Novel photolabile diblock copolymers bearing truxillic acid derivative junctions

Article abstract of DOI:10.1021/ma1016264

Amphiphilic diblock copolymers, poly(ethylene glycol)-block-poly(acrylate), bearing truxillic acid derivatives at the junction point between the two blocks are described. The truxillic acid junction can be selectively cut by UV light, leading to a disassembly of the nano-objects made by self-assembly of the amphiphilic copolymers in water.

Full text of DOI:10.1021/ma1016264

Macromolecules 2011, 44, 159–165 159
DOI: 10.1021/ma1016264
Novel Photolabile Diblock Copolymers Bearing Truxillic
Acid Derivative Junctions
,
†
‡
†,‡
‡,§
Hong Yang,* Lin Jia, Zhifei Wang, Aur ꢀe lie Di-Cicco,
‡,§
,‡,^
Daniel L ꢀe vy, and Patrick Keller*
†
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China,
‡
Institut Curie, Centre De Recherche, CNRS UMR 168, Universit eꢀ Pierre et Marie Curie,
§
2
6 rue d’Ulm 75248 Paris Cedex 05, France, Pict-IbiSA, Institut Curie, Paris, France, and
^
Department of Chemistry and Biochemistry, University of Colorado, Boulder,
Colorado 80309-0215, United States
Received July 20, 2010; Revised Manuscript Received November 22, 2010
ABSTRACT: Amphiphilic diblock copolymers, poly(ethylene glycol)-block-poly(acrylate), bearing truxillic
acid derivatives at the junction point between the two blocks are described. The truxillic acid junction can be
selectively cut by UV light, leading to a disassembly of the nano-objects made by self-assembly of the
amphiphilic copolymers in water.
Introduction
photoirradiation-induced chemical reaction is an irreversible,
permanent photocleavage process. For this approach, basically
Amphiphilic block copolymers have the ability to self-assem-
ble in water to form various nano- or microsized objects, which
1
there are two general strategies. One strategy is using the mono-
mer units as the sacrificial parts. For example, o-nitrobenzyl
acrylates were polymerized to form hydrophobic polymer blocks,
which could be photocleaved to become hydrophilic poly(acrylic
have potential applications in many domains such as drug
2
3
4
5
delivery, biotechnology, catalysis, and materials chemistry.
Recently, polymer micelles and vesicles prepared from amphi-
philic block copolymers have received increasing interest because
several of their morphological parameters can be modified by the
action of external stimuli, either chemical stimuli (pH change,
redox reaction, hydrolysis, enzymatic reaction ) or physical
stimuli (thermal, magnetic, electrical, mechanical (i.e.,
ultrasound sonication), or photochemical ). In particular,
stimuli-triggered disassembly could be used to promote reactions
locally, such as controlling chemical reactions in microfluidics
or in drug delivery.
Light, as a remote stimulus, is an attractive nano-object
disassembling driving force, which has been intensively investi-
gated for two obvious advantages: (1) light can be accurately
targeted and highly selective; (2) in contrast to chemical stimuli,
no acids, bases, or other reagents have to be brought into the
system from outside, which in many cases could be technically
challenging.
Light-responsive polymer micelles/vesicles can be divided into
two main categories, depending on the kind of transformation
brought by the photochemical event: (1) The reversible structural
changes of the chromophores exposed to light modify the
hydrophilic-hydrophobic balances and therefore transform the
nanostructures of micelles/vesicles. Typical photochemically in-
duced transition examples use as chromophores azobenzenes
2
2
acid). Another one is to use polymer blocks as the sacrificial
parts. The latter is very promising and more efficient potentially,
since only one chromophore linker is required, which will need
less light power consumption to be cleaved. Up to now, there are
only a few examples of such photolabile block copolymers in the
6
7
8
9
10
1
1
12
13
2
3
24
1
4
15
literature, based on o-nitrobenzyl, 2-nitrophenylalanine, and
2
5
anthracene photosensitive derivatives (Scheme 1). Herein, we
present novel photolabile diblock copolymers bearing R-truxillic
acid derivatives as photocleavable junctions (Scheme 2B).
Our design was inspired by a well-studied photochemical
system: the cinnamic acid-truxillic acid reversible photochemical
16
1
7
2
6
[
2 þ 2] cycloaddition reaction (Scheme 2A). Cinnamic acid forms,
under illumination with ultraviolet light source with wavelengths
27
above 260 nm, a dimer, truxillic acid, which is stable at elevated
temperature and under a wide range of wavelengths of UV light.
The cyclobutane ring of truxillic acid is however photolabile under
deep-UV light, below 260 nm, giving back the original cinnamic
acid. This [2 þ 2] photodimerization of the cinnamic acid is in fact
very similar to the [4 þ 4] photodimerization of the anthracene
25
developed by Goldbach et al.
Our strategy, starting from R-truxillic acid, was to first
2
8
synthesize an ATRP (atom transfer radical polymerization)
macroinitiator by functionalizing an R-truxillic acid-ATRP
small molecule initiator with the hydrophilic poly(ethylene
glycol) block via ester or amid bonds, and then to prepare the
hydrophobic block via ATRP reaction, to create novel photo-
labile diblock copolymers (Scheme 3).
