A Closed Cavity Strategy for Selective Dipeptide Binding by a Polyaromatic Receptor in Water

[Image: see text] Precise recognition of peptides is a daunting task owing to the substantial number of available amino acids and their combination into various oligo/polymeric structures in addition to the high hydration of their flexible frameworks. Here, we report the selective recognition of a dipeptide through a closed cavity strategy, in contrast to previous synthetic receptors with open cavities. A polyaromatic receptor with a virtually isolated, hydrophobic cavity exclusively binds one molecule of phenylalanine dipeptide from a mixture with its amino acid and tripeptide in water via multiple CH−π and hydrogen-bonding interactions in the complementary cavity. The binding selectivity persists even in the presence of other dipeptides, such as leucine–leucine, leucine–phenylalanine, tyrosine–phenylalanine, tryptophan–tryptophan, and aspartame, revealed by NMR/MS-based competitive binding experiments. ITC studies reveal that the selective binding of the phenylalanine dipeptide is relatively strong (K(a) = 1.1 × 10(5) M(–1)) and an enthalpically and entropically favorable process (ΔH = −11.7 kJ mol(–1) and TΔS = 17.0 kJ mol(–1)). In addition, the present receptor can be used for the emission detection of the dipeptide through a combination with a fluorescent dye in water.