Third-Generation Light-Driven Symmetric Molecular Motors

Article abstract of DOI:10.1021/jacs.7b04412

Symmetric molecular motors based on two overcrowded alkenes with a notable absence of a stereogenic center show potential to function as novel mechanical systems in the development of more advanced nanomachines offering controlled motion over surfaces. Elucidation of the key parameters and limitations of these third-generation motors is essential for the design of optimized molecular machines based on light-driven rotary motion. Herein we demonstrate the thermal and photochemical rotational behavior of a series of third-generation light-driven molecular motors. The steric hindrance of the core unit exerted upon the rotors proved pivotal in controlling the speed of rotation, where a smaller size results in lower barriers. The presence of a pseudo-asymmetric carbon center provides the motor with unidirectionality. Tuning of the steric effects of the substituents at the bridgehead allows for the precise control of the direction of disrotary motion, illustrated by the design of two motors which show opposite rotation with respect to a methyl substituent. A third-generation molecular motor with the potential to be the fastest based on overcrowded alkenes to date was used to visualize the equal rate of rotation of both its rotor units. The autonomous rotational behavior perfectly followed the predicted model, setting the stage for more advanced motors for functional dynamic systems.

Full text of DOI:10.1021/jacs.7b04412

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Article
Third Generation Light-Driven Symmetric Molecular Motors
Jos C. M. Kistemaker, Peter Stacko, Diederik Roke, Alexander Thomas Wolters, G Henrieke
Heideman, Mu-Chieh Chang, Pieter van der Meulen, Johan Visser, Edwin Otten, and Ben L. Feringa
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 19 Jun 2017
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Third Generation Light-Driven Symmetric Molecular Motors
Jos C. M. Kistemaker, Peter Štacko, Diederik Roke, Alexander T. Wolters, G. Henrieke Heideman, Mu-Chieh Chang,
Pieter van der Meulen, Johan Visser, Edwin Otten, Ben L. Feringa*.
Centre for Systems Chemistry, Stratingh Institute for Chemistry and Zernike Institute for Advanced Materials,
Faculty of Mathematics and Natural Sciences, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The
Netherlands.
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KEYWORDS: Light-Driven – Symmetric – Achiral – Unidirectional – Rotary – Molecular – Motor
B.L.Feringa@rug.nl
ABSTRACT: Symmetric molecular motors based on two overcrowded alkenes with a notable absence of a stereogenic
center show potential to function as novel mechanical systems in the development of more advanced nanomachines and
controlled motion over surfaces. Elucidation of the key parameters and limitations of these third generation motors is
essential for the design of optimized molecular machines based on light-driven rotary motion. Herein we demonstrate the
thermal and photochemical rotational behavior of a series of third generation light-driven molecular motors. The steric
hindrance of the core unit exerted upon the rotors proved pivotal in controlling the speed of rotation, where a smaller
size results in lower barriers. The presence of a pseudo-asymmetric carbon center provides the motor with unidirectional-
ity. Tuning of the steric effects of the substituents at the bridgehead allows for the precise control of the direction of dis-
rotary motion, illustrated by the design of two motors which show opposite rotation with respect to a methyl substituent.
A third generation molecular motor with the potential to be the fastest based on overcrowded alkenes to date was used to
visualize the equal rate of rotation of both its rotor units. The autonomous rotational behavior perfectly followed the pre-
dicted model, setting the stage for more advanced motors for functional dynamic systems.
INTRODUCTION
Molecular motors and machines attract major attention
as the introduction of dynamic properties enables a wide
range of responsive functions and adaptive properties in
synthetic materials.1–6 Towards the design of dynamic
functional systems, the use of light as an external stimu-
lus offers particular advantages. Photochromic systems
arguably have the benefit of non-invasive triggering with
the potential of high spatial-temporal precision.7,8 Switch-
ing between two or more states upon irradiation at differ-
ent wavelengths (UV/vis) can be combined with other
Figure 1. (a) Stilbene cis–trans isomerization and degrada-
effectuators (temperature, pH, metal-ion binding, redox)
tion due to ring closing and oxidation. (b) From left to right:
to arrive at multiresponsive behavior.9–13 Prominent clas-
stable switch, 1st generation molecular motor, 2nd generation
ses of photochemical switches include dithienylethenes,14
molecular motor.
stilbenes,15,16 fulgides and fulgimides,17 spiropyran,18
An important synthetic adjustment of a stilbene-like
DASA,19 or azobenzenes20,21
. Stilbenes in particular,
system (Figure 1b), was achieved by Feringa and
Wijnberg, introducing steric overcrowding at the alkene
to form thermally stable chiral forms. This was accom-
plished through the presence of naphthalene moieties
and aliphatic rings at both sides of the central alkene to
prevent ring closing.23 The introduction of stereogenic
centers in these systems (Figure 1b) originally served the
purpose of proving the absolute stereochemistry of its
analogues.24 However, the molecules were found to have a
surprising new property: they are able to undergo a 360
degrees unidirectional rotation around the alkene bond.25
These systems, as a result of successive alterations, be-
though rather easy to prepare, suffer from the undesired
thermal cis-trans isomerizing and degradation due to ring
closing and oxidation towards phenanthrene (Figure
1a).15,16 One of the major interests in our group has been
the synthetic manipulation of stilbenes in order to
achieve stability, increase quantum yield, control over
irradiation wavelengths, directionality of motion upon
isomerization and furthermore structural modifications
to prevent decomposition.22
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came the basis of the first generation synthetic molecular
his right wheel turning anti-clockwise and his left wheel
turning clockwise.
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motors, characterized by their C2 symmetry and its prin-
cipal axis at the double bond connecting upper and lower
halves. Recently functional analogs of these first genera-
tion synthetic motors showed potential in asymmetric
catalysis,26 control of dynamic chirality,27 and as chiral
hosts.28
Here, we would like to report on our investigation and
characterization of the essential features of third genera-
tion molecular motors and the limits of their perfor-
mance, to finally come to demonstrate the unidirectional-
ity of the fastest third generation motor, and potentially
the fastest of all molecular rotary motors based on over-
crowded alkenes designed so far. We first identify the role
of the core’s size on its behavior by a computational study
followed by an experimental verification. Based on those
results, we study the effect of the size of the substituents
at the pseudo-asymmetric carbon atom (the indane
bridgehead C-2, Figure 2) on the behavior of the bis-
overcrowded alkenes using theoretical and experimental
approaches.34–38 After identifying the most desirable struc-
tural features, a suitable candidate was chosen as a model
compound for proving the persistence of unidirectionality
in ultrafast third generation molecular motors.
