Light-switchable vesicles from liquid-crystalline homopolymer-surfactant complexes

Article abstract of DOI:10.1002/anie.201205660

Polymeric onions: A concept of vesicle fabrication based on nonstoichiometric complexation of a polybase with an amphiphilic ligand bearing a sulfonic acid group is developed (see picture). In contrast to conventional polymersomes, the polymer backbones are oriented mainly parallel to the vesicle walls. The vesicles can collapse under UV-irradiation because of a UV-triggered trans-cis isomerization of the azo-group-containing ligand. Copyright

Full text of DOI:10.1002/anie.201205660

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DOI: 10.1002/anie.201205660
Polymersomes
Light-Switchable Vesicles from Liquid-Crystalline Homopolymer–
Surfactant Complexes**
Lei Li, Martin Rosenthal, Heng Zhang, Jaime J. Hernandez, Markus Drechsler, Kim Hꢀ Phan,
Stephan Rꢁtten, Xiaomin Zhu,* Dimitri A. Ivanov,* and Martin Mçller
Vesicles are supramolecular assemblies of natural or synthetic
amphiphilic molecules that enclose a volume with a thin
membrane. In living cells low-molecular-weight phospholi-
pids form vesicles (often termed liposomes) that play a central
role in compartmentalization functions, nutrient transporta-
tion, and DNA protection.[1] Vesicles attract growing interest
because of their various applications ranging from cosmetics
to drug delivery.[2] Polymer vesicles, or polymersomes, formed
by high-molecular-weight compounds, are significantly more
stable to lysis by surfactants than the ones formed from low-
molecular-weight amphiphiles, while preserving low immu-
nogenicity.[3] Polymersomes are generally fabricated from
amphiphilic linear block copolymers,[4] hyperbranched poly-
mers,[5] and dendrimers,[6] or by polymerization of preformed
low-molecular-weight vesicles.[7]
to assume that the complexes are capable to form vesicles
such as lipid–DNA complexes, which self-assemble in a multi-
lamellar structure (LaC) consisting of alternating DNA and
lipid layers.[9] However, in the case of synthetic polymers the
vesicle formation was reported so far only for the complexes
of block ionomers with oppositely charged surfactants.[10] The
stoichiometric homopolymer complexes are generally not
soluble in water, whereas the nonstoichiometric complexes
are known to form “mixed micelles” consisting of clusters of
hydrophobic surfactant chains surrounded by polar polyelec-
trolyte backbones.[11] There is, yet, a unique and versatile
approach for the synthesis of supramolecular complexes by
neutralization of a polybase with amphiphilic acid mole-
cules.[12] It allows for a facile control of the degree of
neutralization (DN), that is, the degree of substitution. The
main question to be addressed here is whether this type of
system is prone to spontaneous curvature of the smectic layers
to eventually form vesicles. The possibility of vesicle forma-
tion from polybase–amphiphilic acid molecules can pave the
way to fabrication of a new type of polymersomes.
Complexation of polymer chains by low-molecular-weight
amphiphiles through noncovalent interactions is a common
tool in the design of nanostructured macromolecular materi-
als.[8] Most frequently, lamellar phases are formed, where
layers of ligands and polymer backbones alternate. It is logical
In this work, we prepared complexes of poly(2-vinyl-
pyridine) (P2VP) with an amphiphilic sulfonic acid, 4’-[3,5-
[*] L. Li, H. Zhang, Dr. H. Phan, S. Rꢀtten, Dr. X. Zhu,
Prof. Dr. M. Mçller
di(trideca-2,4-diynyloxyl)]azobenzene-4-sulfonic
acid
DWI an der RWTH Aachen e.V. and Institute for Technical
and Macromolecular Chemistry of RWTH Aachen University
Forkenbeckstrasse 50, Aachen 52056 (Germany)
E-mail: zhu@dwi.rwth-aachen.de
(Scheme 1), and studied their self-assembly in bulk and in
water suspensions. The presence of an azo group can render
the system photoswitchable,[13] whereas the diacetylene
groups can be used to further stabilize the self-assembled
structure by UV-polymerization.[7a,b,14]
Dr. M. Rosenthal, Dr. J. J. Hernandez, Dr. D. A. Ivanov
Institut de Sciences de Matꢁriaux de Mulhouse
15 rue Jean Starcky, Mulhouse, 68057 (France)
E-mail: dimitri.ivanov@uha.fr
Dr. X. Zhu, Dr. D. A. Ivanov
Moscow State University, Faculty of Fundamental Physical
and Chemical Engineering, GSP-1, 1-51 Leninskie Gory
Moscow, 119991 (Russian Federation)
Dr. M. Drechsler
Macromolecular Chemistry II, University of Bayreuth Universitꢂts-
strasse 30, Bayreuth, 95447 (Germany)
Scheme 1. Chemical structure of complexes of P2VP and 4’-[3,5-di(tri-
deca-2,4-diynyloxyl)]azobenzene-4-sulfonic acid; DN=degree of neu-
tralization.
