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 the joint of the flask, and stir the suspension at 65 &#176;C for 3 hr in a temperature-controlled oil bath.</li>
		<li>Cool the reaction mixture to room temperature and filter the suspension through a filter paper by suction.</li>
		<li>Wash the residue on the filter thoroughly with MeOH until the filtrate becomes visually colorless and dry the residue under reduced pressure.</li>
		<li>Combine the residue and 4&#39;-(4-methylphenyl)-2,2&#39;:6&#39;,2&#34;-terpyridine (216 mg, 0.68 mmol) with a stir bar in a 100 ml single-neck round-bottom flask.</li>
		<li>Add MeOH (22.5 ml) and water (2.5 ml) to the mixture, connect a condenser to the joint of the flask, and stir the suspension at 70 &#176;C for 16 hr.</li>
		<li>Cool the reaction mixture to room temperature and filter the suspension.</li>
		<li>Dry the residue on the filter under reduced pressure and dissolve it in dimethyl sulfoxide (DMSO) (3 ml).</li>
		<li>Add the DMSO solution slowly to an excess of ethyl acetate (EtOAc).</li>
		<li>Filter the resultant suspension, wash the residue on the filter with EtOAc, and dry it under reduced pressure.</li>
	</ol>
	</li>
	<li>Preparation of Pt monomer 3
	<ol>
		<li>Combine the organic precursor (64 CAS RN 1261168-39-1; Figure 1) (360 mg, 0.50 mmol) and Pt(cycloocta-1,5-diene)Cl2 (195 mg, 0.52 mmol) with a stir bar in a 100 ml single-neck round-bottom flask.</li>
		<li>Add MeOH (15 ml) to the mixture, connect a condenser to the joint of the flask, and stir the suspension at 65 &#176;C for 12 hr.</li>
		<li>Cool the reaction mixture to room temperature and filter the suspension.</li>
		<li>Wash the residue on the filter thoroughly with MeOH and dry it under reduced pressure.</li>
	</ol>
	</li>
	<li>Preparation of Rh monomer 4
	<ol>
		<li>Combine the organic precursor (6; Figure 1) (360 mg, 0.50 mmol) and RhCl3&#183;3H2O (137 mg, 0.52 mmol) with a stir bar in a 100 ml single-neck round-bottom flask.</li>
		<li>Add MeOH (50 ml) to the mixture, connect a condenser to the joint of the flask, and stir the suspension at 65 &#176;C for 12 hr under a N2 atmosphere.</li>
		<li>Cool the reaction mixture to room temperature and filter the suspension.</li>
		<li>Wash the residue on the filter thoroughly with MeOH and dry it under reduced pressure.</li>
	</ol>
	</li>
</ol>
2. Preparation of Water-soluble Metal&#8211;Organic Complex Array 1
<ol>
	<li>Fmoc Deprotection from TG Sieber Resin
	<ol>
		<li>Combine as-purchased TG Sieber resin (135 mg) with a stir bar in a 10 ml 2-neck flask bearing a drain at the bottom equipped with a glass filter and a 2-way stop cock (Figure 2a). Connect a 3-way stop cock and a glass stopper to the joints of the flask.</li>
		<li>Exchange the internal atmosphere with N2 by using a vacuum line, and then swell the resin with anhydrous-grade dichloromethane (CH2Cl2) (1 ml) (Figure 2b).</li>
		<li>Add anhydrous-grade dimethylformamide (DMF) (3 ml) and piperidine (1 ml) in this order and stir the mixture for 2.5 hr at room temperature.</li>
		<li>Remove the solution by filtration through the drain. Wash the resin with anhydrous-grade MeOH (3 ml, 3 min stirring) and anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) alternately three times and then with anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) four times (Figure 2c).</li>
		<li>Combine all the solutions obtained in 2.1.4 and dilute them with acetonitrile (CH3CN) to a volume of 50 ml. Transfer an aliquot (1 ml) of the resultant solution into a quartz cuvette with an optical length of 1 cm and dilute it with CH3CN (2 ml).</li>
