Synthesis of biocompatible tadpole-shaped copolymer with one poly(ethylene oxide) (PEO) ring and two poly(ε-caprolactone) (PCL) tails by combination of glaser coupling with ring-opening polymerization

Article abstract of DOI:10.1016/j.polymer.2012.04.023

The biocompatible tadpole-shaped copolymers [cyclic-poly(ethylene oxide) (PEO)]-b-[linear poly(ε-caprolactone) (PCL)]₂ [(c-PEO)-b-PCL₂] with one PEO ring and two PCL tails were synthesized by combination of glaser coupling with ring-opening polymerization (ROP). First, a linear PEO precursor with two alkyne groups at the chain terminal and two hydroxyl groups at the chain middle was prepared by ROP of EO monomer and the following transformation of functional groups. Then, cyclic PEO with two hydroxyl groups at the same site was obtained by the "Glaser" cyclization. Finally, the hydroxyl groups on cyclic PEO directly initiated the ROP of ε-CL monomer to produce the target copolymers (c-PEO)-b-PCL ₂. The target copolymers and intermediates were all well characterized by GPC, MALDI-TOF MS, ¹H NMR and FT-IR.

Full text of DOI:10.1016/j.polymer.2012.04.023

Polymer 53 (2012) 2890e2896
Contents lists available at SciVerse ScienceDirect
Polymer
journal homepage: www.elsevier.com/locate/polymer
Synthesis of biocompatible tadpole-shaped copolymer with one poly(ethylene
oxide) (PEO) ring and two poly( -caprolactone) (PCL) tails by combination of
3
glaser coupling with ring-opening polymerization
*
Xiaoshan Fan, Bing Huang, Guowei Wang , Junlian Huang
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The biocompatible tadpole-shaped copolymers [cyclic-poly(ethylene oxide) (PEO)]-b-[linear poly( 3 -
Received 24 February 2012
Received in revised form
7 April 2012
Accepted 16 April 2012
Available online 4 May 2012
caprolactone) (PCL)]2 [(c-PEO)-b-PCL2] with one PEO ring and two PCL tails were synthesized by
combination of glaser coupling with ring-opening polymerization (ROP). First, a linear PEO precursor
with two alkyne groups at the chain terminal and two hydroxyl groups at the chain middle was prepared
by ROP of EO monomer and the following transformation of functional groups. Then, cyclic PEO with two
hydroxyl groups at the same site was obtained by the “Glaser” cyclization. Finally, the hydroxyl groups on
cyclic PEO directly initiated the ROP of -CL monomer to produce the target copolymers (c-PEO)-b-PCL2.
3
Keywords:
Tadpole-shaped copolymers
Poly(ethylene oxide)(PEO)
The target copolymers and intermediates were all well characterized by GPC, MALDI-TOF MS, 1H NMR
and FT-IR.
Ó 2012 Elsevier Ltd. All rights reserved.
Poly( 3 -caprolactone)(PCL)
1. Introduction
reported the synthesis of amphiphilic tadpole-shaped polymers
(cyclic polystyrene)-b-poly(ethylene oxide) [(c-PS)-b-PEO] via
Since the properties of polymers are inherently dependent on
their architectures, tailored control of polymer architectures has
always attracted attention from polymer chemists [1]. Up to now,
polymers with various kinds of architectures have been synthe-
sized, including linear [2,3], star-shaped [4e7], grafted [8e14],
hyperbranched [15e18], dendrimer [19e22] and cyclic polymers
[23e39]. These increasing diversity in polymer architectures has
offered opportunities in understanding the relationship of archi-
tectures with properties, and developing novel polymer materials
with unprecedented properties and functions. Compared with
other copolymers, cyclic polymers have been less studied due to the
limited accessibility of model compounds. Therefore, the synthesis
of cyclic polymers is still an interesting subject for polymer
chemists.
