news & views ARTIFICIAL MOLECULAR MACHINES
Two steps uphill
An axle-shaped molecule pumps charged rings from solution into an alkyl collection unit, a mechanism that, in two repetitive cycles, takes the system increasingly further from equilibrium.
Steve Goldup
C
ontrolling molecular motion to reproduce the behaviour of macroscopic machines is a rapidly developing field of chemistry 1. In the last two decades, researchers have reported examples of Brownian ratchets2, rotary motors3 and linear motors4. However, designing systems that can work repetitively to move progressively further from equilibrium, a key property of natural molecular machines, remains challenging. Writing in Nature Nanotechnology, Fraser Stoddart and co-workers at Northwestern University now report a minimalistic molecular machine that can successfully pump molecules from solution into a collecting region, iteratively moving the system further from equilibrium5. The authors base their molecular machine on a rotaxane, a molecule comprising a linear axle that is able to restrict the motion of a ring-shaped component threaded onto it. Although rotaxanes are ubiquitous features of many molecular machines, in this case the chemical structure of the axle is such that the motion of the rings can only occur in one direction through a complex mechanism that involves two one-way valves. The key structural features (Fig. 1) of the machine are (i) a positively charged pyridinium unit (red) that acts as the first one-way valve; (ii) a viologen unit (orange) that acts as the pump; (iii) a bulky isopropylphenyl ‘speed bump’ that acts as the second one-way valve (purple); and (iv) an alkyl chain (green) that acts as the collection unit, terminated with a group too large to allow the rings to dethread. The driving force is provided by a reduction– oxidation cycle6 that reversibly loads and expels tetracationic cyclophane rings from the viologen moiety and this, combined with the one-way valves, allows the machine to operate repetitively to move first one, then another ring from solution to the ring collection moiety. The cycle begins with chemical reduction of the ring and the viologen group (step 1) that establishes an attractive interaction between them. As a result, a ring from
solution slips past the pyridinium group to encircle the viologen moiety. Subsequent oxidation (step 2) removes this attractive interaction; indeed, on oxidation the ring and viologen electrostatically repel one another. At this point, although thermodynamic considerations dictate that the ring should escape back to solution, the combined repulsion between the ring in its oxidized state and the pyridinium end group and viologen moieties is sufficient to ensure that the ring takes the path of least resistance and moves to become trapped between the viologen and the speed bump. This repulsive interaction provides the first one-way valve in the cycle. From here the ring slowly slips over the bulky speed bump (step 3) to reach the ring-collecting region of the axle. Thus, over the first cycle the ring is pumped from solution, its thermodynamically preferred position, to the ring collection region of
the axle where it experiences reduced translational freedom (lower entropy) and little or no attractive interactions with the alkyl chain. To start the second cycle the mixture is reduced once again. Although on reduction the thermodynamically preferred outcome is for the trapped ring to return to the viologen unit, the speed bump acts as the second oneway valve by preventing its passage; without the repulsive interaction between the ring and viologen unit, the ring lacks the energy to overcome the activation barrier to slip over the speed bump. Thus, reduction leads to the loading of a second ring from solution onto the viologen unit without the first ring escaping. Subsequent oxidation then sends the second ring over the speed bump to the collector. With two rings captured, the system is now further from the preferred equilibrium
a N
N
O
N
N N N
8
N
N
N
N
O
b First pumping cycle
1
2
3
Second pumping cycle
2+3
1
Figure 1 | Working principle of a molecular pump. a, Chemical structure of the molecular machine. Pyridinium unit, red; viologen, orange; isopropylphenyl, purple; alkyl chain with end group, green; ring, blue. b, Schematic of the molecular pump operation over two cycles. Step 1, reduction; Step 2, oxidation; Step 3, slippage of the ring past the speed bump. Equivalent chemical and mechanical components are colour coded.