		<li>Determine the mol number of deprotected Fmoc moiety (f &#181;mol) based upon the extinction coefficient of piperidine-dibenzofulvene adduct (6,234 at 299 nm)10 and the spectroscopically obtained absorbance (a) of the solution prepared through protocol 2.1.5 according to the following equation: 
		f = 0.05 x 106 x 3 x a/6234</li>
	</ol>
	</li>
	<li>Loading of Ru monomer 2
	<ol>
		<li>Add anhydrous-grade CH2Cl2 (2.5 ml), Ru monomer 2 (64.9 mg, 53.2 &#181;mol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (30.3 mg, 79.8 &#181;mol), anhydrous-grade DMSO (2.5 ml), and N,N-diisopropylethylamine (iPr2NEt) (20 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature (Figure 2d).</li>
		<li>Remove the solution by filtration through the drain. Wash the resin with anhydrous-grade DMSO (3 ml, 5 min stirring) three times, anhydrous-grade MeOH (3 ml, 3 min stirring) and anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) alternately three times, and anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) three times.</li>
		<li>Add anhydrous-grade CH2Cl2 (5 ml), benzoic anhydride (0.28 g, 1.5 mmol), and N-methylimidazole (0.10 ml, 1.5 mmol) in this order under a N2 atmosphere to the washed resin and stir the mixture for 2 hr at room temperature.</li>
		<li>Remove the solution by filtration through the drain. Wash the resin with anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) and anhydrous-grade MeOH (3 ml, 3 min stirring) alternately three times and then with anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) three times.</li>
		<li>Repeat the protocols as described in 2.1.3-2.1.6 to quantify the mol number of loaded Ru monomer 2.</li>
	</ol>
	</li>
	<li>Loading of Fmoc- and side-residue tertiary-butyl (tBu)-protected (L)-glutamic acid (Glu) (7 CAS RN 71989-18-9; Figure 1)
	<ol>
		<li>Add anhydrous-grade CH2Cl2 (4.5 ml), Glu&#183;H2O (39.4 mg, 88.8 &#181;mol), HBTU (50.5 mg, 133.2 &#181;mol), anhydrous-grade DMSO (0.5 ml), and iPr2NEt (50 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature (Figure 2e). 
		&#8203;NOTE: The amounts of Glu&#183;H2O and HBTU are gradually decreased from steps 2.3 to 2.7 to keep their stoichiometry to the reactive -NH2 functionality on the resin constant.</li>
		<li>Repeat the protocols as described in 2.2.2-2.2.4.</li>
		<li>Take a small portion of the resin out of the flask and put it into a mixture of trifluoroacetic acid (CF3CO2H) (2.5 &#181;l), triethylsilane (Et3SiH) (0.5 &#181;l), and 1,2-dichloroethane (47 &#181;l). Sonicate the mixture for 0.5 hr and use the resultant solution for mass spectrometry4,7,8,9 (Figure 3a).</li>
		<li>Repeat the protocols as described in 2.1.3-2.1.6 to quantify the mol number of loaded Glu.</li>
	</ol>
	</li>
	<li>Loading of Pt monomer 3
	<ol>
		<li>Add anhydrous-grade DMSO (4.5 ml), Pt monomer (32.9 mg, 33.3 &#181;mol), HBTU (18.9 mg, 50.0 &#181;mol), anhydrous-grade CH2Cl2 (0.5 ml), and iPr2NEt (20 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature (Figure 2f).</li>
		<li>Repeat the protocols as described in 2.2.2-2.2.5 to quantify the mol number of loaded Pt monomer 3.</li>
	</ol>
	</li>
	<li>Loading of Glu
	<ol>
		<li>Add anhydrous-grade CH2Cl2 (4.5 ml), Glu&#183;H2O (27.8 mg, 62.9 &#181;mol), HBTU (35.8 mg, 94.4 &#181;mol), anhydrous-grade DMSO (0.5 ml), and iPr2NEt (50 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature.</li>
		<li>Repeat the protocols as described in 2.3.2-2.3.4 (Figure 3b).</li>
	</ol>
	</li>
	<li>Loading of Rh monomer 4
	<ol>
		<li>Add anhydrous-grade DMSO (4.5 ml), Rh monomer 4 (21.8 mg, 23.3 &#181;mol), HBTU (13.3 mg, 35.0 &#181;mol), anhydrous-grade CH2Cl2 (0.5 ml), and iPr2NEt (20 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature (Figure 2g).</li>
		<li>Repeat the protocols as described in 2.2.2.</li>
		<li>Repeat the protocols as described in 2.6.1.</li>
