Transmission of Unidirectional Molecular Motor Rotation to a Remote Biaryl Axis

Article abstract of DOI:10.1002/anie.201804716

Molecular motors undergo repetitive directional motions upon external energy input. A profound challenge is the defined transfer of directional motor motions to remote entities at the molecular scale. Herein, we present a molecular setup that allows for the transfer of the directional rotation of a light-powered motor unit onto a remote biaryl axis via an ethylene glycol chain link. Based on a combination of X-ray crystallographic analysis, ECD, and NMR experiments as well as a comprehensive theoretical assessment, we provide evidence for the coupled stepwise directional motions of both molecular units. With the presented setup, facile integration of molecular motor units into larger functional frameworks and complex molecular machines can be explored consciously in the future.

Full text of DOI:10.1002/anie.201804716

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Accepted Article
Title: Transmission of Unidirectional Molecular Motor Rotation to a
Remote Biaryl Axis
Authors: Edgar Uhl, Stefan Thumser, Peter Mayer, and Henry Dube
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10.1002/anie.201804716
Angewandte Chemie International Edition
Transmission of Unidirectional Molecular Motor Rotation to a Remote Biaryl Axis
Edgar Uhl,† Stefan Thumser,† Peter Mayer,† Henry Dube†*
† Ludwig-Maximilians-Universität München, Department of Chemistry and Center for
Integrated Protein Science CIPSM, Butenandtstr. 5-13, 81377 München
E-mail: henry.dube@cup.uni-muenchen.de
Abstract
Molecular motors undergo repetitive directional motions upon external energy input. A
profound challenge is the defined transfer of directional motor motions to remote entities
at the molecular scale. In this work we present a molecular setup allowing to transfer the
directional rotation of a light powered motor unit unto a remote biaryl axis via an
ethylene-glycol chain link. Using a combination of X-ray crystallographic analysis, ECD
and NMR experiments, as well as a comprehensive theoretical assessment we provide
evidence for the coupled stepwise directional motions of both molecular units. With the
presented setup facile integration of molecular motor units into larger functional
frameworks and complex molecular machines can be explored consciously in the future.
Introduction
The construction of molecular machines has currently produced a plethora of different systems
undergoing mechanical motions at the molecular scale upon energy input.[1] One of the most
intriguing types of such machines are molecular motors allowing the generation of
unidirectional rotations at the molecular scale.[1f, 1l, 2] For the latter light induced directional
double-bond isomerizations play a central role.[1l, 2c, 3] We have contributed to this field by
introducing hemithioindigo[4] (HTI) based molecular motors, which provide very fast rotations
powered by visible light irradiation.[5] Having established directional rotations around a
particular bond however represents only the first step towards the projected goal of truly
sophisticated and responsive molecular machines with complex behavior and functions. To this
end means have to be found in which the unidirectional rotations of molecular motors can be
harnessed at the molecular scale and transmitted to entities that are not intrinsic parts of the
motor units. So far unidirectional motor rotations have been applied to catalysis[6] or cell
biology[7] and have also been transmitted to the macroscopic scale via e.g. liquid crystals,[8]
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mechanical entanglement within a gel[9] or a supramolecular artificial-muscle system.[10] The
well-defined transmittance of unidirectional motions to drive a secondary passive molecular
component is a different yet equally challenging problem because of the randomizing power of
the Brownian storm. Such transmittance presents the next crucial step towards the generation
of complex and integrated nano-machinery and currently great efforts are being made in this
direction[11] e.g. using the molecular gearing concept developed by Mislow and others.[12]
In the here presented work we pursue a different approach and provide evidence for a complete
transmittance of the unidirectional 360° double bond rotation of a molecular motor to a remote
aryl unit. By using an ethylene-glycol chain link in macrocycle 1 the intrinsic directional motion
of the motor part can spatially and temporally be relayed to a distant biaryl axis (Figure 1). The
underlying molecular design provides two functions. The motor part itself acts as an
intramolecular anchoring point and establishes a well-defined biaryl “follower” unit. This
asymmetric biaryl unit can then be used as probe for the stepwise detection of the induced
directional motion. To this end NMR and electronic circular dichroism (ECD) spectroscopy as
well as crystallographic analysis and quantum chemical calculations were used as analytical
methods.
