Poly(N-isopropylacrylamide) hydrogels fabricated via click chemistry: Well-defined α,ω-bis propargyl linear poly(N-isopropylacrylamide)s as crosslinkers

Article abstract of DOI:10.1039/c4ra07987f

A series of poly(N-isopropylacrylamide) (PNIPA) hydrogels were fabricated through click chemistry by using a well-defined azido-PNIPA carrying pendant azido groups, and linear α,ω-bis propargyl PNIPAs with different chain lengths. Here linear α,ω-bis propargyl PNIPAs were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization by using a bis propargyl terminal chain transfer agent, whose chain lengths were modulated by changing polymerization conditions. The obtained hydrogels showed increasing ESR values in the swollen state and increasing volume phase transition temperatures (VPTTs) with increasing molecular weights of bis propargyl PNIPAs, ascribed to the lengthening distance between crosslinks and improving hydrophilicity. The incorporation of amine together with crosslinking modified the hydrophilicity of a click hydrogel, resulting in the elevated VPTT and additional pH sensitivity. The present study provided a facile method to regulate swelling properties and/or to impart special functions for PNIPA hydrogels, by adjusting the chain length of crosslinkers or by introducing other functional groups. This journal is

Full text of DOI:10.1039/c4ra07987f

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Poly(N-isopropylacrylamide) hydrogels fabricated
via click chemistry: well-defined a,u-bis propargyl
Cite this: RSC Adv., 2014, 4, 51510
linear poly(N-isopropylacrylamide)s as
crosslinkers†
a
Jianquan Wang, Zeyu Kang,a Bin Qi,a Qiushi Zhou,a Shengyuan Xiaob
*
and Ziqiang Shaoa
A series of poly(N-isopropylacrylamide) (PNIPA) hydrogels were fabricated through click chemistry by using
a well-defined azido-PNIPA carrying pendant azido groups, and linear a,u-bis propargyl PNIPAs with
different chain lengths. Here linear a,u-bis propargyl PNIPAs were synthesized via reversible addition-
fragmentation chain transfer (RAFT) polymerization by using a bis propargyl terminal chain transfer agent,
whose chain lengths were modulated by changing polymerization conditions. The obtained hydrogels
showed increasing ESR values in the swollen state and increasing volume phase transition temperatures
(VPTTs) with increasing molecular weights of bis propargyl PNIPAs, ascribed to the lengthening distance
between crosslinks and improving hydrophilicity. The incorporation of amine together with crosslinking
modified the hydrophilicity of a click hydrogel, resulting in the elevated VPTT and additional pH
sensitivity. The present study provided a facile method to regulate swelling properties and/or to impart
special functions for PNIPA hydrogels, by adjusting the chain length of crosslinkers or by introducing
other functional groups.
Received 1st August 2014
Accepted 6th October 2014
DOI: 10.1039/c4ra07987f
www.rsc.org/advances
aspects, due to their wide potential applications in biomate-
rials, separation, sensors, actuators, and so on.7–11 The appli-
Introduction
cation of RDRP to NIPA enables the design and synthesis
of various well-dened NIPA-based polymers containing special
functional groups. Iron oxide/PNIPA core–shell structure
was constructed via the “graing-from” NMP of NIPA in the
presence of 1,2-diol moiety ended NMP initiator capable of
attaching the surface of Fe2O3 nanoparticles.12 PNIPAs with
different end groups of varying polarity were synthesized
through ATRP of NIPA initiated by corresponding chlor-
opropionate and chloropropionamide compounds in order to
investigate the end group effect on thermal response of PNIPA.13
Azido- or alkynyl- terminated PNIPA polymers with well-dened
structures were easily prepared based on the appropriate
ATRP initiators or RAFT agents, and they were utilized to
perform further click reaction with partner-group-containing
substrates.14–20 In addition, RAFT agents featured with thio-
carbonylthio groups, such as dithioesters and trithiocar-
bonates, facilitate post-polymerization modication of RAFT
polymers for further end-functionalization.21,22 Different tele-
chelic PNIPAs were obtained through aminolysis of thio-
carbonylthio moieties and subsequent Michael addition of the
resulting thiols to a, b-unsaturated carbonyl derivatives in near
quantitative yields.23–25
Reversible-deactivation radical polymerization (RDRP) tech-
niques, also referred to as controlled/living radical polymeri-
zation (CRP), provide powerful tools to design and synthesize
well-dened functional macromolecules with complex archi-
tectures. In general, nitroxide-mediated polymerization (NMP),1
atom transfer radical polymerization (ATRP),2 and reversible
addition-fragmentation chain transfer (RAFT) polymerization3
are the three most commonly used RDRP methods.4 Using these
