Photoinduced release of guest molecules by supramolecular transformation of self-assembled aggregates derived from dendrons

Article abstract of DOI:10.1002/anie.200705271

The missing link: Supramolecular transformation from a vesicle to a fibrous nanostructure has been achievedby photolytic cleavage andsupramolecular reorganization of a dendritic building block containing a 2-nitrobenzyl group (see picture). Furthermore, supramolecular aggregates of an amide dendron with a photoisomerizable azobenzene unit exhibit controlledrelease of encapsulated molecules upon photoirradiation in the aqueous phase. (Figure Presented).

Full text of DOI:10.1002/anie.200705271

Angewandte
Chemie
DOI: 10.1002/anie.200705271
Self-Assembly
Photoinduced Release of Guest Molecules by Supramolecular
Transformation of Self-Assembled Aggregates Derived from
Dendrons**
Chiyoung Park, Jino Lim, Mikyoung Yun, and Chulhee Kim*
Self-assembly provides a unique way to create supramolec-
ular functional materials.[1,2] Since a variety of supramolecules
have been reported to date, the control of architectures and
functions triggered by external stimuli has always been a
challenging subject.[3–7]
Dendrimers and dendrons have been of great interest in a
variety of scientific fields because of their unique assembly
characteristics and functional performances.[8–22] Recently, we
investigated the self-assembly characteristics of amide den-
drons and revealed that the dendrons can self-assemble into
hierachical nanostructures under various conditions.[23–30] The
supramolecular structure of the amide dendrons can be
controlled by tuning the focal functionality of the den-
drons.[29,30] For example, photoisomerizable or photocleavable
units introduced at the focal moiety could be utilized to
control the photoresponsive functions of dendron-based
supramolecular materials. In this regard, we envisioned that
Scheme 1. The structure of the amide dendrons.
the incorporation of stimuli-responsive functional groups in
the amide dendrons would be an effective approach toward
the construction of well-defined stimuli-responsive nanoma-
terials (Scheme 1).[7] The formation of the dendritic architec-
ture is one of the important factors for the self-organization of
the amide dendrons.[23] Thus, the self-assembly of amphiphilic
dendrons would provide opportunities not only for structural
versatility but also for functional modulation of the stimuli-
responsive materials.
Herein we describe the rational design of dendritic
building blocks with a photocleavable unit that can self-
assemble into a vesicular structure and can undergo a
structural transformation on application of a external photo-
stimulus (Figure 1a,b). Furthermore, the introduction of a
photoisomerizable chemical modulator at the focal moiety of
the dendron would provide a tool to control the photo-
activated release of guest molecules from the supramolecular
aggregates of the dendrons (Figure 1c,d). Thus, we have
investigated the photoresponsive release behaviors not only
[*] C. Park, J. Lim, M. Yun, Prof. Dr. C. Kim
Department of Polymer Science and Engineering
Figure 1. Schematic illustrations for the release characteristics of the
vesicles of: a,b)dendron 4 and c,d)dendron 5 upon irradiation with
UV light. Green sphere: calcein, Red: Nile Red.
Hyperstructured Organic Materials Research Center
Inha University, Incheon 402-751 (South Korea)
Fax: (+82)32-865-5178
E-mail: chk@inha.ac.kr
[**] This work was supported by the Korea Research Foundation (KRF-
2007-313-D00205). C.K. also thanks the Korea Health 21 R&D
Project (A062254)and the National R &D Program for Cancer
Control (0620340-1)for financial support.
of hydrophilic guest molecules from the inner water compart-
ment but also of hydrophobic guest molecules from the
membrane of the vesicles derived from the dendritic building
blocks.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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The photocleavable 2-nitrobenzyl ester moiety and pho-
disruption of the vesicular membrane. The release profile was
obtained by using Equation (1).
