"Flex-activated" mechanophores: Using polymer mechanochemistry to direct bond bending activation

Article abstract of DOI:10.1021/ja403757p

We describe studies in mechanochemical transduction that probe the activation of bonds orthogonal to an elongated polymer main chain. Compression of mechanophore-cross-linked materials resulted in the release of small molecules via cleavage of covalent bonds that were not integral components of the elongated polymer segments. The reactivity is proposed to arise from the distribution of force through the cross-linking units of the polymer network and subsequent bond bending motions that are consistent with the geometric changes in the overall reaction. This departure from contemporary polymer mechanochemistry, in which activation is achieved primarily by force-induced bond elongation, is a first step toward mechanophores capable of releasing side-chain functionalities without inherently compromising the overall macromolecular architecture.

Full text of DOI:10.1021/ja403757p

Communication
pubs.acs.org/JACS
“Flex-Activated” Mechanophores: Using Polymer Mechanochemistry
To Direct Bond Bending Activation
Michael B. Larsen and Andrew J. Boydston*
Department of Chemistry, University of Washington, Seattle, Washington 98195, United States
S
* Supporting Information
ABSTRACT: We describe studies in mechanochemical
transduction that probe the activation of bonds orthogonal
to an elongated polymer main chain. Compression of
mechanophore-cross-linked materials resulted in the
release of small molecules via cleavage of covalent bonds
that were not integral components of the elongated
polymer segments. The reactivity is proposed to arise from
the distribution of force through the cross-linking units of
the polymer network and subsequent bond bending
motions that are consistent with the geometric changes
in the overall reaction. This departure from contemporary
polymer mechanochemistry, in which activation is
achieved primarily by force-induced bond elongation, is a
first step toward mechanophores capable of releasing side-
chain functionalities without inherently compromising the
overall macromolecular architecture.
Figure 1. Generalized examples of moieties capable of mechanochem-
ical activation, with the scissile bond(s) highlighted in red. R = site of
polymer attachment; X = F, Cl.
he study and control of mechanochemical transduction in
cycloaddition,9−11 and electrocyclic ring opening of spiropyran
Tmacromolecular systems (i.e., polymer mechanochemistry)
chromophores.12 Collectively, the assortment of demonstrated
holds promise for addressing grand challenges in areas such as
drug delivery, sensory materials, and autonomous self-healing
mechanochemical reactions accessible via polymer elongation
systems and may also provide insights into how biological
spans a range of organic, organometallic, and inorganic
transformations.
systems use physical impetuses to trigger chemical responses.1
Precise control over the distribution of forces at the molecular
level can be achieved through the development of polymeric
materials capable of channeling elongational forces to
mechanophores (i.e., functional groups that are designed to
undergo selective bond scission in response to an external force).
While ubiquitous in the natural world, synthetic analogues
capable of this type of stimulus−response mechanism have only
recently been developed. Within the past decade, investigations
of the effects of mechanical stress upon polymeric materials have
provided macromolecules capable of undergoing well-defined
chemical changes in response to the application of mechanical
force (Figure 1). By the introduction of a mechanophore at a
specific point along the polymer chain, the application of stress to
the polymer as a whole can be coupled to reactivity at a single site.
Early efforts in mechanochemical control and design demon-
strated the selective homolytic scission of weak covalent bonds2
and site specificity.3 Dative metal−ligand bonds have also been
shown to be mechanochemically sensitive, giving rise to force-
activated catalysts.4 Additionally, ring-opening and cyclo-
reversion reactions have provided exciting breakthroughs in
force-guided reactivity, mechanochromics, and potential self-
healing or -reinforcing materials. Key examples include opening
of strained three- and four-membered rings,5−8 formal retro-
A unifying theme in mechanophore designs aimed at bond
scission remains an intuitive approach in which the bonds to be
broken are integral components of the polymer main chains and
thus are elongated in accordance with the general force vectors
being applied to the flanking polymer segments. An exciting
possibility would be the use of polymer scaffolds to control
mechanochemical activation of bonds that are neither
components of the main chain nor directly elongated by the
tensile force within the polymer backbone.13 This mode of
reactivity could enable the release of small molecules from side
chains while preserving the overall macromolecular structure and
also provide new fundamental knowledge on how mechanical
force can be coupled with chemical potential.
