Substrate Discrimination by Cholapod Anion Receptors:  Geometric Effects and the “Affinity−Selectivity Principle”

Abstract

Cholapod anion receptors can achieve high affinities while maintaining compatibility with nonpolar media. Previously they have been shown to transport anions across cell and vesicle membranes. In the present work, the scope of the architecture is expanded and structure-selectivity relationships are investigated. Eight new receptors have been synthesized, with up to six H-bond donor centers. Using Cram's extraction method, these compounds plus five known examples have been tested for binding to seven monovalent anions (tetraethylammonium salts, wet chloroform as solvent). Association constants in excess of 10(10) M(-1) have been measured for several pairings. Selectivities vary with receptor geometry, as expected. More remarkably, they also depend on receptor strength: more powerful receptors show a wider range of binding free energies, and therefore a greater spread of Ka(X-)/Ka(Y-). This "affinity-selectivity" effect can be derived from empirical relationships for H-bond strengths, and could prove widely operative in supramolecular chemistry.

Structure–Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning

“…Cholapod anion affinities in water-saturated chloroform were measured using our previously-reported extraction-based method, with Et 4 N + as counterion. [14] The technique involves the equilibration of cholapods dissolved in chloroform with salts Et 4 N + X − dissolved in water, followed by 1 H NMR analysis to determine the amount of extracted salt. Binding constants K a (X − , CHCl 3 ) can be calculated from the extraction constant K e , and the distribution constant K d for the salt between chloroform and water in the absence of receptor (K a = K e /K d ).…”

“…All possess the 7α,12α-bis(thio)ureidyl motif, which tends to afford high anion affinities. [12,14] The choice of 7α,12α-substituent varied between phenylureidyl, p-nitrophenylureidyl and p-nitrophenylthioureidyl (for numbering, see 1). The NH acidities of these units increase in the order listed, with corresponding enhancements of anion affinities.…”

“…Affinities for Et 4 N + Cl − in chloroform (K a , Cl − , CHCl 3 ) rose from 3.4 × 10 6 M −1 for 1a, via 5.2 × 10 8 M −1 for 1e, to 10 11 M −1 for 2, and transport activities increased accordingly. Compound 2 is among the strongest of the cholapod anion receptors, [13,14] so one might conclude that further advances would be difficult. However, transporters 1 and 2 represent a small fraction of cholapod structural space, and we were interested to explore a wider range of molecules.…”

Anion Separation with Metal–Organic Frameworks

“…Most strategies for anion binding today employ H-bonding or other electrostatic interactions as the basis for recognition, and normal Hofmeister bias still tends to be commonly observed, leading us to conclude that systems so far investigated for separations often lack sufficiently strong and structurally constrained H-bond donor groups. The affinity/selectivity principle recently put forth [27] leads to the expectation that the greatest selectivity will occur with stronger interactions, which will magnify differences in the ability of a given host to accommodate anions of different size or structure. With a sufficiently strong total interaction with a given anion, implying strong individual interactions and with high overall complementarity, it is expected that peak selectivity for that anion will arise when the structure of the host environment is unable to rearrange to accommodate other anions.…”

“…Starting with less effective systems, the bidentate H-bond donors that have been examined appear to be too weak with respect to H-bond strength or rigidity to effect significant departures from Hofmeister bias. In that the anions are still largely open to the influence of solvation, overall complementarity is low, and the affinity/selectivity principle [27] would imply only perturbation or attenuation of Hofmeister bias. These nearnormal Hofmeister systems thus lie in the lower left box in the selectivity model shown in Figure 2.…”