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RESULTS AND DISCUSSION
Figure 2. Schematic design of achiral motors; merging of
two enantiomers of motor 1 (opposite helicities (P,M) and
central chirality (R,S) indicated) gives rise to symmetric dou-
ble overcrowded alkene 2-4 (pseudo-asymmetric carbon at-
om C-2 indicated with 2)
Previously unidirectional rotation has been established
for motor 2 taking advantage of its desymmetrized ana-
logue 3.33 For purposes of developing more advanced na-
nomachines and controlled motion along surfaces, the
ability to tune the rotary speed is considered highly bene-
ficial.32,39 We therefore instigated a theoretical study on
double overcrowded alkenes with a substitution pattern
of two methyl groups on C-2 (R1 = CH3) such as 4 for max-
imum simplicity. Besides 4, four more structural units
were selected starting with a benzene instead of xylene
moiety in the core (5), a p-difluorobenzene (6), a p-
dimethoxybenzene (7) and one where the core xylene
moiety is replaced with a phenanthrene moiety (8) (Chart
1).
In subsequent studies one half of these new dynamic
molecules was symmetrized in order to increase their
speed and quantum yield as well as allowing surface as-
sembly.29–31 Synthetic modifications were introduced to
illustrate that these motors can perform work.32 The de-
symmetrized synthetic unidirectional motors with only
one stereogenic center in the upper half and a symmetric
lower half were adopted as the second generation mo-
lecular motors, in which chirality was shown essential to
ensure unidirectionality (the initial ‘stilbene motive’ is
continually shown in orange in all four structures in order
to illustrate the predominant concept of the isomerizing
alkene connecting two aromatic groups, Figure 1b). Not
surprisingly the question regarding the necessity of a ste-
reogenic center for unidirectionality in rotary motion
emerged. Recently, we reported a novel synthetic meso
motor bearing two overcrowded alkenes and the notable
absence of a stereogenic center, although a pseudo-
asymmetric center is present.33 In fact each individual
alkene still has to experience chirality in order to perform
a unidirectional rotation. This so-called third generation
molecular motor (Figure 2) has two of such alkene moie-
ties with identical groups that can be considered mirror
images of two separate second generation motors. This
third generation motor is especially designed to maintain
unidirectionality of two parallel rotors while avoiding the
stereogenic element (asymmetric carbon center) known
from earlier generations of motors. Both individual al-
kenes experience the pseudo-asymmetry of the bridge
unit (e.g. CFCH3 in 2) and due to the opposite helicity of
these alkenes with respect to the bridge unit both fluo-
rene moieties are rotating in the same direction with re-
spect to the core aromatic group. This symmetry property
relates to a car driver moving forward on a road observing
F
F
O
O
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2
2
2
5
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8
Chart 1. Double overcrowded alkenes with modi-
fied core moieties featuring; benzene (5), p-
difluorobenzene (6), p-dimethoxybenzene (7) and
phenanthrene (8).
Theoretical study of the core-size effect
The theoretical investigation was performed using the
semi-empirical PM6 model to construct a potential ener-
gy surface (PES) from two dihedrals governing the aro-
matic planes for compounds 4–8 (4 as example; Figure
3a). The resulting PES shows a two-fold symmetry with
mirror planes running diagonally through the minima.
The geometries of the minima and transition states were
optimized using DFT B3LYP/6-31G(d,p)40,41 and intrinsic
reaction coordinates (IRC, 4 as example; Figure 3b) were
calculated to ensure the transition states connected the
identified minima. Subsequently the geometries of the
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Figure 3. (a) PES of 4 (PM6, colored from 0 kJ·mol−1 (red) to 150 kJ·mol−1 (violet), x-axis: 1-2-3-4 dihedral (in °); y-axis: 5-6-7-8
dihedral (in °)), (b) IRC’s of TS-4.
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Table 1. Optimized geometries of minima and transition states and their corresponding Gibbs free energies of
4-8 in kJ·mol−1 (DFT ωB97X-D/6-31+G(d,p) in DCM).a
5
6
5
7
4
8
6
7
4
8
Global minimum (Cs)b
Helical minimum P/M (C2)b
Transition State
0.0 (0.4)
41.3 (43.9)
66.9
0.0 (0.0)
45.4 (50.5)
96.0
0.0 (0.7)
46.1 (52.2)
107
0.0 (1.6)
49.4 (56.3)
123
0.0 (0.0)
29.5 (29.5)
132
THI C2ꢀCs T at t = 1 h (°C)
−216
−121
−82.8
−46.6
45.5
½
2xTHI CsꢀCs Tcoalescence (10 Hz) (°C)c
44.0
182
234
310
353
a) Geometries shown with methyl groups facing the reader, the H3C–C–CH3 bonds in the y-z plane and the five-membered ring
core in the x-z plane; . b) energies in kJ·mol−1; eEnergies in brackets for the symmetrical geometries; temperatures in °C. c) Using
k=π·Δv0·2-0.5 to provide the rate at Tcoalescence, k can be used in combination with the calculated barriers to solve the Eyring equa-
tion for T.
minima and transition states were optimized using DFT
ωB97X-D/6-31+G(d,p)42 in dichloromethane (IEFPCM)43,44
which revealed for each compound two global minima
and two metastable local minima (minima and transition
states afforded zero or one imaginary frequency, respec-
tively, and their geometries, energies and calculated bar-
riers are shown in Table 1). The two redundant global
minima have the desired meso geometries and are close
to or have Cs symmetry. The two metastable local minima
were enantiomeric helical configurations and are close to
or have C2 symmetry and connected to the global minima
by the calculated transition states (TS) which constitute
the thermal helix inversions (THI) known for overcrowd-
ed alkenes.
