Mechanical susceptibility of a rotaxane

Article abstract of DOI:10.1021/jacs.9b06960

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 noninterlocked or uncoupled interlocked (i.e., pulled from both

Full text of DOI:10.1021/jacs.9b06960

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Article
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
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Mechanical Susceptibility of a Rotaxane
Min Zhang and Guillaume De Bo*
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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 (soni-
cation) 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.
architecture could accelerate the failure of this material at max-
imal elongation (when the macrocyclic cross-links are forced
against the terminal stoppers of the polymer axles).
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 me-
chanical bonds1 in mechanoresponsive materials2 and molecular
machines,3 and could shed some light on the effect of entangle-
Dethreading
ment 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
Unclipping
Unstoppering
macrocycle respectively (Figure 1).5 A third, non-covalent, dis-
sociation (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 in-
Figure 1. Possible dissociation pathways for a rotaxane under ten-
vestigated but the exact nature of their dissociation pathway(s)
sion. Plain and dashed black arrows denote covalent and non-cova-
lent processes respectively. Red arrows indicate the direction of the
could not be ascertained. Nevertheless, it was shown that a cat-
enane-containing polymer cleaves at the same rate as its non-
force.
interlocked counterparts, suggesting that a catenane architecture
doesn’t significantly alter the mechanical strength of its consti-
RESULTS AND DISCUSSION
tutive covalent bonds.7 On the other hand, overhand knots under
We previously found that the rate of dissociation of a Diels–
tension are predicted to weaken where the strand exits a loop,8a-
Alder mechanophore is reduced if the adduct is incorporated
into the axle of a rotaxane, due to the presence of a competing
b
a spatial arrangement not too dissimilar to the one found in
rotaxanes where the axle passes through the cavity of a macro-
high-stress region at the axle-stopper junction.9 We hypothe-
cycle. Indeed, we have recently shown that a rotaxane architec-
sized that in the absence of another mechanically weak covalent
ture could delay the activation of a mechanophore embedded in
bond, it should be possible to induce a selective cleavage of the
its axle due to the emergence of a competing high-stress region
axle of the rotaxane where the macrocycle meets the stopper.
where the axle is constricted by the macrocycle.9 Here we show
Scheme 1. Mechanical dissociation of a rotaxane via an un-
stoppering pathway*
that the same high-stress region can lead to the selective cleav-
age of a covalent bond in the axle in the absence of a competing
mechanophore. These results suggest that the rotaxane architec-
ture acts as a lever10a-c that accelerates the dissociation of inter-
locked covalent bonds by lowering the total loading force re-
quired to provoke their rupture. This finding has significant im-
plications 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 cross-
links.2 However, our results suggest that their rotaxane
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Page 2 of 6
O
R =
O
O
increase from ~108˚ at E0 to ~136˚ at Emax in 1′, compared to an
OR
O
O
a
Br
1
2
3
4
5
6
7
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′ ten-
sile 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.
n-1
CO2Me
Cl
O
O
-
PF6
O
H
O
Cl
O
H
O
H
y
z
x
N
O
N
O
RO
O
O
1
O
H
O
Cl
8
9
O
OR
O
O
10
11
12
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i
Cl
O
O
O
O
H
H
H
H
O
N
Cl
O
N
O
RO
-
PF6
O
O
2
O
O
O
Cl
Cl
O
O
2
C6H12
1
OR
3
f
H
O
d
j
i
O
O
HO2C
+
c
NH2
Cl
N
O
e
RO
h
O
+
H
g
b
3
4
5
O
O
O
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 ammo-
nium 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 ther-
mal lability of the DA adduct stopper allows for the recovery of
the axle fragment as well.
CoGEF calculations12 on model rotaxane 1′ (DFT B3LYP/6-
31G*, vacuum, no counterion), show a typical 3-stage elonga-
tion profile9 with: an initial energy increase attributed to the am-
monium/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 corre-
sponding to the enthalpic regime where bond deformation oc-
curs (~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; singu-
larly 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) Distribu-
tion 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 rotax-
ane 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
1
MeOH (fraction A). H 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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stopper (ΔδHd,e ~ 0.20 ppm) and the upfield shift of macrocycle
