Synthesis of 128-meric Helical Amide Foldamer with a 16 nm Length

Nanosized molecular structures are important in the realization of superstructures and promising functions in material science and biochemical applications. Helical foldamers have garnered significant attention due to their well-defined structures and high predictability. However, several difficulties, including low reactivity, poor yields, and messy purification, have limited the synthesis of nanosized helical foldamers. Here, we develop an efficient synthetic strategy for nanosized aromatic amide helical foldamers composed of repeating pyridine and quinoline units. By adjusting the solubility of the starting materials, all pure products of each segment-doubling condensation can be readily obtained via precipitation in MeOH, thus avoiding the column chromatography separation process. Thus, we synthesized a series of nanosized aromatic amide helical foldamers with different lengths. In particular, the biggest nanosized aromatic amide helical foldamer, composed of 128 monomers, reaches a length of 16 nm among them. Further, the terminal groups of these nanosized helical foldamers are active, such as amine or carboxyl acid, making them ideal nanosized structural components for constructing biomimetic superstructures or precise supramolecular structures.