approaches, narrow polydispersity macromolecules with
desired molecular weights and architectures can be readily
prepared; as well, special functional moieties can be easily
incorporated to specic position on polymer chains via func-
tional initiators, chain transfer agents (CTAs) and modication
of terminal groups.2,3,5
Poly(N-isopropylacrylamide) (PNIPA), a well-known temper-
ature sensitive polymer whose aqueous solution behaving a
lower critical solution temperature (LCST) around 32 C,6 has
ꢀ
been extensively studied in both fundamental and technical
aSchool of Materials Science and Engineering, Beijing Institute of Technology, Beijing,
100081, China. E-mail: jqwang@bit.edu.cn; Tel: +86-10-68940942
bSchool of Life Science, Beijing Institute of Technology, Beijing, 100081, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra07987f
Click chemistry, usually classied into azide–alkyne cyclo-
addition, thiol–ene addition, and Diels–Alder cycloaddition,
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has been widely used as a forceful tool to fabricate well-dened recrystallized from hexane, AIBN was recrystallized from
and complex structures or to impart special functions. As the ethanol, GMA was passed through basic alumina, and carbon
premier example of these three typical click reactions, azide– disulde (CS2), 1,4-dioxane and tetrahydrofuran (THF) were
alkyne cycloaddition has been applied in many elds including distilled. All other reagents were used as received.
organic synthesis, bioconjugation, polymer preparation and
modication, network formation, etc.26–28 In 2006, Cu(I)-cata-
lyzed azide–alkyne cycloaddition (CuAAC) was pioneeringly
Synthesis of RAFT CTAs
utilized to prepare PVA- and PEG-based hydrogels, opening a S,S0-bis(a,a0-dimethyl-a00-acetic acid) trithiocarbonate (DMAT), a
novel effective crosslinking method for hydrogel fabrication.29,30 bis-carboxyl terminated CTA for RAFT polymerization was
Especially for the click PEG hydrogels, the high efficiency of prepared according to literature.35 In detail, CS2 (13.7 g,
CuAAC click chemistry endowed the resulting hydrogels with 180 mmol), chloroform (53.8 g, 450 mmol), acetone (26.1 g,
more ideal structures and consequent improved mechanical 450 mmol), tetrabutylammonium hydrogen sulfate (1.2 g,
properties.30 Certainly this promising crosslinking strategy has 3.5 mmol), and mineral oil (60 mL) were added into a 500 mL
also been introduced to the construction of PNIPA hydrogels. three-neck round-bottom ask in ice bath, and the mixture was
Zhang's group synthesized a series of PNIPA hydrogels through purged with N2 under stirring. Aer 10 min, 50 wt% sodium
CuAAC, using poly(N-isopropylacrylamide-co-hydroxylethyl hydroxide aqueous solution (100 g, 1.25 mol) was dropped into
methacrylate) [P(NIPA-co-HEMA)], b-cyclodextrin (b-CD), and the above stirring mixture under N2 protection for over 90 min,
cellulose carrying alkyne or azido groups as materials.31–33 Ooi and the reaction was kept for 12 h at room temperature. At the
et al. prepared telechelic azido-ended PNIPAs via RAFT poly- end of the reaction, the mixture was strongly bubbled with N2
merization, followed by click reaction with a tetra-acetylene for 20 min in order to remove the residual chloroform and
crosslinker, obtaining highly regular PNIPA networks.16 Pasale acetone. Then the resultant mixture was added to 500 mL of
and coworkers fabricated multi-responsive hyaluronan-PNIPA water under severely stirring to dissolve the solid, and liquid
hybrid hydrogels using azido-graed hyaluronic acid and a,u- separation was performed to remove oil phase. Slowly dropping
bis propargyl end-capped PNIPA.20 We constructed PNIPA 60 mL of concentrated HCl into the separated aqueous phase in
hydrogels utilizing a well-dened linear PNIPA with pendant water bath, a great deal of yellow precipitate was generated,
azido groups crosslinked by bis- and tetra- alkynyl terminated then it was ltered and washed with water. The collected solid
compounds.34
was recrystallized from ethanol to get yellow crystal (21.3 g, yield
As described above, both RDRP and click chemistry provide 42%). m.p.172–175 ꢀC. 1H-NMR (DMSO-d6) ppm: d 1.67 (s, 12H,
valid strategy for preparation of well-dened polymer struc- >C(CH3)2), 12.77 (s, 2H, –COOH). 13C-NMR (DMSO-d6) ppm:
tures. Therefore it is necessary to prepare well-dened PNIPA d 25.1 (s, –CH3), 55.9 (s, >C(CH3)2), 173.8 (s, –COOH), 219.8 (s, –
hydrogels via the two versatile methods so as to study the C(¼S)S2). HR-MS: m/z 304.99527 [M + Na]+ (C9H14NaO4S3, cal.
structure-property relationship more accurately. In the present 304.99519, err. 0.262 ppm). Elemental analysis: C 37.89 (cal.
work, a series of well-dened a,u-bis propargyl telechelic linear 38.30), H 5.09 (cal. 4.96), S 33.86 (cal. 34.04).
