Noncovalent interactions behind the direct and inverse Hofmeister effects
Rational, synthetic design is implemented in a systematic study of the effect of host shape and properties and manifestations of the reverse Hofmeister effect. Hofmeister specific effects were observed at the molecular level wherein it was shown that key to the effectiveness of some “salting-in” anions is their complementarity to hydrophobic cavities and other binding surfaces. A gamut of responses was observed across a range of hosts possessing different structural and functional motifs. These observations were typically manifest at a relatively low (<20 mM) critical precipitation concentration (CPC). Furthermore, it was shown that at low concentrations, typical observations of screening effects are not observed, and binding-site competition is a predominant factor when multiple anions are present in solution. In terms of quantifying the ion recognition sites of different, similarly charged hosts there is little difference in anion affinity, but large differences are observed in 1/CPC values. Thus, subtle changes in the recognition site have dramatic changes in terms of manifestations of the reverse Hofmeister effect. This is (to the authors best knowledge) the first example of a systematic study sequentially modifying small molecular hosts and utilizing them to study reverse Hofmeister trends. In total 12 hosts and 6 host-guest complexes were examined. These studies demonstrate applications of the reverse Hofmeister effect to generate single crystal X-ray structures, with potential applications in protein and small molecule purifications, separations, and crystallizations.