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Single Molecule Study of Force-Induced Rotation of Carbon−Carbon Double Bonds in Polymers Wenmao Huang,†,∥ Zhenshu Zhu,†,‡,∥ Jing Wen,§,∥ Xin Wang,† Meng Qin,† Yi Cao,*,† Haibo Ma,*,§ and Wei Wang*,† †
Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure and Department of Physics, Nanjing University, Nanjing 210093, P.R. China ‡ Department of Pharmaceutical Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, P.R. China § Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China S Supporting Information *
ABSTRACT: Carbon−carbon double bonds (CC) are ubiquitous in natural and synthetic polymers. In bulk studies, due to limited ways to control applied force, they are thought to be mechanically inert and not to contribute to the extensibility of polymers. Here, we report a single molecule force spectroscopy study on a polymer containing CC bonds using atomic force microscope. Surprisingly, we found that it is possible to directly observe the cis-to-trans isomerization of CC bonds at the time scale of ∼1 ms at room temperature by applying a tensile force ∼1.7 nN. The reaction proceeds through a diradical intermediate state, as confirmed by both a free radical quenching experiment and quantum chemical modeling. The force-free activation length to convert the cis CC bonds to the transition state is ∼0.5 Å, indicating that the reaction rate is accelerated by ∼109 times at the transition force. On the basis of the density functional theory optimized structure, we propose that because the pulling direction is not parallel to CC double bonds in the polymer, stretching the polymer not only provides tension to lower the transition barrier but also provides torsion to facilitate the rotation of cis CC bonds. This explains the apparently low transition force for such thermally “forbidden” reactions and offers an additional explanation of the “lever-arm effect” of polymer backbones on the activation force for many mechanophores. This work demonstrates the importance of precisely controlling the force direction at the nanoscale to the force-activated reactions and may have many implications on the design of stress-responsive materials. KEYWORDS: mechanochemistry, carbon−carbon double bonds, cis-to-trans isomerization, atomic force microscope, force-induced rotation
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activated reactions undergo a pathway that is otherwise inaccessible in heat or light activated processes.2,14−16 Studying the mechanochemical reaction pathway is of fundamental interest for the understanding of chemical reactions on a multiple-dimensional energy landscape. However, although many mechanically active compounds or mechanophores have been discovered, they are limited to the compounds
echanical force has long been considered as a “destructive” factor that typically leads to bond cleavage in a polymer chain.1 Recently, it has been increasingly recognized that force can be used as a “productive” factor to trigger chemical reactions, leading to the burgeoning field of polymer mechanochemistry.2−10 Many mechanically active compounds or mechanophores have been designed and synthesized for various applications, including stress sensing,3,7 self-healing11 and catalysis.5 Moreover, because force is a vector quantity of both magnitude and direction, it can not only lower the activation energy of a reaction but also alter the shape of potential energy surface.12,13 This often makes the force© 2016 American Chemical Society
Received: October 21, 2016 Accepted: November 14, 2016 Published: November 14, 2016 194
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both structural and energetic information on force activated reactions to be revealed.26−41 Recently, SMFS has been evolved as an important tool to study the mechanical force-activated reactions and explore their free energy landscape.26−41 The experimental scheme is depicted in Figure 1. A polymer
containing mechanically labile bonds or strained rings.2,3,7,11,17−19 Such a design strategy is important for selectively triggering the reaction of mechanophores without leading to the scission of the polymer chains and has been a paradigm for searching putative mechanophores.10 Carbon−carbon double bonds (CC) are ubiquitous in many natural and synthetic polymers. Although it is widely known that changing the cis and trans ratio of the CC in polymer could greatly alter the degree of crystallinity and thus their mechanical properties,20,21 CC is generally considered as mechanically inert due to its high bond energy (>600 kJ mol−1). A CC bond involves a σ bond formed by two sp2 orbitals and a π bond formed by two p orbitals. Due to its intrinsic symmetry, rotation of a CC bond requires the breaking of the π bond and the formation of a diradical intermediate,22 which can only occur at high forces close to the breaking force of other bonds in a polymer. As such, a single CC bond does not fulfill the prerequisite for a mechanophore based on our current knowledge. Theoretical works also suggested that isomerization