Versatile synthesis of asymmetrical dendron-like/dendron-like poly(ε-caprolactone)-b-poly(γ-benzyl- L -glutamate) block copolymers

Article abstract of DOI:10.1002/pola.24784

Dendron-like/dendron-like poly(ε-caprolactone)-b-poly(γ-benzyl- L-glutamate) block copolymers with asymmetrical topology (PCL 208-b-PBLG ⁿ, both the subscript and the superscript denote the degree of polymerization and the branch number, respectively; n = 1, 2, and 4) were synthesized by combining ring-opening polymerization (ROP) and click chemistry. The dendron-like propargyl focal point PCL 208 precursor with eight branches was synthesized from the controlled ROP of ε-caprolactone, and then click conjugated with azido focal point poly(amido amine) dendrons to generate the PCL 208-dendrons with multiple primary amine groups. The PCL 208-dendrons were further used as macroinitiators for the ROP of γ-benzyl-L-glutamate N-carboxyanhydride to produce the targeted asymmetrical block copolymers. Their molecular structures and physicochemical properties were thoroughly characterized by means of FT-IR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, and wide angle X-ray diffraction. Both the maximal melting temperature and the degree of crystallinity of PCL block within copolymers decreased with increasing the PBLG branches and/or the chain length, demonstrating that the crystallinity of PCL block was progressively suppressed by PBLG block. Meanwhile, the PBLG block within copolymers progressively transformed from β-sheet to α-helical conformation with increasing the PBLG chain length. Consequently, this provides a versatile strategy for the synthesis of biodegradable and biomimetic block copolymers with asymmetrical dendritic topology.

Full text of DOI:10.1002/pola.24784

Versatile Synthesis of Asymmetrical Dendron-Like/Dendron-Like
Poly(e-Caprolactone)-b-Poly(c-Benzyl-L-Glutamate) Block Copolymers
WEI LIU, CHANG-MING DONG
Department of Polymer Science & Engineering, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University,
Shanghai 200240, People’s Republic of China
Received 3 March 2011; accepted 17 May 2011
DOI: 10.1002/pola.24784
Published online 14 June 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Dendron-like/dendron-like
poly(e-caprolactone)-b-
matography, differential scanning calorimetry, and wide angle
X-ray diffraction. Both the maximal melting temperature and
the degree of crystallinity of PCL block within copolymers
decreased with increasing the PBLG branches and/or the
chain length, demonstrating that the crystallinity of PCL block
was progressively suppressed by PBLG block. Meanwhile, the
poly(c-benzyl-L-glutamate) block copolymers with asymmetrical
topology (PCL8 -b-PBLG , both the subscript and the super-
n
20
script denote the degree of polymerization and the branch
number, respectively; n ¼ 1, 2, and 4) were synthesized by
combining ring-opening polymerization (ROP) and click chem-
8
istry. The dendron-like propargyl focal point PCL precursor
PBLG block within copolymers progressively transformed
from b-sheet to a-helical conformation with increasing the
PBLG chain length. Consequently, this provides a versatile
strategy for the synthesis of biodegradable and biomimetic
block copolymers with asymmetrical dendritic topology.
VC 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym
2
0
with eight branches was synthesized from the controlled ROP
of e-caprolactone, and then click conjugated with azido focal
8
2
8
2
point poly(amido amine) dendrons to generate the PCL 0-
dendrons with multiple primary amine groups. The PCL 0-
dendrons were further used as macroinitiators for the ROP of
c-benzyl-L-glutamate N-carboxyanhydride to produce the tar-
geted asymmetrical block copolymers. Their molecular struc-
tures and physicochemical properties were thoroughly
Chem 49: 3491–3498, 2011
KEYWORDS: biodegradable; dendritic block copolymers; ring-
1
characterized by means of FT-IR, H NMR, gel permeation chro-
opening polymerization; synthesis
INTRODUCTION Over the past three decades, dendritic poly-
mers (e.g., dendrimers, hyperbranched polymers, dendron-
ized polymers, and linear-dendritic copolymers) received
much attention because of their unique solution, bulk, and
hierarchical self-assembly properties, enabling them as a ver-
satile tool to tune the properties of complex functional mate-
sis and properties of linear-dendritic PCL and/or polypeptide
1
,22–25
copolymers were studied by several groups;
however,
no studies on dendritic/dendritic polypeptide/PCL block
copolymers were reported until now.
Since the introduction of ‘‘click chemistry’’ methodology,
both copper-catalyzed azide-alkyne cycloaddition (CuAAC)
and thiol-ene/-yne reactions proved to be the robust and
1
–8
rials.
In particular, they have been fabricated into multi-
scale micro-/nano-structures and soft gels, which are useful
modalities for diagnosis, drug/gene delivery, nanomedicine,
modular strategies for the synthesis of dendritic architec-
26–35
tures.
The intensive efforts were also made on the syn-
9
–12
and tissue engineering.
theses and modifications of biodegradable aliphatic polyesters
(e.g., PCL, polylactides, and polyglycolide) by utilizing click
Owing to their biodegradability and biocompatibility, both al-
iphatic polyesters [e.g., poly(e-caprolactone), PCL] and syn-
thetic polypeptides have been widely investigated for nano-
3
6–40
chemistry.
