Synthesis, self-assembly, fluorescence, and thermosensitive properties of star-shaped amphiphilic copolymers with porphyrin core

Article abstract of DOI:10.1002/pola.24665

Star-shaped amphiphilic poly(ε-caprolactone)-block-poly(oligo(ethylene glycol) methyl ether methacrylate) with porphyrin core (SPPCL-b-POEGMA) was synthesized by combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (AT

Full text of DOI:10.1002/pola.24665

Synthesis, Self-Assembly, Fluorescence, and Thermosensitive Properties
of Star-Shaped Amphiphilic Copolymers with Porphyrin Core
TIANBIN REN,1,2 AN WANG,1 WEIZHONG YUAN,1,2 LAN LI,1 YUE FENG1
1Institute of Nano and Bio-Polymeric Materials, School of Materials Science and Engineering,
Tongji University, Shanghai 200092, People’s Republic of China
2Key Laboratory of Advanced Civil Engineering Materials, Ministry of Education, Shanghai 200092, People’s Republic of China
Received 29 December 2010; accepted 3 March 2011
DOI: 10.1002/pola.24665
Published online 28 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Star-shaped amphiphilic poly(e-caprolactone)-block-
poly(oligo(ethylene glycol) methyl ether methacrylate) with
porphyrin core (SPPCL-b-POEGMA) was synthesized by combi-
nation of ring-opening polymerization (ROP) and atom transfer
radical polymerization (ATRP). Star-shaped PCL with porphyrin
core (SPPCL) was prepared by bulk polymerization of e-capro-
lactone (CL) with tetrahydroxyethyl-terminated porphyrin initia-
tor and tin 2-ethylexanote (Sn(Oct)2) catalyst. SPPCL was
converted into SPPCLBr macroinitiator with 2-bromoisobutyryl
bromide. Star-shaped SPPCL-b-POEGMA was obtained via
ATRP of oligo(ethylene glycol) methyl ether methacrylate
(OEGMA). SPPCL-b-POEGMA can easily self-assemble into
micelles in aqueous solution via dialysis method. The forma-
tion of micellar aggregates were confirmed by critical micelle
formation concentration, dynamic light scattering, and trans-
mission electron microscopy. The micelles also exhibit
property of temperature-induced drug release and the lower
critical solution temperature (LCST) was 60.6 ꢀC. Furthermore,
SPPCL-b-POEGMA micelles can reversibly swell and shrink in
response to external temperature. In addition, SPPCL-b-
POEGMA can present obvious fluorescence. Finally, the con-
trolled drug release of copolymer micelles can be achieved by
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the change of temperatures.
2011 Wiley Periodicals, Inc.
J Polym Sci Part A: Polym Chem 49: 2303–2313, 2011
KEYWORDS: fluorescence; self-assembly; thermosensitive
INTRODUCTION In recent decades, considerable interests
concerning with biodegradable polymers, especially the stim-
uli-responsive polymeric micelles prepared form amphiphilic
block copolymers,1–3 have been aroused by the development
in pharmaceutical and biomedical fields. In aqueous solu-
tions, amphiphilic copolymers can self-assemble into micelles
with core-shell structure due to the aggregation of hydropho-
bic blocks into core and the dispersion of hydrophilic seg-
ments as corona. Some biodegradable materials, particularly
polyesters have their own unique properties such as bio-
degradability, biocompatibility, and permeability.4 For the
core-shell type of polymeric micelles, PCL is usually adopted
as hydrophobic blocks of amphiphilic copolymers, function-
ing as the sustained release reservoir of insoluble or unsta-
ble small molecules.5,6 Meanwhile, outer hydrophilic chains
composed of some stimuli-responsive hydrophilic polymers,
render the micelles enable to exhibit not only improved
water solubility and micelle stability, but also the responsive-
ness to external stimuli, such as temperature, light, ionic
strength, or pH value.
to conjugate functional molecules into polymeric structures,
giving polymers more complex properties inherited from the
functional moieties. Meanwhile, most of them are star-
shaped polymers with multiarmed chains connected to a
core via polymer linking or living polymerization. Further-
more, unlike amphiphilic polymeric micelles based on
liner, grafted polymers7–12 or dendrimers, star-shaped
amphiphilic polymers13–25 not only have well-defined and
flexible architecture, controllable surface functionality, pro-
viding unique properties such as high surface reactivity and
low hydrodynamic radius, but also can be easily prepared,
while dendrimers suffer from complicated preparation pro-
cess. With the development of polymerization techniques,
the star-shaped polymers can be easily obtained by ‘‘living"/
controlled polymerization techniques containing reversi-
ble addition fragmentation chain transfer polymeriza-
tion (RAFT),26–28 atom transfer radical polymerization
(ATRP),29–35 and their combinations with ring-opening poly-
merization (ROP).36,37 For instance, Ranganathan et al.
