Alcohols as Latent Hydrophobes: Entropically Driven Uptake of 1,2-Diol Functionalized Ligands by a Porous Capsule in Water

Alcohols, with hydroxyl groups compositionally
identical to water
itself, are consummate hydrophiles, whose high solubilities preclude
spontaneous self-assembly in water. Nevertheless, the solute–solvent
interactions associated with their highly favorable solvation enthalpies
impose substantial entropic costs, similar in magnitude to those that
drive the hydrophobic assembly of alkanes. We now show that under
nanoconfined conditions this normally dormant “hydrophobicity”
can emerge as the driving force for alcohol encapsulation. Using a
porous molecular capsule, the displacement of endohedrally coordinated
formate ligands (HCO2–) by 1,2-hydroxyl-functionalized l-glycerate (l-gly, l-HOCH2(HO)­CHCO2–) was investigated by van’t Hoff
analysis of variable-temperature 1H NMR in D2O. At pD 5.8, l-gly uptake is enthalpically inhibited. Upon
attenuation of this unfavorable change in enthalpy by cosequestration
of protons within the alcoholic environment provided by encapsulated
diol-functionalized ligands, −TΔS° dominates over ΔH°,
spontaneously filling the capsule to its host capacity of 24 l-gly ligands via an entropically driven hydrophobic response.