A pH-and temperature-sensitive macrocyclic graft copolymer composed of PEO ring and multi-poly(2-(dimethylamino) ethyl methacrylate) lateral chains

Article abstract of DOI:10.1007/s11426-010-3181-2

A novel method for the synthesis of macrocyclic graft copolymers was developed through combination of anionic ring-opening polymerization (AROP) and atom transfer radical polymerization (ATRP). A linear α,ω-dihydroxyl poly(ethylene oxide) with pendant acetal protected hydroxyl groups (l-poly(EO-co-EEGE)) was prepared first by the anionic copolymerization of ethylene oxide (EO) and ethoxyethyl glycidyl ether (EEGE). Then l-poly(EO-co-EEGE) was cyclized. The crude cyclized product containing the linear byproduct was hydrolyzed and purified by being treated with α-CD. The pure cyclic copolymer [c-poly(EO-co-Gly)] was esterified by reaction with 2-bromoisobutyryl bromide, and then used as ATRP macroinitiators to initiate polymerization of 2-(dimethylamino) ethyl methacrylate (DMAEMA), and a series of pH-and temperature-sensitive macrocyclic graft copolymers composed of a hydrophilic PEO as the ring and PDMAEMA as side chains (c-PEO-g-PDMAEMA) were obtained. The behavior of pH-and temperature-sensitive macrocyclic copolymers was studied in aqueous solution by fluorescence and dynamic light scattering (DLS). The critical micellization pH values of macrocyclic graft copolymers and their corresponding linear graft copolymers (l-PEO-g-PDMAEMA) were measured. Under the same conditions, the cyclic graft copolymer with the shorter side chains gave the higher critical micellization pH value. The c-PEO-g-PDMAEMA showed the lower critical micellization pH value than the corresponding l-PEO-g-PDMAEMA. The average hydrodynamic diameters (D_h) of the micelles were measured by DLS with the variation of the aqueous solution pH value and temperature. Science China Press and Springer-Verlag Berlin Heidelberg 2010.

Full text of DOI:10.1007/s11426-010-3181-2

SCIENCE CHINA
Chemistry
•
·
ARTICLES •
SPECIAL TOPIC · Advances in Principles of Polymerization
August 2010 Vol.53 No.8: 1653–1662
doi: 10.1007/s11426-010-3181-2
A pH- and temperature-sensitive macrocyclic graft copolymer
composed of PEO ring and multi-poly(2-(dimethylamino)
ethyl methacrylate) lateral chains
*
PANG XinChang, JING RongKuan, PAN MuGang & HUANG JunLian
Key Laboratory of Molecular Engineering of Polymers, Ministry of Education; Department of Macromolecular Science,
Fudan University, Shanghai 200433, China
Received January 31, 2010; accepted March 19, 2010
A novel method for the synthesis of macrocyclic graft copolymers was developed through combination of anionic ring-opening
polymerization (AROP) and atom transfer radical polymerization (ATRP). A linear ,-dihydroxyl poly(ethylene oxide) with
pendant acetal protected hydroxyl groups (l-poly(EO-co-EEGE)) was prepared first by the anionic copolymerization of ethyl-
ene oxide (EO) and ethoxyethyl glycidyl ether (EEGE). Then l-poly(EO-co-EEGE) was cyclized. The crude cyclized product
containing the linear byproduct was hydrolyzed and purified by being treated with -CD. The pure cyclic copolymer
[c-poly(EO-co-Gly)] was esterified by reaction with 2-bromoisobutyryl bromide, and then used as ATRP macroinitiators to
initiate polymerization of 2-(dimethylamino) ethyl methacrylate (DMAEMA), and a series of pH- and temperature-sensitive
macrocyclic graft copolymers composed of a hydrophilic PEO as the ring and PDMAEMA as side chains (c-PEO-g-
PDMAEMA) were obtained. The behavior of pH- and temperature-sensitive macrocyclic copolymers was studied in aqueous
solution by fluorescence and dynamic light scattering (DLS). The critical micellization pH values of macrocyclic graft co-
polymers and their corresponding linear graft copolymers (l-PEO-g-PDMAEMA) were measured. Under the same conditions,
the cyclic graft copolymer with the shorter side chains gave the higher critical micellization pH value. The c-PEO-g-
PDMAEMA showed the lower critical micellization pH value than the corresponding l-PEO-g-PDMAEMA. The average hy-
h
drodynamic diameters (D ) of the micelles were measured by DLS with the variation of the aqueous solution pH value and
temperature.
macrocyclic PEO, anionic ring-opening polymerization, ATRP, PDMAEMA, pH- and temperature-sensitive
1
Introduction
versatility and simplicity.
The stimuli-responsive polymers, also designated as
“
smart polymers”, which undergo phase transitions in re-
The properties of polymers are closely related to their mo-
lecular structure. Polymers with unique structures, such as
block, star, gradient, and graft structures, have been widely
used in tissue engineering, drug delivery, and micelle
preparation [1–5]. Recent progress in controlled living po-
lymerization has provided an effective tool for preparing
polymers with well-defined structure [6–8] because of its
sponse to environmental stimuli such as pH and temperature,
have been widely investigated in various fields [9–11].
Poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA),
which is a pH- and temperature-sensitive polymer, is one of
the most studied stimuli-responsive polymers in various
fields [12–14] (paints, membranes, and gene delivery sys-
tems).
The cyclic molecules with special properties could find
applications in many fields, such as the formation of organic
*
Corresponding author (email: jlhuang@fudan.edu.cn)
©
Science China Press and Springer-Verlag Berlin Heidelberg 2010
chem.scichina.com
www.springerlink.com

