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Mechanical Susceptibility of a Rotaxane Min Zhang, and Guillaume De Bo J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b06960 • Publication Date (Web): 06 Sep 2019 Downloaded from pubs.acs.org on September 6, 2019
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Journal of the American Chemical Society
Mechanical Susceptibility of a Rotaxane Min Zhang and Guillaume De Bo* School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom ABSTRACT: We have investigated the mechanical dissociation of an ammonium/crown ether rotaxane using experimental (sonication) and computational (CoGEF) methods and found that it breaks faster than its non-interlocked or uncoupled interlocked (i.e. pulled from both sides of the axle) counterparts. This was confirmed by the analysis of the fragments, which are the results of a selective unstoppering reaction. Interestingly, the initial dissociation also triggered the elimination of the axle segment separating the stopper from the ammonium binding station. CoGEF calculations have shown that the constriction of the axle by the macrocycle during the elongation of the rotaxane provokes the accumulation of tensile and torsional stress that ultimately leads to the rupture of a covalent bond in the constricted section of the axle. Overall, these results suggest that the rotaxane architecture acts as a lever that accelerates the dissociation of interlocked covalent bonds. This phenomenon could impact the mechanical properties of slide-ring materials at high strain.
INTRODUCTION What happens when molecular segments are forced against each other in the intimacy of an interlocked structure? This question has important implications for the incorporation of mechanical bonds1 in mechanoresponsive materials2 and molecular machines,3 and could shed some light on the effect of entanglement in polymers under tension.4 In a rotaxane for example, one can identify two main dissociation pathways, unstoppering and unclipping, if a covalent bond scission occurs in the axle or the macrocycle respectively (Figure 1).5 A third, non-covalent, dissociation (deslipping) can also occur if the stopper is small enough (possibly facilitated by deformation of the macrocycle and/or stopper). The mechanical susceptibility (i.e. the ability to resist tensile stress) of rotaxanes6a-b and catenanes7 has been investigated but the exact nature of their dissociation pathway(s) could not be ascertained. Nevertheless, it was shown that a catenane-containing polymer cleaves at the same rate as its noninterlocked counterparts, suggesting that a catenane architecture doesn’t significantly alter the mechanical strength of its constitutive covalent bonds.7 On the other hand, overhand knots under tension are predicted to weaken where the strand exits a loop,8ab a spatial arrangement not too dissimilar to the one found in rotaxanes where the axle passes through the cavity of a macrocycle. Indeed, we have recently shown that a rotaxane architecture could delay the activation of a mechanophore embedded in its axle due to the emergence of a competing high-stress region where the axle is constricted by the macrocycle.9 Here we show that the same high-stress region can lead to the selective cleavage of a covalent bond in the axle in the absence of a competing mechanophore. These results suggest that the rotaxane architecture acts as a lever10a-c that accelerates the dissociation of interlocked covalent bonds by lowering the total loading force required to provoke their rupture. This finding has significant implications for the future development of slide-rings materials (a network of polyrotaxanes connected by their macrocycles). They display a remarkable ability to absorb mechanical energy at low extension due to ‘pulley effect’ of their mobile crosslinks.2 However, our results suggest that their rotaxane
architecture could accelerate the failure of this material at maximal elongation (when the macrocyclic cross-links are forced against the terminal stoppers of the polymer axles).
Dethreading
Unstoppering
Unclipping
Figure 1. Possible dissociation pathways for a rotaxane under tension. Plain and dashed black arrows denote covalent and non-covalent processes respectively. Red arrows indicate the direction of the force.
RESULTS AND DISCUSSION We previously found that the rate of dissociation of a Diels– Alder mechanophore is reduced if the adduct is incorporated into the axle of a rotaxane, due to the presence of a competing high-stress region at the axle-stopper junction.9 We hypothesized that in the absence of another mechanically weak covalent bond, it should be possible to induce a selective cleavage of the axle of the rotaxane where the macrocycle meets the stopper. Scheme 1. Mechanical dissociation of a rotaxane via an unstoppering pathway*
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O
O R=
increase from ~108˚ at E0 to ~136˚ at Emax in 1′, compared to an increase of ~5˚ for b located in the linear part of the axle. An equally modest increase in the corresponding b and d angles is observed in free-thread model 6′ (Figure 2c,e). In fact, in 6′ tensile stress accumulates mostly in the terminal bonds (Figure 2d), where scission is observed in CoGEF calculations. In essence, the ability of the rotaxane architecture to extensively deform the axle in the vicinity of the stopper, enables the activation of chemical bonds that are otherwise unreactive.
