Synthesis and thermo-/pH- dual responsive properties of poly(amidoamine) dendronized poly(2-hydroxyethyl) methacrylate

Article abstract of DOI:10.1021/ma1000783

The first and second generation poly(amidoamine) dendronized poly(2-hydroxylethyl) methacrylate (PGn-macro (n = 1, 2)) were synthesized by the macromonomer approach. The structures and molecular weights of the obtained polymers were characterized by

Full text of DOI:10.1021/ma1000783

4314 Macromolecules 2010, 43, 4314–4323
DOI: 10.1021/ma1000783
Synthesis and Thermo-/pH- Dual Responsive Properties of
Poly(amidoamine) Dendronized Poly(2-hydroxyethyl) Methacrylate
Min Gao,† Xinru Jia,*,† Yan Li,† Dehai Liang,† and Yen Wei‡
†Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and
Physics of the Ministry of Education, College of Chemistry and Molecular Engineering, Peking University,
‡
Beijing 100871 China, and Department of Chemistry, Tsinghua University, Beijing 100084, China
Received January 12, 2010; Revised Manuscript Received April 2, 2010
ABSTRACT: The first and second generation poly(amidoamine) dendronized poly(2-hydroxylethyl) metha-
crylate (PGn-macro (n = 1, 2)) were synthesized by the macromonomer approach. The structures and
molecular weights of the obtained polymers were characterized by 1H NMR, FTIR, and GPC. UV-vis turbi-
dity measurements revealed that all the resultant polymers were thermo-responsive, exhibiting the LCSTs in
the range of 16-33 °C. The polymers also showed pH sensitive for the existence of the tertiary amino groups
in the interior of the pendent dendrons. It was found that the generation of the dendrons, the molecular
weights of the polymers, the concentrations, and the pHs showed great influence on the lower critical solution
temperatures (LCSTs) of the polymer solutions. The higher LCST could be achieved either by increasing the
generation of the dendrons or by decreasing the molecular weight. The dilute polymer solution with lower
pH displayed the higher LCST. For example, the LCST of PG1-macro solution increased significantly with
the pH decreased below 7.0, but the decrease of LCST was much slower at pHg7.0. DLS experiments at
variable temperatures demonstrated that the polymer chains spontaneously aggregated to form large size
particles as increasing the temperature above LCST due to the dehydration of the peripheral butylamide
groups and the enhanced hydrophobic interactions. The morphology of aggregates was directly visualized by
optical microscopy, and uniform spherical aggregates with the diameter of 3-7 μm were observed.
Introduction
by a linear polymer backbone surrounded with certain structural
dendrons at each repeating unit.18 Such polymers may maintain
As stimuli-responsive behavior is a typical feature of bio-
materials, developing stimuli-responsive polymers, especially
polymers with dual- or multiresponsive properties,1-6 remains a
challenge. They have drawn an increasing attention due to their
potential applications in many fields, such as drug delivery, gene
carriers, sensors, catalysis, and chromatography separation.7-12 Up
to now, most of the synthesized stimuli-responsive polymers and
copolymers are classified as linear structures and their respon-
siveness mainly derives from the function of monomers or the
structural arrangement of the macromolecules as to the variation
of environmental conditions. For example, the ratio of hydrophilic
and hydrophobic units may dominate the thermo-responsiveness
of the polymers.13,14 The ionizable moieties create the polymers
with pH-responsiveness.15 Notably, it has been reported recently
that not only the responsive units endow the polymers with environ-
mental sensitivity, but also the location, the special distribution
of these units, and the molecular shape impact the respon-
siveness greatly. Such an architecture effect may generate the
polymers with unpredictable properties. For example, Kono et al.
reported that the lower critical solution temperature (LCST)
of isobutyramide (IBAM) shelled poly(amidoamine) (PAMAM)
and poly(propylenimine) (PPI) dendrimers showedmore remark-
able molecular weight dependence,16 and the heat of phase transi-
tion of the NIPAM-terminated G4.5 or G5 PAMAM dendrimers
was extremely small as compared to the linear PNIPAM, sugges-
ting that the structural features of dendrimers played a crucial
role in determining the thermo-responsive properties.17
the flexibility of the linear polymer chains with lower generation
dendrons as the side groups, and they may display a rigid, cylin-
drical shape by attaching higher generation dendritic side chains.
