Photoresponsive soft nanotubes for controlled guest release

Article abstract of DOI:10.1002/chem.201100179

Light, transformation, release! Self-assembly of a simple amphiphile with an azobenzene unit produced an organic nanotube with 20 nm inner diameter. The trans-to-cis photoisomerization of the azobenzene unit within the solid bilayer membranes of the nanot

Full text of DOI:10.1002/chem.201100179

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DOI: 10.1002/chem.201100179
Photoresponsive Soft Nanotubes for Controlled Guest Release
Naohiro Kameta,*[a] Asuka Tanaka,[b] Haruhisa Akiyama,[c] Hiroyuki Minamikawa,[a]
Mitsutoshi Masuda,[a] and Toshimi Shimizu*[a]
Introduction of stimulus responsiveness into self-assembly
systems has attracted much attention in the field of nano-
and biotechnologies. Light as an external stimulus is of great
importance in terms of remote and accurate control, quick
switch, and easy focus.[1] Control of molecular assembly and
disassembly through photoirradiation is a key principle to
operate photoresponsive gels[2] and liquid crystals.[3] Advan-
ces in supramolecular chemistry have enabled us to achieve
photoresponsive control of the morphological transforma-
tion from a nanofiber to a nanosphere,[4] the contraction of
a large nanosphere into small one,[5] and photoresponsive
tuning of helicity, the helical pitch, and bundle states of
nanofibers.[6] On the other hand, self-assembly of rationally
designed amphiphiles in water has been known to give
nanotubes with well-defined size dimensions and functional-
ized surfaces.[7] The nanotubes have often had more poten-
tial functions than nanofibers, because the hollow cylindrical
structures with 10–100 nm inner diameters can act as con-
tainers for drugs, biomolecules, and nano-objects.[8] Release
control of those encapsulated guests from the nanotubeꢀs
hollow cylinder to bulk solutions is still a challenging task.
Morphological transformation of nanotubes through exter-
nal stimuli should induce guest release. Thermal phase tran-
sition from a solid-state nanotube to a liquid-crystalline-
state vesicle[7] and nanotubes with temperature-tunable di-
ameters[9] have been widely reported. Furthermore, nano-
tube-to-nanosphere and nanotube-to-nanofiber transitions
have already been achieved by environmental changes, such
as pH and salt concentrations,[10] dilution,[11] and complexa-
tion or specific reactions of components in nanotubes with
additives, such as cyclodextrin,[12] poly(propylene glycol),[13]
and enzymes.[14] However, the morphological transformation
of nanotubes through photostimulus has never been report-
ed, although phototriggered polymerization or cross-linking
of nanotubes, which self-assemble from amphiphiles with di-
acetylene or coumarin units, have been investigated.[15]
Herein we present the newly designed and synthesized,
simple amphiphile 1 (Scheme 1) composed of an azoben-
Scheme 1. Molecular structure of amphiphile 1.
zene moiety as a photoresponsive unit and a glycine moiety
as a hydrogen-bonding unit to construct self-assembled
nanotubes, which have the morphological changeability that
accompanies the trans–cis photoisomerization of the azoben-
zene moiety within the tubular wall, consisting of solid bi-
layer membranes. We describe a release control of guest
molecules through the photostimulated transformation from
tubular to fibrous morphologies.
