Department of Chemistry & Biochemistry, Miami University , Oxford, Ohio 45056, United States.
J Am Chem Soc. 2017 Apr 5;139(13):4821-4827. doi: 10.1021/jacs.7b00149. Epub 2017 Mar 27.
Many foldamers, oligomers that adopt well-defined secondary structures, are now known, including many exhibiting functional behavior. However, examples of foldamer subunits within larger architectures remain rare, despite the importance of higher-order structure in biomacromolecules. Here, we investigate the dynamic covalent assembly of short o-phenylenes, a simple class of aromatic foldamers, into twisted macrocycles. o-Phenylene tetramers have been combined with rod-shaped p-phenylene-, tolane-, and diphenylbutadiyene-based linkers using imine formation. Macrocyclization proceeds efficiently, inducing folding of the o-phenylenes. The resulting [3 + 3] macrocycles (three o-phenylenes and three linkers) are shape-persistent, triangular structures with twisted cores and internal diameters up to approximately 2 nm. The homochiral D-symmetric and heterochiral C-symmetric conformers can be distinguished by NMR spectroscopy. Analysis of the conformational distribution for the p-phenylene-linked macrocycle suggests that the o-phenylene units are largely decoupled, with the less-symmetrical configuration therefore entropically favored. Conformational dynamics were assessed by variable-temperature NMR spectroscopy. Confinement within the macrocyclic architecture slows the inversion of the o-phenylene moieties.
许多采用明确二级结构的分子折叠体，即寡聚物，现在已经为人所知，其中许多还表现出了功能行为。然而，尽管更高阶结构在生物大分子中很重要，但在更大的结构中仍然很少有分子折叠体亚基的例子。在这里，我们研究了短邻苯二酚的动态共价组装，邻苯二酚是一类简单的芳香族折叠体，可形成扭曲的大环。邻苯四聚体与棒状的对苯二酚、均三甲苯和二苯丁二烯基连接体通过亚胺形成结合。大环化反应高效进行，诱导邻苯二酚折叠。所得的[3+3]大环（三个邻苯二酚和三个连接体）是形状保持的、三角形结构，具有扭曲的核心和内部直径约为 2nm。通过 NMR 光谱可以区分同手性 D-对称和异手性 C-对称构象。对苯二酚连接的大环的构象分布分析表明，邻苯二酚单元在很大程度上是解耦的，因此不对称配置在热力学上更有利。构象动力学通过变温 NMR 光谱进行评估。大环结构的限制使邻苯二酚部分的反转速度减慢。