PNIPAs with different molecular weights were synthesized
A bis propargyl ended CTA, S,S0-bis(a,a0-dimethyl-a00-prop-
through RAFT polymerization by using an a,u-bis propargyl argyl acetate) trithiocarbonate (BDPT), was prepared by using
terminal CTA. Then these obtained bis-functional PNIPAs acted DMAT as a raw material. DMAT (5.64 g, 20 mmol) was added
as macromolecular crosslinkers to react with a linear PNIPA into a 100 mL three-neck round-bottom ask. Next thionyl
carrying pendant azido groups (azido-PNIPA), to produce chloride (60 mL, 800 mmol) was dropped with stirring under
hydrogels via CuAAC. The effect of bis-functional PNIPAs chain nitrogen protection. Then the mixture was reuxed at 60 ꢀC for
length on hydrogel properties was studied, and the possibility to 3 h, getting a dark-red solution. Unreacted thionyl chloride was
incorporate other functional groups such as amino, carboxyl, or removed under reduced pressure to yield acyl chloride (tan
luminous units together with crosslinking was explored as well. solid). Subsequently, the resultant was dissolved in 15 mL of
The synthetic route of click PNIPA hydrogels is shown in dried dichloromethane (DCM), and added dropwise to the
Scheme 1.
stirring solution including propargyl alcohol (4.48 g, 80 mmol),
dried pyridine (4.74 g, 60 mmol) and dried DCM (15 mL) in ice
bath under nitrogen atmosphere. The reactant mixture was le
to stir at room temperature for 12 h. Aerwards, the resulting
mixture was washed with 0.1 N hydrochloric acid aqueous
Experimental
Materials
N-isopropylacrylamide (NIPA), glycidyl methacrylate (GMA), solution (100 mL ꢁ 3) and water (50 mL ꢁ 3) and dried over
tetrabutylammonium hydrogen sulphate and polystyrene stan- Na2SO4. Then the solvent was removed via rotary evaporation
dards were purchased from TCI (Shanghai) Development Co., and the resultant was washed with hexane and dried in vacuum
Ltd. Thionyl chloride and 4,40-azobis(4-cyanovaleric acid) (V501) to obtain brown viscous liquid (4.68 g, yield 65%). 1H-NMR
were acquired from Alfa Aesar China (Tianjin) Co., Ltd. 2,20- (CDCl3) ppm: d 1.53 (s, 12H, >C(CH3)2), 2.46 (s, 2H, hCH),
Azobis(isobutyronitrile) (AIBN), propargyl alcohol and prop- 4.67 (s, 4H, –CH2–). 13C-NMR, (CDCl3) ppm: d 24.6 (s, –CH3),
argyl amine were obtained from Tianjin Heowns Biochemical 55.5 (s, >C(CH3)2), 172.1 (s, –COO–), 217.6 (s, –C(¼S)S2), 53.3
Technology Co., Ltd. Other chemicals (AR grade) were bought (–CH2O–), 76.8 (C^CH), 75.3 (C^CH). HR-MS: m/z 381.02648
from Beijing Chemicals Co., China. Prior to use, NIPA was [M + Na]+ (C15H18NaO4S3, cal. 381.02649, err. ꢂ0.026 ppm).
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Scheme 1 Synthetic route of a,u-bis functional PNIPAs and hydrogels. (a) Azido-PNIPA was prepared through RAFT polymerization of NIPA and
GMA and following azidation of pendant epoxyls; (b) a,u-bis propargyl PNIPAs were synthesized via RAFT polymerization using bis propargyl
terminal BDPT as CTA; (c) a,u-bis propargyl PNIPAs were applied as crosslinkers to react with azido-PNIPA containing pendant azido-groups
through click chemistry.