Dendronized polymers could be prepared via three general syn-
thetic strategies, including the graft-to, the graft-from, and the
macromonomer approaches.19 One obvious advantage of “the
macromonomer approach” over the other two methods lies in
that the obtained polymers exhibit a quantitative degree of dendron
attachment, which can be defined as “structurally perfect” comb
polymers. Over the last 20 years, many efforts have been paid on
ꢀ
modifying dendronized polymers with various functions. Frechet
et al.20 prepared a pyrrolidinopyridine embedded dendronized
cyclocopolymer through divergent growth techniques. They found
that the microenvironment created by the polyester-type den-
drons could be used to catalyze the difficult esterification of a
tertiary alcohol with pivalic anhydride. Peng et al.21 synthesized a
series of polyfluorenes dendronized with functional carbazole
and oxazole side chains. Because of less aggregation of the main
chains with the steric hindrance of dendritic units, the photo-
luminescent (PL) and electroluminescent (EL) emission color
quality was highly improved. These copolymers were promising
candidates for both efficient pure blue emitters and host materials
for highly efficient phosphorescent PLEDs. Attractively, dendro-
nized polymers with stimuli-responsive properties have been explo-
red. The advantages of such polymers with stimuli-responsiveness
refer to that the responsive motifs can be easily incorporated into
the polymers for the densely packed modifiable peripheral groups
of dendrons; the balance of the molecular structures, for example,
the hydrophilicity-hydrophobicity ratios can be easily tuned by
converting the generation, interior building blocks, and surface
groups of the dendrons; and the unique architecture may lead to
Dendronized polymers, a merger of two concepts of dendri-
mers and polymers, possess the particular structures constructed
*Corresponding author. Telephone: þ86 10 62752102. Fax: þ86 10
62751708. E-mail: xrjia@pku.edu.cn.
pubs.acs.org/Macromolecules
Published on Web 04/16/2010
r 2010 American Chemical Society

Article
Macromolecules, Vol. 43, No. 9, 2010 4315
Scheme 1. Synthesis and Structures of Dendritic Monomers Gn-macro and the Corresponding Dendronized Polymers PGn-macro (n =1, 2)
fast and sharp transitions. Zhang et al. synthesized a series of the
first and second generation dendronized polymethacrylate deri-
vatives using gallic acid as branching point and oligoethylene
glycol (OEG) units as the linker. All these polymers exhibited
sharp phase transitions with negligible hystereses in the aqueous
solution with LCST values in the range of 33-65 °C.22,23 Further
study by Ballauff and Zhang et al. demonstrated that stable and
monodisperse mesoglobules were formed by the second genera-
tion dendronized polymer (PG2) at the temperatures higher than
35 °C (LCST). Interestingly, these globules could completely
dissociate back upon cooling without hysteresis.24 Very recently,
Zhang and co-workers25 successfully synthesized the OEG-based
third generation dendronized polymer (PG3) with a polymeriza-
tion degree of 16 determined by GPC. As the lower generation
counterparts,22,23 PG3 also showed a fast and sharp phase transi-
tion with an apparent LCST of 34 °C in the aqueous solution.
However, dendronized polymers with stimuli-responsive prop-
erties have not been reported extensively and those with thermo-
and pH- dual responsive behavior are still rare. In our previous
study,26 we reported the synthesis of thermo- and pH- dual respon-
sive dendronized polymers (PSADG1-PSADG3) by attaching
butylamide terminated poly(amidoamine) dendrons (DG1-DG3)
to the alternating copolymers of styrene and maleic anhydride. The
LCSTs of the resulting polymers could be tuned by changing gene-
ration and coverage degree of the dendrons, by altering the concen-
tration of the polymers, and also by adding salt and changing
pH of the solutions. However, due to the deficiency of the graft-to
route, the structures of these dendronized polymers were not defi-
ned or well controlled. Herein, we report a new kind of thermo-
and pH- dual responsive dendronized polymers (PGn-macro (n=
1, 2)) composed of a linear poly(2-hydroxyethyl) methacrylate
pendant with butylamide terminated poly(amidoamine) dendrons
(DG1-DG2) at each repeating unit. The polymers were synthe-
sized by the macromonomer route as shown in Scheme 1. The
structures, molecular weights, thermal properties, thermo- and pH-
dual responsive properties were studied by 1H NMR, FTIR, GPC,
DSC, UV-vis, laser light scattering (LLS), and optical microscopy
(OM). All the obtained dendronized polymers were thermo-
responsive and pH-sensitive in 10 mM phosphate buffer. The
LCSTs of the polymers were dependent on the generation of the
dendrons, the molecular weights of the polymers, the concentra-
tion, and the pH of the solutions. These polymers spontaneously
formed larger aggregates that scattered light efficiently upon heat-
ing above LCST.
Experimental Section
Materials. Poly(amidoamine) dendrons DGn (n = 1-2)
(Scheme 1) were synthesized according to the method reported
previously.27 N,N-dimethylformamide, triethylamine, dichloro-
methane, tetrahydrofuran, 2,20-azobis(isobutyronitrile) (AIBN),
and benzoyl peroxide (BPO) were purified according to the
standard procedures. Unless stated otherwise, all the re-
agents and the common solvents were obtained from com-
mercial sources and used as received.
Measurements. 1H NMR and 13C NMR spectra were recor-
ded on 300 MHz (Varian Mercury) or 400 MHz (Bruker) spectro-
meters operated at room temperature, with CDCl3 or DMSO-d6 as
the solvents and tetramethylsilane (TMS) as the internal stan-
dard. FTIR spectra were obtained on a VECTOR 22 Fourier
transform IR spectrometer (Bruker). The electrospray ioniza-
tion mass spectra (ESI MS) were obtained using a APEX IV
Fourier transform ion cyclotron resonance mass spectrometer
(Bruker). For UV-vis turbidity measurements, the LCSTs were
determined on a Varian CARY 1E UV-vis spectrophotometer,
equipped with a BECKMAN 9112AA2E (PolyScience) thermo-
static bath. The heating rate was about 0.5 °C/min. The tempe-
rature of the phase transition (LCST) was defined as the one at
which the transmittance at λ = 550 nm had reached 50% of its
initial value. Through the turbidity measurements, the pHtran values
were also obtained by determining a series of polymer solutions
(0.25 mg mL-1) with different pHs at 25 °C. The pHtran was
defined as the pH at which the transmittance at λ=550 nm had
reached 50% of its initial value (the transmittance at low pH).
A gel permeation chromatograph (GPC) equipped with a Waters
2410 refractive-index detector, a Waters 515 HPLC pump, and

4316 Macromolecules, Vol. 43, No. 9, 2010
Gao et al.
