Anion recognition in water by synthetic host molecules has been a hot and challenging topic. It has been considered difficult because the water molecules compete for the recognition units. In this study, we have successfully created a novel macrocycle that achieves precise recognition through multipoint hydrogen bonding in harmony with the water molecules. Specifically, an N-methylpyridinium amide β-cyclodextrin (β-CD) derivative 1(OTf)₇ was synthesized, whose amide groups are directly attached to each pyranose ring. The pyridinium amide CD encapsulated a monophosphate anion in water, but it did not show interactions with sulfonates or carboxylates, thus a remarkable selectivity was demonstrated. Two monophosphates with different substituents, phenyl phosphate (PhOPO₃^2–) and adamantyl phosphate (AdOPO₃^2–), exhibited interesting contrasting pictures in the inclusion process, which were revealed by a combination of NOESY experiments, ITC measurements, and MD simulations. PhOPO₃^2– was positioned slightly “upper” (closer to the pyridinium amide side) in 1⁷⁺ with the oxygen atom of the phosphate ester R-O-P involved in the hydrogen bonds with the amide N-H, and configurational entropy plays a key role in the inclusion. Meanwhile, AdOPO₃^2– was positioned “lower” (closer to the methoxy rim of CD) with the terminal -PO₃^2– forming hydrogen bonds with the amides, and the hydrophobic effect is a major contributing driving force of the inclusion. The molecular design presented herein to achieve the precise recognition in water and clarification of the detailed mechanisms including the hydration phenomenon would greatly contribute to the development of functional molecules that work in aqueous environments.

中文翻译：

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酰胺环糊精，可识别与水分子协调的单磷酸阴离子


合成宿主分子对水中的阴离子识别一直是一个热门且具有挑战性的话题。这被认为是困难的，因为水分子争夺识别单元。在这项研究中，我们成功创造了一种新的大环，通过与水分子和谐的多点氢键实现精确识别。具体来说，合成了 N-甲基吡啶酰胺 β-环糊精 （β-CD） 衍生物 1（OTf）₇，其酰胺基团直接连接到每个吡喃糖环上。吡啶酰胺 CD 将单磷酸盐阴离子封装在水中，但它没有表现出与磺酸盐或羧酸盐的相互作用，因此表现出显着的选择性。两种具有不同取代基的单磷酸盐磷酸苯酯 （PhOPO₃^2–） 和金刚烷基磷酸盐 （AdOPO₃^2–） 在包合过程中表现出有趣的对比图，这些图片通过 NOESY 实验、ITC 测量和 MD 模拟的组合揭示出来。PhOPO₃^2– 位于 1⁷⁺ 中略微“上”（更靠近吡啶酰胺侧），磷酸酯 R-O-P 的氧原子参与与酰胺 N-H 的氢键，构型熵在包裹体中起关键作用。同时，AdOPO₃^2– 位于“较低”（更靠近 CD 的甲氧基边缘），末端 -PO₃^2– 与酰胺形成氢键，疏水效应是夹杂物的主要驱动力。 本文提出的分子设计实现了在水中的精确识别并阐明了包括水合现象在内的详细机制，这将极大地有助于在水环境中工作的功能分子的发展。