Elemental analysis: C 50.35 (cal. 50.28), H 5.31 (cal. 5.03), of distilled THF in a 30 mL Schlenk tube. The mixture was
S 26.35 (cal. 26.82).
subject to three freeze–pump–thaw cycles, and was stirred
under nitrogen atmosphere in 65 C water bath. The polymer-
ꢀ
ization progress was monitored by extracting 0.5 mL of aliquots
from the polymerization solution at the desired time interval.
The extracted solutions were immediately quenched by opening
in air and cooling in liquid nitrogen. The solvent was removed
under a gentle airstream and subsequent vacuum drying. The
resulting solid was used for 1H-NMR measurement. The
monomer conversion was calculated from the area of signal at
5.6 ppm assigned to the vinyl proton of NIPA and the areas sum
of the isopropyl methine proton signals at 4.0 ppm and
4.1 ppm, corresponding to PNIPA and the remaining NIPA
monomer, respectively.
Preparation of PNIPA polymers
Azido-PNIPA was synthesized through azidation of RAFT copoly-
mer of NIPA and GMA, with polydispersity index (PDI) as low as
1.06. The obtained azido-PNIPA carries 10 mol% azido side groups
relative to the total repeated units in the polymer chain. P(NIPA-co-
GMA) was prepared with 9 : 1 (molar ratio) of NIPA to GMA, using
DMAT as CTA and V501 as initiator, in 1,4-dioxane solution at 75
ꢀC. Aerwards, epoxyl units of GMA in the polymer was azidized
quantitatively. The detailed procedure and characterization have
been reported in our previous paper.34
a,u-bis propargyl PNIPAs were prepared based on RAFT
polymerization of NIPA in the presence of BDPT containing bis
propargyl ends. Typically, NIPA (2.26 g, 20 mmol), BDPT (36 mg,
0.1 mmol) and AIBN (1.6 mg, 0.01 mmol) were dissolved in 6.8 g
PNIPAs with different molecular weights were prepared
through changing the dosage of compounds and polymeriza-
tion time, the detail was listed in Table 1. At the end of
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Table 1 The detailed information of obtained PNIPAs
Mn (kg molꢂ1
)
Samples
[NIPA]/[BDPT]/[AIBN]
Polymerization time (min)
Conversion (%)
Theorya
NMRb
UV-visc
PDI (GPC)
PNIPA2K
PNIPA4K
PNIPA12K
PNIPA18K
30/1/0.1
50/1/0.1
200/1/0.1
250/1/0.1
75
180
120
180
64
68
58
65
2.5
4.2
13.5
18.7
2.2
4.5
12.1
18.2
2.0
4.1
13.1
20.3
1.12
1.20
1.18
1.22
polymerization, the resultant was quickly quenched by opening
in air and cooling in liquid nitrogen. 0.5 mL of the resultant was
taken out for the determination of monomer conversion, and
the le was rotary evaporated to concentrate, followed by
precipitation in diethyl ether. The obtained yellow solid was
puried further by two consecutive reprecipitations from THF
into diethyl ether.
Fabrication of PNIPA hydrogels
In a at-bottom screw-capped glass vial (f 1 cm), the pre-
determined amount of azido-PNIPA and bis propargyl PNIPA,
total weight of which was 200 mg, were dissolved in 750 mg of
DMF. Aer uniform mixing, 25 mL of 0.5 N CuSO4 aqueous
solution and 25 mL of 1.0 N ascorbic acid in DMF were added in
turn. Then the vial was sealed and shaken, and the gel formed
within 15 min. It was le to react for 24 h before the gel was
taken out to immerse in 0.2 N ethylene diamine tetraacetic acid
disodium salt (EDTA$2Na) aqueous solution and then in
ethanol to remove copper ions and unreacted precursors.
Aerwards, the gel was dried and weighed. The mass of xerogel
was divided by 200 to get gel fraction. Through changing the
species of bis propargyl PNIPAs, several hydrogels were
prepared. In addition, amino groups were simultaneously
introduced into a hydrogel in the case that propargyl amine was
added into azido- and propargyl- PNIPAs mixture.
Estimation of a,u-bis propargyl PNIPA molecular weights
The molecular weights (Mn) of samples were obtained by three
methods. Following eqn (1), the theory one was calculated from
monomer conversion that was estimated according to 1H-NMR
spectra of unseparated polymerizing resultant including poly-
mer and residual monomer. For the puried polymers, Mn was
evaluated via eqn (2) using the peak areas at 4.7 ppm and 4.0
ppm, which correspond to propynyl methylene and isopropyl
methine protons, respectively. Furthermore, UV-vis can also be
utilized to measure Mn of a RAFT polymer due to the existence
of a characteristic absorbance at about 310 nm for trithiocar-
bonate group from CTA. Accurately weighed a,u-bis propargyl
PNIPA sample (ꢃ10 mg) was dissolved in ethanol (10 mL),
obtaining ethanol solution with a known polymer concentra-
tion. The UV absorbance of the solution, diluted if necessary, at
310 nm was determined. And the concentration of trithiocar-
bonate group was calculated based on the linear relationship of
absorbance (at 310 nm) and BDPT concentration in ethanol,
which was derived as eqn (3). Further, Mn was reckoned
applying eqn (4).
