Small Machines with Great Potential the Chemistry Nobel Prize 2016

SPG Mitteilungen Nr. 51 Small machines with great potential The Chemistry Nobel Prize 2016

Karl-Heinz Ernst *, Empa, Swiss Federal Laboratories for Materials Science and Technology

The Nobel Prize for Chemistry 2016 was awarded by the Royal Swedish Academy of Sciences to Jean-Pierre Sau- vage, J. Fraser Stoddard and Ben Feringa for the development of molecular machines. The three researchers designed molecules with subunits that move relative to each other in a controlled manner. Some of their molecules can, for example under infuence of light, fulfll work. The laureates laid the foundation for nanoscopic motors, like molecular es- calators, molecular muscles and nanocars and are considered as founders of a new feld in chemistry. Their functional molecules are believed to have a large potential and it is expected that they become useful some day in nanomedicine or as intelligent materials.

Tiniest machines known ging the redox state of the Cu ions induced then a relative Molecular motors are omnipresent in the biological world. movement of the rings [2]. The motor protein kinesin, for example, transports vesicles Around 1990, the group of John Fraser Stoddard in Shef- through the cell by ‘walking’ along microtubules, which rep- feld (UK) designed molecular shuttles based on the class resent the cytoskeleton of the cell. As fuel serves adenosine of rotaxanes. These are intertwined molecules, containing a triphosphate (ATP), inducing the restructuring in the motor dumbbell-shaped part that sticks in a molecular ring (Figure protein needed for the walking motion as well as for adhe- 1b). Changing the redox state of aromatic parts at the ring sion of the kinesin ‘feet’ to the microtubules. Other exam- and the axle of the dumbbell caused again a relative motion ples for motor proteins in eukaryotic cells are dynein, for between both parts of the rotaxane. transport along the microtubules into the opposite direction than kinesin, and myosin, causing the motility needed for muscle function. Inspired by nature’s molecular motors, chemists strive for synthetic approaches towards molecular machines that are able to perform work at the nanoscale. Like machines of the macroscopic world, molecular machines are built up Figure 1. Sketch of catenane and rotaxane synthesis and rearrangement upon stimulus. (© Johan by several interacting ele- Jarnestad, The Royal Swedish Academy of Sciences) ments, which altogether fulfll a certain kind of work. These little structures can be – when Shortly after the turn into the new millennium, Sauvage and triggered by light or electricity – driven to perform different Stoddard presented advanced examples based on rotax- actions. So far, synthetic molecular machines have not left anes, including reversible linear stretching, mimicking mus- the stage of fundamental research, but theoretically their cle action [3] or a nanoescalator (Figure 2) [4]. potential for applications at the nanoscale seems remark- able. However, the challenges to reach such goal some day Molecular revolution: around and around and around are tremendous. and ... During the 1990ies, it was Ben Feringa at the University Moving molecules Groningen, NL, who introduced the frst molecular rotor [5]. A frst important step in the feld of molecular motors was The concept based on a C=C double bond that connected taken by Jean-Pierre Sauvage of Université Strasbourg, two parts, which suffered steric overcrowding because of France, when he established a new route to synthesize cat- bulky groups. Due to its electronic structure this molecule enanes [1]. The ring-like subunits of these molecules are not would prefer a planar confguration, but the overcrowding connected by covalent chemical bonds, but are intertwined causes a helical shape, introducing a 'ratchet' into the mol- (catena lat. for chain, see Figure 1a). Catenanes had been ecule (Figure 3). Driven by light, one part rotates against known before, but Sauvage and coworkers lowered drasti- the other. Usually this happens with equal probability clock- cally the effort needed for obtaining these compounds and wise or counterclockwise, but Feringa’s clever concept in- increased substantially the yield. They connected a ring-like troduced unidirectional rotation due to two steps that are in- unit with a crescent-shaped molecule via copper ions and cluded in the rotation. That is, the electronic excitation of the had the ends of the ‘crescent’ reacting with another cres- molecule by light is followed by a thermally induced vibronic cent-shaped unit in order to close the second ring. Chan- step. The electronic excitation causes a so-called cis-trans isomerization, involving opening and closing of the double bond and rotation of the two units until stopped for steric * The author holds a position as Distinguished Senior Researcher at reasons. However, a subsequent stretching vibration of the Empa and is honorary professor at the University of Zurich. 18 Communications de la SSP No. 51

– can be identical to the initial state. Performing this double step twice, a complete revolution of the rotor is achieved.