To investigate this idea, we considered the effects of bond
angle distortions in modulating chemical reactivity. Geometric
distortions can greatly influence the reactivity and ground-state
hybridization, as observed in contemporary approaches toward
Cu-free azide−alkyne cycloaddition and more traditional
variations in, for example, carbonyl stretching frequencies in
cyclic ketones with various ring sizes.14 Mechanical activation of
Received: April 18, 2013
© XXXX American Chemical Society
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isolated small organic and inorganic molecules, metals and
metalloids, and molecular dopants within polymer matrices has
been intensely studied. In many instances, activation by shearing
can occur through bond bending motions that augment ground-
state geometries and lower HOMO−LUMO energy gaps.1g,15,16
Recently, application of pressure to a polymer matrix doped with
small-molecule mechanophores was found to catalyze mecha-
nochemical isomerization. In this system, as opposed to ground-
state destabilization, a negative activation volume for the reaction
led to an overall lowering of the activation energy with increasing
pressure.17 In contrast, polymer mechanochemistry utilizes the
macromolecular scaffold to direct force vectors to a covalently
attached mechanophore in a precise manner. However, the use of
this approach to accomplish activation primarily through
transient bond angle distortions has not been fully investigated.
Application of stress causes a combination of conformational
changes as a polymer chain is elongated, including both bond
stretching and bending. In most cases, changes in bond angles
require less energy than bond stretching and thus may provide an
overall more efficient means of energy transduction. We
envisioned that “flex activation” could occur in reactions in
which the structural changes are consistent with the linearization
that occurs during polymer elongation. An example of such
reactivity would be cycloreversion reactions that convert main-
chain alkene moieties into alkynes (Figure 2). Notably, although
Figure 3. Calculated potential energies resulting from incremental
increases in the angle θ. Density functional theory calculations were
performed at the B3LYP 6-31G*(d) level using the Gaussian 09
program package.20
cycloreversion corresponded to an estimated activation energy
(Ea) of 35 kcal/mol for the mechanochemical reaction.
Importantly, this Ea value is well within the established range
of mechanochemically accessible pathways.
Encouraged by the computational results, we prepared two
types of cross-linked networks, each containing oxanorborna-
diene mechanophores (Scheme 1): in one, the mechanophore
Scheme 1. Synthesis of the Network with Mechanophore
Cross-Linking Units (4-CL) and the Control Network with
Adsorbed Mechanophore Units (4-ads)
Figure 2. Generalized depiction of mechanophore activation via bond
“flexing” motions induced by application of force.
the internuclear distance of the vinylic atoms would be
lengthened in the overall transformation, the covalent bonds in
the mechanophore that are located along the polymer main chain
would actually become shorter and stronger. Herein we describe
the results of our investigations into this new manifold for
polymer mechanochemistry.
We considered oxanorbornadienes to be promising candidates
to test our hypothesis that “flex activation” can be used in force-
guided reactions. To model the effect of force upon the
oxonorbornadiene architecture, we employed a modified version
of the constrained geometries simulate external force (CoGEF)
method developed by Beyer and recently demonstrated to be in
good agreement with empirical reactivities of mechanophor-
es.6a,9c,18 Briefly, this method entails incremental distortions of
the molecule along a specified coordinate, which upon relaxation
of the rest of the molecule models the effects of mechanical force.
As a simplified version of our experimental mechanophore, we
applied this method to the oxanorbornadiene Diels−Alder
adduct of furan and dimethyl acetylenedicarboxylate (DMAD).
