Dynamic behavior of molecular switches in crystal under pressure and its reflection on tactile sensing

Article abstract of DOI:10.1021/ja511499p

Molecular switches have attracted increasing interest in the past decades, due to their broad applications in data storage, optical gating, smart windows, and so on. However, up till now, most of the molecular switches are operated in solutions or polymer blends with the stimuli of light, heat, and electric fields. Herein, we demonstrate the first pressure-controllable molecular switch of a benzo[1,3]oxazine OX-1 in crystal. Distinct from the light-triggered tautomerization between two optical states, applying hydrostatic pressure on the OX-1 crystal results in large-scale and continuous states across the whole visible light range (from ～430 to ～700 nm), which has not been achieved with other stimuli. Based on detailed and systematic control experiments and theoretical calculation, the preliminary requirements and mechanism of pressure-dependent tautomerization are fully discussed. The contributions of molecular tautomerization to the large-scale optical modulation are also stressed. Finally, the importance of studying pressure-responsive materials on understanding tactile sensing is also discussed and a possible mechanotransduction mode is proposed.

Full text of DOI:10.1021/ja511499p

Article
pubs.acs.org/JACS
Dynamic Behavior of Molecular Switches in Crystal under Pressure
and Its Reflection on Tactile Sensing
Yi Wang,† Xiao Tan,‡ Yu-Mo Zhang,† Shaoyin Zhu,† Ivan Zhang,† Binhong Yu,† Kai Wang,‡ Bing Yang,†
Minjie Li,*,† Bo Zou,*,‡ and Sean Xiao-An Zhang*,†
†State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin 130012, China
‡State Key Laboratory of Superhard Materials, Jilin University, Changchun, Jilin 130012, China
S
* Supporting Information
ABSTRACT: Molecular switches have attracted increasing
interest in the past decades, due to their broad applications in
data storage, optical gating, smart windows, and so on.
However, up till now, most of the molecular switches are
operated in solutions or polymer blends with the stimuli of
light, heat, and electric fields. Herein, we demonstrate the first
pressure-controllable molecular switch of a benzo[1,3]oxazine
OX-1 in crystal. Distinct from the light-triggered tautomeriza-
tion between two optical states, applying hydrostatic pressure on the OX-1 crystal results in large-scale and continuous states
across the whole visible light range (from ∼430 to ∼700 nm), which has not been achieved with other stimuli. Based on detailed
and systematic control experiments and theoretical calculation, the preliminary requirements and mechanism of pressure-
dependent tautomerization are fully discussed. The contributions of molecular tautomerization to the large-scale optical
modulation are also stressed. Finally, the importance of studying pressure-responsive materials on understanding tactile sensing is
also discussed and a possible mechanotransduction mode is proposed.
interactions under increasing pressure. And some new
application potentials for molecular switches could be expected.
Last but not least, the relationship between pressure and
molecular tautomerization would be established and it will shine
light on the longtime unresolved problem on how mechano-
transduction is triggered in the tactile nerve. Therefore,
investigating the switching behavior of molecular switches
under pressure is highly important.
Herein, we demonstrate for the first time that the
tautomerization of a benzo[1,3]oxazine OX-1 (Figure 1) can
be quantitatively tuned with the only parameter of hydrostatic
pressure in the crystal state, which results in remarkable and
continuous optical modulation that covers nearly the entire
visible light range (from ∼430 to ∼700 nm). Such a large-scale
and consecutive absorption modulation has not been achieved
with other methods. And this tautomerization is strictly pressure-
dependent with good reversibility. By comparing with the two
control molecules, OX-2 and IA-1, it is revealed that (i) the low
tautomerization energy barrier is a preliminary requirement for
pressure-controllable tautomerization of molecular switches, (ii)
difference in the compressibility of the two tautomeric species is
the inherent cause of pressure-tunable tautomerization, and (iii)
molecular structural tautomerization contributes more to such a
large-scale optical modulation than the configuration changes.
The new pressure-dependent switching behavior will exhibit new
applications, as an example, OX-1 is used as a good candidate for
INTRODUCTION
■
Reversible molecular transformations are of paramount
importance in many biological and chemical processes.1 Various
molecular tautomeric switches, such as spiropyrans, azoben-
zenes, and diarylethenes, have been hotly investigated to help
understand the function-switching process in biological field, and
also explore their broad applications in data storage, optical
gating, smart windows, and so on.2−9 Up till now, many stimuli
(such as light, heat, and electric field) have already been
demonstrated to be able to switch these molecular switches, but
most of these studies are concentrated on their tautomerization
between the bistable states in solution or in polymer blends10−16
and limited examples show tunable tautomerization in constraint
crystal states.17−19 Pressure is a very common energy input in
chemistry, but it has been rarely used to tune the tautomerization
of molecular switches. Though some scattered examples (e.g.,
piroxicam) show pressure-induced tautomerization in solid
state,20 pressure-responsive tautomeric molecular switches have
not attracted enough attention so far.
Quite different from other stimuli (such as light and heat) that
can be directly absorbed by single molecule and trigger the
tautomerization, the application and propagation of pressure are
through the intermolecular interactions in condensed
states.21−25 Therefore, several fundamental and technological
breakthroughs would be envisioned if the pressure could be used
as a switching stimulus. First, the switching could be achieved in
the crystal state, which is very hard to realize with other stimuli.
Second, the two tautomeric states should be modified to generate
more diversified states by the gradually enhanced intermolecular
Received: November 8, 2014
© XXXX American Chemical Society
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Figure 1. Chemical structures and partial view of the crystal packing of
OX-1, OX-2, and IA-1. In the molecular skeleton, the black and orange
regions represent hydrogen and carbon atoms, respectively. Red, blue,
and green balls correspond to oxygen atoms, nitrogen atoms, and the
center of an aromatic ring, respectively. The black dotted lines indicate
various intermolecular interactions (C−H···π, C−H···N, and π···π
interactions).