OR
O
a Br n-1
O
O
CO2Me
Cl O
H O O N
O
RO
PF 6-
O
H H N
O
O
H O
O
Cl
y O
x
O
O
z
1 Cl
O
OR
O
i
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Cl O
H O N
O
RO
H H N
H O
PF 6
O
O O O
O
O
2
O
O
O
1
f d H O O
RO b
N
e H O g
h
+
OR
3
O
NH 2
Cl Cl
O
2
C6H12
c
Cl
-
O
O
O
Cl
+
5
4
3 O
O
j
i
HO 2C
O Cl
* Red arrows indicate the direction of the force. Conditions: (i) US (20 kHz, 13.0 W/cm2, 1s ON/2s OFF), THF, 5-10˚C.
To explore this possibilty, we have designed rotaxane 1 in which a benzo-21-crown-7 macrocycle is stoppered on the left with a mechanically inert Diels–Alder (DA) adduct11 and on the right with a bulky derivative of tris(4-chlorophenyl)propanoic acid large enough to prevent deslipping under tension (Scheme 1). In other words, this design should only allow the dissociation of the rotaxane architecture via unclipping and/or unstoppering covalent pathways (Figure 1). In the first stage of the polymer elongation, the macrocycle should move away from its ammonium station and travel along the axle of the rotaxane until it reaches the bulky stopper. At this stage, tension starts to build in the portion of the axle constricted by the stretched macrocycle (2, Scheme 1), until a covalent bond breaks, ejecting the stopper (5) and liberating the macrocycle (4). Advantageously, the thermal lability of the DA adduct stopper allows for the recovery of the axle fragment as well. CoGEF calculations12 on model rotaxane 1′ (DFT B3LYP/631G*, vacuum, no counterion), show a typical 3-stage elongation profile9 with: an initial energy increase attributed to the ammonium/crown ether interaction (0 to ~6 Å), a plateau attributed to the shuttling of the macrocycle from the station to the stopper (~6 to ~12 Å) and, finally, a sharp increase in energy corresponding to the enthalpic regime where bond deformation occurs (~12 to ~18 Å, Figure 2a). The culmination of this regime (Emax) is followed by a bond dissociation at a calculated force (Fmax) of 3.13 nN. The structural parameters of the computed structures, such as bond angles (Figure 2b) and bond lengths (Figure 2d), show how torsional and tensile stress accumulate where the axle bends over the bottom of the macrocycle; singularly around bond y (Scheme 1 and Figure 2d), and angles d (Figure 2b) and e (see SI). This large bending is specific to the rotaxane architecture. Angle d for example, undergoes a ~28˚
Figure 2. CoGEF calculations on model rotaxane 1′ and free-thread 6′ (DFT B3LYP/6-31G*). Evolution of energy in 1′ (a) and angles b and d in 1′ (b) and 6′ (c) upon simulated elongation. (d) Distribution of tensile stress in model rotaxane 1′ and free-thread 6′ at Emax. (e) Structure of free-thread models 6 and 6′.
The desired chain-centered macromolecular [2]rotaxane (1, Mn = 37 kDa, Đ = 1.19) was obtained by single electron transfer living radical polymerization (SET-LRP)13 of methyl acrylate initiated from both the macrocycle and the DA stopper (See SI for details). We performed the mechanical activation of rotaxane 1 in THF at 5-10˚C, using high-intensity ultrasound (20 kHz, 13.0 W/cm2, 1s ON/2s OFF). The reaction was stopped after 240 min of sonication. The solvent was then removed and the solid residue was dried for 2 hours under vacuum. Small molecules were extracted by washing the polymer residue with MeOH (fraction A). 1H NMR analysis of the polymer fraction confirms the dissociation of the rotaxane architecture (Figure 3). The downfield shift of bridge protons Hd and He in the DA
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Journal of the American Chemical Society stopper (ΔδHd,e ~ 0.20 ppm) and the upfield shift of macrocycle proton H1 are most indicative of dethreading of the macrocycle. In addition, the intensity of the peaks relating to protons Hi and Hj in the bulky stopper has decreased compared to the intensity of the signals of the DA stopper and the macrocycle, suggesting a dissociation of the bulky stopper during the dethreading event. a
which mainly contains the adduct 8. Surprisingly, the isolated fragment lacks the hexamethylene linker that initially connected the ammonium station to the bulky stopper in rotaxane 1 (Figure 4). This is further confirmed by the similar 1H NMR patterns observed for protons Hf,g,h in the post-sonication mixture and reference 3ref (see SI section 7.5).
