Charge-assisted hydrogen bonding in a bicyclic amide cage: an effective approach to anion recognition and catalysis in water

Abstract

Hydrogen bonding is prevalent in biological systems, dictating a myriad of life-sustaining functions in aqueous environments. Leveraging hydrogen bonding for molecular recognition in water encounters significant challenges in synthetic receptors on account of the hydration of their functional groups. Herein, we introduce a water-soluble hydrogen bonding cage, synthesized via a dynamic approach, exhibiting remarkable affinities and selectivities for strongly hydrated anions, including sulfate and oxalate, in water. We illustrate the use of charge-assisted hydrogen bonding in amide-type synthetic receptors, offering a general molecular design principle that applies to a wide range of amide receptors for molecular recognition in water. This strategy not only revalidates the functions of hydrogen bonding but also facilitates the effective recognition of hydrophilic anions in water. We further demonstrate an unconventional catalytic mechanism through the encapsulation of the anionic oxalate substrate by the cationic cage, which effectively inverts the charges associated with the substrate and overcomes electrostatic repulsions to facilitate its oxidation by the anionic MnO₄ ^-. Technical applications using this receptor are envisioned across various technical applications, including anion sensing, separation, catalysis, medical interventions, and molecular nanotechnology.

Fig. 1. (a) Representative anion receptors with charge-assisted hydrogen bonding functionalities. (b) The structural formula of TPPC³⁺·3Cl⁻ and a summary of its structural features.

Fig. 2. Synthesis of TPPC³⁺·3Cl⁻ using a conventional high dilution approach (method I) and a dynamic approach (method II).

Fig. 3. (a) ¹H NMR spectra (400 MHz, 10% D₂O + 90% H₂O) of TPPC³⁺·3Cl⁻ (0.1 mM) titrated with Na₂SO₄. (b) ITC profile of TPPC³⁺·3Cl⁻ (0.5 mM) titrated with Na₂SO₄ in H₂O.

Fig. 4. (a) ¹H NMR spectra (400 MHz, 10% D₂O + 90% H₂O) of TPPC³⁺·3Cl⁻ (0.2 mM) titrated with Na₂C₂O₄. (b) ITC profile of TPPC³⁺·3Cl⁻ (0.1 mM) titrated with Na₂C₂O₄ in H₂O.

Fig. 5. X-ray single crystal structures of (a) 2Cl⁻·H₂O⊂TPPC³⁺, (b) 2I⁻·H₂O⊂TPPC³⁺, (c) 3CF₃CO₂⁻⊂TPPC³⁺.

Fig. 6. DFT optimized structure of (a) Cl⁻⊂TPPC³⁺, (b) Br⁻⊂TPPC³⁺, (c) I⁻⊂TPPC³⁺, (d) NO₃⁻⊂TPPC³⁺, (e) SO₄²⁻⊂TPPC³⁺, and (f) C₂O₄²⁻⊂TPPC³⁺.

Fig. 7. Reaction formula showing (a) the slow oxidation of oxalate by MnO₄⁻ and (b) its rate acceleration by TPPC³⁺·3Cl⁻. (c) Changes of the UV-vis spectra in a KMnO₄ solution (0.2 mM) over 95 minutes after adding H₂C₂O₄ (1 mM). (d) Changes of the UV-vis spectra in a KMnO₄ (0.2 mM) solution in the presence of 5% TPPC³⁺·3Cl⁻ (0.01 mM) over 95 minutes following H₂C₂O₄ addition (1 mM). (e) The changes in absorbance at 525 nm for a KMnO₄ solution (0.2 mM) over 95 minutes, demonstrating the effects of different loadings of TPPC³⁺·3Cl⁻ as a catalyst on the reaction rate post H₂C₂O₄ (1 mM) addition.

Fig. 8. Schematic illustration of the catalytic cycle of oxalate oxidation catalyzed by TPPC³⁺.