A hemithioindigo molecular motor for metal surface attachment

Article abstract of DOI:10.1039/c8ob02424c

Functionalization of surfaces with responsive molecular entities is currently an important research field allowing the organization of molecular functions in space in a defined way and thus accessing emergent properties not observed in solution. Herein we

Full text of DOI:10.1039/c8ob02424c

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A hemithioindigo molecular motor for metal
surface attachment†
Cite this: DOI: 10.1039/c8ob02424c
Kerstin Hoffmann, Peter Mayer and Henry Dube
*
Functionalization of surfaces with responsive molecular entities is currently an important research field
allowing the organization of molecular functions in space in a defined way and thus accessing emergent
properties not observed in solution. Herein we report on the synthesis of a hemithioindigo molecular
motor bearing thioether feet for surface attachment on its thioindigo fragment. We also give a full theore-
tical description of its ground state energy profile together with an experimental evaluation of the visible
light driven unidirectional rotation in solution. Comparison with the corresponding unsubstituted original
motor shows that after feet-attachment the hemithioindigo molecular motor is fully operative with a
similar maximum attainable speed and degree of unidirectionality.
Received 28th September 2018,
Accepted 22nd October 2018
DOI: 10.1039/c8ob02424c
rsc.li/obc
undesired sideways or flat resting of the motor entity. As both
feet-units cannot adopt a coplanar geometry with the stator
Introduction
Light driven molecular motors1–11 are prototypical molecular fragment, especially the one adjacent to the carbonyl group,
machines12–16 and have entered the realm of applications and they are expected to attain a twisted arrangement leading to
great efforts are currently being made to provide functiona- four distinct interaction points with the metal surface. In this
lized versions for a variety of purposes such as catalysis,17,18 way an upright standing architecture of the motor unit is
water solubility,19 biological interfacing,20,21 polymer attach- expected, which will be tilted sideways because of the nonsym-
ment,22,23 liquid crystal or gel interactions,24,25 molecular reco- metric connection to the two feet-moieties (Fig. 1).
gnition,26,27 folding,28 or surface interactions.29–33 We have
developed hemithioindigo (HTI) based molecular motors6–9
that allow nondamaging visible light to be used as fuel for
their directional motions. After establishing the working
Results and discussion
Synthesis
mechanism of HTI motor derivatives with different steric hin-
drance,7,8 we recently functionalized both the rotor and the
The synthesis of HTI motor 1 (Scheme 1) starts from commer-
cially available 3,5-dichlorobenzenethiol (2), which is con-
stator fragments to transmit their unidirectional double bond
rotation intramolecularly to a remote biaryl axis.9 In the work
presented here we describe a different two-fold functionali-
zation at only the stator fragment to enable upright position-
ing of HTI molecular motors on different metal surfaces. This
work is therefore the first step towards the implementation of
fast and visible light responsive molecular motors on surfaces
to significantly widen the application range of these intriguing
molecular machines as well as open up new possibilities for
integration with sensitive (bio)molecular components. HTI
motor 1 possesses two feet each bearing two thioether substi-
tuents to allow upright standing on metal surfaces and prevent
Ludwig-Maximilians-Universität München, Department für Chemie and Munich
Center for Integrated Protein Science CIPSM, D-81377 Munich, Germany.
E-mail: henry.dube@cup.lmu.de
†Electronic supplementary information (ESI) available. CCDC 1869283–1869288,
1873825. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c8ob02424c
Fig. 1 HTI motor
expected upright attachment on metal surfaces.