(
trans-to-cis isomerization, change of dipole moment, size, and
18
19
shape), spyrobenzopyran (formation of zwitterionic species),
20
triphenylmethane leucohydroxide (generation of charges), and
2
1
cinnamoyl (photodimerization). (2) The chromophores actu-
ally behave as photolabile covalent junctions between the poly-
mer main body and the sacrificial parts. In this case, the
Experimental Section
Materials and Instrumentation. MeO-PEG2000-OH was pur-
chased from Aldrich Inc. MeO-PEG20 I0 0-NH
from Polysciences Inc. The catalyst Cu Br (98%, Aldrich) was
2
was purchased
*
Corresponding authors: Tel 86 25 52090619, Fax 86 25 52090616,
e-mail pkuyh9@gmail.com (H.Y.); Tel 33 1 56246762, Fax 33 1
0510636, e-mail patrick.keller@curie.fr (P.K.).
2
purified as described previously. Monomer n-butyl acrylate
9
4
r 2010 American Chemical Society
Published on Web 12/09/2010
pubs.acs.org/Macromolecules

1
60 Macromolecules, Vol. 44, No. 1, 2011
Scheme 1. Representative Photocleavable Covalent Junctions of Reported Diblock Copolymers
Yang et al.
23-25
Scheme 2. Principle and Design of Applying r-Truxillic Acid Derivatives as Photocleavable Junctions
a
Scheme 3. Synthesis of Diblock Copolymers
a
Reagents and conditions: (i) NEt
3 2 3 2 3
, DCM; (ii) UV, solid state; (iii) 1: (COCl) , DCM; 2: NEt , 5, DCM; (iv) 1: (COCl) , DCM; 2: NEt , PEG-XH,
DCM; (v) CuBr, PMDETA, 1,4-dioxane, 70 ꢀC.
(
n-BA) and cyclohexyl acrylate (99%, Aldrich) were filtered through
a short column of neutral Al before use. Dichloromethane, 1,
-dioxane, and N,N ,N ,N ,N -pentamethyldiethylenetriamine were
2
distilled from CaH under argon. THF was distilled from sodium
benzophenone ketyl under argon. Other chemical reagents were
used without further purification. All nonaqueous reactions were
2
O
3
0
0
00 00
4

Article
Macromolecules, Vol. 44, No. 1, 2011 161
1
1
Figure 1. (A) H NMR spectra of PEG-O-macroinitiator. (B) H NMR spectra of PEG-NH-macroinitiator.
conducted in oven-dried glassware under a dry argon atmosphere.
All flash chromatography was performed using a Macherey-Nagel
MN Kieselgel 60 (0.063-1.2 mm).
Table 1. Characterization of Amphiphilic Diblock Copolymers
a
b
b
w
c
entry
copolymers
M
n
(g/mol) M
(g/mol) M
w
/M
n
R
1
O
All H NMR spectra were obtained using a Bruker HW300 MHz
1
2
3
4
5
6
PEG45- b-PBA28
5130
6050
11670
11400
13890
7160
5900
6660
13890
13680
15720
8680
1.15 33/67
1.10 19/81
1.19 6/94
1.20 12/88
1.13 10/90
1.21 20/80
O
spectrometer and recorded in CDCl (internal reference 7.26 ppm).
3
The molecular weights and the molecular weight distributions of all
the polymers were measured by size exclusion chromatography
PEG45- b-PBA63
O
PEG45- b-PCHA192
N
PEG45- b-PBA108
N
PEG45- b-PBA135
(SEC) using two Waters Styragel HR 5E columns, a Waters
N
PEG45- b-PCHA48
4110 differential refractometer (λ = 930 nm), and a Waters 486
N
7
a
PEG45- b-PCHA36
5550
6240
1.13 25/75
UV detector, in line with a Wyatt miniDAWN light scattering
instrument (Ar laser, λ = 690 nm). THF was used as the eluent at
1
DP (degree of polymerization) of acrylates was determined by H
b
NMR. Molecular weight measurements were analyzed by SEC based
c
on calibration using polystyrene standards. R represents the ratio of
hydrophilic block weight/hydrophobic block weight.
1
mL/min.
The morphological analysis of self-assembled aggregates was
performed by transmission electron microscopy (TEM) on samples
stained by uranyl acetate or by cryogenic transmission electron
microscopy (cryo-TEM) on samples fast frozen in liquid ethane.
TEM images were recorded using a Philips CM120 electron
microscope equipped with a Gatan SSC 1K_1K CCD camera,
and the cryo-TEM images were recorded using a Philips CM
1
Based on H NMR spectra, MeO-PEG2000-O-macroinitiator
contained some unreacted PEG2000-OH while PEG2000-NH-
macroinitiator had no PEG2000-NH left over.
2
Synthesis of PEO-b-PBA/PCHA Copolymers. Typical proce-
dure: MeO-PEG2000-macroinitiator (100 mg, 0.04 mmol), CuBr
120 kV Lab6. Image acquisition and image analysis were performed
at the PICT IBISA Imaging Facility.
