A single synthetic small molecule that generates force against a load

Biological molecular machines are able to rectify random thermal motions to generate directional force and carry out tasks on both the molecular and macroscopic length scales1. Although some artificial nanomachines have been synthesized2-4 and used to collectively carry out mechanical tasks5-8, the direct measurement of the mechanical processes at the single molecule level has yet to be realized. We show that biased Brownian motion of the sub-molecular components in a hydrogen bonded [2]rotaxane9-a molecular ring threaded onto a molecular axle-can be harnessed to generate significant directional forces. We applied a mechanical load to the ring by atomic force microscopy (AFM) cantilever during single molecule pulling-relaxing cycle. Using fluctuation theorems, we were able to relate the measurements of the work done at the level of individual molecules to the free energy change measured previously by ensemble measurements. The results show that individual rotaxane molecules can generate directional forces of similar magnitude to biological machines, and extend the capabilities of AFM-based single molecule mechanics to the world of small molecules. 1. Schilva, M. (ed.) Molecular Motors (Wiley-VCH, Weinheim, 2003). 2. Kinbara, K. & Aida, T. Toward intelligent molecular machines : Directed motions of biological and artificial molecules and assemblies. Chem. Rev. 105, 1377-1400 (2005). 3. Kay, E. R., Liegh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72-191 (2007). 4. Browne, W., Feringa, B. L. Making molecular machines work. Nature Nanotech. 1, 25-35 (2006). 5. Berna, J., Leigh, D. A., Lubomska, M., Mendoza, S. M., Pérez, E. M., Rudolf, P., Teobaldi, G. & Zerbetto, F. Macroscopic transport by synthetic molecular machines. Nature Mater. 4, 704-710 (2005). 6. Liu, Y., Flood, A. H., Bonvallet, P. A., Vignon, S. A., Northrop, B. H., Tseng, H.-R., Jeppesen, J. O., Huang, T. J., Brough, B., Baller, M., Magonov, S., Solares, S. D., Goddard, W. A., Ho, C.-M. & Stoddart, J. F. Linear artificial molecular muscles. J. Am. Chem. Soc. 127, 9745-9759 (2005) 7. Eelkema, R., Pollard, M. M., Vicario, J., Katsonis, N., Ramon, B. S., Bastiaansen, C. W. M., Broer, D. J. & Feringa, B. L. Molecular machines: Nanomotor rotates microscale objects. Nature 440, 163 (2006). 8. Muraoka, T., Kinbara, K., Aida, T. Mechanical twisting of a guest by a photoresponsive host. Nature 440, 512-515 (2006). 9. Kay, E. R. & Liegh, D. A. Hydrogen bond-assembled synthetic molecular motors and machines. Top. Curr. Chem. 262, 133-177 (2005)