A remote stereochemical lever arm effect in polymer mechanochemistry

Article abstract of DOI:10.1021/ja509585g

Molecular mechanisms by which to increase the activity of a mechanophore might provide access to new chemical reactions and enhanced stress-responsive behavior in mechanochemically active polymeric materials. Here, single-molecule force spectroscopy reveals that the force-induced acceleration of the electrocyclic ring opening of gem-dichlorocyclopropanes (gDCC) is sensitive to the stereochemistry of an α-alkene substituent on the gDCC. On the ～0.1 s time scale of the experiment, the force required to open the E-alkene-substituted gDCC was found to be 0.4 nN lower than that required in the corresponding Z-alkene isomer, despite the effectively identical force-free reactivities of the two isomers and the distance between the stereochemical permutation and the scissile bond of the mechanophore. Fitting the experimental data with a cusp model provides force-free activation lengths of 1.67 ± 0.05 and 1.20 ± 0.05 ? for the E and Z isomers, respectively, as compared to 1.65 and 1.24 ? derived from computational modeling.

Full text of DOI:10.1021/ja509585g

Communication
pubs.acs.org/JACS
A Remote Stereochemical Lever Arm Effect in Polymer
Mechanochemistry
Junpeng Wang,† Tatiana B. Kouznetsova,† Zachary S. Kean,† Lin Fan,‡ Brendan D. Mar,‡
Todd J. Martínez,*,‡ and Stephen L. Craig*,†
†Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
‡Department of Chemistry, Stanford University, Stanford, California 94305, United States
S
* Supporting Information
dihalocyclopropanes (gDHCs)17−19 and benzocyclobutene.19
The application of this approach to stereochemical coupling
beyond the mechanophore is shown in Figure 1. The gDCCs
ABSTRACT: Molecular mechanisms by which to in-
crease the activity of a mechanophore might provide access
to new chemical reactions and enhanced stress-responsive
behavior in mechanochemically active polymeric materials.
Here, single-molecule force spectroscopy reveals that the
force-induced acceleration of the electrocyclic ring opening
of gem-dichlorocyclopropanes (gDCC) is sensitive to the
stereochemistry of an α-alkene substituent on the gDCC.
On the ∼0.1 s time scale of the experiment, the force
required to open the E-alkene-substituted gDCC was
found to be 0.4 nN lower than that required in the
corresponding Z-alkene isomer, despite the effectively
identical force-free reactivities of the two isomers and the
distance between the stereochemical permutation and the
scissile bond of the mechanophore. Fitting the exper-
imental data with a cusp model provides force-free
activation lengths of 1.67 0.05 and 1.20 0.05 Å for
the E and Z isomers, respectively, as compared to 1.65 and
1.24 Å derived from computational modeling.
Figure 1. Pictorial representation of the SMFS experiment. The E
(blue) and Z (red) α-alkene stereoisomers open in sequential
transitions at ∼800 and ∼1200 pN, respectively.
ovalent polymer mechanochemistry has provided access
C
to new reactivity and material properties, including
biasing reaction pathways,1 trapping structures that correspond
to force-free transition states,2,3 releasing small molecules4 and
protons,5 activating latent catalysts,6,7 and providing access to
stress-reporting8,9 and stress-strengthening10 materials and
electro-mechano-chemical soft display devices.11 The ability
to tune, and in particular to enhance, the activity of a given
mechanophore1 should be useful in almost all of these contexts.