Figure 2. Comparison of the photoswitchable tautomerization between
spiropyrans and benzo[1,3]oxazines (a); absorption spectra of OX-1
(b) and OX-2 (c) in dichloromethane solution (1 × 10−5 M) under UV
(254 nm 6W) irradiation for different times; absorption spectra of OX-1
(d) and OX-2 (e) in different solvents (1 × 10−5 M) without the external
light stimuli.
a visible colorimetric pressure sensor. In addition, this successful
pressure-responsive molecular switch also helps understand how
the tactile signals are generated in biological system, and a
possible mechanotransduction mode has been proposed.
solvents, the zwitterionic isomers dominate without the external
stimulus of light (Figure 2d). However, OX-2 only exists in
neutral ring-closed isomer in various test solvents (Figure 2e).
This is presumably because the strong electron-donating N,N-
dimethylamino group in OX-1 can stabilize the positive charge in
its zwitterionic isomer well, whereas the strong electron-
withdrawing nitro group in OX-2 makes the conjugated positive
charge less stable.
RESULTS AND DISCUSSION
■
Switching Behavior of OX-1 and OX-2 in Solution and
Crystal States under Ambient Pressure. Benzo[1,3]-
oxazines are newly discovered bistable molecular switches in
2005.26 Though they are structurally similar to the traditional
well-known spiropyrans, they exhibit improved switching speed
and stability owing to noninvolving of cis−trans transition and
the absence of high energy-state conjugated zwitterions during
the tautomerization (Figure 2a).27−31 Thus, benzo[1,3]oxazines
are expected to tautomerize in crystal more easily. Two
benzo[1,3]oxazine derivatives of OX-132−37 and OX-2 with the
same backbone but distinctively different properties were
selected for study. First, their switching behavior was studied in
solution. Both OX-1 and OX-2 exhibit the light-triggered
neutral-to-zwitterionic tautomerization in solution. The neutral
ring-closed isomers of OX-1 and OX-2 are colorless in
dichloromethane, and resultant zwitterionic ring-open isomers
exhibit a purple color and a pale yellow color, respectively
(Figure 2b and c). Besides the photochromic properties, it is
found that their tautomerization happens dynamically in solution
at room temperature from temperature-dependent NMR
analysis (Supporting Information Figure S1). However, OX-1
has much lower energy barrier (ΔG = 11.51 kcal·mol−1) and
higher rate constant (2.5 × 104 s−1) for ring-opening reaction
than those of OX-2 (16.86 kcal·mol−1, 2 s−1) (Supporting
Information Table S1). As a result, the tautomerization of OX-1
is highly dependent on the solution environment. In less-polar
solvents, the neutral isomers dominate, and in high polar
After the study on tautomeric behavior of OX-1 and OX-2 in
solutions, we tried to study their switching behavior in crystals.
The single crystals of OX-1 and OX-2 were obtained by slow
solvent evaporation, and their crystal structures are depicted in
Figure 1 and Supporting Information Table S2. For the OX-1
crystal, there is a very weak absorption sideband between 500 and
600 nm besides the main peak around 430 nm (black line in
Figure 3b), and it is pale yellow in color (Figure 3a). Because the
pale yellow color is uniformly distributed in the whole crystal, we
can exclude the anomalous contamination of a small amount of
purple zwitterionic isomers during the crystallization. Therefore,
it is suggested that there are neutral and zwitterionic isomers
coexisting in the crystal. To prove it, light irradiation (high
pressure mercury lamp, 500 W) was used to shift the
tautomerization equilibrium. As a result, the absorbance at
500−600 nm increased and their color turned to red from yellow
(Supporting Information Figure S3a), which confirms that the
sideband absorption is from the zwitterionic isomers and
dynamic switching of OX-1 surely exists in the crystal. Also,
this is the first demonstration that tautomerization of certain
molecular switch of benzo[1,3]oxazine can exist in crystal at
room temperature without applying the conventional light
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Figure 3. Molecular structure of OX-1 in neutral and zwitterionic forms, and real optical images of an OX-1 crystal with increasing and decreasing
pressure (a) (the balls at the bottom right corner in DAC are ruby pressure markers). In-situ absorption (b) and Raman (c) spectra of the OX-1 crystal in
the DAC with increasing pressure (inset: comparison of the absorption and Raman spectra of OX-1 in the uncompressed and released states).
stimulus. The reasons for the room-temperature tautomerization
in constrained crystals are closely related to the low tautomeric
energy barrier and small configurational change after tautome-
rization as we addressed before. Because the neutral isomers have
lower energy than the zwitterionic isomers (Supporting
Information Figure S4), neutral isomers dominate in the crystal
(92% of OX-1 takes neutral forms in crystal roughly from UV−
vis absorption spectra analysis) (Supporting Information Figure
S6). As a result, only isomers in neutral form are detected in
single crystal X-ray analysis (Figure 1 and Supporting
Information Table S2).
In contrast, for OX-2, its crystal is colorless and transparent
(Figure 4a), and the corresponding absorption spectrum shows
only the absorption band for neutral isomers before 400 nm
(black line in Figure 4b). Accordingly, single crystal X-ray
structure analysis shows that there are only neutral isomers under
ambient pressure. Under UV light (high pressure mercury lamp,
500 W) irradiation, the colorless OX-2 microcrystals turned to
yellow with the appearance of absorption sideband in the visible
light range (Supporting Information Figure S3b), which
indicates that light stimulus can also induce the neutral-to-
zwitterionic tautomerization of OX-2 in crystal. This marvelous
light-triggered tautomerization phenomenon of OX-1 and OX-2
in crystal supplies us with the possibility to investigate the effect
of pressure on tautomeric equilibrium.
anvil cell (DAC) equipment, which can generate hydrostatic
pressure with dozens of gigapascals at room temperature. As
shown in Figure 3a, the crystal of OX-1 is pale yellow with good
optical transparency under ambient pressure. When the external
pressure was gradually increased from 0 to 10 GPa, the color of
the crystal underwent a continuous and remarkable variation
from pale yellow to orange to red, and finally to dark red.
