Stereocontrol as a tool for shaping abiotic, sequence-defined oligourethanes

Nature leverages the primary sequence of proteins to guide the folding of protein chains into specific three-dimensional shapes, which are crucial for their function. Similarly, abiotic polymers can be engineered with a precise arrangement of monomers and stereocenters through multistep iterative synthesis. This study explores experimental and computational methods to examine the folding of model oligourethanes and how stereochemistry can tune secondary structures. Our findings reveal that isotactic oligourethanes can form helical conformation in non-polar aprotic media. The sequence of stereocenters in the polymer backbone fine-tunes the resulting secondary structures and shifts from helical to zig-zag shapes. While extensive research has focused on amide-based backbones due to their similarity to proteins, we demonstrate how to fold urethane-based structures that could be a foundation for developing non-biological polymers with protein-like features. The shape control of oligourethanes is crucial for their envisioned functions, such as catalytic activity and intramolecular interactions with ligands, making stereocontrol a powerful tool for the advanced engineering of polymer properties.