The tadpole-shape is a kind of appealing topology, in which one
macrocycle is connected with one or more tails. It was discovered
that a certain bacterial peptide possessing the tadpole-shape
topology adopts a unique folded structure by threading the tail
chain into the loop segment [40e42]. At the time being, a few
examples of tadpole-shaped polymers with different compositions
and architectures have been reported [23e31]. For example, Li et al.
the “click” cyclization of the linear copolymer PS-b-PEO, which
contains a alkyne group at the junction point and an azide
group at the PS chain end [29]. Recently, Liu et al reported the
synthesis of amphiphilic tadpole-shaped copolymer [cyclic-poly
(N-isopropylacrylamide)]-b-poly(
-caprolactone) [(c-PNIPAM)-b-PCL]
3
and investigated the application of micellar assemblies as
controlled release drug nanocarriers [25]. Tezuka et al reported the
synthesis of unusual topological two-tail tadpole-shaped poly
(tetrahydrofuran)s [poly(THF)s] by an electrostatic self-assembly
and covalent fixation process [28]. Although much effort has been
made, reports of tadpole-shaped polymers, especially biocompat-
ible those, are still rare.
Biocompatible copolymers have been a subject of special
attention due to their potential applications in drug delivery, tissue
engineering and diagnostic biosensors [43e46]. Among them, the
copolymers containing hydrophilic PEO and hydrophobic PCL
segments have been extensively studied due to the biocompati-
bility, hydrophilicity and low protein absorption of PEO, and the
biocompatibility and biodegradability of PCL. Up to now, the PEO
and PCL copolymers with various of architectures have been
synthesized, such as block, star-like, and graft copolymers [47e49].
However, scarce examples of the cyclic polymers containing PEO
and PCL segments have been reported due to the synthetic diffi-
culties. Herein, a biocompatible tadpole-shaped copolymer with
one PEO ring and two PCL tails was obtained by the combination of
* Corresponding author. Tel.: þ86 21 65642384.
E-mail address: gwwang@fudan.edu.cn (G. Wang).
0032-3861/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.polymer.2012.04.023

X. Fan et al. / Polymer 53 (2012) 2890e2896
2891
“Glaser” coupling [50e54] with ring-opening polymerization (ROP)
(Scheme 1).
<100-1000 Å; molecular range: 0-5 ꢁ 104, 5 ꢁ 104-8 ꢁ 106, and
(5e8) ꢁ 106 g/mol, respectively) were calibrated with PEO standard
samples. GPC analysis of the copolymers containing PEO and PCL
segments was performed in THF at 35 ꢀC with an elution rate of
1.0 mL/min on an Agilent 1100 equipped with a G1310A pump,
a G1362A refractive index detector, and a G1314A variable wave-
length detector. One 5 LP gel column (500 Å, molecular range 500-
2. Experimental Section
2.1. Materials
2 ꢁ 104 g/mol) and two 5
mm LP gel mixed bed column (molecular
Ethylene oxdie (EO) (98%, Sinopharm Chemical Reagent Co., Ltd
(SCR)) was dried bycalcium hydride (CaH2) for 48 h and then distilled
under N2 before use. Pentaerythritol (Aldrich, 98%) was dried at 50 ꢀC
under vacuum. Copper(I) bromide (Cu(I)Br) (95%, SCR) was stirred
overnight in acetic acid, filtered, washed with ethanol and diethyl
ether successively, and dried in vacuum. Sodium hydride (NaH) (60%
dispersion in mineral oil, Aldrich) and N,N,N0,N00,N00-pentamethyl-
diethylenetriamine (PMDETA) (99%, Aldrich) were used as received.
range 200-3 ꢁ 106 g/mol) were calibrated by PS standard samples.
1H NMR spectra were recorded on a Bruker (500 MHz) spectrom-
eter in CDCl3 with tetramethylsilane (TMS) as the internal reference
for chemical shifts. The matrix-assisted laser desorption ionization
time-of-flight mass spectrometry (MALDI-TOF MS) measurement
was performed using a Perspective Biosystem Voyager DE-STR
MALDI-TOF MS (PE Applied Biosystems, Framingham, MA). Matrix
solution of dithranol (20 mg/mL), polymer (10 mg/mL), and catio-
nizing salt of sodium trifluoroacetate (10 mg/mL) in THF was mixed
in the ratio of 10:4:2. Fourier Tansform infrared (FT-IR) spectra were
recorded on a NEXUS 470 FT-IR instrument and the polymer solu-
tion was cast on a NaCl disk to form the film.
