Artificial Design of Molecular Motors

Yubai Zhou

Michigan State University November 14, 2012

Designs of Synthetic Molecular Motors

Heat Engine

Electric Motor ATP Synthase

http://galileo.phys.virginia.edu/classes/152.mf1i.spring02/CarnotEngine.pdf Elston, T.; Wang, H.; Oster, G. Nature, 1998, 391, 510.

Motors From Man-Made Scale to Molecular Scale: Similar Designs from Nature

Macroscopic Scale Molecular Scale

Synthetic Molecular Motors: Energy-Directed Conformational (Configurational) Motion

Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem. Int. Ed. 2000, 39, 3348.

Conformer A

Conformer X Conformer B

……

(1) Consumption of Energy

(3) Unidirectional and Repetitive Motion

(2) A Series of Chemical Transformation

Chemical-Driven Rotary Molecular MotorsThe chemical reaction is mechanically coupled to movement and force is directly generated to move the motor forward.

1 Triptycyl Helicene

2 Biary Lactone

First Prototype of Synthetic Motors Based on Triptycyl Helicene

Kelly, T. R.; Silva, H. D.; Silva, R. A. Nature, 1999, 401, 150.

The Idea of Design From A Molecular Brake

Bowyer, M. C.; Bhaskar, K. V. et al. Kelly, T. R. J. Am. Chem. Soc. 1994, 116, 3657.

Chemically Powered Bond RotationBond Rotation Barrier 20-25 kcal·mol-1


Controlled 120° Bond Rotation in Triptycyl Helicene Derivatives


Requirements on Structure to Achieve 360° Continuous Rotation

•  Each blade of the triptycene must be attached an amino group.

•  A good chemoselectivity is required for phosgene delivery to the

amine “firing position”.

•  Successful 120° rotation of the triptycene should be brought by

the phosgene-fueled formation of an intramolecular urethane.

•  The urethane has to be cleaved to allow subsequent repetition of

preceding rotation.

Cai, X.; Damkaci, F. et al. Kelly, T. R. J. Am. Chem. Soc. 2007, 129, 376.

DMAP Induced in Rotating Motor


Directed Acylation of Amine by DMAP

Kelly, T. R.; Cavero, M. Org. Lett. 2002, 4, 2653.

Proposed Process of 360° Rotation


Unexpected Products from Quenching by Methanol


Selective Mono-Acylation via Less Reactive Surrogate for Phosgene


mono-acylated motor1,1’-carbonyldiimidazole

Failure of Staab Equilibrium in Motors


Trifloroacetyl Protection to Give Monoamine


Reasons for Failure to Form UrethaneBürgi-Dunitz intervention

Markey, M. D.; Kelly, T. R. Tetrahedron, 2008, 64, 8381.

Stability of Cyclic Acylpyridinium Salt

Unchanged in MeOH at 100 ℃ for 19 h


Possible Modification to Interfere with the Resonance of DMAP Unit


Comments on Triptycene-system Motors

•  Successful 120° clockwise bond rota6on, but failed in 360° repeated

rota6on with the existence of DMAP unit

•  Phosgene fuel was too reac6ve to give a selec6ve acyla6on of amine

proximate to “firring posi6on”

•  The stable acylpyridinium salt from DMAP and isocyanate impeded

the forma6on of urethane to give con6nuous rota6on

Unidirectional Bond Rotary of Biaryl Lactone from Diastereoselective Ring-Opening

However, the rapid equilibrium of diastereomerization scrambles the direction of bond rotationDahl, B. J.; Branchaud, B. P. Tetrahedron Lett. 2004, 45, 9599.

exo face aIack�

180° Bond Rotation of Bifunctional Biaryl Lactone Derivatives

M axial

Dahl, B. J.; Branchaud, B. P. Org. Lett. 2006, 8, 5841.

360° Rotation of Achiral Biaryl Lactone

Fletcher, S. P.; Dumur, F.; Pollard, M. M.; Feringa, B. L. Science, 2005, 310, 80.

Summary of Chemical-Driven Molecular Motors

l  Unidirectional rotation is controlled by chemical interaction.

l  Chemoselectivity is the main challenge in multifunctionl motors.

l  The chemical accumulation may contaminate the system.

Fletcher, S. P.; Dumur, F.; Pollard, M. M.; Feringa, B. L. Science, 2005, 310, 80.

