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Synthetic oligorotaxanes exert high forces when folding under mechanical load

Abstract

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3,4,5. Recently, combining the exquisite complexity of these two classes of molecules, donor–acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6,7,8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

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Acknowledgements

D.S. thanks the Fonds de la Recherche Scientifique-Fonds National pour la Recherche Scientifique (FRS-FNRS) for his FRIA fellowship. The research was supported by the PDR T.0205.13 project of the FRS-FNRS at University of Liège and by the King Abdulaziz City of Science and Technology (KACST) as part of their Joint Center of Excellence in Integrated Nano-Systems (JCIN) at Northwestern University.

Author information

D.S. and S.H. performed the AFM experiments and analysed the data. C.B. and Z.Z. carried out the oligorotaxane synthesis and characterization studies. A.-S.D. and J.F.S. designed the experiments. A.-S.D. and D.S. wrote the manuscript. All the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Correspondence to Anne-Sophie Duwez.

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Supplementary Figs. 1–5

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Further reading

Fig. 1: Structure formula and co-conformation of the [5]rotaxane of the [0.5(n – 1) + 2] family.
Fig. 2: AFM-based mechanical unfolding of the [5]rotaxane in DMF.
Fig. 3: Pulling–relaxing cycles showing the reformation of one interaction under mechanical load.
Fig. 4: Pulling–relaxing experiments showing the numerous fluctuations between folded and unfolded states and determination of the force exerted by the molecule.