152px;">99.9% D</td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;width:297px;">DMSO-d6</td>
			<td style="width:175px;">Aldrich</td>
			<td align="right" style="width:159px;">156914</td>
			<td style="width:152px;">99.96% D</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:297px;">1,8-diaminooctane</td>
			<td style="width:175px;">Aldrich</td>
			<td style="width:159px;">D22401</td>
			<td align="right" style="width:152px;">98%</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:297px;">1,10-diaminodecane</td>
			<td style="width:175px;">Aldrich</td>
			<td style="width:159px;">D14204</td>
			<td align="right" style="width:152px;">98%</td>
		</tr>
		<tr height="80">
			<td height="80" style="height:80px;width:297px;">1,12-diaminododecane</td>
			<td style="width:175px;">Aldrich</td>
			<td style="width:159px;">D1,640-1</td>
			<td align="right" style="width:152px;">98%</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:297px;">Isonicotinic acid</td>
			<td style="width:175px;">Aldrich</td>
			<td style="width:159px;">I17508</td>
			<td align="right" style="width:152px;">99%</td>
		</tr>
		<tr height="120">
			<td height="120" style="height:120px;width:297px;">1-Propylphosphonic anhydride solution</td>
			<td style="width:175px;">Aldrich</td>
			<td align="right" style="width:159px;">431303</td>
			<td style="width:152px;">50 wt% in ethyl acetate</td>
		</tr>
		<tr height="100">
			<td height="100" style="height:100px;width:297px;">Trans-diaminodichloridoplatinum(II)</td>
			<td style="width:175px;">Aldrich</td>
			<td style="width:159px;">P1525</td>
			<td style="width:152px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Dimethylsulfoxide</td>
			<td style="width:175px;">Sigma-Aldrich</td>
			<td style="width:159px;">Z76855</td>
			<td style="width:152px;">&#62;99.9%, anhydrous</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">N,N&#8217;-dimethylformamide</td>
			<td style="width:175px;">Sigma-Aldrich</td>
			<td align="right" style="width:159px;">227056</td>
			<td style="width:152px;">99.8%, anhydrous</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Triethylamine</td>
			<td style="width:175px;">Sigma-Aldrich</td>
			<td style="width:159px;">T0886</td>
			<td style="width:152px;">&#62;99%</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Nylon filter membranes</td>
			<td style="width:175px;">Whatman</td>
			<td style="width:159px;">7402-004</td>
			<td style="width:152px;">Pore size, 0.2 &#181;m</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Equipment</td>
			<td style="width:175px;"></td>
			<td style="width:159px;"></td>
			<td style="width:152px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Magnetic stirring hotplate</td>
			<td style="width:175px;"></td>
			<td style="width:159px;"></td>
			<td style="width:152px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Magnetic stirring bar&#160;</td>
			<td style="width:175px;"></td>
			<td style="width:159px;"></td>
			<td style="width:152px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Round bottom or three neck flask</td>
			<td style="width:175px;"></td>
			<td style="width:159px;"></td>
			<td style="width:152px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:297px;">Rubber septums of sufficient size for chosen round bottom or three neck flask</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">5 mL hypodermic syringes</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Hypodermic needles</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Rubber party ballons</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Rubber bands</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;width:297px;">A source of N2 gas</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Rotary evaporator</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Drying oven</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">NMR tubes</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">NMR spectrometer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">500 mL beakers</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:297px;">Glass or plastic pipettes</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

amide coupling reaction for the synthesis of bispyridine-based ligands and their complexation to platinum as dinuclear anticancer agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is 1H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.

Los ligandos bispiridina y sus respectivos complejos de platino dinucleares se caracterizan por 1 H, 13 C y 195 Pt RMN (Tablas 1 y 2), y espectroscopia de masas con ionización por electrospray. Puntos de fusión precisas se pueden determinar usando calorimetría diferencial de barrido y la pureza se determina mejor mediante análisis elemental para C, H y N contenido en porcentaje. De mayor uso es de 1 H RMN ya que es rápido y fácil de usar...

Watch this Scientific Journal Video about Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents at JoVE.com

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Este protocolo describe el uso de reacciones de acoplamiento de amida del ácido isonicotínico y diaminoalcanos para formar ligandos puente adecuados para su uso en la síntesis de complejos de platino multinucleares, que combinan aspectos de los medicamentos contra el cáncer BBR3464 y picoplatin.