Propargyl bromide (>99%) and -caprolactone (99%, Aldrich) were
3
purified by distillation from CaH2 under reduced pressure. Tetrahy-
drofuran (THF) (99%, SCR) was refluxed and distilled from potassium
naphthalenide solution. Tin (II) bis(2-ethylhexanoate) (Sn(Oct)2)
(95%, Sigma) was dissolved in dry toluene (10 mg/mL). Diphe-
nylmethyl potassium (DPMK) solution with concentration of
0.64 mol/L was prepared according to the literature [55]. 2-phenyl-
5,5-bis(hydroxymethyl)-1,3-dioxane was synthesized according to
the literature [56]. All other regents and solvents were purchased
from Sinopharm Chemical Reagent Co., Ltd. (SCR) and used as
received except for declaration.
2.3. Synthesis
2.3.1. Synthesis and characterization of 2-phenyl-5,5-
bis(hydroxymethyl)-1,3-dioxane
Typically, a mixture of pentaerythritol (24.0 g, 0.15 mol) and
N0,N-Dimethylformamide (DMF, 150 mL) was heated and stirred
until the solid was completely dissolved. Benzaldehyde (15.3 mL,
0.15 mol) and p-toluenesulfonic acid monohydrate (1.42 g,
7.5 mmol) were added. The solution was heated at 90 ꢀC for 19 h,
and ethyl acetate was added to dissolve the residue after DMF was
evaporated under reduced pressure. The organic solution was
washed successively with aqueous sodium chloride and water, and
then dried over anhydrous MgSO4 overnight. After filtration, the
solvent was evaporated. The resultant solid was recrystallized from
2.2. Characterizaiton
Gel permeation chromatographic (GPC) analysis of PEO homo-
polymers was performed in 0.1 M NaNO3 aqueous solution at 40 ꢀC
with an elution rate of 0.5 mL/min on an Agilent 1100 equipped
with a G1310A pump, a G1362A refractive index detector, and a
G1315A diode-array detector. Three TSK-gel PW columns in
series (bead size: 6, 13, and 13
mm; pore size: 200, >1000, and
Scheme 1. Synthetic route to the tadpole-shaped copolymers (c-PEO)-b-PCL2.

2892
X. Fan et al. / Polymer 53 (2012) 2890e2896
toluene for two times to white solid. 1H NMR (DMSO-d6,d):
3.31 ppm (s, 2H, CH2OH), 3.65 ppm (s, 2H, CH2OH), 3.76 ppm (d,
J ¼ 10.8, Hz, 2H, Ha), 3.88 ppm (d, J ¼ 10.8, Hz, 2H, He), 5.38 ppm (s,
1H, C6H5CH), 7.32e7.38 ppm (m, 5H, C6H5).
completed, the final concentration reached to 0.5860 g/L. The
reaction mixture was allowed to stir for additional 6.0 h, and the
solvent was evaporated under reduced pressure. The residual was
dissolved in water and extracted with CH2Cl2 (2 ꢁ 200 mL). The
organic layer was dried with MgSO4, filtered and concentrated.
After the residual was precipitated into an excess of diethyl ether
two times, the product of cyclic PEO(4) was vacuum dried at 40 ꢀC
2.3.2. Synthesis of a,u-dihydroxy-Poly(ethylene oxide) with two
protected hydroxyl groups at the chain middle [PEO(1)] (Scheme 1)
PEO(1) was synthesized by ROP of EO monomers in THF using 2-
phenyl-5,5- bis(hydroxymethyl)-1,3-dioxane (which contained two
protected hydroxyl groups and two active hydroxyl groups) and
DPMK as co-initiator. The initiator of 2-phenyl-5,5-bis(hydro
xymethyl)-1,3-dioxane (1.31 g, 5.85 mmol) dried by azeotropic
distillation with toluene was dissolved in 140 mL dried THF, then
the solution was introduced into a 250 mL ampoule. The solution of
DPMK in THF (7.70 mL, 5.85 mmol) was slowly added and the
solution took turbid as the alkoxides were formed. The monomers
of EO (30.0 mL, 0.589 mol) were then injected into the ampoule
under nitrogen and the reaction was carried out at 55 ꢀC for 48 h.
After 2.0 mL methanol was added to terminate the polymerization,
the solution was concentrated and precipitated into an excess of
to
a d):
constant weight (yield: 75%). 1H NMR (CCl3D,
3.43e3.62 ppm (m,-(CH2CH2O)n-), 4.62 ppm (s, -CH2C^CCH2-).