j i 2
3
c
1
d, e
b
=
5=
b
c 2
3
Solid-liquid MeOH extraction
1
d
7.5
7.0
6.5
b
d, e
c
6.0 ppm
5.5
5.0
Fraction A
Cl
Cl
7 X
a
4.5
Figure 3. Partial 1H NMR (500 MHz, CDCl3) of rotaxane 1 before (a) and after (b) sonication (240 min), along with macrocycle 4ref (c) and dissociation product 3ref (d) reference polymers. The lettering refers to assignment in Scheme 1. Analysis of MeOH fraction A confirms this picture (Figure 4). 1 H NMR reveals that this fraction mainly contains stopper related compounds (along with low molecular weight PMA, see SI section 7.6). Only two peaks (P1 and P2) can be observed by HPLC in a 1:3 ratio at 4.68 and 10.77 min respectively (Figure 4). These two products were isolated by preparative HPLC and the major product (P2) was identified as acid 5 by NMR and MS. This confirms that the main dissociation pathway involves the rupture of the C-O bond linking the stopper with the rest of the axle (y, Scheme 1). It proved difficult to identify the exact structure of the minor product but MS analysis suggests that it contains triarylmethane fragment 7 with a polarity (HPLC) sitting between alcohol 7c and triarylmethane 7a (Figure 4). The absence of 7a and 7e in the fraction A suggests that the scission of bonds x and z is not favored (Scheme 1). Equally, the absence of 7b precludes any significant decarboxylation. In fact, the contribution of a heterolytic mechanism seems unlikely because the rupture of bond y would leave a very unstable primary cation on the axle side unless the elimination of a proton occurs concomitantly. In both cases, a likely outcome would be the formation of a terminal olefin on the axle, which we do not observe. A bimolecular process, in which the departure of the carboxylate bulky stopper is assisted by the addition of a nucleophile, was also tested by sonicating 1 in presence F3CCH2OH. Incorporation of this alcohol could not be detected in either of the fragments (see SI section 7.9). Heterolytic dissociation on bond z would be more favored but products resulting from the trapping of a trityl cation (such as 7a,c,d) are not observed. Hence it seems more likely that P1 results from the rearrangement of radical 10 because the carboxylic radical can be stabilized upon addition onto one of the chlorophenyl groups (Figure S8).14 We then took advantage of the thermal lability of the DA stopper to isolate the second fragment resulting from the mechanical dissociation of rotaxane 1. The polymer residue of the first extraction was treated with acetic anhydride, then heated in presence of furan to release the maleimide from the axle (Figure 4). MeOH extraction of the resulting mixture gives fraction B,
Cl
1. Ac2O 2. Furan, Δ 3. Solid-liquid MeOH extraction
Fraction B a
b
Fraction B
O
H N
c
N d
O
8
X 7a -H 7b -CH3 7c -OH 7d -OCH3 7e -CH2CO2Me Not observed
e
a
c
b
7ref
f
f
d e
O
O
Figure 4. Isolation and identification of fragmentation products. Fraction A was analyzed by HPLC (ACE 5 µm silica, 1ml/min, Hexane/EtOAc/TFA : 85/15/0.1) and fraction B by 1H NMR (400 MHz, CDCl3). See SI for full spectra.
Taken together these observations suggest a radical process. A plausible mechanism would start with the homolytic scission of the C-O bond in stretched intermediate 2 (Scheme 1), and the formation of alkyl radical 9 and carboxyl radical 10 (Figure 5a). A hydrogen atom abstraction would convert radical 10 to acid 5, while radical 9 would furnish amine 3 after elimination of the hexyl linker. This mechanism is further supported by the formation of amine 12 after irradiation of Barton ester 11,15 which is designed to generate a terminal radical similar to 9 after decarboxylation (Figure 5b). a
2 H N
b
Force
H O
O
O
N
O
9
10 Linker fragment NH 2
3
HO
O
5
N
Linker fragment prematurely
NH 2 + quenched
N H O
O
S hν
H O O
4
11
H O
Solv-H
O
Cl- H 2 N
12
intermediates
Figure 5. (a) Plausible mechanism for the elimination of the hexamethylene linker. Solv-H represents a hydrogen atom donor (typically THF or PMA). (b) A terminal radical similar to 9 can be generated by irradiation of Barton ester 11 with UV light to obtain amine 12. See SI for details.