Waters styragel columns (HT3 and HT4) with DMF containing
0.05 wt % LiBr as an eluent at a flow rate of 1.0 mL/min. Mono-
dispersity polystyrene standards were used for calibration. Diffe-
rential scanning calorimetry (DSC) measurements were carried
out on TA Instruments DSC Q100. Polymer samples were sealed
in aluminum pans. An empty aluminum pan was used as the
reference. A scanning rate of 10.0 °C/min was used for both heat-
ing and cooling processes between -10 and þ180 °C. The glass
transition temperature (Tg) was obtained from the first cooling
run and corresponded to the midpoint of discontinuity in the
heat flow. The dynamic light scattering (DLS) experiments of
PG1-macro at 0.25 mg mL-1 in 10 mM phosphate buffered solu-
tion at different pHs were performed on a Brookhaven gonio-
meter (BI-200SM) equipped with a BI-TurboCorr digital cor-
relator and a thermostatic bath with temperature accuracy of
0.01 °C. A vertically polarized solid-state laser operating at 532 nm
was used as the light source (100 mW, CNI Changchun GXC-III,
China). The stock solutions were filtered through a Millipore
0.45 μm PVDF filter into a dust-free vial. During heating, the
autocorrelation functions were collected when the scattered
intensity at each temperature became stable. The time correla-
tion functions were analyzed with a Laplace inversion program
CONTIN. Optical microscopy images of polymer solutions
were recorded using a Leica DLMP microscope. The polymer
solution was placed on a glass slide and the sample was heated
from room temperature (ca. 18 °C) to 40 °C with the heating rate
of 2 °C/min. The micrographs were recorded by a Digital sight
camera at a specific temperature in the process.
was filtrated, and the filtrate was collected and evaporated in
vacuo. The middle product 2-((4-nitrophenoxy)carbonyloxy)-
ethyl methacrylate (1, Scheme 1) was used without further puri-
fication. Then, a dichloromethane solution of 1 was added drop-
wise to an ice-cooled, stirred solution of 0.56 g (0.50 mmol) DG2
and 0.40 g (4.0 mmol) TEA in dry CH2Cl2 (15 mL). The mix-
ture was stirred at room temperature for 48 h and the solvent
was evaporated in vacuo. The crude product was purified by
dissolution-precipitation repeatedly from methanol/diethyl ether
(1/20) to afford the monomer G2-macro as a light yellow solid
with 51.7% yield (0.32 g). The structure and molecular weight of
the monomer were determined by 1H NMR, 13C NMR, FTIR,
and ESI MS.
G2-macro. This was obtained as a light yellow solid. Yield:
51.7%. 1H NMR (300 MHz, DMSO-d6, TMS, T=298 K): 8.10-
7.45 (br, 10H, CONH), 7.04 (br, 1H, OCONH), 6.02 (s, 1H,
CH2dC), 5.68 (t, 1H, CH2dC), 4.40-4.06 (m, 4H, OCH2CH2O),
3.20-2.98 (m, 20H, NHCH2CH2NH (16H) and CH2CH2N
(4H)), 2.98-2.90 (br, 2H, CH2CH2N (focal)), 2.65 (br, 12H,
CH2CH2CO), 2.44 (br, 6H, CH2CH2N), 2.20 (br, 12H, CH2-
CH2CO), 2.03-1.93 (t, 8H, CH2CH2CH3), 1.85 (s, 3H, CH2d
C(CH3)), 1.60-1.35 (m, 8H, CH2CH2CH3), 0.84-0.78 (t, 12H,
CH2CH2CH3). 13C NMR (75 MHz, DMSO-d6, TMS, T =298
K): 172.19, 171.46, 171.17, 166.40, 155.94, 135.66, 125.93, 63.03,
61.66, 52.10, 49.52, 38.40, 38.27, 37.37, 36.77, 33.07, 18.58,
17.88, 13.57. FTIR (KBr, cm-1): 3522 (br), 3175, 3088, 2966,
2876, 1714, 1648, 1545, 1451, 1378, 1251, 1140, 1034, 661. ESI
MS: calcd for C55H100N14O14, 1181; found, 1182 (M þ H)þ,
1204 (M þ Na)þ, 1220 (M þ K)þ.
Synthesis of Monomer G1-macro. Here, 0.39 g (3.0 mmol) of
2-hydroxyethyl methacrylate (HEMA) and 0.36 g (3.6 mmol) of
triethylamine (TEA) were dissolved in 12 mL of anhydrous THF.
Then a THF solution of 0.71 g (3.5 mmol) of 4-nitrophenyl chloro-
formate was added in an ice bath. After the solution was stirred at
Synthesis of PG1-macro. Conventional radical polymeriza-
tion was performed with 2,20-azobis(isobutyronitrile) (AIBN) as
an initiator in a degassed sealed tube. G1-macro (0.40 g, 0.68
mmol), AIBN (1.9 mg, 0.012 mmol), and dry DMF (0.85 mL)
were placed in a Schlenk tube. After the solution was thoroughly
deoxygenated by three freeze-pump-thaw cycles, the tube was
sealed and heated to 60 °C for 24 h. After being cooled to room tem-
perature, the product was purified by dissolution-precipitation
twice from methanol/diethyl ether (1/40) and dried under vac-
uum for 24 h to yield a polymer as a pale yellow powder. Two
polymers of the first generation, named as PG1-macro (0.35 g,
87.5%) and PG1-macro2 (0.30 g, 90.0%), were synthesized by
using different proportion of AIBN. The detailed polymeriza-
tion conditions are listed in Table 1, and the structure and
molecular weight of the polymers were determined by 1H NMR,
FTIR, and GPC.
