Tuning the Free Energy of Host-Guest Encapsulation by Cosolvent

Supramolecular hosts create unique microenvironments which enable the tuning of reactions via steric confinement and electrostatics. It has been shown that “solvent shaping inside hydrophobic cavities” is an important thermodynamic driving force for guest encapsulation in the nanocage host. Here, we show that even small (5%) changes in the solvent composition can have a profound impact on the free energy of encapsulation. In a combined THz, NMR and ab initio MD study, we reveal that the preferential residing of a single DMSO molecule in the cavity upon addition of ≥5% DMSO results in a considerable change of ΔS from 63-76 cal⋅mol–1⋅K–1 to 23-24 cal⋅mol–1⋅K–1. This can be rationalized by reduction of the cavity volume due to the DMSO molecule which resides preferentially in the cavity. These results provide novel insights into the guest-binding interactions, emphasizing that the entropic driving force is notably influenced by even small changes in the solvent composition. The impact of embedding a single DMSO molecules exceeds the alternative choice of the metal ligand by far. We demonstrate that the local solvent composition within the cage is essential for regulating catalytic efficiency, thus solvent tuning might enable novel applications in supramolecular chemistry in catalysis and chemical separation.