Figure 1
a) Representation of A-1 with the motor part shown in red. b) Structure of racemic A-1 in
the crystalline state. Only the isomer with (R)-configured sulfoxide is shown. c) Structure
of racemic C-1 ((R) isomer) in the crystalline state. d) Side view of A-1 in the crystal. The
oxygen atoms of the rotor and biaryl fragments (red arrows) point to the same side as the
sulfoxide oxygen (black arrow). e) Side view of C-1 in the crystal. The oxygen atoms of
the rotor and biaryl fragments (blue arrows) point to the opposite side as the sulfoxide
oxygen (black arrow).
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Light powered directional motor rotation.
The synthesis of 1 is given in the Supporting Information in full detail. Two thermally stable
isomers of 1 i.e. A-1 (E-configured double bond) and C-1 (Z) are found in solution and in the
crystalline state (Figure 1b-e). For convenience only the structures with (R)-configured
sulfoxide are discussed in the following. Heating a solution of pure C-1 in tetrachloroethane-d2
to 80 °C for 16 h results in a stable composition of 96% A-1 and 4% C-1. This isomer preference
is opposite to the original motor system[5a] and most likely the result of increased strain in the
Z-configured C-1. It translates to a free energy difference between the two isomers of
∆G0 = 2.23 kcal/mol (i.e. 98% A-1 and 2% C-1 at 25 °C). First-order kinetic analysis gave an
energy barrier of ∆G* = 27.1 kcal/mol for the thermal C-1 to A-1 isomerization.
In the crystalline state both A-1 and C-1 possess (M)-helicity around the central double bond.
This is also the stable helicity in the Z and E isomers of the closely related original HTI
motor.[5a] Analysis of the electronic circular dichroism (ECD) spectra of enantiomerically pure
A-1 and C-1 in CH2Cl2 clearly confirmed (M)-helicity for the motor entity, which contributes
mostly to the long wavelength region of the spectra (see section 7 in the Supporting
Information). Irradiation of A-1 with 450 nm light at 23 °C in CD2Cl2 results in a maximum
concentration of 49% C-1 in the photostationary state (pss). Correspondingly, a maximum of
85% A-1 is obtained in the pss at 530 nm irradiation. At –80 °C irradiation of C-1 with 450 nm
light leads to the formation of a new set of signals in up to 75% intensity in the pss (Figure 2a),
which could be assigned to the D-1 isomer by comparison with the original HTI motor and
ECD spectral analysis. When the light is switched off after accumulation of D-1 slow thermal
conversion exclusively to the A-1 isomer is observed at –80 °C (Figure 2a). The thermal decay
kinetics of D-1 correspond to an energy barrier of 14.5 kcal/mol (see section 5 in the Supporting
Information) and are considerably slower than in the original motor system (13.1 kcal/mol).[5a]
Warming the solution containing D-1 to 23 °C and cooling back to –80 °C led to full conversion
of D-1 to A-1 while the concentration of C-1 remained unchanged (Figure 2a). Therefore it was
clearly shown, that the first 180° rotation of the double bond from C-1 to A-1 is completely
unidirectional (at least 95% if 5% remaining D-1 isomer is assumed to be detectable by NMR).
Similar to the original HTI motor irradiation of pure A-1 at –80 °C does not allow observation
of the B-1 isomer because of its very fast thermal decay to C-1 even at this low temperature.[5a,
5c] The corresponding energy barrier can therefore not be larger than 13 kcal/mol (assuming 1.5
min half-life of the isomer to be sufficient for NMR detection). Instead we observed C-1 as the
apparent photoproduct of A-1 irradiation (see Figure 2b and section 5 in the Supporting
Information). The resulting contradiction in the photochemistry of C-1, which seems to enter
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two independent photo-equilibria with A-1 and D-1 gives indirect evidence for the presence of
the B-1 state. Otherwise irradiation of C-1 should directly lead to population of A-1 as well,
which was not observed in the experiments. Overall the behavior of 1 under irradiation at low
temperature mirrors exactly the original HTI motor proving that its double-bond
photoisomerization is fully directional as in the original system (Figure 2).
