Polymer Bulletin

https://doi.org/10.1007/s00289-018-2411-1

ORIGINAL PAPER

Study of phase separation behavior

of poly(N,N‑diethylacrylamide) in aqueous solution
prepared by RAFT polymerization

Mei Wu1 · Haibing Zhang1 · Hongliang Liu2

Received: 1 August 2017 / Revised: 30 December 2017 / Accepted: 20 June 2018

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
A series of poly(N,N-diethylacrylamide) samples with low molecular weights
(1.9 × 103–5.3 × 104) and narrow polydispersities (below 1.5 and usually lower than
1.25) was synthesized by reversible addition-fragmentation chain transfer polymeri-
zation. The phase separation behavior of poly(N,N-diethylacrylamide) in aqueous
solution was investigated by turbidimetry, fluorescent probe technology and DSC.
It is interesting to find that the lower critical solution temperature (LCST) of the
samples increases with increasing molecular weight and remains more or less a con-
stant above a critical molecular weight of 1.2 × 104. At the same time, an inverse
dependence of LCST on the concentration was found and this effect was more
pronounced for lower molecular weight. To further investigate the novel molecu-
lar weight dependence of the LCST, the fluorescent probe study was conducted and
the experimental results demonstrated that there was an increase in hydrophobicity
when decreasing the molecular weight and increasing the concentration and flower-
like micelles were probably formed which can further be proved by TEM.

Keywords Lower critical solution temperature (LCST) · Molecular weight ·

Micelles · Reversible addition-fragmentation chain transfer (RAFT)

Electronic supplementary material The online version of this article (https​://doi.org/10.1007/s0028​

9-018-2411-1) contains supplementary material, which is available to authorized users.

* Hongliang Liu
liuhl@mail.ipc.ac.cn
1
China University of Petroleum-Beijing at Karamay, Karamay 834000,
People’s Republic of China
2
CAS Key Laboratory of Bio‑inspired Materials and Interfacial Science, Technical
Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190,
People’s Republic of China

13
Vol.:(0123456789)
 Polymer Bulletin

Introduction

It is well known that the heat denaturation of small protein obeys an intramolecu-
lar analog of the first-order phase separation, i.e., a protein molecular denatures as
a whole without the coexistence of native and denatured parts in the same molec-
ular [1, 2]. However, this is not the case for large proteins, whose temperature-
induced denaturation has been shown more complex. It has been reported that the
“domain structure” is existed during the heat denaturation of large proteins [3,
4], and some other cases cannot even be ascribed to different structural domains
[5]. This makes it still a challenge to study the heat denaturation of large pro-
teins. Therefore, it is worthwhile to find simple models with 3D structure, which
can also undergo heat separation behaviors. Two typical models of this type are
poly(N-isopropylacrylamide) (PNIPA) [6–12] and poly(N,N-diethylacrylamide)
(PDEA) [13–15]. Furthermore, these thermo-sensitive polymers have potential
utility in drug delivery systems [10, 16–18], superabsorbents [19], and separation
and purity of metal ions [20, 21]. To study the phase separation behavior of these
synthetic polymers would help to better understand the heat denaturation of large
proteins and design intelligent materials as well.
An ample amount of studies are available on the temperature-induced phase
separation in aqueous polymer solutions. The temperature at which the phase sep-
aration occurs is commonly called lower critical solution temperature (LCST) or
cloud point (CP) [10, 16, 22, 23]. Below the LCST, water is a good solvent for
polymers, and the interaction between polymers and water becomes dominant.
In this case, the polymer molecules exist in water as extended coils, surrounded
by ordered water molecules (hydrated shell). This shell of hydration causes a
decrease in the entropy of the system. Thus, the free energy of solution is lowered
by the formation of hydrogen bonds but is raised by the loss of entropy. With
increasing the temperature, water becomes a poor solvent for polymers, and the
hydrophobic interaction among polymers gets stronger and stronger. At tempera-
tures above the LCST, the entropy dominates, and polymer chains twisted with
each other, which causes the phase separation [14].
A large number of reports have shown that the LCST of these thermo-sensitive
polymers is affected by many factors. The addition of salts in the polymer solu-
tions usually decreased the LCST [6, 25], while the present of surfactants has
the opposite effect on the LCST [24–26]. Additionally, the LCST is also influ-
enced by the composition of the cosolvent [27], polymer concentration [28], and
pressure [29]. Investigations on the influence of the molecular weight on the
LCST of thermo-sensitive polymers, however, show a large discrepancy in the
results obtained. The results can be categorized into three types: (1) the LCST
decreases with increasing molecular weight [6, 13, 30]; (2) the LCST increases
with increasing molecular weight [28, 31]; (3) the molecular weight has no influ-
ence on the LCST [9, 32]. Feng et al. [33] have also shown that LCST of PNIPA
is inversely dependent, or directly dependent, or independent on the molecular
weight relying on the different end groups. Recently, the self-assembly of amphi-
philic copolymers containing PNIPA or PDEA has attracted much attention in the

13
Polymer Bulletin

scientific community [34, 35], because of their potential application in nanotech-

nology, electronics and drug delivery. These copolymers have often a fairly low
molecular weight, and the PNIPA or PDEA block is short. Based on the above
considerations, it is worthwhile to further investigate the influence of the molecu-
lar weight on the LCST, especially for the polymers with low molecular weight.
For polymers with low molecular weight, narrow polydispersity is essential, or
else it is no sense to study the influence of the molecular weight. Controlled radical
polymerization techniques including atom transfer radical polymerization (ATRP),
nitroxide radical mediated radical polymerization (NMP) and reversible addition-
fragmentation chain transfer (RAFT) radical polymerization have been extensively
studied and found to be useful in the synthesis of polymers with controlled molecu-
lar weight and narrow polydispersity. The RAFT process has a distinct advantage
over the other controlled radical polymerization processes in that it can be used for a
wide range of monomers that can be polymerized in a wide range of solvents includ-
ing water. Lately, McCormick et al. [36–40] have reported that the RAFT process
can be applied to the polymerization of a series of acrylamides including acryla-
mide, N,N-dimethylacrylamide and N-isopropylacrylamide. However, to our knowl-
edge, there are few studies on the synthesis of PDEA by the RAFT process.
Here, we utilize the RAFT process to successfully synthesize PDEA with con-
trolled low molecular weight and narrow polydispersity. The influence of molecu-
lar weight and polymer concentration on the phase separation behavior has been
fully examined by UV–Vis, fluorescence and DSC measurements, and some new
results are obtained.

Experimental section

Materials

Acrylic acid (AR, Tianjin Chemical Reagent Company, China), benzoyl chloride
(AR, Tianjin Guangfu Research Institute of Fine Chemical and Technology, China),
1,4-dihydroxybenzene (AR, Beijing Beijiao Chemical Plant, China), dichlorometh-
ane (AR, Tianjin First Chemical Reagent Plant, China), diethylamine (AR, Beijing
Chemical Reagent Company, China), magnesium (AR, Tianjin Tianyi Chemical
Reagent Plant, China), iodine (AR, Beijing Chemical Plant, China), bromobenzene
(AR, Sinopharm Chemical Reagent Limited Company, China), benzyl bromide (AR,
Shanghai Kefeng Chemical Reagent Company, China) and anhydrous magnesium
sulfate (AR, Shanghai tongya Fine Chemical Plant, China) were used as received.
Azobis(isobutyronitrile) (AIBN, AR, Shanghai Fourth Reagent Plant, China)
was recrystallized from methanol. Pyrene (Py, 96%, Aldrich Chemical Company)
was recrystallized three times from 95% ethanol. Tetrahydrofuran (THF), carbon
disulfide, diethyl ether, acetone, n-hexane, N,N-dimethylformamide (DMF) were
analytical reagent and purchased from Tianjin Chemical Reagent Limited Company
(China). Double distilled water was used for preparation of sample solutions.