1 bearing thioether feet and illustration of its
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Scheme 1 Synthesis of HTI motor 1. Only the thermodynamically most stable Z isomers are shown for clarity. The structure of original HTI motor 9
is shown for comparison.
verted to the corresponding thioacetic acid 3 via a nucleophilic
substitution reaction in quantitative yield. Intramolecular
Friedel–Crafts acylation delivers dichlorinated benzothio-
phenone 4 in 83%, which is condensed with the known inda-
none 5 to yield HTI 6 as a mixture of Z and E isomers in 85%
combined yield. In this case we use boron trichloride as a
Lewis acid at low temperature, which significantly improves
the yield of this key reaction in the synthesis as compared to
the originally published procedure.6 Synthesis of indanone 5
followed established literature procedures.6,34 Oxidation of 6
with sodium perborate gives the dichlorinated HTI motor 7
again as a mixture of Z and E isomers in a very good combined
yield of 88%. Subsequently motor 7 is connected to the two
“feet”-moieties for surface attachment, each bearing two
thioether based attachment points. To this end Suzuki cross
coupling between HTI motor 7 and boronic acid pinacol ester
8 is employed giving the final functionalized HTI motor 1 in
a satisfactory yield of 45%. Synthesis of 8 followed an estab-
lished protocol for the conversion of aromatic halides into
boronic esters.35
Crystals suitable for structural analysis were obtained for 3
Fig. 2 Structures in the crystalline state of 3 and 4, and racemic Z-6, E-
and 4, and the Z and E isomer of HTI 6, as well as the Z and E
isomers of HTI motor 7 and boronic acid pinacol ester 8 as
shown in Fig. 2. In the crystal, HTIs (6) and the HTI motors (7)
adopt helical structures around the photoisomerizable double
bond with the corresponding dihedral angles dSC8C9C17 of
10.9° (Z-6), 161.6° (E-6), 15.4° (Z-7), and 163.6° (E-7). Therefore
the HTI structures Z-6 and E-6 are also intrinsically chiral but
their helix inversions and thus racemizations are very fast
processes precluding the isolation of enantiomerically pure
samples.
6, Z-7, E-7 and 8. The dihedral torsion angle around the central double
dSC8C9C17 bond is assigned in the structure of Z-6.
6-311G(d,p) level of theory and compared to the experimentally
obtained values (Fig. 3).
Similar to the original HTI motor 9,6,9 motor 1 undergoes
complete unidirectional rotation around its central double
bond upon irradiation with visible light. Its working mecha-
nism is likewise comprised of four distinct steps with alternat-
ing photoisomerizations and thermal helix inversions. Four
diastereomeric structures are populated in a fixed sequence
during the unidirectional rotation. The two most stable
Physical and photophysical properties in solution
To assess the rotation mechanism of HTI motor 1 we con- isomers (isomer A with the E-(S)-(P)/E-(R)-(M) configuration
ducted a comprehensive study using variable temperature and isomer C with the Z-(S)-(P)/Z-(R)-(M) configuration) could
NMR spectroscopy as the main analytical tool. Additionally the be isolated and characterized separately at ambient tempera-
ground state energy profile was calculated on the B3LYP/ ture using mainly NMR spectroscopy in conjunction with a
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observed, which could be attributed to the D-1 isomer. This
isomer is not entirely stable at −80 °C and thermally converts
at this temperature exclusively into the A-1 isomer within
5 min in the dark. During this process no changes in the
signals of the remaining C-1 are seen, thus proving the com-
pleteness of this thermal ratcheting step and therefore also
completing the unidirectionality of the first 180° double bond
rotation. First order kinetic analysis of the thermal decay of
D-1 to A-1 allowed determination of the activation energy of
this thermal process using the Eyring equation. A value of
ΔG* = 13.2 kcal mol−1 was found in this case. Since the com-
plete decay of D-1 to A-1 was seen at −80 °C a lower limit for
the energy difference between these two diastereomers can be
derived under the assumption that a maximum 5% of one
remaining isomer can be detected by NMR spectroscopy. For
this lower limit an energy difference ΔG° = 0.98 kcal mol−1 is
obtained.