1654
PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
nanotubes, ion complexes, and ion transport across mem-
branes [15, 16]. Cyclic polymers, also designated as
ring-shaped polymers, have special properties caused by the
lack of chain ends and circular architecture [17, 18]. Look-
ing for an efficient rout for the preparation of macrocyclic
polymers have been a goal for polymer chemists for a long
time, owing to their unique topology and physical properties
2.2 Measurements
GPC was performed on an Agilent1100 with a G1310A
pump, a G1362A refractive detector, and a G1314A vari-
able wavelength detector. THF was used as the eluent at
3
5 °C at 1.0 mL/min. One 5 m LP gel column (500 Å,
4
molecular range 500–2 × 10 g/mol) and two 5 m LP gel
mixed bed column (molecular range 200–3 × 10 g/mol)
were calibrated with polystyrene standard samples. For
l-poly(EO43.5-co-EEGE) and c-poly(EO10.6-co-Gly), GPC
6
[
19]. Previous studies about cyclic polymers exclusively
focused on the preparation of single polymer ring including
hydrophobic polymers such as cyclic PS, PE [20, 21], and
hydrophilic macrocyclic polymers such as macrocyclic
poly(ethylene oxide) [22, 23]. However, there are relatively
limited reports on the preparation of macrocyclic graft
copolymers, especially stimuli-responsive cyclic graft
copolymers, due to the difficulty of synthesis. The macro-
rings of PEO with multi-PDMAEMA lateral chains
3
analyses were performed in 0.1 M aqueous NaNO at 40 °C
with an elution rate of 0.5 mL/min on the same instrument
except that a G1315A diode-array detector was used to sub-
stitute the G1314A variable wavelength detector. Three
TSK-gel PW columns in series (bead size: 6, 13, 13 m;
pore size: 200 Å, greater than 1000 Å, less than 100–1000
4
4
6
6
(
c-PEO-g-PDMAEMA) may offer interesting properties as
Å; molecular range: 0–5 × 10 , 5 × 10 –8 × 10 , (5–8) × 10
their special properties. The lack of data related to
c-PEO-g-PDMAEMA motivated us to investigate this
system.
We report a novel route for preparing the macrocyclic
graft copolymers (c-PEO-g-PDMAEMA) with pH- and
temperature-sensitive properties by a combination of ani-
onic ring-opening polymerization (AROP) and atom trans-
fer radical polymerization (ATRP). Their pH- and tempera-
ture-sensitive properties were investigated.
g/mol, respectively) were calibrated with PEO standard
samples. The injection volume was 20 L, and the concen-
tration was 5 mg/mL. MALDI-TOF-MS (matrix-assisted
laser desorption/ionization time-of-flight) analysis was car-
ried out on a Voyager DE-STR from Applied Biosystems.
The matrix -cyano-4-hydroxycinnamic acid was dissolved
in THF at a concentration of 40 mg/mL. Potassium
trifluoracetate was used as a cationization agent at typical
concentrations of 5 mg/mL. The sample was dissolved in
THF at approximately 1 mg/mL. Finally, the matrix, salt,
and polymer solutions were premixed in a molar ratio of
2
Experimental
5
:1:5. The premixed solutions were hand-spotted on the
target well and left to dry. All mass spectra were recorded in
the reflector mode and about 1000 laser shots were col-
lected per spectrum. H NMR spectra were obtained at a
2
.1 Materials
1
2
9
-Bromoisobutyryl bromide (98%), 2,2′-bipyridyl (bpy, >
9%), and pyridine (99.5%) were purchased from Aldrich
DMX 500 MHz spectrometer. All the samples were dis-
and Sinopharm Chemical Reagent Co., Ltd. (SCR), respec-
tively, and used as received. CuBr (98%, Acros) was stirred
overnight in acetic acid and filtrated, washed with ethanol
and diethyl ether successively, and dried in vacuo. -
Cyclodextrin (-CD, Aldrich) was used as received.
p-Toluenesulfonyl chloride (TsCl, 98%, Aldrich) and potas-
sium hydroxide (KOH, 96%, Aldrich) were dried under
vacuum prior to use. 2-(Dimethylamino) ethyl methacrylate
solved in CDCl . The ultrafiltration separator was purchased
from the Shanghai Institute of Nuclear Research, Chinese
3
Academy of Sciences, and the cutoff molecular weight of
the poly(ether sulfone) membrane was 20000 g/mol (cali-
brated by globular protein). Steady-state fluorescence spec-
tra of the samples were recorded on an Edinburgh Instru-
ments 920 spectrometer operating at 25 °C. A commercial
laser light scattering (LLS) spectrometer (Malvern Auto-
sizer 4700) was used for dynamic light scattering measure-
ment.
(
DMAEMA, Acros organics 99%) was passed through the
basic alumina column to remove the stabilizer and distilled
over CaH under reduced pressure, and stored at 20 °C
prior to use. DMSO (SCR, 98%) was distilled over CaH
under reduced pressure just before use. Triethylene glycol
was distilled from CaH under reduced pressure and the
2
2
2
.3 Anionic copolymerization of EEGE with EO
The copolymerization of EEGE with EO is shown in
Scheme 1. The typical procedure was shown as follows: A
150 mL kettle was vacuumed at 80 °C for 2 h, and cooled to
room temperature and then to 0 °C. Given volumes of the
initiator solution [triethylene glycol (0.29 mL, 2.19 mmol)
with DPMK (3.5 mL, 2.0 mmol) in a mixture of THF and
DMSO (10/40 v/v, 50 mL)], EEGE (11.1 g, 75.8 mmol), and
EO (30.0 g, 681.8mmol) were introduced successively into
the kettle under magnetic stirring. It was subsequently
2
fraction at 134 °C/90 Pa was collected. THF (99%) was
refluxed over potassium wire and distilled from potassium
naphthalenide solution. EO (SCR, 98%) was dried by CaH
for 48 h and then distilled under N before use. Ethoxyethyl
glycidyl ether (EEGE) and diphenylmethylpotassium
DPMK) were prepared according to previous reports [24,
5]. All the other reagents were purified by common purifi-
cation procedures.
2
2
(
2

PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
1655
ether to obtain the product. The procedure was repeated
twice to obtain the pure cyclized product [c-poly(EO43.5
co-EEGE)].
-
2
.6 Preparation of c-poly(EO-co-Gly) by cleavage of
the ethoxyethyl groups of c-poly(EO-co-EEGE)
The hydrolysis of EEGE segments of the copolymer [25]
required two steps: (1) the cyclized product (3.0 g) was
mixed with 40 mL of formic acid, and the solution was
stirred at 20 °C during 30 min and then poured into metha-
nol. The precipitate was separated and dried in vacuo at
Scheme 1 Synthesis of linear copolymer l-poly(EO-co-EEGE).
heated to 60 °C under stirring for 48 h. The reaction was
terminated by addition of a few drops of acidified methanol.
After all the solvents were removed by reduced distillation,
5
0 °C; (2) the dried product dissolved in a mixture of diox-
ane (25 mL), methanol (15 mL) and KOH methanol solu-
tion (1 N, 10 mL) was refluxed for 24 h, and neutralized
with 5% HCl. After the solvents were removed under re-
duced pressure, the polymer was dissolved in water and
purified by ultra filtration. The filtrated aqueous solution
2 2
the crude product was dissolved in CH Cl , dried over an-
hydrous MgSO and filtered. The yellowy viscous wax-like
4
product, a linear ,-dihydroxyl poly(ethylene oxide) with
pendant protected hydroxylmethyls [l-poly(EO10.6-co-EEGE)],
was obtained in a yield of 94% after CH Cl was removed.
2 2
was concentrated to dryness, dissolved in CH
2 2
Cl , dried
over anhydrous MgSO and filtered. The filtrate was pre-
4
The copolymer l-poly(EO43.5-co-EEGE) was synthesized by
cipitated in diethyl ether and dried in vacuo at 50 °C. The
hydrolyzed cyclic product c-poly(EO43.5-co-Gly) was ob-
tained in a yield of 90 %. It was a white powder.
the same method.
1
3
H NMR (CDCl , , ppm): 4.70–4.73(m, OCH(CH )O),
3
1
.30 (d, OCH(CH )O), 1.19 (t, CH CH O), 3.53–3.80
3
3
2
(
m, CH CH O and CH CH (C H O )O for PEO main
2
2
2
8
12
2
2
.7 Preparation of macroinitiator c-poly(EO43.5-co-
chain).
Gly)(ATRP)
The esterification of hydroxymethyl groups on glycidol
segments of c-poly(EO43.5-co-Gly) with 2-bromoisobutyryl
bromide [26] was performed to prepare the cyclic macroini-
tiator. A typical example was described as follows: 2.0 g of
c-poly(EO43.5-co-Gly) was dissolved in 50 mL anhydrous
pyridine under dry nitrogen, and 0.4 mL of 2-bromoisobu-
tyryl bromide was added dropwise at 0 °C over 20 min un-
der vigorous stirring. The initial yellow color disappeared
immediately, and pyridinium bromide with red-brown color
was precipitated. It was continuously stirred for another 15
min. After that, 5 g of K CO was added to the system at
2
.4 Cyclization of l-poly(EO-co-EEGE)
In a flask, finely-ground KOH (0.44 g) was dispersed in a
mixture of THF and heptane (70/30, v/v, 100 mL) and
stirred under nitrogen at 40 °C. l-Poly(EO43.5-co-EEGE)
(
5.0 g) and TsCl ( 223 mg) were dissolved in 100 mL of
THF in a separate flask. This solution was added dropwise
to the KOH dispersion via a syringe pump over 48 h. After
a further 72 h under reflux (40 °C) the mixture was filtered
and the filtrate was evaporated under reduced pressure. The
crude cyclized product was obtained.
2
3
room temperature. The pyridine was removed by azeotropic
distillation with dry toluene (3 × 40 mL). The residue was
dissolved in water and separated by ultra filtration. The
aqueous solution was concentrated to dryness and dissolved
in CH Cl , dried over anhydrous MgSO and then filtered.
2
.5 Purification of the crude cyclized copolymer
The crude product (4.0 g ) was dissolved in 40 mL of dis-
tilled water (100 g/L), to which an aqueous solution of
2
2
4
-CD (80 mL, 100 g/L) was added at room temperature.
The CH
Cl
2 2
of the filtrate was precipitated in diethyl ether.
The ratio of -CD to the linear byproducts (about 20 %),
which was estimated from the GPC, was 10/1 (w/w). The
resulting clear solution was ultrasonically stirred for 30 min
and then turbid solution appeared. It was allowed to stand
overnight at room temperature and a white precipitate
formed. The mixture was centrifuged and filtered to obtain a
clear aqueous solution. The solvent was distilled and a solid
mixture of the cyclic product, unthreaded -CD or a small
quantity of linear byproducts remained. This solid mixture
was dissolved in dichloromethane and filtered to remove the
unthreaded -CD. The filtrate was precipitated in diethyl
The precipitate was dried in vacuo at 50 °C and the yellowy
1
product with a yield of 95% was obtained. H NMR (CDCl
, ppm): 4.13–4.42 (m, CH OOCC(CH Br)), 1.86(s,
OOCC(CH ) Br), 3.35–3.90 (m, CH CH O and
3
,
2
3 2
)
3
2
2
2
CH CHO for PEO main chain).
2
2.8 Synthesis of macrocyclic graft copolymer c-PEO-
g-PDMAEMA by ATRP
The graft copolymerization of DMAEMA was carried out
using c-poly(EO43.5-co-Gly) with pending bromoisobutyryl

