Photoresponsive dendronized copolymers of styrene and maleic anhydride pendant with poly(amidoamine) dendrons as side groups

Article abstract of DOI:10.1021/ma302358t

A series of photoresponsive dendronized polymers PGn-NB (n = 1, 2, 3) were synthesized by attaching o-nitrobenzyl alcohol-terminated amidoamine dendrons (G1-G3) to the alternating styrene and maleic anhydride copolymer (PSt-alt-PMAh). The structures and the molecular weights of the obtained polymers were characterized by ¹H NMR and FTIR measurements. It is found that the coverage degrees of the dendrons are 74%, 42%, and 26%, respectively, indicating that the numbers of the appended dendrons decrease in the order of G1 > G2 > G3 due to the steric hindrance of higher generation dendrons with more branches. The photocleavable behavior of G1-G3 was detected by UV-vis and ¹H NMR measurements. As a result, G2 showed a faster cleavage rate compared to G1 and G3. The critical aggregation concentration (CAC) of PGn-NB (n = 1, 2, 3), measured by using pyrene as a fluorescence probe, were 0.05 mg/mL (PG1-NB), 0.01 mg/mL (PG2-NB), and 0.03 mg/mL (PG3-NB), which displayed that the structure of PG2-NB was in favor of forming aggregates at lower concentrations. Light scattering study indicated that both the apparent molecular weight and the chain density of the aggregates formed by PG2-NB decreased with the irradiation time. Atomic force microscope (AFM) measurements also showed that the size of the aggregates increased dramatically from 15 to 70 nm before and after UV irradiation, evidencing that the UV light induced structure change. Nile Reds, as the guest molecules, were loaded in the aggregates from PG2-NB, and the release profiles upon UV stimulus were monitored by the fluorescence spectroscopy.

Full text of DOI:10.1021/ma302358t

Article
pubs.acs.org/Macromolecules
Photoresponsive Dendronized Copolymers of Styrene and Maleic
Anhydride Pendant with Poly(amidoamine) Dendrons as Side Groups
Zhijian Wang, Min Gao, Jianbo Sun, Dehai Liang, and Xinru Jia*
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
S
* Supporting Information
ABSTRACT: A series of photoresponsive dendronized
polymers PGn-NB (n = 1, 2, 3) were synthesized by attaching
o-nitrobenzyl alcohol-terminated amidoamine dendrons (G1−
G3) to the alternating styrene and maleic anhydride
copolymer (PSt-alt-PMAh). The structures and the molecular
1
weights of the obtained polymers were characterized by H
NMR and FTIR measurements. It is found that the coverage
degrees of the dendrons are 74%, 42%, and 26%, respectively,
indicating that the numbers of the appended dendrons
decrease in the order of G1 > G2 > G3 due to the steric hindrance of higher generation dendrons with more branches. The
1
photocleavable behavior of G1−G3 was detected by UV−vis and H NMR measurements. As a result, G2 showed a faster
cleavage rate compared to G1 and G3. The critical aggregation concentration (CAC) of PGn-NB (n = 1, 2, 3), measured by
using pyrene as a fluorescence probe, were 0.05 mg/mL (PG1-NB), 0.01 mg/mL (PG2-NB), and 0.03 mg/mL (PG3-NB),
which displayed that the structure of PG2-NB was in favor of forming aggregates at lower concentrations. Light scattering study
indicated that both the apparent molecular weight and the chain density of the aggregates formed by PG2-NB decreased with the
irradiation time. Atomic force microscope (AFM) measurements also showed that the size of the aggregates increased
dramatically from 15 to 70 nm before and after UV irradiation, evidencing that the UV light induced structure change. Nile Reds,
as the guest molecules, were loaded in the aggregates from PG2-NB, and the release profiles upon UV stimulus were monitored
by the fluorescence spectroscopy.
Under UV irradiation, the azobenzene derivatives carry the
isomerization and show different physical properties.22−26
As is well-known, o-nitrobenzyl alcohol derivatives are widely
studied photosensitive compounds.27 The o-nitrobenzyl groups
can be cleaved with UV light (300−365 nm), thus inducing the
photoisomerization of o-nitrobenzyl alcohol derivatives to o-
nitrosobenzaldehyde.28 The activated light wavelength of these
compounds could be tuned by changing the substituent groups
on benzyl rings.29 Various o-nitrobenzyl alcohol derivative-
based photoresponsive systems were constructed including
gels,30−32 micelles,33,34 nanoparticles,35,36 and dendrimers.37
Thayumanavan et al. reported the amphiphilic dendrimers by
linking o-nitrobenzyl ester moieties with the lipophilic units and
the hydrophilic domains. Upon UV irradiation, the cleavage of
the o-nitrobenzyl bonds broke the hydrophilic−lipophilic
balance and disrupted the micelles.38 Recently, Zhao et al.