Fig. 3 Theoretically obtained ground state energy profile of HTI motor
1
(B3LYP/6-311G(d,p) level, black) and the experimentally obtained
When irradiating a solution of pure A-1 at −80 °C direct
conversion to C-1 was observed, which contradicts the earlier
established photoequilibrium between C-1 and D-1 and gives
indirect evidence for the presence of an underlying and
rapidly decaying fourth state – i.e. the B-1 diastereomer. As the
theoretical description predicts an energy barrier of 5.5
values (red). The energy profile is also compared to the experimental
values of the original HTI motor 9 (blue).6,8 Only the (R) configured
isomers are shown for clarity.
thorough theoretical assessment. Their structures are again kcal mol−1 for the thermal decay of B-1 to C-1 it is explainable
very similar to the original motor 9 showing strong helicities why the former state is not observable even at −80 °C. Taken
around the central photoisomerizable double bond and their together these results show that HTI motor 1 is completely
sense being dictated by the neighboring stable sulfoxide unidirectional in its visible light powered rotation and its
stereocenter. A third isomer D with the E-(S)-(M)/E-(R)-(P) con- motion follows the established mechanism for HTI motors.
figuration could directly be observed by low temperature 1H
When comparing the ground state energy profiles of HTI
NMR spectroscopy (see ESI Fig. 18 and 19†). Similar to the motor 1 with the original motor 9 the influence of feet-attach-
original motor 9 the fourth isomeric state B with the Z-(S)-(M)/ ment can be quantified directly (Fig. 3). For both motors the
Z-(R)-(P) configuration possesses very low thermal stability and order of diastereomer stabilities is very similar to that of the C
thus could not be observed directly; however, indirect evidence isomer as the thermodynamically most stable state followed by
is provided for its existence by the apparent contradiction of the A isomer, which appears slightly destabilized for motor 1.
the C isomer entering two different photoequilibria (one with The states
D-1 after irradiation of C-1 and one with A-1, which seems to (>3.0 kcal mol−1 with respect to C). For motor 1 the energies of
convert directly into C-1 after irradiation).
B and D are almost the same with a slightly more stable D
B and D appear significantly destabilized
After calculation of the ground state energy profile of 1 on isomer. For the original motor 1 the elusive B isomer is the
the B3LYP/6-311G(d,p) level of theory, experimental values or third stable state while the D isomer is energetically least
upper or lower limits for these values were obtained as stable. However, as these energies are not directly measurable
described in the following. Heating of the two most stable experimentally, the calculated values have to be taken with
isomers A-1 and C-1 to 100 °C in toluene-d8 led to a stable some caution especially as the theoretically predicted
isomer composition of A-1 : C-1 = 23 : 77 in equilibrium after minimum energy of the A isomer is only in general agreement
20 days of heating. From this equilibrium ratio and first order with the experimentally obtained value. When comparing
kinetic analysis of the thermal isomer interconversion the acti- transition state energies no significant change for the barrier
vation energy barriers for this process could be determined to governing B to C conversion is predicted for 1 as compared to
be 33.5 kcal mol−1 for the Z to E isomerization (C to A conver- motor 9. Comparing the measured transition state energies of
sion) and 32.6 kcal mol−1 for the E to Z isomerization (A to C the corresponding D to A helix inversion no noticeable influ-
conversion). The measured equilibrium constant at 100 °C was ence of the substitution is observed for this barrier, which is
converted into the free enthalpy difference according to the 13.2 kcal mol−1 for 1. Overall HTI motor 1 behaves very similar
Gibbs–Helmholtz equation giving ΔG° = 0.9 kcal mol−1, which to the original HTI motor 9 in its visible light powered
is in general agreement with the theoretical description unidirectional rotation. Therefore, introduction of bulky sub-
(0.2 kcal mol−1). Subsequently a solution of pure C-1 in CD2Cl2 stituents for metal surface attachment at the thioindigo-
was cooled to −80 °C, inserted into a NMR spectrometer and fragment does not impede motor function. Maximum attain-
irradiated with 450 nm within the instrument via a LED- able speeds, which are dictated by the highest kinetic barrier
coupled glass fiber. Upon irradiation, a new set of signals was (the thermal D to A helix inversion) are not altered by substi-
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tution, and the degree of unidirectionality, which is dictated
by the energy differences between D and A as well as between
B and C also seems not to be affected significantly in the
herein presented feet-bearing motor 1.
