Development of rotaxane type molecular ratchets

1. Development of rotaxane typemolecular ratchets M1 Ryo Takabayashi, Tobe laboratory Division of Frontier Materials Science, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University

2. Contents Introduction 1. Molecular Machine 2. Rotaxane 3. Molecular Ratchet Examples of Molecular Ratchets 1. The First Paper 2. The Second Paper Summary - My Approach toward a Molecular Ratchet

3. Molecular Machines What is a molecular machine A molecular machine is an assembly of a distinct number of molecular components that are designed to perform machinelike movements linked to a specific function as a result of an appropriate external stimulation. Molecular brake Molecular switch Rotaxane based Molecular elevator Balzani, V.; Credi, A. Angew. Chemie.2000, 39, 3348-3391. http://nanotechweb.org/cws/article/tech/19281

4. Rotaxane Rotaxane A rotaxane is a supramoleculeconsisting of aring component and a dumbbell-shaped axle component threaded through the ring. Bulky parts called stoppers at the terminal of the axle component prevent the ring component from slipping out. ＋ Dumbbell shaped axle Ring Features of a rotaxane ・Station Most rotaxanes have stations on the axle component. The ring component is stabilized at the station due to interaction between components (e.g. hydrogen bonb). ・Shuttling Shuttling is back-and-forth motion of the ring component between the stations along the axle. • Station • Shuttling

5. Rotaxane-based Simple Molecular Shuttle Simple molecular shuttle The position of the ring was changed due to differentstability between components. ⇒This process is governed by simple thermodynamics. Tian, H.; Wang, Q. Chem. Soc. Rev.2006, 35, 361–374.

6. Sophisticated Molecular Shuttle Sophisticated molecular shuttle Unidirectional motion of the ring was achieved. ⇒This step is similar to that of a ratchet. Stoddart, J. F. et. al. J. Am. Chem. Soc. ASAP.

7. Definition Molecular Ratchet Ratchet : A ratchet is a mechanical device that allows linear or rotary motion in only one direction while preventing motion in the opposite direction. Molecular Ratchet : Molecular machines possessing motions like that of ratchet are called molecular ratchets. A molecular ratchet has unidirectional movement. Forward motion Backward motion To design and construct a molecular ratchet isdifficult, so there arefew reports on molecular ratchets. Research on molecular ratchets which provides new approaches in control of molecular machineshas attracted much attention recently.

8. Face selective translation of a cyclodextrin ring along an axle Oshikiri, T.; Yamaguchi, H.; Takashima, Y.; Harada, A. Chemcommun. 2009, 5515–5517.

9. Previous work Designed Pseuodrotaxane Pseudorotaxane A pseudorotaxanehas no bulky stopper; slipping of the ring component can happen. Axle component The one edge (the left one) is relatively bulky, and the other (the right one) is bulky enough to prevent the ring component from slipping. Thering component can thread the axle, and can slipfrom the left edge. Ring component a-Cyclodextrin (a-CD) The structure of a-Cyclodextrinis similar to that of a cone. a-Cyclodextrin has two faces; the primary face is smaller, the secondary face is larger. (a) Chemical Structure (b) 3D Structure Primary face Secondary face Oshikiri, T.; Takashima, Y. Eur. j. Org. Chem. 2007, 13, 7091–7098.

10. Previous work Mixed in a 1 : 4 molar ratio in D2O at 343 K Easier 0a 0b 0c 0d Correlation between time and degree of complex formation of a-CD with the axle component. a-CD on the 1st station (0aand 0c), a-CD on the 2nd station (0band 0d) with different face directions. Face selective intrusion of the ring into the axle Oshikiri, T.; Takashima, Y. Eur. j. Org. Chem. 2007, 13, 7091–7098.

11. Approach to a Molecular Ratchet By combination of a relatively bulky spacer in the middle of an axle component and a-Cyclodextrin, a pseudorotaxaneexpected to have face selective transportation was designed.

12. Structure Designed Pseudorotaxane Axle component The one edge (the left one) is relatively bulky, and the other (the right one) is bulky enough to prevent the ring component from slipping. The ring component can thread the axle, and can slip from the left edge. A relatively bulky spacer is introduced in the middle of the axle. Ring component a-Cyclodextrin (b) 3D Structure (a) Chemical Structure Primary face Secondary face

13. Experiment The first alkyl station The second alkyl station Mixed in a 1 : 4 molar ratio in D2O at 343 K 1H NMR spectra of the axle without a-CD (b) soon after mixing with a-CD (c) 7 days after mixing at 343 K in D2O These spectra show ・The rate of the threading of a-CD into the axle component was much faster than that of theshuttling between the first alkyl station and the second alkyl station. ・Complexes between the axle componentand a-CD with different face directions on each station were formed.

