This work was supported by the World Premier International Research Center (WPI) Initiative on Materials Nanoarchitectonics and a Grant-in-Aid for Challenging Exploratory Research (No. 26620139), both of which were provided from MEXT, Japan.

1. Preparación de metal Monómeros Complex (2 CAS RN 1381776-70-0, 3 CAS RN 1261168-42-6, 4 CAS RN 1261168-43-7; Figura 1) <ol><li> Preparación de Ru monómero 2 <ol><li> Combinar el precursor orgánico (5 9 CAS RN 1381776-63-1; Figura 1) (380 mg, 0,48 mmol) y [Ru (cimeno p) Cl 2] dímero (224 mg, 0,37 mmol) con una barra de agitación en una 100 de un solo cuello matraz de fondo redondo ml. </li><li> Añadir metanol (MeOH) (25 ml) a la mezcla, conectar un condensador a la articulación del matraz, y se agita la suspensión a 65 ° C durante 3 horas en un baño de aceite de temperatura controlada. </li><li> Se enfría la mezcla de reacción a temperatura ambiente y filtrar la suspensión a través de un papel de filtro por succión. </li><li> Lavar el residuo en el filtro a fondo con MeOH hasta que el filtrado se vuelve visualmente incoloro y se seca el residuo bajo presión reducida. </li><li> Combinar el residuo y 4 &#39;- (4-metilfenil) -2,2&#39;: 6 y# 39;, 2 &quot;-terpiridina (216 mg, 0,68 mmol) con una barra de agitación en 100 ml de una boca del matraz de fondo redondo. </li><li> Añadir MeOH (22,5 ml) y agua (2,5 ml) a la mezcla, conectar un condensador a la articulación del matraz, y se agita la suspensión a 70 ° C durante 16 hr. </li><li> Se enfría la mezcla de reacción a temperatura ambiente y filtrar la suspensión. </li><li> Se seca el residuo del filtro a presión reducida y se disuelven en sulfóxido de dimetilo (DMSO) (3 ml). </li><li> Añadir la solución de DMSO lentamente a un exceso de acetato de etilo (EtOAc). </li><li> Se filtra la suspensión resultante, se lava el residuo sobre el filtro con EtOAc, y se seca bajo presión reducida. </li></ol></li><li> Preparación de Pt monómero 3 <ol><li> Combinar el precursor orgánico (6 4 CAS RN 1261168-39-1; Figura 1) (360 mg, 0,50 mmol) y Pt (cicloocta-1,5-dieno) Cl 2 (195 mg, 0,52 mmol) con una barra de agitación en a 100 ml de un solo cuello matraz de fondo redondo. &lt;/ Li&gt; <li> Añadir MeOH (15 ml) a la mezcla, conectar un condensador a la articulación del matraz, y se agita la suspensión a 65 ° C durante 12 hr. </li><li> Se enfría la mezcla de reacción a temperatura ambiente y filtrar la suspensión. </li><li> Lavar el residuo en el filtro a fondo con MeOH y se seca bajo presión reducida. </li></ol></li><li> Preparación de Rh monómero 4 <ol><li> Combinar el precursor orgánico (6; Figura 1) (360 mg, 0,50 mmol) y RhCl 3 · 3H 2 O (137 mg, 0,52 mmol) con una barra de agitación en 100 ml de un solo cuello matraz de fondo redondo. </li><li> Añadir MeOH (50 ml) a la mezcla, conectar un condensador a la articulación del matraz, y se agita la suspensión a 65 ° C durante 12 hr bajo una atmósfera de N 2. </li><li> Se enfría la mezcla de reacción a temperatura ambiente y filtrar la suspensión. </li><li> Lavar el residuo en el filtro a fondo con MeOH y se seca bajo presión reducida. </li></ol></li></ol&gt; 2. Preparación de metal soluble en agua-orgánico complejo conjunto 1 <ol><li> Fmoc La desprotección de TG Sieber Resina <ol><li> Combine la resina TG Sieber como comprar-(135 mg) con una barra de agitación en un matraz de 10 ml de 2 bocas que lleva un drenaje en el fondo, equipado con un filtro de vidrio y una de 2 vías llave de paso (Figura 2a). Conectar una llave de paso de 3 vías y un tapón de vidrio a las articulaciones del matraz. </li><li> Intercambiar la atmósfera interna con N2 mediante el uso de una línea de vacío, y después hinchar la resina con diclorometano anhidro de grado (CH 2 Cl 2) (1 ml) (Figura 2b). </li><li> Añadir dimetilformamida anhidra grado (DMF) (3 ml) y piperidina (1 ml) en este orden y se agitó la mezcla durante 2,5 hr a temperatura ambiente. </li><li> Retirar la solución por filtración a través del drenaje. Lavar la resina con anhidro de grado MeOH (3 ml, 3 minutos de agitación) y CH anhidro de grado 2 Cl 2 (3 ml, 3min de agitación) alternativamente tres veces y después con anhidro de grado CH 2 Cl 2 (3 ml, 3 minutos de agitación) cuatro veces (Figura 2c). </li><li> Combinar