Correspondingly, in situ UV−vis absorption spectra clearly
revealed that the absorption of crystal OX-1 shifted and
broadened continuously to longer wavelength, demonstrating a
marvelous pressure-tunable absorption across nearly the entire
visible light region (from ∼430 to ∼700 nm) (Figure 3b), and it
has been proven that the absorption spectra will not change with
the prolonging of time at each tested pressure points, which
means the equilibrium is reached right after the pressure is
stabilized (Supporting Information Figure S10). This amazing
optical modulation indicates that multiple optical states are
generated in the simple bistate molecular switch of OX-1 with
the only stimulus of pressure. The phenomenon has distinct
difference with light-triggered tautomerization, which only
results in the appearing of a new absorption peak (Figure 2b
and Supporting Information Figure S3a). The in situ Raman
spectra of OX-1 provide an opportunity to monitor the
molecular structure change with increasing pressure and
understand the absorption/color change. It is found that the
Raman spectra in the wavenumber range of 50−1300 cm−1 are
too weak to be reliably used for analysis, owing to the strong
fluorescent interference (Supporting Information Figure S7).
Dynamic Switching Behavior of OX-1 under High
Pressure. To study the effect of pressure on molecular
tautomerization of OX-1, the sample was put in a diamond
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Figure 4. Molecular structure of OX-2 in neutral forms, and real optical images of an OX-2 crystal with increasing and decreasing pressure (a) (the balls
at bottom left corner in DAC are ruby pressure markers). In-situ absorption (b) and Raman (c) spectra of the OX-2 crystal in the DAC with increasing
pressure (inset: comparison of the absorption and Raman spectra of OX-2 in the uncompressed and released states).
Fortunately, its Raman spectra in the wavenumber range of
1400−1800 cm−1 are clear enough to track the molecular
structure change (Figure 3c). Before compression, there are two
sets of Raman peaks (black line in Figure 3c). According to the
calculation results with B3LYP/6-31+G (d,p)38 (Supporting
Information Figure S8 and Video 1), the first set consists of the
two strong peaks at 1608 and 1647 cm−1, which are assigned to
the two different vibration modes of isolated π-system of N,N-
dimethyl-4-vinyl benzenamine of neutral isomer (black arrow in
Figure 3c); the second set consists of the peaks around 1608,
1540, and 1480 cm−1, which corresponds to the extended
conjugated π-systems of cyanine and nitrophenolate of the
zwitterionic isomer (red arrow in Figure 3c). This result is also in
agreement with our aforesaid assessment that the tautomeriza-
tion is a dynamic equilibrium in its crystal state and the neutral
isomer is thermodynamically favorable under ambient pressure.
When external pressure was applied, both sets of Raman peaks
shifted slowly toward higher frequencies as a result of the
shortening in interatomic distances and strengthening in the
effective force constants.39,40 In the meantime, their relative peak
intensities of zwitterionic isomer to neutral isomer increased
gradually with pressure, indicating external compression have
definitely changed the tautomerization equilibrium. The rough
estimation based on the Raman spectra shows that the
proportion of zwitterionic isomers increases from 8% to 83%
during the compression (Supporting Information Figure S9).
When pressure was removed gradually, both absorption and
Raman spectra of OX-1 recovered concomitantly (Supporting
Information Figure S11 and S12). However, there are some
edges in which the red color does not fade completely in the
microscopy images (Figure 3a), suggesting that some irreversible
alterations on molecular arrangements or conformations occur as
a result of the anisotropic deformation on these edges. Because
the portions of the edges are not much, it did not result in a
significant change in absorption and Raman spectra (Figure 3b
and c inset). Therefore, benzo[1,3]oxazine OX-1 is a good
candidate for pressure-controllable dynamic molecular switch.
Although some spiropyrans have been demonstrated to be
switched by stretching or shearing their polymer blends,41−46
these processes are usually irreversible. Bonds breaking by
stretching or shearing is understandable; however, the
compression-induced bond breaking is uncommon and will be
discussed later.
Performances of OX-2 under High Pressure. The
exciting pressure-tunable dynamic switching process has been
observed in the crystal of OX-1, and continuous optical states can
be built by shifting its tautomerization equilibrium with pressure.
Though OX-2 dose not exhibit stable zwitterionic isomers in
solution or crystal states without external stimuli, pressure is a
powerful tool to shorten intermolecular distance to change
intermolecular interactions and molecular internal energy, which
might give rise to significant effects on the tautomerization of
OX-2 in crystal. To test our hypothesis, we investigate the high
pressure behavior of OX-2. However, a distinctly different
phenomenon is observed (Figure 4). In the pressure range of 0 to
10 GPa, the crystal of OX-2 exhibits much smaller absorption
spectral change (from ∼400 nm to ∼480 nm) (Figure 4b) and
limited color change from colorless to yellow (Figure 4a).
Although the absorption peak of zwitterionic isomer of OX-2 is
around 400 nm with a pale yellow color in solution (Figure 2c),
the spectra change for OX-2 at 10 GPa is concluded not to
originate from its zwitterionic isomers but from enhanced
intermolecular interactions because their Raman spectra only
shows a common shift to high frequencies without any detectable
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new peaks (Figure 4c). The detailed analysis on main Raman
peaks’ shifts as a function of pressure shows that the main peaks
of OX-2 have good linear relationships with pressure, which
indicates that there are not any chemical transitions involved
during this compressed process (0−10 GPa) (Supporting
Information Figure S13).
remarkably different high-pressure responses. For OX-1,
pressure can significantly change tautomerization equilibrium.
