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Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm


Modern-day factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. The idea of manipulating molecular fragments in a similar way has to date only been explored using biological building blocks (specifically DNA). Here, we report on a wholly artificial small-molecule robotic arm capable of selectively transporting a molecular cargo in either direction between two spatially distinct, chemically similar, sites on a molecular platform. The arm picks up/releases a 3-mercaptopropanehydrazide cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry controls the cargo binding to the platform. Transport is controlled by selectively inducing conformational and configurational changes within an embedded hydrazone rotary switch that steers the robotic arm. In a three-stage operation, 79–85% of 3-mercaptopropanehydrazide molecules are transported in either (chosen) direction between the two platform sites, without the cargo at any time fully dissociating from the machine nor exchanging with other molecules in the bulk.

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Figure 1: Multi-stage operation of a bidirectional small-molecule transporter system, 1, that uses a rotary switch to control a molecular robotic arm.
Figure 2: Synthesis of transporter–cargo conjugates Z-2-left and EZ-1-left.
Figure 3: Partial 1H NMR (600 MHz, 295 K, CD2Cl2) spectra of the transporter–cargo conjugates at distinctive stages of operation.
Figure 4: Operation of the molecular transporter to reposition a 3-mercaptopropanehydrazide cargo from blue to green or green to blue platform sites.
Figure 5: Presumed intermediates in the rotary switching 26 and cargo transport mechanism.


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The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC) for funding and the EPSRC National Mass Spectrometry Service Centre (Swansea, UK) for high-resolution mass spectrometry.

Author information




A.M. and D.A.L. planned the project. S.K., A.T.L.L., A.M. and J.S. carried out the experimental work. D.A.L. directed the research. All authors contributed to the analysis of the results and the writing of the manuscript.

Corresponding author

Correspondence to David A. Leigh.

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The authors declare no competing financial interests.

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Kassem, S., Lee, A., Leigh, D. et al. Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm. Nature Chem 8, 138–143 (2016).

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