Tuning CH Hydrogen Bond‐Based Receptors toward Picomolar Anion Affinity via the Inductive Effect of Distant Substituents

• Published in: Angewandte Chemie International Edition 2024-01, Vol.63 (5), p.e202318261-n/a
• Main Authors: Chvojka, Matúš, Madea, Dominik, Valkenier, Hennie, Šindelář, Vladimír
• Format: Article
• Language: English
• Subjects: Acetonitrile; Affinity; Anion Binding; Anions; Bambusurils; Binding sites; Electrons; Halides; Host−Guest Chemistry; Hydrogen bonds; Iodides; Macrocycles; NMR Spectroscopy; Receptors; Selective binding
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202318261

Inspired by nature, artificial hydrogen bond‐based anion receptors have been developed to achieve high anion selectivity; however, their binding affinity is usually low. The potency of these receptors is usually increased by the introduction of aryl substituents, which withdraw electrons from their binding site through the resonance effect. Here, we show that the polarization of the C(sp3)‐H binding site of bambusuril receptors, and thus their potency to bind anions, can be modulated by the inductive effect. The presence of electron‐withdrawing groups on benzyl substituents of bambusurils significantly increases their binding affinities to halides, resulting in the strongest iodide receptor reported to date with an association constant greater than 1013 M−1 in acetonitrile. A Hammett plot showed that while the bambusuril affinity toward halides linearly increases with the electron‐withdrawing power of their substituents, their binding selectivity remains essentially unchanged. Ultrahigh binding affinity of bambusuril receptors toward halides is achieved and continuously increases with increasing electron‐withdrawing power of groups installed on its benzyl substituents, as measured by 1H and 19F NMR spectroscopy.