13
 Polymer Bulletin

Synthesis of monomer and RAFT chain transfer agent

Synthesis of N,N‑diethylacrylamide (DEA)

Acrylic acid (25.5 mL, 0.3 mol), benzoyl chloride (69.7 mL, 0.6 mol) and 1,4-dihy-
droxybenzene (0.05 g) were mixed in a flask. The reaction mixture was placed in a
thermostated oil bath (100–130 °C) and distilled through a rectifying column. The
receiver containing 1,4-dihydroxybenzene (0.05 g) was put in an ice bath to gather
fraction at 60–70 °C (740 mmHg). The crude product was redistilled through the
same column to obtain purified acryloyl chloride by collecting the distillation at
approximately 70 °C (740 mmHg).
78.0 mL diethylamine and 170 mL dichloromethane were mixed in a three-
necked flask immersed in an ice bath. A solution of 17.5 mL acryloyl chloride dis-
solved in 11.0 mL dichloromethane was added dropwise into the flask at 0 °C under
­N2 atmosphere. The reaction mixture was stirred for 4 h, filtered to separate dieth-
ylamine chloride and washed three times with water. After drying over anhydrous
magnesium sulfate, dichloromethane was removed under reduced pressure. The
crude product was distilled under vacuum several times in the presence of 1,4-dihy-
droxybenzene, to yield a colorless oil (91–93 °C/10 mmHg). 1H NMR spectra were
recorded on a 400-MHz Varian Mercury Plus-400BB spectroscopy using ­CDCl3 as
the solvent, δ (ppm): 1.2 (t, 6H, –CH3), 3.4 (q, 4H, –CH2–), 5.7 (dd, 1H, =CH2), 6.3
(dd, 1H, =CH2), 6.5 (dd, 1H, =CH) (Scheme 1) (Fig. S1).

Synthesis of the RAFT chain transfer agent (CTA) benzyl dithiobenzoate (BDTB)

BDTB was synthesized according to the literature [45]. To 100 mL three-necked

flask were added 1 g magnesium turnings and a grain of iodine. 6.28 g (4.2 mL)
bromobenzene and 20 mL THF were mixed in a constant pressure funnel, and then,
one-third of the solution was added dropwise to the flask. The rest of the solu-
tion was gradually added under magnetic stirring, and the system was refluxed for
another 0.5 h to ensure the complete reaction of magnesium turnings.
The solution was maintained at 40 °C in a thermostated bath, and 3.04 g (2.4 mL)
carbon disulfide was added over 15 min. To the resultant dark brown mixture was
added 7.69 g (5.35 mL) benzyl bromide over 15 min; then, the temperature of the
system was raised to 50 °C and the reaction was continued for a further 45 min.
150 mL ice water was added, and the organic products were extracted three times

Scheme 1  Synthesis of N,N-diethylacrylamide (DEA)

13
Polymer Bulletin

Scheme 2  Synthesis of benzyl dithiobenzoate (BDTB)

Table 1  Molecular weight data for PDEA prepared by RAFT and simple free radical polymerization
Samplesa CTA (mmol) CTA/I Time (h) Conv (%)b Mcn Mw/Mdn
MnTh MnUV MnGPC

R1 0.8 8 6 30.0 1196 1586 1884 1.06

R2 0.5 5 6 56.3 3104 2987 3191 1.10
R3 0.4 4 6 64.2 4319 4741 6210 1.12
R4 0.3 3 6 79.9 7011 5293 7337 1.11
R5 0.2 2 6 65.0 8499 7812 8456 1.19
R6 0.15 1.5 6 52.4 9111 10,556 10,157 1.24
R7 0.1 1 6 58.3 15,052 14,469 12,473 1.14
R8 0.07 0.7 6 50.0 18,387 25,023 15,293 1.45
R9 0.04 0.4 6 55.1 35,232 41,490 50,473 1.25
R10 0.03 0.3 6 68.5 58,241 41,645 53,037 1.25
B1 0 0 6 48.4 – – 22,205 2.57
a
R means samples prepared by RAFT, and B means prepared by simple free radical polymerization
b
Determined by gravimetrical method
c
MnTh is the theoretical molecular weight for RAFT; Mn UV is obtained by end-group analysis using UV–
Vis spectrometer; MnGPC is determined by THF-based GPC
d
Estimated by GPC

with ethyl ether (70 mL × 3). The ethereal phase was washed with water (150 mL),
brine (90 mL) and dried over anhydrous magnesium sulfate. The solution was fil-
tered, and the solvent was removed via a rotary evaporator. The crude product was
subjected to column chromatography (silica gel 60, mesh 70–230) with petroleum
ether as eluent. After the removal of solvent under vacuum, BDTB was obtained as
a red oil. 1H NMR (­ CDCl3) δ (ppm): 4.6 (s, 2H, –CH2–), 7.3–7.6 (m, 5H, ArH), 8.02
(m, 2H, ArH) (Scheme 2) (Fig. S2).

Polymerization of DEA

RAFT polymerizations

Polymerizations of DEA were conducted at different CTA/I (I denotes initiator)

ratios to obtain polymers with different molecular weights (R1 ~ 10, see Table 1).
20 mmol (2.64 mL) DEA, 0.1 mmol (0.0164 g) AIBN and a certain amount of
BDTB were mixed in a flask and subjected to three freeze–pump–thaw cycles to

13
 Polymer Bulletin

Scheme 3  RAFT polymerization of DEA

Scheme 4  Simple radical polymerization of DEA

remove oxygen. Polymerization was carried out for 6 h at 85 °C (temperature of oil

bath), and a small amount of acetone was added to dissolve the polymer after termi-
nation of the reaction. The polymer was isolated by precipitation into hexane, redis-
solved in acetone, reprecipitated into hexane and dried at room temperature under
vacuum to give a pinkish solid. Typical 1H NMR spectrum ­(CDCl3) of R6 is shown
in Fig. S3.
Feed polymerization process was carried out to obtain polymer R11 (see Table 1),
which was synthesized in a fashion similar to R2 except that DEA was added in
batches. 0.64 mL DEA was mixed with 0.1 mmol (0.0164 g) AIBN and 0.5 mmol
(0.122 g) BDTB and degassed through three freeze–pump–thaw cycles. Polymeriza-
tion was then conducted at 85 °C, and 0.5 mL degassed DEA (2 mL in total) was
added to the reaction system every other 0.5 h using a syringe, which was performed
four times in total. After reaction for 6 h altogether, the polymer was precipitated,
purified and dried in a manner reported above to give a pinkish solid.
Polymer R12, whose reactant was four times the amount of R7, was synthesized
in the same way with R7. 90 mmol (11.9 mL) DEA, 0.45 mmol (0.0738 g) AIBN
and 0.45 mmol (0.1098 g) BDTB were mixed, degassed and polymerized at 85 °C
for 6 h, and the polymer was precipitated, purified and dried under vacuum to give a
pinkish solid (see Table 1; Scheme 3).

Synthesis of PDEA via simple radical polymerization

20 mmol (2.64 mL) DEA and 0.1 mmol (0.0164 g) AIBN were mixed, degassed and
polymerized in the same way as RAFT polymerization. The final obtained polymer
was a white solid (B1, see Table 1; Scheme 4).

13
Polymer Bulletin

Polymer characterization

For all polymers synthesized in this experiment, conversions were determined

gravimetrically and the yield is listed in Table 1. 1H NMR spectra were recorded
on a Bruker-300 spectroscopy using C ­ DCl3 as the solvent. The average molecular
weights and polydispersities of the polymers were measured by gel permeation chro-
matography (GPC, HP1100, Hypersil, America) equipped with a Waters 515 pump
and a Waters 2410 differential refractometer. THF was used as an eluent at a flow
rate of 1 mL min−1, and polystyrene standards were used for calibration. The molec-
ular weight was also estimated by end-group analysis via a Lambda 35 UV–Vis
spectrophotometer (Perkin–Elmer) at a wavelength of 500 nm.

