Dual stimuli-responsive supramolecular hydrogel based on hybrid inclusion complex (HIC)

Article abstract of DOI:10.1021/ma101437k

A novel dual-responsive supramolecular hydrogel composed of an azobenzene (AZO) end-functionalized block copolymer PDMA-b-PNIPAM (AZO-(PDMA-b-PNIPAM)) and β-cyclodextrin-modified CdS quantum dot (β-CD@QD) has been demonstrated. Based on the host-guest inc

Full text of DOI:10.1021/ma101437k

8086 Macromolecules 2010, 43, 8086–8093
DOI: 10.1021/ma101437k
Dual Stimuli-Responsive Supramolecular Hydrogel Based on Hybrid
Inclusion Complex (HIC)
Jianghua Liu, Guosong Chen,* Mingyu Guo, and Ming Jiang*
The Key Laboratory of Molecular Engineering of Polymers, Ministry of Education, and
Department of Macromolecular Science, Fudan University, 220 Handan Rd., Shanghai 200433, China
Received June 29, 2010; Revised Manuscript Received September 2, 2010
ABSTRACT: A novel dual-responsive supramolecular hydrogel composed of an azobenzene (AZO) end-
functionalized block copolymer PDMA-b-PNIPAM (AZO-(PDMA-b-PNIPAM)) and β-cyclodextrin-mod-
ified CdS quantum dot (β-CD@QD) has been demonstrated. Based on the host-guest inclusion complexa-
tion of AZO of the block copolymers and CD cavities on β-CD@QD, they form a hybrid inclusion complex
(HIC). The HIC contains a QD as the core and the block copolymer as the shell with the PNIPAM block as
the outer layer. Dynamic light scattering (DLS) and UV-vis spectroscopy investigation proved the HIC
structure in diluted solution. Hydrogel formed easily upon heating the aqueous solution of HIC at a
concentration as low as 7 wt %; as a result of PNIPAM, aggregation occurred above the LCST. The inclusion
complex and the domains of the collapsed PNIPAM chains serve as two distinct cross-links and render the
hydrogel excellent dual sensitivity to competitive hosts/guests substitution and to temperature variation.
Furthermore, rheology results quantitatively exhibit the hydrogel formation mechanism and the sol-to-gel
reversibility following the two external stimuli.
Introduction
methyl ether-co-ethyl glycidyl ether) (P2VP-b-PEO-b-P(GME-
co-EGE)) triblock terpolymer prepared by anionic polymeriza-
Macromolecular hydrogels are three-dimensional networks
composed of hydrophilic polymeric backbones and cross-link
regions, enabling it to swell a large amount of water. Recently, the
stimuli-responsive gel/sol transitions of the hydrogels induced
extensive research interest. The stimuli scope includes pH,1 tem-
perature, redox, light,2 magnetic fields, or chemical entities.3 Such
hydrogels as “smart” soft materials have been found promising in
bioapplications4,5 because they could sense environmental changes
and self-induce structural transformations.6-12 In the past couple
of years, introducing reversible noncovalent bonds as cross-
linkers made significant contributions to the research of environ-
mental responsive behavior of hydrogels, especially for redox13
and pH changes.14
Obviously, more stimuli responses would generate more flex-
ibility to further applications of the hydrogels. Thus, to design
and achieve multiresponsiveness within a single piece of soft
material is of significance not only to scientific research but also
to potential applications. However, hydrogels integrated by
independent multiresponsiveness are more challenging than that
with only one stimulus because it may require more critical and
complicated chemical structures. Lots of single responsiveness
hydrogels have been reported while the softmaterials with dual or
even multiple responsive behavior are rare. So far, block copo-
lymer strategy is the most popular and efficient way to achieve
multiresponsiveness. However, if one only relies on block co-
polymer structures to achieve independent dual responsiveness, a
synthetic triblock copolymer is required in which two blocks are
for the dual responsiveness and one block serves as the hydrogel
backbone. Until now, hydrogels with dual and independent
responsiveness are still limited in the literature. For example, poly-
(2-vinylpyridine)-block-poly(ethylene oxide)-block-poly(glycidyl
tion exhibited thermo- and pH-reversible gel formation in aqu-
eous solutions.14 β-CD is a cyclic oligosaccharide composed of
seven glucopyranose units with a hydrophilic external cavity and
hydrophobic internal surface. This particular structure allows it
to selectively accommodate a variety of molecules as guests
(e.g., adamantane, azobenzene, and other suitable molecules).