Finally, we compared the reactivity of rotaxane 1, in which the force is transduced by the intermediacy of the macrocycle, to force-uncoupled rotaxane 13 (Mn = 38 kDa, Đ = 1.20) and free-thread model 14 (Mn = 37 kDa, Đ = 1.20), in which the force is directly applied to the axle (Figure 6).16 The two control polymers have an identical rate of dissociation (2.2×10-5 kDa1 .min-1) meaning that the rotaxane architecture itself has little impact when uncoupled from the force. Rotaxane 1 on the other hand dissociates at a faster rate than the reference polymers
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Journal of the American Chemical Society (3.3×10-5 kDa-1.min-1). This observation is supported by the higher rupture forces obtained from CoGEF calculations for 13′ (Fmax = 5.16 nN) and 14′ (Fmax = 5.26 nN, see Figure S9-10). a
O
2
a Br
n-1
O
O
1 CO2Me O
H O O O
RO
N O
O
O
13 OR
O
PF 6-
i
b
d H O c O
RO b
N
e H O
H H PF 6N
i
12
1
10
O
H H N
H O
c
CO2CH2CH 3 4 3
14 k OR
1/Mt - 1/M0 / 103.kDa-1
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8
13
6
14
4 2 0 0
60 120 180 240 300 360
t / min
Figure 6. Mechanical activation of (a) uncoupled rotaxane 13 and (b) free-thread model 14 lead to unselective cleavage in the PMA backbone. Red arrows indicate the direction of the force. (c) Dissociation kinetics of polymers 1, 13, and 14. Conditions: (i) US (20 kHz, 13.0 W/cm2, 1s ON/2s OFF), THF, 5-10˚C. Solid lines correspond to a linear fit (R2 = 0.977, 0.935, and 0.977 for 1, 13, and 14 respectively). Each point corresponds to the average over 4 sonication experiments. Error bars represent the standard deviation.
This difference in reactivity is explained by the fact that the reference polymers cleave in the PMA backbone, leaving the central axle intact after sonication in both 13 and 14, as shown by 1H NMR (Figure 7) and CoGEF calculations (see SI section 10). This confirms that the bonds constituting the axle are mechanically stronger than the polymer backbone and that force actuation via a rotaxane architecture induces a local increase of stress in the axle (Figure 2d). In essence, the rotaxane architecture acts as a lever10a-c that accelerates the dissociation of an interlocked covalent bond (Figure S10-11).
transduced by the intermediacy of the macrocycle, to its noninterlocked and uncoupled interlocked (i.e. pulled from both sides of the axle) counterparts. We found that the rotaxane dissociates via an unstoppering process in which the axle cleaves selectively at the junction with the terminal stopper. In this particular case, the unstoppering was accompanied by the elimination of the linker separating the binding station from the stopper. This selective cleavage is at the origin of the faster dissociation of the rotaxane-linked polymer compared to the non-interlocked or uncoupled reference polymers. Calculations have shown that the constriction of the axle by the stretched macrocycle results in the accumulation of high tensile, bending, and torsional stress that ultimately leads to the rupture of a covalent bond at the stopper-axle junction. In essence, the rotaxane architecture acts as a lever that accelerates the dissociation of an interlocked covalent bond. Interestingly, the same rotaxane-based mobile cross-links that confers slide-ring materials with shock-absorbing properties at low extension, could be detrimental to the mechanical properties of these materials at high extension. Overall, these results reveal yet another unique property of the mechanical bond that should pave the way to a new class of mechanochemical transformations.
ASSOCIATED CONTENT Supporting Information Detailed descriptions of CoGEF calculations, synthetic procedures, characterization of new compounds, and spectroscopic data. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author *
[email protected] ACKNOWLEDGMENT We thank the Royal Society for a Newton International Fellowship to M.Z. and a University Research Fellowship to G.D.B.
REFERENCES
Figure 7. Partial 1H NMR (500 MHz, CDCl3) of polymers 13 and 14 before (a, c) and after (b, d) sonication (360 min) respectively. The lettering refers to assignment in Figure 6.
