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. Preparazione di metallo monomeri complesse (2 CAS RN 1381776-70-0, 3 CAS RN 1261168-42-6, 4 CAS RN 1261168-43-7; Figura 1) <ol><li> Preparazione di Ru monomero 2 <ol><li> Unire il precursore organico (5 9 CAS RN 1381776-63-1; Figura 1) (380 mg, 0,48 mmol) e [Ru (p -cymene) Cl 2] dimero (224 mg, 0,37 mmol) con un ancoretta in un 100 ml singolo collo pallone a fondo tondo. </li><li> Aggiungere metanolo (MeOH) (25 ml) alla miscela, collegare un condensatore al giunto del pallone, e agitare la sospensione a 65 ° C per 3 ore in un bagno d&#39;olio a temperatura controllata. </li><li> Raffreddare la miscela di reazione a temperatura ambiente e filtrare la sospensione attraverso una carta da filtro mediante aspirazione. </li><li> Lavare il residuo sul filtro accuratamente con MeOH finché il filtrato diventa visivamente incolore e asciugare il residuo a pressione ridotta. </li><li> Combinare il residuo e 4 &#39;- (4-metilfenil) -2,2&#39;: 6 &amp;# 39;, 2 &quot;-terpyridine (216 mg, 0,68 mmol) con un ancoretta in 100 ml pallone a fondo rotondo singolo collo. </li><li> Aggiungere MeOH (22,5 ml) e acqua (2,5 ml) alla miscela, collegare un condensatore al giunto del pallone, e agitare la sospensione a 70 ° C per 16 ore. </li><li> Raffreddare la miscela di reazione a temperatura ambiente e filtrare la sospensione. </li><li> Essiccare il residuo sul filtro a pressione ridotta e si dissolvono in dimetil solfossido (DMSO) (3 ml). </li><li> Aggiungere la soluzione DMSO lentamente ad un eccesso di acetato di etile (EtOAc). </li><li> Filtrare la sospensione risultante, lavare il residuo sul filtro con EtOAc, e asciugare sotto pressione ridotta. </li></ol></li><li> Preparazione di Pt monomero 3 <ol><li> Unire il precursore organico (6 4 CAS RN 1261168-39-1; Figura 1) (360 mg, 0,50 mmol) e Pt (cycloocta-1,5-diene) Cl 2 (195 mg, 0,52 mmol) con un ancoretta in a 100 ml singolo collo pallone a fondo tondo. &lt;/ Li&gt; <li> Aggiungere MeOH (15 ml) alla miscela, collegare un condensatore al giunto del pallone, e agitare la sospensione a 65 ° C per 12 ore. </li><li> Raffreddare la miscela di reazione a temperatura ambiente e filtrare la sospensione. </li><li> Lavare il residuo sul filtro accuratamente con MeOH e asciugare sotto pressione ridotta. </li></ol></li><li> Preparazione di Rh monomero 4 <ol><li> Unire il precursore organico (6; Figura 1) (360 mg, 0,50 mmol) e RhCl 3 · 3H 2 O (137 mg, 0,52 mmol) con un ancoretta in 100 ml singolo collo pallone a fondo tondo. </li><li> Aggiungere MeOH (50 ml) alla miscela, collegare un condensatore al giunto del pallone, e agitare la sospensione a 65 ° C per 12 ore in atmosfera di N 2. </li><li> Raffreddare la miscela di reazione a temperatura ambiente e filtrare la sospensione. </li><li> Lavare il residuo sul filtro accuratamente con MeOH e asciugare sotto pressione ridotta. </li></ol></li></ol&gt; 2. Preparazione di solubile in acqua Metal-Organic Array Complex 1 <ol><li> Fmoc deprotezione da TG Sieber Resina <ol><li> Combinare as-acquistato resina TG Sieber (135 mg) con una ancoretta in un matraccio da 10 ml 2-collo portante un scarico sul fondo dotato di un filtro di vetro e un 2-way rubinetto (Figura 2a). Collegare un rubinetto di arresto a 3 vie e un tappo di vetro per le articolazioni del pallone. </li><li> Sostituire l&#39;atmosfera interna con N 2 utilizzando una linea di vuoto, e poi gonfiare la resina con anidra-grade diclorometano (CH 2 Cl 2) (1 ml) (Figura 2b). </li><li> Aggiungere anidra-grade dimetilformammide (DMF) (3 ml) e piperidina (1 ml) in questo ordine e agitare la miscela per 2,5 ore a temperatura ambiente. </li><li> Rimuovere la soluzione per filtrazione attraverso lo scarico. Lavare la resina con anidra-grade MeOH (3 ml, 3 min agitazione) ed anidra grado CH 2 Cl 2 (3 ml, 3min agitazione) alternativamente tre volte e poi con anidra grado CH 2 Cl 2 (3 ml, 3 min agitazione) quattro volte (figura 2c). </li><li> Combinare tutte le soluzioni ottenute in 2.1.4 e diluire con acetonitrile (CH 3 CN) ad un volume di 