Recently, inclusion complexation between β-cyclodextrin (β-CD)
and guest molecules has been employed as an alternative non-
covalent bond to prepare hybrid system anchoring inorganic
components to polymer chains. In fact, embedding inorganic
nanoparticles or nanosheets into polymer matrices has proved to
be an effective method of enhancing the functionality of the
material.15 Such hybrid hydrogels are reported to have useful
mechanical, optical, or magnetic properties.16,17 Harada et al.18
prepared hybride hydrogel through CD-functionalized carbon
nanotube. Our group introduced β-CD-modified SiO2 nanopar-
ticle as a supra-cross-link to poly(ethylene glycol) (PEG), which
promotes the formation of hybrid hydrogel.19 In the study, the
interaction of silica nanoparticle with PEG was based on the
inclusion complexation between β-CD and adamantane, which is
specific enough to have a well-organized hybrid nanocomposi-
tion. In addition, there are several other kinds of hydrogels that
have been achieved via inclusion complexation of CDs with
guests, including thermo- or pH-dissociative R-CD/PEG pseudo-
rotaxanes20,21 and photoresponsive hydrogel of modified β-CD
with azobenzene grafted polymer reported by the Stoddart22
group.
Quantum dots (QDs) are a large family of inorganic nano-
crystals with quantum-confined physical properties, which have
important advantages including narrow and size-dependent
emission spectra, multicolor excitation, and excellent photo-
stability against photobleaching.23,24 The most commonly used
QDs are of the cadmium chalcogenide group due to ease of
synthesis and handling.25,26 The integration of QDs with different
*Corresponding authors: e-mail guosong@fudan.edu.cn (G.C.), mjiang@
fudan.edu.cn (M.J.); Fax þ86 21-65643919.
pubs.acs.org/Macromolecules
Published on Web 09/16/2010
r 2010 American Chemical Society

Article
Macromolecules, Vol. 43, No. 19, 2010 8087
materials will provide a new generation of fluorescence markers
for biological assay. As a typical kind of soft material, hydrogels
can provide an ideal environment hosting a variety of functional
molecules and nanoparticles, including QDs.
(HIC) rather than triblock copolymer to construct a novel
supramolecular hydrogel with dual responsiveness (Figure 1).
To this end, a β-CD-covered CdS quantum dot (β-CD@QD)
was employed as the core of HIC. In the HIC, the core is
connected to the block copolymer chains of AZO-(PDMA-
b-PNIPAM), by means of the host-guest inclusion com-
plexation between the β-CD on the surface of β-CD@QD
and the azobenzene (AZO) group of the copolymer
(Figure 1). Therefore, in the HIC, surrounding the core,
there are two polymer layers, i.e., the inner layer of poly(N,
N-dimethylacrylamide) (PDMA), which always keeps sol-
vated in water, and the outer layer of PNIPAM, which turns
insoluble to form interchain aggregates when temperature
increases to above the LCST of PNIPAM. Thus, the do-
mains of the collapsed PNIPAM chains would connect HIC
to form the network, i.e., hydrogel. Obviously, this HIC-
based hydrogel possesses two different physical cross-links,
i.e., β-CD@QD connecting polymer chains via supramole-
cular interactions and the temperature-sensitive PNIPAM
domains. The presence of the two independent cross-links
is the basis for realizing dual-responsive properties of the
hydrogels.
In thisstudyof dual-responsive hybrid hydrogels, the key point
is the combination of the two independent cross-links. A new type
of hybrid inclusion complex (HIC) is constructed by connecting
QD with diblock copolymer chains, one block of which has
thermo-responsiveness. The HIC solution can easily be converted
to the designed hybrid hydrogels upon heating. This tailor-made
design renders the hydrogel not only thermo-reversibility but also
responses to supramolecular substitutions. Furthermore, the
effectiveness of this HIC structure brought down the critical
hydrogel concentration to be 7 wt %, a rather low concentration
among that of some reported stimuli-responsive supramolecular
polymeric hydrogels.
Results and Discussion
Design of HIC and Synthesis of AZO-(PDMA-b-PNIPAM).
We aimed to design a star-shaped hybrid inclusion complex
To synthesize AZO-(PDMA-b-PNIPAM) block copoly-
mer, we designed and prepared a novel AZO-functionalized
chain transfer agent (AZO-CTA), which is shown in Scheme 1.
AZO-CTA was prepared by a conventional N,N0-dicyclohex-
ylcarbodiimide (DCC)-mediated esterification of 4-phenyla-
zophenol with S-ethyl-S0-(R,R0-dimethyl-R00-acetic acid)trithi-
ocarbonate (Scheme 1). Then, AZO-CTA was applied for
initiating the polymerization of DMA. The polymerization
was stopped at about 90% monomer consumption, and sub-
sequently, the obtained homopolymer was further utilized as
macroAZO-CTA for the polymerization of NIPAM to yield
AZO-(PDMA-b-PNIPAM) (Scheme 1). Six AZO-(PDMA-b-
PNIPAM) samples with different degrees of polymerization
(DP) and different DP ratios of PDMA to PNIPAM were
prepared as shown Table 1. The theoretical DP and experi-
mental DP of the six polymers are listed. All of the obtained
Figure 1. Schematic structures of β-CD@QD, AZO-(PDMA-b-
PNIPAM), and the hybrid inclusion complex (HIC).