Our group recently designed and synthesized
a novel class of dendron-like/linear PCL- and polypeptide-
based block copolymers by combining CuAAC and ring-
opening polymerization (ROP), which established a platform
1
3–15
medicine and medical scaffolds,
and some of them
1
6
entered clinical trials. To take advantage of synthetic poly-
mers and biomimetic polypeptides, increasing efforts are
made on the hybrids of polypeptides with biomedical poly-
2
2–25,41–46
for nanomedicine and stimuli-sensitive hydrogels.
Herein, the versatile synthesis of dendron-like/dendron-like
1
7–21
mers [e.g., poly(ethylene oxide) and PCL].
Therefore, the
PCL-b-poly(c-benzyl-L-glutamate) block copolymers with
8
n
merger of dendritic polypeptides with dendritic aliphatic
polyesters affords an asymmetrical macromolecular topology
with tunable composition and accessible peripheries, which
holds great potentials in biomedical applications. The synthe-
asymmetrical topology (i.e., PCL -b-PBLG , both the sub-
20
script and the superscript denote the degree of polymeriza-
tion and the branch number, respectively; n ¼ 1, 2, and 4)
was developed by combining ROP and CuAAC (Scheme 1),
Additional Supporting Information may be found in the online version of this article. Correspondence to: C.-M. Dong (E-mail: cmdong@sjtu.edu.cn)
Journal of Polymer Science Part A: Polymer Chemistry, Vol. 49, 3491–3498 (2011) V
2011 Wiley Periodicals, Inc.
C
DENDRITIC POLYMERS, LIU AND DONG
3491

JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 1 A: Synthesis of azido focal point PAMAM dendrons D
PCL 82 0-b-PBLG (n ¼ 2 ¼ 1, 2, and 4) block copolymers.
m
(m ¼ 0, 1, and 2); B: Synthesis of dendron-like/dendron-like
n
m
ꢂ
and their molecular structures and physicochemical proper-
and a refractive index detector (model) at 30 C. The elution
phase was DMF (0.01 mol/L LiBr, elution rate: 1.0 mL/min),
and polystyrene was used as the calibration standard. The
differential scanning calorimetry (DSC) analysis was carried
out using a Perkin-Elmer Pyris 1 instrument under nitrogen
1
ties were thoroughly characterized by means of FT-IR,
H
NMR, gel permeation chromatography, differential scanning
calorimetry, and wide angle X-ray diffraction. Importantly,
this establishes a versatile strategy for the synthesis of bio-
degradable and biomimetic block copolymers with asymmet-
rical dendritic topology.
ꢂ
flow (10 mL/min). All samples were first heated from 20 C
to 140 C at 10 C/min and held for 3 min to erase the ther-
mal history, then cooled to 20 C at 10 C/min, and finally
heated to 140 C at 10 C/min. Wide angle X-ray diffraction
WAXD) patterns of powder samples were obtained at room
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
EXPERIMENTAL SECTION
(
Materials
temperature on a Shimadzu XRD-6000 X-ray diffractometer
with a CuKa radiation source (wavelength ¼ 1.54 Å). The
supplied voltage and current were set to 40 kV and 20 mA,
respectively. Samples were exposed at a scan rate of 2y ¼
e-Caprolactone (CL, Aldrich, 99%) and dimethylformamide
(
DMF, ꢀ99.5%) were distilled from calcium hydride under
reduced pressure and stored over molecular sieves, respec-
tively. Dichloromethane (ꢀ99.5%) and toluene (ꢀ99.5%)
were directly distilled from calcium hydride. Phosphorous
ꢂ
ꢂ
4
/min between 2y ¼ 5 and 40 .
trichloride (PCl , 95.5%) was distilled and diluted in dried
3
Preparation of Azidopropylamine
dichloromethane (PCl :CH Cl ¼ 1:3, v/v) before use. 3-
3
2
2
3-Chloropropylamine hydrochloride (1.0 g, 7.7 mmol) and
sodium azide (1.5 g, 23.1 mmol) were added into 8 mL dis-
tilled water in a round flask. The solution was stirred vigo-
Chloropropylamine hydrochloride (Aldrich, 98%), copper (I)
0
00 00
bromide (Aldrich, 99.999%), N,N,N ,N ,N -pentamethyldiethy-
ꢂ
lenetriamine (PMDETA, Aldrich, 99%), propargyl amine
rously at 80 C for 24 h. After cooling in an ice-water bath,
(
Aldrich, 99%), and stannous octoate (SnOct , Aldrich, 95%)
2
sodium hydroxide (0.46 g) was added into the solution. The
solution was extracted by 30 mL diethyl ether for three times,
and then the combined organic layer was dried by sodium
sulfate. After removing diethyl ether under reduced pressure,
azidopropylamine was obtained in a yield of 83.2% (663.7 mg).
Azidopropylamine was stable if it was stored in refrigerator at
were used as received. Ethylenediamine (99%) and methyl
acrylate (98%) were purchased from Shanghai Sinopharm
Chemical Reagent Corporation and distilled before use.
c-Benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) mono-
mer was synthesized from N-tert-butyloxycarbonyl-c-benzyl-
L-glutamic acid and phosphorous trichloride. The propargyl
focal point poly(amido amine) (PAMAM) typed dendrons
with eight primary amine groups were synthesized as
2
4
ꢂ
1
about 4 C. H NMR (CDCl ): d (ppm) ¼ 1.70ꢃ1.76 (q, 2H,
3
CH CH CH ), 2.79ꢃ2.83(t, 2H, CH NH ), 3.35ꢃ3.39 (t, 2H,
2
2
2
2
2
N CH ). TOF-MS, m/z: calcd for C H N , 101.0749; found,
3
2
3
8
4
2
2
þ
ꢃ1
detailed in our previous publication.