PG1-macro (PG1-macro2). This was obtained as a pale yellow
powder. 1H NMR (400 MHz, DMSO-d6, TMS, T=298 K): 7.95
(br, CONH), 7.82 (br, CONH), 6.91 (br, OCONH), 4.12 (br,
OCH2CH2O), 3.34 (s, H2O), 3.09 (br, NHCH2CH2NH and
CH2CH2N), 2.65 (m, CH2CH2CO), 2.45 (br, CH2CH2N), 2.19
(br, CH2CH2CO), 2.05-2.01 (t, CH2CH2CH3 and CH2C(CH3)
in the main chain), 1.52-1.47 (m, CH2CH2CH3 and CH2C-
(CH3) in the main chain), 0.85-0.81 (t, CH2CH2CH3 and CH2-
C(CH3) in the main chain). (Note: CH2 and CH3 in the main chain
were at 0.80-2.30 ppm and they were shielded by the signals of
protons in the dendrons on the side chain). FTIR (KBr, cm-1):
3524 (br), 3083, 2963, 2875, 1716, 1650, 1545, 1453, 1379, 1250,
1144, 1032, 966, 673. GPC (DMF as eluent): PG1-macro, Mn=
101 K, PDI=1.63; PG1-macro2, Mn =140 K, PDI=1.63.
Synthesis of PG2-macro. Conventional radical polymeriza-
tion was performed with benzoyl peroxide (BPO) as an initiator
in a degassed sealed tube. G2-macro (0.32 g, 0.27 mmol), BPO
(1.3 mg, 0.0055 mmol), and dry methanol (0.46 mL) were placed
in a Schlenk tube. After the solution was thoroughly deoxyge-
nated by three freeze-pump-thaw cycles, the tube was sealed
and heated to 80 °C for 36 h. After being cooled to room tempe-
rature, the product was first purified by dissolution-precipitation
twice from methanol/diethyl ether (1/40) and dried under vac-
uum for 24 h to yield a yellow solid. The unreactive mono-
mers were further removed by dialysis using a dialysis membrane
room temperature for 48 h, the produced white salt TEA HCl was
3
filtrated, and the filtrate was collected and evaporated in vacuo.
The middle product 2-((4-nitrophenoxy)carbonyloxy)ethyl metha-
crylate (1, Scheme 1) was used without further purification and its
structure was proved by 1H NMR spectrum (Figure S1, Supporting
Information). Then, a dichloromethane solution of 1 was added
dropwise to an ice-cooled, stirred solution of 0.91 g (1.7 mmol) of
DG1 and 0.35 g (3.5 mmol) of TEA in dry CH2Cl2 (15 mL). The
mixture was stirred at room temperature for 48 h and the solvent
was evaporated in vacuo. The crude product was purified first by
dissolution-precipitation repeatedly from chloroform/diethyl ether
(1/20) and then through a short silica column quickly to afford the
monomer G1-macro as a pale yellow solid with 78.6% yield (0.77 g).
The structure and molecular weight of the monomer were deter-
mined by 1H NMR, 13C NMR, FTIR, and ESI MS.
G1-macro. This was obtained as a pale yellow solid. Yield:
78.6%. 1H NMR (300 MHz, CDCl3, TMS, T = 298 K): 7.65-
7.40 (br, 2H, CONH), 6.90-6.72 (br, 2H, CONH), 6.13 (s, 1H,
CH2dC), 6.05-5.80 (m, 1H, OCONH), 5.61-5.60 (t, 1H, CH2dC),
4.46-4.20 (m, 4H, OCH2CH2O), 3.35 (s, 8H, NHCH2CH2NH),
3.30-3.20 (m, 2H, CH2CH2N), 2.68 (t, 4H, CH2CH2CO), 2.52
(t, 2H, CH2CH2N), 2.36-2.34 (t, 4H, CH2CH2CO), 2.19-2.14
(t, 4H, CH2CH2CH3), 1.92 (s, 3H, CH2dC(CH3)), 1.70-1.60
(m, 4H, CH2CH2CH3), 0.96-0.91 (t, 6H, CH2CH2CH3). 13C
NMR (75 MHz, CDCl3, TMS, T = 298 K): 174.38, 174.22,
167.14, 156.33, 135.80, 126.00, 62.76, 62.39, 52.57, 50.00, 39.39,
39.23, 38.51, 38.25, 33.42, 18.97, 18.10, 13.60. FTIR (KBr,
cm-1): 3300 (br), 3087, 2962, 2874, 1715, 1647, 1546, 1452,
1377, 1251, 1161, 1046, 946, 691. ESI MS: calcd for C27H48-
N6O8, 584; found, 585 (M þ H)þ, 607 (M þ Na)þ, 629 (M - H þ
2Na)þ.
Synthesis of G2-macro. Here, 0.14 g (1.1 mmol) of 2-hydroxy-
ethyl methacrylate (HEMA) and 0.20 g (2.0 mmol) of triethyl-
amine (TEA) were dissolved in 6 mL of anhydrous THF. Then
a THF solution of 0.27 g (1.3 mmol) of 4-nitrophenyl chloro-
formate was added in an ice bath. After the solution was stirred
at room temperature for 48 h, the produced white salt TEA HCl
3

Article
Macromolecules, Vol. 43, No. 9, 2010 4317
(MW=2000) to afford final product (100 mg, yield: 30.8%). The
detailed polymerization conditions are listed in Table 1, and the
structure and molecular weight of the polymers were determined
by 1H NMR, FTIR, and GPC.
1H NMR spectra of PG1-macro (Figure 2a) and PG2-macro
(Figure 2b), respectively. Because of the shielding effect of
the dendrons, the protons of CH2 and CH3 at 0.80-2.30 ppm
in the main chain were not clearly visible in the spectra.
However, the signals of OCH2CH2O (HEMA) protons and
OCONH (urethane) protons close to the main chain appea-
red as the broad peaks at 3.70-4.50 ppm and 6.65-7.25 ppm,
respectively (Figure 2).
PG2-macro. This was obtained as a light yellow powder. 1H
NMR (400 MHz, DMSO-d6, TMS, T=298 K): 7.95 (br, CONH),
7.83 (br, CONH), 6.98 (br, OCONH), 4.10 (br, OCH2CH2O),
3.34 (s, H2O), 3.08 (br, NHCH2CH2NH and CH2CH2N), 2.64
(br, CH2CH2CO), 2.42 (br, CH2CH2N), 2.18 (br, CH2CH2CO),
2.03-2.00 (t, CH2CH2CH3 and CH2C(CH3) in the main chain),
1.51-1.46 (m, CH2CH2CH3 and CH2C(CH3) in the main chain),
0.84-0.81 (t, CH2CH2CH3 and CH2C(CH3) in the main chain).
