Photoresponsive soft materials: Synthesis and photophysical studies of a stilbene-based diblock copolymer

Article abstract of DOI:10.1002/pola.24973

An amphiphilic diblock copolymer composed of a photoresponsive dialkoxycyanostilbene polymethacrylate and poly(ethylene oxide) (PDACS-b-PEO) was synthesized and its photophysical and aggregation properties were investigated. The amphiphilic nature of the polymer caused it to self-assemble in water, and dynamic light scattering studies indicated formation of spherical aggregates with an average size of 160 nm. Atomic force microscopy images of dried films cast from solutions containing the polymer aggregates revealed supramolecular aggregates with a spherical morphology. Photoisomerization of the stilbene chromophore in PDACS-b-PEO on UV irradiation resulted in the destruction of the self-assembled superstructures which could be attributed both to change in shape of the chromophore from the linear trans isomer to the bent cis isomer which would hinder self-aggregation of the molecules and the higher dipole moment of the cis isomer leading to a reduction of the hydrophobic nature of the stilbene containing block of PDACS-b-PEO. It was observed that hydrophobic dyes such as curcumin could be encapsulated within the hydrophobic interior of the spherical micellar aggregates from which the encapsulated dye could be released on UV irradiation.

Full text of DOI:10.1002/pola.24973

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ARTICLE
Photoresponsive Soft Materials: Synthesis and Photophysical Studies
of a Stilbene-Based Diblock Copolymer
Sajith Menon, Remyamol Thekkayil, Shinto Varghese, Suresh Das
Photosciences and Photonics Section, Chemical Sciences and Technology Division, National Institute for Interdisciplinary
Science and Technology, CSIR, Trivandrum, Kerala 695 019, India
Correspondence to: S. Das (E-mail: sureshdas55@gmail.com)
Received 17 June 2011; accepted 24 August 2011; published online 15 September 2011
DOI: 10.1002/pola.24973
ABSTRACT: An amphiphilic diblock copolymer composed of a
photoresponsive dialkoxycyanostilbene polymethacrylate and
poly(ethylene oxide) (PDACS-b-PEO) was synthesized and its
photophysical and aggregation properties were investigated. The
amphiphilic nature of the polymer caused it to self-assemble in
water, and dynamic light scattering studies indicated formation
of spherical aggregates with an average size of 160 nm. Atomic
force microscopy images of dried films cast from solutions con-
taining the polymer aggregates revealed supramolecular aggre-
gates with a spherical morphology. Photoisomerization of the
stilbene chromophore in PDACS-b-PEO on UV irradiation
resulted in the destruction of the self-assembled superstructures
which could be attributed both to change in shape of the chro-
mophore from the linear trans isomer to the bent cis isomer
which would hinder self-aggregation of the molecules and the
higher dipole moment of the cis isomer leading to a reduction of
the hydrophobic nature of the stilbene containing block of
PDACS-b-PEO. It was observed that hydrophobic dyes such as
curcumin could be encapsulated within the hydrophobic interior
of the spherical micellar aggregates from which the encapsulated
C
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dye could be released on UV irradiation. 2011 Wiley Periodicals,
Inc. J Polym Sci Part A: Polym Chem 49: 5063–5073, 2011
KEYWORDS: aggregates; atom transfer radical polymerization
(ATRP); block copolymers; irradiation; morphology; self-
assembly
INTRODUCTION Amphiphilic molecules can self-assemble in
selective solvents into a number of microstructures.1–5 Com-
pared to small molecular weight molecules, aggregates from
block copolymer amphiphiles are thermodynamically and
kinetically more stable, broadening their potential for tech-
nological applications in a variety of areas such as in biology,
colloid science, and encapsulation technology.6–11 Amphi-
philes self-assemble in solvents above their critical aggrega-
tion concentration with the aid of noncovalent interactions
to form supramolecular structures such as micelles, vesicles,
planar lamellar structures, cones, fibers, and nanotubes.12,13
Several factors such as copolymer composition and concen-
tration, nature of the common solvent and type, and concen-
tration of added ions have been found to control the nature
of the resulting morphologies.14–19 The resulting self-
assembled materials are of considerable interest for utiliza-
tion in various environmental, biomedical, electronics, and
materials applications, including the elimination of pollu-
tants, gene therapy, organic photovoltaics, coatings, and com-
posites.20–22
recently.23–25 Low solubility in water appears to be an intrin-
sic property of many drugs and anticancer agents, in particu-
lar, as many of them are bulky polycyclic compounds.26 If
the molecular target of a drug is located inside the cell, a
drug molecule must have a certain degree of hydrophobicity
to cross the cell membrane.27,28 Interestingly, drug candi-
dates with the highest activities identified by high through-
put screening technologies often have a poor solubility in
water.29 Therapeutic application of hydrophobic, poorly
water-soluble agents is however associated with serious
problems such as poor adsorption and bioavailability,30
embolization of blood vessels,31 and toxicity.32,33
Polymer nanocarriers which can be disrupted by light can
provide a viable solution to this problem.34 As light is a
remote stimulus photoresponsive systems does not require a
structural chemical change like that in the case of pH, oxida-
tion, and reduction responsive systems.35 It is conceivable
that if water insoluble drugs are encapsulated in the hydro-
phobic domains of such nanocarriers, and their release is
triggered by light, then time and the location of release can
be determined by when and where the light is applied.36
Recently, there have been a few reports on polymer micelles
which can be disrupted by UV light.37–46 In such systems,
The use of micelles prepared from amphiphilic copolymers
combining hydrophilic and hydrophobic blocks for solubiliza-
tion of poorly soluble drugs has attracted much attention
Additional Supporting Information may be found in the online version of this article.