todas las soluciones obtenidas en 2.1.4 y diluir con acetonitrilo (CH 3 CN) a un volumen de 50 ml. Transferir una alícuota (1 ml) de la solución resultante en una cubeta de cuarzo con una longitud óptica de 1 cm y se diluye con CH 3 CN (2 ml). </li><li> Determinar el número mol de resto de desprotege Fmoc (f mol) en base al coeficiente de extinción de aducto de piperidina-dibenzofulveno (6,234 a 299 nm) 10 y la absorbancia obtenida espectroscópicamente (a) de la solución preparada a través del protocolo 2.1.5 según la siguiente ecuación: f = 0,05 x 10 6 x 3 x A / 6234 </li></ol></li><li> La carga de Ru monómero 2 <ol><li> Añadir anhidro de grado CH 2 Cl 2 (2,5 ml), Ru monómero 2 </strong&gt; (64,9 mg, 53,2 mmol), 2- (1H-benzotriazol-1-il) -1,1,3,3-tetrametiluronio (HBTU) (30,3 mg, 79,8 mmol), DMSO anhidro de grado (2,5 ml ), y N, N-diisopropiletilamina (i Pr 2 NEt) (20 l) en este orden en una atmósfera de N 2 a la resina se lavó y se agita la mezcla durante 12 horas a temperatura ambiente (Figura 2d). </li><li> Retirar la solución por filtración a través del drenaje. Lavar la resina con anhidro de grado DMSO (3 ml, 5 min de agitación) tres veces, anhidro de grado MeOH (3 ml, 3 min de agitación) y CH anhidro de grado 2 Cl 2 (3 ml, 3 min de agitación) alternativamente tres veces y anhidro de grado CH 2 Cl 2 (3 ml, 3 minutos de agitación) tres veces. </li><li> Añadir CH anhidro de grado 2 Cl 2 (5 ml), anhídrido benzoico (0,28 g, 1,5 mmol), y N metilimidazol (0,10 ml, 1,5 mmol) en este orden en una atmósfera de N 2 a la resina lavada y revolverla mezcla durante 2 horas a temperatura ambiente. </li><li> Retirar la solución por filtración a través del drenaje. Lavar la resina con anhidro de grado CH 2 Cl 2 (3 ml, 3 minutos de agitación) y anhidro de grado MeOH (3 ml, 3 min de agitación) alternativamente tres veces y luego con CH anhidro de grado 2 Cl 2 (3 ml, 3 min de agitación) tres veces. </li><li> Repetir los protocolos como se describe en 2.1.3-2.1.6 para cuantificar el número de moles de monómero cargado Ru 2. </li></ol></li><li> La carga de Fmoc- y terciario-butil-lado residuo (t Bu) -Protegido (L) -glutámico (Glu) (7 CAS RN 71989-18-9; Figura 1) <ol><li> Añadir CH anhidro de grado 2 Cl 2 (4,5 ml), Glu · H2O (39,4 mg, 88,8 mmol), HBTU (50,5 mg, 133,2 mmol), anhidro de grado DMSO (0,5 ml), y i Pr 2 Net ( 50 l) en este orden en una atmósfera de N 2 a la resina lavada y se agitó la mezcla durante 12 hr en la sala de temperatura (Figura 2e). NOTA: Las cantidades de Glu · H2O y HBTU se disminuyen gradualmente desde 2,3 a 2,7 pasos para mantener su estequiometría a la funcionalidad reactiva -NH 2 de la constante de resina. </li><li> Repetir los protocolos como se describe en 2.2.2-2.2.4. </li><li> Tomar una pequeña porción de la resina del matraz y ponerlo en una mezcla de ácido trifluoroacético (CF 3 CO 2 H) (2,5 l), trietilsilano (Et 3 SiH) (0,5 l), y 1,2-dicloroetano ( 47 l). Sonicar la mezcla durante 0,5 horas y el uso de la solución resultante de la espectrometría de masas 4,7,8,9 (Figura 3a). </li><li> Repetir los protocolos como se describe en 2.1.3-2.1.6 para cuantificar el número mol de Glu cargado. </li></ol></li><li> La carga de monómero Pt 3 <ol><li> Añadir anhidro de grado DMSO (4,5 ml), monómero Pt (32,9 mg, 33,3 mmol), HBTU (18,9 mg, 50,0 mmol), CH-anhidro de grado 2Cl 2 (0,5 ml), y i Pr 2 NEt (20 l) en este orden en una atmósfera de N 2 a la resina se lavó y se agita la mezcla durante 12 horas a temperatura ambiente (Figura 2f). </li><li> Repetir los protocolos como se describe en 2.2.2-2.2.5 para cuantificar el número de moles de monómero cargado Pt 3. </li></ol></li><li> La carga de Glu <ol><li> Añadir CH anhidro de grado 2 Cl 2 (4,5 ml), Glu · H2O (27,8 mg, 62,9 mmol), HBTU (35,8 mg, 94,4 mmol), anhidro de grado DMSO (0,5 ml), y i Pr 2 Net ( 50 l) en este orden en una atmósfera de N 2 a la resina se lavó y se agita la mezcla durante 12 horas a temperatura ambiente. </li><li> Repetir los protocolos como se describe en 2.3.2-2.3.4 (Figura 3b). </li></ol></li><li> La carga de Rh monómero 4 <ol><li> Añadir DMSO anhidro de grado (4,5 ml), Rh monómero 4 (21,8 mg, 23,3 mmol), HBTU (13,3 mg, 35,0 mmol), CH anhidro de grado 2 Cl 2 (0,5 ml), y i Pr 2 NEt (20 l) en este orden en una atmósfera de N 2 a la resina lavada y se agitó la mezcla de durante 12 horas a temperatura ambiente (Figura 2g). </li><li> Repetir los protocolos como se describe en 2.2.2. </li><li> Repetir los protocolos como se describe en 2.6.1. </li><li> Repetir los protocolos como se describe en 2.2.2-2.2.5 para cuantificar el número de moles de monómero cargado Rh 4. </li></ol></li><li> La carga de Glu <ol><li> Añadir CH anhidro de grado 2 Cl 2 (4,5 ml), Glu · H2O (20,4 mg, 46,0 mmol), HBTU (26,2 mg, 69,0 mmol), anhidro de grado DMSO (0,5 ml), y i Pr 2 Net ( 50 l) en este orden en una atmósfera de N 2 a la resina se lavó y se agita la mezcla durante 12 horas a temperatura ambiente. </li><li> Repetir los protocolos como se describe en 2.3.2-2.3.4 (Figura 3c). </li></ol></li><li> La carga de 2- [2- (2-metoxietoxi) etoxi] acético (TEG) ácido (8 CAS RN 16024-58-1; Figura 1) <ol><li> Añadir CH anhidro de grado 2 Cl 2 (3 ml), ácido TEG (14 l, 91,0 mmol), HBTU (51,7 mg, 136,5 mmol), CH anhidro de grado 2 Cl 2 (2 ml), y i Pr 2 Net ( 50 l) en este orden en una atmósfera de N 2 a la resina se lavó y se agita la mezcla durante 12 horas a temperatura ambiente. </li><li> Retirar la solución por filtración a través del drenaje. Lavar la resina con anhidro de grado DMSO (3 ml, 5 min de agitación) dos veces, anhidro de grado MeOH (3 ml, 3 min de agitación) y CH anhidro de grado 2 Cl 2 (3 ml, 3 min de agitación) alternativamente tres veces y anhidro de grado CH 2 Cl 2 (3 ml, 3 minutos de agitación) tres veces. </li></ol></li><li> La escisión de la resina al final de la síntesis en fase sólida <ol><li> lavarla resina con éter dietílico (4 ml, 5 minutos de agitación) tres veces, se secan bajo un vacío, y se hincha con anhidro de grado CH 2 Cl 2 (1 ml, 5 min de agitación). </li><li> Añadir una mezcla de CF 3 CO 2 H (0,1 ml), Et 3 SiH (20 l), y 1,2-dicloroetano (1,9 ml) a la suspensión y se agita la mezcla durante 12 horas a temperatura ambiente. </li><li> Retirar la solución por filtración a través del drenaje, añadir una nueva mezcla de CF 3 CO 2 H (0,1 ml), Et 3 SiH (20 l), y 1,2-dicloroetano (1,9 ml) a la resina, y se agita la mezcla de durante 1 hora a temperatura ambiente. </li><li> Repita el paso 2.9.3 hasta que la solución se vuelve visualmente incoloro (Figura 2h). </li><li> Combinar todas las soluciones tal como se obtiene a través de protocolos 2.9.2-2.9.4 y analizar el contenido de la solución resultante mediante espectrometría de masas 4,7,8,9 (Figura 3d). </li><li> Eliminar las especies volátiles de la solución por evaporation y disolver el residuo en una mezcla de CF 3 CO 2 H (0,2 ml), Et 3 SiH (40 l), y 1,2-dicloroetano (3,8 ml). </li><li> Se agita la mezcla durante 24 horas a temperatura ambiente y analizar el contenido de la solución resultante mediante espectrometría de masas 4,7,8,9 confirmar la desprotección completa de los grupos t Bu en los residuos secundarios de 1 (Figura 3E). </li><li> Eliminar las especies volátiles de la solución por evaporación. </li></ol></li><li> Purificación de 1 <ol><li> Sonicar el residuo sólido tal como se obtiene a través del protocolo 2.9 en CH 2 Cl 2 y se decanta la solución. Repita este proceso hasta que la solución se vuelve decantación visualmente incoloro. </li><li> Analizar el contenido del residuo sólido resultante mediante espectrometría de masas 4,7,8,9. </li><li> Lavar el residuo con MeOH (100 l / 10 mg) con sonicación, se decanta la solución, y analizar el contenido de la resultante sOlid residuo mediante espectrometría de masas 4,7,8,9. </li><li> Disolver el residuo (1 mg) en una mezcla de CH 3 CN (90 l) y agua (10 l) por sonicación y combinar la solución resultante con solución salina tamponada con fosfato (800 l, 10 mM, pH = 7,4). Sonicar la mezcla y se incuba a 37 ° C durante 24 horas. </li><li> Extraer la especie de color en el sobrenadante de decantación con una mezcla de 1,2-dicloroetano (500 l), CH 3 CN (20 l), y CF 3 CO 2 H (20 l). Analizar el extracto mediante espectrometría de masas 4,7,8,9 (Figura 3f). </li><li> Repetir la extracción hasta que la fase acuosa se vuelve visualmente incoloro. Combinar las soluciones orgánicas y eliminar las especies volátiles por evaporación. </li></ol></li></ol>