But for OX-2, pressure cannot lead to the tautomerization until
irreversible polymerization occurs. Thus, it is very necessary to
understand in what circumstance pressure can affect the
tautomerization and why pressure can shift the tautomerization
equilibrium. Quite different from stretching or shearing induced
bond breakage of molecular switches in polymers, hydrostatic
pressure leads to the shrinkage in the volume of crystals. Thus, it
can be deduced that the isomer with smaller occupied volume
will be favored under pressure. We first calculate the molecular
volumes of OX-1 in neural and zwitterionic forms by B3LYP/6-
31+G (d,p) calculations38 in a vacuum (Supporting Information
Figure S4). The optimized molecular volume of zwitterionic
isomer of OX-1 is a little larger than that of optimized neutral
isomer (374.610 vs 338.652 cm3·mol−1) because the nitro-
phenolate group trends to rotate around the C−N bond after the
cleavage of C−O bond in vacuum (Supporting Information
Figure S4). From the viewpoint of volume variation, the
compression process seems not to be favorable for the
zwitterionic ring-open isomer of OX-1. But in fact, in the
constraint crystal, especially in a highly compressed state, the
rotation of the C−N bond should not easily take place. Here, we
are inclined to think that the phenol oxygen atom in zwitterionic
isomer of OX-1 is not much deviated from the original positon in
its neutral isomer under isotropic hydrostatic pressure, which is
directly deduced from the evidence that the neutral isomer can
restore immediately when pressure is removed. To test our
deduction, we utilize another stimulus of mechanical grinding to
trigger the tautomerization. The grinding-induced zwitterionic
isomer of OX-1 could stand well for one year under ambient
conditions, and it could not recover to its original state even
when it is heated at 100 °C for 20 min (Supporting Information
Figure S18). This poor reversibility in grinding-induced
tautomerization of OX-1 is just attributed to a large deviation
of the nitrophenolate from its original position caused by the
anisotropic stress-triggered configurational or conformational
variation, and it is difficult for the rebuilding of C−O bond.
Though the molecular volumes of neutral and zwitterionic
isomers do not exhibit significant differences under compression,
the compressibility of two isomers is quite different. Compared
with the relatively rigid cyclized framework of the neutral isomer,
the nitrophenolate fragment in the zwitterionic isomer is more
flexible and compressible, which might be a main driven force for
the pressure-tunable tautomerization of OX-1. In the meantime,
the resultant cyanine structure in the zwitterionic isomer would
be more planar than before, which also favors its high
compressibility.
When pressure reaches 12 GPa, an abrupt color and
absorption spectra change for OX-2 occurs (Figure 4a and 4b).
Thereafter, the color of crystal OX-2 continuously deepens and
finally turns to reddish dark in the middle part of the crystal
(Figure 4a) with its absorption shifting to around 800 nm (Figure
4b). Meanwhile, the Raman spectra gradually vanishes when
pressure is further increased to 18 GPa (Figure 4c), which is a
result of strong background inference of fluorescence. More
interestingly, the color, absorption, and Raman spectra of OX-2
could not recover after the pressure is totally removed (Figure 4).
Further detailed investigation reveals that the OX-2 crystal can
be fully restored to its original state when the pressure reaches
only 10 GPa (Supporting Information Figure S14), and most of it
can recover when the pressure reaches 12 GPa. But when
pressure reaches 14 GPa, the compressed OX-2 cannot recover,
especially for the Raman spectra, which completely disappears
when the pressure is released (Supporting Information Figure
S15). The phenomenon indicates that an irreversible chemical
reaction takes place between 10 and 12 GPa range and only
physical compression with good reversibility is involved before
10 GPa. This irreversible chemical reaction of OX-2 under high
pressure inspires us to investigate whether a similar irreversible
chemical transition also takes place in OX-1 crystal at higher
pressure. To answer this question, we further compressed the
OX-1 crystal to 18 GPa from 10 GPa. As anticipated, when
pressure was removed, the color of OX-1 crystal remained black,
and the absorption and Raman spectra also could not recover to
the original state (Supporting Information Figure S16), which
indicates that OX-1 also undergoes an irreversible chemical
reaction when pressure is high enough.
These irreversible reactions for OX-1 and OX-2 maybe come
from the polymerization of parallel aromatic rings. It has been
demonstrated that the polymerization of benzene will be
triggered when C···C distance between adjacent benzene rings
reach the critical threshold of 2.6 Å.47 In the crystal OX-1 and
OX-2, the distances of their π···π interactions are 3.991 and 3.386
Å (or 3.864 Å) (Figure 1), respectively, which provides a
possibility for the polymerization of aromatic rings under
pressure. In addition, the polymerization of benzene involves
the ring-opening of the benzene ring and transforms an sp2
carbon atom into an sp3 atom.48 Comparing with uncompressed
samples of OX-1 and OX-2, the relative peak intensities of the
saturated C−H to aromatic ring in highly compressed and
irreversible crystals obviously increase (Supporting Information
Figure S17), which further suggests that the irreversible chemical
reactions are originated from the polymerization of the parallel
aromatic rings. To sum up, both OX-1 and OX-2 can undergo
irreversible chemical transformation when they are highly
compressed. But for OX-1, it shows pressure-controllable and
reversible tautomerization in the low pressure range (0−10
GPa). However, OX-2 does not exhibit the tunable tautomeric
equilibrium under compression like OX-1, it only shows
pressure-tunable reversible configuration change at low pressure
(0−10 GPa) and an irreversible polymerization at high pressure.
Understanding the Different High-Pressure Behavior
of OX-1 and OX-2. In the above two sections, it is shown that
two benzo[1,3]oxazine analogues of OX-1 and OX-2 exhibit
Besides the compressibility, we can understand the pressure-
shifted tautomerization from the viewpoint of molecular energy.