(
4
11.5 mg, 0.08 mmol), n-butyl acrylate (220 mg, 1.72 mmol), 1,
-dioxane (0.35 mL), and PMDETA (16.7 μL, 0.08 mmol) were
-
2
A UV lamp (180 mW cm , λ = 365 nm; ELC-4001light
curing unit; Electro-Lite Corp.) and a low-pressure mercury
added into a Schlenk-type flask. The flask was degassed and
exchanged with argon via three freeze-thaw cycles and then
sealed in a pressure tube which was heated at 70 ꢀC for 18 h. The
reaction mixture was diluted with THF and passed through a
short basic aluminum oxide column to remove Cu salts. The
resulting solution was concentrated by rotary evaporation and a
high-vacuum oil pump to remove all the solvent and the
unreacted n-butyl acrylate, finally providing the corresponding
polymer as colorless oil (215 mg).
For MeO-PEG2000-O-macroinitiator, in order to remove
unreacted PEG-OH, the copolymer was further dialyzed against
2
THF-H O (1:3 volume ratios) solution to remove MeO-
PEG2000-OH, using a Spectra/Por regenerated cellulose mem-
brane with a molar mass cutoff of 3500 Da, and then lyophilized
to give a pure compound. Alternatively, the crude copolymer
could also be purified by silica column chromatography (eluting
-
2
vapor pencil-style lamp (3.5 mW cm , λ = 253.7 nm; inert gas
double bore lamp, Jelight Corp.) were used to irradiate the
samples to perform the photochemical reactions respectively at
different wavelengths. A quartz cell (3.0 cm high, 1.0 cm wide,
and 0.1 cm thick) was used to contain sample solutions for
irradiation experiments at 254 nm wavelength.
Synthesis of Intermediates 2, 5, and 6 and Macroinitiator 7.
The detailed experimental procedures and H NMR spectra of
1
compounds 2, 5, 6, and 7 are listed in the Supporting Information.
Typical procedure to prepare the macroinitiators 7: Oxalyl chloride
(760 μL, 8.71 mmol) was added into a solution of compound 6
(450 mg, 0.87 mmol) in 20 mL of dry THF. One drop of DMF was
added into this reaction mixture, which was then allowed to stir for
h at room temperature. The reaction mixture was concentrated by
1
rotary evaporation first and then submitted to a high-vacuum oil
pump to completely remove the volatiles. The residue was redis-
solvents: CH
sent in regular silica gel decomposed the copolymer into two
homopolymers by cutting off the linker. For MeO-PEG2000
2 2
Cl /MeOH, 95/5). However, the trace acids pre-
solved in 10 mL of dry CHCl . Triethylamine (73 μL, 0.52 mmol),
3
-
DMAP (11 mg, 0.09 mmol), and MeO-PEG2000-OH (830 mg, 0.42
mmol) were added into this resulting solution. The reaction mixture
was allowed to stir for 48 h at 60 ꢀC and then poured into a
saturated ammonium chloride solution. The resulting solution was
extracted by CH Cl (100 mL, twice). The combined organic layers
NH-macroinitiator, the above dialysis-lyophilization step was
unnecessary.
Self-Assembly of the Amphiphilic Block Copolymers in Water.
The block copolymers were first dissolved in 1,4-dioxane or
THF at a concentration of 1.0 mg/mL. Deionized water was
then added very slowly (5 μL portions) into 1.0 mL of the
copolymer solution with gentle shaking. After each addition of
water droplet, the solution was left to equilibrate for 5 min. The
cycles of water addition and equilibration were stopped after a
total amount of 1.5 mL of water has been added. The turbid
solution was then dialyzed against deionized water (water
2
2
were washed by H O (40 mL, twice), sodium bicarbonate aqueous
2
solution (40 mL, twice), brine (40 mL, once), dried over sodium
sulfate, and then concentrated by rotary evaporation to a 2 mL
solution, which was precipitated from 100 mL of diethyl ether
to give the desired compound, MeO-PEG2000-O-macroinitiator
(
810 mg), as a white solid.

1
62 Macromolecules, Vol. 44, No. 1, 2011
Yang et al.
changed every 6 h) for 3 days to remove all the organic solvents,
using a Spectra/Por regenerated cellulose membrane with a
molar mass cutoff of 3500 Da.
(4-hydroxybutyl)-2-bromo-2-methylpropanoate (5), which
was prepared by a simple esterification reaction between 1,
4-butanediol (3) and 2-bromo-2-methylpropionyl bromide (4)
and then reacted with monomethoxypoly(ethylene glycol),
Results and Discussion
PEG-OH, or PEG-NH to provide the macroinitiators 7. The
2
macroinitiators were then used in the atom-transfer radical
polymerization (ATRP) of different acrylate monomers to give
the desired amphiphilic diblock copolymers 8.