Scheme 1. Synthetic Route of AZO-(PDMA-b-PNIPAM) Block Copolymer
Table 1. AZO-(PDMA-b-PNIPAM) Block Copolymers Synthesized in This Study
DP(theoretical)a DP(experimental)b
PDId
c
AZO-(PDMAm-b-PNIPAMn)
m
n
m
n
PDICTA
AZO-I-1
AZO-I-2
AZO-I-3
AZO-II-1
AZO-II-2
AZO-III-2
100
100
100
200
200
400
80
120
200
80
120
120
109
104
122
219
230
307
89
138
223
84
133
127
1.13
1.09
1.09
1.14
1.15
1.14
1.13
1.19
1.21
1.16
1.20
1.15
a Indicative theoretical DP of each block. b Determined by 1H NMR. c PDICTA of macroAZO-CTA, determined by GPC results. d PDI of
AZO-(PDMA-b-PNIPAM), determined by GPC results.

8088 Macromolecules, Vol. 43, No. 19, 2010
Liu et al.
polymers show a well-defined structure, exhibiting a relatively
narrow molecular weight distribution indicated by the poly-
dispersity indexes (PDI) below 1.20 determined by GPC
(Figure 2). The block ratios of AZO-(PDMA-b-PNIPAM)
were calculated from the characteristic peak area of methyl
showing that the micelles are spherical with a radius ranging
from 25 to 30 nm, which is consistent with the DLS results.
Inclusion Complexation of AZO-(PDMA-b-PNIPAM)
with β-CD. The AZO-(PDMA-b-PNIPAM) contains AZO
end which may act as a guest to form inclusion complexes
with β-CD in aqueous solution. Formation of the inclusion
complexes of AZO-(PDMA-b-PNIPAM) block copolymer
with free β-CD was proved by UV-vis spectra. The UV-vis
spectra of AZO-I-2 solution alone, and its mixture with
different amount of β-CD after ultrasonic treatment for
1 h, are shown in Figure 4. The peaks at 312 and 424 nm
are the characteristic absorption peaks of AZO units. The
absorption of AZO units at 312 nm gradually decreases while
that around 424 nm increases gradually, accompanying a
hypsochromic shift (about 15 nm) as the molar ratio of CD to
AZO units increases from 0.5 to 80. This is attributed to the
high hydrophobicity and high electron density inside CD
cavities as a result of CD accommodating AZO units.30 The
result implies that, being attached onto the long block
copolymer chain, the AZO group still keeps its ability to
form inclusion complex with β-CD.
1
groups on DMA and NIPAM in the H NMR spectrum,
while DPs were from the ratio of them to that of AZO. Only
AZO-I-2 was employed to hydrogel study in details, while
the others were used to optimize the hydrogel formation
conditions.
Thermo-Responsive Micellization of AZO-(PDMA-b-
PNIPAM). It is well-known that PNIPAM is soluble in
water at room temperature but undergoes a phase separation
at its lower critical solution temperature (LCST, commonly
32 °C)27 This thermo-responsive behavior of AZO-I-2 was
monitored by dynamic light scattering (DLS). The hydro-
dynamic radius of AZO-I-2 in solution (1 mg/mL), as ex-
pected, from around 5 nm of individual polymer coils at low
temperature, starts increasing when temperature increases to
32 °C. Then the size dramatically goes up to the maximum of
38 nm at 36 °C. This indicates the formation of micelles with
a hydrophobic PNIPAM core and a hydrophilic PDMA
shell. When the temperature increases further, the radius of
the micelles begins to decrease from 38 to 23 nm, which is
attributed to further dehydration of the PNIPAM blocks.28,29
The micelle structure has been observed by TEM (Figure 3B),
HIC Formation and Characterization. As the core of HIC,
β-CD@QDs was prepared according to the reported liter-
ature.31 The organic content (β-CD content) of β-CD@QDs
was found to be 48%, as the weight loss from 250 to 450 °C
measured by thermogravity analysis (TGA) (Figure 5). Con-
sidering the diameter of β-CD@QDs observed under HR-TEM
Figure 2. Representative molecular weight distribution of macroAZO-
CTA and the corresponding AZO-(PDMA-b-PNIPAM) block co-
polymers (AZO-I-1, AZO-I-2, and AZO-I-3). Eluent: DMF with LiBr
(0.5 mg/mL).