1656
PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
groups [c-poly(EO43.5-co-Gly)(ATRP)] as macroinitiators. In a
typical process, an ampoule charged with CuBr (31.9 mg,
3 Results and discussion
0
.22 mmol), bpy (34.7 mg, 0.22 mmol), c-poly(EO43.5-co-
= 5400, 0.4 g, 0.074 mmol), and 6 mL of dis-
3.1
EEGE)
Synthesis of parent copolymers l-poly(EO-co-
Gly)(ATRP) (M
n
tilled water was stirred for 20 min and vacuumed by three
freeze-thaw-cycles at the temperature of liquid nitrogen. At
the same time, another ampoule charged with DMAEMA
The anionic ring-opening copolymerization of EO and
EEGE was performed using DPMK as the deprotonating
agent which could readily react with hydroxyl groups to
form alkoxides. In order to control the polymerization rea-
sonably, it is significant that only 20%–40% of the hydroxyl
groups of the triethylene glycol were activated, otherwise
alkoxides would be precipitated [28]. A mixture of DMSO
and THF (v/v: 4/1) was used as the solvent for polymeriza-
tion instead of THF because propagating alkoxides would
be aggregated in pure THF [26]. Under such conditions, all
of the hydroxyl groups of triethylene glycol could effi-
ciently initiate the copolymerization of EO and EEGE be-
cause of the rapid exchange of protons between dormant
hydroxyls and propagating alkoxides, and all the chains
grew at the same rate [29]. The parent copolymers with dif-
ferent contents of EO and different molecular weights were
synthesized through variation of the monomer feed ratio and
initiator volume as shown in Table 1.
(
4 mL, 23.6 mmol) was vacuumed by three freeze-thaw-
cycles at the temperature of liquid nitrogen. The DMAEMA
was then added rapidly to the first ampoule via a syringe
needle and stirred strongly at 10 °C. The reaction solution
turned dark brown and became progressively more viscous.
The released polymerization heat raised the solution tem-
perature. After about 2 h, the ampoule was dipped in liquid
nitrogen to stop the polymerization. The products were dis-
solved in anhydrous methanol, the solution was passed
through the neutral alumina column to remove the catalyst
and then precipitated in cold heptane. The copolymers were
purified twice by dissolution/precipitation with methanol/
heptanes.
2.9 Synthesis of linear graft copolymers l-PEO-g-
PDMAEMA
The copolymer composition could be obtained by using
1
the following formula based on the H NMR data (see Ani-
The l-PEO-g-PDMAEMA was synthesized to be compared
with c-PEO-g-PDMAEMA for investigating their pH- and
temperature-sensitive behaviors. A linear ,-dihydroxyl
poly(ethylene oxide) with pendant protected hydroxyl-
methyls l-poly(EO-co-EEGE) was used. The l-poly(EO-
co-Gly) with pending bromoisobutyryl groups [l-poly(EO-
co-Gly)(ATRP)] was prepared, and a series of linear graft co-
polymers l-PEO-g-PDMAEMA were obtained (the same as
the synthesis route of c-PEO-g-PDMAEMA).
onic Copolymerization of EEGE with EO in Experimental
Section2.3):
4Af
RT 
(1)
Asum  7Af
where R
is the molar ratio of EEGE to EO in the copoly-
T
mer, Asum and A represent the peak area sum of the protons
f
of the main chain and protons of lateral chains methylene
and the peak areas of the methine protons of the EEGE
T
moiety, respectively. The R values of copolymers A and B
2
.10 Determination of critical micellization pH
are 1/10.6 and 1/43.5, respectively, which are nearly
equivalent to the monomer feed ratio of EEGE to EO (1/9
and 1/39). Therefore, the linear ,-dihydroxyl PEO with
pendant acetal protected hydroxyls (l-poly(EO-co-EEGE))
could be described as l-poly(EO10.6-co-EEGE) (A) and
l-poly(EO43.5-co-EEGE) (B). The number of the protected
hydroxyls on the PEO chain could be evaluated by the
Pyrene was used as the fluorescence probe [27]. An acetone
4
solution of 190 L pyrene (2.67 × 10 mol/L) was added to
00 mL water with different pH values and the concentra-
1
7
tion of pyrene was 5.0 × 10 mol/L. Next, 50 L of the co-
polymer solution in N,N-dimethylformamide (DMF) (0.1
g/mL) was added to water containing pyrene to obtain the
solution with the copolymer concentration as 1 mg/mL.
Each copolymer solution was left for 30 min at room tem-
perature to ensure equilibration between the pyrene in the
micelles and that in the aqueous solution. All fluorescence
spectra were recorded at 25 °C.
Table 1 The data of parent copolymers l-poly(EO-co-EPEE)
a)
b)
c)
d)
e)
Sample
R
f
R
T
M
n
M
w
/M
n
N
EPEE
20
3
A
B
1/9
1/10.6
1/43.5
12,500
6,400
1.06
1.16
1/39
a) The feed ratio of EEGE to EO. b) The molar ratio of EEGE to EO in
copolymer poly(EO-co-EEGE) measured by H NMR. c) Number-average
2
.11 Dynamic light scattering studies
1
molecular weight determined by GPC, sample A: calibrated against PS
standards using THF as the eluent; sample B: calibrated against PEO stan-
dards using 0.1 M NaNO as the eluent. d) The polydispersity determined
3
The samples used for fluorescence measurement were used
for dynamic light scattering (DLS) studies. The samples
were measured after they were filtered through a membrane
filter with a nominal pore size of 0.8 m.
by GPC. e) The number of EEGE units in poly(EO-co-EEGE) calculated
1
by the integration of protons from H NMR.

PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
1657
combination of the molecular weight determined by GPC
and H NMR data using eq. (2):
ing formation of the cyclic polymer [33], and a broad
shoulder assigned to chain extended polymer was found at
lower elution time.
The separation and purification of the cyclized product is
a significant step for the next syntheses of macrocyclic graft
copolymers. It was reported that the cyclodextrins (, , and
1
Mn
NEEGE

(2)

146  44 RT

n
where M is the molecular weight of l-poly(EO-co-EEGE),

) could form inclusion complexes with a wide variety of
1
46 and 44 are the molar masses of EEGE and EO, and R
T
low molecular weight compounds as well as linear polymers,
both organic and inorganic [34–36]. After dealing with by
the -CD, as shown in Figure 1(c), the peak of linear chain
extended polymer at lower elution time disappeared .
is the molar ratio of EEGE units to EO units in l-poly(EO-
co-EEGE). The calculated NEEGE values are listed in Table 1.
3
.2 Cyclization of l-poly(EO-co-EEGE) and purification
In order to obtain direct evidence for the formation of the
macro-ring, matrix-assisted laser desorption/ionization time-
of-flight (MALDI-TOF) was used. Figure 2 shows the
The essential work is the closure of linear copolymers
l-poly(EO-co-EEGE) and the purification of the closed
product for the synthesis of macrocyclic copolymers. The
ring closure of l-poly(EO-co-EEGE) was achieved via ether
linkage by reaction with tosyl chloride (TsCl) in the pres-
ence of solid KOH. End-to-end intramolecular coupling was
promoted over intermolecular chain extension by conduct-
ing the reaction at high dilution [C* < 10 mol/L]. This syn-
thesis was based on a method reported by Booth et al. for
the preparation of cyclic PEO [30, 31]. They also reported a
second method for ring closure via an acetal linkage (reac-
MALDI-TOF-MS spectra of linear precursor l-Poly(EO43.5
co-EEGE) (a) and cyclized product c-poly(EO43.5-co-EEGE)
b). The spacing 44.3 and 43.8 amu between the peaks are
-
(
ascribed to the molar mass of the EO and the spacing 146.1
and 146.2 amu for the molar mass of the EEGE unit. The
spacing 14.7, 29.6, 15.2 and 29.9 between the peaks are
ascribed to the difference of the molar mass of different
combinations of EEGE and EO unit, and the molecular-
weight decrease of 18 amu after cyclization reaction sup-
ports the formation of the ether linkage which is consistent
with loss of a water molecule upon ring closure. Thus the
MALDI-TOF provides direct evidence for the closure of
l-poly(EO-co-EEGE).
5
2 2
tion of the ,-dialkoxide with CH Cl ) [32]. We have fol-
lowed the first method because of the relative chemical sta-
bility of the ether linkage compared with the acetal linkage,
which is subject to scission under acidic conditions.
Figure 1(a) shows the GPC curve of the crude cyclized
product using the l-poly(EO43.5-co-EEGE) as a linear pre-
cursor. It is apparent that the chain-extended copolymer,
which is the intermolecular reaction product, coexisted with
the cyclized product. Compared with the original linear co-
polymer (Figure 1(b)), the major peak of the cyclized prod-
uct moved to the higher elution time due to its smaller hy-
3
.3 Synthesis of cyclic ATRP macroinitiator
In order to obtain the reactive hydroxyl groups on the c-poly
(
EO-co-EEGE), the polymers were treated with formic acid
first [37], and the formed polyformate was further saponi-
fied in the KOH dioxane/methanol mixture solution, and
drodynamic volume and the peak molecular weight of Mpl
=
8
000 was changed to Mpc = 6,500 (Mpc/Mpl = 0.81), indicat-
Figure 1 Typical GPC traces. (a) Crude cyclized product of l-poly
EO43.5-co-EEGE). (b) Linear l-poly(EO43.5-co-EEGE). (c) Purified cy-
clized product by -CD (0.1 M NaNO as the eluent).
Figure 2 MALDI-TOF mass spectra of the model copolymer for (a)
linear precursor l-poly(EO43.5-co-EEGE) and (b) cyclization product
c-poly(EO43.5-co-EEGE).
(
3