1
Figure 2
Light powered unidirectional motor rotation of 1. a) Aromatic region of the H NMR
spectra (400 MHz, CD2Cl2) of C-1 recorded at –80 °C before (1) and during (2) irradiation
with 450 nm light for a total of 33 minutes (3), after the light was switched off (4, 5), and
after annealing at 23 °C and cooling back to –80 °C (6). No signals of A-1 are visible until
the light is switched off (spectra 4-6). b) Aromatic region of the 1H NMR spectra (400 MHz,
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CD2Cl2) of A-1 recorded at –80 °C before (1) and during (2) irradiation with 450 nm light
for a total of 33 minutes (3); after the light was switched off (4, 5) and after annealing at
23 °C and cooling back to –80 °C (6). c) Experimentally determined ground state energy
profile for the molecular motor fragment of 1. Energy barriers and lower energy limits for
unstable B-1 and D-1 were determined at –80 °C, the energy difference between A-1 and
C-1 at 80 °C.
Transmittance of the directional motion.
In the crystalline state of A-1 the helicity of the motor fragment is (M), with the aromatic rotor
fragment pointing to the same half space as the sulfoxide oxygen atom at the center part (Figure
1d). The remote biaryl axis is (Sa)-configured and the phenol-oxygen atom also points to the
same half space and is tilted towards the side of the carbonyl group. NOESY cross signals
between protons of the biaryl moiety as well as the ethylene-glycol chain and the center part
prove that this tilt direction is completely retained in solution (Figure 3a). An additional
comprehensive analysis of the ECD absorption spectrum of A-1 was conducted to establish the
absolute configuration of the “follower” biaryl axis in solution. To this end enantiomerically
pure A-1 and C-1 isomers were obtained after separation using chiral HPLC. ECD absorption
spectra were measured in CH2Cl2 at 23 °C and –80 °C. Molecular dynamics calculations in
conjunction with further optimizations at the DFT B3LYP-D3BJ/6-311G(d,p) PCM(CH2Cl2)
level of theory were used in the theoretical assessment of HTI 1 (see section 9 in the Supporting
Information). Absorption and ECD spectra were calculated on the B3LYP-D3BJ/6-311+G(d,p)
PCM(CH2Cl2) level of theory and compared to the experimental spectra. Nearly perfect
agreement between the experimental ECD spectrum of A-1 and the Boltzmann averaged
calculated ECD spectrum of all contributing low-energy conformers was found (see Figure 3c
and sections 7 and 9 in the Supporting Information). Comparison with the quantum chemical
description showed that the biaryl axis can assume both (Ra)- and (Sa)-configuration in solution,
which is different to the crystalline state and reflects the flexibility of the ethylene-glycol chain
in the A-1 isomer. From this analysis it could be shown that the “follower” biaryl unit is
spatially restricted and reflects the conformation of the rotor fragment in its tilt towards the
carbonyl side of the center fragment.
For isomer B-1 no experimental spectra could be obtained due to its kinetically unstable
character. However, in the theoretical analysis only minimum structures with exclusively (Sa)-
configuration of the remote biaryl axis were found, regardless of initial starting geometries
(Figure 3d). Therefore, it is highly likely that also in the B-1 isomeric state the remote biaryl
axis follows the rotor geometry closely.
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In the crystalline state of isomer C-1 the rotor fragment resides in the half space opposite to the
sulfoxide-oxygen atom (Figure 1e). The remote biaryl axis is again (Ra)-configured with the
phenol-oxygen atom pointing to the opposite half space of the sulfoxide-oxygen. Again the
biaryl unit is tilted and its phenol oxygen atom points towards the sulfoxide of the center
fragment, i.e. to the same side as the aromatic rotor fragment. NOESY (Figure 3b) and ECD
spectroscopic analyses (Figure 3e) confirmed, that the conformation of C-1 in solutions is very
similar to the one found in the crystal. Analysis of the ECD spectrum of C-1 recorded in CH2Cl2
established that the biaryl axis is preferably (Ra)-configured in solution (see sections 7 and 9 in
the Supporting Information).
The ECD absorption spectrum of pure D-1 isomer could be obtained in CH2Cl2 at –80 °C. To
this end ECD spectra were recorded after irradiation to the pss of enantiomerically pure samples
of both A-1 and C-1. Starting from either isomer the same ECD spectrum was obtained after
40 min of irradiation with 450 nm light at the low temperature. From this ECD spectrum the
corresponding spectrum of pure D-1 could be extracted by spectra subtraction (see section 8 in
the Supporting Information for details). Comparison of the experimental ECD spectrum of D-
1 with the theoretical description allowed a clear assignment of the biaryl axis’ absolute
configuration, which is solely (Ra)-configured in solution (Figure 3f). Unfortunately no
information about the tilt of the biaryl unit in D-1 could be gleaned from attempts at low
temperature NOESY NMR spectroscopy.