Figure 4. UV-vis spectra of AZO-I-2 block copolymer (2.0 ꢀ 10-5
mol dm-3) in the presence of β-CD (0, 1.0, 2.0, 10, 20, 40, 60, and 80 ꢀ
10-5 mol dm-3 from a to h) after ultrasonic treatment for 1 h.
Figure 3. Hydrodynamic radius (Rh) for block copolymer AZO-I-2 in aqueous solution (A) and TEM image of micelles formed by aggregation of
PNIPAM blocks above LCST (B). Inset: a typical micelle formed by AZO-I-2.

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Macromolecules, Vol. 43, No. 19, 2010 8089
being around 4 nm (Figure S4), the approximate number of
β-CD on QD surface was calculated as 22, assuming the
surface coverage of β-CD was 80%.31 β-CD@QDs and
block copolymer AZO-I-2 were mixed in a diluted aqueous
solution with molar ratio of β-CD to AZO as 1.5:1. After
sonication, the uncomplexed β-CD@QD and/or AZO-I-2
were removed by dialysis (5 ꢀ 104 molecular weigh cutoff).
The obtained HIC was further concentrated and dried by
lyophilization and characterized by TGA (Figure 5). The
organic content of HIC was found to be 89.8%; thus, each
HIC was composed of a β-CD@QD core and block copo-
lymer chains which occupied 63% of CD cavities on the QD
surface (calculation method: see Supporting Information).
To achieve the desired hydrogel structure, the thermo-
aggregation of PNIPAM on HIC should be independent of
inclusion complexation. Thus, the temperature-induced
phase transition of the HIC at a low concentration of 1 mg/
mL (prepared by AZO-I-2 with the molar ratio of β-CD to
AZO is 1.5) was investigated by DLS (Figure 6a). A similar
size variation as to that of AZO-I-2 solution alone was
observed as the temperature increased. Below the LCST of
PNIPAM, the hydrodynamic radius of HIC is 8 nm, higher
than AZO-I-2 alone in solution (5 nm, in Figure 3a), because
the HIC contains a core of quantum dots with a 4 nm dia-
meter. As the temperature increases to LCST, the radius
dramatically increases to 35 nm because of the contraction of
the NIPAM chains, which then induces aggregation of the
HIC particles. The formed aggregates disperse stably in
water due to the low concentration. When the temperature
increases further, the radius decreases to about 20 nm be-
cause of the further dehydration of the collapsed PNIPAM
chains.32 A remarkable feature of the aggregates shown in
TEM image is that they do not have a smooth outline, as
they are composed of several smaller particles (inset in
Figure 6B). This confirmed the formation mechanism we
just addressed.
Formation, Photoluminance, and Rheology Study of Supra-
molecular Hydrogel. In this study, the HIC was used as build-
ing blocks to construct hydrogels. In our simple test tube
inversion observation of the HIC solutions with a series of
concentration from 7 to 25 wt % (weight ratio, the same
below), we found that the yellow fluidic, homogeneous solu-
tions can be converted to slightly turbid free-standing gels at
40 °C after a few minutes. Obviously, the PNIPAM chains on
the periphery of the HICs collapsed and combined together
from different HICs. However, no macroscopic precipitate
was formed as the PDMA chains kept solvated. Therefore,
hydrogel formed, which is featured by two different cross-
links: The first is β-CD@QDs, which connect the network-
forming chains of the block copolymer by supramolecular
interactions, and the second is the collapsed PNIPAM
domains, which link HICs.
The formation of the hydrogel was further monitored by
viscosity-temperature measurements on ARES rheometer
for concentrations of 12, 15, and 25 wt %. We found the
minimum concentration of HIC to form hydrogel after
heating is as low as 7 wt %, while the same block copolymer
alone without β-CD@QD cannot form hydrogel even when
the concentration reached up to 25 wt %. As shown in Figure 7,
the viscosity for block copolymer AZO-I-2 solution with
12 wt % varied little with increasing temperature from 30 to
45 °C, while an abrupt viscosity enhancement for its HIC at the
same concentration was observed from 35 to 40 °C (Figure 7b),
above the LCST of PNIPAM block, indicating the onset of
network formation. Subsequently, the viscosity for HIC was
Figure 7. Temperature dependence of viscosity of (A) block copolymer
AZO-I-2 solution (12 wt %) and (B) the HIC (12 wt %). The digital
photos show the corresponding appearance.
Figure 5. TGA curves of β-CD@QDs (a), HIC (b), and AZO-I-2 (c).
Figure 6. Hydrodynamic radius (Rh) for HIC in aqueous solution (A) and TEM image of HIC in diluted solution above LCST (B).