of CC is impossible under a tensile force. In 2001, a first-principles simulation of cispolyacetylene fragments predicted it is not very likely for cis− trans isomerization to be induced under tensile stress, based on a simplified model analysis of a potential energy scan along the variation of the C−CC−C dihedral angle with fixed terminal carbon−carbon distance.23 A density functional theory (DFT) calculation predicted that stretching cis-1,4-polyisoprene or polybutadiene would only lead to the break of C−C bonds at tensile forces of 6.8 nN and 7.2 nN, respectively.24 No mechanical cis-to-trans isomerization could be observed before rupture of the single C−C bonds. On the contrary, here we report the direct observation of cis-to-trans isomerization of CC bonds in a polymer by mechanical force, which is consistent with a recent report by Radiom group.25 Combining single molecule AFM and quantum chemical modeling, we show that the cis-to-trans isomerization of CC bonds occurs before the break of the backbone of the polymer chain at an experimental time scale of 1 ms at a transition force of ∼1.7 nN. The force-free transition state has a C−CC−C dihedral angle around 76°, distinct from the typical 0° or 180° for the CC bond in the cis or trans conformation, respectively, suggesting the rotation of the CC bond upon stretching. We also directly capture the diradical intermediate state during the force-activated rotation process, which provides direct evidence of the breaking and reformation of CC bond upon rotation. As the cis CC bonds in the polymer are not fully aligned with the direction of the pulling force, they are subjected to both tension and torsion generated upon stretching. We theoretically show that torque can also facilitate the rotation of a CC bond. This explains why the cis-to-trans rotation of CC bonds in our polymer system takes place at much lower force than that for polyisoprene or polybutadiene in which no torsion is generated upon pulling. This finding greatly advances our current knowledge on mechanosensitive polymers and expands the toolbox of mechanophores under high stretching forces.
Figure 1. Schematic diagram of the SMFS experiment. The cis alkene (red) was directly converted to the trans isomer (blue) at a force of ∼1.7 nN in a polymer.
containing cis alkene is linked between the cantilever tip and the substrate. Stretching force is then applied by moving the cantilever against the substrate at a constant speed. Because the end-to-end distance of trans alkene is longer than that of the cis one, we would expect to see the increase of the contour length of the polymer if the transition occurs. In order to apply high stretching forces to the cis alkene, we developed a method that allows the polymers of interest to be covalently linked to both the cantilever tip and the substrate. Anchoring the polymers to the surface is through the surfaceinitiated living ring-opening metathesis polymerization (ROMP) (Figure 2).42 The silane-functionalized norbornene was first harbored to the silicon surface. Then, the third generation Grubbs catalyst opened the ring and subsequently polymerized oxanorbornene monomers. Finally, a high concentration of cis- di-tert-butyl but-2-ene-1,4-diyldicarbamate as the end-capping agent was introduced and followed by trifluoroacetic acid treatment to expose functional groups on the polymer.43 The ROMP yielded a mixture of stereoisomers with ∼53% of alkene in the cis conformation, as determined by 1 HNMR (Figure S1). Because the trans alkenes in the polymer cannot be further elongated, they are mechanically inactive and did not contribute to the contour length change. Thus, a substrate of amine functionalized and surface-tethered monotelechelic oxanorbornene-carboxybetaine polymers was prepared and ready for SMFS study of cis-to-trans isomerization by force. Based on the circular dichoism measurement, the polymer does not form any ordered secondary structures (Figure S2) in PBS buffer. Direct Observation of the Force-Induced cis-to-trans Isomerization of CC Bonds. The polymer was picked up by a N-hydroxysuccinimide (NHS)-functionalized cantilever and stretched at a constant pulling speed of 1000 nm s−1 to investigate whether the cis-to-trans isomerization can indeed take place before the break of covalent bonds in the polymer. The 10 × PBS buffer (pH 7.4) of high salt concentrations was used to screen the charge−charge interactions among the
RESULTS AND DISCUSSION The Design of the Single Molecule Force Spectroscopy Experiments. We used AFM-based single molecule force spectroscopy (SMFS) to investigate the force-activated cis-totrans conversion of alkene in a polymer. AFM can precisely measure the forces in picoNewton resolution and the end-toend changes of a polymer in nanometer resolution, allowing 195
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Figure 2. Synthetic scheme for the surface-grafted polymers used in the SMFS experiments. The amino-terminated end of the polymers can be picked through covalent interaction by NHS-functionalized AFM cantilever tips.