Swelling properties of hydrogels
Preweighted xerogels were immersed in deionized water at
13 ꢀC, and some time later they were taken out and weighed
aer removal of excess surface water with wet lter paper. The
equilibrium was reached until weight of a swollen gel kept
constant. The equilibrium swelling ratio (ESR) value was
calculated with eqn (5).
ESR ¼ (me ꢂ m0)/m0
(5)
Mn (theory) ¼ conversion ꢁ ([NIPA]/[BDPT])
where m0 and me are the weights of xerogel and equilibrated
swollen hydrogel, respectively.
Aerwards, the temperature was increased gradually to 40 ꢀC
by changing the bath temperature. It is worth noting that the
gels were kept at a certain temperature for 48 h to ensure
swelling equilibrium.
ꢁ MNIPA + MBDPT
(1)
Mn (NMR) ¼ 4 ꢁ (I4.0 ppm/I4.7 ppm) ꢁ MNIPA + MBDPT (2)
CBDPT ¼ 0.0113 A
(3)
(4)
For a hydrogel introduced propargyl amine, the pH sensi-
tivity was investigated in phosphate buffer solutions (PBS) at
Mn (UV-vis) ¼ r/CBDPT
where MNIPA and MBDPT mean individual molecular weights of 25 ꢀC. Na3PO4, Na2HPO4, NaH2PO4, HCl, and NaCl were used to
NIPA and BDPT; I4.0 ppm and I4.7 ppm mean peak areas at 4.0 ppm prepare buffer solutions of different pH values with a constant
and 4.7 ppm for obtained PNIPA 1H-NMR spectra, respectively; ionic strength of 0.1 N.
CBDPT means BDPT concentration in ethanol (mol Lꢂ1), A is
In all of the swelling ratio measurements, three hydrogel
absorbance at 310 nm recorded by UV-vis, and r represents samples of the same formulation were used, and the average
polymer concentration in ethanol (g Lꢂ1).
value was taken.
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polymerization formulation and time. The monomer conver-
sion was controlled to a lower level (<70%) in order to avoid
undesirable side reactions and to ensure the retaining of
propargyls on both ends of polymers.3 The detailed polymeri-
zation conditions and some characterizations of obtained
polymers are listed in Table 1. It can be seen that the molecular
weights calculated by various methods show close values, which
prove the well dened nature of obtained PNIPAs in combina-
tion with the measured PDI values lower than 1.25. In addition,
the incorporation of CTA end groups was also conrmed by 1H-
NMR spectra, as revealed in Fig. 2. Meanwhile, the assignment
of peaks is also illustrated. It is necessary to point out that
molecular weights through GPC measurements are relative
ones to polystyrene standards, leading to greater deviation from
real ones. Thus the GPC Mn values were not listed in Table 1,
while only PDI values were shown.
Characterization
1H-NMR spectra were obtained using a Bruker DRX-500 with
CDCl3 or DMSO-d6 as solvent. High-resolution mass spectra
(HR-MS) were obtained using a Bruker Apex IV FTMS, equipped
with an electro spray ion source (ESI), in positive mode. Both
compounds were dissolved in acetonitrile (approx. 1 mmol Lꢂ1
)
and infused into the ion source with a syringe pump (5 mL
minꢂ1). The ow of nebulizer gas was 1.0 L minꢂ1; the ow of
dry gas was 5.0 L sꢂ1; the temperature of the dry gas was 250 ꢀC;
the scan range was 260–400 Da. Elemental analysis of C, H and S
was performed on an Elementar vario EL III. GPC measure-
ments were carried out at room temperature on a Waters
instrument attached to a 2414 refractive index detector, using
DMF as eluent at a ow rate of 1.0 mL minꢂ1, with polystyrenes
as standards. Ultraviolet-visible (UV-vis) absorption spectros-
copy was performed on a PerkinElmer UV-vis spectrometer
(Lambda 35). The morphology of hydrogels was characterized
by scanning electron microscopy (SEM, JSM-6700F). The
swollen hydrogels at 20 ꢀC were lyophilized, and sputtered with
gold before SEM observation.
