Fast, reversible mechanochromism of regioisomeric oxazine mechanophores: Developing in situ responsive force probes for polymeric materials

Article abstract of DOI:10.1016/j.chempr.2021.02.014

To address hysteretic or irreversible mechanochromism found in most bond-scission-based mechanophores, we developed a new family of mechanophores based on the oxazine (OX) structural motif. Three OX regioisomers differing in their point of attachment to the indole ring show variable mechanochromic mechanoresponsiveness in a polydimethylsiloxane (PDMS) matrix. Constrained DFT simulations correlate the experimental findings to molecular scale events; two of the three regioisomers exhibit a force-activated rearrangement, while the third one is mechanochemically inactive. Most significantly, when compared with the spiropyran (SP) and the naphthopyran (NP), the OX mechanophores exhibit faster and reversible mechanochromism without any sign of fatigue. Such a rapid response to mechanical loads is rationalized by the difference between SP and OX scaffolds, given that the SP ring opening is accompanied by a trans-cis isomerization step. These fast-responsive mechanophores are anticipated to bring deeper understanding to a broad range of soft materials by in situ monitoring the local mechanics.

Full text of DOI:10.1016/j.chempr.2021.02.014

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Fast, reversible mechanochromism of
regioisomeric oxazine mechanophores:
Developing in situ responsive force probes for
polymeric materials
Hai Qian, Nathan S. Purwanto,
Douglas G. Ivanoff, Abigail J.
Halmes, Nancy R. Sottos, Jeffrey
S. Moore
n-sottos@illinois.edu (N.R.S.)
jsmoore@illinois.edu (J.S.M.)
HIGHLIGHTS
Oxazines undergo a force-
induced rearrangement reaction
leading to coloration
Oxazine mechanophores show
rapid and reversible
mechanochromism
Three oxazine regioisomers show
variable mechanoresponsiveness
A mechanistic rationalization
explains the rapid
mechanochromism
A mechanophore scaffold based on the oxazine (OX) structural motif was developed to
address the hysteretic or irreversible mechanochromism found in most bond-scission-
based mechanophores. Consistent with density functional theory predictions, three
OX regioisomers with varying polymer attachment positions on the indole ring exhibit
variable mechanochromic mechanoresponsiveness in a polydimethylsiloxane matrix.
Moreover, when compared with the spiropyran and the naphthopyran, the OX
mechanophores exhibit faster and reversible mechanochromism with no phase lag or
any sign of response fatigue.
Qian et al., Chem 7, 1080–1091
April 8, 2021 ª 2021 Elsevier Inc.
https://doi.org/10.1016/j.chempr.2021.02.014

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Fast, reversible mechanochromism of regioisomeric
oxazine mechanophores: Developing in situ
responsive force probes for polymeric materials
Hai Qian,1,2 Nathan S. Purwanto,1,3 Douglas G. Ivanoff,1,3 Abigail J. Halmes,1,2 Nancy R. Sottos,1,3,
*
and Jeffrey S. Moore1,2,4,
*
SUMMARY
The bigger picture
To address hysteretic or irreversible mechanochromism found in
most bond-scission-based mechanophores, we developed a new
family of mechanophores based on the oxazine (OX) structural
motif. Three OX regioisomers differing in their point of attachment
to the indole ring show variable mechanochromic mechanorespon-
siveness in a polydimethylsiloxane (PDMS) matrix. Constrained
DFT simulations correlate the experimental findings to molecular
scale events; two of the three regioisomers exhibit a force-activated
rearrangement, while the third one is mechanochemically inactive.
Most significantly, when compared with the spiropyran (SP) and
the naphthopyran (NP), the OX mechanophores exhibit faster and
reversible mechanochromism without any sign of fatigue. Such a
rapid response to mechanical loads is rationalized by the difference
between SP and OX scaffolds, given that the SP ring opening is
accompanied by a trans-cis isomerization step. These fast-respon-
sive mechanophores are anticipated to bring deeper understanding
to a broad range of soft materials by in situ monitoring the local
mechanics.
