Syntese af en Vandopløseligt Metal-Organic Complex Array
Summary
A potential general method for the synthesis of water-soluble multimetallic peptidic arrays containing a predetermined sequence of metal centers is presented.
Abstract
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.
Introduction
Kontrolleret syntese af komplicerede molekylære strukturer har altid været et stort problem i syntetisk kemi. Ud fra dette synspunkt, at syntetisere multinukleære heterometallic komplekser i en designable mode er stadig en værdig emne at blive udfordret på området for uorganisk kemi på grund af antallet af mulige strukturelle resultater fra ligand-metalleringen tilgang, der almindeligvis anvendes til fremstilling af monomere metalkomplekser. Selv om flere eksempler på multinucleare heterometallic komplekser er blevet rapporteret hidtil 1,2,3, trial-and-error eller besværlige karakter af deres syntese kræver udviklingen af en simpel metode, der er gældende for en lang række strukturer.
Som en ny tilgang til at løse dette problem, vi i 2011 rapporterede en syntetisk metode 4,5 hvor forskellige mononukleære metalkomplekser har en Fmoc-beskyttet aminosyre-delen er sekventielt koblet til at give multimetallisk peptidiske arrays ved hjælp af de protokoller fast-fase polypeptid syntese 6. På grund af den fortløbende karakter polypeptidsyntese, en specifik sekvens af flere metalcentre er rationelt designable ved at styre antallet og rækkefølgen af koblingsreaktioner af disse metalkompleksfarvestoffer monomerer. Senere denne fremgangsmåde blev yderligere modulopbygget at foretage forskellige større og / eller forgrenede array-strukturer ved at kombinere med kovalente binding mellem to kortere arrays 7.
Her vil vi vise, hvordan syntesen af sådanne multimetalliske peptidiske arrays typisk drives ved at vælge den nylig rapporteret WSMOCA (1 8 CAS RN 1827663-18-2, figur 1) som et repræsentativt eksempel. Selv syntesen af en bestemt array er beskrevet i denne protokol, de samme procedurer gælder for syntesen af en bred vifte af forskellige sekvenser, herunder isomerer 9. Vi forventer, at denne protocol vil inspirere flere forskere til at deltage i videnskaben om sekvens-kontrollerede forbindelser, hvor molekylerne undersøgt hidtil har typisk været biopolymerer men sjældent omfatter eksempler på metal-kompleks-baserede arter.
Protocol
Representative Results
Discussion
Perfekt fjernelse af de uønskede kemikalier fra harpiksen ikke altid er muligt blot ved vask med opløsningsmidler, der let kan opløse disse kemikalier. Et centralt teknik til effektivt at vaske harpiksen er at få det til at svulme op og krympe repetitivt så de kemikalier forblive inde vil blive tvunget ud. Dette er grunden til harpiksen i vores procedure behandles med CH2C 2 og MeOH skift som den vaskes (fx protokol 2.1.4).
Som følge af successive flere i…
Divulgations
The authors have nothing to disclose.
Acknowledgements
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.
Materials
| Dichloro(p‐cymene)ruthenium(II), dimer | Kanto Chemical | 11443-65 | |
| Dichloro(1,5-cyclooctadiene)platinum(II) | TCI | D3592 | |
| Rhodium(III) chloride trihydrate | Kanto Chemical | 36018-62 | |
| Phosphate buffered saline, tablet | Sigma Aldrich | P4417-50TAB | |
| NovaSyn TG Sieber resin | Novabiochem | 8.55013.0005 | |
| HBTU | TCI | B1657 | |
| Benzoic anhydride | Kanto Chemical | 04116-30 | |
| Fmoc-Glu(OtBu)-OH・H2O | Watanabe Chemical Industries | K00428 | |
| Trifluoroacetic acid | Kanto Chemical | 40578-30 | |
| Triethylsilane | TCI | T0662 | |
| 2-[2-(2-Methoxyethoxy)ethoxy]acetic acid | Sigma Aldrich | 407003 | Dried over 3Å sieves |
| Dithranol | Wako Pure Chemical Industries | 191502 | |
| N-methylimidazole | TCI | M0508 | |
| N‐ethyldiisopropylamine | Kanto Chemical | 14338-32 | |
| Piperidine | Kanto Chemical | 32249-30 | |
| 4'-(4-methylphenyl)-2,2':6',2"-terpyridine | Sigma Aldrich | 496375 | |
| Dehydrated grade dimethylsulfoxide | Kanto Chemical | 10380-05 | |
| Dehydrated grade methanol | Kanto Chemical | 25506-05 | |
| Dehydrated grade N,N‐Dimethylformamide | Kanto Chemical | 11339-84 | Amine Free |
| Dehydrated grade dichloromethane | Kanto Chemical | 11338-84 | |
| MeOH | Kanto Chemical | 25183-81 | |
| Dimethylsulfoxide | Kanto Chemical | 10378-70 | |
| Ethyl acetate | Kanto Chemical | 14029-81 | |
| Acetonitrile | Kanto Chemical | 01031-70 | |
| 1,2-dichloroethane | Kanto Chemical | 10149-00 | |
| Diethyl ether | Kanto Chemical | 14134-00 | |
| Dichloromethane | Kanto Chemical | 10158-81 |
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