		<li>Repeat the protocols as described in 2.2.2-2.2.5 to quantify the mol number of loaded Rh monomer 4.</li>
	</ol>
	</li>
	<li>Loading of Glu
	<ol>
		<li>Add anhydrous-grade CH2Cl2 (4.5 ml), Glu&#183;H2O (20.4 mg, 46.0 &#181;mol), HBTU (26.2 mg, 69.0 &#181;mol), anhydrous-grade DMSO (0.5 ml), and iPr2NEt (50 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature.</li>
		<li>Repeat the protocols as described in 2.3.2-2.3.4 (Figure 3c).</li>
	</ol>
	</li>
	<li>Loading of 2-[2-(2-methoxyethoxy)ethoxy]acetic (TEG) acid (8 CAS RN 16024-58-1; Figure 1)
	<ol>
		<li>Add anhydrous-grade CH2Cl2 (3 ml), TEG acid (14 &#181;l, 91.0 &#181;mol), HBTU (51.7 mg, 136.5 &#181;mol), anhydrous-grade CH2Cl2 (2 ml), and iPr2NEt (50 &#181;l) in this order under a N2 atmosphere to the washed resin and stir the mixture for 12 hr at room temperature.</li>
		<li>Remove the solution by filtration through the drain. Wash the resin with anhydrous-grade DMSO (3 ml, 5 min stirring) two times, anhydrous-grade MeOH (3 ml, 3 min stirring) and anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) alternately three times, and anhydrous-grade CH2Cl2 (3 ml, 3 min stirring) three times.</li>
	</ol>
	</li>
	<li>Cleavage from the resin at the end of solid-phase synthesis
	<ol>
		<li>Wash the resin with diethyl ether (4 ml, 5 min stirring) three times, dry it under a vacuum, and swell it with anhydrous-grade CH2Cl2 (1 ml, 5 min stirring).</li>
		<li>Add a mixture of CF3CO2H (0.1 ml), Et3SiH (20 &#181;l), and 1,2-dichloroethane (1.9 ml) to the suspension and stir the mixture for 12 hr at room temperature.</li>
		<li>Remove the solution by filtration through the drain, add a new mixture of CF3CO2H (0.1 ml), Et3SiH (20 &#181;l), and 1,2-dichloroethane (1.9 ml) to the resin, and stir the mixture for 1 hr at room temperature.</li>
		<li>Repeat step 2.9.3 until the solution becomes visually colorless (Figure 2h).</li>
		<li>Combine all the solutions as obtained through protocols 2.9.2-2.9.4 and analyze the contents of the resultant solution by mass spectrometry4,7,8,9 (Figure 3d).</li>
		<li>Remove volatile species of the solution by evaporation and dissolve the residue in a mixture of CF3CO2H (0.2 ml), Et3SiH (40 &#181;l), and 1,2-dichloroethane (3.8 ml).</li>
		<li>Stir the mixture for 24 hr at room temperature and analyze the contents of the resultant solution by mass spectrometry4,7,8,9 to confirm the complete deprotection of tBu groups at the side residues of 1 (Figure 3e).</li>
		<li>Remove volatile species of the solution by evaporation.</li>
	</ol>
	</li>
	<li>Purification of 1
	<ol>
		<li>Sonicate the solid residue as obtained through protocol 2.9 in CH2Cl2 and decant the solution. Repeat this process until the decant solution becomes visually colorless.</li>
		<li>Analyze the contents of the resultant solid residue by mass spectrometry4,7,8,9.</li>
		<li>Wash the residue with MeOH (100 &#181;l/10 mg) with sonication, decant the solution, and analyze the contents of the resultant solid residue by mass spectrometry4,7,8,9.</li>
		<li>Dissolve the residue (1 mg) in a mixture of CH3CN (90 &#181;l) and water (10 &#181;l) by sonication and combine the resultant solution with phosphate-buffered saline (800 &#181;l, 10 mM, pH = 7.4). Sonicate the mixture and incubate it at 37 &#176;C for 24 hr.</li>
		<li>Extract the colored species in the decant supernatant with a mixture of 1,2-dichloroethane (500 &#181;l), CH3CN (20 &#181;l), and CF3CO2H (20 &#181;l). Analyze the extract by mass spectrometry4,7,8,9 (Figure 3f).</li>
		<li>Repeat the extraction until the aqueous phase becomes visually colorless. Combine the organic solutions and remove volatile species by evaporation.</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.