Otherwise the contour length change will be different from the measured value (Figure S7). We also observed a similar force plateau using polymers with an unhydrolyzable backbone structure, (Figure S8) which confirmed again that the contour length change cannot originate from the dissociation of five membered ring. Based on the measurement of plateau lengths, we are certain that the force plateaus are indeed the signatures for the cis-to-trans conversion of alkene in the polymer chain. Moreover, the cis-to-trans transition is not reversible. After cisto-trans conversion, when the polymer is relaxed to low force and stretched again, the force−extension curve follows the relaxation curve instead of the initial stretching curve (Figure S9). This indicates that such a cis-to-trans transition by force is permanent to the polymer and cannot be reverted at low force, which is distinct from reversible transitions, such as, the chair− boat transition of the sugar ring in polysaccharides,27 the proline isomerization in elastin,30 and the B−S transition of DNA.29 Instead, such an irreversible transition is comparable to other force-induced change of other mechanophores.31,41 Force-Induced cis-to-trans Isomerization Undergoes a Diradical Intermediate State. As indicated in many organic textbooks, cis-to-trans isomerization of carbon−carbon double bond is generally considered forbidden because its rotation involves the break of the π−π bond and the formation of a diradical intermediate.44 To reveal the force-induced reaction pathway of the cis-to-trans isomerization, we further performed the experiments in the presence of a free radical capturing compound, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), to capture this intermediate state similar to the work reported by Craig and co-workers.45 If one of the two radials was captured by TEMPO, the diradical intermediate cannot be converted to trans double bond anymore, leading to a single bond product with a longer contour length change (Figure 4a). When adding TEMPO to the system, the force−extension curves of the polymer show similar force-plateaus (Figure 4b). However, the
polyelectrolyte chains. At low salt concentrations, it is difficult to pick up the polymer from the surface, probably because the amino groups are buried and forming ionic pairs with the side chain of the polymer (Figure S3). With the covalent linkage, the detaching forces of the polymer can be up to 2.5−3.0 nN (Figure S4). In all force traces reaching a break force above 2.0 nN, we observed a force plateau at ∼1.7 nN, taken from the middle of the transition (Figure S5), which is similar to other mechanically active polymers (Figure 3a).31,36,39,41 Moreover, the plateau length is proportional to the total length of the polymer chain. We normalized 5 representative force traces at a force of 2.0 nN (Figure 3b). Clearly, all force plateaus overlap at similar forces. The distribution of the average transition forces is summarized in Figure 3c. The average plateau force is 1703 ± 86 pN (mean ± SD). It is worth mentioning that the side group does not affect the transition force. We have synthesized additional polymers with different side groups (Figure S6). The transition force for these polymers is similar to the one shown in Figure 2. In order to confirm that the observed force plateau resulted from the cis-to-trans conversion of alkene, we measured the contour length change of the polymer in the transition by fitting the force−extension traces using the extensible freely jointed chain model (eFJC) (Figure 3d).27 The histogram of the contour length changes is shown in Figure 3e. Based on the DFT optimized cis and trans structures of the repeating units in the polymer (Figure 3f) and the percentage of the cis isomers, the expected contour length change for cis-to-trans conversion is calculated to be 8.1%, agreeing well with the experimentally measured value of 8.7 ± 1.2%. The difference may come from the experimental error in determining of the percentage of cis isomers, since the NMR was performed on the free polymers in solution instead of the surface-polymerized ones. It is worth mentioning that the force plateau cannot originate from the dissociation of the allyl ether in the polymer upon stretching. 196
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Figure 3. (a) Typical force traces for the stretching of the polymer containing cis alkene. (b) The normalized force traces shown in (a) at the same force of 2.0 nN. (c) The histogram for the average transition force, calculated based on the second derivative of the force traces, centers at 1703 ± 86 pN (mean ± SD). (d) The contour length of the polymer before (Lc0) and after (Lc) the transition were measured by fitting the force−extension trace using the eFJC model. (e) The histogram of ΔL/Lc for all force−extension traces. Gaussian fitting (blue line) shows the average ΔL/Lc of 8.7 ± 1.2%. (f) Near-planar cis and trans monomer structures by DFT constraint optimization structures theoretically predicted ΔL/Lc to be 8.1%.