7 L. A. Huber, K. Hoffmann, S. Thumser, N. Böcher, P. Mayer
and H. Dube, Angew. Chem., Int. Ed., 2017, 56, 14536–
14539.
8 R. Wilcken, M. Schildhauer, F. Rott, L. A. Huber,
M. Guentner, S. Thumser, K. Hoffmann, S. Oesterling,
R. de Vivie-Riedle, E. Riedle and H. Dube, J. Am. Chem.
Soc., 2018, 140, 5311–5318.
Conclusions
9 E. Uhl, S. Thumser, P. Mayer and H. Dube, Angew. Chem.,
Int. Ed., 2018, 57, 11064–11068.
In summary we present the synthesis, theoretical evaluation,
and experimentally assessed light powered unidirectional
motion of a novel HTI motor 1 endowed with sulfur-based feet
for surface attachment. A quantitative comparison of its solu-
tion properties with the original and closely related HTI motor
9 reveals no detrimental influence of the feet-attachment in
terms of maximum attainable speed or directionality. With
this new molecular motor visible light powered unidirectional
rotations can be brought to the realm of surface chemistry and
will thus be of great value for the conscious construction of
smart and responsive materials as well as tailoring of inte-
grated molecular and supramolecular properties with spatio-
temporal resolution. Our current efforts are inter alia headed
in this direction.
10 S. Kassem, T. van Leeuwen, A. S. Lubbe, M. R. Wilson,
B. L. Feringa and D. A. Leigh, Chem. Soc. Rev., 2017, 46,
2592–2621.
11 J. D. Harris, M. J. Moran and I. Aprahamian, Proc. Natl.
Acad. Sci. U. S. A., 2018, 115, 9414–9422.
12 E. R. Kay, D. A. Leigh and F. Zerbetto, Angew. Chem., Int.
Ed., 2007, 46, 72–191.
13 E. R. Kay and D. A. Leigh, Angew. Chem., Int. Ed., 2015, 54,
10080–10088.
14 D. A. Leigh, Angew. Chem., Int. Ed., 2016, 55, 14506–14508.
15 S. Erbas-Cakmak, D. A. Leigh, C. T. McTernan and
A. L. Nussbaumer, Chem. Rev., 2015, 115, 10081–10206.
16 V. Balzani, A. Credi, M. Venturi and A. Di Fabio, NATO Sci.
Ser., II, 2003, 96, 29–41.
17 J. Wang and B. L. Feringa, Science, 2011, 331, 1429–1432.
18 D. Zhao, T. M. Neubauer and B. L. Feringa, Nat. Commun.,
2015, 6, 6652.
Conflicts of interest
19 A. S. Lubbe, C. Böhmer, F. Tosi, W. Szymanski and
B. L. Feringa, J. Org. Chem., 2018, 83, 11008–11018.
20 A. S. Lubbe, Q. Liu, S. J. Smith, J. W. de Vries,
J. C. M. Kistemaker, A. H. de Vries, I. Faustino, Z. Meng,
W. Szymanski, A. Herrmann and B. L. Feringa, J. Am. Chem.
Soc., 2018, 140, 5069–5076.
21 V. Garcia-Lopez, F. Chen, L. G. Nilewski, G. Duret,
A. Aliyan, A. B. Kolomeisky, J. T. Robinson, G. Wang, R. Pal
and J. M. Tour, Nature, 2017, 548, 567–572.
22 Q. Li, G. Fuks, E. Moulin, M. Maaloum, M. Rawiso, I. Kulic,
J. T. Foy and N. Giuseppone, Nat. Nanotechnol., 2015, 10,
161–165.
