Name: synthesis of a water-soluble metal&#8211;organic complex array
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Description: Watch this Scientific Journal Video about Synthesis of a Water-soluble MetalÃ¢â‚¬â€œOrganic Complex Array at JoVE.com

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. Preparation of Metal Complex Monomers (2 CAS RN 1381776-70-0, 3 CAS RN 1261168-42-6, 4 CAS RN 1261168-43-7; Figure 1)
<ol>
	<li>Preparation of Ru monomer 2
	<ol>
		<li>Combine the organic precursor (59 CAS RN 1381776-63-1; Figure 1) (380 mg, 0.48 mmol) and [Ru(p-cymene)Cl2] dimer (224 mg, 0.37 mmol) with a stir bar in a 100 ml single-neck round-bottom flask.</li>
		<li>Add methanol (MeOH) (25 ml) to the mixture, connect a condenser to ...

<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>

Perfect removal of the undesired chemicals from the resin is not always possible simply by washing with solvents that can easily dissolve those chemicals. A key technique to efficiently wash the resin is to cause it to swell and shrink repetitively so that the chemicals remaining inside will be forced out. This is why the resin in our procedure is treated with CH2Cl2 and MeOH alternately as it is washed (e.g., protocol 2.1.4).
As a consequence of successive multi...

Controlled synthesis of complicated molecular structures has always been a major issue in synthetic chemistry. From this point of view, to synthesize multinuclear heterometallic complexes in a designable fashion is still a worthy subject to be challenged in the field of inorganic chemistry because of the numbers of possible structural outcomes from the ligand-metallation-based approach that is commonly used for the preparation of monomeric metal complexes. Although several examples of multinuclear heterometallic complexes have been reported so far1,2,3, the trial-and-error or arduous nature of their synthesis necessitates the development of a simple method that is applicable for a wide range of structures.
As a new approach to address this issue, in 2011 we reported a synthetic methodology4,5 where various mononuclear metal complexes having a Fmoc-protected amino acid moiety are sequentially coupled to give multimetallic peptidic arrays by using the protocols of solid-phase polypeptide synthesis6. Due to the consecutive nature of polypeptide synthesis, a specific sequence of multiple metal centers is rationally designable by controlling the number and order of the coupling reactions of those metal complex monomers. Later, this approach was further modularized to make various larger and/or branched array structures by combining with the covalent linkage between two shorter arrays7.
Here we will show how the synthesis of such multimetallic peptidic arrays is typically operated by choosing the recently reported WSMOCA (18 CAS RN 1827663-18-2; Figure 1) as a representative example. Although the synthesis of one particular array is described in this protocol, the same procedures are applicable to the synthesis of a wide range of different sequences, including isomers9. We expect that this protocol will inspire more researchers to participate in the science of sequence-controlled compounds, where the molecules investigated thus far have typically been biopolymers but rarely include examples of metal-complex-based species.

<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.

Figure 1 shows the molecular structures of the final target compound, precursors, and intermediates. Figure 2 shows the images of the resin and Figure 3 shows the MALDI-TOF mass spectra of samples at selected procedure steps. Images from Figure 2a to 2h show the changes in the color and appearance of the resin that it undergoes during the reaction steps in section 2 of the protocol. MALDI-TOF mass spectro...

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 MetalÃƒÆ’Ã‚Â¢ÃƒÂ¢Ã¢â‚¬Å¡Ã‚Â¬ÃƒÂ¢Ã¢â€šÂ¬Ã…â€œOrganic Complex Array

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

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 ...

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