Synthesis and Characterization of Amphiphilic Block
Copolymers. The amphiphilic diblock copolymers synthesis
protocol is shown in Scheme 3. Recrystallized trans-cin-
namic acid 1 was irradiated in solid state in open air with a
UV lamp (180 mW cm , λ = 365 nm; ELC-4001 light curing
unit; Electro-Lite Corp.) for 24 h. The corresponding dimer,
R-truxillic acid (2), was first monofunctionalized with
In the above synthetic protocol (Scheme 3), steps i and iii
generated difunctional byproducts in addition to the desired
monofunctional compounds, which could be easily sepa-
rated by flash column chromatography since they were all
small molecules. However, the synthesis and purification of
macroinitiator 7 in step iv was very tedious but was also the
key step in the whole work. Our first try was to use the
-
2
3
0
standard DCC/DMAP coupling reaction to form an ester
bond linking PEG-OH and compound 6, which resulted in a
very low yield. Then, we used oxalyl chloride to activate the
carbonyl acid group to form a carbonyl chloride, which was
reacted with PEG-OH or PEG-NH2 (0.5 mol equiv of
compound 6). Despite several optimization tests, PEG-O-
macroinitiator still had some unreacted PEG-OH inside
(Figure 1A; for detailed integration values, see the Support-
ing Information), which could not be purified in this step.
PEG-NH , as a much stronger nucleophile, provided pure
2
PEG-NH-macroinitiator (Figure 1B). Fortunately, the con-
taminated PEG-OH could be removed in the final stage
through a simple dialysis-lyophilization process.
Seven different amphiphilic diblock copolymers were synthe-
sized and characterized (Table 1). The hydrophilic block was
always monomethoxylpoly(ethylene glycol) (PEG -OH or
45
PEG -NH , MW 2000, DP 45); the hydrophobic block was
2
45
either poly(butyl acrylate) or poly(cyclohexyl acrylate). The
degrees of polymerization of the poly(acrylate) blocks
were determined by H NMR using the integration value of
Figure 2. (A) Deep-UV illumination of R-truxillic acid dimethyl ester.
1
1
(
B) H NMR spectra of R-truxillic acid dimethyl ester: (a) without
illumination, (b) 1 h illumination, (c) 2 h illumination, (d) 4 h illumination.
the methylene protons (-O-CH CH -O-) of PEG as the
2
2
1
N
1
O
Figure 3. H NMR spectra of PEG45- b-PBA135 before illumination (A) and after 8 h illumination (B). H NMR spectra of PEG45- b-PBA28 before
illumination (C) and after 8 h illumination (D).

Article
Macromolecules, Vol. 44, No. 1, 2011 163
O
N
Figure 4. (A) SEC chromatograms of PEG45- b-PBA28 with increasing UV exposure times. (B) SEC chromatograms of PEG45- b-PBA108 with
increasing UV exposure times.
O
reference (see the Supporting Information). Herein, - b- repre-
sents an ester bond linker between PEG and truxillic acid,
while - b- represents an amide bond linker between PEG and
truxillic acid.
N
Model Molecule Illumination Test. Before studying the
photocleavage of amphiphilic diblock copolymers, a simple
model molecule illumination test was performed on a small
molecule, R-truxillic acid dimethyl ester, which is supposed
to be capable of being photocleaved into two cinnamic acid
methyl ester molecules. Assuming the cyclobutane ring of
R-truxillic acid dimethyl ester might have two random cutoff
directions, we should recover both trans-cinnamic acid
methyl ester and cis-cinnamic acid methyl ester (Figure 2A).
The initial concentration of R-truxillic acid dimethyl ester
was 5.0 mg/mL in THF. According to Spectral Database for
3
1
Organic Compounds SDBS, δ 3.81, 6.45, and 7.69 belong
to trans-cinnamic acid methyl ester, while δ 3.71, 5.96, and
6
4
.97 belong to cis-cinnamic acid methyl ester. After 1, 2, and
-
2
h of irradiation (3.5 mW cm , λ = 253.7 nm; inert gas
1
double bore lamp, Jelight Corp.), based on the H NMR
integration value ratio of three methyl protons (R-truxillic
acid dimethyl ester at δ 3.30, trans-cinnamic acid methyl
ester at δ 3.81, cis-cinnamic acid methyl ester at δ 3.71), we
could calculate the molar ratios of the three compounds
(Figure 2B and Supporting Information). Interestingly, the
molar ratio of cis-cinnamic acid methyl ester and trans-
cinnamic acid methyl ester remains constant at 1.3 during
the whole illumination.
Photoirradiation of Diblock Copolymers. We applied proton
NMR and size exclusion chromatography (SEC) techniques to
study the photocleavage of four amphiphilic diblock copoly-
Figure 5. TEM images of block copolymer self-assemblies. In the 1,4-
N
N
dioxane-H O system: PEG45- b-PCHA48 (A) and PEG45- b-PCHA36
2
N
(E). In the THF-H O system: PEG - b-PCHA (B) and PEG45-
b-PCHA36 (F). (C) and (D) show cryo-TEM images of PEG45
b-PCHA48 block copolymer self-assemblies in the 1,4-dioxane-H
system. Scale bar = 100 nm for all the figures.