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><tbody><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&amp;nbsp;</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>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 &amp;Aring; sieves</td></tr><tr><td>Dithranol</td><td>Wako Pure Chemical Industries</td><td>191502</td><td></td></tr><tr><td>&lt;em&gt;N&lt;/em&gt;-methylimidazole</td><td>TCI</td><td>M0508</td><td></td></tr><tr><td>Piperidine</td><td>Kanto Chemical</td><td>32249-30</td><td></td></tr><tr><td>4&#039;-(4-methylphenyl)-2,2&#039;:6&#039;,2&quot;-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&amp;nbsp;</td><td></td></tr><tr><td>Dehydrated grade methanol</td><td>Kanto Chemical</td><td>25506-05&amp;nbsp;</td><td></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&amp;nbsp;</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&amp;nbsp;</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&amp;nbsp;</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...

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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.

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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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 and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework

We present a method for preparing thioester molecules as the masked form of the thiol linkers and their utilization for accessing a semiconducting and porous metal-dithiolene network in the highly ordered single crystalline state. Unlike the highly reactive free-standing thiols, which tend to decompose and complicate the crystallization of metal-thiolate open frameworks, the thioester reacts in situ to provide the thiol species, serving to mitigate the reaction between the mercaptan units and the metal centers, and to improve crystallization consequently. Specifically, the thioester was synthesized in a one-pot procedure: an aromatic bromide (hexabromotriphenylene) reacted with excess sodium thiomethoxide under vigorous conditions to first form the thioether intermediate product. The thioether was then demethylated by the excess thiomethoxide to provide the thiolate anion that was acylated to form the thioester product. The thioester was conveniently purified by standard column chromatography, and then used directly in the framework synthesis, wherein NaOH and ethylenediamine serve to revert in situ the thioester to the thiol linker for assembling the single-crystalline Pb(II)-dithiolene network. Compared with other methods for thiol synthesis (e.g., by cleaving alkyl thioether using sodium metal and liquid ammonia), the thioester synthesis here uses simple conditions and economical reagents. Moreover, the thioester product is stable and can be conveniently handled and stored. More importantly, in contrast to the generic difficulty in accessing crystalline metal-thiolate open frameworks, we demonstrate that using the thioester for in situ formation of the thiol linker greatly improves the crystallinity of the solid-state product. We intend to encourage broader research efforts on the technologically important metal-sulfur frameworks by disclosing the synthetic protocol for the thioester as well as the crystalline framework solid.

Here, we present a one-pot, transition-metal-free synthesis of thiols and thioesters from aromatic halides and sodium thiomethoxide, followed by the preparation of single crystals of a metal-dithiolene network using thiol species generated in situ from the more stable and tractable thioester.

We present a method for preparing thioester molecules as the masked form of the thiol linkers and their utilization for accessing a semiconducting and ...