converted to diradicals, leading to even longer elongation of the polymer (∼15.6%). Since the trans-to-cis transition under force is inhibited, in our experiments we only observe the conversion of cis alkene to the trans isomer instead of obtaining their thermodynamic equilibrium under force. This results also further ruled out the possible dissociation of the allyl ether in the polymer upon stretching, which did not show a radical intermediate. Free Energy Landscape for the Force-Induced cis-totrans Isomerization. Force spectroscopy measurement could provide direct quantitative information about the free energy landscape for the cis-to-trans transition. The force-activated nonequilibrium two-state process has been modeled extensively using either the Bell−Evans model46,47 or the cusp model proposed by Hummer and Szabo.48,49 In both models, it is considered that the activation energy (ΔG⧧) can be lowered by force. However, the distance of the transition state to the ground state along the force direction, Δx⧧, is independent of the applied force in the Bell−Evans model, while it can be
contour length change for the transition becomes much longer (Figure 4c). The average transition force for the plateau is ∼1.1 nN (Figure 4d), and the average contour length change is ∼11.9 ± 0.9% (Figure 4e). Based on the calculation, the length change of the polymer corresponds to the transition of the cis alkene bond to a single bond (∼12.9%). Therefore, our results suggest that upon stretching, the carbon−carbon double bond in the cis alkene is significantly weakened and becomes a diradical at the intermediate state. Interestingly, we found that the transition force is also lowered in the presence of TEMPO, which may suggest that the formation of the diradical is not the rate-limiting step for the cis-to-trans isomerization. The subsequent conversion of the diradical intermediate to the trans conformer has a higher energy barrier. Obviously, capturing the diradical intermediate by TEMPO biased the reaction pathway. The environmental and solvent effects for the force-induced cis-to-trans isomerization would deserve further investigation and will be our next endeavor. Notably, our results clearly show that the trans alkene cannot be activated by force. Otherwise, all trans isomers in the polymer can also be 197
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Figure 4. (a) Possible reaction pathway of force induced cis-to-trans transition of alkene. If the cis-to-trans isomerization of alkene occurs through a diradical intermediate state, the diradical intermediate may be directly caught by TEMPO, leading to a single bond product with longer contour length change. One of the two radicals captured by TEMPO would inhibit the conversion of the intermediate to the trans isomer. (b) The typical force extension curves showed similar force plateaus with lower force and longer contour length change in 32 mM TEMPO buffer. (c) The contour length of the polymer before (Lc0) and after (Lc) the transition measured by fitting the force−extension trace using the eFJC model showed a longer change. Kuhn length (lK) = 0.46 nm; Lc0 = 273 nm; Lc = 311 nm. The segment elasticity changes from 20231 to 46820 pN nm−1 upon the transition. (d) The histogram for the average transition force, calculated based on the second derivative of the force traces, centers at 1124 ± 64 pN (mean ± SD). (e) Gaussian fitting (blue line) shows the average ΔL/Lc of 11.9 ± 0.9%, while the DFT predicted 12.9%, based on those polymer structures.
0.49 Å based on the Bell−Evans model or 0.61 Å based on the cusp model, which is shorter than that for other mechanically activated reactions17,39,41 and is close to that for the rupture of covalent bonds.50 The activation energy barriers obtained by both Bell−Evans model and cusp model (∼125 kJ mol−1) are close to the lower limit of the experimentally estimated activation energy barrier (167−260 kJ mol−1) of cis-to-trans transition for various molecules.51−55 And they are comparable to that for the mechanical force-induced transition of other mechanophores with similar transition forces.41 If the thermal activation pathway shares the same activation barrier, it should be possible to directly observe the cis-to-trans isomerization of the polymer and the increase of thermodynamically more stable trans isomers upon heating. However, even the polymer was heated to 90 °C for 72 h, no cis-to-trans isomerization (Figure S16) could be observed. Similarly, a recent work found that the mechanical and thermal stability of a bond might be independent considering different reaction pathways.56 The estimated activation energy at zero force also depends on the shape of the free energy landscape. If ν in eq 1 is even smaller and the energy landscape is curved up at low force region, then
shortened by force in the cusp model. The force-dependent rate constant k(F) at a given force F can be written as 1/ v − 1 ⧧⎞ ⎛ ⎛ β ΔG⧧[1 − ⎜1 − vF Δx‡ ⎟ νF Δx⧧ ⎞ ⎝ ΔG ⎠ ⎟ k(F ) = k 0⎜1 − e ⎝ ΔG⧧ ⎠
1/ ν
]
(1)