23 J. T. Foy, Q. Li, A. Goujon, J.-R. Colard-Itte, G. Fuks,
E. Moulin, O. Schiffmann, D. Dattler, D. P. Funeriu and
N. Giuseppone, Nat. Nanotechnol., 2017, 12, 540–545.
24 R. Eelkema, M. M. Pollard, J. Vicario, N. Katsonis,
B. S. Ramon, C. W. Bastiaansen, D. J. Broer and
B. L. Feringa, Nature, 2006, 440, 163.
The authors declare no conflicts of interest.
Acknowledgements
We thank the “Fonds der Chemischen Industrie” for a
Chemiefonds stipend (Do 199/53) and the Deutsche
Forschungsgemeinschaft (DFG) for an Emmy Noether fellow-
ship (DU 1414/1-1). We further thank the collaborative
research center (SFB 749/3, A12) and the Cluster of Excellence
“Center for Integrated Protein Science Munich” (CIPSM) for
financial support.
Notes and references
1 N. Koumura, R. W. J. Zijlstra, R. A. van Delden and
B. L. Feringa, Nature, 1999, 401, 152–155.
2 R. A. van Delden, N. Koumura, A. Schoevaars, A. Meetsma
and B. L. Feringa, Org. Biomol. Chem., 2003, 1, 33–35.
25 J. Chen, F. K. Leung, M. C. A. Stuart, T. Kajitani,
T. Fukushima, E. van der Giessen and B. L. Feringa, Nat.
Chem., 2018, 10, 132–138.
3 H. A. Kistemaker, P. Stacko, J. Visser and B. L. Feringa, Nat. 26 M. Vlatkovic, B. L. Feringa and S. J. Wezenberg, Angew.
Chem., 2015, 7, 890–896. Chem., Int. Ed., 2016, 55, 1001–1004.
4 L. Greb and J. M. Lehn, J. Am. Chem. Soc., 2014, 136, 27 S. J. Wezenberg and B. L. Feringa, Org. Lett., 2017, 19, 324–
13114–13117. 327.
5 L. Greb, A. Eichhofer and J. M. Lehn, Angew. Chem., Int. 28 D. Zhao, T. van Leeuwen, J. Cheng and B. L. Feringa, Nat.
Ed., 2015, 54, 14345–14348. Chem., 2017, 9, 250–256.
6 M. Guentner, M. Schildhauer, S. Thumser, P. Mayer, 29 G. London, G. T. Carroll, T. Fernández Landaluce,
D. Stephenson, P. J. Mayer and H. Dube, Nat. Commun.,
2015, 6, 8406.
M. M. Pollard, P. Rudolf and B. L. Feringa, Chem.
Commun., 2009, 1712.
Org. Biomol. Chem.
This journal is © The Royal Society of Chemistry 2018

View Article Online
Organic & Biomolecular Chemistry
Paper
30 J. Vachon, G. T. Carroll, M. M. Pollard, E. M. Mes, 33 K. Y. Chen, O. Ivashenko, G. T. Carroll, J. Robertus,
A. M. Brouwer and B. L. Feringa, Photochem. Photobiol. Sci.,
2014, 13, 241–246.
31 B. Krajnik, J. Chen, M. A. Watson, S. L. Cockroft,
J. C. Kistemaker, G. London, W. R. Browne, P. Rudolf and
B. L. Feringa, J. Am. Chem. Soc., 2014, 136, 3219–
3224.
B. L. Feringa and J. Hofkens, J. Am. Chem. Soc., 2017, 139, 34 N. Etomi, T. Kumamoto, W. Nakanishi and T. Ishikawa,
7156–7159. Beilstein J. Org. Chem., 2008, 4, 15.
32 J. Kaleta, J. Chen, G. Bastien, M. Dracinsky, M. Masat, 35 P. B. Dzhevakov, M. A. Topchiy, D. A. Zharkova,
C. T. Rogers, B. L. Feringa and J. Michl, J. Am. Chem. Soc.,
2017, 139, 10486–10498.
O. S. Morozov, A. F. Asachenko and M. S. Nechaev, Adv.
Synth. Catal., 2016, 358, 977–983.
This journal is © The Royal Society of Chemistry 2018
Org. Biomol. Chem.