Light-controlled formation of vesicles and supramolecular organogels by a cholesterol-bearing amphiphilic molecular switch

Article abstract of DOI:10.1002/chem.201302902

A new responsive material composed of an amphiphilic light-switchable dithienylethene unit functionalized with a hydrophobic cholesterol unit and a hydrophilic poly(ethylene glycol)-modified pyridinium group has been designed. This unique single-molecule system shows responsive light-switchable self-assembly in both water and organic solvents. Light-triggered reversible vesicle formation in aqueous solutions is reported. The molecule shows a different behavior in apolar aromatic solvents, in which light-controlled formation of organogel fibers is observed. The light-triggered aggregation behavior of this molecule demonstrates that control of a supramolecular structure with light can be achieved in both aqueous and organic media and that this ability can be present in a single molecule. This opens the way toward the effective development of new strategies in soft nanotechnology for applications in controlled chemical release systems. A state of light and medium: A unique single-molecule system has been designed that shows responsive self-assembly in both water and organic solvents (see scheme). Light-triggered reversible vesicle formation in aqueous solutions is reported. The cholesterol-bearing amphiphilic dithienylethene molecule shows a different behavior in organic media, in which light-controlled organogel formation is observed. The aggregation behavior of this molecule in different media is described, which opens new avenues in responsive soft materials. Copyright

Full text of DOI:10.1002/chem.201302902

DOI: 10.1002/chem.201302902
Full Paper
&
Supramolecular Chemistry
Light-Controlled Formation of Vesicles and Supramolecular
Organogels by a Cholesterol-Bearing Amphiphilic
Molecular Switch
Jochem T. van Herpt, Jetsuda Areephong, Marc C. A. Stuart, Wesley R. Browne,* and
Ben L. Feringa*[a]
Abstract: A new responsive material composed of an am-
phiphilic light-switchable dithienylethene unit functionalized
with a hydrophobic cholesterol unit and a hydrophilic poly-
(ethylene glycol)-modified pyridinium group has been de-
signed. This unique single-molecule system shows respon-
sive light-switchable self-assembly in both water and organic
solvents. Light-triggered reversible vesicle formation in
aqueous solutions is reported. The molecule shows a differ-
ent behavior in apolar aromatic solvents, in which light-con-
trolled formation of organogel fibers is observed. The light-
triggered aggregation behavior of this molecule demon-
strates that control of a supramolecular structure with light
can be achieved in both aqueous and organic media and
that this ability can be present in a single molecule. This
opens the way toward the effective development of new
strategies in soft nanotechnology for applications in con-
trolled chemical release systems.
Introduction
aggregates only in organic media, which severely limits the
possibilities for biological applications.
The self-assembly of small functional molecules into supra-
molecular structures,[1] including nanofibers,[2] nanotubes,[3]
vesicles,[4] micelles,[5] and gels,[6] is central to the construction
of molecular-based soft nanotechnological devices and materi-
als for applications as diverse as drug delivery,[7] controlled cell
growth,[8] and sensing.[9] Despite considerable progress, control
over the organization by physical and chemical trigger ele-
ments remains a major challenge.[10] A highly promising ap-
proach towards this goal is the use of responsive, or smart,
materials through the integration of addressable functionality,
for example, intrinsic photoresponsive moieties, within the
supramolecular building blocks.[11] This approach opens the
possibility to control self-assembled nanostructures formed
from individual molecules or to change the properties of
supramolecular arrays noninvasively in time and space, by
using light.[3] Dithienylethene photoswitches[12] have played
a central role in addressing such supramolecular systems, in-
cluding nanofibers,[13] nanotubes,[14] metal complexes,[15] surfa-
ces,[16] organogels,[17] polymer aggregates,[18] and liquid crys-
tals.[19] However, most of these systems form supramolecular
Herein, we report a unique single-molecule system that
shows responsive assembly, in both water and organic sol-
vents, which enables reversible photochemical control over
both vesicle and organogel formation, by using the amphiphil-
ic photochromic diaryl ethene 1, functionalized with a choles-
terol unit and a poly(ethylene glycol)-modified pyridinium
moiety (Scheme 1). The cholesterol unit provides hydrophobic
functionality with possible applications to biological mem-
branes. The poly(ethylene glycol)-modified pyridinium group
facilitates sufficient hydration in aqueous environments, in
which aggregation is predominantly driven by hydrophobic in-
teractions.
The aggregation behavior of 1 in aqueous solutions repre-
sents one of the very few examples of fully reversible light-
driven control over vesicle formation in aqueous media[20] and
is, to the best of our knowledge, the first system based on
a single compound as opposed to a mixture of compounds.[10]
Photoresponsive organogelation is a well-described phenom-
enon, but this property is not frequently observed for com-
pounds that also form distinct aqueous supramolecular aggre-
gates, and it offers insight into the behavior of the com-
pound.[21] This behavior could provide opportunities in applica-
tions as diverse as controlled release of compounds in biologi-
cal systems, selective labeling, and control of cell growth.
