Supramolecular Ligation Turns Polymer Folds into Covalent Bonds

Researchers have developed a way to join synthetic polymer chains at the molecular level by combining hydrogen-bond-driven folding with dynamic covalent chemistry. The method uses folding to pre-organize reactive ends, allowing base-catalysed thiolate–disulfide exchange to form covalent links without thermal activation. In their experiments, the resulting extended helical polymers folded into globular structures in solution and formed temperature-responsive entanglements within bulk films.

Chemical ligation is important for extending synthetic polymers, but joining separate chains remains difficult because the reactive end groups must first encounter one another. Their low probability of collision is entropically unfavourable, and covalent bond formation can face a substantial activation barrier. The new strategy addresses both obstacles by drawing reactive polymer segments together through a folding-driven supramolecular polymerization before carrying out the ligation step.

Central to the approach is a set of hydrogen bonds that induce conformational folding and rigidify the polymer backbone. These interactions also create “sticky ends” that promote intermolecular association and supramolecular pre-organization. Once aligned within the assembled structure, the terminal groups are close enough to undergo base-catalysed covalent exchange. The reported chemistry involves thiolate–disulfide groups, converting temporary noncovalent organization into a more permanent covalent connection while retaining the ability of the assembled material to reorganize through dynamic bonds.

The team obtained mechanistic insight by engineering side-chain units that control two distinct features: how readily a polymer segment can fold and how strongly its chains are pre-organized through intermolecular hydrogen bonding. This separation of design elements allowed the researchers to examine the roles of conformation and association in the ligation process. Their results support a pathway in which supramolecular folding first creates the appropriate geometry for covalent joining, followed by dynamic covalent polycondensation that extends the polymer.

The resulting materials are not simply elongated chains. The extended polymeric helices adopt hierarchical, globular architectures in solution, while films of the material exhibit thermo-responsive macromolecular entanglements in the bulk state. These observations show that noncovalent assembly and dynamic covalent polymerization can be combined to produce polymers with controlled secondary structures, even though the reaction does not require heating to overcome an activation barrier. The work is reported in Nature Nanotechnology as a strategy for non-thermal, controllable polycondensation of dynamic polymers. Because the supplied study concerns synthetic materials rather than biological systems, the findings do not establish direct applications in medicine or human clinical benefit.

Subject of Research: Supramolecular folding-assisted covalent ligation of dynamic helical polymers

Article Title: Supramolecular chemical ligation of helical polymers

Article References: Ma, M., Jiang, Z., Li, N., Xu, Y., Qu, D.-H., Tian, H., Feringa, B. L., & Zhang, Q. (2026). Supramolecular chemical ligation of helical polymers. Nature Nanotechnology. https://doi.org/10.1038/s41565-026-02310-1

Image Credits: AI Generated

DOI: 10.1038/s41565-026-02310-1

Keywords: supramolecular chemistry, chemical ligation, helical polymers, dynamic covalent bonds, hydrogen bonding, polycondensation, polymer folding, thiolate–disulfide exchange, thermo-responsive materials, Supramolecular, chemical, ligation