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

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 (Δ H = -11.7 kJ mol -1 and T Δ S = 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.