Polarity-Tolerant Chloride Binding in Foldamer Capsules by Programmed Solvent-Exclusion

Abstract

Persistent anion binding in a wide range of solution environments is a key challenge that continues to motivate and demand new strategies in synthetic receptor design. Though strong binding in low-polarity solvents has become routine, our ability to maintain high affinities in high-polarity solvents has not yet reached the standard set by nature. Anions are bound and transported regularly in aqueous environments by proteins that use secondary and tertiary structure to isolate anion binding sites from water. Inspired by this principle of solvent exclusion, we created a sequence-defined foldameric capsule whose global minimum conformation displays a helical folded state and is preorganized for 1:1 anion complexation. The high stability of the folded geometry and its ability to exclude solvent were supported by solid-state and solution phase studies. This capsule then withstood a 4-fold increase in solvent dielectric constant (εr) from dichloromethane (9) to acetonitrile (36) while maintaining a high and solvent-independent affinity of 105 M–1; ΔG ∼ 28 kJ mol–1. This behavior is unusual. More typical of solvent-dependent behavior, Cl– affinities were seen to plummet in control compounds, such as aryl-triazole macrocycles and pentads, with their solvent-exposed binding cavities susceptible to dielectric screening. Finally, dimethyl sulfoxide denatures the foldamer by putative solvent binding, which then lowers the foldamer’s Cl– affinity to normal levels. The design of this capsule demonstrates a new prototype for the development of potent receptors that can operate in polar solvents and has the potential to help manage hydrophilic anions present in the hydrosphere and biosphere.

Anion Recognition by a Pincer-Type Host Constructed from Two Polyamide Macrocyclic Frameworks Jointed by a Photo-Addressable Azobenzene Switch

“…Molecular recognition can be aided by additional and less-directional ionic, ion-π, hydrophobic, and stacking interactions [7,8]. Together, all of these interactions allow for the complete separation of the often initially highly solvated guest molecule from the external environment [9,10].…”

“…In artificial molecular receptors, a strong and selective binding of anions, such as chloride [11], carboxylates [12][13][14][15], and phosphates [16,17], might be realized by the selection of a proper molecular platform and decorating it with neutral (thio)amide [18][19][20], (thio)urea [19][20][21][22], pyrrole [23,24], and/or cationic ammonium [25], guanidinium [14,26], and imidazolium [27,28] binding groups. Despite enormous progress in the field of anion supramolecular chemistry in recent decades [1,2,19,[29][30][31], the prediction of exact anion affinity and selectivity of a designed receptor is still a challenging task due to difficulties in simulating the correct contribution of solvation and entropy effects on the stability of the supramolecular receptor-anion complex [9,[32][33][34][35][36][37]. This is particularly relevant for the Materials 2022, 15, 692 2 of 15 more demanding chiral anion recognition, as the differences in Gibbs free energy between diastereomeric complexes are usually expected not to exceed 2 kcal•mol −1 .…”

“…in simulating the correct contribution of solvation and entropy effects on the stability of the supramolecular receptor-anion complex [9,[32][33][34][35][36][37]. This is particularly relevant for the more demanding chiral anion recognition, as the differences in Gibbs free energy between diastereomeric complexes are usually expected not to exceed 2 kcal•mol −1 .…”

A Photoresponsive Receptor with a 105 Magnitude of Reversible Anion‐Binding Switching

“…Current work in the field of photoswitchable anion receptors often takes inspiration from nature, taking advantage of the hydrophobic effect, sequestering hydrophobic molecules inside binding pockets [10] . Initial studies employed an indocarbazole‐based foldamer that can adopt helical conformations providing a tubular cavity for anion binding in water; however, no photocontrol was attempted [11] .…”

“…This general framework and its analogs have been used to study a wide range of anions including Cl − , Br − , NO 3 − , CH 3 CO 2 − , H 2 PO 4 − , and HSO 4 − with maximum binding constants of 7.5×10 3 M −1 for H 2 PO 4 − in DMSO. Another approach to anion recognition by Flood and co‐workers [9a,b,10,15] utilizes a photofoldamer between helix and random coil states to alter the affinity switching of chloride guests, which has since been expanded to binding of 11 different anions (Cl − , Br − , NO 2 − , I − , NO 3 − , SCN − , BF 4 − , ClO 4 − , ReO 4 − , PF 6 − , SbF 6 − ) and the binding behavior changes from single to double helixes with increasing anion size. Binding constants for the 1 : 1 complexes were as high as 2.0×10 4 M −1 for I − in MeCN.…”