where k0 is the rate constant at zero force and β = 1/kBT (kB is the Boltzmann constant and T is the temperature); ν = 1 for the Bell−Evans model and 1/2 for the cusp model, respectively. Because each force−extension trace contains multiple cis-totrans transition events, it is possible to directly obtain the forcedependent transition probability from each trace. Notably, k(F) cannot be directly obtained at constant pulling speed experiments, but can be indirectly extracted based on the transition force of the force−extension curves. The detailed fitting procedure can be found in the Supporting Information. A few examples for the fitting are shown in Figures S10−13. The parameter sensitivity of the fitting is also rigorously tested (Figure S14−15). The fitting parameters based on traces taken using multiple cantilevers and on different days are summarized in Table S1. The Δx⧧ for the cis-to-trans transition of alkene is 198
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imentally detected diradical character was also verified through our singly occupied molecular orbital (SOMO) analysis (Figure S18). Therefore, along the cis-to-trans isomerization, the stretched double bond can be expected to transiently break into a diradical TS structure with a further longer bond length and much a reduced reaction barrier. After transition, the bond can return to the double bond state but at the energetically more stable trans conformation. This directly confirms the experimentally observed diradical intermediate state for the cisto-trans isomerization. The force-free activation length, Δx⧧, corresponding to the extension along the polymer backbone that accompanies the change from ground state to transition state, is theoretically determined to be 0.33 Å for cis-to-trans transition by fitting the force−distance curves (Figure 5), which is a bit lower than the experimentally determined values of 0.49 Å based on the Bell− Evans model or 0.61 Å based on the cusp model. Moreover, DFT calculation shows that Δx⧧ would increase to 0.45 Å using a cis−trans alkene dimer, which could be closer to the experimental polymer (Figure S19). On the contrary, Δx⧧ for trans-to-cis transition is also theoretically determined to be −0.10 Å by fitting the force−distance curves (Figure 5), significantly different from the cis-to-trans value. Such a negative value implies that pulling is energetically unfavorable for transto-cis transition because it will require additional activation energy to compete with the pulling force to shorten the end-toend distance for reaching TS (Figure S20). This verifies again that trans-to-cis transition will not occur during mechanical experiments and that the cis-to-trans isomerization is irreversible upon stretching. The DFT calculation also suggests that the free energy barrier for the cis-to-trans isomerization is lower than that for C−C bond homolysis (Figure S17). As a consequence, we are able to observe the cis-to-trans isomerization of CC bonds before the rupture of C−C bonds in the polymer, which occurs at elevated forces. This prediction is also consistent with our experimental results. Caution is needed because it remains difficult to make quantitative comparisons between quantum chemical calculations and experiments. In the calculation, we used a simplified model system instead of the full structure of the polymer to compromise between accuracy and affordable computational cost (the side chain is omitted and the length of the polymer is limited to only one repeat unit). The water solvent effect is approximately accounted by using a continuum solvation model in the calculation, but other realistic environment effects (pH, ionic strength, salt, and etc.) were not included. The Contribution of Torsion to the cis-to-trans Isomerization. Recently, researchers started to consider the direction of applied mechanical force and its effect on mechanochemical transduction along the reaction coordinate.16,57 We found that because the monomer unit contains a five-membered ring, and the pulling direction for each monomer of a polymer is not parallel to the CC bond, but forms a dihedral angle θ of 2.8° for the cis conformer, 19° for TS, and 29° for the trans one based on DFT calculation at the transition force. The C2−C3C4−C5 plane in the structure can be considered as a rigid body before isomerization. Therefore, stretching the polymer not only leads to a tensile force to extend the CC bond but also provides a torque that can facilitate the rotation. The total force acting on the polymer can be decomposed as Ftension as the extension force to elongate the CC bond and lower the free energy barrier and Ftorsion as the
the extrapolation based on the measurements at high force may lead to the underestimation of ΔG⧧ at zero force. Quantum Chemical Characterization of Force-Induced cis-to-trans Isomerization. To further understand the apparent low activation barrier and get the mechanistic insights into the force-activated cis-to-trans transition of alkene, we performed DFT-based quantum chemical modeling of mechanical response of the cis and trans structures of a simplified model molecule of cis-1,2-bis(tetrahydrofuran-2yl)ethane upon stepwise separation of C1 and C5 atoms as well as the possible transition state (Figure 5a−c; detailed
Figure 5. (a−c) Optimized force-free structures of the equilibrium ground states of the cis conformer (a) and the trans conformer (b) and the TS for cis−trans isomerization (c), where the lengths of the central C3C4 bonds are also depicted. The dihedral angles of C2−C3C4−C5 are 0°, 180°, and 76° for these three structures, respectively. (d−f) Energy vs end-to-end distance curves and (g−i) force−distance curves for the structures shown in (a−c).