8090 Macromolecules, Vol. 43, No. 19, 2010
Liu et al.
Figure 8. Temperature dependence of viscosity of (A) block copolymer
AZO-I-2 solution (25 wt %) and (B) the HIC (25 wt %). Digital photos
show the corresponding appearance.
Figure 9. Shear elastic modulus G0 and shear viscous modulus G00 for
HIC of AZO-I-2 in solution at concentration of 12 and 15 wt % as a
function of temperature.
moderately decreasing when the temperature was further
increased above 40 °C.
We also found that when the temperature was further
increased, or the gel was standing at 40 °C even longer, the
hydrogel shrinked a little and a thin and transparent layer of
water appeared on the surface of the hydrogel. This phenom-
enon was not hard to understand by considering the previously
observed collapse of micelles in diluted solution (Figures 3
and 6), caused by dehydration of the NIPAM blocks. It is
worth mentioning that we also observed the shrinking of
hydrogel and small amount of water on the parallel-plate
surface of rheometer at the end of the experiment.
Figure 8 shows the viscosity variation with temperature
for the solutions of AZO-I-2 and its HIC with a concentra-
tion as high as 25 wt %. Over the temperature range from 25
to 45 °C, the viscosity of AZO-I-2 solution varied little,
similar to that at a lower concentration (Figure 7A), while
that of the HIC solution was continuously increasing, ob-
viously different from that of the same HIC at the concen-
tration of 12 wt % (Figure 7). At 40 °C, the viscosity of the
25 wt % solution of HIC reached about 103 Pa s, while it was
only 180 Pa s for the 12 wt % solution. In fact, the hydrogel
formed at 25 wt % was always transparent upon heating to
40 °C and became only slightly turbid after heated to 55 °C.
This might be ascribed to that, at higher concentration, the
motion of HICs was restricted, so the HICs, particularly the
QD cores, did not sufficiently aggregate; instead, they kept
homogeneously dispersed.
It is well-known that the sol-gel transition can easily be
determined from dynamic rheological data. The temperature
at which the elastic modulus G0 curve intersects that of the
viscous modulus G00 indicates the sol-gel transition point.
Figure 9 shows the oscillatory temperature sweep profiles
of HIC (formed by AZO-I-2) at concentrations of 12 and
15 wt %. When the temperature was below 32 °C, both HIC
solutions exhibit obvious viscoelastic response, where G00
was large than G0, as the HIC was in a liquid state. When the
temperature of HIC solution was increased to above 32 °C,
both G0 and G00 increased. However, the enhancement rate of
G0 was larger than that of G00. Then, the sol-gel transition
occurs when G0 = G00 at 40 °C for 12 wt % solution and 41 °C
for 15 wt % solution. In addition, from Figure 9, it was also
evident that higher concentration of HIC led to higher value
of G0 and G00.
Figure 10. Photoluminescence spectra of HIC at concentration of
15 wt % at different temperatures: (a) 25, (b) 30, (c) 35, (d) 40, and
(e) 45 °C (excitation wavelength: 360 nm).
this emission peak did not change much as the temperature
variation is between 25 and 35 °C. A sharp increase of photo-
luminance intensity was detected as the temperature in-
creased from 35 to 40 °C (Figure 10). At the same tempera-
ture range, a dramatic increase of viscosity was observed by
rheological study due to the hydrogel formation (Figure 7). It
is clear that the higher viscosity of HIC solution confined the
movement of QDs leading to a strong enhancement of
photoluminescence. After the temperature was further in-
creased from 40 °C, the intensity of the emission decreased,
which was probably with the shrinkage of the PNIPAM
block.34,35
Reversibility in Gel-Sol Transitions via Thermal Change
and Supramolecular Substitution. The supramolecular hydro-
gel we obtained contains two distinct and independent physi-
cal cross-links. Therefore, cleavage of either one of the cross-
links would lead to disassociation of the hydrogel. The supra-
molecuarhydrogel formed byHIC ofAZO-I-2at 15wt% was
used to demonstrate the thermo-responsive behavior. We
observed that the hydrogel returned to free-flowing, homo-
geneous solution after cooled to room temperature, with the
release of the aggregated PNIPAM chains. This recovered
HIC solution returned to hydrogel again as the temperature
increased above LCST (Figure S8). This sol-to-gel and gel-to-
sol transition was also monitored by the viscosity change with
temperature shown in Figure S8, i.e., the viscosity varies from
about 10 Pa s at 25 °Cto310Pas at40°C andthen to10Pas at
Furthermore, the photoluminance behavior of HIC was
measured before and after the hydrogel formation, which is
an important property of the soft material we obtained.33
HIC inherited the trap-state emissions of QDs31 (Figure S6)
presenting a strong emission around 548 nm. The intensity of

Article
Macromolecules, Vol. 43, No. 19, 2010 8091
25 °C again. This thermoreversible sol-gel transition took
place fast and could be performed repeatedly for several
cycles.