1
2
01.0841 [M þ H] . FT-IR (KBr, cm ): 3434 (mN-H); 2926,
852(mC-H), 2102 (mN:N), 1634 (mC¼O), 1469 (mCO-NH).
Methods
1
H NMR spectroscopy was performed on a Varian Mercury-
00 spectrometer. Tetramethylsilane was used as an internal
Preparation of Azido Focal Point PAMAM Typed
Dendron D1
4
standard. Molecular weight and polydispersity (M /M ; M :
The azido focal point PAMAM typed dendrons groups (i.e.,
D1and D2) were synthesized using a protocol similar to that
described by Lee et al., as shown in Scheme 1. Under vig-
orous stirring, a solution of azidopropylamine (denoted as
D0, 275.9 mg, 2.76 mmol) in methanol (2 mL) was added
dropwise to a cooled solution (ice-water bath) of methyl
w
n
w
weight-average molecular weight, M : number-average mo-
n
4
7
lecular weight) of polymer were determined on a gel perme-
ation chromatograph (GPC, Perkin-Elmer Series 200)
equipped with two linear Mixed-B columns (Polymer Lab
Corporation, pore size: 10 lm, column size: 300 ꢁ 7.5 mm)
3492
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

ARTICLE
acrylate (1.34 mL, 6.9 mmol) in methanol (2 mL) over
(t, 2H, CHCCH N), 3.25ꢃ3.38 (m, 18H, CH ), 2.48ꢃ2.80 (m, 4H,
2
2
6
0 min. The reaction solution was stirred vigorously for 1 h
CH
2
), 2.25–2.40 (m, 320H, COCH
2
CH
2
CH
2
CH
2 2
CH O), 2.15ꢃ2.22
ꢂ
at 0 C and then for an additional 20 h at room temperature
under nitrogen atmosphere. The solution was evaporated, and
then the residue was purified by column chromatography
(m, 17H, NHCOCH CH CH CH
þ
CHCCH N), 1.50ꢃ1.70
2
2
2
2
2
(m, 640H, COCH CH CH CH CH O), 1.30ꢃ1.44 (m, 320H,
2
2
2
2
2
COCH CH CH CH CH O). M
¼ 13,820, M /M ¼ 1.60.
2
2
2
2
2
n,GPC
w
n
(
EtOAc/n-hexane, 1:1, v:v) to afford the desired methyl ester
Then, the propargyl focal point PCL8 precursor was click
1
20
terminated dendron D0.5 (534.1 mg, 75% yield). H NMR
conjugated with azido focal point PAMAM typed dendrons
(
CDCl ): d (ppm) ¼ 1.65ꢃ1.74 (t, 2H, CH CH CH ), 2.38ꢃ2.52
3
2
2
2
8
20
Dm (m ¼ 0, 1, and 2) to generate the macroinitiators PCL -
(m, 6H, CH
2
CH
2
CH
2
NþCH
2
CO), 2.68ꢃ2.78 (t, 4H, CH
2 2
CH CO),
D . A typical procedure was started with the feed ratio of
m
3
.28ꢃ3.35 (t, 2H, N CH ), 3.65ꢃ3.70 (s, 6H, OCH ).
3
2
3
8
reagents [D
m
]/[PCL ]/[CuBr]/[PMDETA] ¼ 2/1/2/2. As a
20
Under vigorous stirring, a solution of D0.5 (1.2413 g, 4.56
mmol) in methanol (6 mL) was added dropwise to a cooled
solution of ethylenediamine (6.1 mL, 91.2 mmol) in methanol
representative example, the click coupling reaction between
D0 (2 mg, 0.02 mmol) and PCL8 (199.0 mg, 0.01 mmol
20
ꢂ
alkyne unit) was conducted at 35 C in a 25 mL Schlenk
flask with 2 mL of DMF as solvent, and both CuBr (2.9 mg,
0.02 mmol) and PMDETA (88 lL, 0.02 mmol, diluted by
20-fold DMF) as catalyst. After 48 h, the copolymer solution
was precipitated in diethyl ether. The white powder was
(
6 mL) over 60 min. The reaction mixture was stirred vigo-
ꢂ
rously for 1 h at 0 C and then for further 96 h at room tem-
perature under nitrogen atmosphere. The solution was evapo-
rated, and then the residue was dried in vacuo at 35 C to give
ꢂ
1
ꢂ
then dried in vacuo at 40 C to give 176.0 mg of PCL -D0
20
8
the azido focal point dendron D1 (1.495 g, 99% yield).
