Buried Solvent Determines Both Anion-Binding Selectivity and Binding Stoichiometry with Hydrogen-Bonding Receptors

Abstract

[reaction: see text] The crystal structure of a tetraurea picket porphyrin-chloride anion complex has previously shown the anion to be situated between two adjacent ureas and hydrogen bonded via four NH protons (J. Am. Chem. Soc. 1998, 120, 11684-11692). The porphyrin receptor also binds a DMSO molecule and utilizes it as a participant in its anion recognition unit, in a manner similar to enzymes that bind water for use as part of their substrate recognition unit. The bound solvent molecule determines the anion-binding affinity, selectivity, and stoichiometry of binding. With a bound DMSO molecule, the tetraurea picket porphyrin is a highly selective receptor for chloride anion and binds all anions with a 1:1 binding stoichiometry. Absent the buried DMSO molecule, the receptor is selective for phosphate anion and binds chloride and phosphate anions with both 1:1 and 1:2 receptor-anion stoichiometries. Additionally, a remarkable reversal in the selectivity of anion complexation between various picket porphyrin receptors is observed, wherein the binding constant ratios change over 3 orders of magnitude as the receptor's number of urea pickets change from four to two. The latter receptor has no urea pickets available to bind to solvent after complexation with an anion. The results demonstrate that anion complexation with hydrogen-bonding receptors in a competitive solvent is enhanced when a ubiquitous solvent molecule is incorporated into the binding motif. In this way, competitive solvent adds to the overall complexation energy and thereby strengthens binding rather than weakens it, as commonly believed. The results are pertinent to drug design, for they suggest that pharmaceuticals need not be completely desolvated to selectively bind to their biological target when water can be included in the binding motif.

Anion Binding versus Intramolecular Hydrogen Bonding in Neutral Macrocyclic Amides

“…Such receptors may be useful in applications such as the transport of anions through lipophilic channels or membranes, where stripping off the solvation shell gives rise to a high energy barrier 43. Recently, a strong impulse to such studies was given by Burns et al,44 who found that anion complexation in a competitive solvent was enhanced when a solvent molecule was incorporated into the binding motif. This strategy is also widely used in Nature, where enzymes bind water for use as a part of their substrate‐recognition domains 44.…”

“…Recently, a strong impulse to such studies was given by Burns et al,44 who found that anion complexation in a competitive solvent was enhanced when a solvent molecule was incorporated into the binding motif. This strategy is also widely used in Nature, where enzymes bind water for use as a part of their substrate‐recognition domains 44. Receptors 4 and 8 may serve as prototype anion receptors of this class.…”

Synthesis of Urea Picket Porphyrins and Their Use in the Elucidation of the Role Buried Solvent Plays in the Selectivity and Stoichiometry of Anion Binding Receptors

“…Our initial studies, detailed in a recent report, vividly demonstrates the affect of a buried organic solvent molecule that was incorporated within urea-picket porphyrin anion receptors. 17 Essentially, the receptor-bound DMSO molecule became an additional anion recognition unit within the receptor pocket ( Figure 1). We have termed this type of receptor-solvent-ligand structure an 'ordered solvent shell' about the anion.…”

Anion Binding Motifs: Topicity and Charge in Amidocryptands

“…Solvent can play a critical role in stabilizing host-guest complexes, as recently noted by Burns and co-workers. 11 In neither complex, however, are the anions encapsulated. Rather, in the chloride structure ( Figure 2, A and B), one chloride is centered between the two quaternized amines at the top of the bowl (Figure 2, A) and tied by four hydrogen bonds to amide hydrogens and water molecules.…”