The redundant global minima possess Cs symmetry for
6 and 8 or deviate marginally from it by twisting the ro-
tors in 4, 5 and 7, although not detectible by NMR due to
the minute barrier of isomerization (Cs symmetric geome-
tries are 0–1.6 kJ·mol−1 higher in energy, Table 1). A similar
phenomenon is observed for the two metastable local
minima in 4–7 which deviate slightly from C2 symmetry
by twisting one of the methyl groups on C-2 lowering the
energy by 3–7 kJ·mol−1. Again, this deviation from sym-
metry would not be observed by NMR since at room tem-
perature the isomerization is very fast in which the aver-
aged geometry is a C2 symmetrical conformation. The
isomerization pathway between the helical minimum and
the global minimum (from now on referred to as C2-x and
Cs-x, respectively) showed increasing thermal barriers for
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helix inversion going from 5 < 6 < 7 < 4 < 8 which corre- lowed where phosphorous pentasulfide was used to afford
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sponds fully with the increase in size of the aromatic core
moiety (Table 1). The temperature at which the half-life is
the bis-thioketone. This indanedithione underwent a Bar-
ton-Kellogg coupling with diazofluorene to give the de-
sired product Cs-5 in good overall yield (50%). Double
overcrowded alkene 9 caused problems in the first step,
producing significant amounts of O-alkylated side-
product which resulted in loss of product during purifica-
tion, providing the C-alkylated product in 9% yield. The
next two steps proceeded in an analogous fashion to the
synthesis of 5 affording the desired Cs-9.
one hour (T at t = 1 h for THI C2ꢀCs) is a good indication
½
of which compound would be most suitable for an NMR
study. This suggests that 5–7 require very low tempera-
tures for NMR measurements that are too low to reach in
an NMR spectrometer, whereas both 8 and 4 are in a
temperature region where measurements can be readily
performed. The two redundant meso configurations (Cs-x
and Cs-x’) can interconvert through C2-x by two helix in-
versions (2xTHI, shown for 4 in Figure 3a). The barrier for
this isomerization can be quantified from the approxi-
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The study of the photochemical and thermal isomeriza-
tions started with compound 4, which was irradiated with
UV-light (365 nm in CH2Cl2, Figure 4a) and at room tem-
perature no change was observed in the UV-vis absorp-
tion spectrum. Irradiation at −65 °C was accompanied by
a bathochromic shift in the absorption-spectrum indica-
tive of an increase in strain over the alkenes pointing to
the formation of a metastable intermediate. After irradia-
tion to the photo-stationary state (PSS), the sample was
allowed to warm up to rt and full reversal to the original
spectra was observed. No signs of fatigue were seen over
tThree cycles of irradiation at low temperature and rever-
sal heating at ambient temperatures did not reveal any
signs of fatigue. During both of these processes an isos-
bestic point was observed at the same wavelength
(459 nm), indicating the absence of side reactions during
these first order reactions. 1H NMR confirmed the identity
of the stable global minimum as Cs-4 by the presence of
three distinct methyl resonances, which is expected of a
Cs symmetrical configuration of 4 but not of C2 (Figure
4b, H9,H10,H11; assignments in Scheme 1). Irradiation to
PSS at low temperatures revealed the metastable state
possessing a C2 symmetrical configuration, corresponding
to C2-4. Following the integrals of the NMR-resonances of
H1 over time at different temperatures enabled the con-
struction of an Eyring plot (Figure 4c) which provided the
energies of activation (ꢀ‡H° 63.2±1.6 kJ·mol−1, ꢀ‡S°
−17.3±7.0 J·K−1·mol−1, ꢀ‡G° 68.3±0.5 kJ·mol−1, t½ = 1 h at T =
−59.4±0.3 °C) in reasonable agreement with the calculated
barrier (ꢀ‡H°calc. 70.3 kJ·mol−1, ꢀ‡S°calc −10.6 J·K−1·mol−1,
ꢀ‡G°calc. 73.4 kJ·mol−1).
1
mate theoretical coalescence temperature of H NMR res-
onances (CH3 group resonances are calculated to be sepa-
rated by ~10 Hz, vide infra). From the calculated coales-
cence temperatures (Table 1), compound 5 appears to be
the only suitable candidate for NMR investigation. To
investigate the THI and 2xTHI processes, compounds 4
and 5 as well as 9 were synthesized, as well as 9 (Scheme
1), ). which dDerivative 9 was expected to have increased
solubility compared with 5 and might provide insight into
substituent effects for future functionalization.
Scheme 1. Synthesis of compounds 4, 5 and 9.
Irradiation of double alkene Cs-5 in n-pentane at −60 °C
did not show any shift in the UV-vis absorption spectrum
(see supporting information for the UV-vis spectrum)
which indicates that either Cs-5 does not undergo a dou-
ble bond isomerization or more likely the thermal barrier
for reversion of C2-5 to Cs-5 is too low to observe the met-
astable species at that temperature. The barrier for ther-
mal helix inversion at room temperature was calculated to
be 25.6 kJ·mol−1 (vide supra) which would allow for a life-
time of 2 ns at −60 °C and a temperature of −215 °C would
be required to allow for a lifetime of 1h. Due to the low
barrier for THI, C2-5 is not expected to be observed over
the experimental temperature range. Photocyclization has
been a problem for an overcrowded alkene without func-
tional groups in the fjord-region,45 however, no photocy-
clization was observed in the case of compound 5 proba-
bly due to insufficient π-orbital overlap. Moreover, no
other photochemistry was observed, such as described for
1,2-distyrylbenzene derivatives,46 likely due to the rigid
cyclopentane. An NMR study confirms the identity of the
Experimental study of core-size
The synthesis of the core structure of overcrowded al-
kenes 4, 5, and 9 started with a double Friedel-Crafts ac-
ylation of dimethyl malonyl chloride on p-xylene afforded
the bis-ketone in high yield (82%). This was transformed
into the bis-thioketone by the use of phosphorous pen-
tasulfide (97%). A Barton-Kellogg coupling of the bis-
thioketone and diazofluorene followed by a desulfuriza-
tion by the use of hexamethylphosphanetriamine (HMPT)
yielded the desired double overcrowded alkene Cs-4
(17%). For compound 5, after double alkylation of indane-
dione with methyl-iodide, an analogous pathway was fol-
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Figure 4. Thermal behavior of 4. a) UV-vis absorption spectrum of Cs-4 in CH2Cl2 at rt, irradiation (365 nm, 30 min) to
PSS at −65 °C and warming to rt (insert: isosbestic point at 459 nm with absorptions during both processes added). b) i: 1H
NMR spectrum of Cs-4 (CD2Cl2, 500 MHz, rt), assignment in Scheme 1. ii: Transferred to a Shigemi tube and irradiated in
NMR to PSS (CD2Cl2, 365 nm, 12 min, 600 MHz, −58 °C). iii: t = 30 min (CD2Cl2, 600 MHz, −58 °C). iv: t = 8 h (CD2Cl2,
600 MHz, −58 °C, x = impurity, presumably acetonitrile). c) Exponential decay curves of the normalized integrals of H1C2-4
over time (left and top axis) and Eyring plot with error bars of 3σ (right and bottom axis).
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stable global minimum Cs-5 by the presence of two dis-
tinct methyl resonances, which is expected of a Cs sym-
metrical conformation of 5 but not of C2. This is corrobo-
rated by the calculated H NMR spectrum of Cs-5 (DFT
giao mPW1PW91/6-311+G(2d,p) in CHCl3) which strongly
agrees with the experimental spectrum (Figure 5).