Here, we show that the remote stereochemistry of coupling
between a cis-substituted gem-dichlorocyclopropane (gDCC)12
mechanophore and the polymer chain that delivers force to the
gDCC has a substantial impact on mechanophore activity,
lowering by >30% (0.4 nN) the force necessary for reactivity on
the 100 ms time scale. The stereochemical influence over
mechanical response occurs without a measurable influence on
the force-free reactivity of the mechanophore, representing a
molecular strategy through which force-free and force-
enhanced reactivity can be decoupled.
are embedded along a polymer backbone via two different
stereochemical attachments (red and blue spheres, Figure 1),
and the sequential opening of the isomers is observed via the
structural transitions that accompany their respective rearrange-
ments. The substrate polymer 4 (Figure 2A) is formed by ring-
opening metathesis polymerization (ROMP)20,21 of co-
monomers of gDCC-bearing cyclooctene 2 and epoxycyclo-
octene 3, in which the epoxides are mechanically inactive in the
force range of interest but increase the attachment force
between the tip of the atomic force microscope (AFM)18 and
the polymer analyte.18 The ROMP yields a mixture of
stereoisomers at the α-alkene substituent on the gDCC.
Polymers are deposited on a surface, and the AFM tip is
brought into contact and then retracted at a velocity of 300
nm/s (see Supporting Information). In all cases where
sufficiently high adhesion forces were obtained, two plateaus22
(plateau forces f* = 780 40 and 1160 60 pN, taken from
Single-molecule force spectroscopy (SMFS) has been used
productively to study covalent mechanochemistry,13−16 and we
have combined SMFS and multi-mechanophore polymers to
quantify the force-accelerated electrocyclic ring-opening
reactivity of a series of mechanophores, such as gem-
Received: September 16, 2014
Published: October 16, 2014
© 2014 American Chemical Society
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Communication
(f* = 1330 pN) observed previously in gDCC polymers that do
not have an α-alkene.18
Similar to the force curves of other multi-mechanophore
embedded polymers,18 the two plateaus are both structurally
and kinetically consistent with the two α-alkene stereoisomers
coupled to the ring opening of gDCC to 2,3-dichloroalkene
products indicated in Figure 1. Structurally, the relative plateau
lengths match those expected based on modeling the
conversion of gDCCs to 2,3-dichloroalkenes. The ratio of E
to Z isomers in 4 obtained after 30 min of ROMP is 1.1:1 (13C
NMR), and computational modeling predicts 4.0% extension
upon ring opening of the E isomer and 2.9% extension in the
case of the Z isomer. In comparison, fits to the experimental
force curves provide extensions of 3.8 0.5% and 2.9 0.3%
for the first and second transition, respectively. Polymerization
of 2 under equilibrium conditions (24 h) yielded polymer 4
with an increased E:Z ratio of 2.3:1.24−26 The plateau forces are
effectively unchanged, but new fractional extensions of 7.3
0.5% and 2.6 0.4% at ∼770 and ∼1160 pN, respectively, vary
with E:Z content as expected (7.5% and 2.3%, respectively,
based on modeling).
The plateau forces are influenced by the actual length of the
trapped polymer subchain, and so the kinetics of the differential
reactivity is quantified by fitting each force curve independently,
using force-free activation energies obtained from thermolysis
experiments (see Supporting Information) and employing the
cusp model27 to describe the force−rate relationship. The cusp
model accounts for changes in the shape of the reaction
potential energy surface as a function of force, including the
position of the transition state, and it has been shown
previously to be well suited for the ring openings of
dihalocyclopropanes.18 Each fit provides a force-free activation
length Δx⧧ that corresponds to the extension along the
polymer backbone that accompanies the change from ground
state to transition state.18 The values of Δx⧧ obtained from the
fits are consistent across multiple samples taken on multiple
days (see Supporting Information), including individual
polymers of different lengths and α-alkene E:Z content (see
Table 1).
As with their fractional extensions, the differential kinetics of
the two transitions can be related back to the α-alkene
stereochemistry. Force-free activation lengths are determined
by modeling the ground and transition state structures
embedded within a polymer under tension applied by imposed
geometric constraints (CoGEF28 calculations), and extrapo-
lated back to zero force (Figure 3). The activation lengths
obtained from the computational modeling for the E- and Z-α-
Figure 2. Synthesis of multi-mechanophore polymer 4 (A).
