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Van 't Hoff Institute for Molecular Sciences Van 't Hoff Institute for Molecular Sciences

Synthetic ‘foldamer’ mimics key properties of biopolymers

UvA researchers contribute with detailed analysis of its helical structure

9 October 2025

In a paper in Nature Chemistry, a team of researchers from the universities of Groningen, Amsterdam, and East China University of Science and Technology present a fully synthetic covalent polymer that mimics the features of biopolymers such as proteins and DNA. Their ‘dual dynamic helical poly(disulfide)s’, featured on the cover of the journal, are capable of reversible folding and molecular recycling. At the University of Amsterdam, Prof. Wybren Jan Buma and his former postdoc Paul Nicu contributed with Vibrational Circular Dichroism and quantum chemical calculations to confirm, in detail, the helical structure of the novel polymers.
Artist's impression of the novel foldamers, as featured on the cover of Nature Chemistry. Image: RUG / Nature Chemistry.

Biopolymers such as proteins and DNA are structurally very dynamic molecules, featuring a unique combination of properties. On the one hand, they can fold in various shapes so that they can perform a multitude of functions (conformational adaptivity). On the other hand, they can easily decompose into their molecular building blocks and, from there on, reassemble. This ‘configurational reversibility’ facilitates the chemical recycling that is essential for the circularity of life.

Constructed from biologically relevant units

For chemists, it is quite a challenge to design and realise a synthetic molecular system that mimics such key features of natural systems, featuring dynamic covalent bonds, structural folding and full recycling capabilities. Synthetic organic chemists at the group of Prof. Ben Feringa at the University of Groningen took on that challenge, and with success.

Image: RUG / Nature Chemistry

In the Nature Chemistry paper, they present a synthetic covalent ‘foldamer’ constructed from biologically relevant units (amino acids, disulfides) that can reversibly adapt between disordered and helical conformations and can recycle itself to the original small molecules. These biopolymer-like features arise from the subtle synergy of noncovalent bonds (H-bonds) and dynamic covalent bonds within a coupled chemical equilibrium. Further in-depth analysis uncovered an unconventional thermodynamic behaviour with non-zero heat capacity change, reminiscent of natural proteins.

Unique fingerprints of the helical structure

An important contribution to the analysis of the novel molecules was made by Wybren Jan Buma, Professor of Molecular Photonics at the University of Amsterdam’s Van ‘t Hoff Institute for Molecular Sciences, and Paul Nicu, one of his former postdoctoral researchers now working in Romania. They contributed to the work by recording and analysing Vibrational Circular Dichroism spectra.

Such spectra provide unique fingerprints of the helical structure of the polymer, but also the extent to which this helical structure persists. In combination with quantum chemical calculations these spectra allowed them to provide unambiguous evidence for the successful construction of the targeted poly(disulfide)-based helical foldamers. It also provided detailed information on the structural properties of these foldamers, such as how many monomers are involved in one turn of the supramolecular assembly.

Paper details

Qi Zhang, Valentin P. Nicu, Wybren Jan Buma, He Tian, Da-Hui Qu & Ben L. Feringa: Dual dynamic helical poly(disulfide)s with conformational adaptivity and configurational recyclability. Nat. Chem. 17, 1462–1468 (2025). DOI: 10.1038/s41557-025-01947-0

See also