To investigate these processes in greater detail com-
pound 9 (Scheme 1) has been synthesized which is ex-
pected to show behavior similar to 5 but with a signifi-
cantly increased solubility. Low temperature UV-vis and
NMR displayed a similar absence of change under irradia-
tion and, similar to Cs-5, presence of Cs symmetry for
compound 9 was shown by NMR (Figure 5, see support-
ing information for UV-vis and 13C NMR spectra). An in-
1
Upon an increase in temperature, coalescence of the
methyl resonances is observed, indicative of the two-step
process in which the Meeq (H11) and Meax (H12) exchange
environment through a double helix inversion. The barri-
er determined by NMR (ꢀ‡G 62.5±1.0 kJ·mol−1) is found to
be lower than the computed barrier (ꢀ‡G°calc 66.9 kJ·mol−1,
vide supra), probably due to a deviation in the calculated
entropy term as was observed for 4. However, it still sug-
gests that at these temperatures the redundant isomers
Cs-5 and Cs-5’ exchange through thermal processes as
shown for 4 in Figure 3a.
1
teresting pattern was observed for the H NMR resonanc-
es of the alkyl chains of Cs-9. The first methylene on each
alkyl displayed a similar significant downfield shift like
the methyl groups of Cs-5, but here the strongest shift was
observed for the pseudo-axial methylene group (H11) in-
stead of the pseudo-equatorial methyl in Cs-5 (H11). Due to
their distinct chemical environments, the two different
alkyl chains follow a peculiar pattern with methylene
groups of the equatorial alkyl chain exhibiting large up-
field shifts. A theoretical study of several rotamers of the
1
alkyl chains of Cs-9 and calculation of their average H
NMR spectrum provided a strong agreement with the
experimental spectrum (R2=0.999, Figure 5, see support-
ing information for details). Increasing the temperature
caused coalescence of the alkyl groups most apparent for
the resonances of H11–H12 at ~2.7 ppm. This allowed for
the determination of the barrier for thermal isomerization
(ꢀ‡G 59.4±1.0 kJ·mol−1) which again is lower than the
computed barrier (ꢀ‡G°calc 65.7 kJ·mol−1, ꢀ‡H°calc
51.7 kJ·mol−1).
Figure 5. Temperature dependent experimental and calcu-
lated 1H NMR spectra of Cs-5 and Cs-9.
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tion. For C2-(M)-9 the C2 axis is indicated by the red dashed
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line and red dot on the calculated geometry on which the red
arrows indicate the movement of the rotors for the two re-
dundant thermal helix inversions.
4
5
Conclusions on the influence of core-size
Molecular motors based on double overcrowded al-
kenes with a benzene moiety in the core show the poten-
tial to be significantly faster than those with a substituted
benzene group. However, compounds 4–9 with Cs sym-
metrical stable meso states do not possess a preference
for either of the two redundant geometries and therefore
no preference for which of the two states undergoes a
photochemical E–Z isomerization (PEZ). The metastable
helical states possess C2 symmetry and therefore both
rotors show an equal probability for undergoing a thermal
helix inversion. Due to the redundancy of the stable states
and the C2 symmetry of the metastable state these rotors
do not prefer a specific direction and are therefore not
unidirectional. On account of the symmetry of the stable
state it is expected that a photochemical E–Z isomeriza-
tion of Cs-9 will produce a photo-stationary state (PSS)
between Cs-9 and racemic C2-9 (Figure 7). This isomeriza-
tion yields a rotation of one of the rotors on Cs-9 and a
rotation of one of the rotors on Cs-9’, in opposite direc-
tion with respect to Cs-9. The metastable C2-9 undergoes
a thermal helix inversion of either of the rotors without
preference because its C2 symmetry as indicated in Figure
7, producing equal amounts of Cs-9 and Cs-9’. Over two
rotational steps (PEZ–THI) the rotations sum up to a net
rotation of zero due to the lack of unidirectionality. This
behavior is expected for all compounds with equally sized
substituents at the bridgehead position such as 4 and 5.
To achieve unidirectional rotation, a form of asymmetry
has to be reintroduced like in 2 and 3, which is achieved
by substituting two differently sized moieties at the in-
dane bridgehead (carbon 2, Chart 1) making it a pseudo-
asymmetric carbon atom.34–38
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 6. Molecular structure of Cs-9 by crystallography
(only one of the two independent molecules is shown)
Conclusive information on the configuration of 9 came
from X-ray crystallography. Crystals suitable for X-ray
diffraction studies were grown by layered diffusion of a
concentrated solution of 9 in dichloromethane on top of
which volumes of, successively, pentane, heptane, and
methanol were layered. The structure determination
shows that there are two independent molecules in the
unit cell (Figure 6, see supporting information for com-
plete unit cell), which have similar metrical parameters.
Both have approximate Cs symmetry (meso configuration)
around the core of the bis-overcrowded alkene 9. The
alkyl group in the equatorial position is in both cases ro-
tated such that the last three C-atoms of the hexyl chain
are located directly above the plane of the fluorene ring,
with Chexyl–fluorene distances of 3.577–4.073 Å. This con-
formation of the equatorial alkyl group agrees with its
1
anomalous upfield shift observed in the H NMR spec-
trum. It is unclear, however, whether this folding in the
solid state is due to packing effects or represents a genu-
ine attractive interaction (see supporting information for
a computational conformational study).
Theoretical study of the substituent effect
Several substitution patterns on the indane bridgehead
were considered and investigated computationally. Cer-
tain sterically interesting substituents such as tert-butyl
(large) and hydrogen and methoxy (smaller than methyl)
were disregarded on account of their synthetic demand
and the expected chemically unstable nature of the result-
ing double overcrowded alkene. Note that for instance
compound 2 (R1=H, Figure 2), featuring a hydrogen in a
double allylic position can readily undergo 1,3-H-shift
removing the pseudo-asymmetric center. After initial cal-
culations on multiple double overcrowded alkenes (DFT
B3LYP/6-31G(d,p),) five were selected (18–22) and studied
in depth (DFT ωB97X-D/6-31+G(d,p) in DCM, Table 2).
For an additional side view perspective of the meso ge-
ometries of 18–22 as well as the calculated enthalpies: see
the supporting information.