Other Factors Associated with the Hydrogel Formation. In
this system, when total weight (including both AZO-(PDMA-
b-PNIPAM) block copolymer and QD nanoparticles) is fixed,
the molar ratio of β-CD to AZO units of the block copolymers
significantly affects the hydrogel formation. We prepared
HIC over different β-CD to AZO ratios and calculated the
number of block copolymer chains on each QD surface
(Table S1). Then we performed the hydrogel formation
experiments and investigated the effect of different molar
ratios. In two extreme cases, i.e., the molar ratio of β-CD and
AZO units being 1:1 and 6:1, neither of them formed hydro-
gels at concentration of 7 wt %, but hydrogels formed when
the concentration is higher than 15 wt %. For the molar ratio
1:1, the concentration of the QD particles is too low to
provide enough binding sites. When the ratio is as high as
6:1, the aggregation of PNIPAM cannot lead to the forma-
tion of hydrogel network as the concentration of the polymer
chains is not enough. We found that the optimum molar
ratio of CD to AZO for the gel formation is 1.5:1, in which
63% CDs on each nanoparticle was occupied by block co-
polymer chains as calculated based on TGA measurements
(Supporting Information).
In order to study the influence of degree of polymerization
(DP) of PNIPAM and PDMA on gelation, a series of AZO-
(PDMA-b-PNIPAM) block copolymers with different DPs
were prepared (Table 1). For the copolymers AZO-I-1,
AZO-I-2, and AZO-I-3 with similar DP of PDMA block
(DPPDMA = 109), AZO-I-1 with the lowest DP of 89 of
PNIPAM block cannot form hydrogel with β-CD@QDs
even at a total concentration of 20 wt % with suitable molar
ratio of CD to AZO (1.5:1). However, for both AZO-I-2 and
AZO-I-3 with higher DPs of PNIPAM being 130 and 223,
hydrogel formation was realized at a concentration as low as
7 wt %. A similar difference was also observed for AZO-II-1
and AZO-II-2 with similar DP around 220 for PDMA but
different DPs for PNIPAM. Therefore, it is clear that the
PNIPAM chains have to be long enough to form the cross-
link region above LCST. In addition, for sample AZO-III-2,
since the length of PNIPAM is enough, further extension of
the length of PDMA does not affect the hydrogel formation.
The viscosity variation of HIC at 12 wt % constructed by
block copolymers with different PDMA and PNIPAM block
length is shown in Figure 12. For copolymers AZO-II-2 and
AZO-III-2, which have enough length of PNIPAM, hydro-
gels can form easily. For AZO-I-2 and AZO-I-3, the longer
the PNIPAM block, the lower the aggregation temperature.
Meanwhile, for sample AZO-I-3, a similar phenomenon of
As the host-guest inclusion complexation between β-CD@
QDs and AZO units of the block copolymer enables them to
serve as cross-link to form network structure, we tried to
recognize the gel-to-sol transitions by introducing competi-
tive host and guest into the hydrogels. When water-soluble
1-adamantanamine powder (ADA, 2 equiv to β-CD unites of
QDs nanoparticles) was added to the hydrogel as a compe-
titive guest, the gel-to-sol transition was observed within
several minutes from top to bottom in the vial. This indicated
that the host-guest interaction between β-CDs and AZOs
dissociated quickly due to the stronger competitive inclusion
complexation of β-CD with ADA. Meanwhile, the hydrogel
can be changed to sol by adding R-CD (2 equiv to AZOs) as a
competitive host to release the same interaction in HIC.
Stronger inclusion complexation of R-CD with AZOs re-
sulted the dissociation of AZOs from β-CDs.36 The resultant
disassociated hydrogels (i.e., sol state) by adding competitive
guest or host were also characterized by rheology measure-
ments, and the results are shown in Figure 11. It was confirmed
that the trend of viscosity variation for the disassociated
hydrogels was almost identical to that of AZO-(PDMA-b-
PNIPAM). Figure 9 shows the images of all transition states.
Obviously, the observations that the supramolecular hydro-
gels were disassociated by adding the competitive guest or
host further supported the proposed HIC structure and its
gelation mechanism (Scheme 2).
Figure 11. Temperature dependence of viscosity of (A) the HIC solu-
tion (12 wt %) and the dissociated hydrogels obtained by adding ADA
(B) and R-CD (C). Digital photos show the corresponding appearance.
Scheme 2. Plausible Formation and Disassociation Mechanisms of the Supramolecular Hydrogel of HIC

8092 Macromolecules, Vol. 43, No. 19, 2010
Liu et al.
