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A tape-reading molecular ratchet

Abstract

Cells process information in a manner reminiscent of a Turing machine1, autonomously reading data from molecular tapes and translating it into outputs2,3. Randomly processive macrocyclic catalysts that can derivatise threaded polymers have been described4,5, as have rotaxanes that transfer building blocks in sequence from a molecular strand to a growing oligomer6,7,8,9,10. However, synthetic small-molecule machines that can read and/or write information stored on artificial molecular tapes remain elusive11,12,13. Here we report on a molecular ratchet in which a crown ether (the ‘reading head’) is pumped from solution onto an encoded molecular strand (the ‘tape’) by a pulse14,15 of chemical fuel16. Further fuel pulses transport the macrocycle through a series of compartments of the tape via an energy ratchet14,17,18,19,20,21,22 mechanism, before releasing it back to bulk off the other end of the strand. During its directional transport, the crown ether changes conformation according to the stereochemistry of binding sites along the way. This allows the sequence of stereochemical information programmed into the tape to be read out as a string of digits in a non-destructive manner through a changing circular dichroism response. The concept is exemplified by the reading of molecular tapes with strings of balanced ternary digits (‘trits’23), −1,0,+1 and −1,0,−1. The small-molecule ratchet is a finite-state automaton: a special case24 of a Turing machine that moves in one direction through a string-encoded state sequence, giving outputs dependent on the occupied machine state25,26. It opens the way for the reading—and ultimately writing—of information using the powered directional movement of artificial nanomachines along molecular tapes.

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Fig. 1: Chiroptical readout of the sequence of a stereochemically encoded molecular tape by a chemically fuelled molecular ratchet.
Fig. 2: CD spectra of the unthreaded components and machine states formed by the stepwise ratcheted operation of 3 along molecular tapes 1 (encoded −1,0,+1) and 2 (encoded −1,0,−1).
Fig. 3: Pulse-fuelled reading of molecular tape 1 (encoded −1,0,+1).

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Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information, or are available from the Mendeley data repository (https://data.mendeley.com/) at https://doi.org/10.17632/k5m7fv49xv.1.

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Acknowledgements

We thank D. Heyes for assistance with CD spectroscopy, the University of Manchester’s Department of Chemistry Services for mass spectrometry, the Engineering and Physical Sciences Research Council (EPSRC; grant no. EP/P027067/1) and the European Research Council (Advanced Grant no. 786630) for funding; Marie Skłodowska-Curie Individual Fellowships (no. H2020-MSCA-IF-2020, to Y.R.) and the EPSRC Centre for Doctoral Training in Integrated Catalysis (no. EP/S023755/1, studentship to R.J.); S. D. P. Fielden for useful discussions; and A. Tanczos (SciComm Studios) for the tape-reading molecular ratchet animation.

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Contributions

Y.R., R.J. and D.J.T. planned and carried out the experiments. D.A.L. directed the research. All authors contributed to the analysis of the results and writing of the manuscript.

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Correspondence to David A. Leigh.

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Extended data figures and tables

Extended Data Fig. 1 Stepwise ratcheted operation of conformationally flexible crown ether 3 along −1,0,+1 stereochemically encoded molecular tape 1.

a, Reagents and conditions: (i) molecular tape 1 (1.0 equiv.), macrocycle 3 (10.0 equiv.), hydrazide 4 (4.0 equiv.), CF3CO2H (6.0 equiv.), CH3CN, rt, 2 h, then, to allow isolation, Et3N (50.0 equiv.), 52%; (ii) [2]rotaxane (S)-BMBA1–7 (1.0 equiv.), thiol 5 (2.0 equiv.), disulfide 6 (20.0 equiv.), Et3N (50.0 equiv.), CD3CN, rt, 16 h, 70%; (iii) [2]rotaxane MT-7 (1.0 equiv.), hydrazide 4 (4.0 equiv.), CF3CO2H (6.0 equiv.), CH3CN, rt, 16 h, then, to allow isolation, Et3N (50.0 equiv.), 75%. Yields determined after isolation by size-exclusion chromatography. b, Partial 1H NMR (600 MHz, CD3CN, 298 K) stack plot of [2]rotaxanes (S)-BMBA1–7 (top), MT-7 (middle), (R)-BMBA2–7 (bottom). c, Low resolution ESI-MS data for [2]rotaxane (S)-BMBA1–7 (top), MT-7 (middle) and (S)-BMBA2–7 (bottom).

Supplementary information

Supplementary Information

Experimental procedures, methods and characterization data.

Supplementary Video 1

Animation of the ratcheting and reading process by the molecular machine. Video credit: A. Tanczos (SciComm Studios).

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Ren, Y., Jamagne, R., Tetlow, D.J. et al. A tape-reading molecular ratchet. Nature 612, 78–82 (2022). https://doi.org/10.1038/s41586-022-05305-9

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