Substituent Effects and Mechanism in a Mechanochemical Reaction

Article abstract of DOI:10.1021/jacs.8b09263

We report the effect of substituents on the force-induced reactivity of a spiropyran mechanophore. Using single molecule force spectroscopy, force-rate behavior was determined for a series of spiropyran derivatives substituted with H, Br, or NO₂

Full text of DOI:10.1021/jacs.8b09263

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Meredith Hyatt Barbee,
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Tatiana B. Kouznetsova,
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Scott L. Barrett, Gregory R.
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Kumar Rastogi, William J.
Brittain, and Stephen L. Craig
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Page J1ooufr1n1al of the American Chemical Society
3
2
force
R
coupled
1
N
O
1
0
R
N
O
rates
SP
MC
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1.0
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Hammett Analysis

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O
N
O
O
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O
O
O
O
O
Grubbs II
m
O
O
1, R=H
2, R=Br
3, R=NO2
P1, R=H
P2, R=Br
P3, R=NO2
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P1
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f* ~ 410 ± 17 pN
f* ~ 360 ± 25 pN
f* ~ 240 ± 14 pN
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Substituent effects and mechanism in a mechanochemical reaction
†
†
x
†
†
Meredith H. Barbee
, Tatiana Kouznetsova , Scott L. Barrett , Gregory R. Gossweiler , Yangju Lin ,
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†
Shiva K. Rastogi , William J. Brittain , and Stephen L. Craig*
†
Department of Chemistry, Duke University, Durham, NC 27708
x
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666
Supporting Information Placeholder
ABSTRACT: We report the effect of substituents on the
force-induced reactivity of a spiropyran mechanophore.
Using single molecule force spectroscopy, force-rate
behavior was determined for a series of spiropyran de-
rivatives substituted with H, Br, or NO2 para to the
breaking spirocyclic C-O bond. The force required to
achieve the rate constants of ~ 10 s-1 necessary to ob-
serve transitions in the force spectroscopy experiments
depends on the substituent, with the more electron with-
drawing substituent requiring less force. Rate constants
at 375 pN were determined for all three derivatives, and
the force-coupled rate dependence on substituent identi-
ty is well explained by a Hammett linear free energy
relationship with a value of ; = 2.9, consistent with a
highly polar transition state with heterolytic, dissociative
character. The methodology paves the way for further
Figure 1. (A) Multi-mechanophore polymers with substitu-
tions as indicated by R synthesized for this study. (B) A
schematic of the single molecule force spectroscopy
(SMFS) experiment and ring-opening of spiropyran (SP) to
merocyananine (MC).
application of linear free energy relationships and physi-
cal organic methodologies to mechanochemical reac-
tions, and the characterization of new force probes
should enable additional, quantitative studies of force-
coupled molecular behavior in polymeric materials.
The precision with which mechanophores can be predic-
tively designed has increased as quantitative experi-
mental and computational studies have provided insights
into structure-activity relationships.2e For example, it has
been shown that even reactions with very similar force-
free activation barriers can have very different force-
coupled reactivities as a result of the polymer structure
and attachment point through which force is delivered.1c,
10Additional benefits will be realized as these emerging
quantitative relationships are mapped onto existing, intu-
itive physical organic frameworks. Here, we report the
effect of substituent on the tension-driven ring-opening
reaction of the classic mechanophore spiropyran (SP) to
the (longer) merocyanine (MC).11 Single molecule force
spectroscopy is used to quantify force-rate relationships
for three spiropyran derivatives with the same attach-
ment points, and the qualitative and quantitative reactivi-
The potential to use mechanochemistry, either in isolated
polymers or in polymeric materials, to trigger a pro-
grammed, desirable covalent molecular response was
first revealed only a decade or so ago. Since that time,
covalent polymer mechanochemistry1 has undergone a
renaissance in which it has been extensively explored by
a number of research groups and for a variety of purpos-
es, including (but not limited to): biasing and probing
reaction pathways,1b, 2 trapping transition states and in-
termediates,3 catalysis,4 release of small molecules and
protons,5 stress reporting,6 stress strengthening,6d, 7 and
soft materials and devices.8 Increasingly creative mech-
anophore designs and new properties continue to emerge
at an ever-accelerating pace.9
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ty trends are well explained by Hammett linear free en- measurement variation in the contour length of the de-
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ergy relationships.