Perkin-Elmer Lambda 35 spectrophotometer. Thermogravi-
metric analysis (TGA) measurements were carried out on a
Perkin-Elmer Pyris-1 series thermal analysis system under a
flowing nitrogen atmosphere at a scan rate of 20 °C min-1 from
100 to 700 °C. Dynamic light scattering studies of AZO-(PDMA-
b-PNIPAM) block copolymers and the assembly of AZO-
(PDMA-b-PNIPAM) and β-CD@QD at concentrations of
1.00 mg/mL in aqueous solution were conducted using ALV/
5000E laser light scattering (LLS) spectrometers at scattering
angle of 90° and temperature of 25-45 °C. CONTIN analysis
was used for the extraction of Rh data. ESI-MS analyses were
performed with a Finnigan MAT 95 (San Jose, CA) model LCQ
ion-trap mass spectrometer equipped with a Finnigan electro-
spray ionization (ESI) source and Xcalibur software. The fluores-
cence spectra of β-CD@QD and HIC at different temperature
were measured by FL920 (Edinburg Instruments), equipped with
a photomultiplier tube (the samples were excited with UV light
of λ = 360 nm). The morphology of block copolymer and HIC
in distilled solution above LCST was analyzed using a Philips
EM-430 transmission electron microscope operated at 30 kV. The
morphology of β-CD@QD was analyzed using high-resolution
TEM on a JEOL JEM2011 electron microscope operating at
200 kV. TEM samples were prepared by spreading a droplet of
diluted solution and drying in air under vacuum overnight at
40 °C on copper grids withstandard carbon-coatedFormvar films
on copper grids.
The rheological behavior of the samples was measured by an
Advanced Rheology Expanded System (ARES, TA), fitted with
a parallel plate (diameter of 50 mm) and circulating environ-
mental system for temperature control. The gap distance be-
tween the two parallel plates was fixed at 0.2 mm. The gel
formation process was investigated by increasing temperature at
a rate of 20 °C/h. The study of the thermoreversibility of samples
(Figure S8) was performed by increase and decrease of tem-
perature at a rate of 60 °C/h. Steady rheology measurements
were performed by steady-step temperature-ram test (strain-
controlled) at the same sheer rate (1 s-1). Dynamic rheology
measurements were performed by oscillatory temperature
sweeps (stress-controlled) at the oscillation frequency of 1 Hz
and the deformation of 0.1.
Figure 12. Temperature dependence of viscosity for HIC with 12 wt %
concentration constructed by (a) AZO-I-2, (b) AZO-I-3, (c) AZO-II-2,
and (d) AZO-III-2.
the reduced viscosity as AZO-I-2 was also observed. This was
due to the dehydration of PNIPAM block, and the released
water may act as lubricant reducing the apparent viscosity
during the stable sweeping measurement. However, for the
copolymer with longer PDMA block (AZO-II-2 and AZO-
III-2), the viscosity increased continuously after the tem-
perature exceeded the LCST of PNIPAM because of the
water absorbance of the longer hydrophilic PDMA, which
eliminated the lubricant phenomenon.
Conclusions
We presented supramolecular hydrogels composed of a single
supramolecular building block named HIC, which was self-
assembled by AZO-(PDMA-b-PNIPAM) block copolymer and
β-CD@QD via inclusion complexation. Parallel to the thermo-
sensitivity contributed from PNIPAM aggregation, gelation
ability of the hybrid core is also effective and tunable by supra-
molecular substitution. The hydrogel kept the innate fluorescence
behavior from quantum dots, which are uniformly distributed in
the hydrogel. This property makes the hydrogel a potential
candidate for biosensor. The construction of the supramolecular
hydrogel via the three-layer HIC may provide a new bottom-up
method for designing stimuli-responsive hydrogels, offering great
promise of a variety of applications.