50 ml. Trasferire un&#39;aliquota (1 ml) della soluzione risultante in una cuvetta di quarzo con un percorso ottico da 1 cm e diluire con CH 3 CN (2 ml). </li><li> Determinare il numero di moli porzione deprotetto Fmoc (f mmol) in base al coefficiente di estinzione di piperidina-dibenzofulvene addotto (6.234 a 299 nm) 10 e l&#39;assorbanza spettroscopicamente ottenuto (a) della soluzione preparata tramite protocollo 2.1.5 secondo la seguente equazione: f = 0,05 x 10 6 x 3 x un / 6234 </li></ol></li><li> Caricamento di Ru monomero 2 <ol><li> Aggiungere anidra grado CH 2 Cl 2 (2,5 ml), Ru monomero 2 </sTrong&gt; (64.9 mg, 53.2 mmol), 2- (1H-benzotriazolo-1-il) -1,1,3,3-tetramethyluronium esafluorofosfato (HBTU) (30,3 mg, 79,8 mmol), anidra-grade DMSO (2,5 ml ), e N, N -diisopropylethylamine (i PR 2 NET) (20 mL) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a temperatura ambiente (figura 2d). </li><li> Rimuovere la soluzione per filtrazione attraverso lo scarico. Lavare la resina con anidro-grade DMSO (3 ml, 5 min di agitazione) per tre volte, anidro-grade MeOH (3 ml, 3 minuti di agitazione) e anidro-grade CH 2 Cl 2 (3 ml, 3 minuti di agitazione) alternativamente tre volte e anidra grado CH 2 Cl 2 (3 ml, 3 min agitazione) tre volte. </li><li> Aggiungere anidra grado CH 2 Cl 2 (5 ml), anidride benzoico (0,28 g, 1,5 mmol), e N -methylimidazole (0,10 ml, 1,5 mmoli) in questo ordine in atmosfera di N 2 alla resina lavata e mescolarela miscela per 2 ore a temperatura ambiente. </li><li> Rimuovere la soluzione per filtrazione attraverso lo scarico. Lavare la resina con anidro-grade CH 2 Cl 2 (3 ml, 3 min agitazione) e anidro-grade MeOH (3 ml, 3 minuti di agitazione) alternativamente tre volte e poi con anidro-grade CH 2 Cl 2 (3 ml, 3 min agitazione) tre volte. </li><li> Ripetere i protocolli, come descritto nella 2.1.3-2.1.6 di quantificare il numero di moli di carico Ru monomero 2. </li></ol></li><li> Caricamento di Fmoc- e terziario-butil-side residuo (t Bu) -protected (L) Acido -glutamic (Glu) (7 CAS RN 71989-18-9; Figura 1) <ol><li> Aggiungere anidro-grade CH 2 Cl 2 (4,5 ml), Glu · H 2 O (39.4 mg, 88,8 mmol), HBTU (50,5 mg, 133.2 mmol), anidra-grade DMSO (0,5 ml), e PR 2 NET ( 50 ml) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a camera TEmperature (figura 2e). NOTA: Le quantità di Glu · H 2 O e HBTU sono gradualmente diminuiti da passaggi 2,3-2,7 per mantenere il loro stechiometria al reattiva funzionalità -NH 2 sulla costante resina. </li><li> Ripetere i protocolli descritti in 2.2.2-2.2.4. </li><li> Prendere una piccola porzione della resina dalla muffola e metterla in una miscela di acido trifluoroacetico (CF 3 CO 2 H) (2,5 ml), trietilsilano (Et 3 SiH) (0,5 ml) e 1,2-dicloroetano ( 47 ml). Sonicare la miscela per 0,5 ore e utilizzare la soluzione risultante per la spettrometria di massa 4,7,8,9 (Figura 3a). </li><li> Ripetere i protocolli, come descritto nella 2.1.3-2.1.6 di quantificare il numero di moli di carico Glu. </li></ol></li><li> Caricamento di Pt monomero 3 <ol><li> Aggiungere anidro-grade DMSO (4,5 ml), Pt monomero (32.9 mg, 33,3 mmol), HBTU (18,9 mg, 50,0 mmol), anidra-grade CH 2Cl 2 (0,5 ml), e Pr 2 NEt (20 microlitri) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a temperatura ambiente (figura 2f). </li><li> Ripetere i protocolli, come descritto nella 2.2.2-2.2.5 di quantificare il numero di moli di carico Pt monomero 3. </li></ol></li><li> Caricamento di Glu <ol><li> Aggiungere anidro-grade CH 2 Cl 2 (4,5 ml), Glu · H 2 O (27.8 mg, 62,9 mmol), HBTU (35.8 mg, 94,4 mmol), anidra-grade DMSO (0,5 ml), e PR 2 NET ( 50 microlitri) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a temperatura ambiente. </li><li> Ripetere i protocolli descritti in 2.3.2-2.3.4 (figura 3b). </li></ol></li><li> Caricamento di Rh monomero 4 <ol><li> Aggiungere anidro-grade DMSO (4,5 ml), Rh monomero 4 (21,8 mg, 23,3 mmol), HBTU (13.3 mg, 35,0 mmol), anidra-grade CH 2 Cl 2 (0,5 ml), ed io Pr 2 netti (20 ml) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare per 12 ore a temperatura