2
45
48
O
N
N
mers: PEG - b-PBA (poly(ethylene glycol)-block-poly(butyl
28
-
O
4
5
N
acrylate)), PEG - b-PCHA (poly(ethylene glycol)-block-
2
45
48
N
poly(cyclohexyl acrylate)), PEG - b-PBA135, and PEG45-
45
N
b-PBA108. The initial concentrations of these amphiphilic
diblock copolymers were all of 5.0 mg/mL in THF. Since our
available mercury lamp had a very low power intensity of
amount of ozone generated in THF solvent. Thus, a shorter
copolymer, PEG45- b-PBA28 dissolved in degassed THF was
illuminated for 8 h in inert gas environment. As shown in
O
-
2
.5 mW cm , we have had to illuminate our copolymer
3
solutions for several hours.
1
Figure 3D, olefin protons around δ 6.5 on H NMR spectra
were clearly visualized, peaks that were absent from the original
N
At first, a series of PEG - b-PBA samples were irradiated
for 6, 8, 12, and 16 h. We expected to observe the olefin protons
45
135
before-illumination sample (Figure 3C).
The photocleavage was also confirmed by SEC. As shown
1
of cinnamic group appearing at δ 7-6 on H NMR spectra.
O
in Figure 4A, when PEG45- b-PBA28 was illuminated for
However, as shown in Figure 3A,B, neither olefin protons nor
even the aromatic protons were visualized. Then, we realized
that our mercury lamp would generate ozone which could
destroy all the olefins and even aromatic rings. Meanwhile,
8 h, it showed a new peak appearing close to the peak of pure
PEG45-OH. A further cleavage-by-irradiation overtime ex-
periment was performed on PEG45- b-PBA108 (Figure 4B).
N
N
since the initial concentrations of PEG - b-PBA was only
135
With increasing times of irradiation, the original peak
intensity decreased while the new peak close to the peak of
45
5.0 mg/mL, a relatively long hydrophobic block (135 BA units)
in the copolymer made the concentration of the R-truxillic acid
linker much lower, which was more susceptible to the trace
pure PEG45-NH
to completely break all the cyclobutane ring junctions.
increased. Finally, 24 h illumination seemed
2

1
64 Macromolecules, Vol. 44, No. 1, 2011
Yang et al.
R = 20/80) and PEG - b-PCHA (R = 25/75) were chosen
N
(
45
36
for the self-assembly experiments in aqueous solution at a low
concentration of 1 mg/mL in deionized water with the aid of 1,
4-dioxane or THF as cosolvent. The morphologies of all the
observed nano-objects are shown in Figure 5.
Analysis by TEM with negative staining revealed that
PEG - b-PCHA formed a mixture of spherical micelles
N
4
5
48
and spherical vesicles in the 1,4-dioxane-H O system
2
(Figure 5A). Cryo-TEM showed vesicles as being the
minority nano-objects (Figure 5C) while micelles were un-
fortunately the majority ones (Figure 5D). In the THF-H O
2
N
system, PEG - b-PCHA self-assembled into irregular
4
5
48
N
micelles (Figure 5B). Another copolymer, PEG - b-
4
5
PCHA , appeared as giving almost pure micelles in 1,4-
3
6
dioxane-H O and THF-H O systems (Figure 5E,F).
2
2
Although we did not find monodisperse vesicle morphology
in these photolabile amphiphilic block copolymer systems,
disassembly of micelles under photoirradiation should still be
N
attractive. When the irregular micelles of PEG - b-PCHA
48
45
sample self-assembled in THF-H O (Figure 6A) was illumi-
2
nated by a deep UV source, the nano-objects were transformed
into much smaller polydisperse condensed nanospheres
(Figure 6B) after 6 h exposure and became micrometer-sized
precipitates (Figure 6C,D) after 24 h exposure. Dynamic light
scattering (DLS) and SEC experiments (Figure 6E,F) con-
firmed these observations. As shown in Figure 6F, 6 h of
irradiation did not break all the block copolymers but changed
the hydrophilic-hydrophobic balance of the whole system, thus
1
changing the morphology of the nano-objects. However, when
all the copolymers were photocleaved after 24 h of irradiation,
the pure hydrophobic polymer chains were not stable in aqu-
eous solution, resulting in their precipitation as solid.
Conclusion
In conclusion, we developed and studied novel photolabile
diblock copolymers bearing R-truxillic acid derivative junctions.
Although the photocleavage of these copolymers requires a
strong UV source (λ < 260 nm) and long irradiation time which
is harmful to cells and tissues, these “proof-of-idea” block
copolymers could still be attractive candidates for applications
in nanoreactors and templates for micro- or nanostructured
materials. Furthermore, since R-truxillic acid derivatives can
survive UV irradiation of λ > 260 nm, wavelengths that are
not supported by o-nitrobenzyl groups, multiblock copolymers
bearing these two photolabile junctions could be selectively cut
off in specific blocks using different wavelengths of light. This will
be the subject of a future publication.
N
Figure 6. (A) TEM images of PEG45- b-PCHA48 self-assembly in
water before illumination (scale bar = 50 nm). (B) TEM images of
PEG45- b-PCHA48 self-assembly in water after 6 h illumination (scale
bar = 50 nm). (C, D) TEM images of PEG45- b-PCHA48 self-assembly
N
N
in water after 24 h illumination (scale bar = 50 nm for C, 1 μm for D).