Under ambient pressure, the energy differences between the
zwitterionic and neutral isomers are 9.17 kcal·mol−1 and 18.28
kcal·mol−1 in vacuum for OX-1 and OX-2, respectively,
according to theoretical calculations (Supporting Information
Figure S4 and S5). That means the neutral isomers are dominant
components for both OX-1 and OX-2 without pressure. During
the shrinkage of crystal volume under pressure, the molecular
energies will be boosted to higher levels by increasing the
molecular tension. Due to the better compressibility and stronger
intermolecular interactions between zwitterionic isomers, the
energy rise of zwitterionic isomer should not be as much as that
of a neutral isomer with increasing pressure. As a result, an
inversion of the relative energy levels distribution between two
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isomers might take place for OX-1 owing to their relatively small
energy difference (Supporting Information Figure S4), and the
zwitterionic isomers of OX-1 with lower energy under high
pressure might be more favorable (Figure 5a). The low
between two isomers should be harder to occur under moderate
compression (0−10 GPa) owing to the high energy differences
between two isomers (Supporting Information Figure S5). On
the other hand, the large tautomerization energy barrier (16.86
kcal·mol−1) (Supporting Information Table S1) makes the
tautomerization hard to happen at room temperature (Figure
5b). When pressure is further increased, the irreversible
polymerization is triggered. Therefore, we can conclude that
the lower tautomerization barrier and smaller energy gap
between the isomers of molecular switches are preliminary
requirements for the pressure-tunable tautomerization process.
Considering the fact that light-stimulus can induce the
tautomerization of OX-1 and OX-2 in both solution and solid
states, we can clearly find that the effects of two energy inputs
(light and pressure) on the molecular tautomerization are quite
different. For light-stimulated tautomerization, the light can be
absorbed by the neutral molecule in both free and restricted
states to excite their electron from ground-state to excited-state,
which then polarizes the molecule and result in the cleavage of
the weak C−O bond to generate zwitterionic isomer. In other
words, the energy of the neutral molecule is boosted by
absorbing the light energy, and then it overcomes the energy
barrier to reach the zwitterionic states. A static UV−vis
absorption change can be detected as long as the zwitterionic
isomer can be stabilized in its microenvironment, otherwise, it
will revert to the neutral isomer instantly.19 For pressure
stimulus, it cannot excite the electron of the molecule to its
excited-state, but instead, it can change the energy of the
molecule by strengthening intermolecular interactions in the
restricted state (e.g., crystal state). As a result, the distribution of
the relatively energy levels of the neutral isomer, the zwitterionic
isomer and the transition state may change with their different
susceptibility to pressure. However, it can only absorb ambient
heat to overcome the energy barrier; therefore, it is difficult to
apply only pressure to induce the tautomerization for molecules
that have high tautomeric energy barriers (e.g., OX-2).
Understanding the Continuous, Large-Scale, and
Reversible Optical Modulation under Pressure and the
Application Potentials. Though the bathochromic shift in
absorption spectra of electronic transition with increasing
pressure has been observed in some organic crystals, polymers,
and metal complexes,49−51 the continuously shifting and
broadening of spectra covering nearly the entire visible region
(from ∼430 to ∼700 nm) for OX-1 are still unusual. For
common polymers or some conjugated organic molecules,
pressure-induced better planarity and strengthened overlap of π-
electrons by shortening intermolecular distance are responsible
for the bathochromic shift in the absorption (around 100
nm).52−55 For OX-1, besides the better planarity and enhanced
intermolecular interactions, we think that the molecular
structural transformation contributes more to the large-scale
spectra bathochromic shift. To confirm this assumption, we
investigated another single crystal of IA-1, which has an
analogous conjugated structure with zwitterionic OX-1 but
lacks structural adjustability (Figure 1 and Supporting
Information Figure S19a). During the compression, an obvious
red-shift in its absorption spectra is observed at the pressure
around 1 GPa. This could be assigned to pressure-induced
molecular planarity. When pressure is further increased to 10
GPa, its absorption spectra exhibit sequentially bathochromic
shift like common organic compounds and accompany with a
color change from pale yellow to orange (Supporting
Information Figure S19a and S19b). But its absorption shifts
Figure 5. Potential energy diagram for the tautomeric equilibriums of
OX-1 (a) and OX-2 (b) under different conditions.
tautomerization energy barrier (ΔG = 11.51 kcal·mol−1) enable
the heterocleavage of the C−O bond happen at room
temperature and shift the tautomeric equilibrium of OX-1
toward zwitterionic isomers. In addition, as mentioned above,
zwitterionic isomer of OX-1 is more favorable in polar
environment in solution (Figure 2d). In a crystal, the zwitterionic
isomer with much larger dipole moment than that of neutral one
(Supporting Information Figure S4), which can supply the polar
environments. When pressure drives the tautomeric equilibrium
of OX-1 to generate more zwitterionic isomers, a more polar
microenvironment is also formed. In return, it will help to
stabilize the newly generated zwitterionic isomers under high
pressure. Therefore, a better compressibility of the zwitterionic
isomer, the smaller energy gap and the inversion of the relative
energy levels between the two isomers, the more polar
microenvironment under high pressure, and low tautomerization
energy barrier together contribute to the pressure-controllable
dynamic switching of OX-1 in crystal.
For OX-2, the molecular energies between two isomers are
also elevated with increasing pressure. However, on the one
hand, the inversion of the relative energy levels distribution
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Figure 6. Illustration of different optical modulations of IA-1, OX-1, and OX-2 under pressure.
only around 40 nm, which indicates that a simple conjugated
system shows limited bathochromic shift in the absorption
spectra (Figure 6). Moreover, in the range of 0−10 GPa, the
absorption wavelength of OX-2 also shifts only 70 nm (Figure 4b
and Supporting Information Figure S14). Therefore, without
chemical structure tautomerization, pressure-induced better
planarity and strengthened overlap of π-electrons can only give
rise to narrow optical modulation in conjugated organic crystals.