The three possible combinations of a methyl, an alkyl
and a phenyl group (compounds 18–20) were selected
because of their interesting potential balance in steric
effects. Both the phenyl as well as the alkyl moiety have
been reported to be slightly or significantly larger than
the methyl group,35,47,48 though there are instances in
Figure 7. Rotational behavior of 9 shown (4 and 5 behave
in the same way). Cs-9 = Cs-9’, produces a racemic mixture of
C2-(M)-9 and C2-(P)-9 upon photochemical E–Z isomeriza-
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Journal of the American Chemical Society
that, similar to 4–7 (vide supra, Table 1), the calculated
which the methyl group has been reported to exhibit a
similar or larger steric effect.49–52 The sterically demand-
ing isopropyl group (compound 21) and small fluorine
atom (compound 22) were selected to realize the largest
difference in steric effect with respect to a methyl group.
For each compound four minima were calculated, similar
to 4–8 (vide supra), of which two were the enantiomeric
helical metastable forms and two were found to represent
the stable meso isomers with either an r or s configura-
tion at the pseudo-asymmetric carbon atom.34–38,53 Note
minima geometries for r-18–22 and s-18–22 deviate slight-
ly from true Cs symmetry by small twists of substituents
or rotors, as can be clearly observed for s-18 and r-21. As
before, this is not expected to be detectible by NMR due
to the low barrier of isomerization which goes through
the true Cs symmetrical geometry (energies shown in
brackets in Table 2).
1
2
3
4
5
6
7
8
For motors 2 and 3 it was shown that the larger substit-
uent prefers a pseudo-axial orientation,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Structures and optimized geometries of minima and transition states and their corresponding Gibbs
free energies of 18-22 (DFT ωB97X-D/6-31+G(d,p) in DCM).a
18
0.0 (10.6)
11.6 (19.1)
48.3
19
0.0 (0.0)
9.0 (9.1)
42.0
20
12.5 (12.5)
0.0 (15.5)
39.0
21
6.8 (55.2)
0.0 (0.4)
28.6
22
0.0 (0.1)
16.2 (17.5)
37.4
r (Cs)
s (Cs)
Helical minima P/M (C1)
TSr P/Mꢀr
67.4
63.5
66.7
78.9
54.2
TSs P/Mꢀs
74.5
75.6
71.6
78.8
67.4
a) Structures shown in experimentally determined most stable isomer with numbers indicating 1H NMR assignments; ge-
ometries shown with substituents facing the reader, the R–C–R bond in the y-z plane and the five-membered ring core in the
x-z plane; alkyl chains of the geometries of 18 and 20 cropped to 3 carbons for clarity; energies in kJ·mol−1; energies in brack-
ets for the Cs geometries.
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Journal of the American Chemical Society
Page 8 of 14
1
2
3
4
5
6
7
8
with the rotor moieties pinching the substituent in the
The double overcrowded alkenes 18–22 were all pre-
pseudo-equatorial orientation.33 The change from a xylene
core as in 4 to a benzene core in 5 increases the pinching
effect of the rotors (Table 1), and the preference for the
larger substituent to adopt the pseudo-axial orientation is
therefore expected to remain present. To exemplify, in r-
18, r-19, r-21 and r-22 the pseudo-axial orientation is oc-
cupied by the methyl group. The larger substituents in 21
and 22 are the isopropyl group and the methyl group,
respectively, and calculations show a preference for these
groups to adopt the pseudo-axial orientation with s-21
and r-22 being lower in energy than their corresponding
diastereomer (Table 2). The calculations presented in
Table 2 also show a preference for r-18, r-19 and s-20 over
their corresponding diastereomer, which suggest the fol-
lowing order for steric effects in these molecules:
Me>Ph>Alkyl.
pared following a similar route (Scheme 2). In the first
step a double condensation of dimethyl phthalate and
symmetric ketones with the aid of sodium hydride affords
the mono-substituted indandiones 10–12 in accordance
with the reported literature procedures.54–56 The second
alkylation using alkylhalides on the indandiones gave rise
to significant amounts of O-alkylated side products. This
was suppressed by the use of phase transfer reagents,
such as Aliquat 336, as well as the addition of potassium
fluoride immobilized on Celite to the reaction mixture.
The combination of both reagents afforded the highest
yield and the best C:O-alkylated product ratio of 13–16,
which was finally further improved on using cesium car-
bonate instead of potassium carbonate. The fluorinated
indandione 17 was obtained from methyl-indandione us-
ing Selectfluor. Bis functionalized indandiones 13–17 were
transformed to the corresponding indandithiones using
phosphorous pentasulfide (or a combination with Lawes-
son’s reagent, see experimental section for details) of
which most products appeared to be rather stable, proba-
bly due to a lack of hydrogens at alpha carbons. Nonethe-
less, the indandithiones were directly submitted to dou-
ble Barton-Kellogg couplings with diazofluorene to afford
the desired double overcrowded alkenes 18–22 (Scheme
2).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The barriers for THI of metastable P/M-18–22 are calcu-
lated to be very low (19.1, 27.7, 21.6, 50.2, and 16.7 kJ·mol−1,
respectively), which makes a PEZ–THI sequence difficult
to detect by conventional UV-vis or NMR techniques. The
barrier for THI for 21 might be the highest for these over-
crowded alkenes, although it would still require a tem-
perature of −113 °C to obtain a half-life of one hour. The
calculated barrier of metastable P/M-22 to r-22 predicts it
to be the fastest molecular motor to date with an ex-
pected half-life of only 109 picoseconds at room tempera-
ture. The barriers for the double inversion of s-18–22 to r-
18–22 or vice versa are calculated to be measurable by
coalescence in 1H NMR (62.9, 66.6, 66.7, 72.1, and
51.2 kJ·mol−1) on the condition that both diastereomers are
observed. The NMR spectra of r-18–22 and s-18–22 were
calculated (DFT giao mPW1PW91/6-311+G(2d,p) in CHCl3,
Figure 8, for enlarged spectra see the supporting infor-
mation) in order to be able to assign the stereoisomer of
the double overcrowded alkenes which were obtained
synthetically.
Scheme 2. Synthesis of third generation molecular
motors 18–22.
Experimental study of the substituent effect
Figure 8. 1H NMR spectra of 18–22. Top: calculated spectrum of the r-isomer; middle: calculated spectrum of the s-isomer; bot-
tom: experimental spectrum (CDCl3) with numbering (see Table 2 for the assignments). Bottom right: correlation of experi-
mental and calculated 1H NMR chemical shifts.
