A Catenane as a Mechanical Protecting Group

Article abstract of DOI:10.1021/jacs.0c01757

Mechanophores (mechanoresponsive molecules) offer great promises for the development of smart force-responsive materials. The activity of a mechanophore can be tuned by altering its structure or the composition of the actuating polymer. Here we show that a [2]catenane can act as a mechanical protecting group by diverting tensional forces away from a mechanically active functional group embedded in one of its rings. This property emerges from the mobility of the two rings of the catenane, which are able to rotate along each other until the tension equalizes over the entirety of the catenated framework. This approach provides a new way to control the mechanical activity of a mechanophore.

Full text of DOI:10.1021/jacs.0c01757

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Communication
A Catenane as a Mechanical Protecting Group
Min Zhang, and Guillaume De Bo
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c01757 • Publication Date (Web): 04 Mar 2020
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A Catenane as a Mechanical Protecting Group
Min Zhang and Guillaume De Bo*
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Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom
Supporting Information Placeholder
are placed on opposite sides of the macrocycle, the tension
spreads equally across the macrocycle, which then
experiences less tension than the linear sections of the
polymer (Figure 1b). Hence any mechanophore placed
within this sort of macrocycle would experience a smaller
elongation than in the linear part of the polymer.
However, this approach requires the macrocycle to be
perfectly symmetrical in regard to the anchorage points.
A catenane architecture can overcome this problem
because the constituting macrocycles will rotate along
each other to a position where the tension is spread
equally over the two rings (Figure 1c).24,33-34 Moreover, it
has been shown that the ultrasonic degradation of a
poly[2]catenane proceeds at the same rate as its non-
interlocked counterparts, suggesting that the catenane
architecture does not negatively impact the mechanical
integrity of the polymer chain.35
ABSTRACT:
Mechanophores
(mechanoresponsive
molecules) offer great promises for the development of
smart force-responsive materials. The activity of a
mechanophore can be tuned by altering its structure or the
composition of the actuating polymer. Here we show that
a [2]catenane can act as a mechanical protecting group by
diverting tensional forces away from a mechanically
active functional group embedded in one of its rings. This
property emerges from the mobility of the two rings of
the catenane, which are able to rotate along each other
until the tension equalizes over the entirety of the
catenated framework. This approach provides a new way
to control the mechanical activity of a mechanophore.
Mechanophores are molecular entities designed to react
upon application of a mechanical force,1 and their
structures can be tailored for specific applications,2 such
as: force-induced catalysis,3 damage-reporting,4 and
material self-strengthening.5 Similarly, their mechanical
activity can be altered by modifying the actuating
polymer,6-10 varying the substituents,11 or changing the
connectivity,12-20 and can be controlled by mechanical21
or photochemical22 gating. Mechanical bonds,23 with their
capacity for large amplitude movements, are ideally
suited
to
interface
mechanical
force
with
mechanophores.24 In fact, we have recently shown that a
rotaxane can be used to tame the mechanical activity of a
mechanophore embedded in its axle.6 However, these
interlocked structures are themselves mechanically
active, and are susceptible to degradation by unstoppering
and related pathways.25 Here we show that a catenane acts
as a mechanical protecting group by spreading the tensile
deformation across the entire framework of the catenane,
thereby protecting a mechanophore incorporated in one of
its rings. This approach provides a new way to control the
mechanical activity of a mechanophore.
Figure 1. Distribution of tensile deformation in
macrocycles (a, b) and a catenane (c) under tension.
We have designed catenane 1 in which a benzo-21-crown-
7 (B21C7) macrocycle is wrapped around a larger 39-
membered ring macrocycle (Figure 2a). The resulting
catenane contains two identical mechanophores built
around a mechanically active furan-maleimide Diels–
Alder (DA) adduct.13 These adducts are placed
strategically within the catenane framework to evaluate
the influence of the catenane architecture in the
transduction of the force towards the mechanophores. In
other words, the activity of the intracyclic adduct
(orange), embedded in the large macrocycle, will be
In a polymer, tension spreads along the shortest path
between the two chain-ends. A macrocycle can be used to
divert tension away from a section of the polymer (Figure
1a).17,26-28 This phenomenon is at the origin of the
mechanical gating concept.21,29-32 If the anchoring points
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compared to the extracyclic adduct (blue), placed along
Page 2 of 7
structure of catenane 10 offers several synthetic routes for
its assembly. We opted for an approach in which alkyne-
terminated rotaxane 8 is initially formed from macrocycle
5, axle 6, and acid chloride 7. We have previously shown
that the maleimide unit terminating axle 6 can act as a
stopper for a B21C7 macrocycle such as 5.6 Perhaps more
surprising, the newly formed ester appeared to be large
enough to maintain the rotaxane architecture of 8
throughout its formation and isolation. Extension of this
1
2
3
4
5
6
7
8
the linear linker joining the small macrocycle to the
actuating polymer. Upon application of a force, the small
macrocycle in 1 should rotate along the larger macrocycle
until it reaches a position where the tension is equalized
either side of the contact point between the two
macrocycles, at the antipode of the polymer anchor (4,
Figure 2a). Because the tension experienced in the linear
segment is then spread equally over the two halves of a
macrocycle, one can expect the extracyclic adduct to
experience a higher deformation, and hence a faster
activation, than its intracyclic counterpart. As a result,
catenane 2 and furan-terminated polymer 3 are the
expected products of the mechanical activation of 1.