reported the synthesis of star copolymers in a sequential
way of RAFT and ATRP,38 whereas Yuan et al. synthesized
dendritic star-block copolymers via a combination of ROP
and ATRP.39
Apart from these stimuli-responsive chains such as PNIPAM
or PDEAEMA, which can provide a wide variety of polymers
with functionality of responsiveness, much attempt was paid
Correspondence to: W. Yuan (E-mail: yuanwz@tongji.edu.cn)
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Journal of Polymer Science Part A: Polymer Chemistry, Vol. 49, 2303–2313 (2011) 2011 Wiley Periodicals, Inc.
PROPERTIES OF STAR-SHAPED AMPHIPHILIC COPOLYMERS, REN ET AL.
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JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
For thermosensitive polymers, lower critical solution temper-
ature (LCST)40–42 plays a key role in the applications of drug
delivery, smart bioactive surfaces, and catalyst. Recently,
ATRP of olig(ethylene glycol) methacrylates (OEGMA) has
attracted increasing interests because of its adjustable LCST
of a wide range by varying length of the ethylene oxide side
chain. Besides its novel thermoresponsive solubility of PEG
chains, these grafted PEG brushes provide external proper-
ties including improved solubility, biocompatibility, nontoxic-
ity, and protein-resistance.41,43,44 This work focuses on the
stimuli responsive porphyrin-bearing star polymers, to
enhance the controlled release capability of their self-
assembled micelles when encapsulating guest molecules, and
to improve the protein-resistance of the micelle applicable in
biomedical filed.
Namely, tetrahydroxyethyl-terminated porphyrin was sued as
an imitator for the ROP of CL to prepare star-shaped poly(e-
caprolactone) with porphyrin core (SPPCL). Then, SPPCLBr
macroinitiator was obtained by the reaction of SPPCL with
2-bromoisobutyryl bromide. SPPCL-b-POEGMA was synthe-
sized by ATRP of OEGMA with SPPCLBr macroinitiator. In
addition, the self-assembly behavior, thermosensitivity, criti-
cal micelle formation concentration (CMC), fluorescence and
drug encapsulation of SPPCL-b-POEGMA were investigated
with UV-visible spectrophotometer (UV-vis), transmission
electron microscopy (TEM), and dynamic light scattering
(DLS) spectrophotometer.
EXPERIMENTAL
Materials
To obtain more properties such as fluorescence,45–47 mole-
cule recognizability,48–50 catalytic capability,51,52 therapy
capability,53,54 and so forth, we conjugated porphyrin as the
core of the star-shaped polymers. Compared with other star
polymers with core molecules including trimethylolpropane,
calixarenes, cyclodextrins and so on,44,55–58 porphyrin, as
one of the important photosensitizers, was attractive because
of its promising photoelectric functions for various applica-
tions containing light-harvesting materials,59,60 optoelec-
tronic devices,61 but also its novel therapeutic capacities
such as tumor targeting and photodynamic therapy62,63 for
biomedical application. However, p-stacking and hydrophobic
interactions in aqueous media leads to the aggregation of
porhyrin and the resulting reduce in effectiveness of photo-
dynamic effect. Herein, we report a porphyrin-conjugated
polymeric micelle, in order to enhance the stability via the
isolation of porphyrin molecules in PCL blocks, meanwhile
to introduce fluorescence and therapeutic properties to
micelle. Moreover, because of the p-stacking, prohyrin-conju-
gated PCL moiety may has advantage in the effectiveness of
encapsulating p-contained hydrophobic molecules. Previous
reports on the combination between phorphyrin and star
polymers are steadily increasing. Fre´chet64,65 and Dong66
reported a functional porphyrin-cored polymeric shell based
on ROP of CL. Holder67 and Cornelissen68 synthesized a
series of star polymers with porphyrin core using ATRP.
These porphyrin-cored polymers lack water solubility and
therefore are limited in further application. Mineo and
Migliardo et al. reported water soluble porphyrin with PEO
arms.69,70 But little work has been conducted with thermo-
sensitive amphiphilic copolymer as arms. Dichtel71 et al.
reported a porphyrin-cored amphiphilic diblock polymer
using thermosensitive OEGMA as hydrophilic monomer. How-
ever, neither the inner chain nor the outer synthesized by
ATRP are degradable. To our knowledge, there are no report
on the star-shaped porphyrin-conjugated degradable and
thermosensitive micelles prepared by the combination of
ROP and ATRP.