reported a new strategy enabling the use of a near-infrared
(NIR) laser to cleave the drug carriers bearing o-nitrobenzyl
groups and subsequently release the payloads. They encapsu-
lated the NaYF4:TmYb upconverting nanoparticles inside the
micelles and found that the emitted photons in the UV region
INTRODUCTION
■
In the past decades, considerable efforts have been paid to
advance our knowledge on developing stimuli-responsive
materials, including the stimulus of pH,1−4 temperature,5,6
redox,7,8 oxidation,9 electric field,10,11 and light12 for various
applications such as drug delivery,13,14 microrobots,15 sen-
sors,16,17 and catalysis.18 Of particular interest are the
photoresponsive materials for their advantages of ease
application, good stability, relative biocompatibility, great
selectivity under remote control at the spatial and temporal
precision, no additives, and environmental friendly.19 In recent
years, more and more photoresponsive systems have been
́
reported to show novel properties; for example, Frechet et al.
reported a PEG-lipid with the 2-diazo-1,2-naphthoquinones
(DNQ) as the hydrophobic end groups. The structure of DNQ
transformed to hydrophilic by UV irradiation at 350 nm,
resulting in the damage of the micelles and release of the
payloads.20 Yang et al. synthesized the novel photolabile
diblock copolymers bearing truxillic acid derivative junctions
that could take a reversible photochemical [2 + 2] cyclo-
addition reaction, such leading to the copolymers break or
combine together under UV irradiation around 260 nm.21
McGrath and co-workers have reported a series of photo-
switchable dendrimers based on the azobenzene structure.
Received: November 15, 2012
Revised: February 2, 2013
Published: February 18, 2013
© 2013 American Chemical Society
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vacuo, and the crude product was purified through a silica column with
activated the o-nitrobenzyl groups and cleaved the polymer
chains when the carriers were exposed to the NIR light.39 Their
results differed from that the o-nitrobenzyl groups were usually
used as a junction40 to combine the hydrophobic and
hydrophilic parts or to decorate them into side chains for
increasing the hydrophobicity and showed great potential for
the application in drug delivery systems.
Dendronized polymers, a merger of two concepts of
dendrimers and polymers, possess the particular structures
constructed by a linear polymer chain surrounded with certain
structural dendrons at the repeating units. The superiority of
such polymers with stimuli-responsiveness refers to easily
incorporating the responsive motifs into the polymers for the
densely packed modifiable peripheral groups of dendrons; the
balance of the molecular structures, for example, the hydro-
philicity−hydrophobicity ratios, can be easily adjusted by
converting the generation, interior building blocks, and surface
groups of the dendrons. Previously, we reported the
dendronized polymers synthesized either by attaching
butylamide-terminated amidoamine dendrons to PSt-alt-
PMAh copolymer or by polymerization of dendron-pendent
2-hydroxylethyl methacrylate.41,42 It was found that the
properties of polymers were dependent on the generation of
the dendrons and the molecular weights.
Herein, we report a kind of novel photoresponsive
dendronized polymer constructed with PSt-alt-PMAh copoly-
mer as the main chain on which jacketed the o-nitrobenzyl
decorated the amidoamine dendrons. We expect to take the
advantages of dendritic side chains with multiple modifiable
end groups, by which affords the polymers with multitudinous
UV light cleavable groups and balances the hydrophilic/
hydrophobic properties of the polymers and further changes
such characters with UV light. In this way, we aim to explore
the self-assembly behavior, guest molecules encapsulation, and
release properties of the obtained dendronized polymers.
THF as the eluent.
G1. This was obtained as a pale yellow solid. Yield: 75%. H NMR
1
(300 MHz, CDCl3, TMS, T = 298 K): 8.14−8.05 (br, 2H, NHCO),
8.00−7.89 (t, 2H, ArH), 7.84−7.74 (t, 2H, ArH), 7.70−7.54 (m, 4H,
ArH), 7.50−7.41 (t, 1H, NHCO), 6.2−5.85 (s, 1H, −CH2NHC
O), 5.55−5.44 (s, 4H, −OCHH2Ar), 3.43−3.27 (m, 8H, NCH2CH2−,
OCNHCH2−), 3.21−3.08 (m, 2H, OCNHCH2CH2−), 2.75−
2.60 (m, 4H, −CH2NHCO), 2.53−2.42 (m, 2H, −CH2CH2N-
(CH2)−), 2.39−2.24 (m, 4H, −CH2CH2CO), 1.52−1.30 (m, 9H,
(CH3)3CO−). ESI FTMS calculated for C33H46N8O12, [M + H]+:
747.32, [M + Na]+: 769.32, [M + K]+: 785.32; found: 747.3, 769.3,
785.3. EA calculated for C, 53.08; H, 6.21; N, 15.01; O, 25.71;
measured: C, 52.99; H, 6.25; N, 14.84. FT-IR: 3333, 3079, 2972, 1703,
1645, 1527, 1450, 1342, 1265, 1155, 1032, 860, 789, 730, 673 cm−1.
Synthesis of G2. G2 was synthesized with the same procedures of
G1. 2.00 g (6.29 mmol) of compound 1 was dissolved in the
anhydrous DMF, and a solution of G2 aminoamine dendron (0.53 g,
0.63 mmol) in 10 mL of anhydrous DMF was added to the mixture
dropwise. After being stirred at room temperature for 48 h, the
solution was evaporated in vacuo, and the crude product was purified
through a silica column using methanol/chloroform (1:5) as the
eluent.