(Note: CH2 and CH3 in the main chain were at 0.80-2.30 ppm
and they were shielded by the signals of protons in the dendrons
on the side chain.) FTIR (KBr, cm-1): 3519 (br), 3260, 3088,
2965, 2878, 1717, 1645, 1546, 1461, 1383, 1252, 1148, 1035, 968,
672. GPC (DMF as eluent): PG2-macro, Mn=86 K, PDI=1.52.
Differential scanning calorimetric (DSC) measurement
was performed to study the thermo-properties of the resulting
Results and Discussion
Synthesis and Characterization of the Dendronized Polymers.
The synthesis of the first and second generation macromono-
mers (Gn-macro (n=1, 2)) and the corresponding dendroni-
zed polymers (PGn-macro (n=1, 2)) are outlined in Scheme 1.
The monomers were prepared via two step reactions, including
the formation of an activated carbonate 1 by reacting hydroxyl
groups of HEMA with 4-nitrophenyl chloroformate, and then
incorporating the dendron through the urethane group. The
monomers were characterized by 1H NMR, 13C NMR spectro-
scopy, and the electrospray ionization mass spectrometer (ESI
MS). The results agreed with the proposed structures.
The free radical polymerization of G1-macro was carried
out in DMF solution at 60 °C with AIBN as an initiator, and
the polymers with different molecular weights, named as
PG1-macro and PG1-macro2 were obtained with excellent
yields (∼90%, Table 1). The second generation dendronized
polymer PG2-macro was prepared in methanol solution at
80 °C using BPO as an initiator with the yield of 30% because
of the poor solubility and strong gelation ability of G2-macro
in DMF. The molar masses of all the polymers were in the
range of 80-140 thousand (Table 1 and Figure S2, Support-
ing Information) determined by GPC with DMF containing
0.05 wt % LiBr as the eluent. These polymers were soluble in
DMF, DMSO, methanol, and water but insoluble in other
common organic solvents, such as THF, chloroform, acetone,
and EtOAc.
Figure 1. FTIR spectra of (a) PG1-macro and (b) PG2-macro.
The structures of these polymers were evidenced by FTIR
spectra. As shown in Figure 1, the characteristic absorbance
peak at 1716 cm-1 was related to the stretching vibration of
CdO of ester groups in the main chain, while the peaks at
1650 and 1545 cm-1 corresponded to amide I (νCdO) and
amide II (δN-H) in the pendent dendrons (Figure 1).
1H NMR measurements were performed to further con-
firm the structures of all the polymers. Figure 2 shows the
Figure 2. 1H NMR spectra of (a) PG1-macro and (b) PG2-macro
(DMSO-d6, 298 K).
Table 1. Synthesis and Properties of Dendronized Polymers PGn-macro (n=1, 2)
polymerization conditionsa
GPC resultsb
10-5Mn
PDI
Tg (°C)c
LCST (°C)d
pHtran
e
polymers
[M] (mol/L)
[I]/[M], %
T (°C)
yield (%)
PG1-macro
PG1-macro2
PG2-macro
0.8
0.8
0.6
1.7
1
2
60
60
80
87.5
90.0
30.8
1.01
1.40
0.86
1.63
1.63
1.52
30.7
32.6
28.6
19.8 (23.8)
15.7 (19.2)
27.6 (33.3)
6.6
6.5
7.8
a [M] and [I] represented the concentration of monomer and initiator, respectively; AIBN and DMF were used as the initiator and solvent for PG1-
macro, and PG2-macro was prepared in methanol with BPO as the initiator. b All the GPC measurements were done in DMF (0.05 wt % LiBr) as the
eluent. c The glass transition temperature (Tg) was determined based on the first cooling scan by DSC analysis under nitrogen. d All the LCST values were
determined by the turbidity measurements with the polymer concentration of 1.0 mg mL-1; The values inside parentheses corresponded to the LCSTs at
the polymer concentration of 0.25 mg mL-1. e The pHtran was defined as the pH at which the transmittance at λ=550 nm had reached 50% of its initial
value (the transmittance at low pH). Through the turbidity measurements, the pHtran values were obtained by determining a series of polymer solutions
(0.25 mg mL-1) with different pHs at 25 °C.

4318 Macromolecules, Vol. 43, No. 9, 2010
Gao et al.
dendronized polymers. As shown in Table 1 and Figure 3,
during the first cooling run, the polymers showed glass
transition temperature (Tg) at 30.7, 32.6, and 28.6 °C for
PG1-macro, PG1-macro2, and PG2-macro, respectively. Si-
milar with our previous report,26 the Tg of PGn-macro
decreased with increasing the generation of dendrons. Such
results might be mainly due to the dendritic architecture. The
higher generation dendrons attached along the polymer
main chain would occupy more room and wrap the polymer
chain inside, resulting in the polymers with softer nature
from the structure of dendrons and leading to a decrease in
Tg. This result was in accordance with that reported by Khan
et al.,28 who found that the Tg of the ethyl cellulose deriva-
tives functionalized with amidoimide dendrons underwent
a significant decrease as a result of the substitution by the
appendage of amidoimide dendrons, especially the G2 dendron-
functionalized polymers showed lower Tg. Additionally,
compared with PG1-macro, PG2-macro showed a noticeable
broadening of the glass transition. This result was in accor-
of end groups, causing the increase of the segmental mobi-
lity. As a result, segmental relaxation times would become
broader, and consequently contributed to a broadening of
the transition. Moreover, PG1-macro2 (Mn = 140 K) exhi-
bited a slightly higher Tg than PG1-macro (Mn =101 K) for
the higher molecular weight of the former. This is reasonable
because, generally, the transition temperature relates closely
with the degree of polymerization (DP). If the intra- and
inter- molecular interactions or the conformation of the
polymer does not change significantly with DP, the Tg will
shift to higher temperatures as the DP increases.