Mechanophores, a family of force-
sensitive molecules, undergo
specific covalent bond changes in
polymeric materials upon
application of an external load.
One of the drawbacks in
mechanoresponsive materials is
that most bond-scission-based
mechanophores exhibit hysteretic
or irreversible mechanochromism.
To address this fundamental
limitation, we developed a family
of fast-responsive
mechanophores based on the
oxazine (OX) structural motif. The
OX mechanophores are not only
rapid and reversible color-
changing mechanophores, but
their responsiveness is also
tunable by regioisomeric
INTRODUCTION
variation. The results highlight
that (1) fast-responding
Compared with specific and rapid mechanosensation observed for a wide range of
1
physiological processes, the precise mechanochemical transformations in poly-
2
mechanophores are useful probes
for visualizing the dynamics of
polymer chains under applied
stress in situ and (2) the structure-
reactivity relationships found in
OX mechanophores reinforce the
rational design of molecular force
probes and novel stimuli-
meric materials are far less explored. Prior to the advent of mechanophores—the
3
family of synthetic force-sensitive molecules —few systematic mechanoresponsive
4
functions were known in synthetic polymers. Covalent incorporation of mechano-
phores into polymer backbones and polymer networks enables precise covalent
5
transformations by externally applied forces. This force-induced transformation is
unique from other stimuli (e.g., light, heat, pH, and chemical triggers) that drive stim-
6
uli-responsive changes. Specifically, mechanoactivation has directional character,
which, in turn, couples to the geometric attributes of the mechanophore through
its pull points, thus providing a means to tune the force responsiveness. In other
words, by modulating the attachment points of a mechanophore in polymer chains,
the force-induced reactivity of the mechanophore and the responsiveness of the ma-
responsive materials.
7
–9
terial vary significantly.
For instance, the naphthopyran (NP) scaffold is broadly
photochemically active, but only one of its three tested regioisomers is validated
1
0
as a mechanophore in bulk materials. Additionally, leveraging stereochemistry
in a mechanophore enables the biasing of reaction pathways—thus generating sym-
1
1,12
metry-forbidden products—by force.
Thus, subtle changes on a mechanophore
skeleton may completely alter its mechanochemical reactivity. This fact is one of the
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most intriguing aspects in mechanophore design, necessitating further investigation
of structure-reactivity relationships.
Mechanophores that undergo optical property changes upon force activation are
particularly intriguing and show usefulness in investigating the mechanics of poly-
meric materials (e.g., studying force-induced chain failures and visualizing mechan-
1
3–18
ical loading of bulk specimens).
phores have been reported, including spiropyran (SP),
To date, several color-changing mechano-
1
9
20
spiro(thio)pyran,
coumarin dimer,
1
0,21
22
23,24
25
26
NP,
rhodamine,
polyladderene,
1,2-dioxetane,
2
7,28
29
anthracene-maleimide adducts,
masked benzooxazole, and stable radical sys-
Most of these mechanophores suffer from two limitations: (1) a hysteretic
3
0–34
tems.
or irreversible mechanochemical response and (2) a slow mechanochemical deacti-
vation. SP is one of the most studied mechanophores; it generates a highly colored
merocyanine (MC) species via a force-induced pericyclic ring-opening reaction. The
most intense color change of the materials incorporating SP requires the polymer to
be held under strain for an extended period of time. When external forces are
removed, the material’s deformation recovers quickly but the color fades away
3
5–37
slowly (Scheme 1A).
We posited that this slow color fading is a molecular kinetic
phenomenon that is intrinsic to the mechanophore. We further hypothesized that
the behavior is due to a double-bond isomerization bottleneck involving the vinyl-
ene bridge during the SP to MC transformation and its subsequent reversion to
SP. Our hypothesis is suggested by studies of the dynamics of the forward and back-
ward reactions. The thermal cis/trans isomerization after the C–O pyran bond
cleavage is a process that proceeds on the ms to ms range of lifetime. In contrast,
the lifetime of the ring-closing process from MC to SP is more than tens of sec-
3
8,39
onds.
pressed within polymeric matrices. Recently, supramolecular mechanophores
Additionally, the isomerization kinetics of photochromes is normally sup-
4
0
4
1–43
were developed to address some of these limitations.