Amida de reacción para la Síntesis de ligandos basados ​​en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. ...

amide-coupling-reaction-for-synthesis-bispyridine-based-ligands-their

Research

JoVE Journal

Chemistry

13.8K vistas.  The University of Sydney.  Este protocolo describe el uso de reacciones de acoplamiento de amida del ácido isonicotínico y diaminoalcanos para formar ligandos puente adecuados para su uso en la síntesis de complejos de platino multinucleares, que combinan aspectos de los medicamentos contra el cáncer BBR3464 y picoplatin. 

Video: Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay

Titanium (IV) and vanadium (V) complexes are highly potent anticancer agents. A challenge in their synthesis refers to their hydrolytic instability; therefore their preparation should be conducted under an inert atmosphere. Evaluation of the anticancer activity of these complexes can be achieved by the MTT assay.
The MTT assay is a colorimetric viability assay based on enzymatic reduction of the MTT molecule to formazan when it is exposed to viable cells. The outcome of the reduction is a color change of the MTT molecule. Absorbance measurements relative to a control determine the percentage of remaining viable cancer cells following their treatment with varying concentrations of a tested compound, which is translated to the compound anticancer activity and its IC50 values. The MTT assay is widely common in cytotoxicity studies due to its accuracy, rapidity, and relative simplicity.
Herein we present a detailed protocol for the synthesis of air sensitive metal based drugs and cell viability measurements, including preparation of the cell plates, incubation of the compounds with the cells, viability measurements using the MTT assay, and determination of IC50 values.

A method for synthesis of air-sensitive titanium and vanadium anticancer agents is described, along with the evaluation of their cytotoxic activity towards human cancer cell line by the MTT Assay.

Anticancerosos complejos metálicos: Síntesis y Evaluación de la citotoxicidad por el ensayo MTT

Titanium (IV) and vanadium (V) complexes are highly potent anticancer agents. A challenge in their synthesis refers to their hydrolytic instability; ...

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 ...

Synthesis of Non-uniformly Pr-doped SrTiO3 Ceramics and Their Thermoelectric Properties

We demonstrate a novel synthesis strategy for the preparation of Pr-doped SrTiO3 ceramics via a combination of solid state reaction and spark plasma sintering techniques. Polycrystalline ceramics possessing a unique morphology can be achieved by optimizing the process parameters, particularly spark plasma sintering heating rate. The phase and morphology of the synthesized ceramics were investigated in detail using X-ray diffraction, scanning electron microcopy and energy-dispersive X-ray spectroscopy. It was observed that the grains of these bulk Pr-doped SrTiO3 ceramics were enhanced with Pr-rich grain boundaries. Electronic and thermal transport properties were also investigated as a function of temperature and doping concentration. Such a microstructure was found to give rise to improved thermoelectric properties. Specifically, it resulted in a significant improvement in carrier mobility and the thermoelectric power factor. Simultaneously, it also led to a marked reduction in the thermal conductivity. As a result, a significant improvement (> 30%) in the thermoelectric figure of merit was achieved for the whole temperature range over all previously reported maximum values for SrTiO3-based ceramics. This synthesis demonstrates the steps for the preparation of bulk polycrystalline ceramics of non-uniformly Pr-doped SrTiO3.

Synthesis of Non-uniformly Pr-doped SrTiO3 Ceramics and Their Thermoelectric Properties

A protocol for the synthesis and processing of polycrystalline SrTiO3 ceramics doped non-uniformly with Pr is presented along with the investigation of their thermoelectric properties.

Síntesis de dopado-Pr no uniformemente SrTiO<sub&gt; 3</sub&gt; Cerámica y sus propiedades termoeléctricas

We demonstrate a novel synthesis strategy for the preparation of Pr-doped SrTiO3 ceramics via a combination of solid state reaction and spark plasma ...

Synthesis and Reaction Chemistry of Nanosize Monosodium Titanate

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the material with Au(III) ions. The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST), with several key modifications, including altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The resultant nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150&#160;nm. The nMST material was found to have a Brunauer-Emmett-Teller (BET) surface area of 285 m2g-1, which is more than an order of magnitude higher than the micron-sized MST. The isoelectric point of the nMST measured 3.34 pH units, which is a pH unit lower than that measured for the micron-size MST. The nMST material was found to serve as an effective ion exchanger under weakly acidic conditions for the preparation of an Au(III)-exchange nanotitanate. In addition, the formation of the corresponding peroxotitanate was demonstrated by reaction of the nMST with hydrogen peroxide.

The surfactant mediated sol-gel synthesis of nanosized monosodium titanate is described, along with preparation of the corresponding peroxide modified material. An ion-exchange reaction with Au(III) is also presented.