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the amphiphilicity of the polymer can be tuned using light.
Photoresponsive amphiphilic polymers aggregate in water
with a hydrophilic corona and a light responsive hydropho-
bic core. Irradiation with light can convert the initially
hydrophobic part into a hydrophilic block there by disturb-
ing the micellar structure and there is considerable interest
in the design of such sysytems.47 Such photoresponsive poly-
mers are becoming increasingly important because of their
applicability as control release systems.
Poly(ethylene oxide) (PEO) is a hydrophilic polymer which
because of its nontoxic, nonantigenic, and nonimmunogenic
properties are widely used in biomedical applications.44,48,49
Amphiphilic block copolymers can be readily synthesized by
linking PEO to hydrophobic polymer chains and thereby
forming aggregates in water.50–54 We report here a novel
photoresponsive diblock copolymer which contains a hydro-
philic block of PEO and a hydrophobic polymethacrylate moi-
ety containing photoisomerizable cyano stilbene units as the
pendant groups (PDACS). This polymer which is abbreviated
as PDACS-b-PEO (Chart 1) contains 112 units of ethylene ox-
ide and 6 units of cyanostilbene. PDACS-PEO forms spherical
micellar aggregates in water with PDACS as the hydrophobic
core. On UV irradiation, linear trans-stilbene would be con-
verted into the bent cis form. As the cis-form is more polar
than the trans-form, photoisomerization would result in a
prominent decrease in hydrophobicity of the polymer leading
to deformation of the micellar aggregates. Using this process
hydrophobic dye trapped within the hydrophobic core of the
polymer micelle can be released on UV light exposure. It
may be note that for better penetration of light for in vivo
applications, systems which are responsive to near infra red
light would be more suitable.55,56
CHART 1
Standards Service). Waters 515 pump connected through
three series of Styragel HR columns (HR-3, HR-4E, and HR-
5E) and Waters model 2487 dual wavelength UV-vis detector
and a Waters 2414 differential refractometer were used for
analyzing the samples. The flow rate of the THF was main-
tained as 1 mL/min throughout the experiments, and the
sample solutions at very dilute concentration were filtered
ꢀ
and injected for recording the GPC chromatograms at 30 C.
Mass spectral analyzes were carried out using a JEOL
JMS600 instrument in FAB ionization mode. Melting points
are uncorrected and were determined on a Mel-Temp II
melting point apparatus. Absorption spectra were recorded
on a Shimadzu UV-3101PC UV-vis-NIR spectrophotometer.