Dichloromethane (CH2Cl2), dimethylformamide (DMF), and
CL (Acros Organic) were purified with CaH2 by vacuum dis-
tillation. Tin 2-ethylhexanoate (Sn(Oct)2; Aldrich) and pyrrole
(Aladdin-Reagent, Shanghai) was distilled under reduced
pressure before use. Oligo(ethylenglyco)-methylether methac-
rylate (OEGMA, 300 g/mol, Aldrich) was passed through a
basic alumina column to remove inhibitor before use. Cop-
per(I) bromide (CuBr, Aldrich) was purified by acetic acid
and then with methanol, stored under argon. Nitrobenzene,
4-hydroxybenzaldehyde, 2-bromoethanol, 18-crown-6, and
other chemicals were obtained from Sinopharm Chemical
Regent Company (SCRC) were of analytical grade and were
used as received. 2-Bromoisobutyryl bromide (Aldrich) was
distilled under reduced pressure.
Measurements
1H NMR
1H NMR data was obtained by a Bruker DMX-500 NMR spec-
trometer with CDCl3 or DMSO-d6 as solvent at room temper-
ature. The chemical shifts were relative to tetramethsilane at
d ¼ 0 ppm for protons.
Gel Permeation Chromatography
Gel permeation chromatography (GPC) measurements were
conducted on a gel permeation chromatographic system,
equipped with a Waters 150C separations module and a
Waters differential refractometer. The molecular weight and
molecular weight distributions were calibrated against poly-
styrene standards, with THF as the eluent at a flow rate of
1 mL/min.
Fluorescence
Fluorescence spectra were performed on a Fluorolog-2 spec-
trofluorometer (Spex Industries, Edison, NJ) under the con-
trol of the dedicated SPEX DM3000F software. Fluorescence
scans were performed at room temperature in the range of
500–800 nm using increment of 1 nm, and an excitation
wavelength of 413 nm, which is at the absorption peak maxi-
mum for free porphyrin. Samples were dissolved in DMF at
the molar concentration of 2 ꢁ 10ꢂ5 mol/L.
In this article, novel and well-defined star-shaped amphi-
philic poly(e-caprolactone)-block-poly(oligo(ethylene glycol)
methyl ether methacrylate) with porphyrin core (SPPCL-b-
POEGMA) was synthesized by combination of ROP and ATRP.
Optical Transmittances
The optical transmittances of polymer aqueous solution (2
mg/mL, distilled water was used as the solvent) at various
temperatures were measured at a wavelength of 480 nm on
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ARTICLE
a UV-visible spectrophotometer (Lambda 35, PerkinElmer).
The temperature of the sample cell was thermostatically con-
trolled using an external superconstant temperature bath.
The solutions were equilibrated for 10 min at each meas-
uring temperature. The LCST value of the polymer solution
was defined as the temperature producing a 50% decrease
in optical transmittance.
After the evaporation of solvent, the crude product was dis-
solved in THF, precipitated in cold diethyl ether, filtered, and
dried to yield (70%) a purple solid.
1H NMR (DMSO-d6, d, ppm): 8.86 (s, 8H, b-pyrrole-H), 8.12
(d, 8H, m-Ar-H), 7.39 (d,8H, o-Ar-H), 5.01 (s, 4H,OH), 4.30
(t, 8H, OCH2CH2), 3.92 (t,8H, HOCH2), ꢂ2.87 (s, 2H, NH).
Synthesis of SPPCL
TEM
The tetrahydroxyethyl-terminated porphyrin as a functional
moiety allows the initiation for ROP of CL to afford the
desired star-shaped polymers. The polymerization was
carried out in the bulk using catalytic amounts of Sn(Oct)2,
as described in the literature.40 A typical polymerization was
carried out as follows. The dried porphyrin initiator (0.61 g,
0.71 mmol), a catalytic amount of Sn(Oct)2 ([CL]/[Sn(Oct)2]
¼ 100) in dry toluene, CL (13 g, 113.6 mmol) and a dry
magnetic stirring bar were added into a flame-dried poly-
merization tube. The mixture was bubbled with argon for
15 min to remove dissolved oxygen, and then evacuating-
refilling process was repeated for three times before the po-
lymerization was carried out at 120 ꢀC under argon atmos-
phere with stirring for 24 h. After cooling down to room
temperature, the reaction mixture was dissolved with
CH2Cl2, and precipitated in methanol. The purified polymer
was dried in a vacuum until constant weight to obtain green
fine powders (91% yield).
Samples for TEM images were taken on a Tecnai-12 Bio-
Twin transmission electron microscope (FEI, Netherlands)
operating at 120 kV. A small drop from the aqueous copoly-
mers solution (200 mg/L, filtered through a 450 nm filter)
was deposited onto carbon-coated copper TEM grid. The
excess of copolymer solution was wiped off with a filter
paper, and the grid was dried under ambient atmosphere
for 1 h.
