N-Arylene Ethynylene Foldamers: Structures and Functions.

Abstract

ConspectusThe construction of synthetic counterparts that mimic the structures and functions of proteins and nucleic acids has become a central focus of research in supramolecular chemistry. Aromatic foldamers are capable of folding into secondary or higher-order structures that resemble those of biomacromolecules. Over the past two decades, a variety of aromatic foldamers have been developed, including N-arylene ethynylene foldamers summarized in this Account. N-Arylene ethynylene foldamers consist of N- and NH-containing aryl heterocycles alternately linked through ethynyl bonds. These foldamers adopt stable helical structures with internal tubular cavities, driven by dipole-dipole and π-stacking interactions. Indolocarbazole-pyridine (IP) foldamers have demonstrated how folding stability and helical handedness can be modulated, with applications in anion recognition and sensing. Moreover, an indolocarbazole-naphthyridine (IN) foldamer with a larger internal cavity enables the binding of simple monosaccharides such as glucose and galactose. Utilizing dynamic covalent bonds and guest-directed synthesis, homochiral foldamers with covalently fixed, one-handed helical cavities have been quantitatively synthesized. These foldamers selectively bind the chiral guests used in their syntheses over enantiomeric or analogous guests. Furthermore, the quantitative assembly of imine-linked foldamers can be achieved from short precursors in the presence of appropriate guests. Interestingly, an imine-linked foldamer forms 2:2 complexes with both methyl β-d-glucopyranoside and methyl β-d-galactopyranoside, with temperature changes inducing complete switching of interacting guests. Each complex contains two identical cavities generated through guest-adaptive folding in a domain-swapping manner, enabling strong and selective binding. Finally, nonclassical helical duplexes are described, exhibiting duplex-to-duplex transformations in response to external stimuli. Future studies in aromatic foldamer chemistry may focus on the development of smart materials, enzyme-like catalysts, and bioapplicable foldamers.