1
G2. This was obtained as a pale yellow solid. Yield: 46%. H NMR
(300 MHz, CDCl3, TMS, T = 298 K): 8.09−8.00 (m, 4H, NHCO,
ArH), 7.64−7.56 (m, 8H, ArH), 7.51−7.39 (m, 6H, ArH), 6.60−6.17
(m, 5H, NHCO), 5.50−5.39 (m, 8H, OCH2Ar), 3.45−3.12 (m,
24H, NCH2CH2CO−, OCNHCH2CH2N), 2.79−2.62 (m, 12H,
OCNHCH2CH2NH−), 2.58−2.47 (m, 6H NHCH2CH2N), 2.42−
2.27 (m, 12H, NCH2CH2CO), 1.51−1.35 (s, 9H, (CH3)3CO−). ESI
FTMS calculated for C69H96N18O24, [M + H]+: 1561.69; found:
1561.7. FTIR: 3418, 3078, 2939, 2852, 2293, 1711, 1650, 1528, 1443,
1353, 1255, 1150, 1035, 860, 786, 732, 669 cm−1.
Synthesis of G3. G3 was synthesized by the same procedures of
G1. 1.60 g of compound 1 (5.03 mmol) was dissolved in the
anhydrous DMF, and a solution of G3 aminoamine dendron (0.55 g,
0.31 mmol) in 10 mL of anhydrous DMF was added into the mixture
dropwise. After being stirred at room temperature for 48 h, the
solution was evaporated in vacuo, and the crude product was purified
through a silica column using methanol/chloroform (1:1) as the
eluent.
EXPERIMENTAL SECTION
1
■
G3. This was obtained as a pale yellow solid. Yield: 29%. H NMR
Materials. Amidoamine dendrons were synthesized according to
the method reported previously.43 PSt-alt-MAh copolymer was kindly
provided by Professor Zichen Li’s group with the number molecular
weight of 10 800 and the PDI of 1.32. N,N-Dimethylformamide,
triethylamine, and tetrahydrofuran were purchased from Chemical
Reagent Beijing Co. and purified according to the standard procedures.
All the reagents and the common solvents were obtained from the
commercial sources and used as received unless stated otherwise.
Synthesis of Compound 1. 1.00 g of o-nitrobenzyl (6.54 mmol)
alcohol was dissolved in anhydrous THF, and 1.20 mL of triethylamine
(TEA) was added dropwise. The mixture was cooled in an ice salt bath
for 20 min. Then a solution of p-nitrophenyl chloroformate (1.56 g,
7.76 mmol) in THF was added dropwise within 10 min. After the
solution was stirred at room temperature for 24 h, the resulting white
salt TEA·HCl was filtrated, and the filtrate was collected and
evaporated in vacuo. The crude product was purified through a silica
column. The structure and molecular weight of the compound 1 were
(300 MHz, CDCl3, TMS, T = 298 K): 8.08−7.98 (m, 8H, NHCO,
ArH), 7.71−7.53 (m, 28H, ArH), 7.47−7.39 (m, 8H, ArH), 6.55−6.39
(m, 8H, NHCO), 5.49−5.39 (m, 16H, OCH2Ar), 3.42−3.15 (m,
48H, NCH2CH2CO−, OCNHCH2CH2N), 2.80−2.64 (m, 28H,
OCNHCH2CH2NH−), 2.58−2.46 (m, 14H, NHCH2CH2N),
2.41−2.26 (m, 28H, NCH2CH2CO), 1.45−1.35 (s, 9H,
(CH3)3CO−). ESI FTMS calculated for C141H196N38O48, [M + H]+:
3191.4, [M + 2H]2+: 1596.2, [M + 3H]3+: 1064.5, [M + 4H]4+: 798.6,
[M + 5H]5+: 639.1, [M + 6H]6+: 532.7; found: 3192.5, 1596.2, 1064.5,
798.6, 639.1, 532.3. FTIR: 3309, 3078, 2941, 2840, 1716, 1650, 1527,
1444, 1347, 1256, 1147, 1035, 860, 787, 733, 671 cm−1.
Synthesis of PGn-NB (n = 1, 2, 3). All the reactions were carried
out with anhydrous DMF as the solvent and the representative
procedures were as follows: 0.30 g of G1 (0.40 mmol) was dissolved in
1 mL of CH2Cl2, and then 0.5 mL of trifluoroacetic acid (TFA) was
added into the mixture dropwise within 5 min. The reaction was
monitored by thin-layer chromatography (TLC). After the solution
was being stirred at room temperature for 1 h, the excess TFA was
evaporated in vacuo, and the crude product was dissolved in 1 mL of
methanol and precipitated in diethyl ether three times. The viscous
liquid (DG1) was measured by 1H NMR to confirm the elimination of
Boc group. 305.6 mg of DG1 (0.40 mmol) was dissolved in the
anhydrous DMF, and 0.2 mL of TEA was added into the mixture
dropwise. A solution of 69.25 mg of PSt-alt-PMAh in 4 mL of DMF
was added into the mixture. After stirred at 60 °C in an oil bath for 48
h, the solution was evaporated in vacuo, and the crude product was
precipitated in THF three times. The obtained precipitate was
1
determined by the H NMR and ESI MS.