Thermo-Responsive Behavior of PGn-macro (n=1, 2). All
the obtained dendronized polymers were water-soluble at
low temperatures. The transparent solutions turned turbid
with temperature increasing, and became clear again as the
temperature decreased, indicating the occurrence of phase
transitions and the reversible thermo-responsiveness. UV-vis
spectroscopy was used to measure the transmittance of the
solution (λ=550 nm) as a function of temperature in order
to determine the LCSTs of PGn-macro (n=1, 2). Figure 4a
shows the transmittance change of PG1-macro and PG2-
macro at 1.0 mg mL-1 in 10 mM phosphate buffered solution
(pH = 7.4). Both of them showed relative sharp transition
with the LCSTs of 19.8 °C for PG1-macro and 27.6 °C for
PG2-macro, demonstrating the dependence of LCSTs on the
generation of dendrons, which was in correspondence with
the report by Zhang et al.22 The reasonable explanations may
involve the balance of hydrophilicity and hydrophobicity in
the polymer structures varied with pendent dendrons. It is
well-known that the ratio of the hydrophobic and hydro-
philic units in a polymer chain is crucial to the alternation of
LCST. In general, hydrophilic segments shift LCST to a
higher temperature,30 and hydrophobic units show the ten-
dency to decrease LCST.31 For the PG1-macro and PG2-
macro, the pendent G1 and G2 dendrons afforded them with
different hydrophilic and hydrophobic compositions. The
G2 dendron possessed more amide moieties that could stron-
gly interact with adjacent water molecules through hydrogen
bonds, which enhanced the hydrophilicity of PG2-macro and
conduced to a higher LCST. Moreover, as shown in the inset
of Figure 4a, the hysteresis was small for PG1-macro during
one heating and cooling cycle. The same phenomenon was also
observed for PG2-macro at the same condition (Figure S3,
Supporting Information). The small hysteresis might be
induced by the hydrogen bonding from the structure of the
polymers. Such result is consistent with that reported for a
series of first and second generation dendronized polymers
by Zhang et al.22,23
dance with that reported by Schluter et al.29 Structurally, the
€
number of branching point will increase with the generation
increasing, which would locally reduce the segmental mobi-
lity responsible for the glass transition. Additionally, inc-
reasing the generation also involves an increase of the number
Figure 3. DSC thermograms of PGn-macro (n=1, 2) polymers based
on the first cooling scan at a cooling rate of 10.0 °C/min under nitrogen
atmosphere. In the figure, the black (a), red (b), and blue (c) curves
represent PG1-macro, PG1-macro2, and PG2-macro, respectively.
Figure 4. Temperature dependence of the transmittance of (a) 1.0 mg mL-1 and (b) 0.25 mg mL-1 of PG1-macro (0), and PG2-macro (Δ) in 10 mM
phosphate buffered solution (pH = 7.4). Inset of Figure 4a: the plots of transmittance vs temperature for 1.0 mg mL-1 solution of PG1-macro
(pH=7.4) during one heating and cooling cycle.

Article
For the most studied linear thermo-responsive polymer,
Macromolecules, Vol. 43, No. 9, 2010 4319
groups were the possible reasons for the moderate decline of
LCST.
poly(N-isopropylacrylamide), the LCST changed only insig-
nificantly with molar masses, for example, the PNIPAM with
the molar masses of 5400 and 1600000 showed only ∼2 °C
deviation in their LCSTs.32 Interestingly, Kono et al.16
reported the LCSTs of the globular structure molecules,
PAMAM or PPI dendrimers with terminal isobutyramide
(IBAM) groups, decreased almost linearly with increasing
the generation of the corresponding dendrimers, and a 30 °C
decrease in the LCST was observed with the molecular weight
increasing from ca. 9150 (G3) to 37800 (G5). Such LCST
dependence on molecular weight is due to the compact spheri-
cal topology of the dendrimers. Chen and co-workers33
reported the LCSTs of the hyperbranched polyethylenimines
(PEI) ended with IBAM groups were much more sensi-
tive to the molecular weight than those of their dendrimer
analogues (PPI dendrimer) due to the topological difference
in the location of functional end-groups. In our case, the
LCSTs of PG1-macro also displayed molecular weight depen-
dence. As shown in Figure 5, the LCST of PG1-macro in
phosphate buffer at pH 7.4 dropped ∼4 °C with Mn rising
from 101 to 140 K. The particular architecture of the dendro-
nized polymer and the unique location of peripheral butylamide
Moreover, the LCSTs of these resultant dendronized
polymers were also dependent on the concentration. Parts
a and b of Figure 4 show the transmittance changes of PG1-
macro and PG2-macro with the concentrations of 1.0 and
0.25 mg mL-1 in 10 mM phosphate buffer, respectively.
Take PG1-macro as an example, the LCST increased from
19.8 to 23.8 °C (Table 1) and the transition zone became broa-
der when the concentration decreased from 1.0 to 0.25 mg mL-1
.
The similar phenomenon was also observed in our previous
report,26 in which the LCST of PSADG2 increased from 29.7
to 34.9 °C with the concentration decreasing from 1.0 to
0.1 mg mL-1 and the transition temperature region became
broader upon dilution.
pH-Responsiveness of PGn-macro (n = 1, 2). The synthe-
sized PG1-macro and PG2-macro showed response to the
variation of pH for the existence of tertiary amino groups in
the interior of pendent dendrons. To demonstrate their pH-
responsiveness, a series of polymer solutions with different
pHs in 10 mM phosphate buffer were prepared, and the
effect of pH on their phase transition behavior was exam-
ined. Figure 6a and 6b show the pH dependence of PG1-
macro and PG2-macro on the optical transmittance at 550 nm.