Mn,GPC ¼ 3,100 g/mol, PDI ¼ 1.07.
2.3.6. Synthesis of tadpole-shaped amphiphilic copolymer with one
PEO ring and two PCL tails [(c-PEO)-b-PCL2] (Scheme 1)
The copolymers (c-PEO)-b-PCL2 were obtained by ROP of -CL
3
monomers using PEO(4) as macro-initiator. The dried cyclic
PEO(4a) (0.300 g, 7.69 ꢁ 10ꢂ5 mol), freshly distilled
-CL (0.340 g,
diethyl ether two times for PEO(1). 1H NMR (CCl3D,
d):
PEO)-b-PCL2. 1H NMR (CCl3D,
d): 3.43e3.62 ppm (m,-(CH2CH2O)n-),
3.43e3.62 ppm (m,-(CH2CH2O)n-), 5.40 ppm (s, C6H5CH),
7.34e7.46 ppm (m, 5H, C6H5). PEO(1a): Mn,NMR ¼ 3,900 g/mol;
Mn,GPC ¼ 3,100 g/mol, PDI ¼ 1.09.
4.62 ppm (s, -CH2C^CCH2-). 1.38 ppm (m, -(COCH2CH2CH2CH2
CH2O)n-), 1.64 ppm (m, -(COCH2CH2CH2CH2CH2O)n-), 2.31 ppm (m,
-
-(COCH2CH2CH2CH2CH2O)n-), 4.06 ppm (m, -(COCH2CH2CH2CH2
-
CH2O)n-); Mn,NMR ¼ 9,500 g/mol; Mn,GPC ¼ 12,700 g/mol, PDI ¼ 1.32.
2.3.3. Synthesis of a,u-dialkyne-Poly(ethylene oxide) with two
protected hydroxyl groups at the chain middle [PEO(2)] (Scheme 1)
PEO(2) was synthesized by modification of hydroxyl groups into
alkyne groups at the chain terminal of PEO(1). PEO(1) (3.51 g,
1.14 mmol) dried by azeotropic distillation with toluene was dis-
solved in 100 mL dried THF, and NaH (1.88 g, 22.8 mmol) was added
into the solution. After the mixture was stirred for 2.0 h, propargyl
bromide (4.2 mL, 22.8 mmol) was added and the mixture was
stirred at room temperature overnight. The residual NaH was
neutralized by adding a few drops of deionized water under rapidly
stirring. After filtration of the formed salts, the solution was
concentrated and precipitated into an excess of diethyl ether two
3. Results and discussion
The biocompatible tadpole-shaped copolymer (c-PEO)-b-PCL2
was synthesized according to the steps shown in Scheme 1. The
a,u-dialkyne-poly(ethylene oxide) with two hydroxyl groups at the
chain middle (PEO(3)) was prepared by ROP of EO monomers using
2-phenyl-5,5- bis(hydroxymethyl)-1,3-dioxane as initiator, fol-
lowed by transformation of functional groups. Cyclization of linear
PEO(3) by “Glaser” coupling offered the cyclic PEO(4) with two
hydroxyl groups at the same site. The target amphiphilic copolymer
(c-PEO)-b-PCL2 was obtained by ROP of
hydroxyl groups on cyclic PEO(4).
3
times for PEO(2). 1H NMR (CCl3D,
d): 2.44 ppm (s, HC^CCH2-),
3.43e3.62 ppm (m,-(CH2CH2O)n-), 4.20 ppm (s, HC^CCH2-),
5.40 ppm (s, C6H5CH), 7.34e7.46 ppm (m, 5H, C6H5).