The self-assembly experiment was performed as follows:
The synthetic amphiphile 1 (1 mg) was dispersed in water
(1 mL), which was heated to reflux, at pH 5–10. The resul-
tant hot aqueous solutions were gradually cooled to room
temperature. TEM observations showed that the self-assem-
bled morphologies strongly depended on the pH conditions,
that is, the protonation/deprotonation states of the amino
groups of 1. Self-assembly of 1 at pH 6.1 gave fibers, where-
[a] Dr. N. Kameta, Dr. H. Minamikawa, Dr. M. Masuda, Dr. T. Shimizu
Nanotube Research Center (NTRC)
National Institute of Advanced Industrial
Science and Technology (AIST)
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba
Ibaraki 305-8565 (Japan)
Fax : (+81)29-861-4545
E-mail: n-kameta@aist.go.jp
as at pH 9.2 sheets formed (Figure S3 and S4 in the Support-
[b] A. Tanaka
+
À
À
ing Information). The ratio NH3 / NH2 at pH 6.1 and 9.2
can be estimated to 95:5 and 5:95, respectively, by using an
acid-dissociation constant (pKa =7.41, Figure S2 in the Sup-
Graduate School of Chemistry
University of Tsukuba, 1-1-1 Tennodai, Tsukuba
Ibaraki 305-8571 (Japan)
porting Information). Selective formation of nanotubes was
[c] Dr. H. Akiyama
+
Nanosystem Research Institute
National Institute of Advanced Industrial
Science and Technology (AIST)
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba
Ibaraki 305-8565 (Japan)
À
À
observed from pH 7.6 ( NH3 / NH2 =40:60) to pH 8.2
+
À
À
( NH3 / NH2 =15:85). TEM images revealed that the
nanotubes had uniform size dimensions, 20 nm inner diame-
ter and 8 nm wall thickness (Figure 1a). Once the nanotubes
were prepared in the appropriate pH range, the tubular
morphology was kept intact for three months in a water so-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100179.
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Figure 2. Amide IR bands (left) and XRD patterns in small-angle regions
(right) of the a,a’) nanotubes, b,b’) cylindrical nanofibers, and c,c’) heli-
cal nanotapes.
Figure 1. TEM images of a) nanotubes, b) cylindrical nanofibers formed
by UV-light irradiation of the nanotubes, and c) helical nanotapes
formed by visible-light irradiation of the cylindrical nanofibers. The
hollow cylindrical space of the nanotubes with 20 nm inner diameters is
visible with phosphotungstate as a negative staining reagent.
bonding between the amide groups. The absorption maxi-
mum of the nanotube (lmax =320 nm) showed a hypsochro-
mic shift compared with that of 1 dissolved in THF (lmax
=
330 nm), indicating that the azobenzene unit of 1 forms H-
type aggregates within the bilayer membranes of the nano-
tube (Figure S6 in the Supporting Information).
We carried out the photoirradiation experiments with a
super-high-pressure mercury lamp (500 W) with appropriate
filters. UV-light irradiation (365 nm) of the nanotube dis-
lution of pH 5–10, although the self-assembly behavior of 1
remarkably depends on the pH conditions, as described
above.
Powder XRD, IR, and UV/Vis spectroscopic measure-
ments afforded information about the molecular packing of
the nanotube. The XRD pattern indicates a single diffrac-
tion peak in the small-angle region (Figure 2a’); this reflects
the membrane-stacking periodicity (d) of the bilayer mem-
branes of the nanotube. The d value (=4.09 nm) is shorter
than twice the extended molecular length (L=2.24 nm),
suggesting that the molecules tilt by 248 within the bilayer
membranes (Figure 4a). The amide-I IR bands of the nano-
tube (1652 and 1629 cmÀ1) were at lower wave numbers
than those of 1 dissolved in THF (1663 and 1644 cmÀ1), in
which 1 exists in a monomolecular, dispersed state (Fig-
ure S5 in the Supporting Information). On the other hand,
the amide-II IR band of the nanotube (1551 cmÀ1) was at a
higher wave number than that of 1 dissolved in THF
(1540 cmÀ1). Such shifts of the IR bands supported that the
molecular packing within the bilayer membranes of the
nanotube was stabilized by the intermolecular hydrogen
persed in water induced a decrease of the p–p* band (lmax
320 nm) of the trans-azobenzene, whereas the p–p* (lmax
=
=
252 nm) and n–p* (lmax =427 nm) bands of the cis isomer
appeared for the first time (Figure 3). The spectral change
attributed to the trans-to-cis isomerization was attained
within 4 min, even though the nanotube consisted of solid
bilayer membranes. The isomerization rate was comparable
to that of azobenzene units tightly packed in a fibrous as-
sembly of b-sheet structures.[16] Continuous visible-light irra-
diation at 436 nm for 15 min gave a spectral change corre-
sponding to the complete recovery of the trans state from
the cis state. UV/Vis diffuse-reflection spectroscopic meas-
urements of lyophilized nanotubes, representing dried sam-
ples, also revealed that the reversible isomerisation of the
azobenzene unit occurs on a time scale similar to that of the
dispersed-solution system (Figure S7 in the Supporting In-
formation).