H
1
8
20
NMR (CDCl ): d (ppm) ¼ 1.60ꢃ1.75 (q, 6H, CH CH CH þNH ),
(88% yield). H NMR (CDCl ) of PCL -D0: d (ppm) ¼
3
2
2
2
2
3
2
2
3
.31ꢃ2.40 (t, 4H, CH CO), 2.46ꢃ2.50 (t, 2H, CH CH CH N),
4.00ꢃ4.12 (m, 320H, COCH CH CH CH CH O), 3.73ꢃ3.76 (t,
2
2
2
2
2
2
2
2
2
.69ꢃ2.75 (t, 4H, CH CH CO), 2.80ꢃ2.84 (t, 4H, CH NH ),
2H, CH -triazole), 3.59ꢃ3.68 (t, 16H, CH OH), 3.25ꢃ3.38 (m,
2
2
2
2
2
2
.25ꢃ3.30 (m, 6H, N CH þCONHCH ), 7.02ꢃ7.08 (s, 2H,
14H, CH ), 2.48ꢃ2.80 (m, 4H, CH ), 2.25-2.40 (m, 320H,
3
2
2
2
2
CONH). TOF-MS, m/z: calcd for C13
H
28
ꢃ1
N
8 2
O , 329.2413; found,
COCH
2
CH
2
CH
2
CH
2
CH
2
O), 2.15ꢃ2.22 (m, 16H, NHCOCH
2 2
CH
þ
3
29.2396 [M þ H] . FT-IR (KBr, cm ): 3434 (mN-H); 2926,
CH CH ), 1.50ꢃ1.70 (m, 640H, COCH CH CH CH CH O),
2
2
2
2
2
2
2
2852(m ), 2102 (m
), 1634 (m ), 1469 (mCO-NH).
1.30ꢃ1.44 (m, 320H, COCH CH CH CH CH O).
C-H
N:N
C¼O
2
2
2
2
2
Preparation of Azido Focal Point PAMAM Typed
Dendron D2
D2 was synthesized from D1 (1.4520 g, 4.42 mmol) using
same method as successive Michael addition of primary
amines with methyl acrylate and amidation of methyl ester
Synthesis of Dendron-Like/Dendron-Like Block
Copolymers PCL8 -b-PBLG (n 5 2 5 1, 2, and 4)
n
m
2
0
8
n
The block copolymers PCL -b-PBLG were synthesized from
20
8
the ROP of BLG-NCA using primary amine-terminated PCL -
20
D
as the macroinitiators in DMF solution at room tempera-
m
8
groups with a large molar excess of ethylenediamine (99%
ture. In a representative reaction, PCL -D0 (200.3 mg, 0.01
20
1
yield). H NMR of D1.5 (CDCl ): d (ppm) ¼ 1.72ꢃ1.76
mmol) was dissolved completely in 2 mL of DMF under nitro-
gen atmosphere, and then a degassed solution of BLG-NCA
(65.8 mg, 0.25 mmol) in 1 mL of DMF was added via a syringe.
The resulting solution was allowed to stir vigorously at room
temperature for 24 h, diluted with THF (3 mL), and then pre-
cipitated dropwise into a large excess of cold methanol
(50 mL). The white precipitate was filtered and dried in vacuo
3
(
q, 2H, CH CH CH ), 2.35ꢃ2.42 (m, 12H, CH CO), 2.50ꢃ2.56
2
2
2
2
(
m, 6H, CH CH CH Nþ CONHCH CH N), 2.70ꢃ2.82 (m,
2
2
2
2
2
1
3
2H, CH
2
CH
2
CO), 3.28ꢃ3.38 (m, 6H, N
3
CH
2
þCONHCH
2
),
1
.64ꢃ3.68 (s, 12H, OCH ), 6.94ꢃ7.00 (s, 2H, CONH). H NMR
3
(
(
(
CDCl ) of D2: d (ppm) ¼ 1.52ꢃ1.66 (s, 8H, NH ), 1.68ꢃ1.76
3
2
q, 2H, CH CH CH ), 2.28ꢃ2.42 (m, 12H, CH CO), 2.42ꢃ2.60
2
2
2
2
ꢂ
8
1
m, 6H, CH CH CH Nþ CONHCH CH N), 2.61ꢃ2.78 (m, 12H,
at 40 C to give 217.4 mg of PCL -b-PBLG (85.2%, yield ¼
2
2
2
2
2
20
17
CH CH CO), 2.78ꢃ2.90 (t, 8H, CH NH ), 3.20ꢃ3.40 (m, 14H,
W
copolymer/[WNCA ꢃ (WNCA/MNCA ꢁ MCO2) þ WPCLꢃD
m
]), in
2
2
2
2
N
2
3
CH
2
þCONHCH
2
), 7.50ꢃ7.58 (s, 4H, CONH), 7.88ꢃ7.95 (s,
which the subscript and the superscript numbers represent the
H, CONH). TOF-MS, m/z: calcd for C H N O , 785.5508;
degree of polymerization and the branch number, respectively.
3
3
69 16
ꢃ1
6
þ
found, 785.5568 [M þ H] . FT-IR (KBr, cm ): 3434 (mN-H);
1
H NMR (DMSO-d ): d (ppm) ¼ 8.0–8.20 (s, 17H, NH), 7.14–
6
2
926, 2852(m ), 2102 (m
), 1634 (m ), 1469 (mCO-NH).