[a] J. T. van Herpt, Dr. J. Areephong, Dr. M. C. A. Stuart, Prof. Dr. W. R. Browne,
Prof. Dr. B. L. Feringa
Stratingh Institute for Chemistry, University of Groningen
Nijenborgh 4, 9747 AG Groningen (NL)
E-mail: w.r.browne@rug.nl
Results and Discussion
b.l.feringa@rug.nl
The synthesis of compound 1o (Scheme 2) is described in the
Supporting Information, and its structure was confirmed by H
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201302902.
1
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not fluorescent, which allows the switching process to be fol-
lowed readily. Compound 1o fluoresces at 516 nm (lexc
=
380 nm) in toluene (Figure 1b), at 610 nm in ethanol (Fig-
ure 1d), and at 550 nm in water (Figure 1 f). The shift in the
emission maximum is most likely solvatochromic, with the mol-
ecules experiencing the most polar environment in ethanol, in
which they are fully dissolved; in water, aggregation (see
below) somewhat reduces the effect. The fluorescence in both
organic and aqueous solution could be switched off and on by
irradiation at l=365 and >500 nm, respectively (Figure 1e,
insert).[23]
The gelation behavior of 1o was determined in a range of
solvents (Table 1). Stable gels were formed in o-, m-, and p-
xylene (1 mgmLÀ1), benzene and toluene, as was confirmed by
rheometry measurements (see Figure 2).
The rheological strain sweep measurements (Figure 2a)
show a plateau region until a strain of 1%, which hints that
larger strains result in the (partial) breakup of the fiber net-
work. The frequency dependence (Figure 2b) of the gels was
found to be largely frequency independent, with the storage
modulus (G’) dominating the loss modulus (G’’). This behavior,
typical of gels, was lost once the samples were converted to
the closed form photochemically (Figure 2a).
Cryo transmission electron microscopy (cryo-TEM) images of
these organogels in xylene and toluene indicate that fibers
were the dominant supramolecular structure formed (Fig-
ure 3b and c). These images are the first examples reported of
cryo-TEM performed by using xylene as the solvent.[24] The
thickness of the gel fibers ((17.0Æ1.0) nm) is uniform and ex-
Scheme 1. Dynamic self-assembly behavior of 1 in aqueous and organic
media upon light-induced switching. Chol: cholesterol; 1o: open form of 1;
1c: closed form of 1).
and 13C NMR spectroscopy, elemental analysis, and MALDI-TOF
mass spectrometry. The photochromic behavior of 1 was char-
acterized in toluene and H2O
(Figure 1). As expected, com-
pound
1
shows reversible
changes in absorbance and fluo-
rescence intensity upon alter-
nate irradiation with ultraviolet
(l=365 nm) and visible (l>
500 nm) light. Upon irradiation
in toluene at l=365 nm, the
colorless solution turned blue
and the absorption band as-
signed to 1c appeared at
649 nm (Figure 1a). Concomi-
tantly, the absorbance of
1o at 372 nm (e=(1.9Æ0.1)ꢁ
104 mÀ1 cmÀ1
)
decreased. The
ratio of 1c to 1o in the photo-
stationary state (pss) was found
to be higher than 98:2.[22] Upon
irradiation at l>500 nm, the
blue color faded and the open-
ring isomer 1o was regenerated.
The absorption maxima of 1o
and 1c in H2O are 377 (e=(1.3Æ
0.1)ꢁ104 mÀ1 cmÀ1) and 647 nm,
respectively (Figure 1e). In the
open state, 1o is fluorescent,
whereas the closed form, 1c, is Scheme 2. Synthesis of amphiphilic dithienylethene 1.
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Figure 1. UV/Vis absorbance (a, c, and e) and fluorescence (b, d, and f) spectra of 1 in a, b) toluene ((2.6Æ0.1)ꢁ10À5 m), c, d) ethanol ((3.2Æ0.1)ꢁ10À5 m), and
e, f) H2O ((2.0Æ0.1)ꢁ10À5 m). Insert: Modulation of fluorescence at 550 nm in water over several switching cycles. PSS: photostationary state.
ceeds the maximum length of compound 1 (3.6 nm) to a large
extent, which indicates that the aggregation occurs at several
hierarchical levels. Both cholesterol[25] and dithienylethene moi-
eties[17] have been shown to be able to form organogels under
certain conditions and it is therefore likely that the aggrega-
tion of compound 1o is due to the cumulative effect of both
moieties.
Upon irradiation of an organogel formed by 1o in toluene
at l=365 nm, a gel-to-sol transition was observed within sec-
onds. The system could be switched fully reversibly between
a gel and the solution state by photochemical ring closing or
opening of the photochromic dithienylethene unit. The sol–gel
transition upon irradiation was confirmed by CD spectroscopy.