Determination of LCST and the critical micelle concentration (CMC)

Determination of LCST by turbidimetry

A Lambda 35 UV–Vis spectrophotometer (Perkin–Elmer) coupled to a shimadzu

TB-85 temperature controller was used to determine the cloud point of the polymer
solution at a wavelength of 500 nm against double distilled water as the reference. A
heating rate of 0.1 °C min−1 was used for the measurement.
The LCST values of aqueous PDEA solutions with different molecular weights
were determined at a concentration of 0.1 wt%. Effect of concentration on the LCST
was also investigated. PDEA samples with higher molecular weight were chosen for
their better solubility and the concentration ranged from 0.1 to 1.5 wt% for R7, R9,
R10 and from 0.1 to 1.0 wt% for R5.

Determination of LCST and cmc by fluorescence measurements

The fluorescence spectra were recorded on a PerkinElmer LS 55 luminescence spec-

trophotometer equipped with a MB-PA/K&Uuml thermostated cell. The excitation
wavelength was set at 330 nm. Excitation slit width was 7.5 nm. Emission slit width
was 5.0 nm for R1, 3.5 nm for R2 and 3.0 nm for other samples. The scan rate was
100 nm min−1. Pyrene was used as a fluorescent probe in this experiment. Aque-
ous solutions of the polymers containing pyrene were prepared as described below.
Stock solution of 1 × 10−3 mol L−1 pyrene in acetone was prepared and then diluted
to 1 × 10−5 mol L−1. 0.6 mL of the diluted stock solution was evaporated in a 10 mL
volumetric flask after which PDEA solution was prepared in the flask, yielding a
6 × 10−7 mol L−1 concentration of pyrene. Solutions were sonicated for 40 min in an
ultrasonic bath and then kept at room temperature for at least 24 h before spectro-
scopic analysis.
Solutions of R1–R10 at a concentration of 0.1 wt% and R10 at different concen-
trations ranged from 0.1 to 1.5 wt% were prepared for LCST and polarity meas-
urements. Emission spectra were recorded as a function of temperature at a heating
rate of 1 °C min−1. The critical micelle concentration (cmc) of PDEA sample was

13
 Polymer Bulletin

determined by recording the fluorescence spectra as a function of polymer concen-

tration at a certain temperature below the LCST. Aqueous solutions of R2, R5, R7
and R10 with different concentrations were prepared for this measurement.

Determination of LCST by microcalorimetry

Calorimetric measurement was taken on a Sapphire differential scanning calorime-

ter (DSC, PerkinElmer) to determine the LCST of PDEA solutions and the enthalpy
of phase separation. The endothermic signal at its minimum (corresponding to the
LCST) was recorded for sample R6–R10 at a concentration of 1.5 wt%. A cell filled
with double distilled water was used as the reference. The scan was performed from
6 to 50 °C at a heating rate of 1 °C min−1.

Transmission electron microscopy (TEM)

TEM measurements were taken using an H-600 TEM instrument (Japan). Aqueous
solutions of R2 (0.5 wt%), R5 (0.5 wt%), R7 (1.5 wt%) and R10 (1.5 wt%) were
casted onto copper grids. After evaporation of the water at 10 °C, the aggregate par-
ticles were observed with the microscope at an accelerating voltage of 100 kV.

Results and discussion

Molecular weight determination of the polymers

The detailed synthesis information is listed in Table 1. In this article, a good con-
trol of the molecular weight is very important including the accuracy of the molec-
ular weight value and a narrow polydispersity. As a result, we will firstly discuss
the determination of the molecular weight of the polymers. We now interpret the
molecular weight data for different polymers analyzed by theoretical calculation, by
UV–Vis spectrometer and by THF-based GPC.
The theoretical molecular weights (Mnth) for RAFT can be calculated by assum-
ing that (1) the efficiency of the dithioester is 100% (i.e., all dithioester groups are
attached to a polymer chain end), (2) the initiation rates of the initiator are low,
which makes always high molar ratios of CTA to primary free radicals, and (3) ter-
mination events (chain transfer to monomer and radical–radical termination) are
negligible [41]. One then has:
[M]0
Mnth = × Xm Mmonomer + MCTA
[CTA]0

where [M]0, ­[CTA]0 are the initial concentrations of the monomer and CTA,
respectively, Xm is the conversion of the monomer (determined by gravimetrical
method), and Mmonomer, MCTA​ are the molecular weights of the monomer and CTA,
respectively.

13
Polymer Bulletin

Moreover, we estimate the number average molecular weights (Mn UV) by end-
group analysis. Full wavelength scan of the BDTB in DMF was carried out from
190 to 1000 nm using UV–Vis spectrometer (Fig. S4). It was found that the π* → π*
absorbance band of the dithioester RAFT moieties was at 305 nm, with its extinc-
tion coefficient as 13,846.52 L mol−1 cm−1, and the n → π* absorbance band was at
500 nm, with its extinction coefficient as 77.25 L mol−1 cm−1. Because the phenyl
groups also had strong absorbance at 305 nm, we chose 500 nm as the measured
wavelength. Assuming that the extinction coefficient of the dithioester is identical
for BDTB and for the polymer, and that the PDEA chains are fully end-group func-
tionalized, we can obtain the MnUV as follows:
m𝜀b
Mn UV =
VA

where m is mass of the polymer, V is the volume of the polymer solution, A is

the absorbance, ε is the extinction coefficient, and b is the thickness of the quartz
cuvette. Comparing the number average molecular weight obtained by the two meth-
ods (see Table 1), there is somewhat difference between them, but nevertheless close
to each other, suggesting a high degree of end-group functionalized, and a good con-
trol of polymerization of PDEA.
The GPC characterization of thermo-sensitive polymers such as PNIPA in THF
involves various problems [42] due to irreversible chain aggregation. However, good
results can be obtained by incomplete drying of polymer (trace amounts of residual
water) and then dissolving in THF [43]. The GPC traces (RI detector) of R1–R10
are shown in Fig. S5.
Figure 1 depicts the comparison of Mnth, MnUV, and MnGPC at various CTA/I
ratios. When CTA/I > 1, they have good agreements with each other, suggesting a

Fig. 1  Number molecular weights (Mn) of PDEA prepared by using RAFT as the function of CTA/I

13
 Polymer Bulletin

high degree of end-group functionalization and a good control of RAFT polymeriza-

tion of PDEA. In contrast, when CTA/I < 1, there are somewhat larger differences
among the three molecular weights, but nevertheless they can still satisfy our needs
for the following research. It should be noted that with a gravimetric determination
of the conversion by precipitation, soluble oligomeric fractions will not be taken
into account, and to some extend the mass loss is inevitable. Therefore, the Mnth
should be slightly lower than MnGPC, which is general consistent with the data as
CTA/I > 1 (as shown in Table 1). This is not the case when CTA/I < 1, and the Mnth
even higher than MnGPC, indicating that some polymer chains are not functionalized
by the RAFT agent [44] and the RAFT polymerization deviates from “living polym-
erization” to some extent.