<ol>
	<li>Takanashi, K., 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=Heterometal+Assembly+in+Dendritic+Polyphenylazomethines.">Heterometal Assembly in Dendritic Polyphenylazomethines.</a> Bull. Chem. Soc. Jpn. 80, 1563-1572 (2007).</li><li>Packheiser, R., Ecorchard, P., R&#252;ffer, T., Lang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heteromultimetallic+Transition+Metal+Complexes+Based+on+Unsymmetrical+Platinum(II)+Bis-Acetylides.">Heteromultimetallic Transition Metal Complexes Based on Unsymmetrical Platinum(II) Bis-Acetylides.</a> Organometallics. 27, 3534-3536 (2008).</li><li>Sculfort, S., Braunstein, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intramolecular+d10-d10+Interactions+in+Heterometallic+Clusters+of+the+Transition+Metals.">Intramolecular d10-d10 Interactions in Heterometallic Clusters of the Transition Metals.</a> Chem. Soc. Rev. 40, 2741-2760 (2011).</li><li>Vairaprakash, P., Ueki, H., Tashiro, K., Yaghi, O. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Metal-Organic+Complex+Arrays.">Synthesis of Metal-Organic Complex Arrays.</a> J. Am. Chem. Soc. 133, 759-761 (2011).</li><li>Jacoby, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis:+Method+Couples+Various+Metals+in+Predetermined+Sequences.">Synthesis: Method Couples Various Metals in Predetermined Sequences.</a> C&amp;EN. 89, (2011).</li><li>White, P., Eds D&#246;rner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthetic+Notes.">Synthetic Notes.</a> Peptide Synthesis 2008/2009. , (2009).</li><li>Sajna, K. V., Fracaroli, A. M., Yaghi, O. M., Tashiro, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modular+Synthesis+of+Metal-Organic+Complex+Arrays+Containing+Precisely+Designed+Metal+Sequences.">Modular Synthesis of Metal-Organic Complex Arrays Containing Precisely Designed Metal Sequences.</a> Inorg. Chem. 54, 1197-1199 (2015).</li><li>Sukul, P. K., 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+Water-Soluble+Metal-Organic+Complex+Array+as+a+Multinuclear+Heterometallic+Peptide+Amphiphile+That+Shows+Unconventional+Anion+Dependency+in+Its+Self-Assembly.">A Water-Soluble Metal-Organic Complex Array as a Multinuclear Heterometallic Peptide Amphiphile That Shows Unconventional Anion Dependency in Its Self-Assembly.</a> Chem. Commun. 52, 1579-1581 (2016).</li><li>Fracaroli, A. M., Tashiro, K., Yaghi, O. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Isomers+of+Metal-Organic+Complex+Arrays.">Isomers of Metal-Organic Complex Arrays.</a> Inorg. Chem. 51, 6437-6439 (2012).</li><li>Gude, M., Ryf, J., White, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+Accurate+Method+for+the+Quantitation+of+Fmoc-Derivatized+Solid+Phase+Supports.">An Accurate Method for the Quantitation of Fmoc-Derivatized Solid Phase Supports.</a> Letters in Peptide Science. 9, 203-206 (2002).</li><li>Merrifield, R. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Solid+Phase+Peptide+Synthesis.+I.+The+Synthesis+of+a+Tetrapeptide.">Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide.</a> J. Am. Chem. Soc. 85, 2149-2154 (1963).</li></ol>