Formation of PNIPA hydrogels
A series of PNIPA hydrogels were fabricated through CuAAC
using well-dened a,u-bis propargyl PNIPAs and azido-PNIPA
with pendant azido moieties, as shown in Scheme 1. Herein,
the azido-PNIPA is the same one as used in our previous paper,34
i.e., there is 10 mol% of azido-containing monomer and 90
mol% of NIPA distributed in polymer chains, which was
synthesized by RAFT polymerization of NIPA and GMA with
molar ratio of 90 to 10 followed by azidation of epoxyl in GMA.
In hydrogel preparation, the individual amounts of azido- and
propargyl-containing PNIPAs were designed based on the
principle that 25 mol% of azido-groups was used to react with
all of the propargyl moieties. Corresponding to the individual
molecular weights of used a,u-bis propargyl PNIPAs, the
hydrogel samples were nominated as G2K, G4K, G12K and
G18K, respectively. It is noteworthy that besides those for
crosslinking, there is still 75 mol% of azido groups theoretically
le on polymer chains, which provide effective sites to simul-
taneously incorporate other useful groups for imparting some
Discussion and results
Preparation of a,u-bis propargyl PNIPAs
In order to prepare well-dened linear PNIPA chains with a
telechelic propargyl moiety on either end, a bis propargyl
functional RAFT CTA named as BDPT was rstly synthesized
based on the esterication of bis carboxyl DMAT and propargyl
alcohol in two steps, with acyl chloride as an intermediate
product. The structures of DMAT and BDPT were conrmed by
1H-NMR, 13C-NMR, HR-MS and element analysis. The relevant
spectra are displayed in Fig. S1–S6.† RAFT polymerization of
NIPA using BDPT and AIBN as CTA and initiator, respectively,
was performed in distilled THF at 65 ꢀC. Fig. 1 shows the
polymerization kinetics of a certain formulation, in line with
the basic characteristics of living polymerization.
Several a,u-bis propargyl PNIPA samples with different
molecular weights were prepared through changing the
Fig. 1 Pseudo-first-order kinetic plot of PNIPA RAFT polymerization.
The polymerization condition is as follows: [NIPA]/[BDPT]/[AIBN] ¼ Fig. 2 1H-NMR spectra of a,u-bis propargyl PNIPAs with different
200/1/0.1, the monomer concentration in THF is 25 wt%, polymeri- macromolecular weights. The resonances of related protons are
zation temperature is 65 ꢀC.
assigned.
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special functions. Herein, as an example, another sample need pointing out that G2K, G4K and G12K samples behaved
named G2K-NH2 with additional pH sensitivity was prepared continuous deswelling process when the temperature was
based on the sample G2K, for which propargyl amine in stoi- gradually elevated from 13 to 32 ꢀC; while G18K appeared
ꢀ
chiometric amount of 75 mol% of azido groups was fed together relatively stable ESR values till 22 C and following signicant
ꢀ
with PNIPA2K. Under the catalysis of CuSO4/ascorbic acid deswelling with further temperature rising to 35 C. Analogue
system, all the samples had the gel fraction higher than 90%, to LCST of a linear PNIPA, volume phase transition temperature
demonstrating the high crosslinking efficiency of click chem- (VPTT) is a parameter to characterize a corresponding hydro-
istry in these systems.
gel.6 Here, VPTT values of samples seem different from
one another by preliminarily judging from the trace of
ESR-temperature curve for each one. For
a
negative
Temperature sensitivity of PNIPA hydrogels
temperature-sensitive hydrogel, VPTT can be dened as the
temperature at which the swelling ratio decreased to a half of its
value at initial temperature, or be regarded as the temperature
at which the swelling ratio of hydrogel decreased most
dramatically.37 According to the former denition, the curves of
ESR versus temperature in Fig. 3 were normalized based on the
data at initial temperature (13 ꢀC), plotted in Fig. 4, where water
retention was dened as the ratio between ESR at a certain
temperature and that at 13 ꢀC. From Fig. 4, the VPTT values are
estimated as follows: G2K: 22.1 ꢀC; G4K: 23.4 ꢀC; G12K: 25.1 ꢀC;
For the prepared PNIPA hydrogels, the change of ESR values
with temperature was examined, and the results are shown in
Fig. 3. In general, the ESR values in swollen state display a
tendency that higher-molecular-weight PNIPA crosslinked
hydrogels have greater swelling capacities. For instance, the
ESR values of G2K, G4K, G12K and G18K are 20, 24, 34 and 48,
respectively, at initial temperature (13 ꢀC); and the ESR
sequence keeps consistence at temperatures below 30 ꢀC. In the
case that the feed ratio of azido to alkynyl groups is xed, for an
a,u-bis propargyl PNIPA to crosslink azido-PNIPA presented in
this work, the higher molecular weight of the former means the
longer distance between crosslinks, which provide larger space
to accommodate water molecules. This result is in agreement
with that of PNIPA hydrogels prepared from azido-PNIPA and
multi-alkynl terminated small molecules researched by us,34
and that of PEG hydrogels derived from PEG-bisazide and a
polyester with pendant alkynyl groups, reported by others.36
Besides, the inuence of hydrophobic groups within polymer
chains is also objective. There are two kinds of hydrophobic
moieties, such as carboxylic acid ester and trithiocarbonate
group (originated from RAFT agent), which are located at both
ends and in the middle of bis propargyl-PNIPA chains, respec-
tively. The lower molecular weight of polymer implies the more
relative content of above two kinds of hydrophobic groups. It is
a potential contribution to cause the discrimination of ESR
values for different hydrogels in swollen state.