In toluene, 1o shows a positive Cotton effect at 402 nm (De=
34.7mÀ1 cmÀ1) in the gel state, with a signal at around 330 nm
attributed to an exciton coupling, which indicates the presence
of tightly packed chiral structures (Figure 4a).[13,17] After irradia-
tion at l=365 nm to form 1c, the CD signal decreases and
eventually disappears, which indicates a loss of the induced
CD signal of the dithienylethene units due to dissolution of
the gel fibers. The lack of a CD signal for both 1o and 1c in
Table 1. Gelation properties of 1o in organic solvents.
Solvent
State[a]
Solvent
State[a]
hexane
i
p
p
1,2-dichloroethane
1-octanol
ethanol
s
s
s
s
s
s
s
s
s
cyclohexane
n-butyl acetate
o-, m-, p-xylene
toluene
g (1)
g (5)
g (10)
p
p
s
THF
1,2-dichlorobenzene
1-propanol
tetraline
DMSO
DMF
benzene
2-propanol
acetonitrile
1,4-dioxane
[a] i: insoluble; p: precipitate; g: gel; s: solution at 40 mgmLÀ1. The
number in parentheses indicates the minimal gelation concentration in
mgmLÀ1
.
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Figure 2. a) Strain sweep (w=1.0 sÀ1) of a toluene gel of compound 1
(10 mgmLÀ1) before (&, &) and after (
^
,
^
) photoinduced ring closure.
Black markers indicate the storage modulus (G’) and white markers indicate
the loss modulus (G’’). b) Frequency sweep (g=0.1%) of a toluene gel of
compound 1.
Figure 4. CD spectra of 1 in the open and the photostationary states in
a) toluene ((2.6Æ0.1)ꢁ10À5 m), b) ethanol (3.2ꢁ10À5 m), and c) water
((2.0Æ0.1)ꢁ10À5 m) before and after irradiation with UV light at l=365 nm
to form the photostationary state.
ethanol confirms earlier observations that 1o and 1c are fully
dissolved in this solvent (Figure 4b).
In aqueous solutions, the CD signal is much stronger in the
open state (1o) than in the closed state (1c; Figure 4c). The
decrease in signal is a manifestation of a change in the pack-
ing parameters and is likely to be due to less tight stacking in
the closed state (see below). In water, 1o forms supramolec-
ular assemblies, as evidenced by cryo-TEM (Figure 5a and b).
The images show lamellar aggregates, which most likely form
due to aggregation driven by hydrophobic interactions of the
cholesterol and the dithienylethene moieties, which are both
known to be capable of (co)forming vesicular aggregates in
aqueous solvents.[23,26]
Upon switching of 1o into its photostationary state (pre-
dominately 1c) by irradiation at l=365 nm, vesicles were ob-
served (Figure 5c and d). In contrast to the results in organic
solvents, in which ring closing led to the disappearance of the
supramolecular aggregates, in aqueous systems, the distinct
packing parameters of the amphiphilic molecule now led to
the formation of vesicles, probably due to a less tight packing
of 1c in the supramolecular aggregate than 1o.
Figure 3. a) Sol–gel phase-transition behavior of 1 (3 mm in toluene) after ir-
radiation with UV (l=365 nm) and visible (l=500 nm) light. Cryo-TEM
images of 1o in b) m-xylene and c) toluene.
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Experimental Section
UVASOL grade solvents were used for spectroscopic measure-
ments. UV/Vis measurements were performed on a JASCO V-630
spectrophotometer. CD spectra were recorded on a Jasco J-815 CD
spectrometer. Fluorescence spectra were recorded by using
a Jasco FP-6200 fluorimeter. Cryo-TEM was performed on a Philips
CM 120 instrument. Rheological measurements were performed on
a MCR 300 rheometer (Anton Paar) by using a parallel plate setup,
equipped with a 25 mm plate (PP25 SS). Samples were introduced
as liquids at 508C, after which the sample was sealed and allowed
to cool to 258C and rest for at least 60 min before measurement.
Acknowledgements
The European Research Council is acknowledged for financial
support through an Advanced Investigator Grant (227897, BLF)
and the Ministry of Education, Culture and Science of the
Netherlands (Gravity program 024.001.035, J.T.H., B.L.F. and
W.R.B.).
Figure 5. a, b) Cryo-TEM images of 1o in water (scale bars: 1 mm and
100 nm, respectively). c, d) Cryo-TEM images of 1c after irradiation at
l=365 nm (scale bars: 1 mm and 100 nm, respectively).
Keywords: gels
supramolecular chemistry · vesicles
· molecular switches · photochromism ·
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a hydrophobic cholesterol unit and a hydrophilic poly(ethylene
glycol)-modified pyridinium group. The incorporation of the
light-switchable functionality allows for photochemical control
over vesicle formation in water and for light-controlled self-as-
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features demonstrate that light control of a supramolecular
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opens the way toward the effective development of new strat-
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Published online on January 16, 2014
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