14. Experiment Mixed in a 1 : 4 molar ratio in D2O at 343 K Correlation between time and degree of complex formation of a-CD with the axle component. a-CD on the 1st station (1aand 1c), a-CD on the 2nd station (1band 1d) with different face directions.

15. Result Kinetic parameters on the shuttling of a-CD (a) between 1aand 1b (b) between 1cand 1d, and then (c) comparison of rate constants on the translation of a-CD in 1a to 1b, and 1c to 1d.

16. Conclusions ・The translation of a-CD on the psuedorotaxanewas kinetically controlled by the well-designed spacer. ・This behavior should be derived from the difference between the transition states of the translations; the activation energy barrier in the case where the wider sideof a-CD faces to the second station of the axle is much lower than that of the opposite direction. ・This is the first observation that a ring is transferred between two stations on an axle molecule with face selectivity.

17. Quantitative Active Transport in [2]Rotaxane Using a One-Shot Acylation Reaction toward the Linear Molecular Motor Makita, Y.; Kihara, N.; Takata, T. J. Org. Chem.2008, 9245–9250.

18. Motivation Schematic representation of a [2]rotaxane-based linear molecular motor and its periodic potential surface. Since unidirectional movement is entropicallyunfavored (DS < 0), the supply of free energy is necessary to realize such movement. Tomake a molecular motor possessing an unidirectional transport system, it is necessarythermodynamically unfavoredchange induced by a certain free energy source.

19. Approach to a Molecular Ratchet × trapped This reaction is very rapid Concept of unidirectional transposition of the ring component in the rotaxane. (a) The ring component is trapped at the ammonium station, so dethreading is prevented. (b) By neutralization of the ammonium group, the ring component is released from the station. Due to the bulky end-cap, the ring component tentatively migrates to the center of the axle component. (c) Before the nonselective slipping of the axle component, a bulky acyl group is introduced on the amino group to prevent dethreading beyond the nitrogen.

20. PreliminaryExperiment Rotaxane1 was synthesized to conduct a preliminary experiment. Features of the rotaxane ・An asymmetric axle component possessing one station ・One stopper (the left one) is relatively bulky, but the ring component can pass on it, and the other (the right one) is bulky enough to prevent the ring component from dethreading. Dethreading ・1 was stable in CD3CN (no dethreading). ・The reaction from 2 to 4 or from 2 to 5 + DB24C8 (the ring component) was very rapid (checked by 1HNMR).

21. Result of PreliminaryExperiment a Initial concentration of 1 was 15 mM. The reactions were carried out at r.t. for 15 min in CD3CN in the presence of 5.0 equivalent of Et3N. b Determined by the 1H NMR spectra of the crude product (isolated yield given in parentheses). c [4]/([4] + [6]) d The reaction was carried out for 24 h. e Not detected. These data show DMAP accelerated the acylation reaction. These data show the more bulky stopper in the left side prevented the ring from dethreadingmore efficiently. These data show the rotaxane formation of 1c by acylation with all three reagents worked very well. ・The simple first order kinetics (t1/2 = 462 h at 333 K in CD3CN) from 1c to 5c. ⇒The dethreading of 1c to form 5c is a thermodynamically favored process in the presence of triethylamine. ・1d was stable under the presence of triethylamine (no dethreading). ⇒The ring component in 2cdethreadedthe axle component not beyond the 3,5-dimethylphenyl end-cap but beyond the neopentyl-type end-cap.

22. Crystal Structures of 1b and 4cr Crystal structure of 1b and 4cr(a) 1b. Hydrogensand PF6- were omitted for clarity. (b) 4cr. Hydrogenswere omitted for clarity.

23. Summary about PreliminaryExperiment ・The migration of the ring component toward the proximate end-cap is thermodynamically favored movement for 1cduring the treatment with triethylamine. However, in the acylation experiments, the ringin 1cmigrated toward a thermodynamically unfavored direction to produce 4cr quantitatively. The movement is unidirectional transport, which was achieved by the local potential surface on the axle of 1c and 2c. ・The effect of the neopentyl-type group as the distantend-cap was examined; The ring can pass over the neopentyl-type end cap, but the dethreading was relatively prevented because of the bulkiness.

24. Experiment and Result Rotaxane7 was synthesized to conduct a main experiment. Features ・An asymmetric axle component possessing one station ・One stopper (the right one) is relatively bulky, but the ring component can pass on that, and the other (the left one) is bulky enough to prevent the ring component from dethreading. trapped × BzCl neopentyl stable at 333 K in DMSO Dethreadingof 8 occurred rapidly at 333 K in CD3CN to form 9 and DB24C8 (t1/2 = 1.2 h) in the absence of triethylamine. With the interaction between the axle component and the ring component, theneopentyl group acts as the sufficiently bulky end-cap to prevent dethreading (in 7). However, without the intercomponent interaction, the neopentyl-type group behaves as the sufficiently small end-cap to allow the dethreadingof the ring component (in 9). The unidirectional transport of the ring was successful.

