Thermodynamic Profiles of Salt Effects on a Host–Guest System: New Insight into the Hofmeister Effect

Isothermal titration calorimetry was used to probe how salts influence the thermodynamics of binding of guests to cavitand 1. Studies involved six Hofmeister salts covering the range of salting-in to strongly salting-out. The latter were found to reduce affinity. The cause of this was competitive binding of the weakly solvated anion to the hydrophobic pocket of the host. At the other extreme of the Hofmeister series, salts increased guest affinity. Two factors for this were evident. At low concentrations the data fitted a previously reported model that accounts for cation condensation to the outer carboxylates of the host (Carnagie, R.; Gibb, C. L. D.; Gibb, B. C., Angew. Chem., Int. Ed. 2014, 53 (43), 11498–11500). At higher concentrations, an as of yet unidentified contribution was observed that was noted to be guest dependent. Midcontinuum salts such as NaClO3 were found to enhance affinity at low concentrations, but weaken it at high concentrations; a nonmonotonic trend attributed to the aforementioned competing phenomena. In combination with previous work, the data presented here reveal that the Hofmeister effect evident in this system can be mostly attributed to solute–salt interactions.