tected polymer. The nature of the (force-free) SP-to-MC
reaction has been the subject of prior work that suggests
that relative contributions of a less polar electrocyclic
reaction and more polar, heterolytic mechanism depend
on solvent and substituent.16 The nature of the mechano-
chemical reaction has not been previously addressed
experimentally, and the trend in f* (H > Br > NO2) is
consistent with a transition state that is largely heterolyt-
ic and polar in character, as electron withdrawing groups
para to the spirocyclic O atom should stabilize the de-
veloping negative charge separation at that position as
the spirocyclic C-O bond is broken.16
Our approach is described in Figure 1. Multi-
mechanophore polymers of the three SP derivatives were
synthesized through previously established entropy driv-
en ring-opening metathesis co-polymerization.12 Epox-
idized cylcooctadiene is used as a co-monomer for better
adhesion to the cantilever tip.10a Polymers were deposit-
ed in dilute solution of tetrahydrofuran and dried after
drop casting onto a silicon surface. Toluene was placed
onto the surface, then constant velocity (300 nm s-1) sin-
gle molecule force spectroscopy measurements were
conducted to measure force as a function of tip-surface
separation.13
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To confirm that the reaction is under kinetic, not ther-
modynamic control on the timescale of the SMFS exper-
iment,17 we conducted a —retracing“ experiment using
P1, which is the fastest derivative to close back to SP.
The cantilever, with polymer still attached after being
pulled through the SP-to-MC transition, was returned to
just above the surface. The approach curves obtained
showed no evidence of a plateau, and they instead were
fully hysteretic (Figure S14, ESI) with no evidence of
ring closing. Even after waiting 2 s (in comparison to
forward transition time scales of ~0.1 s) at the surface
following re-approach, a second extension of the same
polymer shows only partial recovery of the SP (56%)
under effectively force-free (< 5 pN) conditions. The
back reaction of MC to SP therefore does not need to be
considered when analyzing the chain extension kinetics.
The ring-opening of SP to MC releases stored length,
which results in a characteristic plateau in the force-
distance curves (Figure 2). Following previously pub-
lished procedures,14 the change in contour length of the
polymer is determined by fitting to the extended freely
jointed chain model of polymer elasticity. The experi-
mental results (Table 1) are consistent with extension
ratios based on the polymer‘s mechanophore content and
calculated contour length before and after ring-opening
from SP to the possible MC isomers.13, 15 Similarity in
the contour lengths of the MC isomers precludes an ex-
act assignment of MC geometry (Table S4).
Quantitative kinetic information is extracted from the
force curves of each polymer by fitting the transitions to
the Bell18 and Cusp19 models of force-modified chemical
13-14
reactivity, as done previously.10a,
The force-free
activation energy of each SP derivative is obtained from
its force-free reverse rate constant and equilibrium con-
stant (Tables S6 and S7). The fits give Dxfl, the change
in length of the stretched polymer as an embedded SP
moves from the ground to transition state. The Dxfl val-
ues of the three SPs are effectively indistinguishable,
given the uncertainties associated predominantly with
the force-free equilibrium constants. This homology
between reaction mechanism and force sensitivity is
consistent with accepted models of mechanochemical
coupling1e and is reminiscent of an earlier study of
mechanistically similar ligand displacement reactions.20
Figure 2. Representative SMFS curves for P1-3. The
plateau corresponds to an extension of polymer contour
length upon ring-opening of SP to MC. The transition
force f* is the midpoint of each plateau and is calculated
as an average from multiple force curves collected at a
pulling rate of 300 nm s-1.