PDEA synthesis using RAFT process

Selection of the chain transfer agent

BDTB is chosen for this work because reports have shown that it can control the
polymerization of acrylates and acrylamides [45, 46]. Whereas to our knowledge,
there is still no report on synthesizing PDEA by RAFT process using BDTB as the
chain transfer agent.
The choice of the CTA compound is important in synthesis of low molecular
weight distribution polymers, and high transfer constant (Ctr) of the CTA allows
greater flexibility in the choice of reaction conditions. Commonly, the Ctr should
be > 2 to obtain a molecular weight distribution lower than 1.5. Preferably, Ctr > 10
is required to obtain remarkable characteristics of “living polymerization,” such as
pronounced low molecular weight distribution, predictable molecular weight and
line matter of molecular weight with conversion. However, if the reaction is carried
out under conditions whereby the monomer is fed to maintain a lower monomer-
to-CTA ratio, reagents with lower C ­ tr can be used successfully, i.e., the use of feed
addition is advantageous to obtain low molecular weight distribution, but is no need
for high Ctr [45].
In the synthesis of R2 and R11, all the reaction conditions are the same, except
that in the synthesis of R2 the monomer is added at the same time, while R11 adopt
the feed addition. Comparing the data in Table 1, the conversion and molecular
weight of R2 is higher than R11, with almost the same molecular weight distribu-
tion. This can be explained as follows: the Ctr of BDTB is probably high for the
monomer, and low molecular weight distribution can be obtained without feed addi-
tion. However, on the other hand, during the feed addition process the monomer
concentration is much lower, which leads to lower propagation rate and reaction
rate, and as a result causes lower conversion and lower molecular weight. Therefore,
in the present system feed addition is no need, and this in turn also proves that the
choice of BDTB is suitable.

13
Polymer Bulletin

Bulk polymerization

In previous studies based on the RAFT, the process of PNIPA is usually carried
out in benzene or 1,4-dioxane [41, 46]. Being different with NIPA, DEA is liq-
uid under normal conditions, so bulk polymerization is chosen for this work. The
advantages of bulk polymerization are not only to avoid the chain transfer reaction
to solvents but also to facilitate the experimental procedure. However, it should
be mentioned that with the reaction, the viscosity of the system increases greatly,
especially for that with lower CTA-to-initiator ratio (R8, R9 and R10), and even
explosive polymerization occurs during the preparation of B1. High viscosity will
restrict the movements of the polymer chains, and the propagation rates decrease,
which in turn causes more side reactions. This may be one possible reason for
the higher molecular weight distribution of R8, R9 and R10. The same case is for
R12, and its high viscosity is because that the more monomers will lead to rela-
tively higher viscosity with the same reaction time. Therefore, appropriate CTA-
to-initiator ratio and reaction time should be controlled carefully.

Influence of CTA/I ratio

As a general guide in choosing CTA/I ratio for the synthesis of narrow polydis-
persity polymers, CTA/I ratio should be more than 5, while it also can be less
than 5 if the Ctr of the CTA is big enough [45]. Here “I” means the total moles
of initiating radicals formed during the polymerization and it is dependent on the
decomposition rates of the initiator. Increasing the CTA/I ratio, side reactions
can be reduced greatly since the bimolecular termination events are less likely to
occur. Likewise, narrow polydispersities can be obtained. As shown in Table 1,
from R1 to R10, the polydispersities are lower than 1.3, expect R8. In fact, most
of them have the molecular weight distributions less than 1.2. Now, we will dis-
cuss the higher molecular weight distributions of R6 and R8, whose predicted
value are ca. 1.15 and 1.25, respectively. The possible reason is ascribed to the
high reaction temperature in the initial stage of the polymerization (the reaction
temperature reaches to 100 °C due to our occasionally mistakes), which leads to a
faster decomposition rates of AIBN and a corresponding lower CTA/I ratio. As a
result, broader molecular weight distributions than expected are obtained.

Determination of the LCST

The LCST of thermo-sensitive polymers can be determined by several methods,

among which turbidimetry, fluorescence probe and differential scanning calorim-
etry are the most commonly used methods. In this section, the effects of molecu-
lar weight and polymer concentration on the LCST determined by the above three
methods are discussed.

13
 Polymer Bulletin

Determination of the LCST by turbidimetry

Six typical curves of transmittance against temperature at a constant concentration

of 0.1 wt% are shown in Fig. 2a. When the temperature rises, PDEA chains get more
hydrophobic and intermolecular interactions occur, resulting in the formation of
large aggregates that leads to a decrement in the transmittance values at a certain
temperature, known as LCST. The LCST is taken as the intersection of the tangent
to the point of half initial transmittance of the S-shaped transmittance curves with
the extrapolation of the upper horizontal branch of the curves (see lower inset in

Fig. 2  LCST of PDEA determined by using turbidimetry a increases with increasing Mn and b keeps
constant above a critical molecular weight of ca. 1.2 × 104

13
Polymer Bulletin

Fig. 2a). As shown in Fig. 2a, for the polymers with high molecular weight such
as R10, when the temperature reaches the LCST, the transmittance of the polymer
solution decreases sharply. Whereas with decreasing the molecular weight of the
polymer, the transition of the transmittance curves becomes gradual. The similar
results are also obtained by Zhu et al. [13]. In addition, it is surprising that the LCST
of the samples increases with increasing molecular weight and remains more or less
a constant above a critical molecular weight of ca. 1.2 × 104 (see Fig. 2b).
As mentioned in the introduction, most of the researches have shown that the
LCST of the polymer solutions becomes lower as the molecular weight of poly-
mer increases, and the typical thermodynamic theory for polymer solutions with
the LCST also predicts this tendency. For example, Zhu et al. [13] have prepared a
series of polymers of PDEA with different molecular weights (Mn = 9.6 × 103–1.3 ×
106 g mol−1) by fractional precipitation. The LCST behavior of the polymer solu-
tion determined by turbidimetry and DSC has shown that the LCST decreases with
increasing molecular weight and keeps a constant as Mn > 2 × 105. They believe that
this phenomenon is attributed to the difference in the free volumes caused by the
polymer chains and the solvent molecules. This difference is much more significant
for the longer polymer chains, so they undergo phase separation at lower tempera-
ture [47, 48]. Patterson [47] demonstrates that the LCST is proportional to the criti-
cal value of the Flory–Huggins interaction parameter (χc):
)2
𝜒c = 1∕2 1 + r− 1∕2
(

where r is the ratio of the molar volume of the polymer to that of the solvent. It is
obvious that the LCST decreases with the r, while r increases with the length of
the chain, so the LCST of the polymer decreases with the molecular weight of the
polymer.
Reports also show that the molecular weight has no effect on the LCST. Fujishige
et al. [9] claim that the LCST is dependent on neither molecular weight nor polymer
concentration. Whereas the heating rate during their study is so fast that the delicate
difference in LCST can not be observed. Furthermore, the number average molecu-
lar weight of samples is very large in the range of 5 × 104–8.4 × 106, with its mini-
mum value comparable to our maximum value. Our results show that the LCST is
independent on the molecular weight as Mn > 1.2 × 104 (as shown in Fig. 2b), which
is actually accorded with Fujishige to some extent.
Tong et al. [28] also attempt to develop a new mechanism of phase separation
in PNIPA/water solution. They are successful in fractionation of PNIPA and study
two samples with Mw = 4.94 × 104 and 1.01 × 105, and Mw/Mn less than 1.3. They
surprisingly find that PNIPA with higher molecular weight exhibits higher LCST
and believe that upon heating the PNIPA chains in water aggregate together to form
flocci leading to the milky appearance and these flocci are connected to each other
through bridging chains showing an equilibrium modulus.
However, in our opinion, the molecular weight dependence of LCST observed
in this paper is probably due to the end-group residue [33] of the CTA caused dur-
ing the RAFT process. (The structure of the polymer is shown in Scheme 1.) The
reason can be stated from the following two aspects: (1) as mentioned above, from