25. Conclusions ・The direction of transport is influenced by the local potential surface and not by the thermodynamic stability. In other words, it is driven by the gradient of the local potential surface and the free energy due to acylation and not as a result of attractive interactions. ・These features are essential parts of chemical energy-driven unidirectional linear molecular motors. ・The present work demonstrates that imitationof natural molecular motors can be realized in simple molecular systems by a simple reaction that utilizes the local potential surface.

26. Future Work ・An artificial linear molecular motor system can be envisioned to be a simple extension of the transport system, and that was under construction. • (a) to (b): The Bocgroup is deprotected, and the ring component migrates to the thermodynamically stable ammonium station. • (b) to (c): The ammonium groups are acylated by Bocgroup, and the ringcomponent unidirectionallymigrates to the space between the Boc and the neopentyl groups. • (c) to (d): The selective deprotection of the TFA group is followed by application of protonation forces to the ringcomponent in order to move it to the thermodynamically stable ammonium salt station. • (d) to (e): The ammonium group is acylated by TFAA, and the ringcomponent unidirectionally migrates to the space between the TFA and the neopentyl groups.

27. Summary ・Molecular ratchet are molecular machines possessing motions like that of ratchet are called molecular ratchets. A molecular ratchet has unidirectional movement. ・Two molecular machines, which can be called molecular ratchets, are introduced in this presentation. In the first paper, a ring was transferred between two stations on an axle molecule with face selectivity. In the second paper, unidirectional transportation of a ring on an axle molecule was achieved by a well-designed local potential surface.

28. My Approach toward a Molecular Ratchet

29. Process of My Dynamic Potential Change System Dynamic potential change system

30. Structure of Target Molecular Ratchet

31. 以下質問対策

32. Molecular Ratchets A definition of ratcheting in chemical terms “Ratcheting” is the capturing of a positional displacement of a substrate through the imposition of a kinetic energy barrier which prevents the displacement being reversed when the thermodynamic driving force is removed. The key feature of ratcheting is that the ratcheted part of the system is not linked with (i.e., not allowed to exchange the substrate with) any part of the system that it is ratcheted from. Ratcheting is a crucial requirement for allowing a Brownian machine to be reset without undoing the task it has performed. Because it is used to kinetically stabilize an ultimately thermodynamically unfavorable state, ratcheting is intrinsically associated with a sequential logic sequence applied to a Brownian substrate. J. AM. CHEM. SOC. 9 VOL. 128, NO. 12, 2006 In other words Ratcheting means controlling relative motions between components kinetically to an thermodynamically unfavorable states. Research on rotaxanes possessing ratcheting systems, so called molecular ratchets, has been interested in recently.

33. Application of Rotaxaneto Molecular Machines no change after stimulus Sophisticated molecular switch 65 (ratio) 55 stimulus shuttling shuttling 45 35 Virtually The probability of the ring changed virtually. This process is not governed by simple thermodynamics . This can be explained with a ratchet system. Serreli, V.; Lee, C.-F.; Kay, E. R.; Leigh, D. A. Nature 2007, 445 (7127), 523-527

34. Rotaxane-based Simple Molecular Shuttle Simple molecular shuttle stimulus1 stimulus2 This process is governed by simple thermodynamics Tian, H.; Wang, Q.-C. Chem. Soc. Rev. 2006, 35, 361−374.

35. Synthesis (i) a. n-BuLi, diethylamine, THF, 195 K , 1 h; b. 1,8-dibromooctane, THF, 195 K to 323 K , overnight, 35%. (ii) 1-(10-Iodo-decyl)-3,5- dimethylpyridiniumiodide, acetone, reflux, 4 d, 93%. (iii) Methyl iodide, acetone, r.t., 3 d, 15%.

36. Rotaxane Synthesis http://en.wikipedia.org/wiki/Rotaxane

37. Supplementary explanations Pseudrotaxane A pseudrotaxane has no bulky stopper; slipping of a ring component can happen. • a-Cyclodextrin The structure of a-Cyclodextrin similar to that of a cone. a-Cyclodextrin has two faces; the primary face is smaller, the secondary face is larger.

38. PreliminaryExperiment (2) a Initial concentration of 1 was 15 mM. The reactions were carried out at r.t. for 15 min in CD3CN in the presence of 5.0 equivalent of Et3N. b Determined by the 1H NMR spectra of the crude product (isolated yield given in parentheses). c [4]/([4] + [6]) d The reaction was carried out for 24 h. e Not detected.