9
rotaxane
via
copper-catalyzed
azide-alkyne
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cycloaddition37-40 installs the furan-terminated chain
necessary to form the intracyclic adduct. Finally,
precursor 9 was cyclized into catenane 10 through an
intramolecular Diels–Alder reaction. Control macrocycle
11 was assembled using a similar strategy (see SI for
details).
O
O
a
O
O
O
O
N
O
N
Br
H
R =
n
O
O
5
Force
+
O
CO2Me
O
H
O
1
Scheme 1. Synthesis of macromolecular catenane 1*
4
i
RO
O
H
H
O
O
O
O
H
2
3
OR
O
3
N
O
N
O
O
2
O
O
O
N
N
2
O
OR
H
H
O
OR
H
H
H
O
O
-
O
O
O
O
O
O
O
O
O
-
O
O
PF6
O
PF6
HN
O
HN
N
N
N
5
1
2
5
N
O
N
N
H
Via
N
O
N
O
2
OR
O
O
O
O
O
H
H
H
H
H
O
-
O
O
O
O
O
N
O
O
O
4
PF6
HN
O
O
OR
O
N
N
5
N
b
i
2
4
1
ii
5
*Conditions: (i) Et3N, DCM, 16 h, 25 ˚C, 32%. (ii) S10,
Cu(MeCN)4PF6, DCM/MeCN, 25 ˚C, 16 h, 45%. (iii)
Toluene/DMF, 70 ˚C, 20 h, 20%. (iv) methyl acrylate,
CuBr2/Cu0, DMSO, 2 h, r.t. (Mn = 65 kDa, Đ = 1.19).
2, 3
b, c
iii
iv
1
4
d
a
We performed the mechanical activation of catenane 1 in
acetonitrile at 5-10˚C, using high-intensity ultrasound
1
(Figure 2a). H NMR analysis of the sonicated sample
confirms that the dissociation proceeds via the
retrocycloaddition of the extracyclic DA adduct (blue) on
the linear segment joining the crown ether macrocycle to
the PMA (Figure 2). The emergence of characteristic
signals associated with the aromatic (H1, 7.4 ppm; H2/H3,
6.35 ppm) and methylene protons of the furan unit (H4,
5.0 ppm), and the olefinic protons of the maleimide (H5,
6.7 ppm) is diagnostic of furan-terminated polymer 3. In
contrast, the signals expected from the activation of the
intracyclic adduct (Figure 2biv) are absent from the post-
sonication 1H NMR (Figure 2bii). These results
demonstrate the selective activation of the extracyclic
adduct, placed in the linear section of catenane 1.
Figure 2. (a) Mechanical activation of catenane 1.
Conditions: (i) US (20 kHz, 13.0 W/cm2, 1s ON/2s OFF),
CH3CN, 5-10 ˚C, 240 min. Red arrows indicate the direction
of the force. Scissile bonds shown in bold red. (b) Partial 1H
NMR (500 MHz, CDCl3) of catenane 1 before (i) and after
(ii) sonication, along with reference compounds 3ref (iii) and
rotaxane 9 (iv). The lettering refers to assignment in Figure
2a.
Chain-centered macromolecular [2]catenane 1 (Mn = 65
kDa, Đ = 1.19) was obtained by single electron transfer
living radical polymerization (SET-LRP)36 of methyl
acrylate from catenane 10 (Scheme 1). The modular
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O
H
a
O
O
To confirm that the reduced mechanical susceptibility of
H
H
Br
O
O
O
R =
n
1
the intracyclic adduct is a consequence of the catenane
architecture, and not due to its incorporation in a
macrocycle, we performed a similar experiment on
macrocycle 11 (Figure 3a). In 11, the extracyclic adduct
is covalently linked to the N atom that was previously
used as a binding station for the crown ether macrocycle
in 1. This geometry brings the extracyclic DA adduct
closer to the intracyclic adduct than in catenane 1 and in
this case the tension is expected to bypass a large section
of the macrocycle (Figure 1a) and to build up at a similar
rate in both adducts (14, Figure 3a). If the extracyclic
adduct breaks first, macrocycle- and furan-terminated
polymers 12 and 3 should form. Otherwise, the initial
rupture of the intracyclic adduct should lead to
intermediate polymer 15, which can be further broken into
3 and 13. The presence of characteristic signals associated
with the methylene protons of both furan units (H4, 5.0
ppm; Hd 5.2 ppm), and the olefinic protons of both
maleimides (H5, 6.68 ppm; He 6.72 ppm) in the post-
N
N
O
CO2Me
OR
N
H
N
O
2
3
O
OR
3
O
Via
O
O
O
H
O
H
H
O
O
O
O
11
HN
O
N
N
O
O
2
4
5
O
3
H
O
O
N
O
14
15
5
N
N
6
7
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9
O
H
H
O
O
N
N
O
O
i
Force
N
O
3
O
O
10
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O
O
e
O
O
O
H
H
O
O
N
3
O
O
b
a
3
N
N
O
O
N
O
N
O
c
O
O
N
O
OR
O
OR
O
5
O
O
O
O
5
d
O
O
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13
HN
O
2
+
HN
O
2
N
2
3
5
N
N
5
N
OR
4
N
N
1
O
3
b
2, 3, b, c
i
1
sonication H NMR spectrum (Figure 3bii), indicate that
5
ii
e
both intra- and extracyclic adducts have an equal
probability to break (as confirmed by the ~2:1 H5/He and
H4/Hd integration ratio, see section 7.4.2 in SI). In other
words, the activity of a mechanophore is not impacted by
the macrocyclic architecture itself, but by the way the
macrocycle is connected to the actuating polymers.
1
2, 3
4
iii
iv
d
e
b, c
a
Figure 3. (a) Mechanical activation of macrocycle 11.
Conditions: (i) US (20 kHz, 13.0 W/cm2, 1s ON/2s OFF),
CH3CN, 5-10 ˚C, 240 min. Red arrows indicate the direction
of the force. Scissile bonds shown in bold red. (b) Partial 1H
NMR (500 MHz, CDCl3) of macrocycle 11 before (i) and
after (ii) sonication, along with reference compounds 3ref
(iii) and 15ref (iv). The lettering refers to assignment in
Figure 3a.
This is confirmed when comparing the simulated
elongations of model catenane 1′, and model macrocycles
11′ and 16′ (Figure 4). The elongation profile of model
catenane 1′ (Figure 4a), obtained from CoGEF
calculations41 (DFT B3LYP/6-31G*), begins with a low-
energy plateau, corresponding to the rotation of the small
macrocycle away from the binding station, and is
followed by a high-energy extension, which accounts for
the deformation of the covalent bonds composing the
catenane framework.
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increases at a much higher rate upon elongation of
1
catenane 1′ than its intracyclic counterpart. This is due to
the ability of the small macrocycle to freely move around
the larger one to find an equilibrium position where the
tension is spread equally over both halves of the
macrocycles (Figure 4c). The same effect is observed in
model macrocycle 16′ where the actuating groups are
anchored in antipodal positions (Figure 4b-c). In contrast,
the intra- and extracyclic scissile bonds in macrocycle
11′, a model of 11 with a shorter linker, present an
identical mechanochemical coupling (Figure 4b). In this
case, tension follows the shortest path between the two
actuating groups. This results in a highly stressed linear
segment incorporating both DA adducts that leaves the
larger portion of the macrocycle virtually free from
deformation (Figure 4c). Remarkably, the intracyclic
adduct is protected from mechanical force by the catenane
architecture even in the absence of the mechanically labile
extracyclic adduct (Figure 5). In this case, the cleavage of
the terminal C-C bond (blue) is observed upon simulated
elongation of catenane model 17′ (Figure 5).
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Figure 5. Evolution of the length of intra- (orange triangles)
and extracyclic (blue dots) ‘scissile’ bonds (b) in model
catenane 17′ (a) upon simulated elongation (CoGEF, DFT
B3LYP/6-31G*) with intracyclic and extracyclic ‘scissile’
bonds in bold orange and blue respectively.
In conclusion, we have shown that a catenane architecture
can be used as a mechanical protecting group, effectively
diverting tensional forces away from a mechanically
active functional group. This property emerges from the
mobility of the two rings of the catenane, which are able
to rotate along each other until the tension equalizes over
the entirety of the catenated framework. These results
further demonstrate how the combination of mechanical
bonds and mechanical force leads to new
mechanochemical behaviors, and provide a new approach
to control the activity of a mechanophore.
Figure 4. Evolution of energy (a) in catenane 1′, and length
of intra- (orange triangles) and extracyclic (blue dots)
‘scissile’ bonds (b) in model catenane 1′, and macrocycles
11′ and 16′ upon simulated elongation (CoGEF, DFT
B3LYP/6-31G*). Distribution of tensile deformation at Emax
(c) in models 1′, 11′, and 16′. Values obtained from CoGEF
calculations (DFT B3LYP/6-31G*). (d) Structures of
models 1′, 11′, and 16′ with intracyclic and extracyclic
‘scissile’ bonds in bold orange and blue respectively.
This extension culminates with a highly stretched
intermediate (Figure 4c) at Emax and is followed by the
dissociation of the extracyclic adduct. The selectivity of
the dissociation is reflected in the mechanical coupling of
the intra- and extracyclic ‘scissile’ bonds (Figure 4b).
Indeed, the length of the extracyclic scissile bond
ASSOCIATED CONTENT
Supporting Information
Detailed descriptions of CoGEF calculations, synthetic
procedures, characterization of new compounds, and
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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.
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