Yao Huan, Ke Hua, Zhang Xiaobin, Pan San-Jiang, Li Ming-Shuang, Yang Liu-Pan, Schreckenbach Georg, Jiang Wei
Department of Chemistry and Shenzhen Grubbs Institute , Southern University of Science and Technology , Shenzhen 518055 , China.
School of Chemistry and Chemical Engineering , Harbin Institute of Technology , Harbin , 150001 , China.
J Am Chem Soc. 2018 Oct 17;140(41):13466-13477. doi: 10.1021/jacs.8b09157. Epub 2018 Oct 4.
During the last half a century, great achievements have been made in molecular recognition in parallel with the invention of numerous synthetic receptors. However, the selective recognition of hydrophilic molecules in water remains a generally accepted challenge in supramolecular chemistry but is commonplace in nature. In an earlier Communication [ Huang et al. J. Am. Chem. Soc. 2016 , 138 , 14550 ], we reported a pair of endo-functionalized molecular tubes that surprisingly prefer highly hydrophilic molecules over hydrophobic molecules of a similar size and shape. The hydrophobic effect and hydrogen bonding were proposed to be responsible, but their exact roles were not fully elucidated. In this Article, we present a thorough study on the binding behavior of these molecular tubes toward 44 hydrophilic molecules in water. Principal component analysis reveals that the binding strength is weakly correlated to the hydrophobicity, volume, surface area, and dipole moment of guests. Furthermore, molecular dynamics simulations show the hydrophobic effect through releasing the poorly hydrogen-bonded cavity water contributes to the binding of all the hydrophilic molecules, while hydrogen bonding differentiates these molecules and is thus the key to achieve a high selectivity toward certain hydrophilic molecules over other molecules with a similar size and shape. Therefore, a good guest for these molecular tubes should meet the following criteria: the hydrogen-bonding sites should be complementary, and the molecular volume should be large enough to expel all the cavity water but not too large to cause steric hindrance. This rule of thumb may also be used to design a selective receptor for certain hydrophilic molecules. Following these guidelines, a "best-fit" guest was found for the syn-configured molecular tube with a binding constant as high as 10 M.
在过去的半个世纪里，随着众多合成受体的发明，分子识别领域取得了巨大成就。然而，在水中对亲水分子的选择性识别仍然是超分子化学中一个公认的挑战，但在自然界中却很常见。在之前的一篇通讯文章中[黄等人，《美国化学会志》，2016年，138卷，14550页]，我们报道了一对内官能化分子管，令人惊讶的是，它们对高度亲水分子的偏好超过了大小和形状相似的疏水分子。有人提出疏水作用和氢键是其原因，但它们的确切作用尚未完全阐明。在本文中，我们对这些分子管在水中与44种亲水分子的结合行为进行了深入研究。主成分分析表明，结合强度与客体的疏水性、体积、表面积和偶极矩弱相关。此外，分子动力学模拟表明，通过释放氢键结合较弱的腔水产生的疏水作用有助于所有亲水分子的结合，而氢键则区分了这些分子，因此是实现对某些亲水分子相对于其他大小和形状相似分子的高选择性的关键。因此，这些分子管的良好客体应满足以下标准：氢键位点应互补，分子体积应足够大以排出所有腔水，但又不能太大而引起空间位阻。这条经验法则也可用于设计针对某些亲水分子的选择性受体。遵循这些指导原则，发现了一种与顺式构型分子管“最匹配”的客体，其结合常数高达10 M。