ambiente (figura 2g). </li><li> Ripetere i protocolli descritti in 2.2.2. </li><li> Ripetere i protocolli come descritto in 2.6.1. </li><li> Ripetere i protocolli, come descritto nella 2.2.2-2.2.5 di quantificare il numero di moli di carico Rh monomero 4. </li></ol></li><li> Caricamento di Glu <ol><li> Aggiungere anidro-grade CH 2 Cl 2 (4,5 ml), Glu · H 2 O (20.4 mg, 46,0 mmol), HBTU (26.2 mg, 69,0 mmol), anidra-grade DMSO (0,5 ml), e PR 2 NET ( 50 microlitri) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a temperatura ambiente. </li><li> Ripetere i protocolli descritti in 2.3.2-2.3.4 (Figura 3c). </li></ol></li><li> Caricamento di 2- [2- (2-metossietossi) etossi] acetico (TEG) Acido (8 CAS RN 16024-58-1; Figura 1) <ol><li> Aggiungere anidro-grade CH 2 Cl 2 (3 ml), acido TEG (14 ml, 91,0 mmol), HBTU (51,7 mg, 136,5 micromol) anidro-grade CH 2 Cl 2 (2 ml), e PR 2 NET ( 50 microlitri) in questo ordine in atmosfera di N 2 alla resina lavato e mescolare la miscela per 12 ore a temperatura ambiente. </li><li> Rimuovere la soluzione per filtrazione attraverso lo scarico. Lavare la resina con anidro-grade DMSO (3 ml, 5 min di agitazione) due volte, anidro-grade MeOH (3 ml, 3 minuti di agitazione) e anidro-grade CH 2 Cl 2 (3 ml, 3 minuti di agitazione) alternativamente tre volte e anidra grado CH 2 Cl 2 (3 ml, 3 min agitazione) tre volte. </li></ol></li><li> Cleavage dalla resina alla fine della sintesi in fase solida <ol><li> lavaggiola resina con etere etilico (4 ml, 5 min agitazione) per tre volte, asciugare sotto vuoto, e si gonfiano con anidra grado CH 2 Cl 2 (1 ml, 5 min di agitazione). </li><li> Aggiungere una miscela di CF 3 CO 2 H (0,1 ml), Et 3 SiH (20 microlitri) e 1,2-dicloroetano (1,9 ml) alla sospensione e agitare la miscela per 12 ore a temperatura ambiente. </li><li> Rimuovere la soluzione per filtrazione attraverso lo scarico, aggiungere una nuova miscela di CF 3 CO 2 H (0,1 ml), Et 3 SiH (20 microlitri) e 1,2-dicloroetano (1,9 ml) alla resina, e mescolare per 1 ora a temperatura ambiente. </li><li> Ripetere il punto 2.9.3 fino a quando la soluzione diventa visivamente incolore (Figura 2 ore). </li><li> Combinare tutte le soluzioni ottenute tramite protocolli 2.9.2-2.9.4 e analizzare il contenuto della soluzione risultante dalla spettrometria di massa 4,7,8,9 (figura 3d). </li><li> Rimuovere le specie volatili della soluzione da evaporation e riprendere il residuo con una miscela di CF 3 CO 2 H (0,2 ml), Et 3 SiH (40 microlitri) e 1,2-dicloroetano (3,8 ml). </li><li> Mescolare la miscela per 24 ore a temperatura ambiente e analizzare il contenuto della soluzione risultante mediante spettrometria di massa 4,7,8,9 per confermare la deprotezione completa dei gruppi t Bu ai residui indesiderati di 1 (figura 3e). </li><li> Rimuovere le specie volatili della soluzione mediante evaporazione. </li></ol></li><li> Purificazione di 1 <ol><li> Sonicare il residuo solido ottenuto tramite protocollo 2,9 in CH 2 Cl 2 e decantare la soluzione. Ripetere questo processo fino a quando la soluzione diventa decantare visivamente incolore. </li><li> Analizzare i contenuti del residuo solido risultante mediante spettrometria di massa 4,7,8,9. </li><li> Lavare il residuo con MeOH (100 microlitri / 10 mg) con sonicazione, decantare la soluzione, e analizzare il contenuto della risultante sresiduo olid mediante spettrometria di massa 4,7,8,9. </li><li> Sciogliere il residuo (1 mg) in una miscela di CH 3 CN (90 ml) e acqua (10 mL) per sonicazione e combinare la soluzione risultante con PBS (800 ml, 10 mM, pH = 7,4). Sonicare il composto e incubare a 37 ° C per 24 ore. </li><li> Estrarre specie colorate nel supernatante decantare con una miscela di 1,2-dicloroetano (500 ml), CH 3 CN (20 ml) e CF 3 CO 2 H (20 microlitri). Analizzare l&#39;estratto dalla spettrometria di massa 4,7,8,9 (Figura 3f). </li><li> Ripetere l&#39;estrazione fino alla fase acquosa diventa visivamente incolore. Unire le soluzioni organiche e rimuovere le specie volatili per evaporazione. </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.