Compound 1. White solid. Yield: 44%. 1H NMR (300 MHz,
CDCl3, TMS, T = 298 K): 8.34−8.25 (m, 2H, ArH), 8.24−8.17 (br,
1H, ArH), 7.77−7.74 (m, 1H, ArH), 7.74−7.72 (br, 1H, ArH), 7.64−
7.53 (m, 1H, ArH), 7.47−7.38 (m, 2H, ArH), 5.77−5.69 (s, 2H,
ArCH2O). ESI MS: calcd for C14H10N2O7, [M + Na]+: 341; found:
341.
Synthesis of G1. 1.46 g of compound 1 (4.6 mmol) was dissolved
in anhydrous DMF, and a DMF solution of 0.71 g (1.8 mmol) of G1
aminoamine dendron was added to the mixture dropwise. After being
stirred at room temperature for 48 h, the solution was evaporated in
1
characterized by H NMR and FTIR measurements.
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Scheme 1. Synthesis and Structures of PGn-NB
PG1-NB. This was obtained as a yellow solid. Yield: 51%. 1H NMR
(400 MHz, DMSO-d6, TMS, room temperature): 8.31, 8.08, 7.89,
7.75, 7.64, 7.57, 7.41, 7.09, 5.35, 3.08, 2.09. IR (cm−1, KBr): 3323,
2924, 1701, 1655, 1523, 1453, 1342, 1251, 1141, 1031, 858, 731, 703.
PG2-NB. This was obtained as a yellow solid. Yield: 36%. 1H NMR
(400 MHz, DMSO-d6, TMS, room temperature): 8.08, 7.64, 7.57,
7.43, 7.01, 5.35, 3.07, 2.33, 2.09. IR (cm−1, KBr): 3309, 3081, 2943,
1702, 1663, 1524, 1454, 1343, 1253, 1200, 1032, 858, 792, 731, 704.
PG3-NB. This was obtained as a yellow solid. Yield: 21%. 1H NMR
(400 MHz, DMSO-d6, TMS, room temperature): 8.08, 8.01, 7.76,
7.64, 7.58, 7.42, 7.00, 5.35, 3.07, 2.79, 2.28, 2.08. IR (cm−1, KBr):
3306, 3081, 2938, 1715, 1653, 1523, 1343, 1254, 1200, 1032, 858, 792,
731, 702.
F4500 spectrometer (Hitachi). The AFM images of the aggregates of
PG2-NB were recorded by a Nanoscope Scanning Probe Microscopes
System (Digital Instrument). Differential scanning calorimetric (DSC)
measurement was performed on TA Instruments DSC Q100. The
polymer samples were sealed in the aluminum pans. An empty
aluminum pan was used as the reference. A scanning rate of 10.0 °C/
min was used for both heating and cooling processes between −50 and
120 °C. The glass transition temperature (Tg) was obtained from the
second heating run and corresponded to the midpoint of discontinuity
in the heat flow.
Light Cleavable Experiments of the Dendrons Gn (n = 1, 2,
3). All the light-responsive experiments were carried out under the
Blak-Ray B-100AP/R high-intensity UV lamp (100 W, 365 nm). The
samples were put in a platform with a distance of 9 cm under the
Lamp. UV−vis and 1H NMR analyses were used to measure the light-
cleavable properties of the dendrons Gn (n = 1, 2, 3). In the UV−vis
spectra experiments, the concentration of the o-nitrobenzyl group was
fixed at 1.2 × 10−4 mol/L to monitor the cleavage speed. The solution
was added into a quartz pool and put under the UV lamp. For the
NMR measurement, the Gn (n = 1, 2, 3) samples were put into an
NMR glass tube, and the concentration of o-nitrobenzyl group in
DMSO-d6 was fixed at the 0.04 mol/L.
1
Measurements. H NMR spectra were recorded on 300 MHz
(Varian Mercury) and 400 MHz (Bruker) spectrometers operated at
room temperature with CDCl3 or DMSO-d6 as the solvents and
tetramethylsilane (TMS) as the internal standard. FTIR spectra were
recorded on a VECTOR 22 Fourier transform IR spectrometer
(Bruker) with KBr as substrates. UV−vis spectra were obtained on a
Lambda 35 UV/vis spectrometer (PerkinElmer). The slit width was
1.0 nm. A gel permeation chromatograph (GPC) equipped with a
Waters 410 refractive index detector, a Waters 515 HPLC pump, and
Ultrastyragel columns (104, 103, and 500 Å) with THF as an eluent at
a flow rate of 1.0 mL/min. Monodispersity polystyrene standards were
used for calibration. The fluorescence spectra were recorded on a
Critical Aggregation Concentration (CAC) Measurement.