3.1. Synthesis and characterization of
a
,
u
-dialkyne-poly(ethylene
oxide) with two hydroxyl groups at the chain middle
2.3.4. Synthesis of a,u-dialkyne-Poly(ethylene oxide) with two
hydroxyl groups at the chain middle [PEO(3)] (Scheme 1)
First, the well-defined -dihydroxy-poly(ethylene oxide) with
a,u
PEO(3) was obtained by recovery of the protected hydroxyl
group at the chain middle of PEO(2). The PEO(2) was dissolved in
THF and adjusted to be acidic by adding the HCl solution and stirred
for 2.0 h at the room temperature. The solvent was evaporated
under reduced pressure, then the residual was dissolved in water
and extracted with CH2Cl2. The organic layer was dried with
MgSO4, filtered and concentrated under reduced pressure. The
residual was precipitated into an excess of diethyl ether three times
two protected hydroxyl groups at the chain middle (PEO(1)) was
synthesized by ROP of EO monomers using 2-phenyl-5,5-
bis(hydroxymethyl)-1,3-dioxane as initiator and DPMK as co-
initiator. By changing the molar ratio of EO monomers to initiator,
two series of PEO(1) with different molecular weight were
obtained (PEO(1a): Mn,GPC ¼ 3,100 g/mol, PDI ¼ 1.09. PEO(1b):
Mn,GPC ¼ 6,400 g/mol, PDI ¼ 1.08). Fig. 1A showed the GPC trace of
PEO(1a), which showed a unimodal peak with narrow molecular
weight distribution. In a typical 1H NMR spectrum of PEO(1a)
(Fig. 2A), the signals (a) at 7.34 and 7.49 ppm were assigned to the
phenyl-ring protons (C6H5CH(OCH2-)2) and (b) at 5.40 ppm was
assigned to methine proton (C6H5CH(OCH2-)2) of the protective
group, and the signals (c) 3.43e3.64 ppm were assigned to the
methylene protons (-CH2CH2O-) of EO units. The molecular weights
of PEO(1) (Mn,NMR, PEO(1)) were derived by 1H NMR spectra
according to Formula 1:
for PEO(3). 1H NMR (CCl3D,
d): 2.44 ppm (s, HC^CCH2-),
3.43e3.62 ppm (m,-(CH2CH2O)n-), 4.20 ppm (s, HC^CCH2-).
Mn,GPC ¼ 3,800 g/mol, PDI ¼ 1.06.
2.3.5. Synthesis of cyclic Poly(ethylene oxide) with two hydroxyl
groups via “Glaser” coupling [(PEO (4)) (Scheme 1)
PEO(4) was obtained by “Glaser” cyclization between alkyne
groups at the terminal of PEO(3). Into a 1 L round-bottomed flask,
pyridine (700 mL), PMDETA(2.02 ml, 9.71 mmol), Cu(I)Br (1.39 g,
9.71 mmol) were added. In a separate 150 mL flask, linear PEO(3)
(0.410 g, 1.05 ꢁ 10ꢂ5 mol) was dissolved in 100 mL pyridine. Under
vigorously stirring, the solution of linear PEO(3) was slowly added
into the 1 L flask (heated to 50 ꢀC) via a peristaltic pump at a rate of
1.4 mL/h. After the addition of the linear PEO(3) solution was
Ac=4
Ab
Mn;NMR;
¼
ꢁ 44 þ 222
(1)
PEOð1Þ
Where Ac and Ab were the integral areas of the signals at 5.40 ppm
and that at 3.43e3.64 ppm, respectively. The values of 44 and 222

X. Fan et al. / Polymer 53 (2012) 2890e2896
2893
Fig. 1. GPC traces of PEO(1a) (Mn ¼ 3,100 g/mol, PDI ¼1.09) (A), linear PEO(3a) (Mn ¼ 3,800 g/mol, PDI ¼1.06) (B) , cyclic PEO(4a) (Mn ¼ 3,100 g/mol, PDI ¼1.07) (C) and (c-PEO)-b-
PCl2 (5a) (D) ( A, B, C using 0.1 M NaNO3 aqueous solution as eluent; D using THF as eluent).
were the molecular weight of EO monomer unit and the residual of
initiator (C(OCH2-)2((OCH2-)2CH C6H5)), respectively.
was not detected in that of PEO(2a), indicating the propargylation
was performed completely. The propargylation was further verified
by FT-IR analysis, the characteristic signal of the alkyne groups at
3325 cmꢂ1 in the spectrum of PEO (2) appeared clearly (Fig. 4).