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Journal of the American Chemical Society
is in a pseudo-equatorial orientation, placing it in be-
1
2
3
4
5
6
7
8
9
i
ii
O
O
R2
R1
tween the fluorene moieties (see the geometries in Table
2 and the supporting information), whereas in s-19 it is
oriented pseudo-axially giving it much more spatial free-
dom. This suggests the assignment of the major isomer
being s-19 which corresponds fully with the calculated
NMR spectra in which this assignment shows a far
stronger correlation than the opposite combination does.
EXSY NMR was again employed to determine the activa-
tion parameters for the double THI exchange process be-
tween the s and r isomers using the same method as was
used for 18 (Table 3, see supporting information for
NOESY 1D spectra and traces), revealing a similar barrier
of 63.4 kJ·mol−1 for the isomerization of the major isomer
s-19 to the minor isomer r-19.
R1
O
R1
O
R1
: Me
O
O
iii
R1 R2
10
13
:
14:
Me Hex
Ph Me
Ph Dec
O
11:
Ph
12: iPr
15:
10
F
16: iPr Me
O
17
10
11
S
R2
R1
R2
R1
R2
R1
iv
v
13-17
r
s
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
S
18 19 20 21 22
R1
R2
:
Me
Ph
Me
Dec iPr Me
Ph Me F
Hex
:
10
11
12
Reagents and conditions: (i) NaH, toluene, 16 h, rt : 63%, : 31%, : 87%;
(ii) K2CO3, Aliquat 336, KF on Celite, acetonitrile, reflux, 16 h, : 36%,
83%, : 36%, : 84%; (iii) Selectfluor, 96%; (iv) P4S10, Lawesson's reagent,
toluene, 8-16 h; (v) 9-diazo-9H-fluorene, toluene, rt-reflux, 2-24 h, 18: 66%, 19:
23%, 20: 24%, 21: 3%, 22: 14% (over iv and v)
13 14
:
15
16
The 1H NMR spectra of 18–22 were compared to the calcu-
lated spectra and were found to be in close agreement
(Figure 8). It revealed 18–20 to be present in both isomer-
ic forms (r- and s-isomers)38 while 21 and 22 were only
found as a single isomer. At room temperature com-
pounds 18–20 displayed coalescence of several resonanc-
es, though at low temperature (−30 °C) the compounds
1
entered the slow exchange region and clearly resolved H
NMR spectra were obtained. Using several 2D NMR tech-
niques allowed for a complete proton and carbon assign-
ment of the major isomers (see supporting information
for all NMR spectra). The isomers of compound 18 were
found in a 3.0 : 1.0 ratio of which the minor isomer dis-
played a similar effect for the hexyl chain as was observed
for the pseudo-equatorially oriented hexyl chain in 9.53
This suggests the minor isomer to be r-18 and therefore s-
18 to be the major isomer, which was confirmed by the
Figure 9. EXSY NMR of 18. a) NOESY 1D 1H NMR spectrum
of 18 (600 MHz, CDCl3, −3.3 °C, 2 s mixing time). b) normal-
ized integral of r-18 at various mixing times and tempera-
tures.
Table 3. Gibbs free energies of 18–20 for r-s isomer-
ization by EXSY NMR.a
1
comparison of the calculated H NMR spectra to the ex-
perimental one. In this comparison, the s isomer strongly
correlates to the major isomer of 18 and the r isomer cor-
relates to the minor isomer. The presence of coalescence
was predicted by calculations, however, the asymmetry in
the isomer ratio makes the use of the coalescence tem-
perature as a tool to determine the barrier for isomeriza-
tion of double helix inversion slightly unreliable. There-
fore, we made use of temperature dependent 1D EXSY
NMR to determine the activation parameters for the ex-
change process (Figure 9, Table 3, and supporting infor-
mation for further details), which revealed a barrier of
62.0 kJ·mol−1 for the isomerization of the major isomer s-
18 to the minor isomer r-18. The isomers of compound 19
were found in a 2.0 : 1.0 ratio of which the minor isomer
appeared to show five distinct signals for the phenyl sub-
stituent while the major isomer showed three signals
(Figure 8). This suggests that the phenyl in the major
isomer is free to rotate making the hydrogens ortho and
meta to the indane bridgehead chemically identical, while
in the minor isomer the orientation of the phenyl is fixed
giving rise to five different resonances. In r-19 the phenyl
18
60.1±0.3
62.0±0.3
1.9±0.3
19
62.3±0.3
63.4±0.2
1.0±0.1
20
63.1±1.1
67.3±1.1
4.0±0.2
r ꢀ s Δ‡G° / kJ·mol−1
s ꢀ r Δ‡G° / kJ·mol−1
s – r ΔG° / kJ·mol−1
a) Standard state: atmospheric pressure and rt (20 °C)
The isomers of compound 20 were found in an 8.9 : 1.1
ratio and for its aromatic region a nearly identical pattern
is observed as was for 19, while for the aliphatic region a
similar effect is seen in the exchange of a methyl group to
an alkyl as was for 5 and 9 (Figure 8). In both 5 and 19 the
pseudo-axial methyl group is shifted upfield with respect
to the pseudo-equatorially oriented methyl group, while
in both 9 and 20 the first methylene on the pseudo-axial
alkyl group shows a downfield shift with respect to the
pseudo-equatorial position.53 With again a good correla-
tion of the calculated spectra to the experimental 1H NMR
spectrum, the major isomer is assigned as s-20 and the
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Journal of the American Chemical Society
minor as r-20. EXSY NMR revealed barrier of
Page 10 of 14
a
67.3 kJ·mol−1 for the double THI exchange process going
from the major isomer s-20 to the minor isomer r-20
(Table 3, see supporting information for NOESY 1D spec-
tra and traces).
1
2
3
4
5
6
7
8
Considering the performance of overcrowded alkenes
18–20 as molecular motors, one should note that these
systems feature reduced unidirectionality due to the pres-
ence of both isomers. Nonetheless, they still maintain
preferential directionality of their rotary motion. For ex-
ample, in 20 89% rotates in one direction (counterclock-
wise when observed from the left in Table 2) while 11%
rotates in the opposite direction resulting in a reduced
unidirectional yield of 78% (determined from the r-20 : s-
20 ratio at rt, vide supra). This is not an issue in 21 and 22
since they were obtained as single isomers according to 1H
NMR (Figure 8, note that the two resonances in the ali-
phatic region of 22 constitute a doublet due to F-CH3
coupling, belonging to a single isomer). The size differ-
ence predicted s-21 and r-22 to be the most stable isomers
with the larger isopropyl in the pseudo-axial orientation
and the smaller fluorine in the equatorial orientation,
respectively. The calculated spectra were fitted to the ex-
perimental spectra which proved the expected isomers to
agree the best to the experimental spectra (Figure 8).57
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 11. Molecular structure of r-22 by crystallography.