A more direct kinetic analysis of the force-coupled reac-
tions is possible without independent characterization of
the force-free pathways, by extracting the rate constant
of the ring-opening reaction as a function of force direct-
ly from the single molecule force curve (Figure 3),
where the inferred force-rate relationship is independent
of the velocity of the SMFS experiment.21 For example,
at a force of 375 pN, rate constants of 9 s-1 and 32 s-1 can
be obtained directly for 1 and 2, respectively (Figures
S20 and S21). In the constant velocity experiments, SP 3
The force-distance curves of all three polymers show
identical extension as a function of SP content, as ex-
pected since each of the substituted monomers have the
same end to end length in the extended MC. Each SP
derivative, however, shows a different critical force f*,
of around 410 pN, 360 pN, and 240 pN for P1, P2, and
P3. Actual rate constant calculations (see below) are not
derived from f*, however, but are based on fits to the
force curves that account for measurement-to-
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has already fully ring-opened by the time the force
reaches 375 pN, and so we extracted rate constant as a
function of force for P3 over a range from 205 to 257
pN, and extrapolated up to 375 pN to get a force-
coupled rate constant of 1600 s-1 (Figure S22).
Page 8 of 11
product MC has a contributing resonance structure that
is a phenoxide, and so it is noteworthy that here is
roughly half the value = 5.3 for phenol acidity in di-
methyl sulfoxide.23 We expect that
for phenol activity
in toluene would be slightly higher, given its calculated
value in a vacuum (
=14.3),23 and estimates based on
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r
r
r
r
solvent descriptors (Q, Z, and ET(30), see Figure S23-25)
range from ~7.3 to ~13.3. This finding is therefore con-
sistent with a transition state that is intermediate to reac-
tant and product phenoxide structure.
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Substituent effects on the spiropyran ring-opening reac-
tion have been well studied,16b, 24 and our measured val-
ue of
r also correlates well to trends in r seen in similar
spiropyran racemization reactions, which also proceed
through a transition state where the C(sp3-O) bond is
cleaving.16a Racemization rates from Swansburg et al.16a
for spiropyrans with the same substituents as in P1-3 in
acetonitrile and 90:10 hexanes/isopropanol give
r = 2.2
and = 1.5. The larger value obtained in our SMFS
r
r
Figure 3. The rate constant as a function of force for P1-
3, extracted directly from multiple single molecule force
curves for each derivative. For P1 and P2, rate constants
at 375 pN can be obtained directly. For P3, the data is fit
to a log-linear regression and extrapolated to 375 pN.
experiments can again largely be attributed to the less
polar medium (toluene) employed, although for force-
free racemizations in cyclohexane,
r is negative over a
large series of compounds, and for the spiropyrans cor-
responding to P1-3 there is weak correlation. The pre-
sent SMFS analysis is limited in that there are only 3 SP
derivatives, and so this study may not fully capture sub-
tle aspects of the structure-property relationships.
Substituent effects on a wide range of conventional,
force-free reactions have been successfully interpreted
through linear free energy relationships. Of these,
Hammett equations are perhaps the most pervasive and
useful.22 The rate constants obtained at 375 pN (k375
)
Beyond the mechanistic insights into the mechanochem-
ical reaction mechanism, the quantitative linear free en-
ergy relationship will guide the choice of spiropyran
derivatives as a function the desired force and time re-
gimes of various material applications. For example, the
quantitative data on this series of spiropyrans, which
have different force-rate behaviors, will allow us to use
them as probes to correlate SMFS and bulk response
(e.g., to quantify the fraction of polymer chains experi-
encing certain forces within polymer networks) as a
function of material composition, including polarity.
Additionally, differences in decoloration rate for these
SPs allow us to select the derivative with a specific ap-
plication in mind. These H- and Br- substituted mech-
anophores have an additional advantage in that the SP
form is not photoactive and has negligible background
color relative to the NO2- analog, which might provide
advantages in some situations. Comparative applications
using these mechanophores will be facilitated by the fact
that for this series of spiropyrans, the attachment points
are held constant, but the intrinsic reactivity is modified
with local substituent effects.
provide an opportunity to apply the Hammett methodol-
ogy to a force-coupled reaction for the first time. As
shown in Figure 4, the Hammett plot of k375 vs. ꢀpara for
these spiropyrans returns a value of
r = 2.9.