ꢀ
G18K: 28.3 C. It can be inferred that the VPTT shis to lower
values with decreasing molecular weights of a,u-bis propargyl
PNIPAs, and all of them are lower than 32 ꢀC of a conventional
pure PNIPA hydrogel.38 It is known that either LCST or VPTT is
dependent on the hydrophilic/hydrophobic balance of a poly-
mer system, and the incorporation of hydrophobic component
to PNIPA can improve the dehydration of isopropyls and
accompanied hydrophobic interactions with raising tempera-
ture, further leading to a decline in LCST or VPTT.39–41 Inside the
prepared hydrogels, there are hydrophobic trithiocarbonate
group and 3-azido-2-hydroxypropyl methacrylate (azidized
GMA) within azido-PNIPA chains in addition to those in bis
propargyl PNIPA. It is the presence of these hydrophobic
moieties that reduced VPTT values of obtained hydrogels
compared with that of a conventional one (32 ꢀC). As described
above, for a,u-bis propargyl PNIPAs, higher molecular weight of
polymer corresponds to lower relative content of hydrophobic
parts, which in turn makes VPTT deviate from 32 ꢀC to a smaller
As expected, all the PNIPA hydrogels showed deswelling
behavior with increasing temperature, as revealed in Fig. 3. It
Fig. 4 Water retention of samples at different temperatures relative to
Fig. 3 The change of ESR values with temperature for hydrogels. ESR at 13 ꢀC. VPTT became greater with the increasing molecular
Different ESR values were shown in swollen state for various samples; weights of bis propargyl PNIPAs; G2K-NH2 displayed delayed LSCT
G2K-NH2 revealed gentler deswelling with temperature than G2K.
than G2K due to more hydrophilicity of the former.
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extent. And the lower is PNIPA molecular weight, the larger this hydrophobic balance is also affected by amino groups, so
ꢀ
deviation becomes. In this consideration, the changing trend of VPTT of G2K-NH2 is delayed by near 10 C compared with that
VPTT with different samples becomes understandable. of G2K, as demonstrated in Fig. 4.
Furthermore, the distinction in ESR-temperature curve shapes
Moreover, G2K-NH2 sample is imparted with pH sensitivity
of samples, i.e., the continuous alterations for G2K, G4K and because of the incorporation of amine, and ESR values at
ꢀ
G12K samples from 13 to 32 C versus relative constancy from different pH is plotted in Fig. 5. Herein, the swelling media are
13 to 22 ꢀC and subsequent dramatic descent at higher PBSs with an ionic strength of 0.1 N, and the measuring
temperatures for G18K, may be associated with their different temperature is 25 ꢀC. It can be seen that G2K-NH2 has a typical
hydrophilic performances. For less hydrophobic G18K sample, pH responsibility in the range between pH 2 and pH 10: the
hydrophobic interactions arises only when the temperature hydrogel swells highly at pH values below 3; deswelling
ꢀ
reaches a certain degree above 22 C; while for the other three appeares and becomes more seriously with gradually increasing
more hydrophobic samples, hydrophobic interactions has pH values from 4 to 10. The change of ESR values with pH rising
occurred at lower temperatures and it becomes stronger with is easy to understand because there are different protonation
temperature increasing.
levels of amine at lower and higher pH values. Namely, the
On the basis of the existing differences in temperature higher protonation degree of amine at lower pH stands for
sensitivity for various samples described above, it is worthy to stronger hydrophility, and vice versa. Through the curve in
mention that some parameters such as VPTT and swelling Fig. 5, it can be induced that pKa of amino groups in G2K-NH2 is
capacity change (usually corresponding to volume alternation) between 6 and 7, lower than that of propargyl amine (pKa ¼
with temperature variation can be facilely modulated by 8.15),42 probably as a result of the better electron withdrawing
adjusting the chain length of bis propargyl PNIPA crosslinkers, ability of triazole than that of alkyne. In this work, the
in order to meet various demands.
successful introduction of pH sensitive amino groups accom-
panied by crosslinking via click chemistry, provides a good
reference for endowing of other functions such as electro-
chemical, light sensitivities, luminescence, and so on.