The CACs of the dendronized polymers were determined by the
fluorescence method reported previously with pyrene as a probe.44,45
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1
Figure 1. H NMR spectra of (a) PSt-alt-PMAh and (b) PG1-NB.
100 μL of THF solution of pyrene (1.0 × 10−3 mol/L) was added to a
100 mL volumetric flask, and the solvent was removed by the nitrogen
flow. Then the deionized water was added. The DMSO solutions of
PGn-NB (n = 1, 2, 3) were added into the aqueous solution of pyrene
to prepare the samples with various concentrations. The polymer
solutions were equilibrated for 24 h at room temperature. The
fluorescence spectra were recorded on a F4500 spectrometer
(Hitachi). The excitation and emission slit width of the fluorometer
were set at 5.0 and 2.5 nm, respectively. The excitation wavelength was
set up at 339 nm, and the emission spectra were recorded from 360 to
580 nm at a scanning rate of 240 nm/min. The I1 value was defined as
the emission intensity at 374 nm and the I3 value at 384 nm.
Light-Responsive Behavior of the Dendronized Polymers
PGn-NB (n = 1, 2, 3). Both dynamic light scattering (DLS) and static
light scattering (SLS) measurement of PG2-NB (0.05 mg/mL in
deionized water) were performed on a Brookhaven goniometer (BI-
200SM) equipped with a BI-TurboCorr digital correlator 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). For a dilute
solution, the root-mean-square radius of gyration (Rg) can be obtained
from SLS data on the basis of
RESULTS AND DISCUSSION
■
Synthesis of the Dendronized Polymers. PSt-alt-PMAh
copolymer was synthesized by the reversible addition−
fragmentation transfer (RAFT) polymerization with the
number-average molecular weight of 10 800 and the PDI of
1.32 characterized by GPC. Gn (n = 1, 2, 3) were obtained by
the reaction of compound 1 with amino-terminated amido-
amine dendrons. The dendronized polymers PGn-NB (n = 1, 2,
3) were prepared through removing the focal Boc group of the
dendrons with trifluoroacetic acid and then attached them to
the PSt-alt-PMAh copolymer chains via a ring-opening reaction
of exposed NH2 on the periphery of dendrons with maleic
anhydride groups of the copolymer in the excess triethylamine.
The structures and molecular weights of the resulting
1
dendronized polymers were characterized by H NMR and
FTIR measurements. Figure 1 shows the H NMR spectra of
1
PSt-alt-PMAh and PG1-NB. The following changes were
observed: the signal at 5.35 ppm corresponding to the
methylene protons of the o-nitrobenzyl rings appeared, the
peaks around 7.35 ppm emerged, and the peaks at high field
attributed to the backbones of aminoamine dendrons arose as
the broad peaks. These results indicated that the dendrons were
attached to the backbone of the polymer chains. From the
integral ratio of the phenyl protons of the styrene units and the
methylene protons of the o-nitrobenzyl ring at 5.35 ppm, the
coverage degrees of PGn-NB (n = 1, 2, 3) were calculated to be
74%, 42%, and 26%, respectively. Accordingly, the molecular
weights of the dendronized polymers were 2.6 × 104, 3.3 × 104,
and 4.3 × 104 calculated by the equation
2
HC/Rvv(θ) = (1/Mw)[1 + (1/3)Rg q2] + 2A2C
where H = 4π2n2(dn/dC)2/(NAλ4) and q = 4πn/λ sin(θ/2); NA, n, dn/
dC, and λ are Avogadro’s number, the solvent refractive index, the
specific refractive index increment, and the wavelength of light in a
vacuum, respectively. In DLS, by using a Laplace inversion program,
CONTIN, the normalized distribution function of the characteristic
line width was obtained which could be further converted into the
hydrodynamic radius Rh by using the Stokes−Einstein equation D =
kBT/6πηRh, where D, kB, T, and η are the translational diffusive
coefficient, the Boltzmann constant, the absolute temperature, and the
viscosity of the solvent, respectively. The morphologies of the
aggregates before and after UV irradiation were recorded on the
Nanoscope Scanning Probe Microscopes System (Digital Instrument).
All the samples were prepared as follows: 5 μL solution of PG2-NB
was dropped onto a mica platform before irradiation and water was
evaporated in the atmosphere.
Encapsulation and Release of Nile Red. The Nile Red was
chosen as a hydrophobic guest for its stability under UV
irradiation.34,36 0.47 mg (1.5 μmol) of Nile Red and 5.01 mg of
PG2-NB were dissolved in 100 μL of DMSO. 5 μL of the above
solution was added into 5 mL of deionized water to adjust the final
concentration of PG2-NB to be 0.05 mg/mL. The solution was
equilibrated for 24 h at room temperature. The release of the model
guest molecules was measured by the fluorescence spectrometer. The
F4500 fluorescence spectrometer was used to measure the
fluorescence spectra. The excitation and emission slit width were 5.0
and 5.0 nm, respectively. The excitation wavelength was set up at 540
nm, and the emission spectra were recorded from 560 to 750 nm at a
scanning speed of 240 nm/min.