N:N C¼O
C-H
7
1
.34 (m, 85H, Ph), 4.87–5.08 (t, 34H, CH Ph), 4.19ꢃ4.36 (s,
2
7H, COCHNH), 3.92ꢃ4.02 (t, 320H, COCH CH CH CH CH O),
2
2
2
2
2
Preparation of Dendron-Like Macroinitiators
8
2.37ꢃ2.42 (m, 34H, CH
2
CH
2
COOCH
2
Ph), 2.23ꢃ2.28 (t, 320H,
CH
2
PCL -D (m 5 0, 1, and 2)
m
COCH
2
CH
2
CH
2
CH
2
CH
2
O), 1.98ꢃ2.05 (d, 34H, CH
CH CH CH CH
.22ꢃ1.30 (m, 320H, COCH CH CH CH CH O). M ,
2
The multiple amine-terminated dendron-like macroinitiators
8
COOCH
1
17,350, M
2
Ph), 1.45ꢃ1.60 (m, 640H, COCH
2
2
2
2
2
O),
¼
PCL -D (m ¼ 0, 1, and 2) were successfully synthesized in
m
2
2
2
2
2
n GPC
two steps by combining ROP and CuAAC. First, according to
2
2
8
w
/M
n
¼ 1.58.
our previous publication, the clickable dendron-like PCL
with eight branches was synthesized by the controlled ROP
of e-caprolactone using propargyl focal point PAMAM typed
dendron with eight primary amines as initiator and stannous
RESULTS AND DISCUSSION
Synthesis of Dendron-Like/Dendron-Like Block
ꢂ
8
1
Copolymers PCL8 -b-PBLG (n 5 1, 2, and 4)
n
octoate as catalyst at 130 C (PCL , 87.7% yield). H NMR
2
0
20
8
20
(
CDCl3) of PCL :
d
(ppm)
¼
4.00ꢃ4.12 (m, 320H,
From the synthetic viewpoint, the dendron-like/dendron-
like poly(e-caprolactone)-b-poly(c-benzyl-L-glutamate) (PCL-
COCH CH CH CH CH O), 3.59ꢃ3.68 (t, 16H, CH OH), 3.39ꢃ3.47
2
2
2
2
2
2
DENDRITIC POLYMERS, LIU AND DONG
3493

JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
b-PBLG) block copolymers with asymmetrical topology can
be designed by utilizing the well-known divergent and con-
vergent methods, and the ring-opening polymerization
1
–18
(
ROP).
Herein, the dendron-like/dendron-like block
8
n
copolymers PCL -b-PBLG (both the subscript and the
20
superscript denote the degree of polymerization and the
branch number, respectively; n ¼ 1, 2, and 4) were for the
first time synthesized by combining controlled ROP of e-cap-
rolactone (CL), click chemistry for the propargyl focal point
transformation into dendrons having primary amine periph-
ery, and the ROP of c-benzyl-L-glutamate N-carboxyanhydride
(
BLG-NCA), as shown in Scheme 1. First, the dendron-like
8
propargyl focal point PCL20 with eight branches was synthe-
sized by the controlled ROP of CL monomer using a propar-
gyl focal point PAMAM typed dendron as initiator according
to our previous publication, and its actual polymer molecu-
lar weight could be easily determined by H NMR spectros-
2
2
1
copy [Fig. 1(A)]. Second, the azido focal point PAMAM typed
dendrons Dm with primary amine terminal groups (D , m ¼
m
0, 1, and 2) were designed and synthesized using azidopro-
pylamine as an azido focal point according to the divergent
4
7
synthetic procedure, as shown in Scheme 1A. The den-
1
drons Dm were fully characterized by H NMR, FT-IR, and MS
(
see Experimental Section), which demonstrates that they
are pure for the following click reaction. The propargyl focal
point PCL8 precursor was then click conjugated with the
20
azido focal point Dm to produce primary amine-terminated
8
8
20
m
PCL -dendrons (PCL -D , Scheme 1B). FT-IR is a simple
2
0
and useful tool to verify the click conjugation and the pres-
8
20
ence of both PCL and Dm components in the purified PCL -
Dm (Fig. 2). The propargyl focal point (i.e., alkyne group)
8
ꢃ1
within dendron-like PCL20 precursor at about 2098 cm
8
completely disappeared within PCL -D , suggesting that the
20
m
click reaction is nearly quantitative within the error of FT-IR
1
8
method. Moreover, H NMR spectra of PCL -D
m
confirmed
2
0
FIGURE 1 H NMR spectra of PCL (A) and PCL 28 0-D0 (B).
1
8
that the PCL8 precursor was successfully coupled with azido
20
2
0
FIGURE 2 FT-IR spectra of PCL8 pre-
20
8
2
cursor and PCL 0-D
m
macroinitiators.
3494
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

ARTICLE
8
2
n
TABLE 1 Synthesis of Dendron-Like/Dendron-Like PCL 0-b-PBLG (n 5 1, 2, and 4) Block Copolymers with Asymmetrical Topology
a
b
c
c
b
b
d
Entry
PCL8 -b-PBLG1
3
M
n,NMR
M
n,GPC
M
w
/M
n
M
n,PCL
M
n,PBLG
Yield
20,800
24,480
25,500
35,430
42,610
14,110
17,350
18,330
26,570
30,780
1.51
1.58
1.63
1.45
1.62
c
2,260
2,260
2,260
2,260
2,260
660
67.8%
85.2%
75.0%
75.3%
71.4%
2
0
PCL8 -b-PBLG1
3,720
2,190
3,070
4,820
2
0
17
PCL8 -b-PBLG2
2
0
10
PCL8 -b-PBLG4
2
0
14
PCL8 -b-PBLG4
2
0
22
a
Both the subscript and the superscript numbers represent the degree
w n
Both molecular weight (Mn,GPC) and the polydispersity (M /M ) of
of polymerization and the branch number of PCL and PBLG blocks,
copolymers were determined by GPC.
d
respectively.
Yield ¼ Wcopolymer/[(WmonomerꢃWmonomer/MmonomerꢁMCO2) þ Wmacroinitiator].
b
M
n,NMR, Mn, PCL, and Mn,PBLG denote the molecular weights of copoly-
1
mers and the related blocks determined by H NMR (e.g., Fig. 4).