Surface Functionalization of Metal-Organic Frameworks for Improved Moisture Resistance

Metal-organic frameworks (MOFs) are a class of porous inorganic materials with promising properties in gas storage and separation, catalysis and sensing. However, the main issue limiting their applicability is their poor stability in humid conditions. The common methods to overcome this problem involve the formation of strong metal-linker bonds by using highly charged metals, which is limited to a number of structures, the introduction of alkylic groups to the framework by post-synthetic modification (PSM) or chemical vapour deposition (CVD) to enhance overall hydrophobicity of the framework. These last two usually provoke a drastic reduction of the porosity of the material. These strategies do not permit to exploit the properties of the MOF already available and it is imperative to find new methods to enhance the stability of MOFs in water while keeping their properties intact. Herein, we report a novel method to enhance the water stability of MOF crystals featuring Cu2(O2C)4&#160;paddle-wheel units, such as HKUST (where HKUST stands for Hong Kong University of Science &#38; Technology), with the catechols functionalized with alkyl and fluoro-alkyl chains. By taking advantage of the unsaturated metal sites and the catalytic catecholase-like activity of CuII ions, we are able to create robust hydrophobic coatings through the oxidation and subsequent polymerization of the catechol units on the surface of the crystals under anaerobic and water-free conditions without disrupting the underlying structure of the framework. This approach not only affords the material with improved water stability but also provides control over the function of the protective coating, which enables the development of functional coatings for the adsorption and separations of volatile organic compounds. We are confident that this approach could also be extended to other unstable MOFs featuring open metal sites.

Robust functional catechol coatings were produced in one step by direct reaction of the material known as HKUST with synthetic catechols under anaerobic conditions. The formation of homogeneous coatings surrounding the entire crystal is ascribed to the biomimetic catalytic activity of Cu(II) dimers on the external surface of the crystals.

Metal-organic frameworks (MOFs) are a class of porous inorganic materials with promising properties in gas storage and separation, catalysis and sensing. ...

Synthesis of Single-Crystalline Core-Shell Metal-Organic Frameworks

Because of their designability and unprecedented synergistic effects, core-shell metal-organic frameworks (MOFs) have been actively examined recently. However, the synthesis of single-crystalline core-shell MOFs is very challenging, and thus a limited number of examples have been reported. Here, we suggest a method of synthesizing single-crystalline HKUST-1@MOF-5 core-shells, which is HKUST-1 at the center of MOF-5. Through the computational algorithm, this pair of MOFs was predicted to have the matched lattice parameters and chemical connection points at the interface. To construct the core-shell structure, we prepared the octahedral- and cubic-shaped HKUST-1 crystals as a core MOF, in which the (111) and (001) facets were mainly exposed, respectively. Via the sequential reaction, the MOF-5 shell was well-grown on the exposed surface, showing a seamless connect interface, which resulted in the successful synthesis of single-crystalline HKUST-1@MOF-5. Their pure phase formation was proved by optical microscopic images and powder X-ray diffraction (PXRD) patterns. This method presents the potential of and insights into the single-crystalline core-shell synthesis with different kinds of MOFs.

Here, we demonstrate a protocol for the two-step synthesis of single-crystalline core-shells using a non-isostructural metal-organic framework (MOF) pair, HKUST-1 and MOF-5, which have well-matched crystal lattices.

Because of their designability and unprecedented synergistic effects, core-shell metal-organic frameworks (MOFs) have been actively examined recently. ...

Synthesis of Low-Valent MOFs from Multitopic Phosphine Linkers

Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers

Metal-organic frameworks (MOFs) are the subject of intense research focus due to their potential applications in gas storage and separation, biomedicine, energy, and catalysis. Recently, low-valent MOFs (LVMOFs) have been explored for their potential use as heterogeneous catalysts, and multitopic phosphine linkers have been shown to be a useful building block for the formation of LVMOFs. However, the synthesis of LVMOFs using phosphine linkers requires conditions that are distinct from those in the majority of the MOF synthetic literature, including the exclusion of air and water and the use of unconventional modulators and solvents, making it somewhat more challenging to access these materials. This work serves as a general tutorial for the synthesis of LVMOFs with phosphine linkers, including information on the following: 1) the judicious choice of the metal precursor, modulator, and solvent; 2) the experimental procedures, air-free techniques, and required equipment; 3) the proper storage and handling of the resultant LVMOFs; and 4) useful characterization methods for these materials. The intention of this report is to lower the barrier to this new subfield of MOF research and facilitate advancements toward novel catalytic materials.