Mw = 10800 + 53 × (MDGn − 114) × g
where the MDGn are the molecular weight of DGn, 114 is the
molecular weight of CF3COOH, g is the degree of coverage,
and 10 800 and 53 are the molecular weight and the degree of
polymerization of PSt-alt-PMAh, respectively. Obviously, the
average attaching number of dendrons decreased in the order of
PG1-NB > PG2-NB > PG3-NB. Similar phenomena were also
observed by Schluter et al.46,47 and our group in the previous
̈
studies.41 This could be well understood from the architectural
effect. The higher generation dendrons with more branches
prevented the reaction due to the steric hindrance.
The structures of the resulting dendronized polymers were
further confirmed by FTIR measurement. Comparing the FTIR
spectra of PGn-NB (n = 1, 2, 3) to that of PSt-alt-PMAh
(Figure 2), we found that (1) the stretching vibration of N−H
(the amide groups of aminoamine dendrons) and O−H (the
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afford the dendronized polymers with softer nature, leading to a
decrease in Tg.
Light-Cleavable Behavior of Gn (n = 1, 2, 3). UV−vis
measurement was performed to gain insight into the light-
cleavable behavior of Gn (n = 1, 2, 3). Figure 3a shows the
absorption change of Gn (n = 1, 2, 3) in methanol upon UV
irradiation. The absorption wavelength of the samples shifted
from 259 to 280 nm with the increase of irradiation time,
indicating the gradual cleavage of o-nitrobenzyl groups.29−34
However, the isosbestic point could not be observed because of
the simultaneous formation of byproducts. The amino end
groups of attached dendrons might react with o-nitro-
sobenzaldehyde generated from the dendronized polymers by
UV irradiation, which would form imines, dimeric azobenzene,
azoxybenzene compounds, and so on.28,48,49 A similar
phenomenon was also observed by Landfester et al.,32 who
synthesized a novel photolabile divinyl cross-linkers based on o-
nitrobenzyl derivatives to build up photodegradable PMMA
microgels. Figure 3b shows the absorbance change of Gn (n =
1, 2, 3) at 280 nm upon UV irradiation, which evidenced that
G2 degraded faster than G1 and G3. Besides UV−vis
spectroscopy, mass spectroscopy also provided the useful
information about the cleavage products (G2 sample). The
signals of 861, 1222, and 1382 referred to four, two and one o-
nitrobenzyl groups cleaved from G2 dendrons appeared, and
the byproducts of imine at 980, 1515 were also observed
(Figure S6).
Figure 2. FTIR spectra of PS-alt-PMAh and PGn-NB (n = 1, 2, 3).
carboxylic acid) were observed as a broad peak at 3315 cm−1;
(2) the peaks at 1859 and 1776 cm−1 attributed to the
stretching vibration of CO of maleic anhydride disappeared,
while the peak at 1715 cm−1 corresponding to the stretching
vibration of CO of carboxylic acid arose; and (3) the peaks at
1653 and 1524 cm−1 related to the character of amide I(νCO
)
and amide II(δN−H) bands were clearly visible. These results
were in good agreement with the proposed structures. The
detailed materials including 1H NMR results of the
dendronized polymers are described in the Supporting
Information.
1
Such a result is also supported by H NMR measurement.
Differential scanning calorimetric (DSC) measurement was
performed to understand the thermal properties of the obtained
dendronized polymers. During the second heating run, the
polymers showed glass transition temperature (Tg) of 90.6,
79.6, and 71.1 °C for PG1-NB, PG2-NB, and PG3-NB,
respectively (Figure S3). The glass transitions were also
observed during the first cooling run with the cooling rate of
10.0 °C/min (Figure S3). Compared to PS-alt-PMAh (Tg 180
°C), the Tg of the dendronized polymers decreases as the
attaching dendrons with higher generations. This result is in
agreement with our previous report41,42 that the Tg has a
significant decrease as a result of increasing the generation of
dendritic side chains. The generation of dendrons may
dominate the change of Tg despite the less number of higher
generation dendrons appended on the polymer main chains.
Such results might be mainly due to the dendritic architecture.
The higher generation dendrons attached along the polymer
chain would occupy more room and enclose the polymer chain
inside. This would weaken the stiffness of the polymers and
The dendrons were dissolved in DMSO-d6 at the concentration
of 13.33 mg/mL, and then the sample was put under a UV
lamp. Obviously, the signal at 5.35 ppm has a significant
decrease after UV irradiation for 10 h (Figure 4a). Figure 4b
shows the change of integral values of the peaks at 5.35 ppm
(methylene protons of o-nitrobenzyl ring). It decreases as the
UV irradiation time increases. The second-generation dendron
G2 also shows a faster degradable rate than the others. This
order is independent of the solvent. As reported by Cameron
́
and Frechet, the photolysis of the o-nitrobenzyl groups was “a
complex combination of both steric and electronic effects, as
well as the statistics of the hydrogen atom abstraction”.28,48
Under UV irradiation, the o-nitrobenzyl groups will undergo a
hydrogen abstraction process to form a five-ring intermediate,
which then affords the o-nitrosobenzyl aldehyde. In our case,
the detailed reasons for the degradation time order of G2 > G1,
G3 are not clear now, but we think the steric effect may
dominate the photolysis of the o-nitrobenzyl moieties for the
Figure 3. (a) Absorption of methanol solution of G2 with different irradiation time and (b) the absorbance of Gn (n = 1, 2, 3) at 280 nm upon UV
irradiation with times.