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Photoresponsive Nanotubes
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Figure 3. Changes in the absorption spectra upon photoirradiation of
nanotubes dispersed in water.
The trans-to-cis isomerization of the azobenzene unit
through UV-light irradiation induced
a morphological
change from nanotubes to cylindrical nanofibers (Figure 1).
The hollow cylinder with 20 nm inner diameter was clearly
visible by penetration of a negative staining reagent, where-
as the inner diameter of the cylindrical nanofibers was too
narrow to be observed by TEM measurements. The shorter
membrane-stacking periodicity of the cylindrical nanofibers
(d=3.64 nm) compared with that of the nanotubes (d=
4.09 nm) is attributed to the trans-to-cis isomerization within
the bilayer membranes (Figures 2 and 4). The frequencies of
amide-I and -II bands of the cylindrical nanofibers were
higher and lower than those of amide-I and -II bands of the
nanotubes, respectively (Figure 2a,b), supporting weaker hy-
drogen bonds in the cis isomer of 1 than in the trans isomer.
The reversed cis-to-trans isomerization through visible-light
irradiation caused no recovery of the tubular morphology.
Alternatively, the cylindrical nanofibers with several tens of
micrometers in length were transformed into helical nano-
tapes with several hundreds of nanometers in length (Fig-
ure 1c). We achieved the morphological recovery from the
cylindrical nanofibers to the nanotubes by heating to reflux,
that is, the cis-to-trans isomerization was thermally promot-
ed without visible-light irradiation. The molecular packing
of the helical nanotapes formed through visible-light irradia-
tion was different from that of the nanotubes, even though
both assemblies consisted of bilayer membranes of the trans
isomer of 1. The d=4.33 nm of the helical nanotapes was
approximately twice the L=2.24 nm, indicating that the tilt
angle of the trans isomer of 1 within in the bilayer mem-
branes was near 08 (Figure 2 and 4). The difference in the
tilt angle between the helical nanotapes and nanotubes re-
flects the difference in the amide-I and -II bands (Fig-
ure 2a,c). The unique morphological transformation behav-
ior based on the reversible photoisomerization of the azo-
benzene unit has never been seen for preceding supramolec-
ular systems, which show a destruction of the nanostructures
by molecular disassembly based on the trans-to-cis isomeri-
zation and a reconstruction of the same nanostructures by
reassembly based on the reversed cis-to-trans isomeriza-
tion.[16,17]
Figure 4. Schematic representation of the morphological transformation
resulting from photoisomerization of the azobenzene unit within the
solid bilayer membranes. All assemblies are drawn as single-bilayer-mem-
brane structures, although they are actually formed by stacking of two bi-
layer membranes.
The morphological change from the nanotubes to the cy-
lindrical nanofibers through UV-light irradiation should
strongly influence the release behavior of pre-encapsulated
guests in the hollow cylinder of the nanotubes. Figure 5
shows the release ratio of carboxyfluorescein (CF) as a
guest molecule. Without photoirradiation, a constant slow
release of the encapsulated CF was observed from the nano-
tubeꢀs hollow cylinder to a bulk solution at pH 8.2, in which
the anionic CF has no electrostatic interaction with the
Figure 5. Release profiles of CF encapsulated in the nanotubeꢀs hollow
cylinder at pH 8.2 with and without photoirradiation.
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N. Kameta, T. Shimizu et al.
nearly deprotonated amino groups on the nanotube inner
surface (Figure S8 in the Supporting Information and the
open black triangles in Figure 5, indicating a short time
scale). The tubular morphology with the high-axial-ratio
structures contributes to the constant slow release.[18] The
UV-light irradiation promoted the release of 40% of the
CF, as a result of the morphological transformation from the
nanotubes to the cylindrical nanofibers (closed green circles
in Figure 5). On the other hand, about 12 h was required to
reach the release of 40% of the CF from the nanotubeꢀs
hollow cylinder without UV-light irradiation (Figure S8 in
the Supporting Information). Such rapid enhancement of
the release rate was found to be compatible with the equi-
librium time for the trans-to-cis isomerization of the azoben-
zene unit. From 4 min onward, the release rate of CF seems
to be slower (open green circles in Figure 5), indicating that
the cylindrical nanofibers formed through UV-light irradia-
tion have a cavity that is able to store CF. The size of the
hydrophilic cavity is comparable to those of hydrophilic and
hydrophobic cavities of micellelike nanofibers.[19] The width
(15 nm) of the cylindrical nanofibers, estimated from the
TEM image, corresponds to the stacking of the four bilayer
membranes (4ꢂd=14.56 nm), whereas the wall thickness of
the nanotubes corresponds to the stacking of two bilayer
membranes (2ꢂd=8.18 nm). Therefore, the constriction and
shrinking of the nanotubeꢀs hollow cylinder allow the forma-
tion of cylindrical nanofibers. TEM observations of the in-
termediate obtained by short UV-light irradiation for 10 s
support such a transformation process (Figure S9 in the Sup-
porting Information). However, herein we do not confirm
whether the shrinking accompanies the molecular disassem-
bly and reassembly on a time scale shorter than seconds.
