Selective Recognition of Aromatic Amino Acids by a Molecular Cleft in Water

The development of water-soluble hosts for the selective recognition of aromatic amino acids is highly desirable and may serve as a tool to facilitate drug discovery and enable fabrication of sensors for point-of-care monitoring in the context of phenylketonuria disease. This paper presents the synthesis and characterization of a water-soluble molecular cleft which is demonstrated to selectively bind aromatic amino acid guests over other amino acids in aqueous medium, favoring ʟ-Trp over ʟ-Phe and ʟ-Tyr by a factor of approximately five. Host/guest-interaction forces were studied by ¹H-NMR titrations complemented by fluorescence titrations and isothermal titration calorimetry. The here presented results provide a starting point for future optimizations in our efforts to selectively identify and quantify individual aromatic amino acids in aqueous medium.