Cyclodextrin-Based [3]Rotaxane-Crosslinked Fluorescent Polymer: Synthesis and De-Crosslinking Using Size Complementarity

Article abstract of DOI:10.1002/anie.201809171

Vinyl-group-substituted, α-cyclodextrin-based, size-complementary [3]rotaxanes were synthesized as crosslinkers for rotaxane-crosslinked poly(methyl methacrylate) (RCP) by radical polymerization. The size complementarity of the crosslinkers made it possible to de-crosslink the RCP by heating, and the degree of decoupling was monitored by fluorescence intensity, depending on the state of the axle component of the rotaxane crosslink moiety.

Full text of DOI:10.1002/anie.201809171

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Accepted Article
Title: Cyclodextrin-Based [3]Rotaxane-Crosslinked Fluorescent
Polymer: Synthesis and De-crosslinking Using Size-
Complementarity
Authors: Yosuke Akae, Hiromitsu Sogawa, and Toshikazu Takata
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201809171
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10.1002/anie.201809171
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Cyclodextrin-Based [3]Rotaxane-Crosslinked Fluorescent Polymer:
Synthesis and De-crosslinking Using Size-Complementarity
Yosuke Akae, Hiromitsu Sogawa, and Toshikazu Takata*
Abstract: Vinyl group-substituted a-cyclodextrin (CD) based size-
complementary [3]rotaxanes were synthesized as crosslinkers for
rotaxane-crosslinked poly(methyl methacrylate) (RCP) via radical
polymerization. The size-complementarity of the crosslinkers made it
possible to de-crosslink RCP by heating, and the degree of
decoupling could be monitored by fluorescence intensity depending
on the state of the axle component of the rotaxane crosslink moiety.
Rotaxanes, mechanically interlocked molecules, have been
extensively studied from the viewpoints of synthesis, function, and
application.1,2 Rotaxane-based polymers, including topology-
switchable polymers and rotaxane-crosslinked polymers (RCPs),
were developed owing to their unique properties based on the
high mobility of their components.3,4 Among them, we reported the
de-crosslinking ability of RCPs using a crown ether-based size-
complementary rotaxane crosslinker, the axle ends of which were
as large as the wheel cavity.5 Dissociation of the mechanically
Figure 1. De-crosslinking and change in the fluorescence of an a-CD-based
rotaxane crosslinked polymer.
interlocked size-complementary rotaxane moiety induces the de-
crosslinking of RCPs without any damage to the polymer main
chain, whereas dissociation of the typical network polymer is
accompanied inevitably by the breaking of covalent bonds.
Meanwhile, we developed a scheme for an easy one-pot
synthesis of a-cyclodextrin (CD) based size-complementary
[3]rotaxanes via the urea end-cap method,6 which yielded the
corresponding [3]rotaxanes as head-to-head sole isomers with
good yields in spite of the synthetic difficulty of CD-based
rotaxanes in low-molecular-weight systems.7,8 This method has
strong potential for use in the development of mono-substituted
a-CD-based size-complementary [3]rotaxanes, which can be
used as a novel stimuli-responsive units in supramolecular
scaffolds. Herein, we describe the synthesis and characterization
of a novel mono-substituted a-CD-based size-complementary
[3]rotaxane, fabrication of RCPs using a [3]rotaxane as a
crosslinker, and their de-crosslinking behavior (Figure 1). The
degradation process is monitored through unique changes in the
fluorescence of the RCPs depending on the relative location of
the rotaxane components.
O
O
N
O
N
N
(OAc)17
MeO
O
H
N
H
N
N
H
N
H
O
OMe
(OAc)17
N
N
O
N
O
O
1
O
O
N
N
(OAc)17
N
Br
MeO
O
H
N
H
N
N
H
N
H
O
OMe
Br
(OAc)17
N
N
N
O
O
2
[*]
Dr. Y. Akae, Dr. H. Sogawa, Prof. T. Takata
Department of Chemical Science and Engineering
Tokyo Institute of Technology
Figure 2. Synthesis of mono-substituted a-CD-based size-complementary
rotaxane crosslinkers 1 (fluorescent) and 2 (not fluorescent).
2-12-1, O-okayama, Meguro-ku, Tokyo 152-8552 (Japan)
Fax: (+81) 03-5734-2888
E-mail: ttakata@polymer.titech.ac.jp
Novel mono-substituted a-CD-based size-complementary
[3]rotaxanes 1 and 2 were synthesized by urea end-cap method
(Figure 2).6,9 6-Mono-azido-a-CD was used as a starting material
to form a size-complementary [3]rotaxane structure. After the
rotaxane formation, modification reactions were carried out to
introduce fluorescent biphenyl moieties and methacryl
[**]
This work was supported by JST CREST Grant Number
JPMJCR1522, Japan, JSPS KAKENHI Grant Number JP16K17955.
Fellowship to Y. A. from JSPS for Young Japanese Scientists is also
gratefully acknowledgement.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/anie.201809171
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substituents for the polymerization. Peracetylation of the wheels
was conducted to increase the solubility in organic solvents. Size-
complementary [3]rotaxane crosslinker 2 without fluorescent
groups was synthesized to gain the fundamental data for the de-
crosslinking of RCP as discussed later.
1 was studied using 3, which is a size-complementary [3]rotaxane
analog with the same fluorescent-active axle 4 and PAc a-CDs.
First, 4 showed fluorescent signals in DMF, which appears as a
light-green color to the naked eye, whereas a blue-colored
emission was observed in the case of 3 (Figure 3). On the
contrary, UV-Vis spectra of these two compounds showed almost
the same levels of absorption. The solvent dependency of 3 was
further examined to clarify this phenomenon.9 As a result, the
solvatochromism of 3 as a push–pull-type dye was observed.11
Namely, fluorescence exhibited a red shift in polar solvents such
as MeOH, but a blue shift in weak polar solvents such as CHCl3.
Therefore, the fluorescent blue shift caused by PAca-CDs was
considered to have occurred as a result of the reduced polarity
around 4. In other words, the hydrophobicity of PAca-CDs as a
relatively weak polar solvent based on the 36 acetyl units
introduced in the two a-CD wheels induced the blue shift of 4.
Owing to this difference in fluorescence between 4 and PAca-CD-
based [3]rotaxane 3, they could be distinguished via fluorescence
spectroscopy and even by the naked eye, and this characteristic
can be applied to polymer network systems.
The 1H NMR spectra of [3]rotaxanes containing mono-
substituted a-CD 1 and 2 appeared to be severely complicated
compared to those of peracetylated (PAc) derivative 3.9 This
change in the NMR spectra was induced by the asymmetric
structure of the monosubstituted a-CD on each on the 6 glucose
units. The deslipping kinetics of [3]rotaxane 1 and 2 were
observed in a manner similar to that of 3 at temperatures higher
than 100°C.10
Next, free radical polymerization of methyl methacrylate
(MMA) and crosslinker 2 (0.1ꢀmol%) was conducted using
azobis(butyronitrile) (AIBN) at 60°C to obtain RCP-PMMA
(Figure 4). RCP-PMMA was well swollen in several organic
solvents, including PhCl (630 wt%), CHCl3 (750 wt%), and DMF
(400 wt%), depending on the solubility of the trunk polymer.12
RCP-PMMA was stable and did not decompose at room
temperature under the air and in the solvents, indicating the
deslippage did not take place under these conditions.
The de-crosslinking of RCP-PMMA at 100°C in PhCl was
examined (Figure 5A and 5B). Here, PhCl was selected as a
swelling solvent because its boiling point is higher than 100°C,
and RCP-PMMA was well swollen. Complete decomposition of
the gel was observed visually after 12 days (Figure 5B). GPC
measurement revealed the existence of a high-molecular-weight
polymer (Mn = 150 kDa, PDI 3.0) in the PhCl solution after heating,
suggesting the decomposition of the network structure without
chain scission of the trunk polymer itself.9 This de-crosslinking
behavior was observed in DMF as well, which has a suitable
boiling point and swelling property for RCP-PMMA.
Figure 3. Fluorescence spectra of 3, and 4 (10 µM, DMF, 293 K).
Owing to the difficulty in synthesizing monosubstituted a-CD-
based rotaxanes on a large scale, the fluorescence of crosslinker
Figure 4. A) Synthesis of RCP-PMMA and F-RCP-PMMA; (B) Photograph of RCP-PMMA gel swollen in CHCl3.
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Figure 5. (A) De-crosslinking of RCP-PMMA and F-RCP-PMMA; (B) Photographs of RCP-PMMA swollen in PhCl and after heating for 12 days at 100°C; (C)
Photographs of F-RCP-PMMA in DMF and after heating for 18 days at 100°C, and (D) those in the dark with being irradiated by 365ꢀnm light; (E) Photographs of
F-RCP-PMMA in PhCl and after heating for 14 days at 100°C, and (F) those in the dark with being irradiated by 365ꢀnm light.
Meanwhile, fluorescence-active RCP (F-RCP-PMMA) was
synthesized using crosslinker 1 in a manner similar to that of
RCP-PMMA. The stability of F-RCP-PMMA at room temperature
was same as RCP-PMMA. In addition, the swelling ratio of F-
RCP-PMMA showed similar tendency to that of RCP-PMMA (670
wt% in PhCl, 950 wt% in CHCl3, and 460 wt% in DMF),12
suggesting PhCl and DMF could be suitable for the de-
crosslinking in this case as well, in terms of the swelling ratio value
and high boiling point. F-RCP-PMMA swollen in DMF showed
blue fluorescence that could be clearly identified by the eye
(Figure 5D). Gradual de-crosslinking of F-RCP-PMMA in DMF at
100°C was monitored on the basis of the collapse of the gel and
light-green fluorescence in solution phase, indicating the
deslipping of wheels and the diffusion of dumbbell 4. Notably, the
difference in the color of fluorescence between F-RCP-PMMA
and 4 was identified clearly. This result strongly indicated that the
decomposition was induced by the deslipping, which involved the
emergence of dumbbell 4, as opposed to other cleavages
generating independent rotaxane structures. F-RCP-PMMA
almost disappeared after 18 days, and it did not change any more
(Figure 5C and 5D). Furthermore, the gel swollen in PhCl showed
stronger blue-shifted fluorescence than that in DMF, suggesting
that solvatochromism continued to have an effect in the gel status
(Figure 5F). Interestingly, the gel was hardly de-crosslinked in
PhCl, even when it was heated at 100°C for more than two weeks,
as shown in Figure 5E, in which the remained gel was clearly
identified by eyes contrary to Figure 5C. The reason for this
solvent dependence remains unclear. The solubility of dumbbell
4 might affect the decomposition of gels because 4 was highly
soluble in DMF but poorly soluble in PhCl. Meanwhile, the
swelling ratio of F-RCP-PMMA itself in PhCl (670 wt%) was better
than in DMF (460 wt%), which seems inconsistent with the de-
crosslinking behavior results. However, the swelling ratio
depends mainly on the affinity of the trunk polymer to a solvent,
whereas the deslipping reaction occurs around the rotaxane-
crosslinked moiety. In other words, the affinity between the
dumbbell and the solvent could have a more important effect on
the degradation of the rotaxane structure than the swelling ratio,
because the dumbbell moiety, not the trunk polymer, must form a
suitable conformation for the deslipping reaction to occur.
Figure 6A shows the fluorescence spectra of the DMF
solution during the de-crosslinking of F-RCP-PMMA at 100°C.
The spectra agreed completely with the emissions of dumbbell 4
and were not derived from any rotaxane structure. The increase
in intensity was readily apparent in the fluorescence
spectroscopic analysis. When the fluorescence intensity was
plotted against the heating time, steep dissociation was observed
at the start (Figure 6B). After 120ꢀh, the rate of increase in the
fluorescence intensity decreased, but the gel remained at this
time. When we evaluated the dissociation ratio based on the
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fluorescent intensity after 285 h, almost quantitative dissociation
was estimated by comparing to the theoretical value, which was
calculated from the feed ratio of the fluorescent crosslinker 1.9
These results suggested complete deslipping was necessary for
dissociation of the entire gel. It should be emphasized that this
dissociative analysis could be carried out owing to the presence
of a structural-definite crosslinker.
fluorescence of the dumbbell moiety. The fluorescence intensity
increased according to the level of de-crosslinking of the gel,
indicating successful quantitative spectroscopic monitoring of the
degradation process of this type of RCPs. This novel degradable
fluorescent polymer network method can be applied in various
vinyl polymer systems. Work on other applications of this rotaxane
is underway.
Keywords: rotaxane-crosslinked polymer • cyclodextrin • size-
150
A)
Fluorescence
complementary rotaxane • fluorescence
100
50
0
[1]
[2]
M. Xue, Y. Yang, X. Chi, X. Yan, F. Huang, Chem. Rev. 2015, 115, 7398.
(a) S. Hoekman, M. O. Kitching, D. A. Leigh, M. Papmeyer, D. Roke, J.
Am. Chem. Soc. 2015, 137, 7656; (b) Z. Niu, T. L. Price Jr., C. Slebodnick,
H. W. Gibson, Tetrahedron Lett. 2016, 57, 60; (c) T. Ogoshi, D. Yamafuji,
T. Aoki, T. Yamaguchi, Chem. Commun. 2012, 48, 6842; (d) M. Lee, H.
W. Gibson, J. Polym. Sci. Part A 2016, 54, 1647; (e) N. Zhu, K. Nakazono,
T. Takata, Chem. Lett. 2016, 45, 445; (f) R. Hayashi, P. Slavik, Y. Mutoh,
T. Kasama, S. Saito, J. Org. Chem. 2016; (g) B. Lewandowski, G. D. Bo,
J. W. Ward, M. Papmeyer, S. Kuschel, M. J. Aldegunde, P. M. E.
Gramlich, D. Heckmann, S. M. Goldup, D. M. D’Souza, A. E. Fernandes,
D. A. Leigh, Science 2013, 339, 189; (h) P. R. Ashton, I. Baxter, M. C. T.
Fyfe, F. M. Raymo, N. Spencer, J. F. Stoddart, A. J. P. White, D. J.
Williams, J. Am. Chem. Soc. 1998, 120, 2297.
330
400
500
600
670
wavelength [nm]
18000
B)
12000
6000
0
[3]
[4]
(a) S. Suzuki, K. Matsuura, K. Nakazono, T. Takata, Polym. J. 2014, 46,
355; (b) H. Iguchi, S. Uchida, Y. Koyama, T. Takata, ACS Macro Lett.
2013, 2, 461; (c) Z. Chen, D. Aoki, S. Uchida, H. Marubayashi, S. Nojima,
T. Takata, Angew. Chem. Int. Ed. 2016, 55, 2778; (d) G. D. Bo, J. D.
Winter, P. Gerbaux, C.-A. Fustin, Angew. Chem. Int. Ed. 2011, 50, 9093.
(a) D. Aoki, S. Uchida, T. Takata, ACS Macro Lett. 2014, 3, 324; (b) T.
Ogawa, N. Usuki, K. Nakazono, Y. Koyama, T. Takata, Chem. Commun.
2015, 51, 5606; (c) J. Sawada, D. Aoki, S. Uchida, H. Otsuka, T. Takata,
ACS Macro Lett. 2015, 4, 598; (d) K. kato, Y. Okabe, Y. Okazumi, K. Ito,
Chem. Commun. 2015, 51, 16180.
0
100
200
300
time [h]
Figure 6. (A) Fluorescence spectral change of a DMF solution of F-RCP-PMMA
heated at 100°C (lex = 346ꢀnm, 293ꢀK). (B) Time–fluorescence intensity curve
of (A).
[5]
[6]
(a) Y. Kohsaka, K. Nakazono, Y. Koyama, S. Asai, T. Takata, Angew.
Chem., Int. Ed. 2011, 50, 4872; (b) K. Iijima, Y. Kohsaka, Y. Koyama, K.
Nakazono, S. Uchida, S. Asai, T. Takata, Polym. J., 2014, 46, 67.
(a) Y. Akae, H. Okamura, Y. Koyama, T. Arai, T. Takata, Org. Lett. 2012,
14, 2226; (b) Y. Akae, Y. Koyama, S. Kuwata, T. Takata, Chem. Eur. J.
2014, 20, 17132; (c) Y. Akae, Y. Koyama, H. Sogawa, Y. Hayashi, S.
Kawauchi, S. Kuwata, T. Takata, Chem. Eur. J. 2016, 22, 5335; (d) Y.
Akae, T. Arai, Y. Koyama, H. Okamura, K. Johmoto, H. Uekusa, S.
Kuwata, T. Takata, Chem. Lett. 2012, 41, 806.
Another fluorescent-active RCP was synthesized using N,N-
dimethylacrylamide as
a
monomer (F-RCP-PDMAA) for
examining the effect of the trunk polymer.9 F-RCP-PDMAA
swelled well in polar solvents such as MeOH (610 wt%) and water
(730 wt%) according to the affinity of the trunk polymer. The de-
crosslinking of F-RCP-PDMAA in PhCl and DMF was evaluated
in a manner similar to that in the case of F-RCP-PMMA. The
fluorescence and de-crosslinking behavior of F-RCP-PDMAA
were observed in manners similar to those in the case of F-RCP-
PMMA, indicating that the decomposition worked well for another
trunk polymer network as well.
[7]
[8]
(a) K. Uekama, F. Hirayama, T. Irie, Chem. Rev. 1998, 98, 2045. (b) G.
Wenz, B. H. Han, A. Muller, Chem. Rev. 2006, 106, 782.
(a) H. Ogino, J. Am. Chem. Soc. 1981, 103, 1303; (b) Y. L. Zhao, W. R.
Dichtel, A. Trabolsi, S. Saha, I. Aprahamian, J. F. Stoddart, J. Am. Chem.
Soc. 2008, 130, 11294; (c) K. Yamauchi, A. Miyawaki, Y. Takashima, H.
Yamaguchi, A. Harada, J. Org. Chem. 2010, 75, 1040; (d) Y. Suzaki, H.
Endo, T. Kojima, K. Osakada, Dalton Trans. 2013, 42, 16222; (e) A.
Harada, J. Li, M. Kamachi, J. Am. Chem. Soc. 1994, 116, 3192; (f) S.
Kasiouli, F. D. Stasio, S. O. McDonnell, C. P. Constantinides, H. L.
Anderson, F. Cacialli, S. C. Hayes, J. Phys. Chem. B 2013, 117, 5737;
(g) H. Yan, L. Zhu, X. Li, A. Kwok, X. Li, H. Agrenc, Y. Zhao, RSC Adv.
2013, 3, 2341; (h) J. Terao, Y. Konoshima, A. Matono, H. Masai, T.
Fujihara, Y. Tsuji, Beilstein J. Org. Chem. 2014, 10, 2800; (i) L. Zalewski,
J. M. Mativetsky, S. Brovelli, M. Bonini, N. Crivillers, T. Breiner, H. L.
Anderson, F. Cacialli, P. Samorì, Small 2012, 12, 1835; (j) A. Kuzuya, T.
Ohnishi, T. Yamazaki, M. Komiyama, Chem. Asian J. 2010, 5, 2177.
See ESI.
To gain the information about the mechanical properties and
the cross-linking density of RCPs, physical property evaluation
including tensile test should be useful.4c,d,13 However, obtained
RCPs were too fragile to be tolerant of physical tests. The flexible
RCPs suitable for the physical experiments could be prepared by
e.g. changing the matrix polymer. This issue will be attained in a
different work.
In conclusion, novel structure-definite a-CD-based size-
complementary [3]rotaxanes were synthesized using the urea
end-capping method, and they were used as crosslinkers to form
vinyl polymer-based RCPs. Heating the synthesized RCPs
induced deslipping of the size-complementary rotaxane moiety,
resulting in the de-crosslinking of the polymer network. This
dissociation process was observed on the basis of the
[9]
[10] Further detailed deslipping kinetics of [3]rotaxane 3 and the derivatives
was reported in another paper; Y. Akae, H. Sogawa, T. Takata, Angew.
Chem. Int. Ed. 2018, 57, 11742.
[11] (a) P. T. Chou, C. P. Chang, J. H. Clements, K. Meng-Shin, J. Fluoresc.
1995, 5, 369; (b) Y. Niko, S. Kawauchi, G. Konishi, Chem. Eur. J. 2013,
19, 9760; (c) H. W. Gibson, F. C. Bailey, Can. J. Chem. 1975, 53, 2162;
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10.1002/anie.201809171
Angewandte Chemie International Edition
COMMUNICATION
(d) H. W. Gibson, F. C. Bailey, Tetrahedron 1974, 30, 2043; (e) H. W.
Gibson, F. C. Bailey, J. Chem. Soc., Perkin Trans. II 1976, 1575.
[12] The swelling ratio was calculated by following equation: swelling ratio
[wt%] = [(swollen RCP weight) – (dry RCP weight)) / (dry RCP weight)] x
100. For more details, see ESI.
[13] (a) K. Iijima, D. Aoki, H. Otsuka, T. Takata, Polymer 2017, 128, 392; (b)
K. Iwaso, Y. Takashima, A. Harada, Nat. Chem. 2016, 8, 625; (c) Y.
Takashima, Y. Hayashi, M. Osaki, F. Kaneko, H. Yamaguchi, A. Harada,
Macromolecules 2018, 51, 4688.
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Entry for the Table of Contents (Please choose one layout)
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Yosuke Akae, Hiromitsu Sogawa,
Toshikazu, Takata*
Page No. – Page No.
Cyclodextrin-Based [3]Rotaxane-
Crosslinked Fluorescent Polymer:
Synthesis and De-crosslinking Using
Size Complementarity
Vinyl-group-substituted a-cyclodextrin (CD) based size-complementary [3]rotaxanes
were synthesized as crosslinkers for rotaxane-crosslinked poly(methyl methacrylate)
(RCP) via radical polymerization. The size-complementarity of the crosslinkers made
it possible to de-crosslink RCP by heating, and the degree of de-crosslinking could
be monitored from the fluorescence intensity depending on the state of the axle
component of the rotaxane crosslink moiety.
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