structural information can be found in the Supporting Information). As shown in Figure S17, increasing the end-toend distance (rC1−C5) favors a trans conformation from the thermodynamic point of view, as the energy of the stationary state for trans conformation at the same rC1−C5 is considerably lower than that for the cis one by more than 100 kJ·mol−1. This implies that the stretched structure of the cis conformer has a strong tendency to isomerize to a trans one (Figure S17). However, it is well-known that to complete such a transition usually requires overcoming a high-energy barrier unless the central C3C4 double bond can be sufficiently weakened, as has been mentioned before. In our quantum chemical calculation, external force is shown to be able to elongate and thus weaken the C3C4 bond upon pulling until other single bonds in the backbone chain break (Figure S17). The maximum lengths that C3C4 bond can reach upon pulling are 1.43 Å for cis isomer and 1.39 Å for the trans one, respectively. Such C3C4 length for cis conformer (∼1.43 Å) is very close to that of the computed force-free transition state (TS, a first-order saddle point along the reaction coordinate, see Figure 5c and Supporting Information) (1.46 Å), implying that cis-to-trans isomerization would have a much reduced activation barrier under force. The force-free TS illustrated in Figure 5c has a C−CC−C dihedral angle around 76°, distinct from the typical 180° for a CC bond, suggesting the rotation of the CC bond upon stretching. The exper199
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Figure 6. (a) In experimental conditions, due to the link of two tetrahydrofuran rings to the CC bonds, the CC bonds are not aligned to the pulling direction but form a certain angle θ. (b) The force analysis for th cis alkene. Considering the force direction is not parallel to the CC double bond based on the 3D structure in each monomer unit. Therefore, pulling force not only tends to stretch the C3C4 double bonds but also tends to rotate the two single bonds C2−C3 and C4−C5 around it. The force component along the CC bond (Y-axis) that contributes to the tension is Ftension = F cos θ. The force perpendicular to the CC bond that contributes to the torsion is Ftorsion = F sin θ sin φ, where θ and φ are the polar angle and the azimuthal angle, respectively. (The x−y plane is defined by the C1, C3, and C4 atoms, and the x−z plane is perpendicular to the CC bond.) Therefore, total torque generated upon pulling equals F sin θ sin φ × d, where d is the distance between C1 to the line of C3C4 double bond. (c) Because the pulling direction is well aligned with the CC bond of cis polyisoprene and polybutadiene, no torsion is generated for pulling these two polymers.
twisting force to generate the torque and facilitate the rotation (Figure 6a). Torque equals the twisting force (Ftorsion) times the distance between the line of C1 and C5 to the CC bond (d) (Figure 6b). The torque change for the rotation of cis conformer to the transition state at the transition force of ∼1.7 nN is ∼68.2 pN nm, corresponding to a free energy of 41 kJ mol−1. The torque is ∼1/3 of the free energy barrier estimated based the experimental data. It is worth mentioning that the generation of torque is due to the link of two tetrahydrofuran rings to the alkene, which distorts the pulling direction from the direction of the CC bond (Figure 6b). In polyisoprene and polybutadiene, because the pulling direction is well aligned with the CC bond (Figure 6c), no torque can be generated by pulling. We anticipate that much higher force is required to trigger cis-to-trans transition. Indeed, Craig and coworkers did not observe any evidence of isomerization of alkene in polybutadiene up to a stretching force of 2.5 nN (see Figure S14 in the Supporting Information of ref 36).36 Based on this analysis, it is clear that a minute structure change on the polymer backbone could greatly change the torsion applied to the mechanophore. However, for typical bond scission, in which bond rotation is not involved, torsion does not affect the transition force. On the contrary, for the mechanochemistry involving bond rotation, torsion can play a significant role. Such a polymer backbone “lever-arm effect” was also observed for the ring opening of gem-dibromo and gem-dichlorocyclopropanes, and such an effect can be even “remote”.36,39 The author attributed this effect to the change of effective activation lengths. We propose that the contribution of torque to those mechanochemical reactions may provide an additional explanation. Many factors that can change the direction of force applied to the mechanophores, such as containing ring-
shaped units and tacticity of the polymer, can lead to the generation of torque upon pulling. Moreover, the effects of tension and torsion to a mechanochemical reaction can be cooperative from the perspective of multiple dimensional free energy landscape, adding to the complexity of polymer mechanochemistry.