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Figure 3
Conformational analysis of 1 in solution. Calculated ECD spectra were blue shifted 10-
15 nm for better comparability. a) Selected part of the NOESY spectrum (600 MHz,
CD2Cl2, 27 °C) of A-1 showing the tilt of the biaryl unit. b) Selected part of the NOESY
spectrum (600 MHz, CD2Cl2, 27 °C) of C-1 showing the tilt of the biaryl unit. c)
Experimental (red, CH2Cl2, –80 °C) and calculated Boltzmann-averaged (blue) ECD
spectrum of A-1. A mixture with (Ra) and (Sa) configured biaryl axis was found to
account for the ECD. d) Calculated ECD spectra for all low free energy conformers of
B-1. All conformers found possess exclusively (Sa) configured biaryl axes. e)
Experimental (red, CH2Cl2, –80 °C) and best fitting calculated (blue) ECD spectrum of
C-1. The calculated spectrum was obtained from a conformer with (Ra) configured
biaryl axis. f) Experimental (red, CH2Cl2, –80 °C) and best fitting calculated (blue) ECD
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spectrum of D-1. The calculated spectrum was obtained from a conformer with (Ra)
configured biaryl axis.
From our experiments a clear pattern emerges for the light powered motions of molecular motor
system 1. Considering only the motor unit, its behavior is analogous to the original HTI motor
showing complete unidirectionality of its double-bond rotation. This rotation proceeds in four
distinct steps, which are coupled to the remote biaryl unit via the ethylene-glycol linker. Every
step of the directional double-bond rotation is closely followed by the biaryl unit, which is seen
experimentally by its preferred tilt in A-1 and C-1 as well as its absolute configuration, and
likewise by its absolute configuration in B-1 and D-1. Taken together, we could show that the
unidirectional rotation around the motors central double bond is effectively transmitted to the
biaryl single bond of this remote site (Figure 4).
Figure 4
Transmission of directional motor rotation unto the remote chiral biaryl axis of the
follower unit in 1 in four consecutive steps. a) Schematic view of D-1 to visualize the
coupled motion. b) Relative positions of the rotor (blue) and biaryl follower (red) unit
during a full 360° rotation. As there is some degree of flexibility in the macrocyclic
system the position of the follower unit is indicated as pink colored area.
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Conclusion
In this work we present a HTI based motor system 1, which covalently interconnects the rotor
fragment of its molecular motor unit with a distant asymmetric biaryl axis. The biaryl moiety
was used as reporter unit facilitating interpretation of ambient and low temperature NMR and
ECD experiments with regard to particular geometry changes. Together with crystal structure
analysis and theoretical calculations the absolute configuration of the system during the full
360° movement could be deciphered. HTI 1 therefore enabled direct observation of a controlled
transmission of unidirectional motion to a passive and remote part of a molecule. Alternatively
the motion may be described as unidirectional rotation of the benzothiophenone unit within a
cyclophane stator[13] structure.
With the presented molecular setup more sophisticated systems can be devised in the future
allowing to transmit directional motions over considerable distances at the molecular scale with
high precision. Currently we develop a variety of related systems in our laboratory and test their
potential in the context of integrated molecular machines and more advanced functions.
Acknowledgements: H. Dube thanks the “Fonds der Chemischen Industrie” for a Liebig
fellowship (Li 188/05) and the Deutsche Forschungsgemeinschaft (DFG) for an Emmy Noether
fellowship (DU 1414/1-1). We further thank the Deutsche Forschungsgemeinschaft (SFB 749,
A12) and the Cluster of Excellence ’Center for Integrated Protein Science Munich’ (CIPSM)
for financial support.
Keywords: molecular machines • photochemistry • isomerization • hemithioindigo • physical
chemistry
References
[1]
a) E. R. Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. Int. Ed. 2007, 46, 72-191; b) S.
Erbas-Cakmak, D. A. Leigh, C. T. McTernan, A. L. Nussbaumer, Chem. Rev. 2015,
115, 10081-10206; c) E. R. Kay, D. A. Leigh, Angew. Chem. Int. Ed. 2015, 54,
10080-10088; d) D. A. Leigh, Angew. Chem. Int. Ed. 2016, 55, 14506-14508; e) S.
Kassem, A. T. L. Lee, D. A. Leigh, V. Marcos, L. I. Palmer, S. Pisano, Nature 2017,
549, 374-378; f) S. Erbas-Cakmak, S. D. P. Fielden, U. Karaca, D. A. Leigh, C. T.