DLS
The hydrodynamic diameter and the particle size distribu-
tion of the copolymer micelles were determined using a DLS
spectrophotometer (DLS, Autosizer 4700, Malvern) equipped
with an argon ion laser operating at 480 nm with a fixed
scattering angle of 90ꢀ. All samples for DLS were redispersed
in deionized water (1 mg/mL), sonicated for 30 s in an ice/
water bath, and filtered through a 450 nm filter.
CMC
Mn,NMR ¼ 15500, Mn,GPC ¼ 13900, Mw/Mn ¼ 1.40. 1H NMR
(CDCl3, d, ppm): 9.16 (s, 8H, b-pyrrole-H), 8.18 (d, 8H, m-Ar-
H), 7.35 (d, 8H, o-Ar-H), 4.65 (t, 8H, OCH2CH2), 4.51 (t, 8H,
HO-CH2), 4.06 (t, CH2O in PCL), 3.65 (t, terminal CH2O in
PCL), 2.31 (t, COCH2 in PCL), 1.65 (m, CH2 in PCL), 1.38 (m,
CH2 in PCL).
CMC of SPPCl-b-POEGMA copolymer in aqueous solution was
studied on
a LS55 luminescence spectrometer (Perkin-
Elmer) and pyrene was used as a hydrophobic fluorescent
probe. 0.2 mL of pyrene solutions (6 ꢁ 10ꢂ6 M in acetone)
were added to containers, and the acetone was allowed to
evaporate. Two milliliter of copolymer aqueous solutions at
different concentrations were then added to the containers
containing the pyrene residue. Each aqueous sample solu-
tions with various polymer concentrations from 2 ꢁ 10ꢂ3 to
0.25 mg/mL contained the same concentration (6 ꢁ 10ꢂ7
M) of excess pyrene residue. Emission wavelength was
carried out at 390 nm, and excitation spectra were recorded,
ranging from 300 to 360 nm. The excitation and emission
bandwidths were 5 and 5 nm, respectively. From the pyrene
excitation spectra, the intensity ratio I342 was analyzed as a
function of the polymer concentration. A CMC value was
determined from the intersection of the tangent to the curve
at the inflection with the horizontal tangent through the
points at low concentration.
Synthesis of SPPCLBr
A typical example is given below. SPPCL (5 g, 0.289 mmol)
was dissolved in anhydrous CH2Cl2 (125 mL) under stirring.
To this solution was added triethylamine (351 mg, 3.47
mmol) under argon at room temperature. The mixture was
stirred and cooled to 0 ꢀC with ice bath. Then, 2-bromoiso-
butyryl bromide (789 mg, 3.47 mmol) in anhydrous CH2Cl2
(20 mL) was added dropwise to the mixture within 30 min.
The reaction was stirred for 24 h at room temperature
before the solution was washed with NaHCO3 aqueous
solution (100 mL), and deionized water (100 mL ꢁ 2). The
organic layer was dried overnight with MgSO4. After evapo-
ration of solvent, the resulting product was purified by
precipitating from cold methanol.
Synthesis of Tetrahydroxyethyl-Terminated Porphyrin
Tetrahydroxyethyl-terminated porphyrin was synthesized
from 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphy-
rin (THPP) (prepared according to literature72) and 2-bro-
moethanol according to the literature with minor modifica-
tion.73 Briefly, THPP (1.14 g, 1.68 mmol), K2CO3 (2.91 g) and
18-crown-6 (65 mg) were added to DMF (200 mL). 2-Bro-
moethanol (1.9 g, 15.2 mmol) was added, and the reaction
Mn,NMR ¼ 16300, Mn,GPC ¼ 14400, Mw/Mn ¼ 1.41. 1H NMR
(CDCl3, d, ppm): 9.16 (s, 8H, b-pyrrole-H), 8.18 (d, 8H, m-Ar-
H), 7.35 (d, 8H, o-Ar-H), 4.65 (t, 8H, OCH2CH2), 4.51 (t, 8H,
HOCH2), 4.06 (t, CH2O in PCL), 3.65 (t, terminal CH2O in
PCL), 2.31 (t, COCH2 in PCL), 1.926 (s, (CH3)2CBr), 1.65 (m,
CH2 in PCL), 1.38 (m,CH2 in PCL).
ꢀ
system was vigorously stirred at 140 C overnight under the
Synthesis of SPPCL-b-POEGMA
argon atmosphere. Then, DMF was evaporated and the solid
was dissolved in THF and extracted with deionized water.
The organic layer was obtained by the addition of brine.