Here, we tested our hy-
pothesis using the [1,3]oxazine (OX) motif as a constitutional variation of the SP
mechanophore.
We first conceived the idea of the putative new mechanophore from OX, given that it
is a previously known photochromic and halochromic switch (Scheme 1B). Unlike SP
and NP, OX undergoes a purely ring-opening reaction with no double-bond isom-
4
4,45
erization involved upon irradiation or protonation.
The colored zwitterionic
(
ZI) species thermally reverts back within the ns to ms range, which is orders of magni-
4
6,47
tude faster than the MC/SP transformation.
We then synthesized three OX
regioisomers, investigated their mechanochemical responsiveness in bulk polydi-
methylsiloxane (PDMS), and compared their in situ mechanical response with that
of SP and NP mechanophores during loading and unloading cycles. Finally, we ratio-
nalized the regioisomeric mechanoresponsiveness and rapid mechanochromism of
OX mechanophores using density functional theory (DFT) calculations and a mech-
anochemical coupling analysis.
1Beckman Institute for Advanced Science and
Technology, Urbana, IL, USA
RESULTS AND DISCUSSION
2Department of Chemistry, Urbana, IL, USA
Design and synthesis of OX regioisomers
3Department of Materials Science and
Engineering, University of Illinois at
Urbana-Champaign, Urbana, IL, USA
Prior to the synthesis of OX regioisomers, CoGEF (constrained geometries simulate
4
8
external force) simulations were performed to predict the mechanochemical reac-
tivity of the OX core with target substitutions on the indole ring (Figure 1; Table S3).
Simulations consisted of a stepwise elongation of the distance between two methyl
carbons (the pulling points) on terminal groups from a zero-force equilibrium
geometry, while monitoring total energies of optimized and constrained geometries
4Lead contact
*Correspondence: n-sottos@illinois.edu (N.R.S.),
jsmoore@illinois.edu (J.S.M.)
https://doi.org/10.1016/j.chempr.2021.02.014
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Scheme 1. Molecular engineering for fast mechanochromism
(
A) Colorless spiropyran (SP) and naphthopyran (NP) isomerize into blue and orange merocyanines
under mechanical force, respectively. The scale bar, 2 mm.
B) Postulated mechanochemical transformation of a photochromic and halochromic oxazine (OX)
(
core into a colored zwitterionic isomer.
until bond rupture occurred. The maximum slope in a plot of energy versus extension
over the entire elongation process represents the rupture force (Fmax) of a cleaved
4
9
bond. Interestingly, simulations predict that the OX regioisomer substituted at
5
0
the 4-position undergoes an OX CÀO bond cleavage and becomes the ZI species.
An estimated Fmax of 3.7 nN was found, a value that is close to those of SP (4.5 nN)
1
0,37
and NP (4.0 nN) mechanophores.
Although the 5-substituted OX regioisomer
demonstrated a similar bond cleavage, to achieve this a longer displacement and
a greater Fmax (4.2 nN) are required. In contrast, the OX regioisomer substituted
at the 6-position exhibited a homolytic cleavage of the acetyl C–C(O) bond with
the highest Fmax value at 5.9 nN, suggesting that this regioisomer is possibly non-
responsive to tensile forces.
Having computational results as benchmarks, we synthesized OX regioisomers teth-
ered with terminal alkenes for network incorporation (Schemes 2A and 2B, See de-
tails in the supplemental information). Retrosynthetic dissociations of the target
OX regioisomers suggest the OX Precursors and p-dimethylaminobenzaldehyde
seen in Scheme 2A as the required constituents, which are coupled together via
an acid-catalyzed condensation reaction. The OX Precursors were directly prepared
N
by coupling indole and benzyl bromide derivatives via an S 2 substitution, followed
5
1,52
by a deprotonation-induced ring-closing mechanism.
