Substrate discrimination by cholapod anion receptors: geometric effects and the "affinity-selectivity principle".

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.

An extraction-based assay for neutral anionophores: the measurement of high binding constants to steroidal receptors in a nonpolar solvent.

The extraction-based protocol for measuring binding constants, developed by Cram and co-workers, has been extended for use with anionic substrates. The method is especially useful for high-affinity receptors, allowing very high binding constants to be measured in nonpolar solvents. Distribution constants K(d) between chloroform and water have been obtained for tetraethylammonium chloride and bromide, thus calibrating the method for these two substrates. Application to steroidal podands 5-9 has confirmed the ability of electron-withdrawing groups to enhance hydrogen-bond donor capabilities. Binding constants of approximately 3 x 10(7) M(-1) have been measured for the most powerful receptor 7. An X-ray crystal structure of 15, the methyl ester analogue of 7, reveals a well-defined binding site preorganised for anion recognition.