toisomerizable azobenzene unit were introduced at the focal
point of the amide dendron to construct supramolecular
structures with a photoswitchable function as shown in
Scheme 1. Dendrons 1, 2, and 3 with the focal poly(ethylene
glycol) unit (Mn = 750, PEG750) were prepared by following
the literature procedure.[23,29,30] As summarized in Scheme 1,
dendron 4 with a focal photocleavable unit was prepared by
coupling dendron 1 with 2-nitrobenzyl alcohol. Dendron 5,
which contains a photoisomerizable focal moiety, was synthe-
sized by coupling dendron 2 with azobenzene-4-carbonyl
chloride. Structural characterization of the products were
carried out by using 1H NMR, 13C NMR, and FTIR spectros-
copy as well as MALDI-TOF MS (see Figure S1 in the
Supporting Information).
The suparmolecular assembly and transformation of
dendron 4 with a photocleavable functionality were inves-
tigated in the aqueous phase. In a basic aqueous phase,
dendron 4 formed a vesicular structure (10 mm NaOH) with a
hydrodynamic radius of 113 nm (PDI = 0.184), as determined
by dynamic light scattering (DLS) analysis. A gel filtration
experiment coupled with DLS measurements confirmed the
existence of water entrapped in the interior of the spherical
supramolecular assembly.
Release percentage ð%Þ ¼ ðItÀI0Þ=ðI1ÀI0Þ 100
ð1Þ
I0 is the initial fluorescence intensity, It is the fluorescence
intensity at time t, and I1 is the fluorescence intensity after
addition of Triton X-100. Transmission electron microscopy
(TEM) and scanning electron microscopy (SEM) analysis
showed the presence of spherical nanostructures with diam-
eters of 100–200 nm in aqueous solution (10 mm NaOH;
Figure 2b and Figure S2a in the Supporting Information).
Exposure of the solution to UV light (l = 350 nm)
resulted in photocleavage of 2-nitrobenzyl unit, which
resulted in the absorption band of dendron 4 at 265 nm
decreasing and the absorption band at 310 nm increasing
(Figure 3a). The DLS autocorrelation functions were mea-
sured to investigate the assembly behavior in aqueous
solution (10 mm NaOH) after irradiation (l = 350 nm) of
the vesicle solution of dendron 4 with UV light. CONTIN
analysis of the autocorrelation functions showed a broad
distribution of particles with an average hydrodynamic radius
(Rh) of approximately 215 nm (Figure 3b). The slope of the
angular dependence of the apparent diffusion coefficient
(Dapp) was found to be 0.033 (Figure 3c), which is consistent
For gel filtration, an aqueous solution of a water-soluble
dye—resorufin sodium salt—was added to a solution of
dendron 4 in THF.[30,31] After removal of the THF under
reduced pressure, the solution was passed through a Sephadex
G-100 column (2.5 ” 20 cm) and 36 fractions collected
(2.5 mL each). All the fractions were subjected to dynamic
light scattering and fluorescence measurements to obtain
elution profiles. As shown in Figure 2a, the DLS and
fluorescence experiments showed that the self-aggregates
(average diameter 180–350 nm) containing the water-soluble
dye were eluted in fractions 11–14. The vesicular structure of
dendron 4 was further evidenced by investigating the release
profile of the entrapped water-soluble dye molecules before
and after addition of Triton X-100 (Figure 2b). In the case of
the vesicle of dendron 4 loaded with resorufin sodium salt, the
12th fraction underwent self-quenching of the fluorescence,
which arose as a consequence of its high local concentration
inside the vesicle. After addition of Triton X-100, self-
quenching no-longer occurred because of the egress of the
water-soluble dye from the vesicle—the surfactant caused
Figure 3. a)Change in the absorption spectra of vesicles of dendron 4 in
aqueous solution (10 mm NaOH)in response to UV light. b)Autocorrela-
tion functions and size-distribution histogram of a cylindrical micelle of
dendron 4 (4 mgLÀ1 in H2O)at different scattering angles. c)Angular
dependence of the apparent diffusion coefficient for cylindrical micelles of
4. d)TEM and e)SEM images of the fibrous nanostructures obtained from
vesicles of 4 in aqueous phase after irradiation with UV light for 10 min
(negative staining with 2 wt% uranyl acetate). f) Release profiles of calcein
from vesicles of 4 in aqueous solution (10 mm NaOH).