rimozione perfetta delle sostanze chimiche indesiderate dalla resina non è sempre possibile semplicemente lavando con solventi che possono facilmente sciogliere tali sostanze. Una tecnica chiave per lavare in modo efficiente la resina è quello di provocare a gonfiarsi e ridurre ripetutamente in modo che le sostanze chimiche residue all&#39;interno saranno costretti fuori. Ecco perché la resina nella nostra procedura viene trattata con CH 2 Cl 2 e MeOH alternativamente come viene lavato (ad e...

sintesi controllata di strutture molecolari complesse è sempre stata una questione importante nella chimica di sintesi. Da questo punto di vista, per sintetizzare complessi heterometallic multinucleate in modo designable è ancora un soggetto degno di essere impugnata nel campo della chimica inorganica a causa del numero di possibili risultati strutturali dal approccio basato ligando-metallazione che viene comunemente utilizzato per la preparazione di complessi metallici monomerici. Sebbene alcuni esempi di complessi heterometallic multinucleate sono stati segnalati finora 1,2,3, la prova ed errore o usurante della loro sintesi richiede lo sviluppo di un metodo semplice che è applicabile per una vasta gamma di strutture. Come un nuovo approccio per affrontare questo problema, nel 2011, abbiamo riportato una metodologia sintetica di 4,5 dove i vari complessi metallici mononucleare che hanno un residuo amminoacido Fmoc-protetti sono in sequenza accoppiati per dare piùmetallico array peptidici utilizzando i protocolli di fase solida polipeptide sintesi 6. A causa della natura consecutivo di sintesi polipeptide, una sequenza specifica di molteplici centri metallici è razionalmente designable controllando il numero e l&#39;ordine delle reazioni di accoppiamento di tali monomeri complessi metallici. Più tardi, questo approccio è stato ulteriormente modulare per fare i vari grandi e / o ramificati strutture di array, combinando con il legame covalente tra due matrici più brevi 7. Qui mostreremo come la sintesi di tali matrici peptidici multimetallic è tipicamente gestito scegliendo il WSMOCA recentemente riportato (1 8 CAS RN 1827663-18-2; figura 1) come un esempio rappresentativo. Sebbene la sintesi di un particolare vettore è descritto in questo protocollo, le stesse procedure sono applicabili alla sintesi di una vasta gamma di differenti sequenze, compresi gli isomeri 9. Ci aspettiamo che questo protoCol ispirerà più ricercatori a partecipare alla scienza di composti sequenza controllata, in cui le molecole studiate finora sono state in genere biopolimeri, ma raramente sono esempi di specie metallo-complesso-based.