13
 Polymer Bulletin

the thermodynamic point of view, the difference in the free volume between poly-
mer chains and solvents becomes larger with longer polymer chains, which causes
a decrease in the Flory–Huggins interaction parameter (χc), and thereafter a lower
LCST. (2) During the RAFT process, the hydrophobic end group (dithioester) will
be inevitable introduced to the polymer chains, and the proportion of the dithioester
is higher for lower molecular weight polymers, which causes stronger hydropho-
bicity. As a result, the polymer chains tend to associate with each other, and even
flower-like micelles will be formed. In this case, the hydrophobic end groups aggre-
gate to form the core of the flower-like micelle, and the polymer chains will be
“pulled” together, i.e., the average distance of the polymer segments decreases and
the local concentration of the polymer increases. With raising the temperature, the
hydrophobic groups (ethyl groups) gather more easily, and the polymer chains twist
with each other to generate aggregation. Therefore, the phase separation occurs at
lower temperature for lower molecular weight polymers. On the contrary, for higher
molecular weight polymers, the proportion of the hydrophobic end groups (dithi-
oester groups) falls, leading to the decreasing of hydrophobicity and the weakening
of association. This, in turn, results in a rising of LCST. When Mn > 1.2 × 104, the
content of the dithioester groups in the polymer chains is so small that their influ-
ence can be neglected. Furthermore, when the molecular weight is big enough, the
influence of the length of the polymer chains is little. So the LCST keeps a constant
above a critical molecular weight of ca. 1.2 × 104. Here, it should be noted that the
effect of molecular weight on LCST is attributed to the combination of the above
two aspects; however, the latter plays a dominant role. Therefore, the overall result is
that the LCST increases with increasing molecular weight.
In the present paper, we also investigate the influence of polymer concentration
on the LCST. The effect of polymer concentration on four different molecular weight
samples is shown in Fig. 3. It is clearly found that the LCST decreases with increas-
ing polymer concentration, and the higher of the polymer concentration, the deeper
of the transmittance curve (see inset in Fig. 3). It can also be found if one looks at
Fig. 3 carefully that the concentration dependence of the LCST is more pronounced
for lower molecular weight samples, and the molecular weight dependence of the
LCST is more pronounced for higher polymer concentrations. For example, for R10,
the LCST difference between 0.1 and 1.0 wt% solution is 2.16 °C, while it can be
reached to 5.58 °C for the same cases of R5. The LCST value between R7 and R9
at a constant concentration of 0.1 wt% is almost the same. However, with increasing
polymer concentration, the LCST of R9 is obviously higher than the same concen-
tration of R7, and the difference in the LCST between R9 and R7 is enhanced from
1.33 to 2.44 °C when the polymer concentration is raised from 0.3 to 1.5 wt%.
Being different from the effect of molecular weight on the LCST, the concentra-
tion dependence of the LCST in the studies is generally the same, i.e., the LCST
decreases with increasing polymer concentration [49, 50]. This can be interpreted
with the effective Flory–Huggins interaction parameter χeff [51, 52], where χeff is a
function of both temperature (T) and concentration (C), i.e., χeff = χeff (T, C). The
effects of temperature and polymer concentration on the polymer aggregates in poly-
mer solution have been theoretical studied in several reports [53, 54]. At a certain
temperature, when the concentration is raised, the solvent condition of the polymer

13
Polymer Bulletin

Fig. 3  LCST of PDEA as a function of concentration of PDEA solutions

will change from good solvent to poor solvent, which causes the increment of χeff,
and the concentration dependence of χeff is ascribed to the interaction between intra-
chain and interchain contacts [55]. Anyway, at higher concentration the association
gets stronger and the polymer molecules are prone to aggregate, and this leads to the
decrease in the LCST.
Just recently, Nyström et al. [50] synthesize three low molecular weight samples
of PNIPA with narrow polydispersity, and they find that the LCST of PNIPA shifts
to lower temperatures when the molecular weight and the polymer concentration
increase. Moreover, with increasing polymer concentration, the molecular weight
dependence of the LCST is less pronounced and eventually vanishes. In our studies,
we find that the lower of the polymer molecular weight, the more pronounced con-
centration dependence of the LCST. Particularly, an opposite result is obtained: the
molecular weight dependence of the LCST is more pronounced at higher polymer
concentration. This different phenomenon is also attributed to the chemical struc-
ture of the PDEA prepared by the RAFT process. As discussed above, for the lower
molecular weight polymers, the proportion of the hydrophobic dithioester groups is
larger. With increasing the polymer concentration, accompanied by the increase in
the dithioester groups, the association tendency among the polymer molecules and
the dithioester groups becomes stronger, and the hydrophobicity of the system will
be enhanced greatly, so the LCST reduces more. On the contrary, with increasing the
polymer concentration, the increment of the dithioester groups’ concentration is less
obvious due to the lower proportion of the dithioester groups in the higher molecu-
lar weight polymers. As a result, when the polymer concentration is increased, the
LCST reduces less compared to the lower molecular weight polymers. This is also
the reason that the molecular weight dependence of the LCST is more pronounced at
higher polymer concentration.

13
 Polymer Bulletin

Determination of the LCST and the polarity investigation of the polymer solution
by fluorescence probe study

In the above section, we assume that the molecular weight dependence of the LCST
is due to the end groups (dithioester groups), which causes the PDEA samples with
lower molecular weight more hydrophobic, and lower LCST thereafter. In order to
further investigate the phase separation behavior, fluorescence probe technique is
used to study the polarity of the polymer solution at different temperatures. In these
experiments, pyrene is chosen as the probe because of the fine structure of its fluo-
rescence emission spectrum, especially the ratio I3 (384 nm)/I1 (373 nm) is highly
sensitive to the changes in the polarity of its microenvironment [56, 57], and the
ratio I3/I1 can be used as the benchmark of the environmental polarity. Typical fluo-
rescence emission spectra of pyrene in 0.1 wt% PDEA solutions are shown in Figs.
S6 and S7. The ratio I3/I1 increases as the probe (pyrene) is transferred from a polar
environment to a nonpolar one.
The results obtained by fluorescence measurements are listed in Table 2. On
the one hand, comparing the ratio I3/I1 of the same sample below and above
the LCST, it can be found that the ratio I3/I1 increases greatly with increasing
temperature, indicating a more hydrophobic environment around the probe. The
temperature dependence of the ratio I3/I1 has also been studied, and we define
the temperature at which the ratio I3/I1 increases obviously as the LCST (see

Table 2  LCST and I3/I1 for PDEA solutions prepared by RAFT

Samples Man LCST (°C) ΔHe (J/g) I3/I1
b c d e
T < LCSTf T > LCSTg

R1 1884 14.6 14.1 – – – 1.39 1.72

R2 3191 23.3 18.3 – – – 0.77 1.19
R3 6210 27.3 28.0 – – – 0.74 1.04
R4 7337 29.6 29.1 – – – 0.71 0.96
R5 8456 30.1 29.8 – – – 0.66 0.87
R6 10,157 30.9 29.9 26.3 23.3 – 0.65 0.81
R7 12,473 32.2 31.0 27.8 31.3 14.7 0.64 0.76
R8 15,293 32.2 30.0 28.8 31.3 21.3 0.62 0.70
R9 50,473 32.2 31.0 30.2 30.2 8.7 0.63 0.71
R10 53,037 32.4 30.9 30.0 30.2 6.0 0.62 0.70
a
Determined by GPC
b
Measured by UV–Vis spectrometer (polymer concentration 0.1 wt%; heating rate 0.1 °C min−1)
c
Measured by fluorescence spectrometer (polymer concentration 0.1 wt%; heating rate 1 °C min−1)
d
Measured by UV–Vis spectrometer (polymer concentration 1.5 wt%; heating rate 0.1 °C min−1)
e
Measured by DSC (polymer concentration 1.5 wt%; heating rate 1 °C min−1)
f
Measured by fluorescence spectrometer (polymer concentration 0.1 wt%). For R1 and R2, the tempera-
ture is 7.4 and 14.2 °C, respectively; for the other samples, the temperature is 21 °C
g
Measured by fluorescence spectrometer (polymer concentration 0.1 wt %). For R1 and R2, the tempera-
ture is 30 °C and for the other samples the temperature is 42 °C

13
Polymer Bulletin

Table 2). It can be seen that the LCSTs obtained by this method have good
accordance with that obtained by turbidimetry. Four typical curves of the ratio
I3/I1 as a function of temperature are depicted in Fig. S8. On the other hand, we
can also see that the ratio I3/I1 decreases with increasing the molecular weight
of the samples until a critical molecular weight of ca. Mn = 1.2 × 104, whether
below or above the LCST (see Fig. 2b). As we know, the higher ratio I3/I1 means
that the surrounding environment of the probe is more hydrophobic. That is to
say, the hydrophobicity of the PDEA with lower molecular weight is stronger
than that with higher molecular weight, which, in turn, proves our assumption,
that the lower of the molecular weight the more hydrophobic of the polymer.

