Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
J Org Chem. 2022 Apr 15;87(8):5158-5165. doi: 10.1021/acs.joc.1c03128. Epub 2022 Mar 25.
The affinity of small molecules for biomolecular cavities is tuned through a combination of primary and secondary interactions. It has been challenging to mimic these features in organic synthetic host molecules, however, where the cavities tend to be highly symmetric and nonpolar, and less amenable to chemical manipulation. Here, a host molecule composed of a TREN ligand and cyclotriveratrylene moiety was investigated. Size-matched polar guests were encapsulated within the cavity via triple protonation of the TREN moiety with various sulfonic acids. X-ray crystallography confirmed guest encapsulation and identified three methanesulfonates, -toluenesulfonates, or 2-naphthalenesulfonates hydrogen-bonded with HTREN at the periphery of the cavity. These structurally diverse counteranions were shown by H NMR spectroscopy to differentially regulate guest access at the three portals, and to undergo competitive displacement in solution. This work reveals "counteranion tuning" to be a simple and powerful strategy for modulating host-guest affinity, as applied here in a TREN-hemicryptophane.
小分子与生物分子腔的亲和力是通过初级和次级相互作用的结合来调节的。然而，在有机合成主体分子中模拟这些特征具有挑战性，因为这些腔往往具有高度对称和非极性，并且不易进行化学修饰。在这里，研究了一种由 TREN 配体和环三藜芦醇部分组成的主体分子。通过 TREN 部分与各种磺酸的三重质子化，将大小匹配的极性客体包封在腔中。X 射线晶体学证实了客体的封装，并确定了三个甲磺酸酯、对甲苯磺酸盐或 2-萘磺酸盐与腔边缘的 HTREN 通过氢键相互作用。通过 1H NMR 光谱证明这些结构多样的抗衡阴离子可在三个入口处不同程度地调节客体的进入，并在溶液中进行竞争性取代。这项工作表明“抗衡阴离子调谐”是一种简单而强大的调节主客体亲和力的策略，在这里应用于 TREN-hemicryptophane。