The authors have nothing to disclose.

eliminación perfecta de los productos químicos no deseados de la resina no siempre es posible simplemente por lavado con disolventes que pueden disolver fácilmente esos productos químicos. Una técnica clave para lavar eficientemente la resina es causar que se hinche y encoger de forma repetitiva de manera que los productos químicos que quedan en el interior serán forzados hacia fuera. Esta es la razón por la resina en nuestro procedimiento se trata con CH 2 Cl 2 y MeOH alternativamente ya q...

la síntesis controlada de estructuras moleculares complejas siempre ha sido un tema importante en la química sintética. Desde este punto de vista, para sintetizar complejos heterometálicos multinucleares de una manera diseñable sigue siendo un tema digno de ser cuestionado en el campo de la química inorgánica, debido al número de posibles resultados estructurales desde el enfoque basado en ligando-metalación que se utiliza comúnmente para la preparación de complejos de metales de monómeros. Aunque varios ejemplos de complejos multinucleares heterometálicos se han reportado hasta el momento 1,2,3, el ensayo y error o penosidad de su síntesis requiere el desarrollo de un método sencillo que es aplicable a una amplia gama de estructuras. Como un nuevo enfoque para abordar este problema, en 2011 se informó de una metodología sintética 4,5 donde varios complejos metálicos mononucleares que tienen un resto aminoácido protegido con Fmoc se acoplan secuencialmente para dar múltiplesmetálico matrices peptídicos mediante el uso de los protocolos de síntesis de polipéptidos en fase sólida 6. Debido a la naturaleza consecutiva de la síntesis de polipéptidos, una secuencia específica de múltiples centros metálicos es racionalmente designable mediante el control del número y orden de las reacciones de acoplamiento de los monómeros de complejos metálicos. Más tarde, este enfoque fue más modular para hacer varios más grande y / o ramificados estructuras de matriz mediante la combinación con el enlace covalente entre dos matrices más cortos 7. Aquí vamos a mostrar cómo la síntesis de tales matrices peptídicos multimetálicos es típicamente operado por la elección de la WSMOCA informó recientemente (1 8 CAS RN 1827663-18-2; Figura 1) como un ejemplo representativo. Aunque la síntesis de una matriz particular se describe en este protocolo, los mismos procedimientos son aplicables a la síntesis de una amplia gama de diferentes secuencias, incluyendo los isómeros 9. Esperamos que este protocol inspire a más investigadores a participar en la ciencia de los compuestos de secuencia controlada, donde las moléculas investigadas normalmente hasta el momento han sido biopolímeros, pero rara vez se incluyen ejemplos de especies basada complejo de metal.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Dichloro(p&#8208;cymene)ruthenium(II), dimer</td>
			<td>Kanto Chemical</td>
			<td>11443-65</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloro(1,5-cyclooctadiene)platinum(II)</td>
			<td>TCI</td>
			<td>D3592</td>
			<td></td>
		</tr>
		<tr>
			<td>Rhodium(III) chloride trihydrate</td>
			<td>Kanto Chemical</td>
			<td>36018-62</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate buffered saline, tablet</td>
			<td>Sigma Aldrich</td>
			<td>P4417-50TAB&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>NovaSyn TG Sieber resin</td>
			<td>Novabiochem</td>
			<td>8.55013.0005</td>
			<td></td>
		</tr>
		<tr>
			<td>HBTU</td>
			<td>TCI</td>
			<td>B1657</td>
			<td></td>
		</tr>
		<tr>
			<td>Benzoic anhydride</td>
			<td>Kanto Chemical</td>
			<td>04116-30</td>
			<td></td>
		</tr>
		<tr>
			<td>Fmoc-Glu(OtBu)-OH&#12539;H2O</td>
			<td>Watanabe Chemical Industries</td>
			<td>K00428</td>
			<td></td>
		</tr>
		<tr>
			<td>Trifluoroacetic acid</td>
			<td>Kanto Chemical</td>
			<td>40578-30</td>
			<td></td>
		</tr>
		<tr>
			<td>Triethylsilane</td>
			<td>TCI</td>
			<td>T0662</td>
			<td></td>
		</tr>
		<tr>
			<td>2-[2-(2-Methoxyethoxy)ethoxy]acetic acid</td>
			<td>Sigma Aldrich</td>
			<td>407003</td>
			<td>Dried over 3&#197; sieves</td>
		</tr>
		<tr>
			<td>Dithranol</td>
			<td>Wako Pure Chemical Industries</td>
			<td>191502</td>
			<td></td>
		</tr>
		<tr>
			<td>N-methylimidazole</td>
			<td>TCI</td>
			<td>M0508</td>
			<td></td>
		</tr>
		<tr>
			<td>N&#8208;ethyldiisopropylamine</td>
			<td>Kanto Chemical</td>
			<td>14338-32</td>
			<td></td>
		</tr>
		<tr>
			<td>Piperidine</td>
			<td>Kanto Chemical</td>
			<td>32249-30</td>
			<td></td>
		</tr>
		<tr>
			<td>4&#39;-(4-methylphenyl)-2,2&#39;:6&#39;,2&#34;-terpyridine</td>
			<td>Sigma Aldrich</td>
			<td>496375</td>
			<td></td>
		</tr>
		<tr>
			<td>Dehydrated grade dimethylsulfoxide</td>
			<td>Kanto Chemical</td>
			<td>10380-05&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Dehydrated grade methanol</td>
			<td>Kanto Chemical</td>
			<td>25506-05&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Dehydrated grade N,N&#8208;Dimethylformamide</td>
			<td>Kanto Chemical</td>
			<td>11339-84</td>
			<td>Amine Free</td>
		</tr>
		<tr>
			<td>Dehydrated grade dichloromethane</td>
			<td>Kanto Chemical</td>
			<td>11338-84</td>
			<td></td>
		</tr>
		<tr>
			<td>MeOH</td>
			<td>Kanto Chemical</td>
			<td>25183-81&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Dimethylsulfoxide</td>
			<td>Kanto Chemical</td>
			<td>10378-70</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Kanto Chemical</td>
			<td>14029-81</td>
			<td></td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>Kanto Chemical</td>
			<td>01031-70&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>1,2-dichloroethane</td>
			<td>Kanto Chemical</td>
			<td>10149-00</td>
			<td></td>
		</tr>
		<tr>
			<td>Diethyl ether</td>
			<td>Kanto Chemical</td>
			<td>14134-00&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>Kanto Chemical</td>
			<td>10158-81</td>
			<td></td>
		</tr>
	</tbody>
</table>

