Foldamers With Two Distinct Helical Motifs Controlled by Solvent.

Abstract

Abiotic foldamers that switch between distinct, well-defined geometries are rare. Here, we report a structurally simple series of oligomers with alternating ortho-phenylene and 2,3-pyrazinylene repeat units. Deconvolution of variable-temperature 1H NMR spectra, with the help of ab initio chemical shift predictions, shows that the oligomers favor a compact, arene-stacked helix in chloroform but a structurally distinct extended helix in acetone. The longest oligomer investigated, a heptamer, exhibits nearly perfect solvent-switching behavior at low temperature, effectively doubling its length in acetone compared to chloroform. X-ray crystallography confirms that the hybrid backbone is capable of both folding motifs. While arene-arene stacking drives folding in chloroform, nonclassical intramolecular C⁠─H⁠⋯⁠N hydrogen bonds appear to be more important in acetone. Both geometries are enthalpically favored in their respective solvents, highlighting how a balance of weak, competing interactions can be harnessed to achieve large-scale geometry changes in synthetic foldamers.