McTernan, D. J. Tetlow, M. R. Wilson, Science 2017, 358, 340-343; g) M. R. Wilson,
J. Sola, A. Carlone, S. M. Goldup, N. Lebrasseur, D. A. Leigh, Nature 2016, 534, 235-
240; h) G. De Bo, M. A. Y. Gall, S. Kuschel, J. De Winter, P. Gerbaux, D. A. Leigh, Nat.
This article is protected by copyright. All rights reserved.

10.1002/anie.201804716
Angewandte Chemie International Edition
Nanotechnol. 2018; i) C. Cheng, P. R. McGonigal, S. T. Schneebeli, H. Li, N. A.
Vermeulen, C. Ke, J. F. Stoddart, Nat Nano 2015, 10, 547-553; j) H. Li, C. Cheng, P.
R. McGonigal, A. C. Fahrenbach, M. Frasconi, W. G. Liu, Z. Zhu, Y. Zhao, C. Ke, J. Lei,
R. M. Young, S. M. Dyar, D. T. Co, Y. W. Yang, Y. Y. Botros, W. A. Goddard, 3rd, M. R.
Wasielewski, R. D. Astumian, J. F. Stoddart, J. Am. Chem. Soc. 2013, 135, 18609-
18620; k) A. Coskun, M. Banaszak, R. D. Astumian, J. F. Stoddart, B. A. Grzybowski,
Chem. Soc. Rev. 2012, 41, 19-30; l) N. Koumura, R. W. J. Zijlstra, R. A. van Delden,
B. L. Feringa, Nature 1999, 401, 152-155; m) D. Zhao, T. van Leeuwen, J. Cheng, B.
L. Feringa, Nat. Chem. 2017, 9, 250-256; n) J. P. Sauvage, Angew. Chem. Int. Ed.
2017, 56, 11080-11093; o) J. F. Stoddart, Angew. Chem. Int. Ed. 2017, 56, 11094-
11125; p) J. D. Badjić, V. Balzani, A. Credi, S. Silvi, J. F. Stoddart, Science 2004, 303,
1845-1849; q) T. Muraoka, K. Kinbara, T. Aida, Nature 2006, 440, 512-515; r) V.
Balzani, A. Credi, M. Venturi, Molecular Devices and Machines—Concepts and
Perspectives for the Nanoworld, Wiley-VCH, 2008.
[2]
a) S. Kassem, T. van Leeuwen, A. S. Lubbe, M. R. Wilson, B. L. Feringa, D. A. Leigh,
Chem. Soc. Rev. 2017, 46, 2592-2621; b) J. V. Hernandez, E. R. Kay, D. A. Leigh,
Science 2004, 306, 1532-1537; c) H. A. Kistemaker, P. Stacko, J. Visser, B. L.
Feringa, Nat. Chem. 2015, 7, 890-896.
[3]
[4]
a) L. Greb, J. M. Lehn, J. Am. Chem. Soc. 2014, 136, 13114-13117; b) L. Greb, A.
Eichhofer, J. M. Lehn, Angew. Chem. Int. Ed. 2015, 54, 14345–14348.
a) P. Friedländer, Chem. Ber. 1906, 39, 1060-1066; b) V. A. Izmail'skii, M. A.
Mostoslavskii, Ukr. Khem. Zh. 1961, 27, 234-237; c) K. Ichimura, T. Seki, T.
Tamaki, T. Yamaguchi, Chem. Lett. 1990, 9, 1645-1646; d) T. Lougheed, V.
Borisenko, T. Hennig, K. Rück-Braun, G. A. Woolley, Org. Biomol. Chem. 2004, 2,
2798-2801; e) S. Kitzig, M. Thilemann, T. Cordes, K. Rück-Braun, ChemPhysChem
2016, 17, 1252-1263; f) T. Cordes, T. Schadendorf, B. Priewisch, K. Rück-Braun,
W. Zinth, J. Phys. Chem. A 2008, 112, 581-588; g) W. Steinle, K. Rück-Braun, J. Org.
Lett. 2003, 5, 141-144; h) S. Kitzig, K. Rück-Braun, J. Pept. Sci. 2017, 23, 567-573;
i) J. E. Zweig, T. R. Newhouse, J. Am. Chem. Soc. 2017, 139, 10956-10959; j) S.