Under acidic conditions, the recovery of hydroxyl groups on
The
a,u-dialkyne-poly(ethylene oxide) with two protected
hydroxyl groups at the chain middle (PEO(2)) were obtained by
reaction between hydroxyl groups at the end of PEO(1) and prop-
argyl bromide in the presence of NaH. Compared the 1H NMR
spectrum of PEO(2a) with that of PEO(1a) (Fig. 2), the newsignals (f)
at 2.44 ppm and (g) at 4.20 ppm can be assigned to the alkynyl
protons (-CH2C^CH) and methylene protons(-CH2C^CH) of the
propargyl groups. The relative integration ratio of the signals (f) and
(b) was about 2:1, indicating that the propargylation efficiency was
almost 100%. The propargylation procedure was also verified by
MALDI-TOF mass spectrum. From Fig. 3, we could observe an
increase of 2 ꢁ 38.9 Da from peak (224.3 (C12H16O4) þ44.0
(EO) ꢁ n þ 23.0 (Naþ) ¼ 4122.5 Da) of PEO(1a) to peak (224.3
PEO(2) gave the
a,u- dialkyne-poly(ethylene oxide) with two
hydroxyl groups (PEO(3)). In the 1H NMR spectrum of PEO(3a)
(Fig. 2C), the signals (a) at 7.34 and 7.49 ppm of the phenyl-ring
protons (C6H5CH(OCH2-)2) and (b) at 5.40 ppm of methine proton
(C6H5CH(OCH2-)2) of the protective group disappeared thoroughly,
confirming that the hydrolysis was complete. Compared with the
MALDI-TOF mass spectrum of PEO(2a), that of PEO(3a) decreased
88.1 Da, nearly the molecular weight of a protective group (Fig. 3).
The trace of PEO(2a) was not detected in MALDI-TOF mass spec-
trum of PEO(3a), further confirming the hydrolysis was complete.
Thus, the precursor of PEO(3a) with two alkyne groups at the chain
terminal and two active hydroxyl groups at the chain middle was
successfully synthesized.
(C12H16O4) þ44.0 (EO)
ꢁ
n
þ39.1 (C3H3)
ꢁ
2
þ
23.0
(Naþ) ¼ 4200.3 Da) of PEO(2a), which corresponded to the molec-
ular weight of two propargyl groups. Moreover, the trace of PEO(1a)
Fig. 2. 1H NMR spectra of PEO(1a) (A), PEO (2a) (B), linear PEO(3a) (C) and cyclic PEO(4a) (D) in CDCl3.

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X. Fan et al. / Polymer 53 (2012) 2890e2896
Fig. 3. MALDI-TOF mass spectra of PEO(1a) (A), PEO(2a) (B), and PEO(3a) (C) with dithranol as matrix and sodium trifluoroacetate as cationizing salt.
3.2. Synthesis and Characterization of cyclic Poly(ethylene oxide)
with two hydroxyl groups at the same site
linear precursors because of the more compact conformation by
cyclization. Compared the GPC trace of cyclic PEO(4a) with that of
linear PEO(3a) (Fig. 1), it can be seen that the former clearly shifted
to the lower molecular weight area. The < G > value, the ratio of the
apparent peak molar mass of cyclic PEO(4) to that of linear PEO(3),
were 0.81 and 0.92 (Table 1), which were coincident with the
reported data in literatures [23e37]. On the other hand, the
The intramolecular cyclization by “Glaser” coupling between
alkyne groups on linear PEO(3) offered the cyclic PEO(4) containing
two active hydroxyl groups at the same site. It was well known that
the hydrodynamic volume of cyclic polymers is smaller than their
Fig. 4. FT-IR spectra PEO(1a) (A), linear PEO(3a) (B) and cyclic PEO(4a) (C).

X. Fan et al. / Polymer 53 (2012) 2890e2896
2895
Table 1
The data of the tadpole-shaped copolymers (c-PEO)-b-PCl2.
Entry
PEO(3)
PEO(4)
<G>b
(c-PEO)-b-PCL2 (5)
Mn,NMRc [g/mol]
Mn,GPC [g/mol]
PDIa
Mp [g/mol]
Mn,GPC [g/mol]
PDIa
Mp [g/mol]
Mn,GPCd [g/mol]
PDId
a
a
a
a
a
b
3,800
7,100
1.06
1.12
4,100
8,500
3,100
6,500
1.07
1.15
3,300
7,800
0.81
0.92
9,500
16,800
12,700
20,900
1.32
1.22
a
Determined by GPC using PEO as standard and 0.1 M aqueous NaNO3 as eluent.
b
c
The ratio of the apparent peak molar masses (Mp) were derived from the GPC of cyclic PEO to their linear precursors.
