Relative hydrophilicities of and formamides.

Secondary formamides are widely encountered in biology and exist as mixtures of both and isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to the aqueous medium. NMR spectroscopic experiments reveal a modest preference (<1 kcal/mol) for aqueous solvation of the formamide terminals over the isomers. With diformamides, the supramolecular approach allows staging of intramolecular competition between short-lived species with subtle differences in hydrophobic properties.