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• Isotactic oligourethanes form helical secondary structures. • Stability of helix depends on the solvent environment. • In nonpolar media, a hydrogen-bond-rich, tight 2.6 14 helix helix is formed. • Increasing medium polarity leads to less stable, solvent-exposed, wide 4 22 helix. Sequence-defined and stereocontrolled polymers offer a platform for engineering synthetic macromolecules that can mimic the structural sophistication and folding behavior of natural proteins. Among them, oligourethanes represent a promising class due to their synthetic accessibility, tunable stereochemistry, and potential for intramolecular hydrogen bonding. Here, we report a comprehensive study of solvent-dependent folding of the isotactic oligourethane backbone, revealing how medium polarity and hydrogen-bonding interactions dictate the formation and stability of defined secondary structures. Using a combined approach of molecular dynamics and NMR spectroscopy, we identified two distinct helical motifs: the compact, hydrogen-bond-rich 2.6 14 helix and the less stable, solvent-exposed 4 22 helix. Our findings demonstrate that nonpolar aprotic environments uniquely stabilize the 2.6 14 helix, while polar and protic solvents disrupt its hydrogen-bonding network. This work highlights the critical role of the environment in shaping the conformational landscape of abiotic polyurethanes. It provides fundamental knowledge for designing protein-mimicking materials that could perform under non-physiological conditions.
Szatko et al. (Sat,) studied this question.