CONCLUSIONS We have investigated the mechanical dissociation of a rotaxane built around a secondary ammonium and benzo-21-crown7 macrocycle experimentally, by sonication, and computationally, using the CoGEF method. We have compared the mechanical susceptibility of this rotaxane, in which the force is
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(1) Bruns, C. J.; Stoddart, J. F. The Nature of the Mechanical Bond; From Molecules to Machines; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2016. (2) Ito, K.; Mayumi, K.; Kato, K. Polyrotaxane and Slide-Ring Materials; The Royal Society of Chemistry: Cambridge, 2016. (3) Erbas-Cakmak, S.; Leigh, D. A.; McTernan, C. T.; Nussbaumer, A. L. Artificial Molecular Machines. Chem. Rev. 2015, 115, 10081– 10206. (4) Saitta, A. M.; Klein, M. L. First-Principles Study of Bond Rupture of Entangled Polymer Chains. J. Phys. Chem. B 2000, 104, 2197– 2200. (5) De Bo, G. Mechanochemistry of the Mechanical Bond. Chem. Sci. 2018, 9, 15–21. (6) (a) Sagara, Y.; Karman, M.; Verde-Sesto, E.; Matsuo, K.; Kim, Y.; Tamaoki, N.; Weder, C. Rotaxanes as Mechanochromic Fluorescent Force Transducers in Polymers. J. Am. Chem. Soc. 2018, 140, 1584–1587. (b) Stoll, R. S.; Friedman, D. C.; Stoddart, J. F. Mechanically Interlocked Mechanophores by Living-Radical Polymerization From Rotaxane Initiators. Org. Lett. 2011, 13, 2706–2709. (7) Lee, B.; Niu, Z.; Craig, S. L. The Mechanical Strength of a Mechanical Bond: Sonochemical Polymer Mechanochemistry of Poly(Catenane) Copolymers. Angew. Chem. Int. Ed. 2016, 55, 13086– 13089.
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Journal of the American Chemical Society (8) (a) Stauch, T.; Dreuw, A. Knots “Choke Off” Polymers Upon Stretching. Angew. Chem. Int. Ed. 2016, 55, 811–814. (b) Klein, M. L.; Saitta, A. M.; Soper, P. D.; Wasserman, E. Influence of a Knot on the Strength of a Polymer Strand. Nature 1999, 399, 46–48. (9) Zhang, M.; De Bo, G. Impact of a Mechanical Bond on the Activation of a Mechanophore. J. Am. Chem. Soc. 2018, 140, 12724– 12727. (10) (a) Wang, J.; Kouznetsova, T. B.; Kean, Z. S.; Fan, L.; Mar, B. D.; Martinez, T. J.; Craig, S. L. A Remote Stereochemical Lever Arm Effect in Polymer Mechanochemistry. J. Am. Chem. Soc. 2014, 136, 15162–15165. (b) Klukovich, H. M.; Kouznetsova, T. B.; Kean, Z. S.; Lenhardt, J. M.; Craig, S. L. A Backbone Lever-Arm Effect Enhances Polymer Mechanochemistry. Nat. Chem. 2013, 5, 110–114. (c) Klukovich, H. M.; Kean, Z. S.; Ramirez, A. L. B.; Lenhardt, J. M.; Lin, J.; Hu, X.; Craig, S. L. Tension Trapping of Carbonyl Ylides Facilitated by a Change in Polymer Backbone. J. Am. Chem. Soc. 2012, 134, 9577–9580. (11) Stevenson, R.; De Bo, G. Controlling Reactivity by Geometry in Retro-Diels–Alder Reactions Under Tension. J. Am. Chem. Soc. 2017, 139, 16768–16771. (12) Beyer, M. The Mechanical Strength of a Covalent Bond Calculated by Density Functional Theory. J. Chem. Phys. 2000, 112, 7307– 7312.
(13) Anastasaki, A.; Nikolaou, V.; Nurumbetov, G.; Wilson, P.; Kempe, K.; Quinn, J. F.; Davis, T. P.; Whittaker, M. R.; Haddleton, D. M. Cu(0)-Mediated Living Radical Polymerization: a Versatile Tool for Materials Synthesis. Chem. Rev. 2016, 116, 835–877. (14) Interestingly, sonication of stopper 5 alone shows the formation of P1, albeit to a lower extent that in the sonication of 1 (see Supporting Information section 7.8). This could indicate that formation of carboxyl radical 10 occur in the cavitation bubbles, further supporting a radical mechanism for the mechanical dissociation of 1. (15) Barton, D. H. R.; Crich, D.; Motherwell, W. B. New and Improved Methods for the Radical Decarboxylation of Acids. J. Chem. Soc. Chem. Comm. 1983, 17, 939–941. (16) Sonication of 6 confirmed the mechanical inertness of the stopper (see SI section 7.3). However, the kinetic studies were performed on synthetically more accessible models 13 and 14.
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