Solvent-Dependent Linear Free-Energy Relationship in a Flexible Host–Guest System

Abstract

Supramolecular chemistry provides an effective strategy for the molecular recognition of diverse molecules. Significant efforts to design synthetic hosts have enabled the successful binding of many types of guests; however, less is known about how host−guest environments influence binding. Herein, we present a comprehensive study in which we measure the host− guest binding of a bis(arylethynyl phenylurea) host with a chloride guest in eight solvents spanning E T (30) values ranging from nonpolar (40.7 kcal mol −1 ) to polar (47.4 kcal mol −1 ). Polar solvents show significantly weaker binding in comparison to nonpolar solvents, and the bulk solvent polarity parameter, E T (30), shows a linear free-energy relationship with respect to the free energy of binding in the host−guest complex. These studies provide a better understanding of how host−guest binding in flexible receptors is governed by their environments and highlight the importance of host reorganization contributions in the free energy of binding. In addition, these studies highlight that preorganization may not be as important as previously thought for weak binding in which enthalpic contributions are smaller versus in polar solvents where solvent effects are magnified.

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

“…The design of receptors that can capture anions across a range of environments is important for water purification, − clean energy production, − and the extraction of high-value ions. − These needs continue to motivate exploration of new strategies to control anion affinities in water, − across a variety of organic solvents − and in biphasic systems. ,,− ,, It is proving relatively straightforward to design receptors ,− in silico to bind anions effectively in low-polarity organic solvents (ε r < 10) that have weak interaction with dissolved molecules. When those same receptors are deployed in more polar solvents, however, the recognition is more challenging.…”

“…When those same receptors are deployed in more polar solvents, however, the recognition is more challenging. It is routinely seen − ,,,− that greater penalties are incurred in polar solvents for the desolvation of both host − and guest ,, during complexation to weaken affinities. Recently, it has also been shown how hydrogen bonds in anion-receptor complexes get weaker in polar solvents with better screening of the electrostatic component of stabilization.…”

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

“…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 .…”

Deuterium equilibrium isotope effects in a supramolecular receptor for the hydrochalcogenide and halide anions

“…To deconvolute and better understand the role of both C-H/D hydrogen bond donor polarity and solvent on the DEIE of Cl À binding in these receptors, a systematic study of these two variables would be required, similar to those previously reported, which we intend to pursue in future work. 14,27,28 Analysis of the data for competitive titrations of 2 H/D with Br À revealed no DEIE at any of the tracked 13 C NMR signals; however, each calculated DEIE has a relatively large percent error (0.99-4.64%, compared to 0.20% for the DEIE of Cl À binding), which could potentially obscure small DEIEs. We attribute these large percent errors to a limitation in the Perrin method that assumes that the hosts are fully bound by guest at saturation.…”