Light-Driven Rotary Molecular Motors

Light-Driven Molecular Motors

Mechanism of Motor Rotation

Structure Modification

Motor-Controlled LC Reorganization

Motor-Controlled Asymmetric Catalysis

M- and P- Axial Helicity in Molecules

Photochemical and Thermal isomerization of Overcrowded Biphenanthrylidenes

Koumura, N.; Zijlstra, R. W. J. et al. Feringa, B. L. Nature, 1999, 401, 152.

Energy Diagram of Rota0on Cycle

Pollard, M. M.; Klok, M.; Pijper, D.; Feringa, B. L. Adv. Funct. Mater. 2007, 17, 718.

Structure Analysis of Overcrowded Alkenes

1.341 Å

1.347 Å

111.22°

122.76°123.18°

ter Wiel, M. K. J.; van Delden, R. A.; Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 14208.

Steric Interaction in Thermal Helix Inversion

Steric interactions in the fjord region

Pollard, M. M.; Klok, M.; Pijper, D.; Feringa, B. L. Adv. Funct. Mater. 2007, 17, 718.

Ultraviolet and Circular Dichroism Spectra to Lable Motor 1

Koumura, N.; Zijlstra, R. W. J. et al. Feringa, B. L. Nature, 1999, 401, 152.

Unexpected Changes of i-Propyl-Substituted Motors in Photochemical Process

solid dotted


Thermal Helix Inversion Monitored by NMR


Rotary Cycle of i-Propyl-Substituted Motors


Rate Acceleration by Structure Modification






Possible Ways to Improve the Motors

•  Accelerating the rate of rotation to control the unidirectional motion

by overcoming the “Brownian storm” from molecular collision and

vibration.

•  Functionalization to allow incorporation with more complex

molecular structure, able to be involved in certain chemical process.

Pollard, M. M.; Klok, M.; Pijper, D.; Feringa, B. L. Adv. Funct. Mater. 2007, 17, 718. Pollard, M. M.; Meetsma, A.; Feringa, B. L. Org. Biomol. Chem. 2008, 6, 507.

Rotation Acceleration with Five-Membered Ring Systems

ter Wiel, M. K. J.; van Delden, R. A.; Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2003, 125, 15076. Pollard, M. M.; Meetsma, A.; Feringa, B. L. Org. Biomol. Chem. 2008, 6, 507.

The thermal helix conversion is the rate-determined step in bond rotation.

Rotation Cycle of Five-Membered Ring Motors

1.4 h 4.2 h


Half-time of Thermal Helix Conversion

Molecular Motors

Cis-isomer helix conv.

Trans-isomer helix conv.

Overall Process

1 32 min 439 h 2 ~20 ha

2A 18 min 317 h 3 74 min 18 s 40 min4 >36 hb 1.2 sc

a. 50% conversion at 110 ℃ monitored by 1H-NMR;b. 20 min at 60 ℃;c. at -20 ℃.ter Wiel, M. K. J.; van Delden, R. A.; Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 14208. Pollard, M. M.; Meetsma, A.; Feringa, B. L. Org. Biomol. Chem. 2008, 6, 507.

Energy Barrier of Thermal Helix Conversion

Molecular Motors

Cis-isomer helix conv. ΔG(kJ·mol-1)

Trans-isomer helix conv. ΔG(kJ·mol-1)

1 91 1072 124, 131a

2A 91 1073 95 844 101 71

a. the conversion contains two steps.ter Wiel, M. K. J.; van Delden, R. A.; Meetsma, A.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 14208. Pollard, M. M.; Meetsma, A.; Feringa, B. L. Org. Biomol. Chem. 2008, 6, 507.

Structure Analysis of Cis- and Trans-isomers with Five-membered Ring


1.352 Å104.6°

1.350 Å104.1°

Design of Second Generation Light-Driven Rotary Motors

Rotor

Stator

Koumura, N.; Geertsema, E. M. et al. Feringa B. L. J. Am. Chem. Soc. 2002, 124, 5037.

Tuning the Speed of Rotary Motion of Motors with Symmetric Lower Moieties

Motor Energy Barrier (kJ·mol-1) Half-time (h) Photochemistry

Ratio

6 105.2 184 8:927 105.6 215 13:878 100.5 26.3 23:779 110.1 1283 23:77

10 106.0 233 8:9211 91.8 0.67 1:9912 94.4 2.01 1:9913 102.7 60.1 25:75

Koumura, N.; Geertsema, E. M. et al. Feringa B. L. J. Am. Chem. Soc. 2002, 124, 5037.