To mimic linearization of the ene−diester moiety, the angle θ
indicated in Figure 3 was incrementally increased from its value
in the ground-state geometry.19 As can be seen in Figure 3, the
expected increase in the calculated potential energy of the
mechanophore was observed until the point at which cyclo-
reversion occurred spontaneously. The value of ΔE just prior to
was used as a cross-linking unit that would experience extensional
force upon application of stress; in the other, the mechanophore
was adsorbed into a cross-linked material. Diol 1 was prepared
from acetylenedicarboxylic acid and 1,6-hexanediol via Fischer
esterification. Benzyl furfuryl ether (2) was chosen as the diene in
place of furan to avoid issues of volatility with the latter. Diol 1
and furan 2 reacted smoothly via [4 + 2] cycloaddition to provide
the corresponding oxanorbornadiene (not shown) in moderate
yield. Subsequent reaction with methacryloyl anhydride
furnished difunctionalized cross-linker mechanophore 3. The
cross-linked network 4-CL, in which the mechanophore serves as
the cross-linking unit, was prepared according to a procedure
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Communication
previously reported by Moore and co-workers.7 For comparison,
we also prepared mechanophore 5, which is incapable of
functioning as a cross-linking unit during acrylate polymer-
ization. For this control system, 1,6-hexanediol dimethacrylate
(6) was used as a cross-linker, ultimately providing a material in
which the oxanorbornadiene mechanophore was adsorbed into
the material but not covalently attached (4-ads). Copolymeriza-
tion of a monoacrylate variant of 3 and methyl acrylate in the
presence of benzoyl peroxide (BPO) and N,N-dimethylaniline
confirmed the stability of the mechanophore under the
polymerization conditions (see the Supporting Information).
After polymerization and cross-linking had ensued, each
network was soaked in CH2Cl2 or MeOH for 2-h cycles to
remove unincorporated small molecules. Multiple soak cycles
were conducted until no additional small molecules were
detected in the solution, as judged by GC−MS. The amounts
of 3, 5, and 6 in the combined soak solutions were quantified and
used to infer the amounts of these species that were incorporated
into the cross-linked networks. By adjusting the feed ratios of the
reactants, we prepared samples of 4-CL with estimated
mechanophore/cross-linker 3 contents of ca. 5 and 14 mol %.
Similarly, samples of 4-ads were prepared and determined to
contain 17 mol % mechanophore 5 and 19 mol % cross-linker 6; a
4-ads network with lower mechanophore and cross-linker
contents (7 and 11 mol %, respectively) was also prepared.
To evaluate the mechanochemical reactivity of each network,
we conducted compression experiments on each sample at
different pressures. Samples were loaded into a Carver press and
subjected to sustained pressures as indicated in Figure 4. After 30
mechanophore 3, greater activation was observed from the
network having a greater density of 3. These results support a
nonthermal activation mechanism, since thermal effects would
be expected to influence the reactivity to the same extent in the
two different variants of 4-CL. Additionally, compression of 4-
CL for 1 min at 600 MPa gave essentially the same % activation
(3.0%) as compression for 30 min (3.3%), consistent with
mechanical activation mechanisms.6c Importantly, compression
and analysis of each 4-ads sample resulted in little or no
activation at each pressure, further supporting the mechano-
chemical origins of the cycloreversion reaction. These results
suggested to us that the released amounts of 2 detected in the
compression experiments could not be attributed to thermal or
pressure-induced activation.
Additional support for the proposed origin of 2 was obtained
via confocal Raman spectroscopy (Figure 5). The spectra of
Figure 4. Plots of mechanophore % activation as a function of applied
pressure, as judged by GC−MS analysis of soak solutions after
●
compression of 4-CL with 14 mol % 3 (black ), 4-CL with 5 mol %
○
3 (black ), 4-ads with 17 mol % 5 and 19 mol % 6 (red ×), and 4-ads
□
with 7 mol % 5 and 11 mol % 6 (red ). Each data point is an average of
two independent compression experiments.
Figure 5. Raman spectra of (top to bottom) control mechanophore 5
and cross-linked PMA absent any mechanophore; network 4-ads (17
mol % 5) before and after compression at 1200 MPa for 30 min; 4-CL (5
mol % 3) before and after compression at 1200 MPa for 30 min; and 4-
CL (14 mol % 3) before and after compression at 1200 MPa for 30 min.