synthesis of a water-soluble metal&#8211;organic complex array

We demonstrate a method for the synthesis of a water-soluble multimetallic peptidic array containing a predetermined sequence of metal centers such as Ru(II), Pt(II), and Rh(III). The compound, named as a water-soluble metal-organic complex array (WSMOCA), is obtained through 1) the conventional solution-chemistry-based preparation of the corresponding metal complex monomers having a 9-fluorenylmethyloxycarbonyl (Fmoc)-protected amino acid moiety and 2) their sequential coupling together with other water-soluble organic building units on the surface-functionalized polymeric resin by following the procedures originally developed for the solid-phase synthesis of polypeptides, with proper modifications. Traces of reactions determined by mass spectrometric analysis at the representative coupling steps in stage 2 confirm the selective construction of a predetermined sequence of metal centers along with the peptide backbone. The WSMOCA cleaved from the resin at the end of stage 2 has a certain level of solubility in aqueous media dependent on the pH value and/or salt content, which is useful for the purification of the compound.

Figura 1 muestra las estructuras moleculares de los finales compuesto objetivo, precursores y productos intermedios. La Figura 2 muestra las imágenes de la resina y la Figura 3 muestra los espectros de masas MALDI-TOF de muestras en los pasos de procedimiento seleccionadas. Las imágenes de la figura 2a a 2h muestran los cambios en el color y la apariencia de la resina que se somete durante las etapas d...

Watch this Scientific Journal Video about Synthesis of a Water-soluble MetalÃ¢â‚¬â€œOrganic Complex Array at JoVE.com

Synthesis of a Water-soluble Metal&#8211;Organic Complex Array

A potential general method for the synthesis of water-soluble multimetallic peptidic arrays containing a predetermined sequence of metal centers is presented.

Síntesis de un conjunto complejo de metal-orgánico soluble en agua

We demonstrate a method for the synthesis of a water-soluble multimetallic peptidic array containing a predetermined sequence of metal centers such as ...

synthesis-of-a-water-soluble-metalorganic-complex-array

Research

JoVE Journal

Chemistry

9.8K vistas.  National Institute for Materials Science. A potential general method for the synthesis of water-soluble multimetallic peptidic arrays containing a predetermined sequence of metal centers is presented.

Video: Synthesis of a Water-soluble Metal–Organic Complex Array

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

The development of fluorescent indicators represented a revolution for life sciences. Genetically encoded and synthetic fluorophores with sensing abilities allowed the visualization of biologically relevant species with high spatial and temporal resolution. Synthetic dyes are of particular interest thanks to their high tunability and the wide range of measureable analytes. However, these molecules suffer several limitations related to small molecule behavior (poor solubility, difficulties in targeting, often no ratiometric imaging allowed). In this work we introduce the development of dendrimer-based sensors and present a procedure for pH measurement in vitro, in living cells and in vivo. We choose dendrimers as ideal platform for our sensors for their many desirable properties (monodispersity, tunable properties, multivalency) that made them a widely used scaffold for several biomedical devices. The conjugation of fluorescent pH indicators to the dendrimer scaffold led to an enhancement of their sensing performances. In particular dendrimers exhibit reduced cell leakage, improved intracellular targeting and allow ratiometric measurements. These novel sensors were successfully employed to measure pH in living HeLa cells and in vivo in mouse brain.

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors

Fluorescence sensors are powerful tools in life science. Here we describe a methodology to synthesize and use dendrimer-based fluorescent sensors to measure pH in living cells and in vivo. The dendritic scaffold enhances the properties of conjugated fluorescent dyes leading to improved sensing properties.

Síntesis, Entrega y Celular<em&gt; En vivo</em&gt; Aplicación de sensores de pH basadas en dendrímeros

The development of  fluorescent indicators represented a revolution for life sciences. Genetically  encoded and synthetic fluorophores with sensing ...

Investigación

Química

Atomically Defined Templates for Epitaxial Growth of Complex Oxide Thin Films

Atomically defined substrate surfaces are prerequisite for the epitaxial growth of complex oxide thin films. In this protocol, two approaches to obtain such surfaces are described. The first approach is the preparation of single terminated perovskite SrTiO3 (001) and DyScO3 (110) substrates. Wet etching was used to selectively remove one of the two possible surface terminations, while an annealing step was used to increase the smoothness of the surface. The resulting single terminated surfaces allow for the heteroepitaxial growth of perovskite oxide thin films with high crystalline quality and well-defined interfaces between substrate and film. In the second approach, seed layers for epitaxial film growth on arbitrary substrates were created by Langmuir-Blodgett (LB) deposition of nanosheets. As model system Ca2Nb3O10- nanosheets were used, prepared by delamination of their layered parent compound HCa2Nb3O10. A key advantage of creating seed layers with nanosheets is that relatively expensive and size-limited single crystalline substrates can be replaced by virtually any substrate material.

Various procedures are outlined to prepare atomically defined templates for epitaxial growth of complex oxide thin films. Chemical treatments of single crystalline SrTiO3 (001) and DyScO3 (110) substrates were performed to obtain atomically smooth, single terminated surfaces. Ca2 Nb3 O10- nanosheets were used to create atomically defined templates on arbitrary substrates.