Acknowledgment. This research was supported in part by
National Natural Science Foundation of China (Grant No.
(E) DLS size distribution by intensity graph of the formed nano-objects
before illumination and after 6 h illumination. (F) SEC chromatograms
2
1002012) and Agence Nationale de la Recherche (Award No.
N
of PEG45- b-PCHA48 with increasing UV exposure times.
ANR-07-MAPR-0020-02), and by NSF MRSEC (Grant No.
DMR-0820579). We thank Dr. J. Plastino for her critical reading
of the manuscript.
Photoirradiation of Self-Assembled Nano-objects. Our ul-
timate goal was to observe a UV-light-induced disassembly
of the nano-objects made by self-assembly of the amphiphilic
block copolymers in water. The ideal scenario was to have an
original self-assembled vesicle broken after photoirradia-
tion. In order to get vesicles, we chose to use a much stiffer
PCHA (poly(cyclohexyl acrylate)) hydrophobic block in-
stead of PBA (poly(butyl acrylate)) since the cyclohexyl ring
system is much more rigid which would help build the
hydrophobic shells of vesicles.
Supporting Information Available: Details of the synthesis
and characterization; H NMR spectra. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
1
References and Notes
(
1) (a) Discher, D. E.; Eisenberg, A. Science 2002, 297, 967–973. (b)
Kita-Tokarczyk, K.; Grumelard, J.; Haefele, T.; Meier, W. Polymer
2005, 46, 3540–3563. (c) Kukula, H.; Schlaad, H.; Antonietti, M.;
Forster, S. J. Am. Chem. Soc. 2002, 124, 1658–1663. (d) Riess, G.
Prog. Polym. Sci. 2003, 1107–1170.
3
2
On the basis of our previous experiences, when the hydro-
philic block/hydrophobic block weight ratio, R, is between
2
0/80 and 40/60, the block copolymer has better chance to
(2) (a) Joralemon, M. J.; McRae, S.; Emrick, T. Chem. Commun. 2010,
46, 1377–1393. (b) York, A. W.; Kirkland, S. E.; McCormick, C. L.
N
form vesicles in aqueous solution. Thus, PEG - b-PCHA
48
45

Article
Macromolecules, Vol. 44, No. 1, 2011 165
Adv. Drug Delivery Rev. 2008, 1018–1036. (c) Ganta, S.; Devalapally,
H.; Shahiwala, A.; Amiji, M. J. Controlled Release 2008, 126, 187–
04. (d) Discher, D. E.; Ortiz, V.; Srinivas, G.; Klein, M. L.; Kim, Y.;
Christian, D.; Cai, S.; Photos, P.; Ahmed, F. Prog. Polym. Sci. 2007,
2, 838–857. (e) Mahmud, A.; Xiong, X. B.; Aliabadi, H. M.;
Martinez, T. J.; Moore, J. S. J. Am. Chem. Soc. 2010, 132, 4558–4559.
(c) Gao, Z. G.; Fain, H. D.; Rapoport, N. J. Controlled Release 2005,
102, 203–222. (d) Nelson, J. L.; Roeder, B. L.; Carmen, J. C.; Roloff, F.;
Pitt, W. G. Cancer Res. 2002, 62, 7280–7283.
2
3
(15) (a) Goodwin, A. P.; Mynar, J. L.; Ma, Y.; Fleming, G. R.; Frechet,
J. M. J. J. Am. Chem. Soc. 2005, 127, 9952–9953. (b) Alvarez-
Lorenzo, C.; Bromberg, L.; Concheriro, A. Photochem. Photobiol.
2009, 85, 848–860.
Lavasanifar, A. J. Drug Targeting 2007, 15, 553–583. (f) Nishiyama,
N.; Kataoka, K. Pharm. Ther. 2006, 112, 630–648.
(
(
3) (a) Alemdaroglu, F. E.; Herrmann, A. Org. Biomol. Chem. 2007, 5,
1
311–1320. (b) Taubert, A.; Napoli, A.; Meier, W. Curr. Opin. Chem.
(16) (a) DeMello, A. J. Nature 2006, 442, 394–402. (b) Song, H.; Chen,
D. L.; Ismagilov, R. F. Angew. Chem., Int. Ed. 2006, 45, 7336–7356.
(17) Fomina, N.; McFearin, C.; Sermsakdi, M.; Edigin, O.; Almutairi,
A. J. Am. Chem. Soc. 2010, 132, 9540–9542.
Biol. 2004, 8, 598–603.
4) (a) Vriezema, D. M.; Aragon ꢁe s, M. C.; Elemans, J. A. A. W.;
Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M. Chem. Rev.
2
005, 105, 1445–1490. (b) Rodionov, V.; Gao, H.; Scroggins, S.;
Unruh, D. A.; Avestro, A.-J.; Frechet, J. M. J. J. Am. Chem. Soc.
010, 132, 2570–2572.
(18) (a) Mabrouk, E.; Cuvelier, D.; Brochard-Wyart, F.; Nassoy, P.; Li,
M.-H. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 7294–7298. (b)
Wang, G.; Tong, X.; Zhao, Y. Macromolecules 2004, 37, 8911–8917.