Representative force curves of 4 with a:b = 1.1:1 (B) and 2.3:1 (C)
obtained by SMFS at a retraction velocity of 300 nm/s. The blue and
red regions of the plateaus are determined by inspection and provided
to guide the eye only. Actual changes in contour length are determined
by fitting the pre- and post-transition regions of the force curves to
extended freely jointed chain models.
the midpoint of the transition23) were observed in the force−
extension curve (Figure 2B,C), in contrast to the single plateau
Table 1. SMFS Data of Polymer 4, Including Plateau Forces, Extensions in Contour Length (Observed and Theoretical), and
Activation Lengths (Obtained from Fitting SMFS Curves and Modeling) for Different Contents of E and Z Isomers
Lf/Li
Δx⧧ (Å)
a
b
c
polymerization time (h)
0.5
mechanophore/α-alkene content
f* (pN)
SMFS
modeling
SMFS
modeling
23% E isomer
21% Z isomer
800 40
1.038 0.005
1.029 0.003
1.040
1.029
1.65 0.03
1.21 0.04
1.65
1.24
1160 50
24
40% E isomer
18% Z isomer
770 40
1.073 0.005
1.026 0.004
1.075
1.023
1.68 0.05
1.20 0.05
1.65
1.24
1160 70
a
b
1
Determined from H NMR and 13C NMR. Ratio of contour length after plateau to that before plateau; the contour length is obtained by fitting
the pre- and post-transition force curves to a modified freely jointed chain model as described previously.18 Ratio of contour length after plateau to
that before plateau; the contour length is obtained by modeling (for details, see Supporting Information). All data were obtained at a retraction
velocity of 300 nm/s.
c
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Journal of the American Chemical Society
Communication
Figure 3. Force−distance curves of Z-alkene-gDCC ground state (A), Z-alkene-gDCC transition state (B), E-alkene-gDCC ground state (C), and E-
alkene-gDCC transition state (D). The contour lengths Lc shown for each structure are obtained by extrapolating the force−distance curve to zero
force.
alkene-bearing gDCCs are 1.65 and 1.24 Å, respectively, as
compared to 1.67 0.05 and 1.20 0.05 Å determined from
the experimental fits.
in a theoretical analysis of a subset of atoms that did not extend
out at least three bonds from the active mechanophore.
ASSOCIATED CONTENT
The extent of precision in the agreement is likely somewhat
fortuitous, given the qualitative assumption of a cusp model to
capture the effect of force on the positions of the ground and
transition states, but even the relative values confirm the
influence of the α-alkene stereochemistry. The difference in the
force-coupled kinetics is effectively entirely due to enhanced
mechanochemical coupling in the E isomer; calculations
confirm the expectation that the stereochemistry of the α-
alkene has no significant effect on the thermal barrier of the
force-free electrocyclic ring opening of gDCC (see Supporting
Information).
■
S
* Supporting Information
Synthetic details; NMR and GPC-MALS characterization; AFM
experiments; thermolysis data. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
todd.martinez@stanford.edu
stephen.craig@duke.edu
Notes
Relative to its Z isomer, the E isomer of the α-alkene
therefore acts as a phenomenological “lever”, in that it provides
a greater mechanical advantage for a given applied force. Here,
a stereochemical mutation, three bonds removed from the bond
that is breaking, increases by almost 40% how the extension of
the polymer chain is coupled to the torqueing motions that
accompany the disrotatory gDCC ring opening. This structural
perturbation is more subtle than, but just as effective as,
incorporating cis-1,3-cyclopentyl connections along the poly-
mer backbone on both side of the gDCCs, as reported
previously.18 Looking ahead, this and similar stereochemical
handles might be useful for tuning mechanochemical activity29
essentially independently of force-free thermal reactivity. While
different theoretical approaches have been applied to explore
covalent polymer mechanochemistry,30,31 our results under-
score the importance of considering remote structural effects in
the analysis,32,33 as the differences here would not be revealed
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This material is based on work supported by the U.S. Army
Research Laboratory and the Army Research Office under grant
W911NF-12-1-0337 and the National Science Foundation
(DMR-1122483). The authors thank B. Akhremitchev for
providing the original force−extension modeling code.
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