Determination of the LCST and enthalpy (ΔH) of the polymer solution by DSC

As previously discussed, χc = 1/2(1 + r−1/2)2, where r increases with augment-

ing the molecular weight of the polymers, so it is clear that χc will decrease
for longer polymer chains. While χc is proportional to the interaction energy
between the polymer and solvent, it is inevitable that the enthalpy during the
phase separation of PDEA solutions will depress with increasing the molecular
weight of the polymers. Four DSC thermograms of R7–R10 with concentration
of 1.5 wt% are exhibited in Fig. 4. The enthalpy of phase separation of PDEA
solutions can be calculated from the DSC thermogram, and it is equal to the area
of the endothermic peak (see Fig. 4). It is obvious that the enthalpy (ΔH) gets
smaller for higher molecular weight polymers, e.g., for lower molecular weight
polymers of R7 (Mn = 12,473) and R8 (Mn = 15,293), the enthalpy changes are
14.7 and 21.3 J g−1, respectively; while for R9 and R10 with higher molecular
weight of 50,473 and 53,037, the enthalpy changes are only 8.7 and 6.0 J g−1.
The value obtained here is well consistent with that reported by Idziak et al. [14]
(ΔH = 22.9 J g−1 for Mn = 2.0 × 104 g mol−1 PDEA sample).
In addition, we can also gain the LCST of the polymer solution, and the
LCST is determined from the lowest point of the endothermic peak. From the
data shown in Table 2, the LCSTs obtained by DSC are somewhat different from
that obtained by turbidimetry, but nevertheless close to each other. Research-
ers have reported that the effect of heating rate on the LCST values obtained
by DSC is less pronounced than that obtained by turbidimetry [14]. Generally
speaking, reliable results can be obtained by turbidimetry when the heating rate
is not higher than 0.1 °C min−1. However, there is also limitation to determine
the LCST by DSC. We have just discussed that the enthalpy change is small
for high molecular weight polymers. Therefore, it is not difficult to imagine that
when the molecular weight of the polymer is big enough, the endothermic peak
in the DSC curve will be small and it will be hard to determine the LCST, which
will enhance the experiment error. That is to say, DSC is suitable for determina-
tion of the LCST when the molecular weight of the polymer is not too high.

13
 Polymer Bulletin

Fig. 4  Determination of the LCST and enthalpy (ΔH) of the polymer solution of R7–R10 by DSC

Micellization behaviors

We believe that the abnormal molecular weight dependence of the LCST is

mainly due to the hydrophobic end groups (dithioester groups) in the polymer
chains, and flower-like micelles are likely to be formed. As we all know, fluo-
rescence techniques have been used with great success in study the formation of
micelles [57–60], and the critical micelle concentration (cmc) is usually deter-
mined by fluorescence spectrum using pyrene as a probe [57, 61, 62], and the
ratio I3/I1 is very helpful for determining the location of the pyrene probe in the
micelles. Figure 5 shows the ratio I3/I1 as a function of logarithm of the poly-
mer concentration (log C) in aqueous solution, and the cmc value is taken as the
intersection of the tangent to the curve at the inflection with horizontal tangent
through the points at low polymer concentration. At low concentrations, the ratio
I3/I1 takes the value characteristic of pyrene in water, and at high concentrations
it takes the value of pyrene in the hydrophobic environment. From the data in
Fig. 5, it can be seen that the ratio I3/I1 has no obvious change at low concentra-
tions, while it increases remarkably above a critical concentration, which sug-
gests the formation of micelles. The cmc values of R2, R5, R7 and R10 are 158.5,

13
Polymer Bulletin

Fig. 5  Determined CMC of R2 (a), R5 (b), R7 (c), and R10 (d) are 158.5, 288.4, 1148 and 1318 mg/L,
respectively

288.4, 1148, and 1318 mg/L respectively (Fig. 5). It is obvious that the lower
molecular weight, the lower cmc value, which indicates that the lower molecu-
lar weight samples are much easier to form micelles and this also, confirms the
proposed explanation about the molecular dependence of the LCST. A schematic
demonstration of the formation of micelles during the phase separation is pre-
sented in Fig. 6. The morphology of the formed micelles is studied by TEM tech-
nology, and four typical images are shown in Fig. 7.

Conclusions

In conclusion, we have reported the synthesis of PDEA by RAFT process. The

molecular weights of the produced polymers have been totally characterized by end-
groups analysis (UV–Vis spectrometer) and GPC and compared with the theoretical
value calculated based on the “living” radical polymerization process. The results
indicate that the RAFT process can be well controlled by using BDTB as the CTA,
especially when the CTA/I ratio is higher than 1.
We have subsequently systematically studied the phase separation behaviors
of the PDEA aqueous solutions by turbidimetry, fluorescence probe technique
and DSC. The LCSTs obtained by these methods have good agreement with each
other. Moreover, it is worthy noting that the LCST increases with increasing

13
 Polymer Bulletin

Fig. 6  Schematic demonstration of micelles formation during the phase separation

Fig. 7  TEM images of the formed micelles of R2 (a), R5 (b), R7 (c), and R10 (d)

molecular weight and keeps more or less a constant above a critical molecular
weight of ca. 1.2 × 104 g mol−1. Meanwhile, an inverse dependence of the LCST
on the polymer concentration is found and the effect is more pronounced for
lower molecular weight.

13
Polymer Bulletin

The abnormal molecular weight dependence of the LCST is ascribed to the larger
proportion of the dithioester groups in the lower molecular weight polymers, which
causes the more hydrophobic nature of the lower molecular weight polymers, and
even the formation of flower-like micelles. This hypothesis is further confirmed by
fluorescence measurements. It is indeed that the lower molecular weight polymers
are much more hydrophobic and a relatively lower cmc value. The morphology of
the micelles can also be observed by TEM more directly. In other words, we can
draw a conclusion that the abnormal molecular weight dependence of the LCST is
related to the polymerization method, which will necessarily introduce different end
groups (hydrophilic or hydrophobic) to the polymer chains. Now, it will be easier to
explain the discrepancy in the LCST values reported previously. Taking Ref. [63]
for example, PDEA with a diphenyl group (hydrophobic) at the chain end has a
LCST at about 30 °C, while for the PDEA without diphenyl group but almost the
same molecular weight, the LCST can be 8 °C higher. Another case is Ref. [64]. The
authors have reported that the LCST of PDEA is approximately 30 °C prepared by
group transfer polymerization and by radical polymerization, but higher LCST of
more than 40 °C is observed for the PDEA prepared by anionic polymerization, and
they claim that no simple correlation between the molecular weight and the LCST
exists. This is because that besides the influence of the molecular weight of the poly-
mers, the polymerization method also plays an important role on the LCST, which
in turn, supports our assumption. From the results obtained in our present research,
we can better understand the major factors that influence the LCST of the PDEA. As
guidance, we can design some new types of PDEA with specific LCST, and this will
make it a better candidate in bioscience and chemical engineering.

Acknowledgements This research is supported by the National Natural Science Foundation (21404109)
and Science Foundation of China University of Petroleum-Beijing at Karamay (RCYJ2016B-03-003,
RCYJ2016B-02-005).