Nevertheless, the simple physical compression usually exhibits
good reversibility. But when the threshold pressure for chemical
reaction reaches, an irreversible polymerization is triggered in the
OX-2 crystal. As a result, an abrupt and obvious spectra shift
(around 100 nm) is observed. Also, with the going of the
chemical reaction, the absorption spectra of OX-2 bathochromi-
cally shift to around 800 nm and cover almost entire visible
region (Figure 4b). Based on the above discussions, we can find
that chemical transition in crystal plays an important role on the
large-scale optical modulation. But for reversible and large-scale
optical modulator, the irreversible polymerization mode (such as
OX-2) is not ideal (Figure 6).
induce its physical property changes (such as light absorption,
dielectric constant, conductivity, etc.) and bring about new
applications for molecular switches, such as large-scale optical
modulation materials, energy storage materials, pressures
sensors, and so on. However, we do not have the facility so far
to measure all these properties. Here, as an example, we show the
application potentials of OX-1 as both a rough visible pressure
indicator and a relatively accurate pressure sensor. As we can see
in Figure 3a, the color change at every 1 GPa pressure increment
can be clearly distinguished, which endorses OX-1 as a good
candidate for a convenient and rough colorimetric pressure
indicator just like pH test strips. What’s more, the Raman peak’s
shift at 1608 cm−1 is linear with pressure (Figure 7), which
provides another opportunity for OX-1 to sense pressure more
precisely. Most importantly, the process is reversible, after three
cycles of compressions and decompressions, the Raman spectra
of OX-1 could still revert to the original state (Figure 7 inset).
The good reversibility would be of benefit to its practical
application. We expect that new properties and applications will
The continuous, large-scale, and reversible optical modulation
of OX-1 in crystal can be ascribed to its pressure-controllable
tautomerization before reaching the threshold pressure of
irreversible chemical reaction. Under ambient pressure, the
neutral and zwitterionic isomers of OX-1 coexist in crystal with
absorption maximums at 426 and 574 nm, respectively
(Supporting Information Figure S2), which means that OX-1
has two different compression starts (with ∼150 nm gaps). When
OX-1 is compressed, external pressure shortens intermolecular
distance to drive the absorptions of two isomers bathochromic
shift from their different starts. In addition, the ratio of two
isomers is variable with increasing pressure. In this way, the two
coexisting isomers of OX-1 with pressure-tunable ratios and
bathochromic shift degree finally result in the large-scale optical
modulation. At the same time, the tautomerization of OX-1
between two isomers is strictly pressure dependent. Thus, its
optical modulation is well reversible (Figure 6 and Supporting
Information Video 2).
Figure 7. Shift of the Raman peak at 1608 cm−1 of OX-1 with pressure
(inset: peak values of OX-1 at 1608 cm−1 under three cycles of
compression and decompression).
The above demonstrated novel pressure-controlled, large-
scale structural adaption to pressure for OX-1 will undoubtedly
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be further explored for molecular switches where research
facilities allow.
Reflection of the Pressure-Controlled Molecular
Tautomerization on Tactile Sensing. As we stress in the
beginning of the paper, developing pressure-responsive molec-
ular switches is on the one hand for the development of novel
functional materials, and on the other hand for understanding the
tactile sensation mechanism of biological system. It is well known
that the key of tactile sensing is transforming a mechanical signal
into an electrical signal, in which external mechanical stimuli
induce the ion channels to open and finally generate the electrical
signal. However, we have little knowledge on how mechanical
force induces the ion channels to open. Although some
piezoproteins have been revealed to be related to the
mechanotransduction, the working mechanisms of the mecha-
noreceptors are still unclear.56,57 Our research results here show
the following two facts: (1) even in confined solid state, dynamic
molecular tautomerization (reversible bond heterocleavage) are
still possible at room temperature and (2) external pressure can
shift the tautomerization equilibrium by changing the relative
energy levels of the two isomers, transforming the “less polar”
neutral isomers to the “highly polarized” zwitterionic isomers. In
this way, the molecular switches work as a nanopiezoelectric
machine, transforming the mechanical energy to electric
potential. Because the mechanotransduction process also relies
on the mechanical-to-electrical signal transition in a tactile nerve,
we propose that one possible path of mechanotransduction is
also rely on the reversible bond heterocleavage.
Choosing from the amino acid library, we think it is unlikely
that the less polar covalent bond will be broken in a protein to
result in zwitterionic forms. However, the ubiquitous supra-
molecular bonds can be easier to break and result in polarized
zwitterionic species by heterocleavage. Also, we suggest one of
the most probable supramolecular bond is the polar hydrogen
bond between the acidic groups (e.g., carboxylic acid, phenol)
and basic groups (e.g., amino, imidazolyl) in the proteins. The
interaction modes between the acidic and basic groups can vary
with their pKa and pKb depending on their associated structures
and microenvironment. If the acidity of the acidic group is not
strong enough to protonate the basic group, they can form
neutral supramolecules by hydrogen bonds; conversely,
zwitterions of carboxylate anion and ammonium cation are
generated. The pKa and pKb of the amino acid are constants at a
certain temperature in solution. However, our results show that
force can trigger the molecular reaction that does not dominate at
ambient pressure to occur at higher pressure by increasing the
molecular interactions in solid state. Our previous study also
elucidates that the molecular acidity of a conjugated amphoteric
molecules can also be enhanced with mechanical force, and a
proton transfer is triggered subsequently.58 Although we cannot
give the details of how molecular acidity and basicity in protein
can be modified by intermolecular interaction under mechanical
force so far, we strongly believe that proton transfer between the
neutral acid−base pair in protein is possible under a mechanical
trigger; as a result, the neutral to ionic state transformation will
lead to the closed ion channel to open and realize the
mechanotransduction (Figure 8). Our next focus will be
concentrated on developing other dynamic mechanoresponsive
small molecular systems and shine further light on tactile sensing
mechanism. In the meantime, computational modeling will be
carried out in proteins to test the possibilities of proton transfer
in our proposed model.