The excitation and emission spectra were recorded on a
SPEX Fluorolog F112X spectrofluorimeter. Steady-state pho-
tolysis was carried out using the output from a 200 W high-
pressure mercury lamp filtered through a 340 nm Oriel
band-pass filter. Differential scanning calorimetry analysis
was carried out under nitrogen, using Perkin-Elmer DSC-7
differential scanning calorimeter at a heating rate of 10 ꢀC
minꢁ1. Thermal gravimetric analysis was performed using
Perkin-Elmer Pyris-6 instrument. Dynamic light scattering
(DLS) measurements were done by using a Nano ZS Malvern
instrument using a 4-mW He-Ne laser (k ¼ 632.8 nm) and
equipped with a thermo stated sample chamber. Samples for
scanning electron microscopy were provided with a thin
gold coating using JEOL JFC-1200 fine coater. Scanning elec-
tron microscopy images were recorded using a JEOL JSM-
5600 LV instrument. Atomic force microscopy (AFM) images
were recorded under ambient conditions using NTEGRA
Prima - NT-MDT, Russia, scanning probe microscope oper-
ated in tapping mode. Microfabricated silicon cantilever tips
(NSG 20) with a resonance frequency of 260–630 kHz and a
force constant of 20–80 Nmꢁ1 were used. The tip curvature
radius was 10 nm. The scan rate was 1 Hz. To prepare sam-
ples for AFM measurements, a drop of the polymer colloidal
solution was placed on a glass slide and the solution was
allowed to evaporate at room temperature in air. Transmis-
sion electron microscopy (TEM) images were recorded using
a FEI-TEC NAI 30 G2 S-Twin, 300 kV HRTEM microscope
with an accelerating voltage of 100 kV. Samples were
EXPERIMENTAL
Materials
N,N,N0,N0,N00-Pentamethyldiethylenetriamine (PMDETA), poly
(ethylene oxide)monomethyl ether, 3,4-dihydroxy benzalde-
hyde, dodecyl bromide, 4-methylbenzonitrile, N-bromosucci-
nimide, methacrylic acid, 2-bromo-2-methylpropionic acid,
triethylphosphate, dicyclohexylcarbodiimide, 4-(N,N-dimethy-
lamino)pyridine, and curcumin were purchased from Aldrich
and used without further purification. CuBr (98%, Aldrich)
was stirred in glacial acetic acid overnight, filtered, and then
it was washed with ethanol and dried under vacuum over-
night. Solvents were purchased locally and purified using
standard procedures before use.
Analysis and Measurements
1H and 13C NMR spectra were recorded on Bruker DPX 500
MHz spectrometer using tetramethylsilane as the internal
standard and chloroform-d (CDCl3) as the solvent. FTIR spec-
tra were recorded on a Shimadzu IR Prestige-21 Fourier
transform infrared spectrophotometer. The molecular
weights of the polymers were determined by gel permeation
chromatography (GPC) in tetrahydrofuran (THF) using poly-
styrene standards for the calibration. The GPC was calibrated
with different polystyrene standards having molecular
weights ranging from 2950 to 177,000 g/mol (Polymer
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prepared by drop-casting aqueous solutions of PDACS-b-PEO
on a carbon coated copper grids under ambient conditions.
The solvent was allowed to evaporate at room temperature.
TEM images were obtained without staining.
product was purified by column chromatography using hex-
ane as eluent and (100–200) mesh silica as stationary phase
to give 3 (4.04 g, 71%).
IR (in KBr)/cmꢁ1: 2918, 2848, 1724, 1687, 1585, 1510,
1274, 1165, 1132, and 806. 1H NMR (500 MHz, CDCl3,
Me4Si, ppm): 9.83 (1H, s, ACHO), 7.42 (1H, d, J ¼ 8 Hz, aro-
matic), 7.26 (1H, s, aromatic), 6.96 (1H, d, J ¼ 8.5 Hz, aro-
matic), 6.10 (1H, s, ¼¼CH2), 5.55 (1H, s, ¼¼CH2), 4.10 (6H, t,
AOCH2A), and 0.89 (3H, t, ACH3). 13C NMR (125 MHz,
CDCl3, Me4Si, ppm): 191.04, 167.57, 154.67, 149.42, 136.56,
129.85, 126.64, 125.13, 111.74, 110.91, 69.12, 64.85, 31.92,
29.05, 25.98, 22.69, 18.34, and 14.12. HRMS (m/z): 559.98
[MþH]þ.
Synthesis and Characterization
Synthesis of 4-(Dodecyloxy)-3-hydroxybenzaldehyde (1)
3,4-Dihydroxybenzaldehyde (10.0 g, 72 mmol), dodecylbro-
mide (18.02 g, 72.5 mmol), and K2CO3 (20.0 g, 145 mmol)
ꢀ
were suspended in 10 mL DMF and heated at 90 C for 12 h
.The reaction mixture was then poured into ice cold water,
precipitated compound was filtered. The precipitate was
redissolved in DCM and washed with water. Trace amount of
water was removed by adding sodium sulphate and the
excess solvent was distilled off. The product was purified by
column chromatography using hexane as an eluent and (100–
200) mesh silica as stationary phase to give 1 (15.44 g, 67%).
IR (in KBr)/cmꢁ1: 3439, 2920, 2848, 1683, 1512, 1276, and
1002. 1H NMR (500 MHz, CDCl3, Me4Si, ppm): 9.83 (1H, s,
ACHO), 7.44 (1H, d, J ¼ 8 Hz, aromatic), 7.41 (1H, s, aro-
matic), 6.95 (1H, d, J ¼ 8 Hz, aromatic), 5.85 (1H, s, AOH),
4.14 (2H, t, AOCH2A), and 0.89 (3H, t, ACH3). 13C NMR
(125 MHz, CDCl3, Me4Si, ppm): 191.07, 151.36, 146.21,
130.4, 124.54, 114.03, 110.88, 69.3, 31.9, 29.52, 25.91,
22.68, and 14.11. HRMS (m/z): 308.39 [MþH]þ.