<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.

La figura 1 mostra le strutture molecolari dei composti finali di destinazione, precursori, e intermedi. La Figura 2 mostra le immagini della resina e la figura 3 mostra gli spettri di massa MALDI-TOF dei campioni a gradini procedura selezionata. Immagini da Figura 2a a 2h mostrano i cambiamenti nel colore e l&#39;aspetto della resina che subisce durante le fasi di reazione nella sezione 2 del protocollo...

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.

Sintesi di una serie complessa Metal-Organic solubile in acqua

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 Views.  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.

Sintesi, Consegna Cellulare e<em&gt; In vivo</em&gt; Applicazione di sensori di pH basati Dendrimero

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

Ricerca

Chimica

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.

Modelli atomicamente definiti per epitassiale crescita di ossido Complex Thin Films

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.

Acqua in emulsioni olio: un nuovo sistema di montaggio idrosolubili proteine ​​clorofilla vincolante con pigmenti idrofobi

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.

Sintesi ed esfoliazione della discotici zirconio Fosfati di ottenere cristalli liquidi colloidale

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 diretto, Early Stage Guanidinylation protocollo per la sintesi di complessi Aminoguanidine contenenti prodotti naturali

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.

Sintesi e caratterizzazione di supramolecolari colloidi

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.

Chemio-enzimatico di sintesi della N- glicani matrice dello sviluppo e dell'anticorpo HIV profilatura

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.

Rimozione eterogenei di rutenio solubile in acqua dell'olefina metatesi catalizzatore da mezzi acquosi tramite interazione 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.

Produzione additiva negativa del complesso a forma di carburi di 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.

Sali fusi sintesi di nanoparticelle di ossido di metallo complesso

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