375
Figure 4. Hammett plot of log (kR375/ kH
3, where ꢀpara is 0, 0.23, and 0.78.
) vs. ꢀpara for P1-
The small data set of three substituents precludes a de-
tailed evaluation of potentially subtle contributions;
nonetheless, some insights are possible. The positive
slope is consistent with the expected increase in rate as
electron withdrawing substituents stabilize the develop-
ing negative charge on the spirocyclic oxygen.16a The
To the best of our knowledge, this analysis is the first
application of linear free energy relationships to mecha-
nochemical processes. The results of the Hammett anal-
ysis are consistent with a force-coupled reaction mecha-
nism and evolution in electronic structure that is polar in
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Journal of the American Chemical Society
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SMFS curves and fitting. The Supporting Information is
available free of charge on the ACS Publications website.
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AUTHOR INFORMATION
Corresponding Author
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D.; Potisek, S. L.; Ong, M. T.; Braun, P. V.; Martinez, T. J.; White, S. R.;
Moore, J. S.; Sottos, N. R. Force-Induced Activation of Covalent Bonds in
Mechanoresponsive Polymeric Materials. Nature 2009, 459, 68-72; (b)
Chen, Y.; Spiering, A. J. H.; KarthikeyanS; Peters, G. W. M.; Meijer, E.
W.; Sijbesma, R. P. Mechanically Induced Chemiluminescence from
Polymers Incorporating a 1,2-Dioxetane Unit in the Main Chain. Nat.
Chem. 2012, 4, 559-562; (c) Ducrot, E.; Chen, Y.; Bulters, M.; Sijbesma,
R. P.; Creton, C. Toughening Elastomers with Sacrificial Bonds and
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*stephen.craig@duke.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank Will Trautman and Anthony DiLauro for helpful
discussions and Dr. Peter Silinski and Dr. George Dubay
for assistance with mass spectrometry. This work is sup-
ported by the National Science Foundation (CHE-1808518
to S.L.C. and DMR-1205670 to W.J.B). M.H.B. acknowl-
edges fellowship support from DoD (Air Force Office of
Scientific Research, NDSEG Fellowship, 32 CFR 168A).
This work was performed in part at the Duke University
Shared Materials Instrumentation Facility (SMIF), a mem-
ber of the North Carolina Research Triangle Nanotechnolo-
gy Network (RTNN), supported by the National Science
Foundation (Grant ECCS-1542015) as part of the National
Nanotechnology Coordinated Infrastructure (NNCI).
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Tamaoki, N.; Weder, C. Rotaxanes as Mechanochromic Fluorescent Force
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Yajima, H.; Ito, M.; Takahara, A.; Otsuka, H. Mechanochromic Dynamic
Covalent Elastomers: Quantitative Stress Evaluation and Autonomous
Recovery. ACS Macro Letters 2015, 4, 1307-1311.
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a Multi-Mechanophore Benzocyclobutene Polymer. ACS Macro Lett.
2015, 4, 834-837; (b) Zhang, H.; Gao, F.; Cao, X. D.; Li, Y. Q.; Xu, Y. Z.;
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8. (a) Wang, Q.; Gossweiler, G. R.; Craig, S. L.; Zhao, X. Cephalopod-
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for on-Demand Fluorescent Patterning. Nat. Commun. 2014, 5, 4899; (b)
Gossweiler, G. R.; Brown, C. L.; Hewage, G. B.; Sapiro-Gheiler, E.;
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Table 1. Polymer Characterization and Force Curve Fitting
a. Determined from previously published data.13
b. Mole fraction by 1H NMR.
SP contentb Lf/Li (calc) Lf/Li (calc) Lf/Li (obs)
f*
Dxfl (BE), Dxfl
Polymer
(CTC)
(TTT)
nm
(Cusp), nm
1
0.46
0.48
0.45
1.11
1.17
1.15±0.0 410±17
3
0.19±0.0 0.22±0.0
06
009
2
1.11
1.11
1.17
1.13
1.15±0.0 358±25
4
0.22±0.0 0.25±0.0
08 09
3a
1.15±0.0 240±14
2
0.19±0.0 0.21±0.0
12 13
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