The rapid enhancement of the release ratio just after UV-
light irradiation is ascribed to a compulsive spout of the en-
capsulated CF through the morphological change and the
shrinking process (closed green circles in Figure 5). On the
other hand, the slow release from 4 min onward occurred
from the cavity of the cylindrical nanofibers, which was
formed as the result of the shrinking of the nanotubeꢀs
hollow cylinder. The visible-light irradiation after the UV-
light irradiation for 15 min eventually released all of the re-
tained CF in the cylindrical nanofibers, as a result of the
morphological transformation from cylindrical nanofibers to
helical nanotapes (closed red circles in Figure 5). The com-
plete release of CF within 10 min, under visible-light irradia-
tion, was clearly related to the time required for the cis-to-
trans isomerization. Because the helical nanotapes have no
cavity for storing CF, as expected from the complete release,
the helical nanotapes may be a result of unrolling of the cy-
lindrical nanofibers.[7]
lated morphological transformation enabled us to precisely
control the release of the guest molecules. The present study
should open ways to develop smart soft materials applicable
in switching devises, actuators, nanopipettes, as well as in
drug-delivery systems.
Experimental Section
Synthesis and identification of amphiphile 1 are presented in the Sup-
porting Information (Figure S1). The chemical yield of the nanotube was
estimated by the following procedure: The aqueous solution obtained by
self-assembly of the amphiphilic monomer 1 (1.0 mg, 3.1 mmol) in water
(1 mL) was filtered through a membrane, with 0.2 mm pore size, to sepa-
rate monomers that did not take part in nanotube formation. The
amount of recovered 1 was calculated to be 0.015 mmol by UV/Vis spec-
troscopy. Therefore, the chemical yield of the nanotube against the initial
amount of 1 can be estimated to be 99.5%.
Preparation of the nanotubes encapsulating CF was performed by mixing
an aqueous solution of CF (60 mg, 159 mmol) with the lyophilized nano-
tubes (5.0 mg, 15 mmol) at pH 9, adjusted by NaOH. Electrostatic interac-
tions between the anionic CF and the inner/outer surfaces of the nano-
tubes can be suppressed at pH 9, because of deprotonation of the amino
groups on both surfaces. Capillary action enabled the nanotubes to en-
capsulate CF. After aging overnight, the solution was filtered through a
polycarbonate membrane with 0.2 mm pore size. The residual nanotubes
were washed several times to remove CF outside of the nanotubes. The
complete destruction of the nanotubes by addition of 5% Triton X-100
caused a fluorescence recovery of CF (maximum fluorescence intensity
at 520 nm: F0), indicating that the encapsulated CF that has no fluores-
cence, because the self-dimerization in the confined nanospace was
forcedly released to bulk media. The amount of encapsulated CF in the
nanotube (5.0 mg) was estimated to be 1.5 mg. The fluorescence intensity,
Ft, of released CF after a certain time, with and without photoirradiation,
was monitored. The release rate (%) of CF was calculated on the basis
of the ratio of fluorescence intensity, 100ꢂ(Ft/F0).
Acknowledgements
This Research was partly supported by Grant-in-Aid for Young Scientists
(B) No. 21710117 from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology (MEXT).
Keywords: host–guest
systems
·
nanostructures
·
photochemistry · self-assembly · supramolecular chemistry
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Received: January 18, 2011
Published online: April 6, 2011
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