Plantillas Atómicamente definidos para crecimiento epitaxial de óxido complejo Películas Delgadas

Atomically defined substrate surfaces are prerequisite for the epitaxial growth of complex oxide thin films. In this protocol, two approaches to obtain ...

Water in Oil Emulsions: A New System for Assembling Water-soluble Chlorophyll-binding Proteins with Hydrophobic Pigments

Chlorophylls (Chls) and bacteriochlorophylls (BChls) are the primary cofactors that carry out photosynthetic light harvesting and electron transport. Their functionality critically depends on their specific organization within large and elaborate multisubunit transmembrane protein complexes. In order to understand at the molecular level how these complexes facilitate solar energy conversion, it is essential to understand protein-pigment, and pigment-pigment interactions, and their effect on excited dynamics. One way of gaining such understanding is by constructing and studying complexes of Chls with simple water-soluble recombinant proteins. However, incorporating the lipophilic Chls and BChls into water-soluble proteins is difficult. Moreover, there is no general method, which could be used for assembly of water-soluble proteins with hydrophobic pigments. Here, we demonstrate a simple and high throughput system based on water-in-oil emulsions, which enables assembly of water-soluble proteins with hydrophobic Chls. The new method was validated by assembling recombinant versions of the water-soluble chlorophyll binding protein of Brassicaceae plants (WSCP) with Chl a. We demonstrate the successful assembly of Chl a using crude lysates of WSCP expressing E. coli cell, which may be used for developing a genetic screen system for novel water-soluble Chl-binding proteins, and for studies of Chl-protein interactions and assembly processes.

This manuscript describes a simple and high-throughput method for assembling water-soluble proteins with hydrophobic pigments that is based on water-in-oil emulsions. We demonstrate the effectiveness of the method in the assembly of native chlorophylls with four variants of recombinant water-soluble-chlorophyll binding proteins (WSCPs) of Brassica plants expressed in E. coli.

Emulsiones agua en aceite: Un nuevo sistema para el ensamblaje de las proteínas de unión de clorofila-solubles en agua con pigmentos hidrófobos

Chlorophylls (Chls) and bacteriochlorophylls (BChls) are the primary cofactors that carry out photosynthetic light harvesting and electron transport. ...

Synthesis and Exfoliation of Discotic Zirconium Phosphates to Obtain Colloidal Liquid Crystals

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and engineers. Growth of such anisotropic nanocrystals through a simple chemical method is a challenging task. In this study, we fabricate discotic nanodisks of zirconium phosphate [Zr(HPO4)2&#183;H2O] as a model material using hydrothermal, reflux and microwave-assisted methods. Growth of crystals is controlled by duration time, temperature, and concentration of reacting species. The novelty of the adopted methods is that discotic crystals of size ranging from hundred nanometers to few micrometers can be obtained while keeping the polydispersity well within control. The layered discotic crystals are converted to monolayers by exfoliation with tetra-(n)-butyl ammonium hydroxide [(C4H9)4NOH, TBAOH]. Exfoliated disks show isotropic and nematic liquid crystal phases. Size and polydispersity of disk suspensions is highly important in deciding their phase behavior.

A two dimensional model material of discotic zirconium phosphate was developed. The inorganic crystal with lamellar structure was synthesized by hydrothermal, reflux, and microwave-assisted methods. On exfoliation with organic molecules, layered crystals can be converted to monolayers, and nematic liquid crystal phase was formed at sufficient concentration of monolayers.

Síntesis y exfoliación de Discotic circonio fosfatos para obtener cristales líquidos coloidal

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and ...

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

Un directa, Protocolo Guanidinylation Etapa Temprana para la Síntesis de complejos productos naturales que contiene aminoguanidina-

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

Síntesis y caracterización de supramoleculares Coloides

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Chemo-enzymatic Synthesis of N-glycans for Array Development and HIV Antibody Profiling

We present a highly efficient way for the rapid preparation of a wide range of N-linked oligosaccharides (estimated to exceed 20,000 structures) that are commonly found on human glycoproteins. To achieve the desired structural diversity, the strategy began with the chemo-enzymatic synthesis of three kinds of oligosaccharyl fluoride modules, followed by their stepwise &#945;-selective glycosylations at the 3-O and 6-O positions of the mannose residue of the common core trisaccharide having a crucial &#946;-mannoside linkage. We further attached the N-glycans to the surface of an aluminum oxide-coated glass (ACG) slide to create a covalent mixed array for the analysis of hetero-ligand interaction with an HIV antibody. In particular, the binding behavior of a newly isolated HIV-1 broadly neutralizing antibody (bNAb), PG9, to the mixture of closely spaced Man5GlcNAc2 (Man5) and 2,6-di-sialylated bi-antennary complex type N-glycan (SCT) on an ACG array, opens a new avenue to guide the effective immunogen design for HIV vaccine development. In addition, our ACG array embodies a powerful tool to study other HIV antibodies for hetero-ligand binding behavior.

Chemo-enzymatic Synthesis of N-glycans for Array Development and HIV Antibody Profiling

A modular approach to the synthesis of N-glycans for attachment to an aluminum oxide-coated glass slide (ACG slide) as a glycan microarray has been developed and its use for the profiling of an HIV broadly neutralizing antibody has been demonstrated.