Second Generation Motors with Fused Five Membered Ring System

Motor Energy Barrier (kJ·mol-1) Half-time (s) Photochemistry

Ratio15A 88 587 25:75

15B 85 190 14:86

15C 84 95 11:89

15D 60 5.73x10-3 12:88

16 79 15 33:67

17 38 5.74x10-7 a NAa. 2.3 h at 115 K

Vicario, J.; Walko, M.; Meetsma, A.; Feringa B. L. J. Am. Chem. Soc. 2006, 128, 5127. Kulago, A. A.; Mes, E. M. et al. Feringa B. L. J. Org. Chem. 2010, 75, 666.

Summary: Steric Effect on Half-time of Thermal Helix Conversion

•  Ground state energy of unstable isomers depends on the geometry of overcrowded alkenes

•  Increasing the size of substituents makes the isomers with pseudo-equatorial substituents more sterically strained.

•  Less steric interaction at fjord region gives large decrease of energy barrier. Motors with fused five membered ring have a released space in the fjord region for trans-isomer, but even more crowded for cis-isomers.

•  The second generation motors are able to reduce the energy barrier significantly by changing the bridging atoms.

Vicario, J.; Walko, M.; Meetsma, A.; Feringa B. L. J. Am. Chem. Soc. 2006, 128, 5127.






Rotational Reorganization of Liquid Crystalline Films Induced by Doped Molecular Motors

Rod Rotation on the Doped Cholesteric LC Film: Observed Helix Twisting Power of Motors

liquid crystal with embedded molecular motor

glass rod (28 µm)Eelkema, R.; Pollard, M. M. et al. Feringa B. L. J. Am. Chem. Soc. 2006, 128, 14397.

Possible Mechanism of Rotational Reorganization of LC Films

𝑝= [𝛽 ∙𝑐 ∙(𝑒𝑒)]↑−1 p – the pitch of cholesteric liquid crystalls; β – the HTP of the dopant; c – the concentration of the dopant;

Eelkema, R.; Pollard, M. M. et al. Feringa B. L. J. Am. Chem. Soc. 2006, 128, 14397.

AFM Images of Corrugated LC Film Surface

Eelkema, R.; Pollard, M. M. et al. Feringa B. L. J. Am. Chem. Soc. 2006, 128, 14397.

Helical Polymer Functionalized Molecular Motors: Light-Controlled Helicity in LC Phase

Pijper, D.; Jongejan, M. G. M.; Meetsma, A.; Feringa B. L. J. Am. Chem. Soc. 2008, 130, 4541

molecular chirality

macromolecular chirality

Supramolecular chirality

Full Photocontrol of Supramolecular Helicity in LC Phase

(2’S)-‐(P)-‐18-‐PHIC (2’S)-‐(M)-‐18-‐PHIC

Pijper, D.; Jongejan, M. G. M.; Meetsma, A.; Feringa B. L. J. Am. Chem. Soc. 2008, 130, 4541

Molecular Motors in Asymmetric Reac0on






Beyond the Traditional Asymmetric Catalysis

Wang, J.; Feringa, B. L. Science, 2011, 331, 1429.

The Design of Bifunctional Molecular Motors


Previous Work on Bifunctional Organocatalyst

Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672. Rana, N. K.; Selvakumar, S.; Singh, V. K. J. Org. Chem. 2010, 75, 2089.

Rotation Cycle of Bifunctional Motors


UV and CD Spectral Changes of Isomerization


Bifunctional Motor Catalyzed Michael Addition(P,P)-trans-18 R/S = 51/49 �

(M,M)-cis-18 R/S= 25/75 �

(P,P)-cis-18 R/S = 77/23 �


Transition State in Asymmetric Catalysis


Comments on Motors as Asymmetric Catalysts

•  The light-driven rotary molecular motors may be a useful tool in

developing new asymmetric catalysis systems.

•  The bifunctional molecular motors shown significant

stereochemical interplay based on the geometry of transition state

in Michael addition.

•  There is a long way to improve the stereoselectivity and more

reactions are going to be explored.

Triptycyl Helicene

Overcrowded Alkene

Biaryl Lactone

Summary

Acknowledgement

l  Dr. Wulff

l  Dr. Borhan

l  Dr. Jackson

l  My lab members

Yong, Hong, Wynter, Wenjun, Xin, Xiaopeng, Mathew,

Munmun, Anil, Dima, Nilanjana

l  My friends

l  My family

Artificial Design of Molecular Motors

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