Synthesis of Azobenzene-Protected RAFT Chain Transfer
Agent (AZO-CTA). Trithiocarbonate acid (S-ethyl-S0-(R,R0-
dimethyl-R00-acetic acid)trithiocarbonate) was prepared as pre-
viously reported.39 AZO-protected CTA was prepared by a
conventional N,N0-dicyclohexylcarbodiimide (DCC)-mediated
esterification of 4-phenylazophenol with trithiocarbonate acid
precursor as follows: Trithiocarbonate acid (2.24 g, 0.01 mol,
1 equiv) and 4-phenylazophenol (1.98 g, 0.01 mol, 1 equiv) were
dissolved in dry dichloromethane (80 mL) in an ice bath, and the
mixed solution was purged with nitrogen for 10 min, followed by
dropping dichloromethane solution of DCC (4.16 g 0.02 mol,
2 equiv) and 4-(N,N-dimethylamino)pyridine (DMAP) (0.245 g,
0.002 mol, 0.2 equiv). After the reaction was carried out at room
temperature for 24 h, the resultant mixture was filtered, and the
filtrate was concentrated, dissolved in chloroform, and washed
with water twice. The organic layer was then dried with MgSO4,
filtered, and concentrated. The residual concentrated solution
was chromatographed on silica gel with chloroform as eluent to
obtain AZO-CTA. Yield: 3.55 g (84%). 1H NMR (CDCl3): δ =
1.33-1.38 (t, 3H, CH3), 1.84-1.87 (s, 6H, C(CH3)2), 3.31-3.38
(q, 2H, CH2), 7.22-7.27 (d, 2H, azobenzene-HR), 7.46-7.54
(m, 3H, azobenzene-Hγ), 7.87-7.96 (m, 4H, azobenzene-Hβ).
ESI-MS: 426.3 [M þ Na]þ.
Experimental Section
Materials. N-Isopropylacrylamide (NIPAM, recrystallized
three times from benzene/hexane (65:35 v/v) prior to use) and
N,N-dimethylacrylamide (DMA, distilled under reduced pres-
sure before polymerization) were purchased from Tokyo Kasei
Kagyo Co. 4-Phenylazophenol (97%) was purchased from Alfa
Aesar. β-Cyclodextrin (β-CD, CP, recrystallized twice from
deionized water) and azodiisobutyronitrile (AIBN, CP, recrys-
tallized from ethanol before use) were supplied by Sinopharm
Chemical Reagent Co. Per-7-thio-β-cyclodextrin was prepared
according to the literature.37,38 Modified CdS quantum dots
(β-CD@QD) was prepared by following reported procedure.31
Unless specially mentioned, all other chemicals were used as
received.
Characterizations. 1H NMR spectra were recorded with a
JEOL ECA-400 spectrometer. Samples were prepared in CDCl3-d.
Gel permeation chromatography (GPC) analysis was carried
out with a Waters Breeze 1525 GPC analysis system with two PL
mix-D column, using DMF with 0.5 M LiBr as eluents at the
flow rate of 1 mL/min at 80 °C, PEO calibration kit (purchased
from TOSOH) as the calibration standard. UV-vis spectra were
recorded in a conventional quartz cell (light path 10 mm) on a
Typical Synthesis of AZO-PDMA MacroRAFT CTA
(MacroAZO-CTA) through RAFT. A typical procedure em-
ployed for the preparation of macroAZO-CTA was as follows:
AZO-protected CTA (0.2020 g, 0.5 mmol), AIBN (0.01642 g, 0.1
mmol), N,N-dimethylacrylamide (4.957 g, 50 mmol), and 5 mL
of 1,4-dioxane were added in a 25 mL flask equipped with a
magnetic stirring bar. After degassed by freeze-pump-thaw

Article
Macromolecules, Vol. 43, No. 19, 2010 8093
cycles for three times, the mixed solution was immediately
transferred to preheated 70 °C oil bath to initiate the polymer-
ization. After 4 h, the polymerization was quenched by liquid
N2, and the resulting mixture was precipitated in diethyl ether.
The precipitate was dissolved in THF and then precipitated
again into an excess of diethyl ether. The above dissolution-
precipitation cycle was repeated three times. The final product
was dried in vacuum, yielding a yellow solid (4.38 g, 87%,
Supporting Information Available: Figures S1-S9 and
Table S1. This material is available free of charge via the Internet
at http://pubs.acs.org.
References and Notes
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n,GPC = 4.78 ꢀ 103, Mw,GPC/Mn,GPC = 1.09). The degree
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1
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1
weight of macroAZO-CTA determined by H NMR is 1.06 ꢀ
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at δ 7.89-7.98 and NIPAM at δ 1.05-1.25 region in 1H NMR
(Figure S3). Other AZO-(PDMA-b-PNIPAM) block copolymers
with different degrees of polymerization were prepared through a
similar preparation procedure.
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containing 0.88 mL of water. After β-CD@QDs was dissolved
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the block copolymer is ca. 1.5:1. The resultant mixture was stirred
for more than 3 days to ensure the inclusion complexation com-
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5 ꢀ 104) and lyophilization. HIC with other CD to AZO ratios were
prepared by the same procedure. The hydrogel was formed after
heating at 40 °C for 1 h under desired concentration. Other
hydrogels were prepared through a similar method.
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Acknowledgment. We thank National Natural Science
Foundation of China (NNSFC No. 20834004, 20904005, and
20774021) and Ministry of Science and Technology of China
(2009-CB930400) for financialsupport. G.C. alsothanks Heather
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