Incorporation of amine to G2K
In order to examine the possibility of simultaneously intro-
ducing functional groups to a network during click cross-
linking, stoichiometric propargyl amine of le azido groups
(0.75 equivalents) was fed together with prequantitative
PNIPA2K-propargyls of azido groups (0.25 equivalents). The
swelling property dependence on temperature was studied
along with other hydrogel samples, and the results are shown in
Fig. 3 and 4. In comparison with G2K, G2K-NH2 sample deco-
rated with amino groups reveals increased ESR values and
higher VPTT value. Comparing both samples, the increment of
G2K-NH2 ESR relative to that of G2K is small at temperatures
SEM photographs of freeze-dried hydrogel networks
In order to characterize internal network structures of hydro-
gels, SEM measurement was performed for freeze-dried
samples, which had been swollen at 20 ꢀC, and the SEM
photographs are shown in Fig. 6. It can be observed that G4K
has bigger pore size than G2K because the former one has
longer distance between crosslinks and corresponding higher
water content. While for G12K and G18K with much higher ESR
values, the pore size seems not higher than that of G4K, and
porous structure of G18K clearly becomes non-uniform. In fact,
higher water content corresponds to lower polymer fraction in
hydrogel, resulting in thinner pore walls. In this case, the sup-
porting force of crosslinked networks becomes weaker, and the
ꢀ
below 16 C, and such a increment becomes especially signi-
cant in the range from 20 ꢀC to 35 ꢀC, as demonstrated in Fig. 3.
For a hydrogel, the ESR value, an indicative of water sorption
capacity, relies on the water affinity of hydrogel components
and network structure. Here the so called network structure
may mean the spaces to hold water molecules in networks,
which is related with crosslinking density. In this research, both
G2K and G2K-NH2 samples should have similar crosslinking
density due to the same dosage of PNIPA2K, i.e., the mesh size
in their fully swollen hydrogels should be approximate. In this
regards, water sorption capacity of G2K-NH2 is restrained to
some extent by stretched chains between crosslinks although
hydrophilic amines is incorporated, because it has been highly
swollen at such low temperatures, like the case of G2K. There-
fore, the ESR difference between G2K and G2K-NH2 at temper-
atures below 16 ꢀC is not so notable. Aerwards, the
hydrophobic interaction in hydrogels becomes stronger and
stronger with increasing temperature due to the dehydration
of isopropyls. However, this interaction is suppressed to a larger
degree due to the existence of hydrophilic amino groups,
leading to the slowing down of G2K-NH2 ESR changing
Fig. 5 Effect of pH on ESR values for G2K-NH2 at 25 ꢀC. The different
protonation levels of amino groups decided the ESR values at various
with temperature increasing. In addition, the hydrophilic/ pH values.
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Fig. 6 SEM photographs of freeze-dried hydrogel networks.
partial shrinking and/or collapse is unavoidable in the course of samples according to SEM observation. In summary, this work
freeze-drying.43 Meanwhile interconnected porous structure is provides an effective approach to adjust temperature sensitivity
observed for G18K sample, which should arise from combined or to modify some special properties, by controlling the chain
action of high water content and freeze-drying process. length of crosslinkers or by introducing other functional
Comparing the cases of G4K and G2K-NH2, both have similar groups, in order to satisfy various application demands. For
water content at 20 ꢀC before freeze-drying (Fig. 3), but the instance, when they were used as temperature responsive
porous structure of the former is relatively regular and that of sensors or actuators, their sensitivities or motion amplitudes
the latter is interconnected. Actually, G2K-NH2 sample has more can be easily modulated by designing hydrogel formulations.
crosslinkages than G4K, and the introduced amine helps the
former one to absorb more water than its analogue G2K. Thus
the interactions between polymer and water molecules as well
Acknowledgements
as water structures and properties inside G2K-NH2 and G4K
samples may be somewhat different, causing the difference of
their network structures.
This work was nancially supported by National Natural
Science Foundation of China (21004005).
Notes and references
Conclusions
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