Figure 2. a)Elution profile of the gel filtration of vesicles of dendron 4
in aqueous solution (10 mm NaOH). Each fraction was subjected to
DLS and fluorescence measurement. b)Release profile of resorufin
sodium salt from vesicles of dendron 4. The inset shows the TEM
image of vesicles of dendron 4 in aqueous solution (10 mm NaOH).
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with the value predicted for cylindrical aggregates (0.03).[32]
Interestingly, a fibrous nanostructure with a width of about
10 nm was observed by TEM after irradiation of the vesicular
solution of dendron 4 with UV light (l = 350 nm; Figure 3d).
The SEM experiment also revealed the fibrous suprastructure
of dendron 4 after irradiation (l = 350 nm, Figure 3e). After
the photolysis, dendron 4 would be converted into dendron 1,
which can self-assemble into rodlike nanostructures in
aqueous solution (10 mm NaOH), as reported previously
(see Figure S2b in the Supporting Information).[29] These
results indicate that the vesicles of dendron 4 undergo
supramolecular reorganization to form a fibrous nanostruc-
ture after photolysis of the 2-nitrobenzyl focal moiety from
the building block (dendron 4) in aqueous solution (10 mm
NaOH). Furthermore, these results suggest that the vesicles
of dendron 4 can be used as photoresponsive nanocarriers.
Therefore, we investigated the photoresponsive release
characteristics of the vesicle. The release of calcein molecules
entrapped within the vesicle of dendron 4 was suppressed in
the dark (Figure 3 f). However, when vesicles of dendron 4
were exposed to UV light (350 nm), the entrapped dye
molecules were released from the interior of the vesicles.
Most of the dye molecules were released from the vesicle
after irradiation with UV light for 10 min (Figure 3 f), which
suggests that the photolysis of the 2-nitrobenzyl ester from
dendron 4 triggers the transformation of the vesicle into the
fibrous structure with concurrent release of the encapsulated
molecules (Figure 1a).
For another approach to control the photoinduced release
characteristics of the supramolecular aggregates of the
dendron, we prepared dendron 5 with a focal azobenzene
moiety which formed self-assembled structure in the aqueous
phase. CONTIN analysis of the autocorrelation function
showed a monomodal distribution with a translational
diffusive mode (see Figure S3a,b in the Supporting
Information). The average hydrodynamic radius of the
aggregates formed from dendron 5 as measured by DLS
was 119 nm (PDI = 0.097). The slope of the angular depend-
ence of the apparent diffusion coefficient (Dapp) was zero, and
the size of the aggregates was constant for the investigated
range of angles, which confirmed the spherical shape of the
aggregates (see Figure S3c in the Supporting Information).[33]
The TEM image of the self-aggregate derived from dendron 5
in an aqueous phase showed a vesicular structure (Figure 4a).
The spherical shape of the aggregates was also confirmed by
SEM analysis (Figure 4b). The gel filtration experiment with
the resorufin sodium salt confirmed the existence of water
entrapped in the interior of the spherical supramolecular
assembly of dendron 5 (see Figure S4a in the Supporting
Information). The 27th fraction isolated by the gel filtration
experiment was observed by confocal laser scanning micro-
scopy (CLSM), which confirmed that the water-soluble dye
molecules were entrapped in the interior of the vesicle, as
shown in Figure 4c. The vesicular structure was further
evidenced by investigating the release profile of the entrap-
ped water-soluble dye molecules before and after addition of
Triton X-100 (see Figure S4b in the Supporting Information).