Synthesis of 4-Cyanobenzylbromide (4)
4-methylbenzonitrile (10.0 g, 85.4 mmol) and N-bromosucci-
nimide (19.0 g, 103 mmol) were dissolved in 40 mL of dry
CCl4, added a speck of azobisisobutyronitrile and heated to
ꢀ
80 C. After 12 h the solution was concentrated and kept for
crystallization to give 4 (8.0 g, 48%).
1H NMR (500 MHz, CDCl3, Me4Si, ppm): 7.65 (2H, d, J ¼ 8.5
Hz, aromatic), 7.51 (2H, d, J ¼ 7.8 Hz, aromatic), and 4.48
(2H, s, ACH2Br). 13C NMR (125 MHz, CDCl3, Me4Si, ppm):
142.83, 132.60, 129.73, 118.37, 112.21, and 31.48.
Synthesis of Diethyl-4-cyanobenzylphosphonate (5)
Synthesis of 4-(Dodecyloxy)-3-(12-hydroxydodecyloxy)
benzaldehyde (2)
Compound 4 (14.98 g, 76.8 mmol) and triethylphosphate
(15.3 mL, 92.2 mmol) were added to a 250 mL round-bottom
Compound 1 (5.0 g, 16 mmol), 12-bromododecane-1-ol (8.67
g, 32.7 mmol) and K2CO3 (6.76 g, 49.0 mmol) were sus-
pended in 10 mL DMF and heated at 90 ꢀC for 12 h. The
reaction mixture was then poured into ice cold water, pre-
cipitated compound was filtered and redissolved in DCM,
washed with water and separated. Trace amount of water
was removed by adding sodium sulphate and the excess sol-
vent was distilled off. The product was purified by column
chromatography using hexane as eluent and (100–200)
mesh silica as stationary phase to give 2 (5.6 g, 70%).
IR (in KBr)/cmꢁ1: 3,334, 3,080, 2,918, 2,848, 1,678, 1,273,
1,130, 1,064, 1,238, and 806. 1H NMR (500 MHz, CDCl3,
Me4Si, ppm): 9.83 (1H, s, ACHO), 7.42 (1H, d, J ¼ 8 Hz, aro-
matic), 7.39 (1H, s, aromatic), 6.96 (1H, d, J ¼ 8 Hz, aro-
matic), 4.09 (4H, t, AOCH2A), 3.63 (2H, t, ACH2AOH), and
0.90 (3H, s, ACH3). 13C NMR (125 MHz, CDCl3, Me4Si, ppm):
191.07, 154.68, 149.41, 129.66, 111.73, 110.91, 69.12, 63.08,
32.81, 31.92, 29.44, 25.94, 22.69, and 14.12. HRMS (m/z):
492.81 [MþH]þ.
ꢀ
flask (RB) and heated to 100 C for 12 h. After 12 h tempera-
ture was raised to 130 ꢀC and excess triethylphosphate was
removed by purging argon. The product was purified by col-
umn chromatography using hexane as eluent and (100–200)
mesh silica as stationary phase to give 5 (11.67 g, 60%).
1H NMR (500 MHz, CDCl3, Me4Si, ppm): 7.62 (2H, d, J ¼ 8.1
Hz, aromatic), 7.43 (2H, d, J ¼ 8 Hz, aromatic), 4.04 (4H, q,
P(OCH2CH3)2), 3.23 (2H, d, ACH2PO), and 1.27 (6H, t,
P(OCH2CH3)2). 13C NMR (125 MHz, CDCl3, Me4Si, ppm):
137.59, 132.26, 130.57, 118.68, 110.88, 62.44, 34.65, and
16.36.
Synthesis of 12-(5-(4-Cyanostyryl)-2-(dodecyloxy)phenoxy)
dodecyl methacrylate (6)
To a solution of compound 5 (2.16 g, 7.53 mmol) in THF,
NaH (752 mg, 31.4 mmol) was added at ice temperature. Af-
ter stirring the reaction mixture for 10 min compound 3
(3.5 g, 6.3 mmol) was added drop wise and the resulting
mixture was stirred for 4 h in argon atmosphere. Excess
NaH was filtered off. The product was purified by column
chromatography by using silica as stationary phase and 5%
EtOAc/hexane as eluent to give product 6 (2.4 g, 68.5%).