8
focal point D . Compared with the PCL precursor, the rep-
due, those at 2.42 ꢃ 2.37 and 2.05 ꢃ 1.98 ppm assignable
to the methylene groups (ꢃCH CH ꢃCOOBz), and those at
m
1
20
8
2
resentative H NMR spectrum of PCL -D0 clearly shows
0
2
2
that new signals at about 1.85 ppm (a) typical of methene
proton assignable to D0 appeared, and the original methyl-
ene peak adjacent to alkyne shifted down to 3.74 ppm (a ),
which is indicative of the occurrence of triazole ring [Fig.
(B)]. Taken together, these results indicate that the propar-
4.36 ꢃ 4.19 ppm assignable to the backbone (ꢃCHꢃ) of
PBLG, and the typical PCL proton signals. Note that the
degree of polymerization of PBLG within these copolymers
can be precisely calculated by the integral ratio of proton e
to proton i or g. Moreover, FT-IR spectra confirmed the pres-
ence of both PCL and PBLG components in these block
copolymers. As shown in Figure 5, the block copolymers ex-
0
1
8
gyl focal point PCL2 precursor was quantitatively trans-
formed into PCL -D by the click conjugation with the azido
0
8
2
0
m
ꢃ1
focal point Dm.
hibit the strong amide I bands at 1650 and 1625 cm , and
ꢃ1
amide II bands at 1545 cm for PBLG segments, the distinct
8
The PCL -D with multiple primary amine groups were fur-
ther used as the macroinitiators for the ROP of BLG-NCA
monomer to produce the targeted asymmetrical block
2
0
m
ꢃ1
ꢃ1
stretching bands at 2946 cm (CH) and 1727cm (C¼O) for
ꢃ1
PCL block, and the broad absorption at 3200 – 3600 cm for
n
the PBLG backbone (NH) and the PAMAM dendrons (NH and
8
copolymers PCL -b-PBLG , and the detailed results are com-
2
0
NH ). Taken together, these results convincingly demonstrated
8
2
piled in Table 1. Compared with that of the original PCL20
precursor, the elution peak of these block copolymers shifted
toward a lower elution time region coupled with a moderate
polydispersity, demonstrating the successful synthesis of the
purified block copolymers (Fig. 3).
that dendron-like/dendron-like PCL-b-PBLG block copolymers
with asymmetrical topology were successfully synthesized by
combining ROP and CuAAC, as shown in Scheme 1.
As the PBLG with different chain length assumes a-helix
and/or b-sheet conformations, which characteristically
presents the vibrational peaks assignable to the amide I
As a representative example (Fig. 4 and Supporting Informa-
1
8
1
17
tion S1), the H NMR spectrum of PCL -b-PBLG block co-
2
0
ꢃ1
ꢃ1
ꢃ1
band at ꢄ1650 cm
and amide II band at ꢄ1550 cm
,
,
polymer clearly show the typical PBLG proton signals at 7.34
ꢃ 7.14 and 5.08 ꢃ 4.87 ppm assignable to the benzyl resi-
ꢃ1
and the amide bands at ꢄ1630 cm
and ꢄ1530 cm
FIGURE 3 The GPC traces of PCL precursor and PCL8 -b-
8
2
0
20
n
FIGURE 4 H NMR spectrum of PCL -b-PBLG1
1
8
PBLG block copolymers.
.
2
0
17
DENDRITIC POLYMERS, LIU AND DONG
3495

JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 5 FT-IR spectra of PCL80-
2
n
b-PBLG block copolymers.
2
4,25,41
PBLG1 and PCL -b-PBLG mainly assumed an a-helix con-
8
4
respectively.
Thus, the secondary conformation of
17 20 22
PBLG segment within these block copolymers can be easily
characterized by FT-IR. As shown in Figure 5, it can be
formation, while both a-helix and b-sheet conformations
8
2
8
4
existed within PCL -b-PBLG and PCL -b-PBLG . Note that
2
0
10
20
14
8
8
1
observed that the longer PBLG segment within PCL -b-
the shorter PBLG segment within PCL -b-PBLG mainly pre-
20 3
20
sented a b-sheet conformation. These results indicate that the
secondary conformation of PBLG within copolymers can be
tuned by changing the PBLG chain length, which is consistent
1
7,18,24,25,41
with that reported in literature.
This result can be
further clarified by the following DSC and WAXD analyses.
DSC and WAXD Analyses
The PBLG with a long chain length often shows a liquid crys-
talline phase transition with a small endothermic enthalpy,
which is indicative of its conformational transition from 7/2
2
4,25,41
a-helix to 18/5 a-helix.