Síntesis y Reacción Química de tamaño nanométrico monosódico titanato

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST-1 como un catalizador heterogéneo para la Síntesis de la vainillina

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

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 ...

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single molecule level. An electrostatic self-assembly and covalent fixation (ESA-CF) process is used for the synthesis of the cyclic poly(tetrahydrofuran) (poly(THF)). The diffusive motion of individual cyclic polymer chains in a melt state is visualized using single molecule fluorescence imaging by incorporating a fluorophore unit in the cyclic chains. The diffusive motion of the chains is quantitatively characterized by means of a combination of mean-squared displacement (MSD) analysis and a cumulative distribution function (CDF) analysis. The cyclic polymer exhibits multiple-mode diffusion which is distinct from its linear counterpart. The results demonstrate that the diffusional heterogeneity of polymers that is often hidden behind ensemble averaging can be revealed by the efficient synthesis of the cyclic polymers using the ESA-CF process and the quantitative analysis of the diffusive motion at the single molecule level using the MSD and CDF analyses.

A protocol for the synthesis and characterization of diffusive motion of cyclic polymers at the single molecule level is presented.

Síntesis de polímeros cíclicos y caracterización de su movimiento difusivo en el estado fundido en la molécula de un solo nivel

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single ...

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance imaging (MRI). Their purpose is to enhance the relaxation rate of water protons in tissue, thus increasing the MR image contrast and the specificity of the MRI measurements. Current clinically approved contrast agents are low molecular weight molecules that are rapidly cleared from the body. The use of dendrimers as carriers of paramagnetic chelators can play an important role in the future development of more efficient MRI contrast agents. Specifically, the increase in local concentration of the paramagnetic species results in a higher signal contrast. Furthermore, this CA provides a longer tissue retention time due to its high molecular weight and size. Here, we demonstrate a convenient procedure for the preparation of macromolecular MRI contrast agents based on poly(amidoamine) (PAMAM) dendrimers with monomacrocyclic DOTA-type chelators (DOTA &#8211; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate). The chelating unit was appended by exploiting the reactivity of the isothiocyanate (NCS) group towards the amine surface groups of the PAMAM dendrimer to form thiourea bridges. Dendrimeric products were purified and analyzed by means of nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Finally, high resolution MR images were recorded and the signal contrasts obtained from the prepared dendrimeric and the commercially available monomeric agents were compared.

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

This protocol describes the preparation and characterization of a dendrimeric magnetic resonance imaging (MRI) contrast agent that carries cyclen-based macrocyclic chelates coordinating paramagnetic gadolinium ions. In a series of MRI experiments in vitro, this agent produced an amplified MRI signal when compared to the commercially available monomeric analogue.

Preparación y<em&gt; In Vitro</em&gt; Caracterización de los agentes de contraste basados ​​en dendrímeros de Imágenes por Resonancia Magnética

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance ...

Synthesis of Platinum-nickel Nanowires and Optimization for Oxygen Reduction Performance

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen reduction reaction. Spontaneous galvanic displacement was used to deposit Pt layers onto Ni nanowire substrates. The synthesis approach produced catalysts with high specific activities and high Pt surface areas. Hydrogen annealing improved Pt and Ni mixing and specific activity. Acid leaching was used to preferentially remove Ni near the nanowire surface, and oxygen annealing was used to stabilize near-surface Ni, improving durability and minimizing Ni dissolution. These protocols detail the optimization of each post-synthesis processing step, including hydrogen annealing to 250 &#176;C, exposure to 0.1 M nitric acid, and oxygen annealing to 175 &#176;C. Through these steps, Pt-Ni nanowires produced increased activities more than an order of magnitude than Pt nanoparticles, while offering significant durability improvements. The presented protocols are based on Pt-Ni systems in the development of fuel cell catalysts. These techniques have also been used for a variety of metal combinations, and can be applied to develop catalysts for a number of electrochemical processes.

&#160; The protocol describes the synthesis and electrochemical testing of platinum-nickel nanowires. Nanowires were synthesized by the galvanic displacement of a nickel nanowire template. Post-synthesis processing, including hydrogen annealing, acid leaching, and oxygen annealing were used to optimize nanowire performance and durability in the oxygen reduction reaction.

Síntesis de nanocables de platino y níquel y optimización de rendimiento de reducción de oxígeno

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

Preparación de iones Aziridinium bicíclica estable y su apertura para la síntesis de Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Amida de reacción para la Síntesis de ligandos basados ​​en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos

Amida de reacción para la Síntesis de ligandos basados en bispiridina y su complejación a Platinum como dinucleares Agentes anticancerígenos