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An artificial molecular machine that builds an asymmetric catalyst

Nature Nanotechnology volume 13, pages 381–385 (2018)Cite this article

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Abstract

Biomolecular machines perform types of complex molecular-level tasks that artificial molecular machines can aspire to. The ribosome, for example, translates information from the polymer track it traverses (messenger RNA) to the new polymer it constructs (a polypeptide)1. The sequence and number of codons read determines the sequence and number of building blocks incorporated into the biomachine-synthesized polymer. However, neither control of sequence2,3 nor the transfer of length information from one polymer to another (which to date has only been accomplished in man-made systems through template synthesis)4 is easily achieved in the synthesis of artificial macromolecules. Rotaxane-based molecular machines5,6,7 have been developed that successively add amino acids8,9,10 (including β-amino acids10) to a growing peptide chain by the action of a macrocycle moving along a mono-dispersed oligomeric track derivatized with amino-acid phenol esters. The threaded macrocycle picks up groups that block its path and links them through successive native chemical ligation reactions11 to form a peptide sequence corresponding to the order of the building blocks on the track. Here, we show that as an alternative to translating sequence information, a rotaxane molecular machine can transfer the narrow polydispersity of a leucine-ester-derivatized polystyrene chain synthesized by atom transfer radical polymerization12 to a molecular-machine-made homo-leucine oligomer. The resulting narrow-molecular-weight oligomer folds to an α-helical secondary structure13 that acts as an asymmetric catalyst for the Juliá–Colonna epoxidation14,15 of chalcones.

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Fig. 1: Assembly of an artificial molecular machine system that builds an asymmetric catalyst.
Fig. 2: Assembly of molecular machine–track conjugate 1 by elongation of rotaxane 2 with polymer 3.
Fig. 3: Operation of machine–track conjugate 1.
Fig. 4: α-Helicity of operation product oligoleucines before (9) and after (12) post-operational modification and their asymmetric Juliá–Colonna epoxidation of furyl chalcone 13.

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Acknowledgements

The authors thank M. Turner and J. Behrendt for assistance with the SEC instrumentation, J. Clayden and M. De Poli for assistance with CD measurements and G. Smith for MALDI analysis of earlier related systems. The UMONS MS laboratory acknowledges the Fonds National de la Recherche Scientifique (FRS-FNRS) for its contribution to acquisition of the Waters QToF Premier and Synapt G2-Si mass spectrometers and for continuing support. This research was funded by the Engineering and Physical Sciences Research Council (EP/P027067/1). The authors thank the Royal Society for a University Research Fellowship (to G.D.B.) and a Research Professorship (to D.A.L.).

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Authors and Affiliations

  1. School of Chemistry, University of Manchester, Manchester, UK

    Guillaume De Bo, Malcolm A. Y. Gall, Sonja Kuschel & David A. Leigh

  2. Organic Synthesis and Mass Spectrometry Laboratory, Interdisciplinary Center for Mass Spectrometry (CISMa), University of Mons, Mons, Belgium

    Julien De Winter & Pascal Gerbaux

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  1. Guillaume De Bo
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Contributions

G.D.B., M.A.Y.G. and S.K. planned and carried out the experimental work. J.D.W. and P.G. performed the MS analysis of polymers 1 and 3. D.A.L. directed the research. All authors contributed to the analysis of the results and the writing of the manuscript.

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Correspondence to David A. Leigh.

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De Bo, G., Gall, M.A.Y., Kuschel, S. et al. An artificial molecular machine that builds an asymmetric catalyst. Nature Nanotech 13, 381–385 (2018). https://doi.org/10.1038/s41565-018-0105-3

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