Star-shaped SPPCL-b-POEGMA were synthesized by ATRP
of oligo(ethylenglyco)-methylether methacrylate (OEGMA) in
anhydrous DMF with SPPCLBr as macroinitiator. In a general
PROPERTIES OF STAR-SHAPED AMPHIPHILIC COPOLYMERS, REN ET AL.
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JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 1 Synthesis of SPPCL-b-POEGMA
by the combination of ROP and ATRP.
[Color figure can be viewed in the online
issue, which is available at wileyonlinelibrary.
com.]
procedure, SPPCLBr (0.3 g, 0.068 mmol of C-Br), OEGMA
(2.03 g, 6.8 mmol), bpy (46 mg, 0.3 mmol), and anhydrous
DMF (3 mL) were added into a dried flask with a magnetic
stirring bar. The mixture was bubbled with argon for 15 min
to remove dissolved oxygen, and then degassed with three
freeze-evacuate-thaw cycles after purified CuCl (21 mg, 0.15
mmol) was quickly added. The polymerization was per-
formed at 60 ꢀC for 120 min. Then, the experiment was
stopped by exposing the catalyst to air and cooling down to
b-POEGMA4 (50 mg) was dissolved in DMF (10 mL) prior to
dialysis against distilled water for 72 h using a dialysis mem-
brane with a molecular weight cut-off of 8000–12,000
(SCRC, Shanghai). The concentration of the copolymers in
aqueous solution was calculated according to the polymer
weight and the volume of above micelles solution. Desired
micelles concentrations can be adjusted for different charac-
terization by diluting the micelle solution with certain
amounts of deionized water.
0
ꢀC in an ice/water bath. The crude product was dissolved
Drug Loading and In Vitro Drug Release
in THF and passed through a neutral aluminum oxide column
to remove the copper catalysts and subsequently purified by
dialysis against water for 72 h using a dialysis membrane with
a molecular weight cut-off of 8000–12,000 (SCRC, Shanghai).
The water in the resulting polymer aqueous solutions was
removed by azeotropic distillation with ethanol. The crude
products were dissolved in small amounts of CH2Cl2 and pre-
cipitated in methanol. The precipitates were filtered, dried in a
vacuum oven until a constant weight.
Camptothecin (CPT) (4 mg) and SPPCL-b-POEGMA (20mg)
were dissolved in 10 mL of DMF. The solution was put into
a dialysis tube (MWCO: 8000–12000 g/mol, SCRC, Shanghai)
and subjected to dialysis against 1000 mL of distilled water
ꢀ
at 25 C for 24 h. The UV absorbance of the dialysis solution
was used to determine the amount of unloaded CPT (at 365
nm), which was used to calculate the encapsulation effi-
ciency (EE%). The total amount of CPT fed initially in PBS
(10 mM, pH 7.4) solution was 1.9 mg. The EE% is defined as:
SPPCL-b-POEGMA4: Mn,NMR ¼ 81300, Mn,GPC ¼ 67000, Mw/
Mn ¼ 1.34. 1H NMR (CDCl3, d, ppm): 4.06 (t, CH2O in PCL),
3.54–3.70 (CH2CH2O in POEGMA), 3.38 (s, terminal CH3O of
the EG block in POEGMA), 2.31 (t, COCH2 in PCL), 1.53–2.01
(CH2 on the backbone of POEGMA), 1.65 (m, CH2 in PCL),
1.38 (m, CH2 in PCL), 0.56–1.02 (CH3 on the backbone of
POEGMA).
total amount of CPT ꢂ unloaded amount of CPT
EE% ¼
total amount of CPT
ꢁ 100%
The EE% was found to be 47%.
RESULTS AND DISCUSSION
Preparation of SPPCL-b-POEGMA Micelles
Synthesis of SPPCL-b-POEGMA
The star-shaped copolymer micelles in aqueous solution
were prepared by the dialysis method. For instance, SPPCL-
The synthesis procedure of SPPCL and SPPCL-b-POEGMA is
illustrated in Scheme 1. The tetrahydroxyethyl-terminated
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ARTICLE
FIGURE 1 1H NMR spectra of (a) tetrahydroxyethyl-terminated porphyrin in d6-DMSO, (b) SPPCL in CDCl3, (c) SPPCLBr in CDCl3,
and (d) SPPCL-b-POEGMA in CDCl3.
porphyrin was used as initiator to synthesize the SPPCL.
Then, SPPCLBr macroinitiator for the subsequent ATRP of
OEGMA was obtained by the bromoesterification of SPPCL
with 2-bromoisobutyryl bromide. SPPCL-b-POEGMA was
prepared from SPPCL macroinitiator and OEGMA via ATRP.