Synthesis of 12-(2-(Dodecyloxy)-5-formylphenoxy)dodecyl
methacrylate (3)
Compound 2 (5.0 g, 10 mmol), methacrylic acid (1.7 mL, 20
mmol), 4-(N,N-dimethylamino)pyridine (1 speck) were sus-
IR (in KBr)/cmꢁ1: 2,916, 2,848, 2,223, 1,714, 1,516, 1,174,
1
ꢀ
pended in 40 mL dry DCM, stirred at 0 C and dicyclohexyl-
and 1,136. H NMR (500 MHz, CDCl3, Me4Si, ppm): 7.60 (4H,
carbodiimide (3.16 g, 15.3 mmol) was added under argon
atmosphere. The reaction mixture was then stirred at room
temperature for 24 h. It was filtered and the precipitate of
dicyclohexyl urea was washed several times with DCM. The
solvent was removed under reduced pressure and crude
m, aromatic), 7.17 (1H, d, aromatic), 7.07 (1H, d, J ¼ 8 Hz,
aromatic), 6.99 (1H, d, aromatic), 6.95 (1H, d, aromatic),
6.89 (1H, d, J ¼ 8.1 Hz, aromatic), 6.11 (1H, s, ¼¼CH2), 5.56
(1H, s, ¼¼CH2), 4.16 (2H, t, AOCOCH2), 4.07 (4H, d,
ArAOCH2), and 0.89 (3H, t, ACH3). 13C NMR (125 MHz,
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FIGURE 1 (a) Changes in the UV/vis spectra of PDACS-b-PEO in THF on UV irradiation (b) Changes in the fluorescence emission
spectra (kex ¼ 353 nm) of PDACS-b-PEO in THF on UV irradiation.
CDCl3, Me4Si, ppm): 167.58, 149.28, 142.22, 136.55, 132.46,
129.6, 126.73, 125.5, 121.96, 119.16, 111.75, 110.01, 69.19,
64.84, 31.92, 29.7, 26.02, 22.69, 18.34, and 14.12. HRMS (m/
z): 658.39 [MþH]þ.
IR (in KBr)/cmꢁ1: 2,932, 28,881, 2,352, 22,249, 1,771, 1,491,
1,132. 1H NMR (500 MHz, CDCl3, Me4Si, ppm): 7.57 (4H, m,
aromatic), 7.10 (3H, m, aromatic), 6.85 (2H, m, aromatic),
4.00 (6H, m, AOCOCH2A, 2 ꢂ AOCH2A), 3.65 (4H, m,
AOCH2CH2A), 3.38 (3H, s, AOCH3), 1.24–1.48 (45H, m, 2 ꢂ
AOCH2(CH2)10A, AC(CH3)CH2A, ACH2CH3) and 0.86 (3H,
m, CH3CCH2A). 13C-NMR (125 MHz, CDCl3, Me4Si, ppm): d ¼
132.25, 130.23, 126.35, 122.22, 119.76, 113.06, 112.56,
111.23, 70.37, 69.25, 31.74, 29.43, 25.82, 22.51, 13.96. GPC
Synthesis of PEO-Br (7)
Poly(ethylene glycol)monomethyl ether (Mn ¼ 5000 g/mol,
20 g, 4 mmol) was reacted with 2-bromo-2-methylpropionic
acid (0.75 g, 4.4 mmol) in the presence of 1,3-dicyclohexyl
carbodiimide (1.1 g, 5.3 mmol) and a catalytic amount of
dimethylaminopyridine (80 mg, 0.62 mmol) in dichlorome-
thane (130 mL). Precipitated dicyclohexyl urea was filtered
off and washed with dichloromethane. The macroinitiator
was purified by dissolving it in THF, filtering the solution,
concentrated, and finally precipitated in diethyl ether to get
7 (17.18 g, 86%).
(THF): Mn
¼
9166, Mw/Mn
¼
1.39. Anal. calcd. for
[(C43H63NO4)6 (C2H4O)112]: C–65.18, H–9.37, N–0.95; Found:
C–68.12, H–10.88, N–1.23.
RESULTS AND DISCUSSION
IR (in KBr)/cmꢁ1: 2,886, 2,741, 2,698, 1,965, 1,732, 1,458,
1,342, 1,277, 1,272, 1,240, 1,103. 1H NMR (500 MHz, CDCl3,
Me4Si, ppm): 4.33 (2H, dd, AOCOCH2A), 3.65 (4H, m,
AOCH2CH2A), 3.38 (3H, s, AOCH3) and 1.94 (6H, s,
AOCOC(CH3)2Br). 13C-NMR (125 MHz, CDCl3, Me4Si, ppm): d
¼ 72.54, 71.68, 70.30, 69.96, 68.51, 61.35, 58.79, 30.55. GPC
Photoresponsive Behavior of PDACS-b-PEO
In pure THF, PDACS-b-PEO exhibited a typical stilbene
absorption spectrum with an intense band at 348 nm corre-
sponding to the trans-isomer and a weak band at 238 nm.