[**] Financial support from the German Research Foundation and the
French Agence Nationale de la Recherche (DFG-ANR project
“T2T”), MO 628/13-1, and IUPAC project PAC-PAL-10-02-26 is
gratefully acknowledged. D.A.I. thanks the Russian Ministry of
Science and Education (project for financial support of leading
scientists, grant number 11.G34.31.0055 from 19.10.2011). L.L.
thanks the Chinese Scholarship Council for financial support. The
authors are grateful to Dr. Wim Bras and Dr. Giuseppe Portale from
the DUBBLE beamline (ESRF, France) for fruitful discussions and
excellent technical support. M.D. thanks for support from the
“Bayreuth Institute for Macromolecular Research” (BIMF) and the
“Bayreuth Center for Colloids and Interfaces” (BZKG).
According to small-angle X-ray scattering (SAXS) data,
the supramolecular complexes corresponding to different DN
values, namely 25, 50, and 100%, exhibit lamellar structures.
This is concluded from the set of characteristic h00 reflections
visible in the medium-angle range (see Figure S1 in the
Supporting Information). The layer thickness calculated using
several orders of the 100 reflection equals 6.02 nm and is
largely independent from the DN for the values above 25%.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201205660.
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Importantly, for a DN value of 25% the 100 reflection is
shifted towards low angles (d = 7.78 nm) and noticeably
broadened. This fact can be attributed to the increased
concentration of structural defects in this system containing
an excess of P2VP chains. Indeed, the structure of this
complex marks a transition from amorphous P2VP to a liquid-
crystalline (LC) polymer complex, and is at the verge of the
LC phase formation. The length of the sulfonic acid molecule
in the assumption of the fully stretched alkyl chain con-
formation is about 3.6 nm, so the smectic layer can be viewed
as a bilayer of the ligand with partially interdigitating alkyl
tails and the head groups linked to the P2VP backbones.
Different ways of vesicle preparation have been tried. For
example, we were not able to directly disperse the complexes
into water through thin-film hydration. However, upon
injection of tetrahydrofuran (THF) solutions of the com-
plexes with DN values of 25 and 50% into a large amount of
water, stable turbid dispersions were obtained. The complex
with a DN of 100% seems to be too hydrophobic to be
dispersed in water in this way. For the complex with a DN of
25% the dynamic light scattering (DLS) measurements
showed a bimodal distribution of dispersed particles with
two median diameters of 2.1 mm and 42 nm (Figure S2). Using
optical microscopy the formation of spherical particles with
an average diameter of (4.5 Æ 1.4) mm was observed (Fig-
ure S3). At the same time, cryo-field emission scanning
electron microscopy (FESEM) micrographs confirmed the
formation of microsized vesicles with a thin membrane
(Figure 1). The membrane thickness was estimated to be
less than 20 nm, so it possibly comprises one or just a few
smectic layers.
Figure 2. A typical cryo-TEM micrograph of the multilamellar vesicles
formed by the complex with a DN value of 25% together with the
corresponding 1D power spectral density function (PSD, inset). The r
stands for the reciprocal distance in nmÀ1
.
The vesicle structure was also addressed by SAXS which
revealed a strong interference maximum at 6.55 nm (Fig-
ure 3a). This value is in good agreement with the d spacing in
the cryo-TEM micrographs. In addition, it is rather close to
the smectic spacing of the complex in the bulk (see Figure S1).
Figure 3. a) SAXS curve measured for water suspension of vesicles
formed by the complex with DN=25% and b) the corresponding
interface distribution function g1(d). The distances L1 and L2 indicated
on the right panel stand for the thickness of the two constitutive
sublayers of the smectic layer with a total thickness LB.
The only minor difference between the SAXS patterns of the
complex in water dispersions and in the bulk is that the
vesicles exhibit a faint second order of the main interference
maximum whereas this peak is not observed for the bulk
sample. This difference can be accounted for by slight
variations in the relative thickness of the constitutive
sublayers of the smectic layer because of a limited swelling
of the P2VP-rich phase in water.
A more detailed analysis of the vesicle microstructure was
performed using a 1D interface distribution function (IDF)[15]
(Figure 3b). The IDF of the vesicles exhibits a shape typical of
a two-phase lamellar system. The first minimum at 6.45 nm
corresponds to the nearest-neighbor distance of the layered
Figure 1. Cryo-FESEM micrographs of microsized vesicles formed by
the complex with a DN value of 25%.
The nanoparticles with the size below 500 nm were
visualized by cryo-TEM. Figure 2 shows the internal structure
of these particles which consist of concentric alternating
layers; therefore, they can be assigned to onionlike multi-
lamellar vesicles. The characteristic spacing of 6.7 nm was
derived from the one-dimensional power spectral density
function computed from the micrographs (see the inset in
Figure 2).
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stack, being virtually identical to the value obtained from
cryo-TEM. The maximum at 4.63 nm can be attributed to the
most probable thickness of the sublayer containing the P2VP
backbones and complexed sulfonic acid groups, while the
maximum at 1.81 nm corresponds to the adjacent alkyl-chain
layer. The sharp first two positive peaks indicate that the
sublayers have a relatively narrow distribution of thickness.