Figure 1(b) shows the 1H NMR spectrum of SPPCL. Com-
pared with the spectrum of porphyrin initiator seen in
Figure 1(a), not only the corresponding peaks of protons
attributed to porphyrin appear, but also the major peaks
attributed to protons of PCL moiety can be detected at 4.01,
2.32, 1.66, and 1.39 ppm. It demonstrates that the tetrahy-
droxyethyl-terminated porphyrin can initiate the ROP of CL
effectively. The conversion of CL monomer was found to be
90.7%, which was calculated according to the ratio of proton
peaks at 4.01 ppm and 3.65 ppm, the typical signals for
ACH2A and ACH2OH protons on PCL moieties, respectively.
The integration of proton peaks at 9.16 ppm (the b-pyrrole
on prophyrin moiety) is similar to that of 3.65 ppm, indicat-
ing no PCL homopolymer formed during ROP procedure, and
thus the four armed structure containing 36 repeat CL units
on each arm was successfully synthesized. Moreover, proton
signal of b-pyrrole appeared at 8.86 ppm [Fig. 1(a)] shifts to
9.16 ppm [Fig. 1(b)], proton signal of NH at A2.81 ppm dis-
appeared after ROP [Fig. 1(b)], whereas the position of other
protons at 8.12 and 7.39 ppm on prophyrin moiety have no
significant change. This is ascribed to that complexation
between tin ion and porphyrin took place which is consist-
ent with the fact transient green appeared immediately
when adding tin catalyst to mixture, and polymerization did
not undertake in 72 h until the amount of tin ion was raised
to 1.6 times of porphyrin. Comparing to 1H NMR spectrum
of SPPCL in Figure 1(b),
a new peak at 1.93 ppm
corresponding to the methyl protons in the bromoethyl
group (A(CH3)2Br) of the macroinitiator can be detected in
Figure 1(c), revealing that the terminal hydroxyl groups of
PCL have reacted with 2-bromoisobutyryl bromide.
SPPCL-b-POEGMA copolymers were synthesized by ATRP of
OEGMA with SPPCLBr as macroinitiator at 50 ꢀC in DMF
with [OEGMA]:[C-Br]:[CuBr]:[bpy] ¼ 100:1:2.2:4.4. As shown
in Figure 1(d), the peaks attributed to POEGMA block can be
detected clearly. The results of ATRP of OEGMA are listed in
Table 1. The molecular weight of the copolymer determined
1
by H NMR and GPC were all increased with the evolution of
polymerization. The kinetic plot for the ATRP of OEGMA
polymerization was also investigated. The ratio of the
PROPERTIES OF STAR-SHAPED AMPHIPHILIC COPOLYMERS, REN ET AL.
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JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
TABLE 1 Results for ATRP of OEGMA with Star-Shaped SPPCLBr Macroinitiator
Time
Conversiond
(%)
a
b
c
c
Sample
(min)
Mn,th
Mn,NMR
Mn,GPC
Mw/Mn
SPPCL-b-POEGMA1
SPPCL-b-POEGMA2
SPPCL-b-POEGMA3
SPPCL-b-POEGMA4
SPPCL-b-POEGMA5
a
10
20
24,800
29,100
22,700
26,200
48,700
81,300
1,04,400
d
18,800
22,100
43,600
67,000
90,900
2.09
1.68
1.64
1.34
1.23
6.3
9.9
60
53,100
29.9
57.4
76.9
120
180
86,100
1,09,600
Mn.th ¼ Mmonomerꢁ([monomer]/[C-Br])ꢁ4ꢁConversion%þMmacroinitiator
,
Calculated from: [(Wp-Wi)/Wm] ꢁ 100%, where Wp, Wi, and Wm were
the weight of the star-shaped copolymer produced, and the initial
weights of the related macroinitiator and monomer, respectively.
[monomer]/[C-Br] ¼100.
b
Mn,NMR was determined by 1H NMR spectroscopy of star-shaped
copolymer.
c
Mn,GPC and Mw/Mn were determined by GPC analysis with polystyrene
standards. THF used as eluent.
integral areas of the methylene protons at 1.38 ppm in PCL
to that of the methyl protons at 3.38 ppm on POEGMA of
the resulted SPPCL-b-POEGMA copolymer was used to calcu-
late the ratio of PCL and POEGMA in copolymers. As shown
in Figure 2, the semilogarithmic plot of the OEGMA conver-
sion against the reaction time had a linear increase and
crossed near the zero point as expected for a controlled po-
lymerization. The result demonstrates that the first order
kinetics can be maintained under a relatively low conversion
with avoiding the polymeric radical-coupling reactions, sug-
gesting that macroinitiators retained the activity of the bro-
mide at chain terminus during the course of polymerization,
and therefore constant concentration of active species were
available for subsequent reactivation. Here, [M0] and [Mt] are
the initial monomer concentration and the monomer concen-
tration at time t, respectively. It can be seen from Figure 3
that Mn,NMR were increased linearly with time, indicating
that the molecular weight of the star-shaped copolymer
could be manipulated by the control of monomer conversion.