On photolysis with 355 nm light, a decrease in intensity in
the 355 nm region and a small increase in intensity in the
238 nm region due to the formation of cis-isomer57,58 was
observed [Fig. 1(a)]. The linear trans-isomer exhibits a sharp
emission at 434 nm but the bent cis form is nonfluores-
cent.58 Irradiation with 355 nm light resulted in a gradual
decrease in the emission at 355 nm corresponding to the
formation of the cis-isomer [Fig. 1(b)] and the process is
schematically depicted in Figure 2. The photoinduced isom-
(THF): Mn
¼
5078, Mw/Mn
¼
1.12. Anal. calcd. for
[(C2H4O)112]: C–54.53, H–9.15; Found: C–53.22, H–8.88.
Synthesis of PDACS-b-PEO
CuBr (15 mg, 0.11 mmol) was added to a 10 mL RB flask
containing compound 6 (500 mg, 0.76 mmol), 7 (500 mg,
0.10 mmol), and N,N,N00,N0,N00-Pentamethyldiethylenetriamine
(17.43 mg, 0.10 mmol) in 1,4-Dioxan (3 mL). As soon as
CuBr was added, the color changed to pale green indicating
the start of polymerization. The flask was then sealed with a
rubber septum and was purged with argon for 20 min. The
flask was placed in a preheated oil bath at 85 ꢀC for 24 h.
The viscous liquid was dissolved in THF and was passed
through neutral alumina column to remove the catalyst and
was then concentrated and precipitated in hexane to get
PDACS-b-PEO (650 mg, 65%). The obtained polymer was
purified by repeated precipitation from THF into hexane and
dried.
1
erization was also confirmed by H NMR (see Supporting In-
formation). To find out whether the isomerization process
was thermally reversible the irradiated solution was kept in
ꢀ
the dark at 60 C for 2 h. The absorption spectra and emis-
sion spectra did not show any significant change which indi-
cated that the cis-form was stable and did not revert back to
the trans-form. The advantage of stilbene chromophores
compared to azobezene chromophores is that in the former
case the photoisomerization process is quite clean whereas
in the latter case a photostationary state is reached.59
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FIGURE 2 (a) Schematic illustration of the photoisomerization of stilbene units present in the polymer chain. [Color figure can be
viewed in the online issue, which is available at wileyonlinelibrary.com.]
Aggregation Studies of PDACS-b-PEO
were almost uniform in size with an average diameter of
160 nm with a PDI value of 0.116. It may be noted that DLS
studies on unfiltered solutions gave similar results.
Because of the amphiphilic nature of this copolymer it was
expected that it could form supramolecular aggregates in
water. To confirm this we carried out DLS measurements on
aqueous solutions of the polymer. For DLS measurement,
aggregates of PDACS-b-PEO in water were prepared using
the following procedure. PDACS-b-PEO (1 mg) was dissolved
in 1 mL THF, to which 1 mL of deionized water was added
at a rate of 500 lL/h to induce aggregation. The solution
progressively became turbid during water addition indicating
aggregation. This is because when water is gradually added
to a homogeneous solution of PDACS-b-PEO in THF, the sol-
vent becomes progressively worse for the DACS block; and
after a critical amount of water has been added, PDACS
starts to self-assemble resulting in the formation of aggre-
gates. Following this, 9 mL water was added quickly to
quench the aggregates and THF was removed by evaporation
at room temperature. The solution was filtered through a
0.45 lm filter (Millipore Millex-HV) before use. Figure 3
shows the DLS measurements of the diblock copolymer
PDACS-b-PEO in water. DLS studies showed that the particles
AFM studies were carried out to further characterize the
morphology of the aggregates. The same solution which was
filtered through 0.45 lm filter for DLS measurements was
used for AFM measurements. For AFM measurements one
part of the colloidal solution was cast on a glass slide and
dried. Another part of the solution, was exposed to UV light
(355 nm) in a quartz cuvette for 1, 2, and 3 h and each of
these solutions were cast and dried on different glass slides
for AFM observation. Figure 4 shows the AFM images
obtained from the four solutions. AFM images of these
micelles before irradiation showed a high density of spheres.
