Self-assembly is a powerful method to obtain large discrete functional molecular architectures. When using a single building block, self-assembly generally yields symmetrical objects in which all the subunits relate similarly to their neighbours. Here we report the discovery of a family of self-constructing cyclic macromolecules with stable folded conformations of low symmetry, which include some with a prime number (13, 17 and 23) of units, despite being formed from a single component. The formation of these objects amounts to the production of polymers with a perfectly uniform length. Design rules for the spontaneous emergence of such macromolecules include endowing monomers with a strong potential for non-covalent interactions that remain frustrated in competing entropically favoured yet conformationally restrained smaller cycles. The process can also be templated by a guest molecule that itself has an asymmetrical structure, which paves the way to molecular imprinting techniques at the level of single polymer chains.
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The authors declare that all the data supporting the findings of this study are available within the article, in the source data files and in the Supplementary Information. Mass and NMR spectra are stored locally in native format and are available upon request. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 1942977 for (4b)16 and 1999456 for (4d)23, respectively. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.
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We thank P. van der Meulen and J. Kemmink for their assistance with the NMR experiments and analysing the data. We thank I. Melnikov (ID23-1, ERSF) and G. Pompidor (PETRA III, DESY) for assistance during data collection at the synchrotron beamlines. This research was supported by the ERC (AdG 741774), the EU (MCIF 745805−DSR), NWO (VICI grant), Zernike Dieptestrategie and the Dutch Ministry of Education, Culture and Science (Gravitation program 024.001.035).
The authors declare no competing interests.
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Supplementary Figs. 1–126 and Tables 1–4.
Crystal structure of macrocycle (4b)16.
Crystal structure of macrocycle (4d)23.
Raw UPLC chromatograms, raw temperature-dependent CD spectral data and ion-mobility data.
Crystallographic information file including structure factor for the structure of (4b)16.
Crystallographic information file including structure factor for the structure of (4d)23.
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Pappas, C.G., Mandal, P.K., Liu, B. et al. Emergence of low-symmetry foldamers from single monomers. Nat. Chem. 12, 1180–1186 (2020). https://doi.org/10.1038/s41557-020-00565-2