Prior to this coupling re-
action, nitrophenolate and regioisomeric hydroxyindole derivatives were first func-
tionalized with terminal olefins that allow the covalent incorporation of OX re-
3
5
gioisomers into PDMS networks.
The ring-opening behavior of the three OX regioisomers (i.e., OX-1, OX-2, and
OX-3) was first evaluated in solution using NMR and UV-vis spectroscopies. The
1
2
H NMR spectrum of OX-1 shows a characteristic –CH N– proton resonance, H8,
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Figure 1. Computational predictions of target oxazine mechanophores
CoGEF calculations for three OX regioisomers were performed at the B3LYP/6–31G* level of
theory. At each elongation step, a constrained geometry optimization was performed. The total
energy and the distance between pulling points (green balls) for the initial equilibrium geometry
˚
were set as 0 kJ/mol and 0 A, respectively. See details in supplemental information. The scissile
bond is indicated with a dotted line, the color of which corresponds to the pull point on the
indole ring.
at d 4.62 ppm (Figure S3A). Upon the addition of trifluoroacetic acid (TFA), these
resonance peaks undergo a large downfield shift to d 5.58 ppm. Concomitantly, pro-
ton resonances on the indole ring, the –CH=CH– vinylene bridge, and the p-N(Me)
2
phenyl group are also shifted downfield (Figure S3B). These shifts suggest the forma-
4
7
tion of a p-extended indolium cation with a more planar geometry. The coupling
constant of the –CH=CH– protons remains almost unchanged before (J = 16.0 Hz)
and after (J = 15.1 Hz) the ring-opening reaction, indicating an exclusive trans
configuration. Similar changes are also observed in both OX-2 and OX-3 species
1
(
Figures S4 and S5). Besides the changes in H NMR spectra, the ring-opening rear-
rangement of OX regioisomers is also accompanied with a significant color change.
Upon the addition of TFA, a colorless solution of OX-1, with an absorption maximum
(lmax) at 307 nm, turns into a purple solution with a new band at lmax = 565 nm (Fig-
ure S2A, see details in the supplemental information). In OX-2 and OX-3, new ab-
sorption bands at lmax = 563 and 566 nm were observed, respectively (Figures
S2B and S2C). Such negligible difference in lmax suggests that varying the substitu-
ent position on the indole ring insignificantly affects the absorption properties of
opened OX regioisomers. Prior to the ring-opening rearrangement, the OX-2 re-
gioisomer exhibits an intrinsically more intense purple color than the other two.
This observation is most likely attributed to the higher percentage of the opened
OX-2 species stabilized by the electron-donating para-substituent on the indole
ring. To further understand the color origin of OX regioisomers, we dissect the
OX structures into two fragments: the indolium (IN) chromophores (i.e., IN-1,
IN-2, and IN-3) and a p-nitrophenolate derivative (See synthesis in the supplemental
information). The former shows lmax at 546–548 nm, resembling the lmax of proton-
ated OX regioisomers, while the latter only has a lmax at 339 nm (Figure S2). These
results suggest the IN moieties are the dominant color-inducing source for OX ring-
opening products. From a design standpoint, this observation offers a practically
useful way to modulate the optical properties of OX derivatives without significantly
altering the mechanochemical behavior. By comparison, the color of conjugated MC
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species is determined by the entire molecular structure rather than any partial moi-
ety. Changes in MC geometry under varying forces are far more complicated when
3
5
involving a multi-color transition that makes it less ideal as a molecular probe.