The spectra were recorded on highly ordered pyrolytic graphite with λex
= 785 nm.
min of sustained stress, the sample was placed in CH2Cl2 to
facilitate diffusion of released small molecules. The CH2Cl2
solutions were then analyzed by GC−MS and NMR spectros-
copy. The GC−MS method was optimized to ensure that
analysis of solutions containing 3 and 5 would not result in false-
positive detection of 2. Without applied stress, no furan was
observed in the soak solution, indicating to us that no
background amount of furan was released as a result of, for
example, mechanochemical activation upon swelling or
inadvertent physical adsorption during synthesis. Over the
applied pressure range from 0 to 1200 MPa, we observed a
monotonic increase in the % activation of the cross-linked
mechanophore for both samples of 4-CL. While the same trend
was observed for 4-CL containing 5 and 14 mol %
control mechanophore 5 and poly(methyl acrylate) (PMA)
cross-linked via incorporation of 6 without any mechanophore
are shown in the top panel for reference. Prior to compression,
the Raman spectrum of each 4-CL sample showed only signals
consistent with the mechanophore and the polymer network.
After compression at 1200 MPa, each sample of 4-CL displayed a
new band at ca. 2250 cm−1, consistent with known stretching
frequencies of acetylenedicarboxylates. This indicated to us that
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Journal of the American Chemical Society
Communication
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Sottos, N. R.; White, S. R.; Braun, P. V.; Moore, J. S. J. Am. Chem. Soc.
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(8) For examples of electrocyclic ring opening of benzocyclobutene,
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cycloreversion with concomitant alkyne formation was the likely
origin of 2, consistent with the computational predictions and
envisioned flex activation. The Raman spectra of 4-ads before
and after compression at 1200 MPa were essentially indis-
tinguishable, and no alkyne formation was apparent.
In summary, we have demonstrated a fundamentally unique
mechanochemical transduction process in mechanophores that
undergo scission along bonds that are not components of the
elongated polymer main chain, resulting in a net strengthening of
the bonds in the polymer backbone. A unique aspect of the
design is the use of the macromolecular scaffold to direct
activation by means of bond bending induced by mechanical
stress on the material. This “flex activation” method has been
supported through experimental and computational studies. An
exciting feature of these materials is their ability to undergo
mechanochemical transduction to release small molecules
capable of diffusing out of the polymer matrix. We anticipate
that the successful development of flex-activated mechanophores
will open a new avenue for the investigation of materials that
respond to physical stimulus, both from the standpoint of
mechanophore design and in the incorporation of these
structures in advanced functional materials.
ASSOCIATED CONTENT
■
S
* Supporting Information
Detailed experimental procedures, characterization of all new
compounds, and complete ref 20. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
boydston@chem.washington.edu
(12) (a) 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. (b) Davis, D. A.;
Hamilton, A.; Yang, J.; Cremar, L. D.; Van Gough, D.; 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.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(13) Boulatov, R. Pure Appl. Chem. 2011, 83, 25.
We thank the University of Washington, the University of
Washington Royalty Research Fund, and the Army Research
Office Young Investigator Program (Grant W911NF-11-1-0289)
for financial support and Professor Xiaosong Li and Joseph May
for assistance with the CoGEF calculations.
(14) (a) Sletten, E. M.; Bertozzi, C. R. Acc. Chem. Res. 2011, 44, 666.
(b) Hall, H. K., Jr.; Zbinden, R. J. Am. Chem. Soc. 1958, 80, 6428.
(15) (a) Gilman, J. J. Mater. Res. Soc. Symp. Proc. 2004, 800, AA7.6.1.
(b) Gilman, J. J. Science 1996, 274, 65.
(16) For a discussion of shock-driven changes in electronic structure
that are manifested in mechanochemical reactions, see: Luty, T.; Ordon,
P.; Eckhardt, C. J. J. Chem. Phys. 2002, 117, 1775.
(17) (a) 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.
Pressure-induced mechanochromism has been demonstrated in
spiropyrans and bianthrones, in which the smaller volume of the
colored (product) form leads to pressure-induced changes in
thermodynamic equilibria. See: (b) Wilson, D. G.; Drickamer, H. G. J.
Chem. Phys. 1975, 63, 3649. (c) Fanselow, D. L.; Drickamer, H. G. J.
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