Thus, the thermal behavior and
conformation of both PCL and PBLG segments can be charac-
8
1
3
terized by DSC (Fig. 6 and Table 2). As for PCL -b-PBLG
2
0
with shorter PBLG segment, the maximal melting temperature
ꢂ
(
T
m
) of PCL segment was given at T
m
¼ 50.9 C, and no liquid
crystalline phase transition temperature (T ) of PBLG was
LC
discerned. However, for the other block copolymers with
TABLE 2 The Melting and Crystallization Properties of PCL80-b-
2
n
PBLG (n 5 1, 2, and 4) Block Copolymers
a
b
c
T
m, PCL
ꢂ
T
LC,PBLG
ꢂ
DH
m
d
Entry
( C)
( C)
(J/g)
c
X (%)
8
1
PCL 0-b-PBLG
50.9
48.0
50.0
50.2
47.6
ꢃ
54.5
42.6
45.4
29.8
3.0
39.0
30.5
32.5
21.3
2.1
2
3
PCL -b-PBLG1
8
105.9
2
0
17
PCL -b-PBLG2
8
95.8
2
8
0
10
PCL -b-PBLG4
96.5
2
0
14
PCL -b-PBLG4
8
109.1
2
0
22
a
T
m, PCL denotes the maximal melting temperature of PCL in the sec-
ond heating run.
b
T
LC,PBLG denotes the liquid crystalline phase transition temperature of
PBLG in the first heating run.
c
DH
m
denotes the melting enthalpy of PCL block in the second heating
run.
8
2
n
FIGURE 6 DSC curves of PCL 0-b-PBLG copolymers in the first
d
X denotes the degree of crystallinity of PCL block within these
c
copolymers, where Xc ¼ DHm/DH0
, DH0
¼ 139.6 J/g.
heating run (A) and in the second heating run (B), respectively.
m;PCL
m;PCL
3496
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA

ARTICLE
longer PBLG segment, the TLC with a small and broad endo-
ꢂ
thermic enthalpy could be observed at about 96–109 C, sug-
gesting at least a partial a-helical conformation for PBLG
block. Note that the TLC of PBLG slightly increased with
increasing the PBLG chain length, and the liquid crystalline
phase transition process was irreversible [Fig. 7(B)]. In addi-
tion, the liquid crystallinity (LC) of PBLG was characterized
by polarized optical microscopy (POM), as shown in Support-
ing Information S2, which demonstrated that the LC phase of
ꢂ
PBLG segment mainly occurred at about 120 C. Moreover,
both the Tm and the degree of crystallinity (X ) of PCL block
c
within copolymers decreased with increasing the PBLG
branches and/or the chain length, demonstrating that the
crystallinity of PCL block was progressively suppressed by
PBLG block.
As shown in Figure 8, all the block copolymers exhibited the
ꢃ1
crystalline diffraction peaks at about 1.51 and 1.68 Å for
8
2
n
FIGURE 8 WAXD patterns of PCL 0-b-PBLG copolymers.
the PCL block, while the diffraction intensity of PCL block was
progressively attenuated with increasing the PBLG branches
and/or the chain length. This result is in good agreement
8
1
3
with that determined by DSC. Moreover, PCL -b-PBLG
20
ꢃ1
presents a diffraction peak at about 0.39 Å , suggesting a b-
2
4,25,41
sheet conformation of PBLG segment.
However, the dif-
ꢃ1
fraction peak gradually shifted to about 0.45 Å
with the
increasing PBLG chain length, indicating an a-helical confor-
8
4
22
mation of PBLG segment within PCL -b-PBLG . These results
2
0
are consistent with the above FT-IR and DSC analyses.
CONCLUSIONS
8
n
A new class of dendron-like/dendron-like PCL -b-PBLG
2
0
(
n ¼ 1, 2, and 4) block copolymers with asymmetrical topol-
ogy was successfully synthesized by combining CuAAC and
ROP. The dendron-like propargyl focal point PCL8 precursor
20
with eight branches was click conjugated with azido focal
8
point PAMAM dendrons to generate the PCL -D with mul-
2
0
m
tiple primary amine groups, which were then used as macro-
initiators for the ROP of BLG-NCA monomer to produce the
targeted asymmetrical block copolymers. Both the maximal
melting temperature and the degree of crystallinity of PCL
block within copolymers decreased with increasing the PBLG
branches and/or the chain length, demonstrating that the
crystallinity of PCL block was progressively suppressed by
PBLG block. Meanwhile, the PBLG block within copolymers
progressively transformed from b-sheet to a-helical confor-
mation with increasing the PBLG chain length. These results
were concomitantly confirmed by FT-IR, DSC, and WAXD
techniques. Importantly, this study establishes a versatile
strategy for the synthesis of biodegradable and biomimetic
block copolymers with asymmetrical dendritic topology.
The authors are grateful for the financial support of National
Natural Science Foundation of China (20874058 and 21074068)
and Shanghai Leading Academic Discipline Project (B202).
REFERENCES AND NOTES
ꢂ
ꢂ
1 Wurm, F.; Frey, H. Prog Polym Sci 2011, 36, 1–52.
FIGURE 7 Expanded regions (60 C–140 C) of DSC curves of
PCL 82 0-b-PBLG copolymers in the first heating run (A) and in
the second heating run (B), respectively.
n
2 Wilms, D.; Stiriba, S. E.; Frey, H. Acc Chem Res 2010, 43,
129–141.
DENDRITIC POLYMERS, LIU AND DONG
3497

JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
3
4
Franc, G.; Kakkar, A. K. Chem Soc Rev 2010, 39, 1536–1544.
Carlmark, A.; Hawker, C. J.; Hult, A.; Malkoch, M. Chem Soc
26 Iha, R. K.; Wooley, K. L.; Nystrom, A. M.; Burke, D. J.; Kade,
M. J.; Hawker, C. J. Chem Rev 2009, 109, 620–5686.
Rev 2009, 38, 352–362.
Rosen, B. M.; Wilson, C. J.; Wilson, D. A.; Peterca, M.; Imam,
M.; Percec, V. Chem Rev 2009, 109, 6275–6540.