Author Spotlight: Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers  

Here, we describe a protocol for the synthesis of low-valent metal-organic frameworks (LVMOFs) from low-valent metals and multitopic phosphine linkers under air-free conditions. The resulting materials have potential applications as heterogeneous catalyst mimics of low-valent metal-based homogeneous catalysts.

Metal-organic frameworks (MOFs) are the subject of intense research focus due to their potential applications in gas storage and separation, biomedicine, ...

Triazole and Tetrazole Functionalized Zr-MOFs Synthesis and Characterization

Synthesis of Triazole and Tetrazole-Functionalized Zr-Based Metal-Organic Frameworks Through Post-Synthetic Ligand Exchange

Metal-organic frameworks (MOFs) are a class of porous materials that are formed through coordination bonds between metal clusters and organic ligands. Given their coordinative nature, the organic ligands and strut framework can be readily removed from the MOF and/or exchanged with other coordinative molecules. By introducing target ligands to MOF-containing solutions, functionalized MOFs can be obtained with new chemical tags via a process called post-synthetic ligand exchange (PSE). PSE is a straightforward and practical approach that enables the preparation of a wide range of MOFs with new chemical tags via a solid-solution equilibrium process. Furthermore, PSE can be performed at room temperature, allowing the incorporation of thermally unstable ligands into MOFs. In this work, we demonstrate the practicality of PSE by using heterocyclic triazole- and tetrazole-containing ligands to functionalize a Zr-based MOF (UiO-66; UiO = University of Oslo). After digestion, the functionalized MOFs are characterized via various techniques, including powder X-ray diffraction and nuclear magnetic resonance spectroscopy.

Author Spotlight: Functionalizing Metal-Organic Frameworks: Advancements, Challenges, and the Power of Post-Synthetic Ligand Exchange 

Post-synthetic ligand exchange (PSE) is a versatile and powerful tool for installing functional groups into metal-organic frameworks (MOFs). Exposing MOFs to solutions containing triazole- and tetrazole-functionalized ligands can incorporate these heterocyclic moieties into Zr-MOFs through PSE processes.

Metal-organic frameworks (MOFs) are a class of porous materials that are formed through coordination bonds between metal clusters and organic ligands. ...

Synthesis and Discovery of Phosphonate-Based MOFs: A Solvothermal Approach

Discovery and Synthesis Optimization of Isoreticular Al(III) Phosphonate-Based Metal-Organic Framework Compounds Using High-Throughput Methods

High-throughput (HT) methods are an important tool for the fast and efficient screening of synthesis parameters and the discovery of new materials. This manuscript describes the synthesis of metal-organic frameworks (MOFs) from solution using an HT reactor system, resulting in the discovery of various phosphonate-based MOFs of the composition [Al2H12-x(PMP)3]Clx&#8729;6H2O (H4PMP = N,N &#39;-piperazine bis(methylenephosphonic acid)) for x = 4, 6, denoted as Al-CAU-60-xHCl, containing trivalent aluminum ions. This was accomplished under solvothermal reaction conditions by systematically screening the impact of the molar ratio of the linker to the metal and the pH of the reaction mixture on the product formation. The protocol for the HT investigation includes six steps: a) synthesis planning (DOE = design of&#160;experiment) within the HT methodology, b) dosing and working with in-house developed HT reactors, c) solvothermal synthesis, d) synthesis workup using in-house developed filtration blocks, e) characterization by HT powder X-ray diffraction, and f) evaluation of the data. The HT methodology was first used to study the influence of acidity on the product formation, leading to the discovery of Al-CAU-60&#8729;xHCl (x = 4 or 6).

Author Spotlight: Accelerating Discovery in Microporous Material Chemistry 

The targeted synthesis of new metal-organic frameworks (MOFs) is difficult, and their discovery depends on the knowledge and creativity of the chemist. High-throughput methods allow complex synthetic parameter fields to be explored quickly and efficiently, accelerating the process of finding crystalline compounds and identifying synthetic and structural trends.

High-throughput (HT) methods are an important tool for the fast and efficient screening of synthesis parameters and the discovery of new materials. This ...

