Flexibility Coexists with Shape-Persistence in Cyanostar Macrocycles.
Flexibility Coexists with Shape-Persistence in Cyanostar Macrocycles.
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DOI：
10.1021/jacs.6b00712
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发表时间：
2016-04-13
影响因子：
15
通讯作者：
Flood AH
中科院分区：
文献类型：
--
作者：
Liu Y;Singharoy A;Mayne CG;Sengupta A;Raghavachari K;Schulten K;Flood AH
形状持久的大环是合成、分子识别和层次自组装的有吸引力的功能靶标。这种大环是不可折叠的，几何上定义良好，它们的传统特征是具有重复单元和低构象灵活性。在这里，我们发现有必要在面对高度灵活但形状持久的宏观循环时改进这些想法。如果一个分子在受到外部刺激（如热、光和氧化还原化学）的扰动时，其形状发生了微小的变化，则该分子具有形状持久性。为了支持这一观点，我们首次对大环的形状持久性、构象空间和由此产生的函数之间的关系进行了研究。我们用一种叫做蓝星的星形大循环来做到这一点，它既灵活又具有形状持久性。我们采用分子动力学（MD）、密度泛函理论（DFT）和核磁共振实验。考虑热浴作为刺激，我们发现单个大循环有332个可接近的构象，烯烃在短时间尺度（0.2 ns）内通过上下和内外运动快速相互转化。这些相互转换的构象将单个蓝星分类为柔性的。为了确定并确认蓝星具有形状持久性，我们表明它在这些构象中具有高达87%的形状相似性。为了进一步验证这一想法，我们使用二甘酸与单个大循环的结合作为客人诱导的刺激。这个客体对构象空间几乎没有影响。然而，包含两个大环的2:1三明治复合物的形成提高了刚性，并显著地将构象分布转向完美的碗状结构。总的来说，本研究扩大了形状持久大环的范围，当且仅当它们的构象具有相似的形状时，包括柔性大环。
Shape-persistent macrocycles are attractive functional targets for synthesis, molecular recognition, and hierarchical self-assembly. Such macrocycles are non-collapsible and geometrically well-defined, and they are traditionally characterized by having repeat units and low conformational flexibility. Here, we find it necessary to refine these ideas in the face of a highly flexible yet shape-persistent macrocycles. A molecule is shape-persistent if it has a small change in shape when perturbed by external stimuli (e.g., heat, light, and redox chemistry). In support of this idea we provide the first examination of the relationships between a macrocycle’s shape persistence, its conformational space, and the resulting functions. We do this with a star-shaped macrocycle called cyanostar that is flexible as well as being shape-persistent. We employed molecular dynamics (MD), density functional theory (DFT), and NMR experiments. Considering a thermal bath as a stimulus we found a single macrocycle has 332 accessible conformers with olefins undergoing rapid interconversion by up-down and in-out motions on short time scales (0.2 ns). These many interconverting conformations classify single cyanostars as flexible. To determine and confirm that cyanostars are shape-persistent, we show that it has a high 87% shape similarity across these conformations. To further test the idea, we use the binding of diglyme to the single macrocycle as guest-induced stimulation. This guest has almost no effect on the conformational space. However, formation of a 2:1 sandwich complex involving two macrocycles enhances rigidity and dramatically shifts the conformer distribution towards perfect bowls. Overall, the present study expands the scope of shape-persistent macrocycles to include flexible macrocycles if and only if their conformers have similar shapes.