Foldameric receptors with domain-swapping cavities capable of selectively binding and transporting monosaccharides

Abstract

The development of synthetic receptors capable of selectively binding and transporting saccharides is crucial but highly challenging. In this study, two foldameric receptors 1 and 2, consisting of two repeating monomers, indolocarbazole and naphthyridine units, with different aromatic spacers in the middle of their sequences, have been synthesised. These receptors fold into helical conformations, and the two strands of each receptor are assembled to create domain-swapping cavities for binding monosaccharides by multiple hydrogen bonds. According to ¹H NMR, CD spectroscopy, mass spectrometry, and ITC experiments, receptor 1 forms two distinct 2 : 2 complexes with methyl β-D-galactopyranoside and methyl β-D-glucopyranoside: (1-MM)₂⊃(methyl β-D-galactopyranoside·2H₂O)₂ and (1-MP)₂⊃(methyl β-D-glucopyranoside)₂. Despite being composed of identical foldamer strands, these two complexes exhibit notably different folding and assembly modes to achieve optimal stability. The binding affinities of 1 for methyl β-D-galactopyranoside and methyl β-D-glucopyranoside are estimated to be log K = 12.7 and 13.3, respectively, in 5% (v/v) DMSO/CH₂Cl₂. On the other hand, receptor 2 forms a stable 2 : 2 receptor/guest complex with methyl β-D-glucopyranoside, (2-MP)₂⊃(methyl β-D-glucopyranoside)₂, with an association constant of log K = 13.9, which is significantly higher than that of methyl β-D-galactopyranoside (log K = 11.1) and methyl α-D-glucopyranoside (log K = 10.6). Furthermore, receptor 2 facilitates the selective transport of methyl β-D-glucopyranoside over other glycosides across an organic phase (CH₂Cl₂) in U-tube experiments.