Wiedbrauk, H. Dube, Tetrahedron Lett. 2015, 56, 4266-4274; k) S. Wiedbrauk, B.
Maerz, E. Samoylova, A. Reiner, F. Trommer, P. Mayer, W. Zinth, H. Dube, J. Am.
Chem. Soc. 2016, 138, 12219-12227; l) S. Wiedbrauk, T. Bartelmann, S. Thumser,
P. Mayer, H. Dube, Nat. Commun. 2018, 9, 1456; m) H. Dube, J. Rebek, Jr., Angew.
This article is protected by copyright. All rights reserved.

10.1002/anie.201804716
Angewandte Chemie International Edition
Chem. Int. Ed. 2012, 51, 3207-3210; n) M. Guentner, E. Uhl, P. Mayer, H. Dube,
Chem. Eur. J. 2016, 22, 16433-16436.
[5]
a) M. Guentner, M. Schildhauer, S. Thumser, P. Mayer, D. Stephenson, P. J. Mayer,
H. Dube, Nat. Commun. 2015, 6, 8406; b) L. A. Huber, K. Hoffmann, S. Thumser, N.
Böcher, P. Mayer, H. Dube, Angew. Chem. Int. Ed. 2017, 56, 14536-14539; c) R.
Wilcken, M. Schildhauer, F. Rott, L. A. Huber, M. Guentner, S. Thumser, K.
Hoffmann, S. Oesterling, R. de Vivie-Riedle, E. Riedle, H. Dube, J. Am. Chem. Soc.
2018, 140, 5311-5318.
[6]
[7]
[8]
a) J. Wang, B. L. Feringa, Science 2011, 331, 1429-1432; b) D. Zhao, T. M.
Neubauer, B. L. Feringa, Nat. Commun. 2015, 6, 6652.
V. Garcia-Lopez, F. Chen, L. G. Nilewski, G. Duret, A. Aliyan, A. B. Kolomeisky, J. T.
Robinson, G. Wang, R. Pal, J. M. Tour, Nature 2017, 548, 567-572.
a) R. Eelkema, M. M. Pollard, J. Vicario, N. Katsonis, B. S. Ramon, C. W. Bastiaansen,
D. J. Broer, B. L. Feringa, Nature 2006, 440, 163; b) T. Orlova, F. Lancia, C.
Loussert, S. Iamsaard, N. Katsonis, E. Brasselet, Nat. Nanotechnol. 2018, 13, 304-
308.
[9]
a) Q. Li, G. Fuks, E. Moulin, M. Maaloum, M. Rawiso, I. Kulic, J. T. Foy, N.
Giuseppone, Nat. Nanotechnol. 2015, 10, 161-165; b) J. T. Foy, Q. Li, A. Goujon, J.-
R. Colard-Itte, G. Fuks, E. Moulin, O. Schiffmann, D. Dattler, D. P. Funeriu, N.
Giuseppone, Nat. Nanotechnol. 2017, 12, 540-545.
[10] J. Chen, F. K. Leung, M. C. A. Stuart, T. Kajitani, T. Fukushima, E. van der Giessen, B.
L. Feringa, Nat Chem 2018, 10, 132-138.
[11] P. Štacko, J. C. M. Kistemaker, T. van Leeuwen, M.-C. Chang, E. Otten, B. L. Feringa,
Science 2017, 356, 964-968.
[12] a) K. Mislow, Acc. Chem. Res. 1976, 9, 26-33; b) Z. Rappoport, S. E. Biali, Acc. Chem.
Res. 1997, 30, 307-314; c) H. Iwamura, K. Mislow, Acc. Chem. Res. 1988, 21, 175-
182; d) D. K. Frantz, A. Linden, K. K. Baldridge, J. S. Siegel, J. Am. Chem. Soc. 2012,
134, 1528-1535.
[13] For definitions of rotor and stator units see: G. S. Kottas, L. I. Clarke, D. Horinek, J.
Michl, Chem. Rev. 2005, 105, 1281-1376.
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Table of Contents Figure
The directional rotation of a hemithioindigo based molecular motor is effectively transmitted
to a remote asymmetric biaryl axis via an ethylene-glycol chain. This coupled directional
motion was analyzed by X-ray crystallography, NMR and ECD spectroscopy at different
temperatures as well as a thorough theoretical treatment. With the presented setup directional
motions can now be relayed to other functional entities against the equilibrating Brownian
motion on the molecular scale with high precision.
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