Self-Assembly of Polymer-Grafted Metal Organic Framework Monolayers

Synthesis and Characterization of Self-Assembled Metal-Organic Framework Monolayers Using Polymer-Coated Particles

Metal-organic frameworks (MOFs) are materials with potential applications in fields such as gas adsorption and separation, catalysis, and biomedicine. Attempts to enhance the utility of MOFs have involved the preparation of various composites, including polymer-grafted MOFs. By directly grafting polymers to the external surface of MOFs, issues of incompatibility between polymers and MOFs can be overcome. Polymer brushes grafted from the surface of MOFs can serve to stabilize the MOF while enabling particle assembly into self-assembled metal-organic framework monolayers (SAMMs) via polymer-polymer interactions.
Control over the chemical composition and molecular weight of the grafted polymer can allow for tuning of the SAMM characteristics. In this work, instructions are provided on how to immobilize a chain transfer agent (CTA) onto the surface of the MOF UiO-66 (UiO = Universitetet i Oslo). The CTA&#160;serves as initiation sites for the growth of polymers. Once polymer chains are grown from the MOF surface, the formation of SAMMs is achieved through self-assembly at an air-water interface. The resulting SAMMs are characterized and shown to be freestanding by scanning electron microscopy imaging. The methods presented in this paper are expected to make the preparation of SAMMs more accessible to the research community and thereby expand their potential use as a&#160;MOF-polymer composite.

Author Spotlight: Exploring Self-Assembled MOF-Polymer Composites

A protocol for the synthesis and characterization of self-assembled metal-organic framework monolayers is provided using polymer-grafted, metal-organic framework (MOF) crystals. The procedure shows that polymer-grafted MOF particles can be self-assembled at an air-water interface resulting in well-formed, free-standing, monolayer structures as evidenced by scanning electron microscopy imaging.

Metal-organic frameworks (MOFs) are materials with potential applications in fields such as gas adsorption and separation, catalysis, and biomedicine. ...

Molecular Orbital (MO) Theory

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes featuring the ligand 1,1&#39;-bis(diphenylphosphino)ferrocene (dppf): M(dppf)Cl2, where M = Ni or Pd. While both of these transition metal complexes are 4-coordinate, they exhibit different geometries at the metal center. Using molecular orbital (MO) theory in conjunction with 1H NMR and Evans method, we will determine the geometry of these two compounds.

Molecular Orbital MO Theory: Predicting Geometry of Transition Metal Complexes

Source: Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
This protocol serves as a guide in the synthesis of two metal complexes ...

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Inorganic Chemistry

Synthesis of an Oxygen-Carrying Cobalt(II) Complex

Source: Deepika Das, Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
Bioinorganic chemistry is the field of study that investigates the role that metals play in biology. Approximately half of all proteins contain metals and it is estimated that up to one third of all proteins rely on metal-containing active sites to function. Proteins that feature metals, called metalloproteins, play a vital role in a variety of cell functions that are necessary for life. Metalloproteins have intrigued and inspired synthetic inorganic chemists for decades, and many research groups have dedicated their programs to modeling the chemistry of metal-containing active sites in proteins through the study of coordination compounds.
The transport of O2 is a vital process for living organisms. O2-transport metalloproteins are responsible for binding, transporting, and releasing oxygen, which can then be used for life processes such as respiration. The oxygen-carrying cobalt coordination complex, [N,N&#39;-bis(salicylaldehyde)ethylenediimino]cobalt(II) [Co(salen)]2&#160;has been studied extensively to gain understanding about how metal complexes reversibly bind O2.1
In this experiment, we will synthesize [Co(salen)]2 and study its reversible reaction with O2 in the presence of dimethylsulfoxide (DMSO). First, we will quantify the amount of O2 consumed upon exposure of [Co(salen)]2 to DMSO. We will then visually observe the release of O2 from the [Co(salen)]2-O2 adduct by exposing the solid to CHCl3.

Synthesis of an Oxygen-Carrying [Cosalen]2 Complex

Source: Deepika Das, Tamara M. Powers, Department of Chemistry, Texas A&#38;M University
Bioinorganic chemistry is the field of study that investigates ...

Synthesis of a Water-soluble Metal–Organic Complex Array

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