NATURE NANOTECHNOLOGY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturenanotechnology
© 2015 Macmillan Publishers Limited. All rights reserved
1
news & views position (both rings in solution). The rings are now at a higher effective molarity and experience significantly larger inter-ring electrostatic repulsion than in solution. The pump therefore does work on the system. On each cycle, the system captures some of the energy consumed by the pump as chemical potential energy and moves further from equilibrium, although the exact amount of potential energy stored is hard to estimate. To achieve this, Stoddart and co-workers demonstrate fine control over the kinetics and thermodynamics of the motion of the rings. This is an extremely challenging task and it must be noted that even relatively small modifications to the spacing between the viologen and the pyridinium are sufficient to obliterate the working of the molecular machine. The researchers liken the behaviour of their machine to biological machines
2
that transport ions and molecules across membranes against a concentration gradient. In keeping with this analogy, the next task would be to extend this device beyond two cycles to do more work and store more energy. However, in this initial version, the ring-collecting region is too small to accommodate more than two rings. This limitation could be overcome either by simply extending the axle or, more excitingly, by embedding such machines in membranes to pump molecules between compartments, in a form of artificial active transport. In addition to the aesthetic value of producing minimalist models of complex biological machinery, a long-term challenge in the field of artificial molecular machines is to find ways to do useful work either at the macroscopic level on the surrounding environment or at the molecular level by
controlling the chemistry of the system and eventually materials properties. The work by Stoddart and co-workers takes this possibility two steps closer. ❐ Steve Goldup is in the Department of Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, UK. e-mail: [email protected] References
1. Astumian, R. D. Phys. Chem. Chem. Phys. 9, 5067–5083 (2007). 2. Chatterjee, M. N., Kay, E. R. & Leigh, D. J. Am. Chem. Soc. 128, 4058–4073 (2006). 3. Ruangsupapichat, N., Pollard, M. M., Harutyunyan, S. R. & Feringa, B. L. Nature Chem. 3, 53–60 (2011). 4. von Delius, M., Geertsema, E. M. & Leigh, D. A. Nature Chem. 2, 96–101 (2010). 5. Cheng, C. et al. Nature Nanotech. http://dx.doi.org/10.1030/ nnano.2015.96 (2015). 6. Cheng, C. et al. J. Am. Chem. Soc. 136, 10–13 (2014).
Published online: 18 May 2015
NATURE NANOTECHNOLOGY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturenanotechnology
© 2015 Macmillan Publishers Limited. All rights reserved
Two steps uphill
An axle-shaped molecule pumps charged rings from solution into an alkyl collection unit, a mechanism that, in two repetitive cycles, takes the system increasingly further from equilibrium.
Steve Goldup
C
ontrolling molecular motion to reproduce the behaviour of macroscopic machines is a rapidly developing field of chemistry 1. In the last two decades, researchers have reported examples of Brownian ratchets2, rotary motors3 and linear motors4. However, designing systems that can work repetitively to move progressively further from equilibrium, a key property of natural molecular machines, remains challenging. Writing in Nature Nanotechnology, Fraser Stoddart and co-workers at Northwestern University now report a minimalistic molecular machine that can successfully pump molecules from solution into a collecting region, iteratively moving the system further from equilibrium5. The authors base their molecular machine on a rotaxane, a molecule comprising a linear axle that is able to restrict the motion of a ring-shaped component threaded onto it. Although rotaxanes are ubiquitous features of many molecular machines, in this case the chemical structure of the axle is such that the motion of the rings can only occur in one direction through a complex mechanism that involves two one-way valves. The key structural features (Fig. 1) of the machine are (i) a positively charged pyridinium unit (red) that acts as the first one-way valve; (ii) a viologen unit (orange) that acts as the pump; (iii) a bulky isopropylphenyl ‘speed bump’ that acts as the second one-way valve (purple); and (iv) an alkyl chain (green) that acts as the collection unit, terminated with a group too large to allow the rings to dethread. The driving force is provided by a reduction– oxidation cycle6 that reversibly loads and expels tetracationic cyclophane rings from the viologen moiety and this, combined with the one-way valves, allows the machine to operate repetitively to move first one, then another ring from solution to the ring collection moiety. The cycle begins with chemical reduction of the ring and the viologen group (step 1) that establishes an attractive interaction between them. As a result, a ring from