(c) Liu, X.; Jiang, M. Angew. Chem., Int. Ed. 2006, 45, 3846–3850. (d)
Desponds, A.; Freitag, R. Langmuir 2003, 19, 6261–6270.
(19) (a) Li, C.; Zhang, Y.; Hu, J.; Cheng, J.; Liu, S. Angew. Chem., Int.
Ed. 2010, 49, 5120–5124. (b) Konak, C.; Rathi, R. C.; Kopeckova, P.;
Kopecek, J. Macromolecules 1997, 30, 5553–5556.
2
(
5) (a) Ahn, S. K.; Kasi, R. M.; Kim, S. C.; Sharma, N.; Zhou, Y. X.
Soft Matter 2008, 4, 1151–1157. (b) Discher, B. M.; Hammer, D. A.;
Bates, F. S.; Discher, D. E. Curr. Opin. Colloid Interface Sci. 2000, 5,
1
25–131.
(
6) (a) Smith, A. E.; Xu, X. W.; McCormick, C. L. Prog. Polym. Sci.
2
010, 35, 45–93. (b) Wang, Y.; Xu, H.; Zhang, X. Adv. Mater. 2009,
(20) Kono, K.; Nishihara, Y.; Takagishi, T. J. Appl. Polym. Sci. 1995,
56, 707–713.
21, 2849–2864. (c) Meng, F. H.; Zhong, Z. Y.; Jan, F. Biomacromole-
cules 2009, 10, 197–209. (d) Li, M. -H.; Keller, P. Soft Matter 2009, 5,
27–937. (e) Rapoport, N. Prog. Polym. Sci. 2007, 32, 962–990. (f)
Rijcken, C. J. F.; Soga, O.; Hennink, W. E.; van Nostrum, C. F. J.
Controlled Release 2007, 120, 131–148.
7) (a) Du, J.; Wang, Y.; Lewis, A. L.; Armes, S. P. J. Am. Chem. Soc.
(21) Yuan, X.; Fischer, K.; Sch €a rtl, W. Langmuir 2005, 21, 9374–9380.
(22) (a) Jiang, X.; Lavender, C. A.; Woodcock, J. W.; Jeremiah, W.;
Zhao, B. Macromolecules 2008, 41, 2632–2643. (b) Ionov, L.; Diez, S.
J. Am. Chem. Soc. 2009, 131, 13315–13319.
(23) (a) Kang, M.; Moon, B. Macromolecules 2009, 42, 455–458. (b)
Schumers, J. M.; Gohy, J. F.; Fustin, C. A. Polym. Chem. 2010, 1, 161–
163. (c) Katz, J. S.; Zhong, S.; Ricart, B. G.; Pochan, D. J.; Hammer,
D. A.; Burdick, J. A. J. Am. Chem. Soc. 2010, 132, 3654–3655. (d)
Sundararjan, S.; Sengupta, S.; Ibele, M. E.; Sen, A. Small 2010, 6,
1479–1482.
9
(
2005, 127, 17982–17983. (b) Borchert, U.; Lipprandt, U.; Bilang, M.;
Kimpfler, A.; Rank, A.; Peschka-S €u ss, R.; Schubert, R.; Lindner, P.;
F €o rster, S. Langmuir 2006, 22, 5843–5847. (c) Chiu, H.-C.; Lin, Y.-W.;
Huang, Y.-F.; Chuang, C.-K.; Chern, C.-S. Angew. Chem., Int. Ed.
2008, 47, 1875–1878. (d) Bellomo, E. G.; Wyrsta, M. D.; Pakstis, L.;
Pochan, D. J.; Deming, T. J. Nature Mater. 2004, 3, 244–248. (e)
Rodriguez-Hernandez, J.; Lecommandoux, S. J. Am. Chem. Soc.
(24) Peters, F. B.; Brock, A.; Wang, J.; Schultz, P. G. Chem. Biol. 2009,
16, 148–152.
2
005, 127, 2026–2027. (f) Klaikherd, A.; Nagamani, C.; Thayumanavan,
(25) Goldbach, J. T.; Russell, T. P.; Penelle, J. Macromolecules 2002, 35,
4271–4276.
S. J. Am. Chem. Soc. 2009, 131, 4830–4838. (g) Liu, C.; Hillmyer, M. A.;
Lodge, T. P. Langmuir 2009, 25, 13718–13725.
(26) (a) Lendlein, A.; Jiang, H.; Junger, O.; Langer, R. Nature 2005, 434,
879–882. (b) Akabori, S.; Habata, Y.; Nakazawa, M.; Yamada, Y.;
Shindo, Y.; Sugimura, T.; Sato, S. Bull. Chem. Soc. Jpn. 1987, 60,
3453–3455. (c) Caccamese, S.; Maravigna, P.; Montaudo, G.; Recca,
A.; Scamporrino, E. J. Polym. Sci., Polym. Chem. Ed. 1978, 16,
3123–3130. (d) Caccamese, S.; Maravigna, P.; Montaudo, G.; Recca,
A.; Scamporrino, E. J. Polym. Sci., Polym. Chem. Ed. 1979, 17,
1463–1471.