This is attributed to that the star-shaped polymer has a
smaller hydrodynamic volume density in comparison to the
linear polystyrene as a calibration standard for GPC mea-
surement. As shown in Table 1, the complexation of tin ion
can affect not only the ROP of CL, but also the ATRP of
OEGMA, leading to a relatively broad molecular weight dis-
tribution. This may be ascribed to the subsidiary reaction
between Sn(II) and Cu(II). With the aid of oxidation of
Sn(II), the competition from the reduction of Cu(II) may
adversely affect the reverse reaction of ATRP, consequently
increasing the concentration of active species and leading to
a broad distribution.
The GPC traces of SPPCL, SPPCLBr, and SPPCL-b-POEGMA
are shown in Figure 4. It can be seen that the traces are
monomodal, suggesting that no mixture of star and linear
polymers was formed.
UV-Vis and Fluorescence of SPPCL-b-POEGMA
Fluorescence of SPPCL-b-OEGMA was investigated by fluores-
cence spectroscopy. Porphyrin was used as a counterpart
with the concentration of 2 ꢁ 10ꢂ5 mol/L in DMF. The
However, the molecular weights determined by GPC (Mn,GPC
)
were lower than those determined by 1H NMR (Mn,NMR).
FIGURE 2 Semilogarithmic plots of monomer consumption
versus time for the ATRP polymerization of OEGMA using
SPPCLBr as the initiator in DMF.
FIGURE 3 Dependence of Mn and Mw/Mn on time for ATRP of
OEGMA in DMF at 50 ꢀC.
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ARTICLE
tion, consistent with the blue shift of emission bands
appeared in the fluorescence spectra. Furthermore, the inser-
tion of tin ion was again demonstrated by the UV-vis spectra.
As shown in Figure 5, concomitant with the typical Q-band
of free base porphyrin disappearing at 519 nm, both the
SPPCL and SPPCL-b-POEGMA clearly displayed tow Q-bands
at 565 and 605 nm which were attributed to the tin
porphyrin complex. The two spectra were closet to each
other, manifesting tin ion was not replaced by Cu(II) during
ATRP procedure. As a note, no significant reduction of the
fluorescence intensity was found after polymerization, sug-
gesting that SPPCL-b-POEGMA is capable of applications in
fluorescence materials.
Self-Assembly Behavior of SPPCL-b-POEGMA
The micelle formation was studied by fluorescence probe
technique with use of pyrene. Excitation spectra of pyrene in
the SPPCL-b-POEGMA solutions are shown in Figure 6. Con-
comitant with the increase in concentration of copolymer,
there was a growing tendency of fluorescent intensity. It is
worthy to note that intensity curves are closest to each other
at low concentrations, however, obvious growing tendency
only can be found at relatively high concentrations. This is
ascribed to that pyrene preferentially aggregates into the
hydrophobic core of the micelles, allowing the change of the
photophysical properties. The maximum intensity at 342 nm
is plotted against the logarithm of polymer concentration in
Figure 8, indicating the CMC value is around 33.9 mg/L. The
low degree of hydrophobic porpyrin-PCl moiety may result
in such low CMC value.
FIGURE 4 GPC traces of SPPCL, SPPCLBr, and SPPCL-b-
POEGMA4. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]
maximum-excitation wavenumber of porphyrin was 440 nm
according to the exciton spectrum. Figure 5 shows the fluo-
rescence spectra of porphyrin, SPPCLBr, and SPPCL-b-
POEGMA and the typical UV-vis absorption bands of por-
phyrins (Soret-band and Q-bands) and the difference in the
Q-bands between porphyrin and polymers contained porphy-
rin. In the UV-vis spectra, both polymers contained porphy-
rin exhibit red-shifts and decreased number of Q-bands in
comparison to that of porphyrin molecule. The introduction
of tin ion and polymer chains induces distortion in the por-
phyrin plane. As a result, red-shifting in the UV-vis spectra
occurred due to the lack of the expected resonance interac-
TEM was used to investigate the morphology of the micelles.
The micelles of SPPCL-b-POEGMA were prepared in aqueous
solution by dialysis method at room temperature. The typical
TEM image of the micelles of SPPCL-b-OEGMA is shown in
Figure 7. It can be seen that SPPCL-b-POEGMA amphiphilic
copolymers can self-assemble into stable and uniform spheri-
cal micelles. PCL block is hydrophobic and POEGMA block is
FIGURE 5 Absorbance and fluorescent spectra of porphyrin,
SPPCL, and SPPCL-b-POEGMA4 in DMSO solution with the
concentration of 2 ꢁ 10ꢂ5 mol/L. [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com.]
