Solvent-Dependent Linear Free-Energy Relationship in a Flexible Host-Guest System.

Supramolecular chemistry provides an effective strategy for the molecular recognition of diverse molecules. Significant efforts to design synthetic hosts have enabled the successful binding of many types of guests; however, less is known about how host-guest environments influence binding. Herein, we present a comprehensive study in which we measure the host-guest binding of a bis(arylethynyl phenylurea) host with a chloride guest in eight solvents spanning ET(30) values ranging from nonpolar (40.7 kcal mol-1) to polar (47.4 kcal mol-1). Polar solvents show significantly weaker binding in comparison to nonpolar solvents, and the bulk solvent polarity parameter, ET(30), shows a linear free-energy relationship with respect to the free energy of binding in the host-guest complex. These studies provide a better understanding of how host-guest binding in flexible receptors is governed by their environments and highlight the importance of host reorganization contributions in the free energy of binding. In addition, these studies highlight that preorganization may not be as important as previously thought for weak binding in which enthalpic contributions are smaller versus in polar solvents where solvent effects are magnified.