Take PG1-macro as an example, when pH increased to ca. 6.6,
the polymer solution transferred from transparency to opacity
because of the aggregation of the polymers, indicating the
polymers were more hydrophilic at lower pH and became
hydrophobic at higher pH. That was on account of the proto-
nation and deprotonation of tertiary amino groups at different
pHs. Furthermore, as shown in Figure 6a, the phase transition
of the G1 and G2 dendron-jacketing polymers appeared at
pHtran (defined as the pH at which the transmittance reached to
50% of its initial value) of 6.6 and 7.8, respectively. The higher
pHtran of PG2-macro was attributed to the more hydrophilicity
of G2 dendrons. Moreover, the remaining transmittance at
elevated pH for the solution of PG2-macro at 25 °C was around
70%, suggesting the aggregates were either not so big or not
compact, and thus not capable of scattering light efficiently.34
Besides the generation, the molecular weight of polymers
also showed influence on the pH-responsive behavior. As
shown in Figure 6b, the pHtran of PG1-macro2 (Mn=140 K)
was ca. 6.5 that was slightly lower than that of PG1-macro
(Mn = 101 K). Additionally, it was also observed that the poly-
mer with higher Mn showed a much sharper transition. The
reason is unknown so far, and more samples need to be exami-
ned before drawing the conclusions, but more hydrophobicity
Figure 5. Temperature dependence of the transmittance of 1.0 mg mL-1
PG1-macro with different molecular weights in 10 mM phosphate
buffered solution (pH = 7.4). Inset: plots of transmittance vs tempera-
ture for 0.25 mg mL-1 PG1-macro (0, Mn = 101 K) and PG1-macro2
(9, Mn = 140 K) in 10 mM phosphate buffer.
Figure 6. pH dependence of the transmittance at λ = 550 nm of(a) PG1-macro (0) and PG2-macro (Δ) and (b) PG1-macro (0, Mn = 101 K) and PG1-
macro2 (9, Mn = 140 K) at 25 °C in 10 mM phosphate buffered solutions. The concentration of the polymers was 0.25 mg mL-1
.

4320 Macromolecules, Vol. 43, No. 9, 2010
Gao et al.
deriving from a much longer main chain of the high molecular
weight polymers might be mainly responsible for the results.
Laser Light Scattering Studies. Laser light scattering study
of the polymer in dilute solution (0.25 mg mL-1) at different
pHs provided a better understanding of the thermally indu-
ced phase transition behavior. Figure 7 shows the tempera-
ture dependence of the excess scattered intensity of PG1-
macro solutions at the scattered angle of 90° at pH 5.5 (weak
acidicity), 7.0 (neutrality), and 8.6 (weak basicity), respec-
tively. With increasing the temperature, the excess scattered
intensity increased for all the solutions at different pHs,
yielding the transition temperatures (LCST) of 32, 18, and
12 °C at pHs 5.5, 7.0, and 8.6, respectively (inset of Figure 7).
The delayed transition of PG1-macro with decreasing pH
below 7.0 was due to the protonation of the tertiary amino
groups in the interior of dendrons. Under such conditions,
the hydrophobic attraction of the peripheral butylamide
groups was weakened because of the electrostatic repulsion
between the positively charged tertiary amino groups. As a
result, a much higher LCST was obtained. On the contrary,
the LCST of the polymers decreased slowly at pH above 7.0.
Our findings were similar to those reported by Kono et al.,16
who found that the LCSTs of the peripheral isobutyramide
(IBAM) modified PAMAM dendrimers were almost the
same at pH above 7.2, but increased greatly upon decreasing
pH below 7.2.
Figure 8 shows the size distributions of PG1-macro at
0.25 mg mL-1 with increasing temperature at different pHs.
Before the transition points, the solutions were optically clear.
However, a bimodal distribution (especially at 30°) was
observed at the measured pHs (Figure 8, parts a, a0, and a00).
The fast mode with Rh,app of about 10 nm was attributed to
the separated polymer chains. The size and area ratio of the
slow mode were pH dependent. They could be caused either
by the incompatibility between the segments35,36 or by extra-
ordinary behavior of polyelectrolyte (at pH 5.5) in aqueous
solutions without enough salt.37,38 At pH 7.0 and 8.6, the fast
mode gradually disappeared with increasing temperature
above LCST. Meanwhile, the slow mode increased in size
Figure 7. Temperature dependence of the excess scattered intensity of
PG1-macro at 0.25 mg mL-1 in phosphate buffered solutions at pH 5.5
(0), pH 7.0 (O), and pH 8.6 (Δ). The scattered angle is 90°. The inset
shows the pH dependence of the LCST of PG1-macro.
Figure 8. The representative size distribution curves of PG1-macro at 0.25 mg mL-1 at pH 5.5 (a, b, c), pH 7.0 (a0, b0, c0), and pH 8.6 (a00, b00, c00) during
the heating process. The rectangular and triangular symbols denote the data collected at 90° and 30°, respectively.

Article
Macromolecules, Vol. 43, No. 9, 2010 4321
and area ratio. Eventually, only one narrowly distributed
component existed in the system (Figure 8, parts c0 and c00).
This was a typical temperature-induced aggregation process.
However, this was not the case at pH 5.5, where the size of the
slow mode decreased with temperature (Figure 8, parts b
and c), indicating that the origin of the slow mode was
different from those at elevated pHs.