Feringa’s group went on to improve this concept, including speeding up the rotation. The climax of the concept, however, became realized as the so-called nanocar. Feringa’s group synthesized a molecule that involved four rotor units connected to a single molecular chas- sis. Careful design of the stereochemistry of the ro- tors led to identical sens- es for all rotor revolu- tions. Driven by electrons emanating from the tip of scanning tunneling microscope, the molecule Figure 4. Excitation of Feringa's na- performed unidirectional nocar by inelastic electron tunneling translational motion on a in a scanning tunneling microscope copper surface (Figure 4) (from reference [6]). [6].

A personal involvement As the 2009 president of the prestigious Stereochemistry Figure 2. (a) Extension and contraction of a rotaxane-based 'mo- Bürgenstock Conference, Ben Feringa invited the author to lecular muscle'. (b) Schematic representation of a rotaxane-based give a presentation about his research on various aspects of 'elevator'. (© Johan Jarnestad, The Royal Swedish Academy of molecular surface chirality, which also comprised molecular Sciences). dynamics induced by inelastic electron tunneling and scanning tunneling microscopy. After my talk Ben asked me over a beer at the bar if we could shine UV-light into our instru- ment in order to show unidirectional motion of a molecule containing four rotor units. I denied that we were able to perform light-induced experiments at that stage, but proposed to excite the molecule with electrons instead. Being focused on light, Ben seemed to hesitate, but having a beer again at the very same place a year later, we fnally agreed to try it with electrons. Ben sent us Tibor Kudernac from Groningen, who spent three months in our lab as visiting scientist. He perfectly teamed up with Manfred Parschau, a senior staff scientist in my group. Tibor fnally succeeded and brought proof of concept that the nanocar undergoes – fuelled by electrons – unidirectional motion on the surface. After being published as cover story in Nature in 2011, the nanocar got large attention in the media throughout the world – a hype that returned to us in October in 2016 [7].

References [1] C. O. Dietrich-Buchecker, J. P. Sauvage, J. P. Kintzinger, Tetrahedron Figure 3. Principle of a Feringa rotor. A molecular system under- Lett. 1983, 24, 5095. goes a cis-trans inversion upon irradiation at the C=C bond bet- [2] A. Livoreil, C. O: Dietrich-Buchecker, J. P. Sauvage, J. Am. Chem. Soc. ween two parts of a molecule, which leads to a stereochemically 1994, 116, 9399. less-favored state. This one is released thermally; vibrations – in [3] M. C. Jimenez, C. Dietrich-Buchecker, J. P Sauvage, Angew. Chem. Int. Ed. 2000, 39, 3284. particular the C=C stretch vibration – allows a relaxation into a [4] J. D. Badjic, V. Balzani, A. Credi, S. Silvi, J. F. Stoddart, Science 2004, state which is identical to the initial state [a) and c) are related by 303, 1845. rotation of the entire molecule by 180°]. Dashed bonds represent [5] N. Koumura, R. W. J. Zijlstra, R. A. van Delden, N. Harada, B. L. Ferin- molecular parts behind the paper plane, bold bonds above the pa- ga, Nature 1999, 401, 152. per plane. [6] T. Kudernac, N. Ruangsupapichat, M. Parschau, B. Maciá, N. Katsonis, S. R. Harutyunyan, K. H. Ernst, B. L. Feringa, Nature 2011, 479, 208. double bond caused another partial rotation with a substan- [7] For the media coverage see www.empa.ch/mss. tial lower barrier into forward direction. Overall, this double step caused a rotation of 180°, which – based on the design