Control of Helix Screw-Sense Preference in Dynamic Foldamers of meso Symmetry Built From Chiral Monomeric Units.

Abstract

Meso oligoureas are dynamic hydrogen-bonded foldamers capable of reversible helix polarity inversion but have so far been limited to symmetrical meso-cyclohexane-1,2-diamine monomeric units, limiting both sequence diversity and structural modification. Here, we report the synthesis and characterization of meso and "near-meso" oligoureas assembled exclusively from chiral units, thereby expanding the accessible sequence space. Despite their overall symmetry, meso oligoureas display sequence-dependent helix-forming propensities. Controlled desymmetrization of terminal groups induces a preferred helix screw-sense, while binding of achiral hydrogen-bond acceptors reverses the directionality of the intramolecular hydrogen-bonding network, leading to sequence-dependent screw-sense inversion. Structural, spectroscopic, and solution studies consistently support this stimulus-responsive folding behavior.