Figure 9 compares the temperature dependence of the
Rh,app (measured at 30°) of the slow mode (aggregate) in
PG1-macro solutions at different pHs. It was obvious that
the transition temperature of PG1-macro decreased with in-
creasing pH, which was in accordance with the results drawn
from the excess scattered intensity (Figure 7). Figure 9 also
showed that the change of the aggregate size was highly pH-
dependent. The higher the pH, the larger and sharper inc-
rease in Rh,app. At pH 8.6, where PG1-macro was not charged
at all, the Rh,app increased from 150 nm at 10 °C to 950 nm at
16 °C, corresponding to a factor of 6. While at pH 7.0, the
size of the aggregates increased from 250 to 375 nm, by a
factor of 1.5. At the pH (5.5) where the tertiary amino groups
were protonated, a decrease in Rh,app was observed. As
shown in the inset of Figure 9, the size of the aggregates
remained almost no change below 31 °C. A sudden drop in
size was observed at the transition point of 32 °C, after which
it was maintained at ca. 60 nm with further raising the tem-
perature. Considering that the Rh,app of single polymer chain
was about 10 nm, thermo-induced aggregation did occur at
pH 5.5, as demonstrated by the increase in the excess
scattered intensity (Figure 7). The drop in size was due to
the unidentified slow mode of charged PG1-macro. It was
known that the nature of the slow mode of polyelectrolyte in
aqueous solution without enough salt was electrostatic,37,38
while the thermo-induced aggregation was caused mainly by
hydrophobic attraction. The different nature of the two
driving forces resulted in the abnormal change in size. On
the other hand, the size changes in Figure 9 clearly indicated
that electrostatic repulsion of the dendrons significantly
weakened the degree of aggregation caused by hydrophobic
attraction.
The size distribution of PG2-macro was also measured by
laser light scattering in a dilute solution (0.25 mg mL-1) at
pH 7.4. The results are shown in Figure 10. Compared with
the first generation polymer PG1-macro, the second genera-
tion PG2-macro exhibited a much higher LCST at the same
conditions (28 °C) (Figure 10a). Moreover, the variation of
the size distribution of PG2-macro with increasing tempera-
ture was similar to that of PG1-macro. The area ratio of the
fast mode gradually decreased with increasing temperature
Figure 9. Temperature dependence of Rh,app of 0.25 mg mL-1 PG1-
macro at 30° at pH 5.5 (0), pH 7.0 (O), and pH 8.6 (Δ) in phosphate-
buffered solutions. The inset magnifies the curve at pH 5.5.
Figure 10. (a) Temperature dependence of the excess scattered intensity of PG1-macro (0) and PG2-macro (O) at 0.25 mg mL-1 in phosphate buffered
solutions at pH 7.4. The scattered angle is 90°. (b) Temperature dependence of Rh,app of 0.25 mg mL-1 PG1-macro (0) and PG2-macro (O) measured at
30° in phosphate buffered solutions. (c, c0, and c00) The representative size distribution curves of PG2-macro at 0.25 mg mL-1 at pH 7.4 during the
heating process. The rectangular and triangular symbols denote the data collected at 90° and 30°, respectively.

4322 Macromolecules, Vol. 43, No. 9, 2010
Gao et al.
the generation of the pendent dendrons and molecular weight of
the polymers. DLS experiments at variable temperature demon-
strated that, as the temperature increased, the polymers formed
larger aggregates with different Rh,app at different pHs through the
dehydration and strengthened hydrophobic interactions. In con-
clusion, the LCST of these new dendronized polymers could be
adjusted not only by changing generation of jacketing dendrons
and molecular weight of the polymers, but also by altering the
concentration and pH of the solutions. Furthermore, the macro-
monomer route gives dendronized polymers with “perfect” and
well-defined structures that could be easily controlled. Such
materials may become potential candidates spanning a broad
temperature range for drug delivery, sensors, and separation mate-
rials etc.
Acknowledgment. This work is financially supported by the
National Natural Science Foundation of China (20774003 and
20974004) to X.-R.J.
Supporting Information Available: Figures showing 1H
NMR spectrum of 1, GPC traces for PGn-macro (n = 1, 2),
plots of transmittance vs temperature for PG2-macro (pH=7.4)
during one heating and cooling cycle, a series of optical micro-
graphs of PG2-macro solution in the process of cooling, and the
ESI MS spectra of G1-macro and G2-macro. This material is
available free of charge via the Internet at http://pubs.acs.org.
Figure 11. Optical micrographs of PG1-macro (a, b) and PG2-macro
(c, d) in the phosphate buffer at pH 7.4. The temperatures of the
solutions maintained at 18 °C (a), 25 °C (b), 20 °C (c), and 36 °C (d),
respectively. The concentration of solution is 1.0 mg mL-1
.
and totally disappeared at the temperature above LCST.
Meanwhile, the size and area ratio of the slow mode inc-
reased, and finally only one narrowly distributed component
existed in the system (Figure 10, parts c, c0, and c00). However,
a larger and sharper increase in Rh,app was observed for PG2-
macro. The Rh,app of the aggregates increased from 260 nm at
25 °C to 560 nm at 32 °C, by a factor of 2 (Figure 10b).
Optical Microscopy Studies. Optical microscopy (OM)
was used to directly monitor the morphology of the aggrega-
tes in polymer solutions. Take PG2-macro as a representa-
tive, as shown in Figure 11c and d, only a small amount of
aggregates was observed in solutions below LCST (20 °C),
while more uniform spherical aggregates with the diameter
of 3-7 μm appeared as the temperature increased to 36 °C
(above LCST), at which the solution turned turbid. It was
indicated that the polymer chains spontaneously aggregated
together to form the large aggregates when the temperature
increased above LCST, which could scatter the light effici-
ently. Upon cooling, the aggregates disappeared gradually
and the solution returned to the original one as the tempera-
ture dropped below LCST, suggesting the reversible thermo-
sensitivity of these dendronized polymers (Figure S4, Support-
ing Information).
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