1658
PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
hydroxyl groups were recovered. Thus the c-poly
EO-co-EEGE) was transformed to c-poly(EO-co-Gly) with
multi-pending hydroxyl groups.
lymerization of 2-(dimethylamino) ethyl methacrylate
(DMAEMA) has been intensively investigated because
poly(DMAEMA) is a useful water-soluble, pH- and tem-
perature-sensitive polymer. In this work, the ATRP of
DMAEMA was carried out in water at 10 °C using the Bpy/
CuBr catalyst system. The results of ATRP by using two
kinds of c-poly(EO-co-Gly)ATRP with different bromoisobu-
tyryl groups density as cyclic macroinitiators are shown in
Table 3.
(
The hydroxyl groups of the cyclized product c-poly-
(
EO-co-Gly) were esterified with 2-bromoisobutyryl bro-
mide to obtain cyclic macroinitiators with narrow molecular
weight distribution as shown in Table 2, and the complete
esterification of the hydroxyl groups of c-poly(EO-co-Gly)
1
was confirmed by H NMR. The hydroxyl group conversion
was calculated by eq. (3)



4 
3

 Ae

RT

E 
100%
(3)
T
2
Asum
where E is the conversion efficiency of hydroxyl groups of
T
e
c-poly(EO-co-Gly), Asum and A represent the integral area
of the protons of PEO main ring (the peaks at  =3.35–3.90)
and the integral area of the protons linked to the ester (the
T
peaks at  = 4.13–4.42), and R is the molar ratio of EEGE
to EO in the original linear copolymer l-poly(EO-co-EEGE)
1
T
measured by H NMR. The E value is nearly 100%, sug-
gesting that hydroxyl groups are completely converted to
bromoisobutyryl units.
3.4 Synthesis of macrocyclic graft copolymer c-PEO-g-
PDMAEMA by ATRP
The procedure for the synthesis of c-PEO-g-PDMAEMA
using cyclic macroinitiators is shown in Scheme 2. The po-
Table 2 GPC data of the cyclic macroinitiators
c-Poly(EO-co-Gly)
c-Poly(EO-co-Gly)(ATRP)
a)
Sample
b)
b)
c)
c)
M
n
M
w
/M
n
M
n
w n
M /M
A
B
6800
5200
1.29
1.23
11,800
5,400
1.10
1.12
a) Samples A and B are coincident with the sample number in Table 1. b)
Number average molecular weight (M ) and molecular weight distribution
/M ) determined by GPC, calibrated against PEO standards using 0.1
M NaNO as the eluent. c) Number average molecular weight (M ) and
molecular weight distribution (M /M ) determined by GPC, calibrated
against PS standards using THF as the eluent.
n
(M
w
n
3
n
w
n
Scheme
PDMAEMA.
2
Synthesis of macrocyclic graft copolymer c-PEO-g-
Table 3 Data of macrocyclic graft copolymers c-PEO-g-PDMAEMA
a)
4
b)
c)
4
d)
e)
Initiator
Entry
M
n
(×10 )
M
w
/M
n
M
n,NMR (×10 )
7.49
N
DMAEMA
20.1
R
f
A
1
A
2
A
3
A
4
2.24
2.59
1.23
2.22
1.48
1.36
1.51
1.46
22
30
25
40
f)
A
8.28
22.6
1.80
22.3
g)
B
2.54
38.1
a) Number-average molecular weight determined by GPC, calibrated against the PS standard. b) The polydispersity determined by GPC. c) MnNMR is cal-
culated by the formula: Mn,NMR = Mn c-poly(EO-co-Gly)(ATRP) + NOH  NDMAEMA  MDMAEMA, Mn c-poly(EO-co-Gly)(ATRP) is the molecular weight of Mn c-poly(EO-co-Gly)(ATRP) de-
rived by GPC, NOH is the hydroxyl number on c-poly(EO-co-Gly), and MDMAEMA is the molecular weight of DMAEMA. d) The average number of
1
DMAEMA on the grafting chain of the final copolymers is calculated from the H NMR data. e) The feed ratio of DMAEMA to Br-atom (NBr). f)
c-Poly(EO10.6-co-EEGE) as a precursor. g) c-Poly(EO43.5-co-EEGE) as a precursor.

PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
1659
1
The final products were characterized by GPC and H NMR
showed that not every initiating site in the backbone gener-
ated a side chain and incomplete initiation was always at-
tributed to steric hindrance due to the high density of initi-
ating centers. In our case, however, the density of initiating
centers in the macrocyclic PEO is lower than that reported
in previous reports, so higher initiation efficiency is antici-
pated. The initiation efficiency of bromoisobutyryl for
1
shown in Figures 3 and 4. According to H NMR spectrum,
the degree of polymerization of PDMAEMA side chains
was obtained by eq. (4):
NPDMAEMA  A 2 A 6




(4)
j
f
1
where NPDMAEMA is the average number of DMAEMA on
each side chain (Table 3), A and A represent the integral
area of the methylene protons ( = 2.55–2.80 ppm (m,
CH CH N)) of the grafted PDMAEMA chains and the
integral area of methyl protons at the -end of the
PDMAEMA side chains, respectively.
ATRP could be estimated from the H NMR spectrum (Fig-
ure 4) in eq. (5):
j
f