Mechanoresponsiveness of OX regioisomers in bulk materials
We prepared dogbone-shaped PDMS films incorporating either one of the three OX
regioisomers or the control compound (Figure S6). Three OX regioisomers difunc-
tionalized with terminal olefins were incorporated as crosslinkers (0.2 wt %) into
PDMS networks via Pt-catalyzed hydrosilylation (Scheme 2C). This reaction is
completely selective for the terminal olefin (control experiments validated that the
central OX double-bond linkage remains intact when terminal vinyl groups are fully
consumed under hydrosilylation conditions (Figure S1)). A control specimen incor-
porating the OX-1 Control with a single olefin was also prepared. These OX-cross-
5
3
linked PDMS specimens are transparent but exhibit a slight purple hue. This color
was bleached by suspending the materials in triethylamine vapor for a few seconds
prior to usage (See details in the supplemental information).
We investigated the mechanoresponsiveness of PDMS films incorporating different
OX regioisomers (i.e., OX-1, OX-2, and OX-3 connected at the 4-, 5-, and 6-posi-
tions, respectively) using a setup for simultaneously recording mechanical and
optical measurements (Figure S7). Consistent with CoGEF predictions, extension
of the dogbone-shaped PDMS films incorporating OX-1 mechanophores produced
a purple color change in the gauge region with an absorption enhancement at lmax
=
5
2
68 nm, confirming the predicted mechanochemical transformation (Figures 2A and
E; Scheme 1B). Under the strain rates used in this study, the appearance of the color
change for OX-1 coincided with the loading rate, and no lag in color appearance was
noticed. When tensile forces were removed, the purple color faded in less than a sec-
ond. This process was repeated multiple times (up to 10 cycles) without noticeable
color fatigue (Figures 2M and 2N; Video S1). For OX-2, the PDMS films also demon-
strate a reversible mechanochemical response (Figures 2B, 2F, S10; Video S2),
consistent with the CoGEF simulation. Additionally, the unloaded OX-2 films are
inherently more purple than the OX-1 ones before deformation (Figures 2E versus
2
F) (as observed in solution phase [vide supra]), correlating to an initially higher
UV absorbance at 0% strain (Figures 2A versus 2B). Based on these observations,
we conclude that OX-1 is a preferred mechanophore design over OX-2. As predicted
by the CoGEF simulation, the OX-3 film did not exhibit a mechanochromic behavior
5
4
(
Figures 2C and 2G; Video S3), but showed a deep purple color change after its
suspension in TFA vapors (Figure 2K). Color generation by TFA vapor confirms the
presence of a halochromic, albeit mechanochemically inactive, OX regioisomer.
The specimens incorporating OX-1 Control compounds showed no color change af-
ter deformation (Figures 2D, 2H, and 2L; Video S4), confirming that force transduc-
tion across the molecule is necessary for successful mechanochemical activation.
Mechanochemical relaxation of OX mechanophores was evaluated in PDMS mate-
rials by in situ monitoring the absorption change of the specimens during stress-
relaxation experiments loaded to a constant strain. Interestingly, maintaining the
OX-1 specimens under different tensile strains (e = 100%, 150%, and 200%) leads
to absorption (lmax = 568 nm) decays, rather than an enhancement previously
3
5–37
observed in a SP mechanophore (Figures 2O and S13).
The higher tensile stress
(
larger uniaxial deformation), the steeper the initial decay, which mirrors the stress-
relaxation curves (Figure 2O). Specifically, power-law fittings (Equation S3) of stress
relaxation and corresponding absorption decay curves are in good agreement with
5
5,56
each other (Figure S13 for OX-1 and S14 for OX-2, Table S2),
suggesting a close
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Scheme 2. Covalent incorporation of mechanophores into a polymeric network
(
(
(
(
A) Retrosynthesis of oxazine scaffold.
B) Chemical structures of oxazine regioisomers (OX-1, OX-2, and OX-3) and reference compounds
OX-1 Control, SP, and NP).
C) Schematic representation of incorporating vinyl-terminated constitutes (0.2 wt % for OX and SP,
1
.5 wt % for NP) into dogbone-shaped PDMS polymer networks via platinum-catalyzed
hydrosilylation. The scale bar, 2 mm.
relationship between macroscopic stresses exerted on mechanophores and their
molecular ring-closing relaxation. These results highlight the potential utility of
OX mechanophores to in situ monitor polymer mechanics at the molecular scale.
