Cucurbit[ n ]urils ( n = 7, 8) can strongly bind neutral hydrophilic molecules in water

It is challenging to recognize neutral hydrophilic molecules in water. Effective use of hydrogen bonds in water is generally accepted to be the key to success. In contrast, hydrophobic cavity is usually considered to play an insignificant role or only to provide a nonpolar microenvironment for hydrogen bonds. Herein, we report that hydrophobic cavity alone can also strongly bind neutral, highly hydrophilic molecules in water. We found that cucurbit[ n ]urils ( n = 7, 8) bind 1,4-dioxane, crown ethers and monosaccharides in water with remarkable affinities. The best binding constant reaches 10 7 M −1 for cucurbit[8]uril, which is higher than its binding affinities to common organic cations. Density functional theory (DFT) calculations and control experiments reveal that the hydrophobic effect is the major contributor to the binding through releasing the cavity water and/or properly occupying the weakly hydrated cavity. However, hydrophobic cavity still prefers nonpolar guests over polar guests with similar size and shape.