The Effects of the Solvents on the Macrocyclic Structures: From Rigid Pillararene to Flexible Crown Ether

The differences in the macrocyclic structures lead to different flexibilities, and yet the effect of solvents on the conformations is not clear so far. In this work, the conformations of four representational macrocyclic molecules (pillar[5]arene, p-tert-butyl calix[6]arene, benzylic amide macrocycle and dibenzo-18-crown-6) in three solvents with distinct polarity have been studied by all-atom molecular dynamics simulations. The structural features of the macrocycles in the solvents indicate that the conformations are related to the polarity of the solvents and the formation of hydrogen bonds. For the pillar[5]arene, the benzylic amide macrocycle and the dibenzo-18-crown-6, that cannot form intramolecular hydrogen bonds, the polarity of solvents is the major contributing factor in the conformations. The formation of intramolecular hydrogen bonds, in contrast, determinates the conformations of the calix[6]arene. Furthermore, the slight fluctuations of the structures will result in tremendous change of the intramolecular hydrogen bonds of the macrocycles and the intermolecular hydrogen bonds between the macrocycles and the solvents. The current theoretical studies that serve as a basis for the macrocyclic chemistry are valuable for the efficient structural design of the macrocyclic molecules.

大环结构的差异会导致其柔性各不相同，而目前溶剂对大环构象的影响尚未明确。本研究通过全原子分子动力学模拟（all-atom molecular dynamics simulations），系统研究了四种典型大环分子——柱[5]芳烃（pillar[5]arene）、对叔丁基杯[6]芳烃（p-tert-butyl calix[6]arene）、苄基酰胺大环（benzylic amide macrocycle）与二苯并-18-冠-6（dibenzo-18-crown-6）在三种极性各异的溶剂中的构象。大环在溶剂中的结构特征表明，其构象与溶剂极性及氢键的形成密切相关。对于无法形成分子内氢键的柱[5]芳烃、苄基酰胺大环与二苯并-18-冠-6，溶剂极性是影响其构象的主导因素。与之相对，分子内氢键的形成则决定了对叔丁基杯[6]芳烃的构象。此外，大环结构的细微波动即可引发大环分子内氢键以及大环与溶剂间分子间氢键的显著变化。本研究作为大环化学的重要理论基础，可为大环分子的高效结构设计提供关键参考。