27 Meldal, M.; Tornøe, C. W. Chem Rev 2008, 108, 2952–3015.
5
28 Johnson, J. A.; Finn, M. G.; Koberstein, J. T.; Turro, N. J.
Macromol Rapid Commun 2008, 29, 1052–1072.
6
7
8
9
Tomalia, D. A. Prog Polym Sci 2005, 30, 294–324.
29 Le Droumaguet, B.; Velonia, K. Macromol Rapid Commun
2
008, 29, 1073–1089.
Liang, C.; Fr e´ chet, J. M. J. Prog Polym Sci 2005, 30, 385–402.
Gao, C.; Yan, D. Prog Polym Sci 2004, 29, 183–275.
Calderon, M.; Quadir, M. A.; Sharma, S. K.; Haag, R. Adv
3
0 Hawker, C. J.; Wooley, K. L. Science 2005, 309, 1200–1205.
3
1 Hoyle, C. E.; Bowman, C. N. Angew Chem Int Ed 2010, 49,
1
540–1573.
Mater 2010, 22, 190–218.
3
2 Hoyle, C. E.; Lowe, A. B.; Bowman, C. N. Chem Soc Rev
10 intzer, M. A.; Simanek, E. E. Chem Rev 2009, 109, 259–302.
2
010, 39, 1355–1387.
11 Wolinsky, J. B.; Grinstaff, M. W. Adv Drug Deliv Rev 2008,
3
3 Kade, M. J.; Burke, D. J.; Hawker, C. J. J Polym Sci Polym
60, 1037–1055.
Chem 2010, 48, 743–750.
12 Svenson, S.; Tomalia, D. A. Adv Drug Deliv Rev 2005, 57,
3
3
3
4 Lowe, A. B. Polym Chem 2010, 1, 17–36.
2
106–2129.
5 Hoogenboom, R. Angew Chem Int Ed 2010, 49, 3415–3417.
6 Jiang, X.; Vogel, E. B.; Smith, M. R., III; Baker, G. L. Macro-
13 Couet, F.; Rajan, N.; Mantovani, D. Macromol Biosci 2007, 7,
701–718.
molecules 2008, 41, 1937–1944.
7 Riva, R.; Schmeits, S.; J e´ r oˆ me, C.; J e´ r oˆ me, R.; Lecomte, P.
Macromolecules 2007, 40, 796–803.
1
4 Schlaad, H. Adv Polym Sci 2006, 202, 53–73.
3
15 Klok, H. A.; Lecommandoux, S. Adv Polym Sci 2006, 202,
75–111.
3
8 Xu, N.; Lu, F. Z.; Du, F. S.; Li, Z. C. Macromol Chem Phys
16 Mintzer, M. A.; Grinstaff, M. W. Chem Soc Rev 2011, 40,
2
007, 208, 730–738.
173–190.
3
9 Sun, X. L.; Stabler, C. L.; Cazalis, C. S.; Chaikof, E. L. Biocon-
1
1
1
7 Osada, K.; Kataoka, K. Adv Polym Sci 2006, 202, 113–153.
8 Gauthier, M. A.; Klok, H. A. Chem Commun 2008, 2591–2611.
9 Zhang, G.; Zhang, R.; Wen, X.; Li, L.; Li, C. Biomacromole-
jugate Chem 2006, 17, 52–57.
4
0 Parrish, B.; Breitenkamp, R. B.; Emrick, T. J Am Chem Soc
2
005, 127, 7404–7410.
cules 2008, 9, 36–42.
0 Sun, J.; Deng, C.; Chen, X. S.; Yu, H. J.; Tian, H. Y.; Sun, J.
R.; Jing, X. B. Biomacromolecules 2007, 8, 1013–1017.
1 Li, Y.; Cui, L.; Li, Q.; Jia, L.; Xu, Y.; Fang, Q.; Cao, A. Bioma-
cromolecules 2007, 8, 1409–1416.
4
1 You, Y.; Chen, Y.; Hua, C.; Dong, C. M. J Polym Sci Polym
2
Chem 2010, 48, 709–718.
4
2 Chen, Y.; Pang, X. H.; Dong, C. M. Adv Funct Mater 2010,
2
2
0, 579–586.
4
3 Chen, Y.; Dong, C. M. J Phys Chem B 2010, 114, 7461–7468.
22 Hua, C.; Peng, S. M.; Dong, C. M. Macromolecules 2008, 41,
6686–6695.
44 Sun, L.; Sun, L. J.; Zhu, M. Q.; Dong, C. M.; Wei, Y. J Polym
Sci Polym Chem 2010, 48, 4583–4593.
23 Yang, Y.; Hua, C.; Dong, C. M. Biomacromolecules 2009, 10,
2310–2318.
45 Liu, W.; Dong, C. M. Macromolecules 2010, 43, 8447–8455.
24 Hua, C.; Dong, C. M.; Wei, Y. Biomacromolecules 2009, 10,
46 Sun, L.; Yang, Y.; Dong, C. M.; Wei, Y. Small 2011, 7,
1140–1148.
401–406.
25 Peng, S. M.; Chen, Y.; Hua, C.; Dong, C. M. Macromolecules
47 Lee, J. W.; Kim, J. H.; Kim, B. K.; Kim, J. H.; Shin, W. S.;
2009, 42, 104–113.
Jin, S. H. Tetrahedron 2006, 62, 9193–9200.
3498
WILEYONLINELIBRARY.COM/JOURNAL/JPOLA