Based on the SAXS data, a packing model for the
complex of a DN value of 25% in the vesicles has been
proposed (Figure 4). The amphiphilic sulfonic acid molecules
sites, this system offers a possibility to incorporate different
functional molecules into the vesicle structure.
Since the vesicles contain photosensitive azo groups, it
was instructive to follow the impact of the trans–cis photo-
isomerization on the vesicle structure. To this end, the vesicles
were irradiated by UV light (254 nm), and were simultane-
ously studied by UV/Vis spectroscopy (Figure 5, top panel).
The intensity of the absorption band at 350 nm corresponding
to the p–p* transition of the azo group gradually decreased
with exposure time, indicating a trans–cis transition. After
90 min of irradiation, the complex was precipitated (see the
inset in Figure 5, top panel).
Figure 4. Proposed molecular model of the vesicles formed by the
complex with a DN value of 25%.
form bilayers and the P2VP backbones are sandwiched
between them. The shell of the microsized vesicles most
probably consists of only one or a few such bilayers.
According to cryo-FESEM measurements, the ligand mole-
cules alone do not form particles in water. The complex
corresponding to a DN value of 50% can be dispersed in
water and particles of about 200 nm in size were formed as
shown by DLS and cryo-FESEM, however, no formation of
vesicles was evidenced. Therefore, it seems that the vesicles
can only be formed at low DN values such as 25%. This fact
can be explained as follows. On the one hand, the excess of
P2VP favors the formation of chain entanglements and
thereby improves the mechanical properties of the vesicles.
Importantly, the polymer chains here are oriented mainly
parallel to the vesicle wall. This orientation makes the system
more stable than conventional polymersomes where the
backbones are perpendicular to the layers.[3b] Indeed, one
can see in Figure 2 that the system tolerates a high curvature
of the walls: the radius of the layer can be as small as 50 nm.
On the other hand, at low DN values the sulfonic acid
molecules have a high degree of freedom and are able to slide
along the P2VP chains to adapt to the local curvature and
environment. This adjustment mechanism would become
impeded at higher DN values. The minimum DN value at
which the vesicles are formed likely reflects the transition
point from an amorphous P2VP-rich system to a LC polymer
complex. It is also important to mention that although P2VP
is hydrophilic, it is insoluble in water at neutral pH. Therefore,
no dissociation of the complex is expected under these
conditions. Finally because of a large amount of free binding
Figure 5. Top panel: UV/Vis spectra of the complex with a DN value of
25% in water upon UV irradiation. The concentration of the complex
is 0.1 mgmLÀ1. Bottom panel: Cryo-TEM micrographs of the multilayer
vesicles before (left) and after (right) UV irradiation for 45 min.
The impact of UV light on the morphology of the vesicles
was also examined by cryo-TEM (Figure 5, bottom). Upon
UV irradiation, we can observe the appearance of deformed
vesicles with locally disrupted regions. Importantly, the
smectic layering in these regions has completely disappeared.
We used grazing-incidence SAXS (GISAXS) to investigate
the structure of the thin films prepared by a drop-casting
method from suspensions of vesicle before and after UV ir-
radiation (Figure S4). It can be seen that the smectic order in
the complexes vanishes after 90 min of UV exposure. Mean-
while, the disappearance of the vesicle particles is evidenced
by DLS measurements. The cis isomer has a bent shape with
a low anisometry, which can perturb the LC order in the
vesicles.[16] Therefore, it can be concluded that the collapse of
the vesicles results from the UV-induced isomerization.
During this process the vesicles lose their fine microphase-
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Tanner, P. Baumann, R. Enea, O. Onaca, C. Palivan, W. Meier,
Acc. Chem. Res. 2011, 44, 1039 – 1049.
separated layered structure and transform to isotropic
droplets that are no more stabilized by the outer hydrophilic
shell of P2VP. It is noteworthy that, during UV irradiation no
absorption bands in the range of 500 to 600 nm were detected,
indicating that no polymerization of the diacetylene groups
has occurred. This is possibly due to the progressive
disruption of the smectic phase during UV irradiation.
In conclusion, we demonstrate for the first time that a LC
complex of a polybase and amphiphilic sulfonic acid with
a DN value of 25% forms unilamellar microsized as well as
onionlike multilamellar nanosized vesicles. The structure of
the complex in the vesicles was found to be similar to that in
the bulk, where the polymer backbones are sandwiched
between the bilayers formed by the ligand molecules. In
contrast to conventional polymer vesicles, the polymer chains
in this system are mainly parallel to the vesicle surface,
contributing to their mechanical stability. A large amount of
remaining free binding sites makes it possible to incorporate
different functional molecules into the vesicles. Furthermore,
a collapse of the vesicles can be induced by UV irradiation
because of the trans–cis transition of the azo groups, which
leads to the isotropization of the layered structure. This
feature could make this system promising for controlled
delivery applications.
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Received: July 16, 2012
Revised: September 6, 2012
Published online: October 10, 2012
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Keywords: photoisomerization · polymersomes · self-assembly ·
supramolecular complexes · vesicles
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