(
8) (a) Power-Billard, K. N.; Spontak, R. J.; Manners, I. Angew.
Chem., Int. Ed. 2004, 43, 1260–1264. (b) Ma, N.; Li, Y.; Xu, H.;
Wang, Z.; Zhang, X. J. Am. Chem. Soc. 2010, 132, 442–443. (c)
Napoli, A.; Valentini, M.; Tirelli, N.; M €u ller, M.; Hubbell, J. A. Nature
Mater. 2004, 3, 183–189. (d) Wang, X.; Wang, H.; Coombs, N.;
Winnik, M. A.; Manners, I. J. Am. Chem. Soc. 2005, 127, 8924–
8
925. (e) Cerritelli, S.; Velluto, D.; Hubbell, J. A. Biomacromolecules
2
007, 8, 1966–1972. (f) Dong, W.-F.; Kishimura, A.; Anraku, Y.;
(27) (a) Bernstein, H. I.; Quimby, W. C. J. Am. Chem. Soc. 1943, 65,
1845–1846. (b) Chi, Y.-M.; Nakamura, M.; Yoshizawa, T.; Zhao, X.-Y.;
Yan, W.-M.; Hashimoto, F.; Kinjo, J.; Nohara, T.; Sakurada, S. Biol.
Pharm. Bull. 2005, 28, 1776–1778.
(28) Wang, J.; Matyjaszewski, K. J. Am. Chem. Soc. 1995, 117, 5614–
5615.
(29) Li, M. H.; Keller, P.; Grelet, E.; Auroy, P. Macromol. Chem. Phys.
Chuanoi, S.; Kataoka, K. J. Am. Chem. Soc. 2009, 131, 3804–3805.
9) (a) Ahmed, F.; Pakunlu, R. I.; Brannan, A.; Bates, F.; Minko, T.;
Discher, D. E. J. Controlled Release 2006, 116, 150–158. (b) Sanson,
C.; Schatz, C.; Le Meins, J. F.; Brulet, A.; Soum, A.; Lecommandoux, S.
Langmuir 2010, 26, 2751–2760.
10) (a) Azagarsamy, M. A.; Sokkalingam, P.; Thayumanavan, S. J. Am.
Chem. Soc. 2009, 131, 14184–14185. (b) Amir, R. J.; Zhong, S.; Pochan,
D. J.; Hawker, C. J. J. Am. Chem. Soc. 2009, 131, 13949–13951.
11) (a) Dimitrov, I.; Trzebicka, B.; Muller, A. H. E.; Dworak, A.;
Tsvetanov, C. B. Prog. Polym. Sci. 2007, 32, 1275–1343. (b)
Morishama, Y. Angew. Chem., Int. Ed. 2007, 46, 1370–1372. (c) Li,
Y.; Lotiz, B.; McCormick, C. L. Angew. Chem., Int. Ed. 2006, 45,
(
(
(
2002, 203, 619–626.
(30) Neises, B.; Steglich, W. Angew. Chem. 1978, 90, 556–557.
(31) http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/direct_frame_top.cgi.
(32) (a) Yang, J.; Levy, D.; Deng, W.; Keller, P.; Li, M.-H. Chem.
Commun. 2005, 4345–4347. (b) Yang, J.; Pinol, R.; Gubellini, F.; Levy,
D.; Albouy, P.-A.; Keller, P.; Li, M.-H. Langmuir 2006, 22, 7907–7911.
(c) Pinol, R.; Jia, L.; Gubellini, F.; Levy, D.; Albouy, P.-A.; Keller, P.;
Cao, A.; Li, M.-H. Macromolecules 2007, 40, 5625–5627. (d) Boisse,
S.; Rieger, J.; Di-Cicco, A.; Albouy, P.-A.; Bui, C.; Li, M.-H.; Charleux,
B. Macromolecules 2009, 42, 8688–8696. (e) Xu, B.; Pinol, R.; Nono-
Djamen, M.; Pensec, S.; Keller, P.; Albouy, P.-A.; Levy, D.; Li, M.-H.
Faraday Discuss. 2009, 143, 235–250. (f) Jia, L.; Cao, A.; Levy, D.;
Xu, B.; Albouy, P.-A.; Xing, X.; Bowick, M. J.; Li, M.-H. Soft Matter
2009, 5, 3446–3451.
5
792–5795.
(
(
(
12) Liu, T. Y.; Hu, S. H.; Liu, D. M.; Chen, S. Y.; Chen, I. W. Nano
Today 2009, 4, 52–65.
13) Yan, Q.; Yuan, J.; Cai, Z.; Xin, Y.; Kang, Y.; Yin, Y. J. Am. Chem.
Soc. 2010, 132, 9268–9270.
14) (a) Caruso, M. M.; Davis, D. A.; Shen, Q.; Odom, S. A.; Sottos,
N. R.; White, S. R.; Moore, J. S. Chem. Rev. 2009, 109, 5755. (b)
Kryger, M. J.; Ong, M. T.; Odom, S. A.; Sottos, N. R.; White, S. R.;