一个水溶性金属 - 有机络合物阵列合成
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
复杂分子结构的控制合成一直是合成化学的一个重大问题。从这个观点来看，以合成多核异金属配合物在一个可设计方式仍然是一个值得受试者中，因为通常用于从基配体的金属化的方法可能的结构的结果的数字无机化学领域中受到挑战编制单体金属配合物。虽然多核异金属配合物的几个例子迄今1,2,3报道，试验和错误或它们的合成的艰巨性就必须一个简单的方法，该方法适用于大范围的结构的的发展。
作为一种新的方法来解决这个问题，在2011年，我们报道了合成方法4,5在具有Fmoc保护氨基酸部分单核的各种金属络合物依次偶合，得到多通过固相多肽合成6的协议金属肽阵列。由于多肽合成的连续性质，多个金属中心的特定序列是通过控制那些金属络合物单体的偶联反应的数量和顺序合理设计性。以后，该方法进一步模块化通过用两个较短的阵列7之间的共价键相结合，使各种更大和/或支链的阵列结构。
在这里，我们将展示如何这样多金属肽阵列的合成通常是通过选择最近报道WSMOCA（1 8 CAS RN 1827663-18-2; 图1）操作作为代表例。虽然一个特定阵列的合成在此协议的描述，相同的程序适用于宽范围的不同的序列，各异构体9的合成。我们预计，这一原山口将激发更多的研究人员参加序列控制化合物的科学，其中该分子研究迄今还典型地是生物聚合物，但很少包括的金属配合物为基础的物种的例子。
Protocol
Representative Results
Discussion
完美除去从树脂上不希望的化学物质的不总是可能简单地通过与可以容易地溶解的化学品的溶剂洗涤。一个关键的技术能够有效地洗涤树脂是以使其膨胀并反复收缩，使剩余的内部的化学品将被压出。这就是为什么在我们的程序将树脂用CH 2 Cl 2和MeOH处理交替，因为它是洗涤（ 例如，协议2.1.4）。
作为连续多非量化偶联反应的结果，在作为切割的混合物…
Divulgazioni
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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