4


2
2
 3  A

f
RT

ET 
100%
(5)
6Asum
The initiation efficiency in the synthesis of some copoly-
mers by ATRP has been widely studied. Reports [38, 39]
where E
ATRP, Asum represents the integral area of all protons of the
PEO main chain, and R is the molar ratio of EEGE to EO
in copolymer c-poly(EO-co-EEGE). The calculated E val-
T
is the reaction efficiency of bromoisobutyryl for
T
T
ue is as high as 97.7%, which indicated that nearly all the
bromoisobutyryl groups took part in the polymerization.
3
.5 Measurement of critical micellization pH
The pH-induced micellization behaviors of copolymers
have been investigated [40, 41]. However, no report was
published on the macrocyclic graft copolymers. Therefore,
we investigated the pH-induced micellization behaviors of
cyclic graft copolymers in water solution by determining
their critical micellization pH values.
The critical micellization pH values were examined by
fluorescence technique using pyrene as the probe. Pyrene
fluorescence is very sensitive technique for detecting the
formation of copolymer micelles. Pyrene is highly hydro-
phobic and has very low solubility in water so it migrates
preferentially into the hydrophobic micelle cores. A red
shift was observed in the pyrene fluorescence spectra, and
there were changes in relative peak intensities [42–44]. In
our work, the protocol based on the analysis of pyrene
emission spectra reported by Gast et al. was employed [45].
Figure 3 GPC traces of the graft copolymer c-PEO-g-PDMAEMA. Sam-
ple A c-poly(EO10.6-co-Gly)(ATRP) as the macroinitiator, entry A and entry
1
A
2
in Table 3.
Figure 5 shows the variation in the intensity ratio (I
1 3
/I ) vs
solution pH for macrocyclic graft copolymers c-PEO-g-
PDMAEMA. As the solution pH increases, the PDMAEMA
becomes progressively deprotonated. The critical pH values
for micellization were estimated from the reduced I /I ratio,
1 3
which indicates a more hydrophobic environment for the
pyrene probe. The critical micellization pH value estimated
2
for c-PEO-g-PDMAEMA (sample A in Table 3) is pH 6.05.
As a comparison, the critical micellization pH value for the
corresponding linear graft copolymer l-PEO-g-PDMAEMA
is pH 6.68 (Figure 5). The critical micellization pH values
of other macrocyclic graft copolymers (Table 3) and their
corresponding linear graft copolymers were determined
under the same conditions, and all the results are listed in
Table 4. These results indicate that cyclic graft copolymer
c-PEO-g-PDMAEMA with the same PEO macrocycle and
1
Figure 4 H NMR spectrum of c-PEO-g-PDMAEMA (entry A
3
1
in Table
3
; solvent CDCl ).

1660
PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
3.6 Dynamic light scattering studies on stimuli-sensitive
properties of macrocyclic graft copolymer c-PEO-g-
PDMAEMA in aqueous media
The hydrophilicity of PDMAEMA may vary with the solu-
tion pH: when the pH is lower than the critical micellization,
PDMAEMA chains are hydrophilic and soluble in water.
However, when the solution pH increases, PDMAEMA
becomes progressively deprotonated and turns to hydropho-
bic. In our case, at low pH values, the macrocyclic graft
copolymer c-PEO-g-PDMAEMA was dissolved in the
aqueous solution as mono-molecules. As the solution pH
was raised over the critical micellization pH, the PDMAEMA
graft chains turned to hydrophobic which caused the forma-
tion of micelles composed of the PDMAEMA core. Figure 6
shows the dynamic light scattering (DLS) results for c-PEO-
g-PDMAEMA at 1 mg/mL concentration. When the pH was
lower than the critical micellization pH, cyclic copolymers
were molecularly dissolved, with an intensity-average hy-
Figure 5 Determination of the critical pH for micellization of the mac-
rocyclic graft copolymer c-PEO-g-PDMAEMA (sample A in Table 3) and
the corresponding linear copolymer l-PEO-g-PDMAEMA at 25 °C from
pyrene emission spectra (excitation wavelength ex = 333 nm; the copoly-
mer concentration was 1 mg/mL in each case).
2
drodynamic diameter (D
low scattering intensity. As the solution pH was raised, the
cyclic copolymer A with longer graft chain PDMAEMA
h
) of approximately 10 nm and very
2
longer side chains shows lower critical micellization pH
value. This difference may be mainly caused by the differ-
ent percentages of PDMAEMA side chains. With the solu-
tion pH increasing, PDMAEMA side chains become pro-
gressively deprotonated and hence hydrophobic, so the cy-
clic graft copolymer with longer PDMAEMA side chains is
more hydrophobic, leading to the formation of micelles with
PDMAEMA cores in lower pH water solution.
The data listed in Table 4 shows that the critical micelli-
zation pH value of cyclic graft copolymer is lower than that
of the corresponding linear graft copolymer. These lower
critical micellization pH values are related to the cyclic
structure of graft copolymers. Although the graft chains
PDMAEMA of either cyclic copolymers or linear copoly-
mers are progressively hydrophobic with water solution pH
increasing, the cases are different for them. For c-PEO-
g-PDMAEMA, the whole macrocyclic molecule is consid-
ered as a cage and its compact structure makes cyclic
molecules readily assemble into micelles in lower pH water
solution, compared with the corresponding ring-opening
graft copolymer l-PEO-g-PDMAEMA.
started to form the micelles, and the micellization occurred
above pH 6.05. Between pH 6.05 and 8.50, micellization
was not complete: dynamic light scattering revealed two
populations at 10 and 80 nm, corresponding to dissolved
chains (unimers) and micelles, respectively. At pH 8.50 or
higher, DLS revealed solely one population corresponding
to micelles. The D
h
of the micelles decreased from 80 to 68
nm as the solution pH was further increased from 8.50 to
10.40. It was caused by the fact that the micelles became
more compact due to further deprotonation of the
PDMAEMA chains. Above pH 10.40, the micelle size does
not change significantly.
In addition to the pH-sensitive property, the side chain
PDMAEMA is temperature-sensitive. It exhibits lower critical
Table 4 The critical micellization pH values of the macrocyclic graft
copolymer and the corresponding linear copolymer
Sample
A
1
/a
1
A
2
/a
2
A
3
/a
3
4 4
A /a
Critical pH
6.18/6.85
: l-poly(EO10.6-co-EEGE) as the precursor (sample A
in Table 3, their corresponding comb-like copolymer a and a
/a and A /a : l-poly(EO43.5
and A
6.05/6.68
6.40/6.97
6.23/6.83
A
1
/a
1
and A
2
/a
2
1
and
A
N
2
1
2
(a
1
:
-
PDMAEMA = 19.7; a
2
: NPDMAEMA=23.1)). A
3
3
4
4
co-EEGE) as the precursor (sample A
sponding linear copolymer a and a (a
0.1)).
3
4
in Table 3, their corre-
h
Figure 6 Variation of intensity-average hydrodynamic diameter (D )
3
4
3
: NPDMAEMA = 22.9; a
4
: NPDMAEMA
=
1 2
with pH for the macrocyclic graft copolymers (sample A and A in Table
4
3) at 1 mg/mL in water at 25 °C.

PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
1661
solution temperature (LCST) phase behavior and precipi-
tates from neutral or basic aqueous solution between 32 and
dynamic light scattering (DLS). The critical micellization
pH values of macrocyclic graft copolymers and their corre-
sponding linear graft copolymers (l-PEO-g-PDMAEMA)
were measured. Under the same conditions, the cyclic graft
copolymers with the shorter side chains gave the higher
critical micellization pH values. The c-PEO-g-PDMAEMA
shows the lower critical micellization pH values than the
corresponding l-PEO-g-PDMAEMA. The average hydro-
5
0 °C, depending on its molecular weight and solution pH
[46–49]. When the temperature is lower than LCST,
PDMAEMA chains are hydrophilic and soluble in water, and
when the temperature is higher than LCST, PDMAEMA
turns to hydrophobic. Figure 7 shows the variation of D
a function of temperature for the c-PEO-g-PDMAEMA
sample A in Table 3) at 1 mg/mL at different solution pH.
At pH 2.68, the copolymer is soluble in water solution with
of approximately 10 nm (the whole temperature range:
4–53 °C). At pH 8.50, below 47 °C the micelle size shows
little change with D being about 90 nm. Above 47 °C, the
h
as
(
2
dynamic diameters (D
h
) of the micelles were measured by
DLS with the pH value and temperature’s variation.
D
h
1
We appreciate the financial support from the National Natural Science
Foundation of China ( 20874013).
h
scattering intensity increased, accompanied by an increase
in the aggregate size from 90 to about 200–300 nm in di-
ameter. Concerning pH 12.76, above 35 °C the scattering
intensity increased abruptly, accompanied by a dramatic
increase in the aggregate size from about 100 to about
1
2
3
Riess G. Micellization of block copolymers. Prog Polym Sci, 2003,
8, 1107–1170
Soo PL, Eisenberg A. Preparation of block copolymer vesicles in so-
lution. J Polym Sci Part B: Polym Phys, 2004,42, 923–938
Rodriguez-Hernandez J, Checot F, Gnanou Y, Lecommandoux S.
Toward 'smart' nano-objects by self-assembly of block copolymers in
solution. Prog Polym Sci, 2005, 30, 691–724
Hadjichristidis N, Iatrou H, Pitsikalis M, Pispas S, Avgeropoulos A.
Linear and non-linear triblock terpolymers. Synthesis, self-assembly
in selective solvents and in bulk . Prog Polym Sci, 2005, 30, 725–782
Zhang M, Muller A. Cylindrical polymer brushes. J Polym Sci Part A:
Polym Chem, 2005, 43, 3461–3481
2
3000–4000 nm in diameter. Because of progressive increase
of the solution temperature, the PDMAEMA graft chains
approach its cloud point and become hydrophobic. Pre-
sumably, the changing hydrophilic-hydrophobic balance
leads to micellar fusion.
4
5
6
Chiefari J, Chong YK, Ercole F, Krstina J, Jeffery J, Le TPT, Ma-
yadunne RTA, Meijs GF, Moad CL, Moad G, Rizzardo E, Thang SH.
Living free-radical polymerization by reversible addition-fragmenta-
tion chain transfer: The RAFT process. Macromolecules, 1998, 31,
4
Conclusions
A novel method for the synthesis of macrocyclic graft co-
polymers was developed through combination of anionic
ring-opening polymerization (AROP) and atom transfer
radical polymerization (ATRP). A series of pH- and tem-
perature-sensitive macrocyclic graft copolymers composed
of a hydrophilic PEO as the ring and PDMAEMA as side
chains (c-PEO-g-PDMAEMA) were obtained. The behavior
of pH- and temperature-sensitive macrocyclic copolymers
was studied in aqueous solution using fluorescence and
5
559–5562
7
8
9
Perrier S, Takolpuckdee P. Macromolecular design via reversible ad-
dition-fragmentation chain transfer (RAFT)/Xanthates (MADIX) po-
lymerization. J Polym Sci Part A: Polym Chem, 2005, 43, 5347–5393
Moad G, Chong YK, Postma A, Rizzardo E, Thang SH. Advances in
RAFT polymerization: the synthesis of polymers with defined
end-groups. Polymer, 2005, 46, 8458–8468
Osada Y, Gong JP. Soft and wet materials: Polymer gels. AdV Mater,
1
998, 10, 827–837
1
0
1
2
Galaev IY, Mattiasson B. ‘Smart’ polymers and what they could do in
biotechnology and medicine. Trends Biotechnol, 1999, 17, 335–340
Gillies ER, Fréchet JMJ. Development of acid-sensitive copolymer
micelles for drug delivery. Pure Appl. Chem. 2004, 76, 1295–1307
Camail M, Essaoudi H, Margaillan A, Vernet JL. Copolymérisation
radicalaire de méthacrylates de 2-aminoéthyle avec le méthacrylate
de méthyle. Eur Polym Mater, 1995, 31, 1119–1125
1
1
1
1
1
1
3
4
5
6
Du R, Zhao J. Properties of poly (N,N-dimethylaminoethyl methacry-
late)/polysulfone positively charged composite nanofiltration mem-
brane. J Membr Sci, 2004, 239, 183–188
Jones RA, Poniris MH, Wilson MR. (P)DMAEMA is internalised by
endocytosis but does not physically disrupt endosomes. J Controlled
Release, 2004, 96, 379–391
Gokel GW, Leevy WM, Weber ME. Crown ethers: Sensors for ions
and molecular scaffolds for materials and biological models. Chem
ReV, 2004, 104, 2723–2750
Gibson SE, Lecci C. Amino acid derived macrocycles - An area
driven by synthesis or application. Angew Chem Int.Ed, 2006, 45,
1
364–1377
1
7
8
Semlyen JA. Synthetic Cyclic Polymers. Large Ring Molecules. New
York: Willy, 1996
Ederle Y, Naraghi KS, Lutz P. Synthesis of cyclic micromolecules. In:
Synthesis of Polymers. Schluter AD, Ed. Mater Science and Tech-
nology Series, 1999. Willy
1
Figure 7 Variation of the intensity-average hydrodynamic diameter (D
with temperature for the macrocyclic graft copolymer (sample A in Table
) at 1 mg/mL and different pH values in water.
h
)
2
3
19 Semlyen JA. Cyclic Polymers, 2nd ed. Dordrecht, the Netherlands:

1662
PANG XinChang, et al. Sci China Chem August (2010) Vol.53 No.8
Kluwer Academic. 2000
Macromolecules, 2000, 33, 4472–4477
2
0
Oike H, Hamada M, Eguchi S, Danda Y, Tezuka Y. Novel synthesis
of single- and double-cyclic polystyrenes by electrostatic self-assembly
and covalent fixation with telechelics having cyclic ammonium salt
groups. Macromolecules, 2001, 34, 2776–2782
Bielawski CW, Benitez D, Grubbs RH. An “endless” route to cyclic
polymers. Science 2002, 297, 2041–2044
37 Taton D, Leborgne A, Sepulchre M, Spassky N. Synthesis of chiral
and racemic functional polymers from glycidol and thioglycidol.
Macromol Chem Phys, 1994, 195, 139–148
38 Neugebauer D, Sumerlin BS, Matyjaszewski K, Goodhart B, Sheiko
SS. How dense are cylindrical brushes grafted from a multifunctional
macroinitiator. Polymer, 2004, 45, 8173–8179
39 Sumerlin BS, Neugebauer D, Matyjaszewski K. Initiation efficiency
in the synthesis of molecular brushes by grafting from via atom
transfer radical polymerization. Macromolecules, 2005, 38, 702–708
40 Lobb EJ, Ma I, Billingham NC, Armes SP, Lewis AL. Facile syn-
thesis of well-defined, biocompatible phosphorylcholine-based
methacrylate copolymers via atom transfer radical polymerization at
20 degrees C. J Am Chem Soc, 2001, 123, 7913–7914
41 Ma YH, Tang YQ, Billingham NC, Armes SP. Well-defined bio-
compatible block copolymers via atom transfer radical polymeriza-
tion of 2-methacryloyloxyethyl phosphorylcholine in protic media.
Macromolecules, 2003, 36, 3475–3484
42 Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, Riess
G, Croucher MD. Poly(styrene-ethylene oxide) block copolymer mi-
celle formation in water: A fluorescence probe study. Macromole-
cules, 1991, 24, 1033–1040
43 Lee AS, Gast AP, Bütün V, Armes SP. Characterizing the structure of
pH dependent polyelectrolyte block copolymer micelles. Macromolecules,
1999, 32, 4302–4310
44 Thurmond KB, Kowalewski T, Wooley KL. Shell Cross-linked
knedels: A synthetic study of the factors affecting the dimensions and
properties of amphiphilic core-shell nanospheres. J Am Chem Soc,
1997, 119, 6656–6665
2
2
2
2
2
1
2
3
4
5
Sun T, Yu GE, Price C, Booth C. Cyclic polyethers. Polymer, 1995,
3
6, 3775–3778
Yu GE, Sinnathamby P, Price C, Booth C. Preparation of large cyclic
poly(oxyethylene)s. Chem Commun, 1996, 31–32
Fitton AH, Jane D, Miller R. Synthesis of simple oxetanes carrying
reactive 2-substituents. Synthesis, 1987, 1140–1142
Taton D, Borgne A, Sepulchre M, Soassky N. Synthesis of chiral and
racemic functional polymers from glycidol and thioglycidol. Macro-
mol Chem Phys, 1994, 195, 139–148
Maier S, Sunder A, Frey H, Mulhaupt R. Synthesis of poly(glycerol)-
block-poly(methyl acrylate) multi-arm star polymers. Macromol
Rapid Commun, 2000, 21, 226–230
Chen J, Jiang M, Zhang Y, Zhou H. Fluorescence studies on hydro-
phobic associations of fluorocarbon-modified poly(acrylic acid) solu-
tions. Macromolecules, 1999, 32, 4861–4866
Angot B, Taton D, Gnanou Y. Amphiphilic stars and dendrimer-like
architectures based on poly(ethylene oxide) and polystyrene. Mac-
romolecules, 2000, 33, 5418–5426
2
2
2
2
3
6
7
8
9
0
Feng XS, Taton D, Chaikof EL, Gnanou Y. Toward an easy access to
dendrimer-like poly(ethylene oxide)s. J Am Chem Soc, 2005, 127,
1
0956–10966
Yan ZG, Yang Z, Price C, Booth C. Cyclization of poly(ethylene gly-
col)s and related block copolymers. Makromol Chem Rapid Commun,
45 Kalyanasundaram K, Thomas JK. Environmental effects on vibronic
band intensities in pyrene monomer fluorescence and their applica-
tion in studies of micellar systems. J Am Chem Soc, 1977, 99,
2039–2044
46 Butun V, Billingham NC, Armes SP. Synthesis and aqueous solution
properties of novel hydrophilic-hydrophilic block copolymers based
on tertiary amine methacrylates. Chem Commun, 1997, 671–672
47 Lee AS, Gast AP, Butun V, Armes SP. Characterizing the structure
of pH dependent polyelectrolyte block copolymer micelles. Macro-
molecules, 1999, 32, 4302–4310
48 Butun V, Armes SP, Billingham NC. Synthesis and aqueous solution
properties of near-monodisperse tertiary amine methacrylate ho-
mopolymers and diblock copolymers. Polymer, 2001, 42, 5993–6008
49 Vamvakaki M, Billingham NC, Armes SP. Synthesis of controlled
structure water-soluble diblock copolymers via oxyanionic polym-
erization. Macromolecules, 1999, 32, 2088–2090
1
993, 14, 725–732
3
3
3
1
2
3
Yu GE, Sinnathamby P, Price C, Booth C. Preparation of large cyclic
poly(oxyethylene)s. Chem Commun, 1996, 1, 31–32
Sun T, Yu GE, Price C, Booth C, Cooke J, Ryan AJ. Ostwald ripen-
ing in polyethylene blends. Polymer, 1995, 36, 3369–3775
Laurent BA, Grason SM. An efficient route to well-defined macro-
cyclic polymers via “click” cyclization. J Am Chem Soc, 2006, 128,
4
238–4239
Lutz F, Tietze. Domino reactions in organic synthesis. Chem Rev,
996, 96, 115–136
3
3
4
5
1
Harada A, Nishiyama T, Kawaguchi Y, Okada M, Kamachi M.
Preparation and characterization of inclusion complexes of aliphatic
polyesters with cyclodextrins. Macromolecules, 1997, 30, 7115–7118
Harada A, Nishiyama T, Kawaguchi Y, Okada M, Kamachi M.
Complex formation of poly(epsilon-caprolactone) with cyclodextrins.
3
6