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 H NMR patterns
observed for protons Hf,g,h in the post-sonication mixture and
1
2
3
4
5
6
7
8
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.
1
reference 3ref (see SI section 7.5).
a
j
i
3
b
c
2
1
d, e
=
=
5
b
c
9
10
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12
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Solid-liquid
MeOH
extraction
1
2
Cl
Cl
Fraction A
X
7
d
7a
-H
7b -CH3
7c
X
b
d, e
c
a
-OH
7d -OCH3
7e -CH2CO2Me
Not observed
Cl
a
7.5
7.0
6.5
6.0
ppm
5.5
5.0
4.5
1. Ac2O
2. Furan, Δ
3. Solid-liquid
MeOH
Fraction B
Fraction B
1
Figure 3. Partial H NMR (500 MHz, CDCl3) of rotaxane 1
before (a) and after (b) sonication (240 min), along with macro-
cycle 4ref (c) and dissociation product 3ref (d) reference poly-
mers. The lettering refers to assignment in Scheme 1.
O
b
c
extraction
c
f
H
b
a
7ref
N
d
e
f
d
N
O
e
O
8
O
Analysis of MeOH fraction A confirms this picture (Figure 4).
1H NMR reveals that this fraction mainly contains stopper re-
lated 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 struc-
ture of the minor product but MS analysis suggests that it con-
tains triarylmethane fragment 7 with a polarity (HPLC) sitting
between alcohol 7c and triarylmethane 7a (Figure 4). The ab-
sence 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 con-
tribution 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 concom-
itantly. 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. Incorpora-
tion of this alcohol could not be detected in either of the frag-
ments (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 rad-
ical 10 because the carboxylic radical can be stabilized upon ad-
dition onto one of the chlorophenyl groups (Figure S8).14
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 for-
mation of amine 12 after irradiation of Barton ester 11,15 which
is designed to generate a terminal radical similar to 9 after de-
carboxylation (Figure 5b).
O
a
Force
b
H
O
Cl-
11
H2
N
2
O
N
H
N
N
O
O
4
O
S
H
H
9
10
Linker
fragment
O
hν
Linker
fragment
Solv-H
O
prematurely
quenched
intermediates
NH2
O
+
N
O
NH2
12
HO
H
3
5
O
Figure 5. (a) Plausible mechanism for the elimination of the hexa-
methylene linker. Solv-H represents a hydrogen atom donor (typi-
cally THF or PMA). (b) A terminal radical similar to 9 can be gen-
erated 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 kDa-
1.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
We then took advantage of the thermal lability of the DA stop-
per to isolate the second fragment resulting from the mechanical
dissociation of rotaxane 1. The polymer residue of the first ex-
traction was treated with acetic anhydride, then heated in pres-
ence of furan to release the maleimide from the axle (Figure 4).
MeOH extraction of the resulting mixture gives fraction B,
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(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).
Page 4 of 6
transduced by the intermediacy of the macrocycle, to its non-
interlocked and uncoupled interlocked (i.e. pulled from both
sides of the axle) counterparts. We found that the rotaxane dis-
sociates via an unstoppering process in which the axle cleaves
selectively at the junction with the terminal stopper. In this par-
ticular case, the unstoppering was accompanied by the elimina-
tion 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 co-
valent bond.
1
2
3
4
5
6
7
8
CO2CH2CH3
a
O
c
2
12
10
8
4
a
Br
1
1
3
n-1
O
CO2Me
O
O
O
O
H
13
O
H
H
O
N
OR
N
O
RO
O
O
-
PF6
O
H
O
9
6
13
i
10
11
12
13
14
15
16
17
18
19
20
21
22
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14
4
O
b
d
-
PF6
H
H
H
H
14
c
2
N
OR
N
k
O
e
RO
b
O
i
0
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 transfor-
mations.
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) Disso-
ciation 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 corre-
spond 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 soni-
cation experiments. Error bars represent the standard deviation.
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.
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 me-
chanically 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 architec-
ture acts as a lever10a-c that accelerates the dissociation of an in-
terlocked covalent bond (Figure S10-11).
AUTHOR INFORMATION
Corresponding Author
*guillaume.debo@manchester.ac.uk
ACKNOWLEDGMENT
We thank the Royal Society for a Newton International Fellowship
to M.Z. and a University Research Fellowship to G.D.B.
REFERENCES
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CONCLUSIONS
We have investigated the mechanical dissociation of a rotax-
ane built around a secondary ammonium and benzo-21-crown-
7 macrocycle experimentally, by sonication, and computation-
ally, using the CoGEF method. We have compared the mechan-
ical susceptibility of this rotaxane, in which the force is
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