The photoresponsive release characteristics of the vesicle
derived from dendron 5 were investigated. The UV/Vis
Figure 4. a)TEM and b)SEM images of the vesicle of dendron 5.
c)CLSM image of vesicles of dendron 5 with entrapped resorufin
sodium salt (scale bar=5 mm). d) TEM image of vesicles of dendron 5
after irradiation with UV light (l=350 nm)for 1 h. e)Change in the
absorbance at 325 nm of vesicles of dendron 5 on alternately irradiat-
ing with UV and visible light. f)(i)Photocontrolled release profile of
calcein from the vesicle of dendron 5 after periodic irradiation with UV
and visible light. Black circles and open circles indicate irradiation with
UV (l=350 nm)and visible light ( l>400 nm)for 3 min, respectively.
(ii)Release profile of calcein from the vesicle of dendron 5 in the dark.
spectra of the vesicles showed the changes in the absorbtion
profile upon irradiation with UV (l = 350 nm) and visible
irradiation (l > 400 nm; see Figure S5 in the Supporting
Information). Upon irradiation with UV light, the UV/Vis
spectra of the vesicle of dendron 5 showed an increase in the
intensity of the absorption band at 425 nm and a decrease in
the absorption band at 325 nm, which indicated that trans-to-
cis isomerization of the focal azobenzene unit had occurred
(see Figure S5 in the Supporting Information). In contrast, the
absorption at 325 nm of vesicles of dendron 5 increased in
intensity upon exposure of the solution to visible light. This
process can be repeated with alternating irradiation with UV
and visible light as shown in Figure 4e. It was confirmed
through DLS and TEM experiments that the vesicular
structure was not noticeably deformed by irradiation with
UV light (l = 350 nm) for 60 minutes (Figure 4d). The DLS
analysis showed that the average Rh value of the vesicle was
116 nm (PDI = 0.171), which is similar to that of the vesicle
before irradiation with UV light (see Figure S3b in the
Supporting Information). The TEM experiment also con-
firmed the spherical shape of the vesicle after irradiation with
UV light. However, the permeability of the vesicle was
dependent on the photoisomerization of the focal azo moiety.
The permeability coefficient (P) of vesicles of dendron 5 to
calcein was determined as 1.0 ” 10À9 cmsÀ1 at 258C in the
dark.[34] Upon exposure to UV light (l = 350 nm), the cis-
azobenzene moiety in the vesicle membrane gave rise to
remarkably enhanced permeability (P = 8.6 ” 10À8 cmsÀ1) as a
result of a repulsive interaction[35] between the geometrically
distorted amphiphiles, which would lead to an enhanced
release of encapsulated molecules from the vesicle (Fig-
ure 4 f). On the other hand, the permeability of vesicles of
dendron 5 to calcein decreased after exposure to visible light
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(P = 1.0 ” 10À9 cmsÀ1). The rate of calcein release increased
of the vesicle. The use of dendritic building blocks in these
supramolecular approaches would provide a unique method-
ology to construct stimuli-responsive smart materials.
after irradiation with UV light (l = 350 nm) and was sup-
pressed by exposure to visible light (l > 400 nm), which also
indicates that the photoinduced release of clacein was
triggered by photoisomerization of the focal azobenzene
moiety. Hence, this moiety could behave as a “valve” with an
“on-off” function under specific stimulus in a photorespon-
sive release system (Figure 1c).
We also investigated the capability of the vesicles of 4 and
5 to release hydrophobic molecules from their hydrophobic
compartment in response to UV light (l = 350 nm) by using
Nile Red, a hydrophobic fluorescent guest (Figure 1b,d). The
release of Nile Red molecules from the membrane of the
vesicle into the aqueous phase was monitored by fluorescence
spectroscopy since the fluorescence intensity of Nile Red is
lower in aqueous solution than in the hydrophobic environ-
ment of the vesicle membrane.[36,37] In the case of vesicles of 4
(Figure 5a) the fluorescence of Nile Red decreased upon
irradiation with UV light, thus indicating that the release of
Received: November 16, 2007
Published online: March 10, 2008
Keywords: dendrons · nanostructures · photochemistry ·
.
self-assembly · vesicles
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