Conclusions on the influence of substituent-size
The combined data shows the following order for steric
effects of the substituents at the indane bridgehead in 18–
22: i-Pr>Ph>Alkyl>Me>F. However, just based on the data
for 19 and 20 (Table 3) one might expect the methyl group
to be larger than the alkyl group (s–r ΔG° being smaller
for 19 than for 20) highlighting the very subtle interplay
of these steric moieties with the rest of the molecule. It is
also clear that this deviates from the calculated order,
which predicted the steric effect of the methyl group to
be larger than those of the phenyl and alkyl groups (vide
supra). The calculated barriers for the double THI ex-
change process of s-18–20 to r-18–20 agree well with the
experimental barriers (ΔΔ‡G° 0.9, 3.2, and 4.3 kJ·mol−1,
Table 2 and Table 3) while the agreement in the opposite
process of r-18–20 to s-18–20 is much weaker (ΔΔ‡G° 14.4,
13.3, and 4.0 kJ·mol−1, Table 2 and Table 3). To improve the
correspondence between theory and experiment it might
be necessary to employ different functionals, add diffuse
functions or increase the basis set. The combined experi-
mental data also confirms that in the third generation
molecular motors s-21 and r-22 opposite directions of ro-
tation take place while both possess a >95% unidirection-
al yield (since the opposite diastereomer is not observed
Figure 10. Molecular structures of s-19 and s-20 by crystal-
lography.
1
in H NMR). As expected, no changes are observed in the
To obtain additional information on the structure and
stereochemistry of the double overcrowded alkenes, crys-
tals suitable for X-ray diffraction analysis were grown by
layered diffusion of concentrated solutions of 19, 20, and
22 in dichloromethane on top of which volumes of, suc-
cessively, pentane, heptane, and methanol were layered
(from 18 and 21 no suitable crystals were obtained). The
structure determination confirmed the expected meso
configuration of the bis-overcrowded alkenes, moreover,
19 and 20 were both only found with an s configuration at
the pseudo-asymmetric carbon atom (Figure 10). While
this clearly shows a preference for both compounds to
crystallize in a single configuration, it should not be used
as independent proof for the assignment of the major
isomer in solution since either isomer could have pos-
sessed a stronger tendency towards crystallization. How-
ever, NMR indicates only a single isomer of 22 to be pre-
sent, and its X-ray analysis confirmed the computational
prediction and NMR assignment, by showing 22 to pos-
sess an r configuration on the pseudo-asymmetric carbon
atom (Figure 11).
NMR resonances at high or low temperature, or after ir-
radiation at room or low temperature. This is due to the
very low barrier for THI in combination with the sym-
metry of the rotors. In order to prove that these fast third
generation molecular motors are able to undergo rotation
of the fluorene units under photo-irradiation, asymmetry
has to be introduced in the rotor units.
Rotation of an ultrafast 3rd generation motor
To unequivocally demonstrate the unidirectional rotary
motion, methoxy substituents were introduced in the
rotor parts of the ultrafast motor with a benzene moiety
as its core. Using methoxy-diazofluorene and the indandi-
thione of 17 in a Barton-Kellogg coupling (as in Scheme 2)
afforded the desired desymmetrized double overcrowded
alkene 23 as a statistical mixture of the four isomers (iso-
mers shown in Scheme 3, for synthetic scheme see sup-
porting information). This mixture was subjected to su-
percritical fluid chromatography (SFC) (45% 2-propanol
in CO2, Chiralpak ID at 3.5 mL·min−1, 40 °C, 160 bar)
which allowed the isolation of each isomer (Figure 13,
isomers sequentially numbered and corresponding to the
configurations numbered in Scheme 3). The four isomers
are indistinguishable by UV-vis as can be seen from their
nearly identical UV-vis absorption spectra (Figure 13).
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Journal of the American Chemical Society
However, 19F and H NMR allowed for the assignment of
the individual isomers where the enantiomers of 23 (iso-
mers 1 and 3) displayed identical NMR spectra and were
assigned based on their retention time in analogy to 3.33
Irradiation of an isolated isomer of 23 is expected to allow
it to undergo a photochemical E–Z isomerization to be
directly followed by a thermal helix inversion. This pro-
duces the two connected isomers according to Scheme 3
in an approximate 50:50 ratio, which go on to produce
both the starting isomer as well as the final isomer con-
nected to those isomers again in a 50:50 ratio. Finally, this
last isomer is formed but at the same time undergoes
isomerization producing the two intermediate isomers
again. The rates presented in the kinetic scheme (Scheme
3) are formulated in rate equations which were solved
using matrix methods58 providing the following integrat-
ed rate laws (see supporting information for derivation
and expanded formulas):
lamp (365 nm) was positioned. A high concentration was
used to allow the sampling to be only 4 ꢁl, to keep the
change in total volume as small as possible, and simulta-
neously ensuring the process lasts long enough for the
collection of sufficient data. While the samples were be-
ing irradiated, aliquots for SFC analysis were taken at reg-
ular intervals and the chromatograms were integrated
and the normalized integrals plotted against time (Figure
12).
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢁ
ꢂ
ꢄ
ꢋꢌ
ꢋꢌ ꢋꢌ
ꢒ
-23ꢃꢆ ꢇ ꢈꢉꢊ ꢄ ꢇ ꢈꢎꢊꢋꢌ ꢄ ꢇ ꢈꢐꢊ
ꢂ
Z,E
(1)
(2)
(3)
(4)
ꢍ
ꢏ
ꢑ
ꢁ
ꢁ
ꢁ
ꢁ
ꢂ
ꢁ
ꢀ
ꢀ
ꢀ
ꢀ
R
,
Z
,
E
-23ꢃꢄ ꢅ ꢀ
R
,
ꢋꢌ
ꢄ
-23ꢃꢆ ꢇ ꢓꢉꢊ ꢄ ꢇ ꢓꢎꢊꢋꢌ
ꢍ
ꢏ
ꢂ
ꢁ
ꢂ
E
r
,
E
,
E
-23ꢃꢄ ꢅ ꢀ
r
,
E
,
ꢁ
ꢂ
ꢄ
ꢋꢌ
ꢋꢌ ꢋꢌ
-23ꢃꢆ ꢇ ꢔꢉꢊ ꢄ ꢇ ꢔꢎꢊꢋꢌ ꢄ ꢇ ꢔꢐꢊ
ꢍ
ꢏ
ꢑ
ꢒ
ꢂ
ꢁ
S,Z
ꢂ
E
S,
Z
,
E
-23ꢃꢄ ꢅ ꢀ
,
ꢋꢌ
ꢄ
ꢏ
-23ꢃꢆ ꢇ ꢕꢉꢊ ꢄ ꢇ ꢕꢎꢊꢋꢌ
ꢂ
Z,Z
ꢍ
ꢂ
ꢁ
r
,
Z
,
Z
-23ꢃꢄ ꢅ ꢀ
r
,
where [X]e describes the final concentration, kV and kW
Figure 12. SFC integrals normalized over time of the four
isolated isomers of 23 under 365 nm irradiation at rt.
are compiled rate factors including k1–k4, Ax–Dx are com-
piled pre-exponential factors (including [X]0 and k1–k4)
and t is time.