Comparison of OX with SP and NP mechanophores in in situ mechanochemical
response
To quantify the in situ mechanochemical response, we monitored the changes in
red-green-blue (RGB) channel intensities under tensile strain (Figure S9). Ratios of
channel intensities (e.g., R/G, B/G, and R/B) were plotted as a function of strain
change and the B/G channel ratio was selected as the output response for compar-
ison between mechanophores (Figure 3A for OX-1, Figure S10A for OX-2, Fig-
ure S12A for SP, and Figure S12B for NP). In OX mechanophores, the B/G ratio
increased when the strain was accumulated from 0% to 200%, and then decreased
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Figure 2. Mechanoresponsiveness of OX regioisomers in PDMS specimens
(
A–L) UV-vis absorption spectra and corresponding optical images (scale bar, 1 mm) of dogbone-shaped PDMS specimens incorporating (A and E)
OX-1, (B and F) OX-2, (C and G) OX-3, and (D and H) OX-1 Control before (A–D, black dash line) and after (A–D, red solid line) tensile load (strain (e) =
00%). The absorbance at 650 nm (A650) under the e = 0% is normalized to zero; pH-induced reversible color change of dogbone-shaped PDMS
specimens incorporating (I) OX-1, (J) OX-2, (K) OX-3, and (L) OX-1 Control.
2
À1
À1
(
M and N) (M) Loading (0.012 s ) and unloading (0.525 s ) stress-strain cycles for the PDMS specimens incorporating OX-1 mechanophores were
recorded between 0% and 200% strains, and (N) the absorbance change at lmax = 568 nm was monitored for up to 10 cycles.
O) Stress relaxation (lines) under different tensile strains (e = 100%, 150%, and 200%) and corresponding UV absorption decay (dots) of the OX-1-based
(
PDMS specimens were collected as a function of time. The change in the absorbance at lmax = 568 nm was recorded every 5 min, and then normalized to
the absorbance recorded at 0 min.
once released. In great contrast, the SP and NP mechanophores displayed no signif-
5
7
icant enhancement in channel ratios during the first cycle. When SP and NP spec-
imens were maintained at 200% strain for a period of time, channel ratios gradually
5
8
changed, indicating slow responses of SP and NP mechanophores. Even at varying
strain rates, the OX-1 mechanophore exhibited nearly identical mechanochemical
responses (Figure S11). The threshold activation strain of the OX-1 was determined
to be ca. 90%, which was smaller than the ca. 125% observed for the OX-2
(
Figure 3B). This difference in onset activation strain of two OX mechanophores is
5
9,60
attributed to their intrinsic difference in color at 0% strain
and mechanorespon-
siveness (vide infra).
We then compared OX with SP and NP mechanophores with respect to their mech-
anochemical responsiveness and reversibility (Figure 3C). During continuous
loading-unloading cycles (up to eight cycles were tried), both OX-1 and OX-2 me-
chanophores demonstrated almost instantaneous and reversible mechanochemical
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Figure 3. In situ mechanochemical response of OX mechanophores in PDMS specimens
(
A) In situ monitoring the R/G, B/G, and R/B channel ratios (dash lines) of the specimens
incorporating OX-1 mechanophores in one loading and unloading cycle (e: 0%/200%/0%), and
the representative images (blue dash circles) are shown. The B/G ratio provides a continuous
enhancement when the strain is changed from 0% to 200%; therefore, this ratio is selected as a
common output for result comparison and analysis.
(
(
B) Relative changes in the B/G intensity ratio of OX-1 and OX-2 mechanophores, where D(B/G) =
B/G) À (B/G) , and (B/G) is the value at 0% strain. The error bands for channel ratios (in A and B) are
0
0
estimated based on the standard deviation of the average of three measurements.