References
1. Privalov PL (1979) Stability of proteins small globular proteins. Adv Protein Chem 33:167–241.
https​://doi.org/10.1016/S0065​-3233(08)60460​-X
2. Privalov PL, Creighton TE (eds) (1992) In protein folding. W. H. Freeman & Co, New York, p 83
3. Privalov PL (1982) Stability of proteins: proteins which do not present a single cooperative system.
Adv Protein Chem 35:1–104. https​://doi.org/10.1016/S0065​-3233(08)60468​-4
4. Freire E, Murphy KP (1991) Molecular basis of co-operativity in protein folding. J Mol Biol
222:687–698. https​://doi.org/10.1016/0022-2836(91)90505​-Z
5. Bychkova VE, Berni R, Rossi GL, Kutyshenko VP, Ptitsyn OB (1992) Retinol-binding protein is
in the molten globule state at low pH. Biochemistry 31:7566–7571. https​://doi.org/10.1021/bi001​
48a01​8
6. Schild HG, Tirrell DA (1990) Microcalorimetric detection of lower critical solution temperatures in
aqueous polymer solutions. J Phys Chem 94:4352–4356. https​://doi.org/10.1021/j1003​73a08​8
7. Shunsuke K, Sokei S, Takahiro O, Tomohiro H, Koichi U, Cheng H, Tetsuo A (2017) NMR studies
of water dynamics during sol-to-gel transition of poly(N-isopropylacrylamide) in concentrated aque-
ous solution. Polymer 109:287–296. https​://doi.org/10.1016/j.polym​er.2016.12.063
8. Takanori T, Tomohiro H, Koichi U, Yukiteru K, Taka-Aki A, Tatsuya S, Noboru K, Yasuy-
uki T (2016) Effects of syndiotacticity on the dynamic and static phase separation properties of

13
 Polymer Bulletin

poly(N-isopropylacrylamide) in aqueous solution. J Phys Chem B 120:7724–7730. https​://doi.

org/10.1021/acs.jpcb.6b032​00
9. Fujishige S, Kubota K, Ando I (1989) Phase transition of aqueous solutions of poly(N-isopropy-
lacrylamide) and poly(N-isopropylmethacrylamide). J Phys Chem 93:3311–3313. https​://doi.
org/10.1021/j1003​45a08​5
10. Kenji M, Tomonari S, Kenichiro K (2016) Liquid–liquid phase separation of N-isopropylpropiona-
mide aqueous solutions above the lower critical solution temperature. Sci Rep 6:24657. https​://doi.
org/10.1038/srep2​4657
11. Wu C, Zhou SQ (1995) Laser light scattering study of the phase transition of poly(N-isopropy-
lacrylamide) in water. 1. Single Chain. Macromolecules 28:8381–8387. https​://doi.org/10.1021/
ma001​28a05​6
12. Zeng F, Zheng X, Tong Z (1998) Network formation in poly(N-isopropyl acrylamide)/water
solutions during phase separation. Polymer 39:1249–1251. https​://doi.org/10.1016/s0032​
-3861(97)00471​-0
13. Lessard DG, Ousalem M, Zhu XX (2001) Effect of the molecular weight on the lower critical solu-
tion temperature of poly(N,N-diethylacrylamide) in aqueous solutions. Can J Chem 79:1870–1874.
https​://doi.org/10.1139/cjc-79-12-1870
14. Idziak I, Acoce D, Lessard D, Gravel D, Zhu XX (1999) Thermosensitivity of aqueous solutions of
poly(N,N-diethylacrylamide). Macromolecules 32:1260–1263. https​://doi.org/10.1021/ma981​171f
15. Mitsuhiro M, Ryo W, Takanori T, Taka-Aki A, Tatsuya S, Noboru K, Yasuyuki T (2016) Rapid
phase separation in aqueous solution of temperature-sensitive poly(N,N-diethylacrylamide). Macro-
mol Chem Phys 217:2576–2583. https​://doi.org/10.1002/macp.20160​0239
16. Plate NA, Lebedeva LI, Valuev LI (1999) Lower critical solution temperature in aqueous solutions
of N-alkyl-substituted polyacrylamides. Polym J 31:21–27. https​://doi.org/10.1295/polym​j.31.21
17. Okano T (1993) Molecular design of temperature-responsive polymers as intelligent materials. Adv
Polym Sci 110:179–197. https​://doi.org/10.1007/BFb00​21133​
18. Miyajima M, Yoshida M, Sato H, Omichi H, Katakai R, Higuchi WI (1994) In vitro release of
9-β-d-arabinofuranosyladenine from thermo-responsive copoly(acryloyl-l-proline methyl ester/sty-
rene) gels. Eur Polym J 30:827–831. https​://doi.org/10.1016/0014-3057(94)90011​-6
19. Chen JP, Hsu (1997) Preparations and properties of temperature-sensitive poly(N-
isopropylacrylamide)-chymotrypsin conjugates. J Mol Catal B Enzym 2:233–241. https​://doi.
org/10.1016/s1381​-1177(96)00032​-x
20. Xue W, Champ S, Huglin MB (2001) New superabsorbent thermoreversible hydrogels. Polymer
42:2247–2250. https​://doi.org/10.1016/S0032​-3861(00)00550​-4
21. Snowden MJ, Thomas D, Vincent B (1993) Use of colloidal microgels for the absorption of heavy
metal and other ions from aqueous solution. Analyst 118:1367–1369. https​://doi.org/10.1039/
AN993​18013​67
22. Heskins M, Guillet JE (1968) Solution properties of poly(N-isopropylacrylamide). J Macromol Sci
A2:1441–1455. https​://doi.org/10.1080/10601​32680​80519​10
23. Taylor LD, Cerankowski LD (1975) Preparation of films exhibiting a balanced temperature depend-
ence to permeation by aqueous solutions—a study of lower consolute behavior. J Polym Sci
11:2551–2570. https​://doi.org/10.1002/pol.1975.17013​1113
24. Eliassaf J (1978) Aqueous solutions of poly(N-isopropylacrylamide). J Appl Polym Sci 22:873–874.
https​://doi.org/10.1002/app.1978.07022​0328
25. Lee LT, Cabane B (1997) Effects of surfactants on thermally collapsed poly(N-isopropylacrylamide)
macromolecules. Macromolecules 30:6559–6566. https​://doi.org/10.1021/ma970​4469
26. Staikos G (1995) Viscometric study of the coil-globule transition of poly(N-isopropylacryla-
mide) in solutions of surfactant. Macromol Rapid Commun 16:913–917. https​://doi.org/10.1002/
marc.1995.03016​1206
27. Schild HG, Muthukumar M, Tirrell DA (1991) Cononsolvency in mixed aqueous solutions of
poly(N-isopropylacrylamide). Macromolecules 24:948–952. https​://doi.org/10.1021/ma000​04a02​2
28. Tong Z, Zeng F, Zheng X (1999) Inverse molecular weight dependence of cloud points for aqueous
poly(N-isopropylacrylamide) solutions. Macromolecules 32:4488–4490. https​://doi.org/10.1021/
ma990​062d
29. Otake K, Karaki R, Ebina T, Yokoyama C, Takahashi S (1993) Pressure effects on the aggregation
of poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylic acid) in aqueous solu-
tions. Macromolecules 26:2194–2197. https​://doi.org/10.1021/ma000​61a00​8