In Figure 12 the black curves are equations 1–4 fitted
against the experimental data points by least squares
analysis in a single fit providing a small residual error and
a high coefficient of determination (R2 = 0.997) (see sup-
porting information for details of fitting). The observed
behavior agrees with the proposed rate laws and proves
the hypothesized connectivity as displayed in the rota-
tional cycle in Scheme 3. Starting from any isomer of 23
there is an exponential decay of the initial isomer coupled
with exponential formation of the two isomers directly
connected to it, while the isomer across from the initial
isomer experiences a delayed formation resulting in S-
shaped curves (Figure 12).59 Starting from the meso iso-
mers of 23 (isomers 2 and 4) there is no preference for
either of the connected isomers, expressed in nearly iden-
tical formation curves of the two enantiomeric isomers of
23 (isomers 1 and 3), while starting from one of the enan-
tiomers, a small preference appears to exist for the for-
mation of isomer 2 over isomer 4. This is expressed in a
deviation of the final ratios from a simple statistical 1:1:1:1
ratio to a ratio of 0.99 : 1.11 : 0.99 : 0.90 (for isomer 1:2:3:4)
starting from any of the isomers. Isomers 1 and 3 of 23 are
expected to behave identically on account of their enanti-
omeric relationship and therefore result in identical final
ratios.
Scheme 3. Rotational cycle of 23.
O
O
k1
hν,ꢀ
F
F
hν,ꢀ
O
k3
O
23
23
2:(r,E,E)-
1:(R,Z,E)-
hν,ꢀ
k2
hν,ꢀ
k4
hν,ꢀ
hν,ꢀ
k3
k1
k4
hν,ꢀ
O
O
F
F
O
hν,ꢀ
k2
O
23
4:(r,Z,Z)-
23
3:(S,Z,E)-
Concentrated solutions in CH2Cl2 of the individual iso-
mers 1–4 of 23 purged with argon were placed in the au-
tosampler of the SFC machine, in front of which a UV-
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Figure 13. SFC chromatogram of 23 and the corresponding UV-vis spectra, 19F NMR and 1H NMR spectra of the individu-
al isomers 1–4 with the numbering corresponding to the isomers shown in Scheme 3 (UV-vis spectra are offset for clarity).
All experiments result in isomer 2 [(r,E,E)-23] as the
major isomer and isomer 4 [(r,Z,Z)-23] as the minor iso-
mer (this relationship is confirmed by an H NMR study,
control of rotary motion of third generation molecular
motors is essential for the design of more advanced mo-
lecular machines based on light-driven rotary motion.
1
see supporting information for details). The origin of this
behavior is twofold: (i) enantiomeric isomers 1 and 3 both
slightly favor rotation of one rotor over the other by 2%
(normalized rates k1=1.02 and k2=0.98), likely due to iso-
mers 1 and 3 being chiral and therefore possessing an
asymmetric potential energy surface in the excited state,
and (ii) the rate of rotation is 8% smaller for isomer 2
with respect to isomer 4 (normalized rates k3=0.91 and
k4=1.08) leading to an accumulation of isomer 2, which
could be caused by a higher quantum yield of isomer 4
with respect to isomer 2. Nonetheless, no matter what the
origin of this small deviation from statistical is, it would
not play a role in the third generation motors 21 and 22
with symmetric rotors. With the use of compound 23 it is
shown that, even though the thermal step is too fast to be
measured in a conventional way, these motors still un-
dergo light-driven rotation and studies using ultra-fast
spectroscopy to identify the metastable states and quanti-
fy the barriers involved are currently ongoing.
ASSOCIATED CONTENT
Supporting Information. Detailed synthetic and experi-
mental procedures and characterizations. Additional chro-
matographic and spectroscopic studies, derivation of inte-
grated rate laws, and computational details. Supporting data:
Figures S1-S7, Tables S1-S7 and Scheme S1-S9. This material is
available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* b.l.feringa@rug.nl.
Author Contributions
All authors have given approval to the final version of the
manuscript.
ACKNOWLEDGMENT
This work was supported financially by the Netherlands
Organization for Scientific Research (NWO-CW), The Royal
Netherlands Academy of Arts and Sciences (KNAW),
NanoNextNL of the Government of the Netherlands and 130
partners, the European Research Council (ERC; advanced
grant no. 694345 to B.L.F.) and the Ministry of Education,
Culture and Science (Gravitation program no. 024.001.035).
We thank Thom C Pijper for fruitful discussions on DFT cal-
culations.
CONCLUSIONS
We have demonstrated the thermal and photochemical
rotational behavior of a series of third generation light-
driven molecular motors. The steric hindrance around the
core proved to be decisive in the tuning of the potential
speed of double overcrowded alkenes. Computational
1
prediction of H NMR spectra was used to support the
assignment of experimental spectra as well as the relative
configurations. The presence of a pseudo-asymmetric
center has been shown to be essential to achieve unidirec-
tional rotation. Careful modification of the steric bulk of
the substituents on the bridgehead allows for the precise
control over the direction of rotation as clearly illustrated
by the opposite directionality with respect to the methyl
substituent taken place in motors 21 and 22. Motor 22 has
the potential to be the fastest unidirectional motor based
on overcrowded alkenes to date and its desymmetrization
into motor 23 allowed for the visualization of the equal
rate of rotation of the two rotor units which perfectly fol-
lowed the predicted model for their rotational behavior.
This detailed study on elucidating key parameters for
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Third generation molecular motors are symmetric and notably lack a stereogenic center. Their potential as prime
movers in ever more advanced nanomachines and for controlled motion over surfaces makes the study of their key
parameters and limitations essential. Tuning the steric crowding at several sites in the motors proved pivotal in
controlling the direction of their disrotary motion and speed of rotation. An ultrafast symmetric motor was used to
demonstrate their autonomous rotational behavior.
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