Determined by 1H NMR using Formula 3.
d
Determined by GPC using THF as eluent.
unimodal peak of GPC trace for cyclic PEO(4a) meant that no
intermolecular byproduct was produced during the cyclization
process. From the 1H NMR spectrum in Fig. 2D, it can be seen that
the signal for the methine proton (-CH2C^CH) of alkynyl group at
2.44 ppm disappeared completely after cyclization. And the
molecular weights of PEO(4) (Mn, NMR, PEO(4)) were derived by 1H
NMR spectra according to Formula 2:
Where the values of 90 and 38 were the mass of the removed acetal
groups (C6H5CH-) and propargyl groups (-CH2ChC-), respectively.
As shown in the MALDI-TOF mass spectra (Fig. 5), the molec-
ular weight of cyclic PEO(4a) almost differred 2.0 Da with its
precursor of linear PEO(3a), which also confirmed the successful
cyclization. After “Glaser” cyclization, the characteristic signal of
the alkyne groups at 3325 cmꢂ1 in the spectrum of PEO(2) also
disappeared clearly (Fig. 4). Based on these results above, we can
conclude that the cyclization was successful, and the cyclic
Mn;NMR;
¼ Mn;NMR; PEOð1Þ ꢂ 90 þ 38 ꢁ 2
(2)
PEOð4Þ
Fig. 5. MALDI-TOF mass spectra of cyclic PEO(4a) (A) and linear PEO(3a) (B) with dithranol as matrix and sodium trifluoroacetate as cationizing salt.
Fig. 6. 1H NMR spectrum of (c-PEO)-b-PCl2 (5a) in CDCl3.

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X. Fan et al. / Polymer 53 (2012) 2890e2896
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The target copolymers (c-PEO)-b-PCL2 with one PEO ring and
two PCL tails were obtained by the ROP of -CL monomer using
3
cyclic PEO(4) as macro-initiator. In Fig. 1D, the GPC trace of
(c-PEO)-b-PCL2 (5a) was a unimodal peak, which indicated that the
polymerization proceeded smoothly. In a typical 1H NMR spectrum
of (c-PEO)-b-PCL2 (5a) (Fig. 6), the signals (h) at 2.31 ppm, (i) at
1.64 ppm, (j) at 1.38 ppm and (k) at 4.06 ppm can be attributed to
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the characteristic signals of the -CL units. The molecular weight of
3
PCL tails can be calculated by the relative integration of signals (c)
and (i) (Table 1), and the molecular weights of (c-PEO)-b-PCL2 (5)
(Mn, NMR, (c-PEO)-b-PCL2) were derived by 1H NMR spectra according to
Formula 3:
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doi:10.1002/pola.25965.
Ak=2
Mn; NMR;PEOð4Þ
Mn; NMR; ðcꢂPEOÞꢂbꢂPCL2
¼
ꢀ
ꢁ
ꢁ114
Ac=
ꢁ4
44
þMn; NMR;PEOð4Þ
(3)
Where Ak was the integral area of the signals at 4.06 ppm, the value
of 114 was the molecular weight of -CL monomer unit. The others
3
were the same as defined before and the data were shown in
Table 1. These results above showed that the biocompatible
copolymer (c-PEO)-b-PCL2 (5) were successfully synthesized.
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5083.
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J Am Chem Soc 2003;125:12382.
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4. Conclusion
In summary, a novel biocompatible tadpole-shaped copolymers
consisting one PEO ring and two PCL tails were successfully
synthesized by the combination of “Glaser” coupling with ROP
mechanism. Both of the PEO and PCL segments are the known to be
biocompatible, and it is expected that the copolymer (c-PEO)-b-
PCL2 may exhibit some unique properties due to the unusual
architecture and might be found some biomedical applications.
This work also presented a novel method to copolymers with
defined architecture and compositions.
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Acknowledgement
[47] Kang JM, Beers KJ. Biomacromolecules 2006;7:453.
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2003;36:8253.
We appreciate the financial support to this research by the
Natural Science Foundation of China (No. 21004011, 20974021) and
the Specialized Research Fund for the Doctoral Program of Higher
Education of China (No. 20090071120015).
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