13
Polymer Bulletin

30. Xue W, Huglin MB, Jones TGJ (2003) Parameters affecting the lower critical solution tempera-
ture of linear and crosslinked poly(N-ethylacrylamide) in aqueous media. Macromol Chem Phys
204:1956–1965. https​://doi.org/10.1002/macp.20030​0008
31. Zheng X, Tong Z, Xie XL, Zeng F (1998) Phase separation in poly(N-isopropyl acrylamide)/
water solutions I. cloud point curves and microgelation. Polym J (Tokyo) 30:284–288. https​://
doi.org/10.1295/polym​j.30.284
32. Elizaveta IT, Vladimir NU, Vanda BL, Stanislav IK, Valentina EB, Oleg BP (1995) ”Domain”
coil-globule transition in homopolymers. Macromolecules 28:7519–7524. https​://doi.
org/10.1021/ma001​26a03​2
33. Ru GY, Feng JW (2001) Effect of end groups on phase transition and segmental mobility of
poly(N-isopropylacrylamide) chains in ­D2O. J Polym Sci B Polym Phys 49:749–755. https​://doi.
org/10.1002/polb.22237​
34. Lazzari M, Liu GJ, Lecommandoux S (2006) Block copolymers in nanoscience. Wiley-VCH,
Weinheim
35. Malmsten M (2002) Surfactants and polymers in drug delivery. Marcel Dekker, New York
36. Vasilieva YA, Thomas DB, Scales CW, McCormick CL (2004) Direct controlled polymerization
of a cationic methacrylamido monomer in aqueous media via the RAFT process. Macromol-
ecules 37:2728–2737. https​://doi.org/10.1021/ma035​574d
37. McCormick CL, Lowe AB (2004) Aqueous RAFT polymerization: recent developments in
synthesis of functional water-soluble (co)polymers with controlled structures. Acc Chem Res
37:312–325. https​://doi.org/10.1021/ar030​2484
38. Thomas DB, Convertine AJ, Myrick LJ, Scales CW, Smith AE, Lowe AB, Vasilieva YA, Ayres
N, McCormick CL (2004) Kinetics and molecular weight control of the polymerization of
acrylamide via RAFT. Macromolecules 37:8941–8950. https​://doi.org/10.1021/ma048​199d
39. Donovan MS, Sumerlin BS, Lowe AB, McCormick CL (2002) Controlled/“living” polymeriza-
tion of sulfobetaine monomers directly in aqueous media via RAFT. Macromolecules 35:8663–
8666. https​://doi.org/10.1021/ma020​9996
40. Thomas DB, Sumerlin BS, Lowe AB, McCormick CL (2003) Conditions for facile, controlled
RAFT polymerization of acrylamide in water. Macromolecules 36:1436–1439. https​://doi.
org/10.1021/ma025​960f
41. Ganachaud F, Monteiro MJ, Gilbert RG (2000) Molecular weight characterization of poly(N-
isopropylacrylamide) prepared by living free-radical polymerization. Macromolecules 33:6738–
6745. https​://doi.org/10.1021/ma000​3102
42. Yang HJ, Cole CA, Monji N, Hoffman AS (1990) Preparation of a thermally phase-separating
copolymer, poly(N-isopropylacrylamide-co-N-acryloxysuccinimide), with a controlled number
of active esters per polymer chain. J Polym Sci Part A Polym Chem 28:219–226. https​://doi.
org/10.1002/pola.1990.08028​0116
43. Ganachaud F, Monteiro MJ, Gilber RG, Dourges MA, Thang SH, Rizzardo E (2000) Molecular
weight characterization of poly(N-isopropylacrylamide) prepared by living free-radical polym-
erization. Macromolecules 33:6738–6745. https​://doi.org/10.1021/ma000​3102
44. Moad G, Rizzardo E, Thang SH (2008) Radical addition–fragmentation chemistry in polymer
synthesis. Polymer 49:1079–1131. https​://doi.org/10.1016/j.polym​er.2007.11.020
45. Le TP, Moad G, Rizzardo E, Thang SH (1998) PCT Int Appl 9(801):478
46. Arotcaréna M, Heise B, Ishaya S, Laschewsky A (2002) Switching the Inside and the outside of
aggregates of water-soluble block copolymers with double thermoresponsivity. J Am Chem Soc
124:3787–3793. https​://doi.org/10.1021/ja012​167d
47. Patterson D (1969) Free volume and polymer solubility. A qualitative view. Macromolecules
2:672–677. https​://doi.org/10.1021/ma600​12a02​1
48. Wang F, Saeki S, Yamaguchi T (1999) Absolute prediction of upper and lower critical solution
temperatures in polymer/solvent systems based on corresponding state theory. Polymer 40:2779–
2785. https​://doi.org/10.1016/S0032​-3861(98)00480​-7
49. Liu Y, He JP, Xu JT, Fan DQ, Tang W, Yang YL (2005) Thermal decomposition of cumyl dith-
iobenzoate. Macromolecules 38:10332–10335. https​://doi.org/10.1021/ma051​3970
50. Pamies R, Zhu KZ, Nyström B (2009) Thermal response of low molecular weight poly-(N-
isopropylacrylamide) polymers in aqueous solution. Polym Bull 62:487–502. https​://doi.
org/10.1007/s0028​9-008-0029-4

13
 Polymer Bulletin

51. Malcolm GN, Rowlinson JS (1957) The thermodynamic properties of aqueous solutions of poly-
ethylene glycol, polypropylene glycol and dioxane. Trans Faraday Soc 53:921–931. https​://doi.
org/10.1039/TF957​53009​21
52. Baulin VA, Halperin A (2002) Concentration dependence of the flory χ parameter within two-state
models. Macromolecules 35:6432–6438. https​://doi.org/10.1021/ma020​296o
53. Matsuyama A, Tanaka F (1990) Theory of solvation-induced reentrant phase separation in polymer
solutions. Phys Rev Lett 65:341–344. https​://doi.org/10.1103/PhysR​evLet​t.65.341
54. De Gennes PG (1991) A model for the tack of molten polymers. CR Acad Sci Paris Ser II
313:1415–1418
55. Painter PC, Berg LP, Veytsman B, Coleman MM (1997) Intramolecular screening in nondilute poly-
mer solutions. Macromolecules 30:7529–7535. https​://doi.org/10.1021/ma970​792q
56. Kalyanasundaram K, Thomos JK (1997) Environmental effects on vibronic band intensities in pyr-
ene monomer fluorescence and their application in studies of micellar systems. J Am Chem Soc
99:2039–2044. https​://doi.org/10.1021/ja004​49a00​4
57. Wilhelm M, Zhao CL, Wang YC, Xu RL, Winnik MA (1991) Poly(styrene-ethylene oxide) block
copolymer micelle formation in water: a fluorescence probe study. Macromolecules 24:1033–1040.
https​://doi.org/10.1021/ma000​05a01​0
58. Turro NJ, Grätzel M, Braun A (1980) Photophysical and photochemical processes in micellar sys-
tems. Angew Chem Int Ed Eng 19:675–696. https​://doi.org/10.1002/anie.19800​6751
59. Tang WT, Hadziioannou G, Smith BA, Frank C (1988) Facile method for labelling polystyrene with
various fluorescent dyes. Polymer 29:1313–1317. https​://doi.org/10.1016/0032-3861(88)90062​-6
60. Major MD, Torkelson JM, Brearly AM (1990) Fluorescence energy transfer studies of styrene-iso-
prene diblock copolymer solutions. Macromolecules 23:1700–1710. https​://doi.org/10.1021/ma002​
08a02​5
61. Nagasaki Y, Okada T, Scholz C, Lijima M, Kato M, Kataoka K (1998) The reactive polymeric
micelle based on an aldehyde-ended poly(ethylene glycol)/poly(lactide) block copolymer. Macro-
molecules 31:1473–1479. https​://doi.org/10.1021/ma971​294k
62. Astafieva I, Zhong XF, Eisenberg A (1993) Critical micellization phenomena in block polyelectro-
lyte solutions. Macromolecules 26:7339–7352. https​://doi.org/10.1021/ma000​78a03​4
63. Itakura M, Inomata K, Nose T (2000) Aggregation behavior of poly(N,N-diethylacrylamide) in
aqueous solution. Polymer 41:8681–8687. https​://doi.org/10.1016/S0032​-3861(00)00267​-6
64. Freitag R, Baltes T, Eggert M (1994) A comparison of thermoreactive water-soluble poly-N,N-
diethylacrylamide prepared by anionic and by group transfer polymerization. J Polym Sci Part A
Polym Chem 32:3019–3030. https​://doi.org/10.1002/pola.1994.08032​1603

13