Chemo-enzimático síntesis de N- glicanos para el desarrollo de la matriz y el anticuerpo del VIH perfiles

We present a highly efficient way for the rapid preparation of a wide range of N-linked oligosaccharides (estimated to exceed 20,000 structures) that are ...

Heterogeneous Removal of Water-Soluble Ruthenium Olefin Metathesis Catalyst from Aqueous Media Via Host-Guest Interaction

A highly efficient transition metal catalyst removal method is developed. The water-soluble catalyst contains a newly-designed NHC ligand for the catalyst removal via host-guest interactions. The new NHC ligand possesses an adamantyl (guest) tethered linear ethylene glycol units for hydrophobic inclusion into the cavity of a &#946;-cyclodextrin (&#946;-CD) host compound. The new NHC ligand was applied to a Ru-based olefin metathesis catalyst. The Ru catalyst demonstrated excellent activity in representative ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP) reactions in aqueous media as well as organic solvent, CH2Cl2. After the reaction was complete, the lingering Ru residue was removed from the aqueous solution with the efficiency of more than 99% (53 ppm of Ru residue) by simple filtration utilizing a host-guest interaction between insoluble silica-grafted &#946;-CD (host) and the adamantyl moiety (guest) on the catalyst. The new Ru catalyst also demonstrated high removal efficiency via extraction when the reaction is run in organic solvent by partitioning the crude reaction mixture between layers of diethyl ether and water. In this way, the catalyst stays in aqueous layer only. In organic layer, the residual Ru amount was only 0.14 ppm in the RCM reactions of diallyl compounds.

A removable water-soluble N-heterocyclic carbene (NHC) ligand in aqueous media via host-guest interaction has been developed. We demonstrated representative olefin metathesis reactions in water as well as in dichloromethane. Via either host-guest interaction or extraction, the residual ruthenium (Ru) catalyst was as low as 0.14 ppm after the reaction.

Extracción heterogénea del catalizador de metátesis de olefinas rutenio solubles en agua de medios acuosos mediante interacción Host-Guest

A highly efficient transition metal catalyst removal method is developed. The water-soluble catalyst contains a newly-designed NHC ligand for the catalyst ...

Negative Additive Manufacturing of Complex Shaped Boron Carbides

Boron carbide (B4C) is one of the hardest materials in existence. However, this attractive property also limits its machineability into complex shapes for high wear, high hardness, and lightweight material applications such as armors. To overcome this challenge, negative additive manufacturing (AM) is employed to produce complex geometries of boron carbides at various length scales. Negative AM first involves gelcasting a suspension into a 3D-printed plastic mold. The mold is then dissolved away, leaving behind a green body as a negative copy. Resorcinol-formaldehyde (RF) is used as a novel gelling agent because unlike traditional hydrogels, there is little to no shrinkage, which allows for extremely complex molds to be used. Furthermore, this gelling agent can be pyrolyzed to leave behind ~50 wt% carbon, which is a highly effective sintering aid for B4C. Due to this highly homogenous distribution of in situ carbon within the B4C matrix, less than 2% porosity can be achieved after sintering. This protocol highlights in detail the methodology for creating near fully dense boron carbide parts with highly complex geometries.

A method called negative additive manufacturing is used to produce near fully dense complex shaped boron carbide parts of various length scales. This technique is possible via the formulation of a novel suspension involving resorcinol-formaldehyde as a unique gelling agent that leaves behind a homogenous carbon sintering aid after pyrolysis.

Fabricación aditiva negativa del complejo en forma de carburos de boro

Boron carbide (B4C) is one of the hardest materials in existence. However, this attractive property also limits its machineability into complex shapes for ...

Molten-Salt Synthesis of Complex Metal Oxide Nanoparticles

The development of feasible synthesis methods is critical for the successful exploration of novel properties and potential applications of nanomaterials. Here, we introduce the molten-salt synthesis (MSS) method for making metal oxide nanomaterials. Advantages over other methods include its simplicity, greenness, reliability, scalability, and generalizability. Using pyrochlore lanthanum hafnium oxide (La2Hf2O7) as a representative, we describe the MSS protocol for the successful synthesis of complex metal oxide nanoparticles (NPs). Furthermore, this method has the unique ability to produce NPs with different material features by changing various synthesis parameters such as pH, temperature, duration, and post-annealing. By fine-tuning these parameters, we are able to synthesize highly uniform, non-agglomerated, and highly crystalline NPs. As a specific example, we vary the particle size of the La2Hf2O7&#160;NPs by changing the concentration of the ammonium hydroxide solution used in the MSS process, which allows us to further explore the effect of particle size on various properties. It is expected that the MSS method will become a more popular synthesis method for nanomaterials and more widely employed in the nanoscience and nanotechnology community in the upcoming years.

Here, we demonstrate a unique, relatively low-temperature, molten-salt synthesis method for preparing uniform complex metal oxide lanthanum hafnate nanoparticles.

Sales fundidas síntesis de nanopartículas de óxidos metálicos complejos

The development of feasible synthesis methods is critical for the successful exploration of novel properties and potential applications of nanomaterials. ...