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Figure 4. 1H NMR spectrum of (a) G2 upon UV irradiation with time and (b) the change of the intergral values of the peaks at 5.35 ppm toward
times with UV irradiation.
Figure 5. TEM images of the aggregates in water (a) PG1-NB, (b) PG2-NB, and (c) PG3-NB Concentration: 0.05 mg/mL.
Scheme 2. Schematic Mechanism of the Aggregation and Cleavage of PGn-NB (n = 1, 2, 3) in the Solution under UV Irradiation
multiple groups on the periphery of the dendritic side chains.
Such structures have steric effect apparently and may be in
favor of the hydrogen atom abstraction. The degradation of the
dendronized polymers was characterized by the GPC experi-
ments. Figure S7 shows the GPC traces of the PG1-NB
dendronized polymers before (black) and after (red) UV
irradiation for 10 h in DMF. It was found that the elution time
increased from 9.00 to 9.65 min after irradiation, indicating the
decrease of the molecular weight of PG1-NB dendronized
polymers and the degradation of the o-nitrobenzyl groups on
the periphery.
Aggregation Behavior of PGn-NB (n = 1, 2, 3). The
dendronized polymers PGn-NB (n = 1, 2, 3) are expected to
display an amphiphilic property. Therefore, the self-assembly of
these amphiphilic dendronized polymers was studied by using
pyrene (Py) as a probe. The critical aggregation concentration
(CAC) of these polymers was determined by following the
change of I1/I3 ratio of pyrene with increasing polymer
concentration because the I1/I3 ratio would decrease as pyrene
transferred from a hydrophilic to a hydrophobic environment.45
The original plots are shown in Figure S9. The CAC values are
in the order of PG1-NB (0.05 mg/mL) > PG3-NB (0.03 mg/
mL) > PG2-NB (0.01 mg/mL), suggesting that PG2-NB self-
organizes to ordered aggregates more readily than PG1-NB and
PG3-NB. The higher CAC value of PG3-NB may be due to the
low grafting rate of G3 dendrons with relatively large size,
which cannot afford the polymers with better hydrophobic and
hydrophilic balance. PG1-NB has higher dendron coverage, but
G1 dendron is less hydrophobic than G2, such leading to PG2-
NB showing the lowest CAC value. However, compared to
other types of the amphiphilic polymers, the resulting
dendronized polymers showed very low CACs. Such a result
is consistent with our previous report that all the CAC values of
poly(aminoamine) dendrimers with a shell of aromatic
chromophores are very low in the range of 10−5−10−7 M.50
Figure 5a−c shows the TEM images of the aggregates from
PGn-NB (n = 1, 2, 3). The spherical aggregates with ca. 80 nm
(PG1-NB), 50 nm (PG2-NB), and 130 nm (PG3-NB) in
diameter are observed. The formation of spherical aggregates
can be attributed to the amphiphilic structure of PGn-NB (n =
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1, 2, 3), i.e., hydrophilic dendritic branches; hydrophobic
styrene unites in the main chain and o-nitrobenzene at the
periphery of the dendrons. The hydrophilic branches of
dendrons and the carboxyl groups in the polymer main chains
tumble out to occupy more room in water. To minimize the
energy in water, the hydrophobic aromatic moieties in the
polymers tend to pack together with the aid of π−π interaction
to form the hydrophobic domain as illustrated in Scheme 2.
When the o-nitrobenzyl groups were changed into the
dimethoxy-substituted derivates, the first-generation dendron-
ized polymers (PG1-2MeONB) shows a lower CAC value as
0.01 mg/mL, compared with the same generation PG1-NB,
indicating that the dimethoxy groups in the phenyl ring
provided the periphery of dendrons with the enhanced
hydrophobic property, and expedited them bending into the
PS-enriched core (Figure S12).
studied time period. However, the Rg,app increases significantly
at the same time (Figure 6A). The Rg/Rh ratio is a practical
parameter to describe the particle conformation in dilute
solution.51 As shown in the inset in Figure 6B, the Rg,app/Rh,app
ratio increases from 1.2 to 1.6 in 30 min. Combining the
decrease of scattered intensity and the increase of Rg,ap/Rh,app
ratio, it demonstrates that the tightly combined aggregates
become loose and the Mw,app of the aggregates decreases due to
the cleavage of o-nitrobenzyl groups by UV light. A proposed
mechanism of the aggregation is shown in Scheme 2. As
mentioned previously, the hydrophobic o-nitrobenzyl groups
on the periphery of the dendrons tended to enter the inter core
composed of styrene groups on the polymer main chain upon
folding the flexible dendritic branches, with which formed the
outer hydrophilic shell. Upon UV irradiation, the periphery of
dendrons became more hydrophilic because the o-nitrobenzyl
groups were cleaved from the exterior of them, thus the
branches of the dendrons would extend into the outer
hydrophilic environment rather than folding into the inner
hydrophobic domains. Therefore, the aggregates became loose
and the Mw,app was reduced, as demonstrated by the decrease of
the scattered intensity (Figure 6B).