solution slips past the pyridinium group to encircle the viologen moiety. Subsequent oxidation (step 2) removes this attractive interaction; indeed, on oxidation the ring and viologen electrostatically repel one another. At this point, although thermodynamic considerations dictate that the ring should escape back to solution, the combined repulsion between the ring in its oxidized state and the pyridinium end group and viologen moieties is sufficient to ensure that the ring takes the path of least resistance and moves to become trapped between the viologen and the speed bump. This repulsive interaction provides the first one-way valve in the cycle. From here the ring slowly slips over the bulky speed bump (step 3) to reach the ring-collecting region of the axle. Thus, over the first cycle the ring is pumped from solution, its thermodynamically preferred position, to the ring collection region of
the axle where it experiences reduced translational freedom (lower entropy) and little or no attractive interactions with the alkyl chain. To start the second cycle the mixture is reduced once again. Although on reduction the thermodynamically preferred outcome is for the trapped ring to return to the viologen unit, the speed bump acts as the second oneway valve by preventing its passage; without the repulsive interaction between the ring and viologen unit, the ring lacks the energy to overcome the activation barrier to slip over the speed bump. Thus, reduction leads to the loading of a second ring from solution onto the viologen unit without the first ring escaping. Subsequent oxidation then sends the second ring over the speed bump to the collector. With two rings captured, the system is now further from the preferred equilibrium
a N
N
O
N
N N N
8
N
N
N
N
O
b First pumping cycle
1
2
3
Second pumping cycle
2+3
1
Figure 1 | Working principle of a molecular pump. a, Chemical structure of the molecular machine. Pyridinium unit, red; viologen, orange; isopropylphenyl, purple; alkyl chain with end group, green; ring, blue. b, Schematic of the molecular pump operation over two cycles. Step 1, reduction; Step 2, oxidation; Step 3, slippage of the ring past the speed bump. Equivalent chemical and mechanical components are colour coded.
NATURE NANOTECHNOLOGY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturenanotechnology
© 2015 Macmillan Publishers Limited. All rights reserved
1
news & views position (both rings in solution). The rings are now at a higher effective molarity and experience significantly larger inter-ring electrostatic repulsion than in solution. The pump therefore does work on the system. On each cycle, the system captures some of the energy consumed by the pump as chemical potential energy and moves further from equilibrium, although the exact amount of potential energy stored is hard to estimate. To achieve this, Stoddart and co-workers demonstrate fine control over the kinetics and thermodynamics of the motion of the rings. This is an extremely challenging task and it must be noted that even relatively small modifications to the spacing between the viologen and the pyridinium are sufficient to obliterate the working of the molecular machine. The researchers liken the behaviour of their machine to biological machines
2
that transport ions and molecules across membranes against a concentration gradient. In keeping with this analogy, the next task would be to extend this device beyond two cycles to do more work and store more energy. However, in this initial version, the ring-collecting region is too small to accommodate more than two rings. This limitation could be overcome either by simply extending the axle or, more excitingly, by embedding such machines in membranes to pump molecules between compartments, in a form of artificial active transport. In addition to the aesthetic value of producing minimalist models of complex biological machinery, a long-term challenge in the field of artificial molecular machines is to find ways to do useful work either at the macroscopic level on the surrounding environment or at the molecular level by
controlling the chemistry of the system and eventually materials properties. The work by Stoddart and co-workers takes this possibility two steps closer. ❐ Steve Goldup is in the Department of Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, UK. e-mail: [email protected] References
1. Astumian, R. D. Phys. Chem. Chem. Phys. 9, 5067–5083 (2007). 2. Chatterjee, M. N., Kay, E. R. & Leigh, D. J. Am. Chem. Soc. 128, 4058–4073 (2006). 3. Ruangsupapichat, N., Pollard, M. M., Harutyunyan, S. R. & Feringa, B. L. Nature Chem. 3, 53–60 (2011). 4. von Delius, M., Geertsema, E. M. & Leigh, D. A. Nature Chem. 2, 96–101 (2010). 5. Cheng, C. et al. Nature Nanotech. http://dx.doi.org/10.1030/ nnano.2015.96 (2015). 6. Cheng, C. et al. J. Am. Chem. Soc. 136, 10–13 (2014).
Published online: 18 May 2015
NATURE NANOTECHNOLOGY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturenanotechnology
© 2015 Macmillan Publishers Limited. All rights reserved