Figure 8. Possible working mechanism of piezoprotein in tactile sensing
system.
CONCLUSIONS
■
In summary, we have presented a pioneered pressure-control-
lable molecular switch of OX-1, which realizes the bistable state
to continuous state transition in a crystal by pressure-enhanced
intermolecular interactions. When pressure increases from 0 to
10 GPa, a continuous and reversible large-scale absorption
modulation across the whole visible light range (from ∼430 to
∼700 nm) is realized. The pressure-controllable molecular
tautomerization is found to be related to its low tautomeric
energy barrier of tautomerization, the small energy gap between
the two isomers, and the strong environmental sensitivity of the
tautomerization equilibrium. In contrast, the relatively high
tautomeric energy barrier, and weak environmental sensitivity of
the tautomerization equilibrium make OX-2 lack of a dynamic
switching behavior in crystal. The molecular tautomerization
ratio increment from the original 8% to 83% for OX-1 is found to
contribute more to the large-scale optical modulation than the
configuration change. This novel reversible pressure-dependent
color and Raman shift show the application potential in pressure
sensors. Results from our experiments not only enrich the
understanding on the dynamic structural tautomerization in
crystal and the adaption of molecular structure to microenviron-
ments but also inspire us to propose a possible model of
hydrogen-bond heterocleavage for mechanotransduction in
tactile sensing.
ASSOCIATED CONTENT
* Supporting Information
Detailed experimental procedures and characterization data for
the OX-1, OX-2, and IA-1. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
■
Corresponding Authors
*liminjie@jlu.edu.cn
*zoubo@jlu.edu.cn
*seanzhang@jlu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors acknowledge Prof. Bingbing Liu for IR spectra
measurements and Prof. Bing Zhao for discussion on Raman
spectra. We thank NSFC (51373068 and 91227202) and the
program of Chang Jiang Scholars and Innovative Research Team
in University (IRT101713018) for financial support.
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Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.; Peralta,
J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.;
Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.;
Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich,
S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.;
Fox, D. J. Gaussian 09, Revision A.01; Gaussian, Inc.: Wallingford, CT,
2009.
(39) Wang, K.; Duan, D.; Wang, R.; Lin, A.; Cui, Q.; Liu, B.; Cui, T.;
Zou, B.; Zhang, X.; Hu, J.; Zou, G.; Mao, H. K. Langmuir 2009, 25,
4787−4791.
(40) Tan, X.; Wang, K.; Li, S.; Yuan, H.; Yan, T.; Liu, J.; Yang, K.; Liu,
B.; Zou, G.; Zou, B. J. Phys. Chem. B 2012, 116, 14441−14450.
(41) Davis, D. A.; Hamilton, A.; Yang, J.; Cremar, L. D.; Gough, D. V.;
Potisek, S. L.; Ong, M. T.; Braun, P. V.; Martínez, T. J.; White, S. R.;
Moore, J. S.; Sottos, N. R. Nature 2009, 459, 68−72.
REFERENCES
■
(1) Godsi, O.; Peskin, U.; Kapon, M.; Natan, E.; Eichen, Y. Chem.
Commun. 2001, 2132−2133.
(2) Berkovic, G.; Krongauz, V.; Weiss, V. Chem. Rev. 2000, 100, 1741−
1753.
(3) Minkin, V. I. Chem. Rev. 2004, 104, 2751−2776.
(4) Natansohn, A.; Rochon, P. Chem. Rev. 2002, 102, 4139−4175.
(5) Irie, M. Chem. Rev. 2000, 100, 1685−1716.
(6) Zhu, M. Q.; Zhang, G. F.; Li, C.; Aldred, M. P.; Chang, E.; Drezek,
R. A.; Li, A. D. Q. J. Am. Chem. Soc. 2011, 133, 365−372.
(7) Tian, Z.; Wu, W.; Wan, W.; Li, A. D. Q. J. Am. Chem. Soc. 2011, 133,
16092−16100.
(8) Yam, V. W. W.; Lee, J. K. W.; Ko, C. C.; Zhu, N. J. Am. Chem. Soc.
2009, 131, 912−913.
(9) Poon, C. T.; Lam, W. H.; Wong, H. L.; Yam, V. W. W. J. Am. Chem.
Soc. 2010, 132, 13992−13993.
(10) Kawata, S.; Kawata, Y. Chem. Rev. 2000, 100, 1777−1788.
(11) Szacilowski, K. Chem. Rev. 2008, 108, 3481−3548.
(12) Li, K.; Xiang, Y.; Wang, X.; Li, J.; Hu, R.; Tong, A.; Tang, B. Z. J.
Am. Chem. Soc. 2014, 136, 1643−1649.
(13) Raymo, F. M.; Alvarado, R. J.; Giordani, S.; Cejas, M. A. J. Am.
Chem. Soc. 2003, 125, 2361−2364.
(42) Lee, C. K.; Davis, D. A.; White, S. R.; Moore, J. S.; Sottos, N. R.;
Braun, P. V. J. Am. Chem. Soc. 2010, 132, 16107−16111.
(43) Kingsbury, C. M.; May, P. A.; Davis, D. A.; White, S. R.; Moore, J.
S.; Sottos, N. R. J. Mater. Chem. 2011, 21, 8381−8388.
(44) Beiermann, B. A.; Kramer, S. L. B.; Moore, J. S.; White, S. R.;
Sottos, N. R. ACS Macro Lett. 2012, 1, 163−166.
(45) Grady, M. E.; Beiermann, B. A.; Moore, J. S.; Sottos, N. R. ACS
Appl. Mater. Interfaces 2014, 6, 5350−5355.
(14) Jiang, G.; Song, Y.; Guo, X.; Zhang, D.; Zhu, D. Adv. Mater. 2008,
20, 2888−2898.
(15) Tian, H.; Yang, S. Chem. Soc. Rev. 2004, 33, 85−97.