Photodegradation of the Aggregates of PGn-NB (n =
1, 2, 3). The light scattering was employed to monitor the
photodegradation behavior of the dendronized polymers by
taking PG2-NB as an example. Figure 6A shows the change of
The photodegradation behavior of the dendronized polymers
was also confirmed by the morphology change of the aggregates
from PG2-NB before and after UV irradiation monitored by
AFM (Figure 7). The height of the aggregates was about 15 nm
(the height curves is shown in Figure 7a, inset) without UV
stimulus; however, the height of assemblies obviously increased
to about 70 nm with UV irradiation (the height curves is shown
in Figure 7b, inset). The size increasing of the aggregates may
be due to the degradation of the light-sensitive groups under
UV irradiation, such leading to break the intrinsic balance of the
amphiphilic properties of the polymers and inducing the
reorganization of the assemblies. The result is consistent with
that reported for the degradation of an amphiphilic block
copolymer containing nitrobenzyl groups in the main chain by
Zhao et al.34
Encapsulation and Release of the Guest Molecules.
To explore the encapsulation and release behavior of the
aggregates from the dendronized polymers, Nile Red (NR), a
commonly used fluorescence probe showing fluorescence with
strong dependence on the effective polarity of the environ-
ment52−54 and good stability under UV irradiation, was
entrapped into the aggregates of PG2-NB at a concentration
of 0.05 mg/mL. Figure 8a shows the fluorescence emission
spectra of NRs loaded in the aggregates before and after UV
irradiation in 120 min. Figure 8b displays the plots of
normalized fluorescence vs time for the sample without and
with UV irradiation in different times of irradiation. It is found
that the fluorescence intensity of NRs has no obvious change in
the absence of UV light (Figure 8b, black dots), indicating the
stable encapsulation of NRs in a hydrophobic environment.
However, when the sample was irradiated by UV light, the
fluorescent intensity dropped gradually (Figure 8b, red dots)
and achieved 60% in 3 h. This is indicative of disintegration of
the aggregates and the release of NRs molecules that contacted
with water consequently, such quenched the fluorescence of
them.
Figure 6. (A) Rh,app (hollow triangles) and Rg,app (black dots) of the
PG2-NB in water. (B) Time evolution of the excess scattered intensity
at 30° and the Rg,app/Rh,app ratio (the inset) of PG2-NB in water (0.05
mg/mL).
Rh,app (subscript app represents “apparent”) (hollow triangles)
and Rg,app (black dots) of the sample (0.05 mg/mL) with the
UV irradiation time. Before UV irradiation, only one mode
corresponding to the aggregates is observed at every scattered
angle (data not shown); the Rh,app is 95 nm after extrapolating
to zero angle. After UV irradiation, the excess scattered
intensity decreases greatly (Figure 6B) while the Rh,app of the
aggregates remains almost constant (Figure 6A) during the
CONCLUSIONS
■
In conclusion, we synthesized a series of photolabile
dendronized polymes PGn-NB (n = 1, 2, 3) through a graft-
to route by combination of PSt-alt-PMAh copolymer and o-
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Figure 7. AFM images of the aggregates of PG2-NB in water (a) before and (b) after UV irradiation.
Figure 8. (a) Fluorescence changes of Nile Red encapsulated in the aggregates of PG2-NB (0.05 mg/mL) in water with UV irradiation for different
times. (b) Plots of the fluorescence intensity of NRs at 630 nm vs irradiation time.
nitrobenzyl-terminated amidoamine dendrons with amino
groups at the focal point. The coverage degree of aminoamine
dendrons decreased as the generation increasing due to the
steric hindrance of the higher generation dendrons. All the
dendrons and the dendronized polymers showed photolabile
properties. Specially, G2 showed a faster degradation rate than
G1 and G3. The CAC values of the dendronized polymers
decreased in the order of PG1-NB > PG3-NB > PG2-NB,
which demonstrated that the structure of PG2-NB achieved
better hydrophobic and hydrophilic balance, leading to easily
form aggregates. The original aggregates were destroyed and
became loose under UV irradiation evidenced by laser light
scattering and AFM measurements. The guest encapsulation
and release properties of the resulting dendronized polymers
were explored by using NR as a model compound. The
fluorescence intensity of NRs dropped upon UV irradiation,
indicating the degradation of the polymers and the release of
the payloads. The photoresponsive dendronized polymers with
the concrete arrangement of hydrophilic and hydrophobic units
differ from conventional ones. Such a system may be potential
candidates for drug delivery systems.
AUTHOR INFORMATION
Corresponding Author
*E-mail xrjia@pku.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is financially supported by the National Natural
Science Foundation of China (21174005 and 21274004) to
X.R.J. The authors thank Prof. Zichen Li and Dr. Wenxi Ji for
the helpful supply of PSt-alt-PMAh alternating copolymer.
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