CONCLUSIONS In this work, we demonstrated that cis alkene can be directly converted to the trans one at a stretching force of ∼1.7 nN using single molecule force spectroscopy. We experimentally and theoretically confirmed that the force-induced cis-to-trans transition of alkene proceeds through a diradical intermediate state. Typically, the isomerization of alkene is difficult and is only reported for a few highly conjugated systems. The alkene we used in this study cannot be converted from cis to trans conformers by heat. Yet mechanical force can be used to trigger such reaction. This indicates the great power of mechanical force for the triggering of reactions otherwise “forbidden” in thermal activated processes. The demonstration of the forceinduced cis-to-trans transition of alkene may also greatly expand the toolbox of available mechanophores. We propose that stretching a polymer might generate both tension and torsion, depending on the structure of polymer backbone. They can collectively facilitate mechanochemical reactions. Such a “leverarm effect” can be implemented in different polymers, which may greatly expand the toolbox of mechano-sensitive polymers. From the material perspective, applications involving high transition forces may benefit from cis alkene containing materials of both high mechanical strength and high toughness, which are critical for load bearing. 200
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METHODS
Haibo Ma: 0000-0001-7915-3429
Synthesis of the Surface-Grafted Polymer Containing cisAlkene. We used surface-initiated living ROMP to synthesize the surface-grafted polymer. The detailed synthesis procedures can be found in the Supporting Information. Briefly, a silicon wafer was cut into 1 × 1 cm2 slides and cleaned with chromosulfuric acid solution. Then, these silicon substrates were immersed into an anhydrous toluene solution containing 1% (v/v) of 5-triethoxysilylbicyclo[2.2.1] hept-2-ene:ethoxytrimethylsilane (1:200 v/v) to obtain the norbornene decorated substrates. Then oxanorbornene monomers were polymerized on the surface using the third-generation Grubbs catalyst in an argon-filled Schlenk bottle using a mixture of anhydrous dichloromethane and 2,2,2-trifluoroethanol (1:1 v/v) as the solvent. The polymerization proceeded for 1 h at room temperature. Subsequently, cis-di-tert-butyl but-2-ene-1,4-diyldicarbamate was added into the bottle as the end-capping agent. Finally, ethyl vinyl ether was added to deactivate the Ru catalyst, and the protecting groups for the monomers were cleaved using 20% (v/v) TFA. Single Molecule AFM Measurements. Single molecule AFM experiments were carried out on a commercial AFM (JPK Force Robot 300) at room temperature (∼22 °C). Standard silicon nitride (Si3N4) cantilevers were purchased from Bruker (type: MLCT). The D or E cantilevers (spring constant ∼0.05 or 0.1 N m−1) were used in all experiments, and the spring constant was calibrated using equipartition theorem for each experiment. The cantilevers were modified with NHS to pick up the NH2-terminated polymers on the substrates. The experiments were done in 10 × PBS buffer at pH 7.4. During each SMFS experiment, the cantilever was brought into contact with the surface at a contact force of ∼1000 pN for ∼2 s to react with the amino groups on the end of the surface-immobilized polymers and pulled back to obtain the force−extension curves of the polymers. The pulling speeds were 1000 nm s−1 for all experiments. All force curves were collected by commercial software from JPK and analyzed using custom-written protocol in Igor 6.0 (Wavemetrics, Inc.). The detailed data analysis procedures can be found in the Supporting Information. Quantum Chemical Modelings. The equilibrium geometries of both cis and transform ground states of 1,2-bis(tetrahydrofuran-2yl)ethene were optimized by the DFT with M06-2X exchange− correlation functional and 6-31G(d) basis set. During the mechanical stretching process, two terminal carbon atoms were displaced from each other step by step (0.2 Å for each step) until the bonding geometries were noticeably distorted. Constrained geometrical optimizations were then performed after each movement. To model the TS of cis−trans isomerization of 1,2-bis(tetrahydrofuran-2yl)ethene, TS geometrical optimizations were performed using the Berny algorithm in Gaussian 09 program followed by frequency analysis and intrinsic reaction coordinate examination. The diradical character of TS was also verified by SOMO analysis. All calculations were implemented with the consideration of water solvation by polarizable continuum model model and carried out by using the Gaussian 09 program.58 Details about the modeling methodology of activation length please see Supporting Information.