C) In situ monitoring the B/G ratio change (solid lines) of PDMS specimens incorporating various
(
mechanophores (i.e., OX-1, OX-2, SP, and NP) over eight loading-unloading cycles, and the time-
dependent mechanical strain change (dash line). The higher B/G ratios observed in the OX-2
specimens (red line) at 0% strain are attributed to the inherently more purple color of the OX-2 than
the OX-1 mechanophore before deformation. Linear regression of the B/G ratio as a function of
cycles represents a gradual accumulation of MC species; the error bands represent 95%
confidence; the slope for SP specimens is positive, while the slope for NP specimens is negative. In
À1
loading and unloading cycles the strain rate is maintained at 0.206 s , unless otherwise noted.
responses with no phase lag or response fatigue observed. In contrast, the slow
mechanochemical responses of both SP and NP mechanophores resulted in only mi-
nor cumulative changes in the B/G ratio after multiple loading-unloading cycles
(
Videos S5 and S6 for SP and NP, respectively). This observation suggests that color-
ation of the MC species accumulates gradually, and color-induced change persists
on the timescale of the loading frequency.
Rationale of mechanoresponsiveness and rapid mechanochromism of OX
mechanophores
Following the work reported by Craig and co-workers, we evaluated the regioiso-
meric mechanoresponsiveness of OX mechanophores by mechanochemical
1
2,36
coupling analysis.
This method reveals force-coupled geometry changes, high-
lighting the relationship between force and ring-opening equilibrium. Tensile forces
exerted on terminal methyl carbons of OX regioisomers drive their thermodynamic
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Figure 4. Rationale of regioisomeric and rapid mechanochromism of oxazines
(
A) The force-free end-to-end contour length change (DL = L
regioisomer (L ) to corresponding ring-opening ZI product (L
B) DL and Fmax comparison between OX regioisomers.
C) The full range of CoGEF simulations for OX (purple), SP (blue), and NP (orange) scaffolds with two methoxy carbon pulling points were compared at
z
À L
o
) between two methyl carbon pulling points (green balls) is calculated from each OX
o
z
). For detailed calculations, see Figures S16–S18 in the supplemental information.
(
(
the B3LYP/6–31G* level of theory. Steps I and II represent force-induced ring-opening transformation and cis/trans isomerization, respectively, and
corresponding Fmax for both steps are calculated. In all three cases, the step I is the ring-opening transformation, followed by a cis/trans isomerization
as the step II only shown in SP and NP scaffolds. Protons are omitted for clarity.
6
1
equilibria toward ZI isomers (Figure 4A). Calculating the force-free distance with
CoGEF between terminal loading points in both OX (L ) and ZI (L ) isomers leads
to an end-to-end contour length change (DL = L ). The DL of the OX regioisomer
À L
substituted at 4-position was estimated at 2.21 A, which is larger than that of other
o
z
z
o
˚
˚
OX regioisomers substituted at the 5- and 6-positions (1.56 and 0.47 A, respectively)
(
Figure 4B). According to the relationship between the equilibrium constant (K) of a
6
1
reversible reaction and the external force (F), d ln K=dF = DL=kBT, the larger the
DL, the lower the required force is for detectable mechanochromism. This rationale
is supported by the facts that (1) the OX-1 has a lower Fmax and onset strain than the
OX-2 mechanophore (Figures 3B and 4B); (2) the OX-3 regioisomer shows no mecha-
nochromism, exhibiting the lowest DL (Figures 1, 2C, 2G, and 4B); and (3) the
decreasing trend of mechanochemical couplings is supported by the increasing
F
max from OX-1 to OX-3 regioisomers (Figure 4B).