FIGURE 6 Excitation spectra of pyrene at kem ¼ 390 nm with
increasing concentrations of SPPCL-b-POEGMA4 copolymer
and the plots of the intensity at 342 nm vs. log C.
PROPERTIES OF STAR-SHAPED AMPHIPHILIC COPOLYMERS, REN ET AL.
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JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 8 Temperature dependence of micelle size and optical
transmittance at 480 nm for SPPCL-b-POEGMA4 aqueous solu-
tion with the concentration of 2 mg/mL.
50% decrease in optical transmittance. It can be found that
above the LCST, the micelles aggregated together by the driv-
ing force of strong hydrophobic interactions, consistent with
the decrease in optical transmittance and the increase in mi-
cellar size. Figure 9 indicates an enclosed photograph of the
optical transmittance changes. It can be seen that the poly-
meric micelles dispersed in aqueous solution took on clear
and turbidity dispersions respectively during a reversible
cooling and heating cycles. Figure 9 also shows the curve of
optical transmittance as a function of temperature for the
micelle solution of SPPCL-b-POEGMA at the concentration of
2 mg/mL. The solutions were equilibrated for 10 min for
each measuring temperature which were chosen as above
and below LCST. The fluctuating value of transmittance
FIGURE 7 TEM image of SPPCL-b-POEGMA4 micelles in aque-
ous solution (0.2 mg/mL). [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
hydrophilic, so that this amphiphilic copolymer of SPPCL-b-
OEGMA can self-assemble into micelles. It is reasonable that
hydrophobic PCL is in the core of the micelles, whereas the
hydrophilic block is in corona of the micelles. Considering
the CMC value is below the concentration (200 mg/L) for
TEM characterization, the formed micelle should be aggre-
gates from individual molecule. Investigated by DLS, the 45
nm of average diameter and monomodal size distribution of
the sample are consistent with the results studied by TEM.
Thermosensitivity of SPPCL-b-POEGMA
To investigate the thermosensitive property of SPPCL-b-
POEGMA, the LCST was examined by the optical transmit-
tance of a polymeric micelle aqueous solution. Figure 8 rep-
resents the curves of transmittance with the increase of tem-
perature, revealing the temperature dependence of optical
transmittance at 480 nm for the polymer aqueous solution.
It can be seen that during the first step, along with the tem-
perature increasing, the optical transmittance shows a slight
increase, whereas the average diameters determined by DLS
(Fig. 8) exhibit a decreased trend. These results attribute to
the fact that as the temperature is raised, the hydrogen
bonding interaction between the copolymers and water mol-
ecules subsequently moderates in the case of the enhanced
thermal motion of water molecules. Therefore, the outer
hydrophilic chains consequently shrank, which leads to a
smaller diameter of micelles. However, a repulsive force due
to the increased hydrophobicity of micelles causes large
aggregates and an increase in optical transmittance. The op-
tical transmittance decreases drastically with the tempera-
ture ranging from 60 ꢀC to 62 ꢀCconsequently. The LCST
value is found at 60.6 ꢀC, as the temperature producing a
FIGURE 9 Plots of optical transmittance as a function of tem-
perature for SPPCL-b-POEGMA4 aqueous solution with the
concentration of 1 mg/mL (5 min for each temperature, four
heating/cooling cycles between 25 and 65 ꢀC).
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ARTICLE
macroinitiator was obtained by the bromoesterification of
SPPCL with 2-bromoisobutyryl bromide. Subsequently,
SPPCLBr was used as macroinitiator to afford the ATRP of
OEGMA. Investigation shows that SPPCL-b-POEGMA has no
significant reduction in fluorescence intensity when com-
pared with porphyrin in DMSO solution. The conformation of
micellar aggregates self-assembled in aqueous solution was
confirmed by fluorescence spectra, DLS and TEM. The
micelles show thermo-sensitive switching behavior and ex-
hibit the temperature induced drug release profile. There-
fore, SPPCL-b-POEGMA has the potential applications in bio-
medicine and biotechnology fields, such as fluorescent tracer,
dug and catalyst carrier, probe for molecular recognition,
and agents for photodynamic therapy.
The authors gratefully acknowledge the financial support of the
National Natural Science Foundation of China (nos. 20804029
and 30800230) and Shanghai Foundation for Development of
Science and Technology (no. 0852nm03600).
FIGURE 10 Drug release of CPT encapsulated micelle self-
assembled from SPPCL-b-POEGMA4 copolymer.
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that the micelles of SPPCL-b-POEGMA in aqueous solution
are stable. To some extent, the obtained thermosensitive
amphiphilic copolymers possess the combined properties of
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