The concentration of these spherical micelles decreased on
continued UV irradiation and practically no micelles were
observed in the solution exposed to UV light for 3 h. DLS
analysis confirmed the above observation which showed that
that the solution after 3 h UV irradiation contained only pol-
ydisperse particles with an average size of 39 nm. The ab-
sorbance of the solution in the 700–800 nm region where
FIGURE 3 Size distributions of PDACS-b-PEO aggregates in water. [Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
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FIGURE 4 AFM images of spherical micelles of PDACS-b-PEO in water: (a) before irradiation, (b) after UV irradiation for 1 h, (c) after
UV irradiation for 2 h, and (d) after UV irradiation for 3 h.
the chromophores do not have absorption is attributable to
scattering of light. A significant decrease in the absorbance
value in this region on irradiation was indicative of the solu-
tions becoming less turbid, which can again be attributed to
dissolution of the irradiated block polymer. The gradual dis-
appearance of the micellar aggregates on UV irradiation can
be explained as follows. Photoisomerization of trans-stilbene
results in the formation of cis-stilbene which as a result of
its higher dipole moment is less hydrophobic than the trans-
form. Consequently, UV irradiation increases the overall
hydrophilicity of the polymer and due to the relatively short
length of the DACS block, this increase is sufficient enough
to break the colloidal aggregates on irradiation. TEM was
further used to characterize the micellar morphology. TEM
images of the colloidal solution established that the aggre-
gates have micellar morphology as there was no sharp con-
trast difference between the periphery and core of the aggre-
gates. Figure 5 shows the changes in the TEM images of a
micellar solution of PDACS during various stages of UV irra-
diation. Thus, microscopic investigation conclusively revealed
that the amphiphilic polymer forms well-defined spherical
micellar aggregates in water which can be almost entirely
dissociated with the help of UV light. The particle size meas-
ured using AFM and TEM for the diblock copolymer was
much larger (ꢃ500 nm) when compared with the DLS mea-
surement which indicated particles with an average diameter
of 160 nm. A possible explanation for this is that DLS meas-
urements are done in the solution state whereas AFM and
TEM measurements are done in the dried state, during
which the smaller particles present in water, can combine to
form larger spheres during solvent evaporation process.
Encapsulation and Photo-Controlled Release of Curcumin
From Supramolecular Aggregates of PDACS-b-PEO
Curcumin is the principal curcuminoid of the popular Indian
curry spice turmeric, which has been used historically as a
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FIGURE 5 TEM images of spherical micelles of PDACS-b-PEO in water: (a) before irradiation, (b) after UV irradiation for 1 h, (c) af-
ter UV irradiation for 2 h, and (d) after UV irradiation for 3 h.
component of Indian ayurvedic medicine. In vitro and animal
studies have suggested that curcumin has antitumor, antioxi-
dant, antiarthritic, antiamyloid, anti-ischemic, and anti-
inflammatory properties.60 In addition, it may be effective in
treating malaria, prevention of cervical cancer, and may
interfere with the replication of HIV virus.61 There is also
circumstantial evidence that curcumin improves mental func-
tions.62 The structure of curcumin is show in Chart 2.
Because of its limited solubility and instability in the gut
very little of curcumin which is ingested is absorbed by the
body. In 2007, a polymer nanoparticle encapsulated formula-
tion of curcumin (nanocurcumin)63 has been synthesized
which has the potential to bypass many of the shortcomings
associated with free curcumin, such as poor solubility and
poor systemic bioavailability.
Figure 6(b). As can be seen from the Figure 5(a) curcumin
has negligible absorption in the range of 340–360 nm, its
maximum absorption is centered at ꢃ423 nm.
To incorporate curcumin into the core of the micelles 1.0 mg
of the polymer and 0.06 mg of curcumin were dissolved in 1
mL THF. To this 1 mL of water was added drop wise. After
dilution with 9 mL of water and complete evaporation of
THF the resultant solution was filtered through a 0.45 lm
filter. Curcumin exhibits very low absorbance and emission
in pure water owing to its very low solubility in water;
Curcumin could be solubilized in water using the supramo-
lecular aggregates of PDACS-b-PEO. Figure 6(a) shows the
absorption spectra of PDACS-b-PEO and curcumin in THF.
The emission spectrum of curcumin in THF is shown in
CHART 2
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FIGURE 6 (a) UV/vis spectra of PDACS-b-PEO and curcumin THF (b) Fluorescence emission spectra (kex ¼ 423 nm) of curcumin
in THF.
however, as the dye was incorporated into the micelles, the
dispersion exhibited a strong fluorescent emission at 499
nm. In addition, the emission maximum displayed a blue-
shift for the dye in the aggregate system compared with that
in pure THF, indicating that curcumin molecules reside in a
more hydrophobic environment (compared with that of THF)
inside the micelles. Figure 7(a,b) show the absorption and
emission spectra of curcumin encapsulated in the polymer
aggregates in water.
355 nm light, the emission intensity of curcumin decreases
with time of irradiation. On the other hand, the emission
band of stilbene at 437 nm first decreases and then starts to
increase on continued UV irradiation. The decrease in curcu-
min emission on UV irradiation is because of its control
release from the polymer aggregates into water due to the
formation of the comparatively more polar cis-stilbene,
which ensures a decrease in hydrophobicity of the polymer
resulting in the dissociation of the polymer aggregates. As
the released curcumin are water insoluble it gets
precipitated.