Rapid mechanochromism of OX mechanophores was compared with that of SP and
NP mechanophores in a full range of CoGEF simulation (Figure 4C). For tensile me-
chanochromism of specimens, an incorporated mechanophore was elongated
from a colorless to a colored geometry. Assuming elongation rates for each mecha-
nophore are approximately equal and extremely slow, we employ a full range of iso-
metric CoGEF simulations to evaluate quasi-static isomerization of mechanophores
6
2
and how mechanical responses are influenced. All three mechanophore scaffolds
i.e., OX, SP, and NP) exhibit near equivalent Fmax (I) for the central C–O bond cleav-
age (Figure 4C, step I). However, to reach cleavage displacements, SP and NP
(
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scaffolds are stretched nearly thrice as far as the OX one. After immediate cleavage, a
planar IN chromophore with an intense color emerges instantaneously from the OX
scaffold. For SP and NP scaffolds, distorted MC species with variable absorptivities
3
8,39
35
are generated,
complicating their mechanochromism. To reach relatively sta-
ble trans-MC species, distorted ones are continuously stretched until the double-
bond isomerizes (Figure 4C, step II), which may delay the mechanical response of
SP and NP mechanophores. In summary, a shorter displacement for the cleavage,
a simpler ring-opening process, and the absence of double-bond isomerization after
the ring-opening rearrangement explain why OX mechanophores are more ideal mo-
lecular force probes. For mechanophore deactivation, the rapid ring-closing kinetics
4
6,47
of ZI isomers most likely explains the fast decoloration of PDMS specimens.
Conclusions
In summary, we have demonstrated a new mechanophore scaffold based on the
switchable OX, which exhibits regioisomeric mechanoresponsiveness and rapid me-
chanochromism in PDMS materials. By varying polymer attachment positions on the
indole ring, we systematically tuned mechanochemical reactivity of different OX re-
gioisomers. DFT calculations (CoGEF) predicted and mechanochemical tests vali-
dated the most responsive OX regioisomer. The trend of the mechanochemical
reactivity was further understood by analyzing the force-coupled geometry changes.
In contrast to SP and NP mechanophores, OX displays in situ mechanochromism,
and the optical property changes mirror macroscopic deformation and stress-relax-
ation profiles. We attribute this in situ mechanochromism to the lack of the addi-
tional configurational rearrangement of opened OX mechanophores under external
forces. The emergence of these rapid responsive mechanophores has potential for
in situ monitoring of polymer mechanics. The structure-reactivity relationships for
OX mechanophores reiterate molecular engineering as a tool to facilitate the design
of molecular force probes and novel stimuli-responsive materials. Future research
will focus on the development of OX-based multi-color mechanophores and their
combined mechanochromism in polymeric materials.
EXPERIMENTAL PROCEDURES
Resource availability
Lead contact
Further information and requests for additional details should be directed to and will
be fulfilled by the Lead Contact, Jeffrey S. Moore (jsmoore@illinois.edu).
Materials availability
This study did not generate new unique reagents.
Data and code availability
The published article includes all datasets generated or analyzed during this study
SUPPLEMENTAL INFORMATION
Supplemental Information can be found online at https://doi.org/10.1016/j.chempr.
2
021.02.014.
ACKNOWLEDGMENTS
The research was financially supported by the AFOSR Center of Excellence (FA9550-
2
0-1-0194). The authors also thank the Beckman Institute for Advanced Science and
Technology for the facilities and support to conduct this research. H.Q. and D.G.I.
would like to thank Dr. Tae Ann Kim for the remote assistance of setting up
Chem 7, 1080–1091, April 8, 2021 1089

ll
Article
mechanical testing instrument. H.Q. gratefully acknowledges Dr. Yun Liu for compu-
tational discussion.
AUTHOR CONTRIBUTIONS
H.Q. conceived the research; H.Q., N.S.P., and A.J.H. performed synthesis; H.Q.
and N.S.P. performed solution-phase studies and prepared the PDMS films; H.Q.,
N.S.P., and D.G.I. performed mechanochemical testings; H.Q. performed computa-
tional studies; H.Q. wrote the original draft; H.Q., N.S.P., D.G.I., A.J.H., N.R.S., and
J.S.M. reviewed and edited the paper until the final version. N.R.S. and J.S.M. pro-
vided guidance during all stages of the project.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Received: November 9, 2020
Revised: January 26, 2021
Accepted: February 11, 2021
Published: March 11, 2021
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