(16) Tan, W.; Zhang, Q.; Zhang, J.; Tian, H. Org. Lett. 2009, 11, 161−
164.
́
(17) Benard, S.; Yu, P. Chem. Commun. 2000, 65−66.
(18) Patel, D. G.; Benedict, J. B.; Kopelman, R. A.; Frank, N. L. Chem.
Commun. 2005, 2208−2210.
(46) Beiermann, B. A.; Kramer, S. L. B.; May, P. A.; Moore, J. S.; White,
S. R.; Sottos, N. R. Adv. Funct. Mater. 2014, 24, 1529−1537.
(47) Ciabini, L.; Santoro, M.; Gorelli, F. A.; Bini, R.; Schettino, V.;
Raugei, S. Nat. Mater. 2007, 6, 39−43.
(19) Harada, J.; Kawazoe, Y.; Ogawa, K. Chem. Commun. 2010, 46,
2593−2595.
(20) Sheth, A. R.; Lubach, J. W.; Munson, E. J.; Muller, F. X.; Grant, D.
J. W. J. Am. Chem. Soc. 2005, 127, 6641−6651.
(21) Schettino, V.; Bini, R. Phys. Chem. Chem. Phys. 2003, 5, 1951−
1965.
(48) Ciabini, L.; Santoro, M.; Bini, R.; Schettino, V. J. Chem. Phys.
2002, 116, 2928−2935.
(49) Taran, M. N.; Langer, K.; Koch-Muller, M. Phys. Chem. Miner.
̈
2008, 35, 175−177.
(22) Kaupp, G. CrystEngComm 2009, 11, 388−403.
(23) Baig, R. B. N.; Varma, R. S. Chem. Soc. Rev. 2012, 41, 1559−1584.
(24) Ariga, K.; Mori, T.; Hill, J. P. Adv. Mater. 2012, 24, 158−176.
(25) Jezowski, S. R.; Zhu, L.; Wang, Y.; Rice, A. P.; Scott, G. W.;
Bardeen, C. J.; Chronister, E. L. J. Am. Chem. Soc. 2012, 134, 7459−
7466.
(50) Byrne, P. J.; Richardson, P. J.; Chang, J.; Kusmartseva, A. F.; Allan,
D. R.; Jones, A. C.; Kamenev, K. V.; Tasker, P. A.; Parsons, S. Chem.
Eur. J. 2012, 18, 7738−7748.
(51) Fanetti, S.; Citroni, M.; Malavasi, L.; Artioli, G. A.; Postorino, P.;
Bini, R. J. Phys. Chem. C 2013, 117, 5343−5351.
(52) Shirotani, I.; Hayashi, J.; Takeda, K.; Kawamura, H.; Inokuchi, M.;
Yakushi, K.; Inokuchi, H. Mol. Cryst. Liq. Cryst. 2007, 461, 111−122.
(53) Chandrasekhar, M.; Guha, S.; Graupner, W. Adv. Mater. 2001, 13,
613−618.
(26) Tomasulo, M.; Sortino, S.; Raymo, F. M. Org. Lett. 2005, 7, 1109−
1112.
(27) Tomasulo, M.; Sortino, S.; White, A. J. P.; Raymo, F. M. J. Org.
Chem. 2005, 70, 8180−8189.
(54) Webster, S.; Batchelder, D. N. Polymer 1996, 37, 4961−4968.
(55) Shirotani, I. Platinum Met. Rev. 1987, 31, 20−23.
(56) Coste, B.; Mathur, J.; Schmidt, M.; Earley, T. J.; Ranade, S.;
Petrus, M. J.; Dubin, A. E.; Patapoutian, A. Science 2010, 330, 55−60.
(57) Roudaut, Y.; Lonigro, A.; Coste, B.; Hao, J.; Delmas, P.; Crest, M.
Channels 2012, 6, 234−245.
(28) Tomasulo, M.; Sortino, S.; Raymo, F. M. Adv. Mater. 2008, 20,
832−835.
(29) Tomasulo, M.; Deniz, E.; Benelli, T.; Sortino, S.; Raymo, F. M.
Adv. Funct. Mater. 2009, 19, 3956−3961.
(30) Tomasulo, M.; Raymo, F. M. J. Mater. Chem. 2005, 15, 4354−
4360.
(58) Wang, Y.; Li, M.; Zhang, Y.-M.; Yang, J.; Zhu, S.; Sheng, L.; Wang,
X.; Yang, B.; Zhang, S. X. -A. Chem. Commun. 2013, 49, 6587−6589.
(31) Prostota, Y.; Berthet, J.; Delbaere, S.; Coelho, P. J. Dyes Pigm.
2013, 96, 569−573.
(32) Deniz, E.; Tomasulo, M.; Sortino, S.; Raymo, F. M. J. Phys. Chem.
C 2009, 113, 8491−8497.
(33) Deniz, E.; Ray, S.; Tomasulo, M.; Impellizzeri, S.; Sortino, S.;
Raymo, F. M. J. Phys. Chem. A 2010, 114, 11567−11575.
(34) Cusido, J.; Battal, M.; Deniz, E.; Yildiz, I.; Sortino, S.; Raymo, F.
M. Chem.Eur. J. 2012, 18, 10399−10407.
(35) Zhu, S.; Li, M.; Sheng, L.; Chen, P.; Zhang, Y.; Zhang, S. X. -A.
Analyst 2012, 137, 5581−5585.
(36) Xie, X.; Crespo, G. A.; Bakker, E. Anal. Chem. 2013, 85, 7434−
7440.
(37) Zhu, S.; Li, M.; Zhang, Y.; Tang, S.; Yang, J.; Wang, Y.; Sun, L.;
Sheng, L.; Yang, B.; Zhang, S. X. -A. RSC Adv. 2013, 3, 19752−19755.
(38) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
I
DOI: 10.1021/ja511499p
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX