Photoresponsive pseudopolyrotaxane hydrogels based on competition of host-guest interactions

Article abstract of DOI:10.1002/anie.201000141

Competitive advantage: The reversible assembly and disassembly of a polyethylene glycol (PEG)/α-cyclodextrin (α-CD) pseudopolyrotaxane (PPR) hydrogel is achieved (see picture). In a ternary system with a photoresponsive azobenzene compound, alternating UV

Full text of DOI:10.1002/anie.201000141

Angewandte
Chemie
DOI: 10.1002/anie.201000141
Rotaxane Hydrogels
Photoresponsive Pseudopolyrotaxane Hydrogels Based on
Competition of Host–Guest Interactions**
Xiaojuan Liao, Guosong Chen, Xiaoxia Liu, Wenxue Chen, Fener Chen, and Ming Jiang*
Reversibility is a basic and crucial feature of supramolecular
been extensively studied as the hydrogels show very promis-
ing uses as biomedicine materials. There is now good
[
1]
[8]
systems. In designing and fabricating new supramolecular
materials, the realization of reversibility is particularly
important as it could enable these substances to be superior
to conventional materials. An excellent example is an
elastomer reported recently, made of small functional mole-
cules which form both long chains and cross-linkers through
intermolecular multiple hydrogen bonding. When broken or
cut, the elastomer can be simply repaired by just bringing
together the fractured surfaces and allowing the recovery of
understanding of the formation mechanisms and structures of
such PPR hydrogels, but little has been explored concerning
their dissociation and reassembly, though increasing temper-
[
9]
[9b,c]
ature and shearing
could make the hydrogel turn to a sol.
Herein, we demonstrate a facile photocontrollable supra-
molecular route to realize the disassembly and reassembly of
the PPR hydrogels. The addition of a photoresponsive
compound containing an azobenzene moiety to the PPR
hydrogel was found to be effective in converting the hydrogels
to transparent solutions. By subsequent alternation of UVand
visible irradiation, reversible sol-to-gel and gel-to-sol tran-
sitions were observed. Thus, the widely investigated PEG/a-
CD PPR hydrogel is proved to be “active” in supramolecular
chemistry, and the reversible nature of supramolecular
materials is fully realized.
[
2]
the hydrogen bonding.
There are plenty of reports on supramolecular assemblies
of polymers showing reversible responses to environmental
changes; however, these are mostly based on the inherent
stimuli-sensitive properties of the building blocks, such as the
temperature-induced coil–globule transition of poly(N-iso-
[
3]
propyl acrylamide) (PNIPAM) and pH-induced protonation
[4]
of poly(vinyl pyridine), rather than the reversibility of the
supramolecular interactions. Therefore, taking full advantage
of the reversibility of the noncovalent interactions to con-
struct supramolecular materials is still a big challenge. This
has drawn increasing interest in recent years, and has led to a
series of promising results. For example, some hydrophobi-
cally modified water-soluble polymers realized sol–gel tran-
sition as a result of the reversible interactions of cyclodextrin
In our study, the PPR hydrogel (Figure 1a) was prepared
by using PEG10K (molecular weight 10000) and a-CD in
water as described in reference [7c]. The concentrations of
[5]
and alkyl chains. The assembly and disassembly of poly-
meric vesicles can be controlled by photosensitive interac-
[
6]
tions between cyclodextrin and azobenzene compounds.
The self-assembly of polyethylene glycol (PEG) and
a-cyclodextrins (a-CDs) to form linear pseudopolyrotaxane
(
PPR), with PEG as the axis and a-CDs as threaded rings, was
Figure 1. Hydrogels and sols: a) PEG/a-CD hydrogel; b) PEG/a-CD/
Azo-C1-N sol; c) sol in (b) after UV irradiation; d) gel in (c) after
[
7]
reported by Harada et al. Since the ability of PPR to form
physical hydrogels was first reported in 1994, the system has
+
visible-light irradiation; e) sol in (b) after equivalent a-CD to Azo-C1-
+
N
was added.
[
*] X. J. Liao, G. S. Chen, X. X. Liu, Prof. M. Jiang
Key Laboratory of Molecular Engineering of Polymers of Ministry of
Education, Department of Macromolecular Science
Fudan University, Shanghai 200433 (P. R. China)
Fax: (+86)21-6564-3919
À1
PEG and a-CD had to be higher than 0.1 gmL , and the gel
formed in about 4 h. The inclusion complexation between the
PEG guest and CD host, and the threaded a-CD forming
microcrystals that acted as physical cross-linkers were the
basic factors for hydrogel formation. To dissociate the PPR
hydrogels of PEG/a-CD, a competitive guest 1-[p-(phenyl-
E-mail: mjiang@fudan.edu.cn
W. X. Chen, Prof. F. E. Chen
Fudan–DSM Joint Lab, Department of Chemistry
Fudan University, Shanghai 200433 (P. R. China)
+
azo)benzyl]pyridinium bromide (Azo-C1-N ) (see Figure 2,
[
**] This work is supported by the NNSF (Nos. 20774021, 20834004),
the Ministry of Science and Technology of China (2009-CB930400),
and the STC of Shanghai (07DJ14004).
and Scheme S1 and Figure S1 in the Supporting Information)
was synthesized. The presence of the quaternary pyridine
+
group in Azo-C1-N ensures its good solubility in water. Azo-
+
Supporting information for this article (synthesis of Azo-C1-N ,
+
+
C1-N , as expected, shows clear reversible trans–cis isomer-
photoisomerization conversion of Azo-C1-N , NOESY spectrum of
+
+
ization under UV and visible irradiation (Figure S2 in the
Supporting Information). As equivalent molar amounts of
cis-Azo-C1-N /a-CD, and association constant for trans-Azo-C1-N /
a-CD) is available on the WWW under http://dx.doi.org/10.1002/
anie.201000141.
+
trans-Azo-C1-N to a-CD in water were added to the
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+
The addition of Azo-C1-N to the hydrogel causes
remarkable changes (Figure 2, curve c), that is, the aromatic
+
proton signals of Azo-C1-N shift to a low field (from d =
8
.00 ppm of Figure 2, curve e, to d = 8.11 ppm) and the proton
signals of a-CD to a high field (from d = 3.92 ppm of Figure 2,
curve b, to d = 3.66 ppm). Such changes are exactly the same
as that observed for the reference system containing Azo-C1-
+
N and a-CD only as a result of the formation of the host–
guest complex (Figure 2, curve d). In this ternary system of
+
PEG/a-CD/Azo-C1-N , the most interesting observation is
that the integral area of PEG signals returns to the initial
value (9.70, S1.6 and Figure S3 in the Supporting Informa-
tion) shown in Figure 2, curve a, before gelation. It means that
+
after mixing Azo-C1-N with the hydrogel, all the PEG chains
that were bound to the hydrogel become free chains. In other
words, the complexed a-CD molecules were pulled out from
the PEG chains driven by the host–guest interaction between
+
a-CD and Azo-C1-N . This argument is confirmed by a
supplementary experiment as follows. In the PEG/a-CD/Azo-
+
C1-N solution (Figure 1b), in which all the a-CD forms a
+
complex with Azo-C1-N , additional a-CD equivalent to
+
Azo-C1-N was added. The hydrogel (Figure 1e) re-formed
in 2 h as a result of the PEG chains threading into the cavities
1
of the newly added host a-CD. In addition, the H NMR
+
spectrum of PEG/Azo-C1-N was recorded (Figure 2,
curve h). No shift was observed, thus showing that Azo-C1-
+
N has no interactions with PEG.
Dynamic laser light scattering (DLS) performed in very
dilute solutions was used to monitor the formation of linear
PPR and its dissociation. The concentration of PEG was
0.01 gmL , much lower than that used to form the hydrogel,
so the PPR could form but no precipitation and gelation took
place. As shown in Figure 3 (curve a), the solution of
1
À1
Figure 2. H NMR spectra of a) PEG/a-CD solution, b) PEG/a-CD
+
+
+
hydrogel, c) PEG/a-CD/Azo-C1-N , d) a-CD/Azo-C1-N , e) Azo-C1-N ,
f) PEG, g) a-CD, and h) PEG/Azo-C1-N solutions in D O.
+
2
hydrogel and the mixture was ultrasonicated, the gel turned
into a transparent sol in a few minutes (Figure 1b). Sub-
sequent UV irradiation at 365 nm of the resultant sol made it
return to a hydrogel (Figure 1c). This hydrogel went to a sol
again as it was irradiated by visible light (Figure 1d). Such gel-
to-sol and sol-to-gel transitions were realized repeatedly as
visible and UV irradiation was alternately performed.
1
H NMR studies provided important insight into the
nature of hydrogel formation and dissociation. The results
are shown in Figure 2 and Figure S3 in the Supporting
Information. Curves a and b in Figure 2 refer to the mixtures
of PEG and a-CD 2 and 24 h after mixing of the components,
respectively. The former is a sol and the latter is a gel.
Interestingly, for the former the spectrum is a simple sum of
the spectra of PEG (Figure 2, curve f) and a-CD (Figure 2,
curve g), whereas in the latter obvious changes are observed.
All the proton signals of a-CD become much broader and the
integral area of PEG protons at 3.62 ppm decreases from 9.18
to 6.87, with integration of the H1 proton of a-CD as
reference. The changes are, of course, caused by the threading
of PEG chains into a-CD cavities and crystallization of the
complexed a-CD, both of which retard the molecular
mobility.
Figure 3. DLS results for PEG (c), PEG/a-CD (a), and PEG/a-
CD/Azo-C1-N (g) aqueous solutions.
+
PEG10K alone shows a relatively narrow hydrodynamic
radius distribution with a peak value of 3 nm. Mixing this
PEG10K solution with a-CD causes a remarkable change in
the distribution curve, that is, three peaks appear (Figure 3,
curve b). The middle one is the same as that of Figure 3
curve a, which is obviously associated with the free PEG10K.
The right-hand peak, with a size ranging from about 50 to
200 nm, is attributed to the PEG/a-CD linear complex and its
4
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aggregate PPR. In addition, a small peak of size less than
nm is observed, which is no doubt from the free a-CD.
opportunities for the free a-CD molecules to move and be
threaded by the PEG chains again.
1
Finally, Figure 3 curve c clearly shows the great change caused
by adding Azo-C1-N to the solution of a-CD and PEG10K:
The difference in the binding ability of the trans- and cis-
Azo-C1-N with a-CD was also estimated by isothermal
+
+
the peak associated with the PPR aggregates completely
disappears. This reflects PPR dissociation caused by pulling
the complexed a-CD molecules out of the PEG chains, driven
titration calorimetry (ITC). The enthalpy changes (DH)
during mixing of the guest Azo-C1-N solution (0.3 mmol)
and the host a-CD solution (1 equiv) before and after UV
irradiation are recorded in Figure 5. Here, the single-injection
+
+
by the inclusion complexation of a-CD and Azo-C1-N . The
presence of the small molecular complex is indicated by the
small peak located at less than 1 nm. Therefore, in the ternary
system only free PEG chains and the complex of a-CD and
+
Azo-C1-N exist.
1
All the results from H NMR spectroscopy and DLS
indicate that the host–guest interaction between trans-Azo-
+
C1-N and a-CD was so strong that, in the ternary system,
+
trans-Azo-C1-N competed with and replaced PEG forming
+
the trans-Azo-C1-N /a-CD complex and releasing the PEG
chains. However, when the ternary solution underwent UV
irradiation for about 1.5 h and was then kept in the dark at
4
8C overnight, PPR hydrogel was regenerated (Figure 1c).
The regeneration of the hydrogel implies that the interaction
+
between a-CD and Azo-C1-N becomes much weaker when
the latter is converted from the trans to the cis form. This
+
Figure 5. Heat observed by ITC in the titration of Azo-C1-N by a-CD
in SIM mode, before (c) and after (g) UV irradiation.
point of view is confirmed by our 2D NMR measurements.
1
As shown in Figure 4, the H NOESY spectrum of Azo-
+
C1-N /a-CD in D O clearly displays a series of NOE
2
correlation peaks between H3/H5 of a-CD, which point to
mode (SIM) was used. The heat of dilution of the a-CD
solution was measured as a control and subtracted from the
corresponding data. The heat released before UV irradiation
was 939 mcal, whereas after irradiation it decreased to
3
23 mcal only. However, this finding cannot be simply
attributed to the contribution of the cis form. As is well
known, trans and cis isomers of the azobenzene moiety
[10]
1
undergo dynamic balance. By H NMR measurements it
+
was calculated that the trans isomer of Azo-C1-N is present
at about 90 and 22% before and after UV irradiation,
respectively (Figure S5 in the Supporting Information), which
is generally in agreement with data reported in the litera-
[10c]
ture.
Considering that after UV irradiation, about a fifth of
the azobenzene groups remain in the trans form, which makes
the major contribution to the measured very low DH, the
association between the cis form and a-CD is very weak.
Figure S6 (Supporting Information) shows the titration curve
+
for a-CD and Azo-C1-N before UV irradiation, from which
4
À1
the association constant of 1.46 ꢀ 10 m was obtained. This
+
Figure 4. NOESY spectrum of Azo-C1-N /a-CD aqueous solution
before UV irradiation.
value is very close to those reported for other azobenzene
[11]
+
compounds in the literature. For a-CD and cis-Azo-C1-N ,
the association constant is not detectable from the ITC
titration curve as the interaction is too weak.
+
the cavity, and the protons Ha–Hd of the azobenzene moiety:
peaks A between H3/H5 and Hb as well as Hc, peaks B
between H3/H5 and Hd, and peak C between H5 and Ha.
These NOE correlation peaks indicate that the trans form of
We also studied the complexation between Azo-C1-N
and a-CD by circular dichroism spectroscopy. As shown in
+
Figure 6a, the spectrum of Azo-C1-N /a-CD in water shows a
large positive band at 330 nm and a small negative band at
+
the azobenzene moiety in Azo-C1-N is deeply included in
450 nm, which are assigned to the p–p* transition of trans-
+
+
the hydrophobic cavity of a-CD. However, all of these
correlation peaks disappeared after UV irradiation of the
solution, as shown in Figure S4 in the Supporting Information,
which indicates that the azobenzene moiety of cis-Azo-C1-N
was excluded from the cavity of a-CD. This provides
Azo-C1-N and n–p* transition of cis-Azo-C1-N , respec-
[
12]
tively. This result indicates that the azobenzene moiety of
trans-Azo-C1-N inserts in the a-CD cavity with its electronic
+
+
transition moment parallel to the a-CD axis. Meanwhile, the
+
azobenzene moiety of cis-Azo-C1-N just lies on the a-CD
Angew. Chem. Int. Ed. 2010, 49, 4409 –4413
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Communications
Scheme 1. Preparation of the photoresponsive PPR hydrogels.
into solution by simply adding the competitive guest trans-
+
Azo-C1-N , which replaces PEG units to form complexes
with
a-CD. After UV irradiation, the PPR hydrogel regenerates
+
because Azo-C1-N in the cis form loses its ability to complex
with a-CD and then the latter is threaded by the PEG chain
again. Subsequent irradiation by visible light makes the
hydrogel convert to a solution. The photocontrollable gel-to-
sol and sol-to-gel processes can be repeated for cycles. The
simplicity of preparation, commercial availability, and bio-
compatibility of the materials bode well for future applica-
tions of the hydrogels in various fields.
Figure 6. Circular dichroism spectra of an aqueous solution of Azo-C1-
N /a-CD (a) and diluted sol of PEG/a-CD/Azo-C1-N (b), before
+
+
(
c) and after (g) UV and visible-light (a) irradiation. C(Azo-
+
À3
+
C1-N )=1ꢀ10 m, n(a-CD):n(Azo-C1-N )=1:1.
Received: January 10, 2010
Published online: May 17, 2010
[
12a]
surface with its moment parallel to the a-CD axis.
After
Keywords: cyclodextrins · host–guest systems · rotaxanes ·
sol–gel processes · supramolecular chemistry
UV irradiation (365 nm), the positive circular dichroism band
at 330 nm dramatically decreases as most of the azobenzene
moiety turns into the cis form and then escapes from the
a-CD cavities. The resultant small band is attributed to the
remaining trans isomer. After subsequent visible-light
.
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(
435 nm) irradiation, the spectrum recovers almost to its
original value, which suggests that a-CD moves back to the
azobenzene moiety.
[
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ternary system prepared by adding Azo-C1-N (1 equiv) to
[
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remarkable to see that Figure 6b shows exactly the same
spectra and variation with irradiation as those shown in
Figure 6a. This means that in the solution formed by mixing
2
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+
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5
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interactions (Scheme 1). Our studies proved that the strength
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+
CD > PEG/a-CD > cis-Azo-C1-N /a-CD. PEG10K and
a-CD form PPR hydrogel in water. The hydrogel transfers
4
412
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Angew. Chem. Int. Ed. 2010, 49, 4409 –4413
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4413