Author Contributions ∥
These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS We thank Dr. Hoff Wouter and Ying Li for proofreading and valuable discussion. This work is supported by the National Natural Science Foundation of China (nos. 11334004, 21522402, 21373109, 81301317, and 91127026), the National Basic Research Program of China (no. 2013CB834100), and the Fundamental Research Funds for the Central Universities. REFERENCES (1) Sohma, J. Mechanochemistry of Polymers. Prog. Polym. Sci. 1989, 14, 451−596. (2) Hickenboth, C. R.; Moore, J. S.; White, S. R.; Sottos, N. R.; Baudry, J.; Wilson, S. R. Biasing Reaction Pathways with Mechanical Force. Nature 2007, 446, 423−427. (3) Caruso, M. M.; Davis, D. A.; Shen, Q.; Odom, S. A.; Sottos, N. R.; White, S. R.; Moore, J. S. Mechanically-Induced Chemical Changes in Polymeric Materials. Chem. Rev. 2009, 109, 5755−5798. (4) Davis, D. A.; Hamilton, A.; Yang, J.; Cremar, L. D.; Van Gough, 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. (5) Piermattei, A.; Karthikeyan, S.; Sijbesma, R. P. Activating Catalysts with Mechanical Force. Nat. Chem. 2009, 1, 133−137. (6) Weder, C. Mechanochemistry: Polymers React to Stress. Nature 2009, 459, 45−46. (7) Chen, Y.; Spiering, A. J.; Karthikeyan, S.; Peters, G. W.; 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. (8) May, P. A.; Moore, J. S. Polymer Mechanochemistry: Techniques to Generate Molecular Force via Elongational Flows. Chem. Soc. Rev. 2013, 42, 7497−7506. (9) Wiggins, K. M.; Brantley, J. N.; Bielawski, C. W. Methods for Activating and Characterizing Mechanically Responsive Polymers. Chem. Soc. Rev. 2013, 42, 7130−7147. (10) Li, J.; Nagamani, C.; Moore, J. S. Polymer Mechanochemistry: From Destructive to Productive. Acc. Chem. Res. 2015, 48, 2181−2190. (11) Diesendruck, C. E.; Peterson, G. I.; Kulik, H. J.; Kaitz, J. A.; Mar, B. D.; May, P. A.; White, S. R.; Martinez, T. J.; Boydston, A. J.; Moore, J. S. Mechanically Triggered Heterolytic Unzipping of a Low-CeilingTemperature Polymer. Nat. Chem. 2014, 6, 623−628. (12) Beyer, M. K.; Clausen-Schaumann, H. Mechanochemistry: The Mechanical Activation of Covalent Bonds. Chem. Rev. 2005, 105, 2921−2948. (13) Ribas-Arino, J.; Marx, D. Covalent Mechanochemistry: Theoretical Concepts and Computational Tools with Applications to Molecular Nanomechanics. Chem. Rev. 2012, 112, 5412−5487. (14) Konopka, M.; Turansky, R.; Reichert, J.; Fuchs, H.; Marx, D.; Stich, I. Mechanochemistry and Thermochemistry are Different: Stress-Induced Strengthening of Chemical Bonds. Phys. Rev. Lett. 2008, 100, 115503. (15) Jagannathan, B.; Elms, P. J.; Bustamante, C.; Marqusee, S. Direct Observation of a Force-Induced Switch in the Anisotropic Mechanical Unfolding Pathway of a Protein. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 17820−17825. (16) Wang, J.; Kouznetsova, T. B.; Craig, S. L. Reactivity and Mechanism of a Mechanically Activated Anti-Woodward-HoffmannDepuy Reaction. J. Am. Chem. Soc. 2015, 137, 11554−11557. (17) Lenhardt, J. M.; Black, A. L.; Craig, S. L. GemDichlorocyclopropanes as Abundant and Efficient Mechanophores in
ASSOCIATED CONTENT
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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.6b07119. Materials, methods, and supporting figures and table (PDF)
AUTHOR INFORMATION Corresponding Authors
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Yi Cao: 0000-0003-1493-7868 201
DOI: 10.1021/acsnano.6b07119 ACS Nano 2017, 11, 194−203
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