On excitation of the curcumin/micellar dispersion with UV
light (353 nm), it was observed that the characteristic fluo-
rescence emission for stilbene at 437 nm was reduced to a
small hump and an emission band at 491 nm corresponding
to that of curcumin was observed, suggesting fluorescence
resonance energy transfer (FRET) from stilbene to curcumin.
Figure 9 shows the fluorescence emission spectra of the
polymer solution with encapsulated curcumin before and af-
ter UV light exposure (excitation wavelength, 353 nm); in
comparison, the emission spectrum of the polymer solution
without curcumin, prepared under the same conditions, is
also shown.
The photochemically controlled release of curcumin was con-
firmed by monitoring the changes in the absorption and
emission spectra as a function of irradiation time (Fig. 8).
Emission spectra in Figure 8(b) provide evidence for the
encapsulation and release of curcumin following UV irradia-
tion of the aqueous polymer solution. On irradiation with
For the polymer solution without curcumin, there is only the
emission of stilbene at 437 nm while for the polymer aque-
ous solution containing curcumin, excitation at 353 nm,
where curcumin has negligible absorption, resulted in the
FIGURE 7 (a) UV/vis spectra and (b) Fluorescence emission spectra (kex ¼ 353 nm) of copolymer aggregates containing curcumin
in water.
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FIGURE 8 (a) Changes in UV/vis spectra and (b) Fluorescence emission spectra (kex ¼ 353 nm) of polymer aggregates in water con-
taining curcumin on UV irradiation.
fluorescence emission of curcumin centered at 491 nm. This
can be attributed to FRET between the polymer and the dye,
which indicates the close distance between them. This sup-
ports the view that curcumin is encapsulated within the
hydrophobic core of the self-assembled polymer. The photoi-
somerization of stilbene and release of curcumin were
revealed by dramatic decrease in their fluorescence emission
after UV irradiation, as released curcumin molecules are
water insoluble. Scheme 1 illustrates this strategy. The slight
enhancement of stilbene emission on continued UV irradia-
tion can be attributed to the fact that when more and more
curcumin molecules are released from the polymer micelles
energy transfer process becomes less efficient which results
in the slight enhancement in stilbene emission. Here it can
be argued that the decrease in curcumin emission is not due
to the release of encapsulated curcumin but due to the for-
mation of nonfluorescent cis-stilbene which inhibits FRET. To
prove that this argument is invalid we took the ratio of the
absorbance at 353 nm of the curcumin encapsulated aggre-
gates before and after irradiation and multiplied that factor
to the emission spectra of the curcumin encapsulated solu-
tion obtained after UV irradiation. The corrected spectra
exactly superimposes with the emission spectra of the nonir-
radiated polymer solution without curcumin. The corrected
emission spectra clearly proved that the curcumin is in fact
getting released from the polymer aggregates on UV irradia-
tion. Also direct excitation of the curcumin encapsulated so-
lution at the absorption maxima of curcumin (423 nm)
before and after UV irradiation where PDACS-b-PEO has no
absorption revealed that curcumin emission is mostly
quenched after UV irradiation (See Supporting Information).
Thus, we have succeeded in controlling the solubilization of
FIGURE 9 Fluorescence emission spectra (kex ¼ 353 nm) of polymer micelles in water containing curcumin before and after UV
irradiation compared to that of the nonirradiated micellar solution without curcumin. (b) Photograph of an aqueous solution of
PDACS-b-PEO; without curcumin, (left) with encapsulated curcumin (right). [Color figure can be viewed in the online issue, which
is available at wileyonlinelibrary.com.]
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SCHEME 1 Schematic representation of the encapsulation of curcumin within the hydrophobic core of the polymer aggregates
and its release on disruption of the polymer aggregates by UV light. [Color figure can be viewed in the online issue, which is avail-
able at wileyonlinelibrary.com.]
curcumin in water by utilizing the cis–trans isomerization of
stilbene chromophores. This is achieved through UV irradia-
tion which causes an increase in solubility of the resultant
polymer in water sufficient enough for the dissociation of
the micellar aggregates. The dye encapsulated polymer
aggregates in the absence of UV irradiation was found to be
stable up to a period of 2 months as there was no character-
istic change in the fluorescence spectra of the solution dur-
ing this time.
The authors thank J. D. Sudha for GPC and TG analysis, M. R.
Chandran for SEM and Robert Philip for TEM measurements.
This is contribution no. PPD-316 from NIIST-PPG. S.M. thank
UGC, Government of India for research fellowships.
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