Metal-directed dynamic formation of tertiary structure in foldamer assemblies: Orienting helices at an angle
Metal-directed dynamic formation of tertiary structure in foldamer assemblies: Orienting helices at an angle
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DOI：
10.1002/chem.200800988
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Huc, Ivan
中科院分区：
文献类型：
--
作者：
Delsuc, Nicolas;Hutin, Marie;Huc, Ivan
许多非天然折叠低聚物--或Folda-ACHTUNGRENNUNGmer--已被证明采用定义明确的螺旋或延伸构象，类似于生物聚合物的二级结构。[1]人们对折叠低聚物的兴趣源于这样一个前景，即如果生物聚合物的形式可以被模拟，它们的功能也可以被模拟，甚至被进一步扩展，从而打开了无数应用的前景。因此，Folamer化学的一条主要发展路线是对功能的研究；例如，生物活性[2，3]和分子识别特性。[4，5]然而，即使在自然界中，孤立的二级结构相对于三级或四级结构实现的功能也很少。因此，另一条折叠剂的开发路线和合成化学中的一个主要挑战是详细地设计、生产和表征由几种非天然次要元素组成的人工折叠物体。最近在这个方向上采取的关键步骤使人们能够在固态中首次表征人工的“三级”或“四级”折叠图案。[6]在这项工作中，目标不仅是使用非自然支架简单地再现自然图案，而且还探索自然界中不存在的图案。在这里，我们报告了使用金属络合物作为低聚螺旋链段之间的动态连接元件。具体地说，一个金属络合物被用来连接和定义两个螺旋的相对取向，就像蛋白质中的转角结构一样，但以一个非传统的角度。一个四面体CuI离子在两个螺旋之间提供了大致垂直的取向，而一个八面体FeII中心以几乎平行的方式取向两个螺旋。8-氨基-2-喹啉羧酸的芳香族低聚酰胺(S)在固体和各种溶剂中具有特别稳定的螺旋构象。[7]它们为以模块化方式构建大的多螺旋、折叠结构提供了坚实的基础。几个报告描述了AOA S的不可逆共价连接。[6A，8]或者，使体系自组织的动态连接促进了合成，并允许人们利用热力学平衡来探索给定体系的S的内在偏好。因此，我们着手探索使用基于金属络合物的可逆连接来连接AOA S。由胺、6-甲基-2-甲酰基吡啶和CuI(方案1)[10]动态地形成亚胺-CuI络合物非常适合于这一目的，因为它易于实现，并且因为两个水平的逆转。
A number of non-natural folding oligomers—or folda-ACHTUNGTRENNUNGmers—have been shown to adopt well-defined helical or extended conformations resembling the secondary structures of biopolymers.[1] Interest in foldamers stems from the prospect that if the forms of biopolymers can be mimicked, their functions may be mimicked as well and even be further expanded, thereby opening the perspective of countless applications. Thus, one major line of development in foldamer chemistry is the investigation of function; for example, biological activity [2, 3] and molecular-recognition properties.[4, 5] However, even in nature, isolated secondary structures achieve little function relative to tertiary or quaternary structures. Another line of foldamer development and a major challenge in synthetic chemistry is thus to elaborate strategies to design, produce, and characterize artificial, folded objects composed of several non-natural secondary elements. Key steps recently taken in this direction have allowed the first characterizations of artificial “tertiary” or “quaternary” folded motifs in the solid state.[6] In this endeavor, the objective is not simply to reproduce natural patterns using non-natural scaffolds, but also to explore patterns that do not exist in nature. Here we report on the use of metal complexes as dynamic connection elements between oligomeric helical segments. Specifically, a metal complex was used to connect and define the relative orientation of two helices, as does a turn structure in proteins, but at an unconventional angle. A tetrahedral CuI ion was shown to impart a roughly perpendicular orientation between two helices, whilst an octahedral FeII center oriented two helices in an almost parallel fashion.Aromatic oligoamides (AOA s) of 8-amino-2-quinoline carboxylic acid adopt particularly stable helical conformations in the solid state and in a wide variety of solvents.[7] They provide a firm foundation upon which to build in modular fashion towards large multi-helical, folded architectures. Several reports describe the irreversible covalent attachment of AOA s.[6a, 8] Alternatively, dynamic linkages that let the system self-organize facilitate synthesis and allow one to use thermodynamic equilibration to probe a given system s intrinsic preferences.[9] We thus set out to explore the use of reversible linkages based on metal complexes to connect AOA s. The dynamic formation of imine–CuI complexes from amines, 6-methyl-2-formylpyridine and CuI (Scheme 1)[10] was well-suited for this purpose, because it is simple to implement and because the two levels of reversi-