Binding Hydrated Anions with Hydrophobic Pockets

Abstract

Using a combination of Isothermal Titration Calorimetry and quantum and MD calculations, we demonstrate that relatively soft anions have an affinity for hydrophobic concavity. The results are consistent with the anions remaining partially hydrated upon binding, and suggest a novel strategy for anion recognition. Graphical abstractThe challenges associated with anion recognition are well known. 1 They have a range of geometries, may be pH sensitive, and are larger than the equivalent isoelectronic cations and have a lower charge to radius ratio. This diffuse nature means that across all the classes of functional groups utilized to bring about recognition, 1-2 those involving Coulombic attraction and hydrogen bonding have proven to be the most popular. This is particularly true for anion recognition in aqueous solution, where these strategies have been utilized to counter the strong interactions between the anion and its hydration shell. 3 Thus most of the reported hosts for anions that function in pure/buffered water are cationic. 4 Moving away from this strategy is the idea of utilizing halogen bonds for recognition; 5 an approach that takes advantage of the orthogonality between the requirements for forming halogen bonds, and those for forming hydrogen bonds; if the latter is not utilize, competition with water is less important.An alternative strategy is not to compete with the waters of hydration but to bind the anion with its solvation shell. Although a wide range of ditopic receptors have been synthesized and studied, 6 in general supramolecular chemistry has focused on the recognition of singular species. But why not recognize a hydrated anion rather than a "naked" one? Although this posses many challenges, it sidesteps the energetic requirements of ion desolvation, and has Correspondence to: Steven W. Rick; Bruce C. Gibb. Supporting Information. NMR and ITC titration experiments and details of the quantum and MD simulations. One of the key requirements for the recognition of hydrated anions is undoubtedly a large, well-defined, binding pocket; the circumambient nature of which allows for multi-point recognition. 8,9,10,11 But what are the specifics of such pockets? How many waters of hydration are easily removed from an anion, and is there a preferred hydration geometry for each anion type? Although much has been learned about isolated water clusters 12 and the solvation requirements of ions, 13 what we know of the structural requirements for recognizing hydrated ions is -to our knowledge -limited to the solid state. 14 We recently showed that perchlorate (ClO 4 − ) has an affinity for the hydrophobic pocket of cavitand 1, and that this association is dependent on the nature of other salts. 15 Furthermore, ClO 4 − binding is able to induce Hofmeister effects in the binding of amphiphilic guests to HHS Public Access 1. 16 Here we demonstrate that anion binding to the concavity of 1 is general, use ITC to identify that these complexation events are strongly exothermic and entropically penalized...

The aqueous supramolecular chemistry of cucurbit[n]urils, pillar[n]arenes and deep-cavity cavitands

“…Moreover, this competition has been shown to replicate the salting-in phenomenon of the Hofmeister effect. 48 This relatively strong anion affinity can again be ascribed to the true concavity of 5a .…”

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

“…86 The lowhanging fruit here are relatively weakly solvated salting-in anions such as SCN -that have an affinity for non-polar binding sites. Can macrocycles show these types of effects with more strongly solvated anions such as Cl -?…”

The Chaotropic Effect as an Assembly Motif in Chemistry

“…It should be noted that indications for the affinity of anions to hydrophobic binding sites existed early in the literature81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103 but were in part attributed to a putative hydrophobic (or lipophilic) property of large anions, implying the hydrophobic effect as driving force. The hydrophobic and chaotropic effect can and need to be conceptually distinguished for the reason stated above and also because the hydrophobic nature of a solute is subject to a conventional definition, which chaotropic ions do not fulfill.…”