Self-assembling molecular dumbbells: From nanohelices to nanocapsules triggered by guest intercalation

Article abstract of DOI:10.1002/anie.200600971

(Figure Presented) Dumbbells that are not dumb: Dumbbell-shaped molecules based on a hexa-p-phenylene derivative self-assemble into well-defined left-handed helical fibers in aqueous solution. These helical nanofibers convert reversibly into hollow nanocapsules by intercalation of aromatic guest molecules (red spheres).

Full text of DOI:10.1002/anie.200600971

Communications
Intercalations
DOI: 10.1002/anie.200600971
Self-Assembling Molecular Dumbbells: From
Nanohelices to Nanocapsules Triggered by Guest
Intercalation**
Ja-Hyoung Ryu, Ho-Joong Kim, Zhegang Huang,
Eunji Lee, and Myongsoo Lee*
Controlled self-assembly of incompatible molecular compo-
nents is a challenging topic of interdisciplinary research in
chemistry, biology, and materials science.[1] For example, self-
assembling molecules consisting of rodlike aromatic and
flexible aliphatic segments have proved to be promising
scaffolds for well-defined supramolecular structures, such as
vesicles, tubules, and twisted ribbons.[2] Precise control of
molecular arrangements at the supramolecular level is
essential to obtain well-defined nanoscopic architectures
with specific shape. Recently, we showed that incorporation
of a conjugated rod into an amphiphilic dumbbell-shaped
molecular architecture results in the formation of a helical
nanostructure consisting of hydrophobic aromatic cores
surrounded by hydrophilic flexible segments that are exposed
to the aqueous environment.[3] We also showed that rod
building blocks in rigid–flexible macrocycles self-assemble
into a discrete barrel-like structure with hydrophilic chan-
nels.[4]
Scheme 1. Representation of the reversible transformation of helical
fibers into a spherical capsule.
When dissolved in a solvent suitable for the oligoether
block such as water, 1 self-assembles into an aggregate
structure because of its amphiphilic characteristics. The
aggregation behavior of the compound was subsequently
studied in aqueous solution by using UV/Vis, fluorescence,
and circular dichroism (CD) spectroscopies (see the Support-
ing Information). The absorption spectrum of 1 in aqueous
solution (0.01 wt%) exhibits a broad transition with a
maximum at 278 nm and a shoulder at 332 nm arising from
the tripodal biphenyl segments and the conjugated rod block,
respectively. The fluorescence spectrum of 1 in chloroform
(0.01 wt%) excited at 332nm exhibits two strong emission
maxima at 381 and 400 nm. However, the emission maximum
in aqueous solution is red-shifted with respect to that
observed in chloroform, which is indicative of aggregation
of the conjugated rod segments.[6] CD spectra of aqueous
solutions of 1 show a positive Cotton effect followed by a
negative Cotton effect at higher wavelengths with the CD
signal passing through zero near the absorption maximum of
the oligo(phenylene) chromophore, thus indicating the for-
mation of a helical superstructure with a preferred handed-
ness.[7]
Dynamic light-scattering (DLS) experiments were per-
formed with 1 in aqueous solution to further investigate its
aggregation behavior.[8] Analysis of the autocorrelation
function with the CONTIN program shows a broad peak
corresponding to an average hydrodynamic radius (RH) of
approximately 60 nm. The angular dependence of the appar-
ent diffusion coefficient (Dapp) was measured, and the
gradient of the slope was 0.03, which is consistent with the
value predicted for anisotropic objects (see the Supporting
Information).[9] The formation of cylindrical micelles was
further confirmed by using the Kratky plot, which shows a
linear angular dependence on the intensity of the light
scattered by the aggregates (see the Supporting Information).
In addition to DLS experiments, static light-scattering (SLS)
experiments were performed in aqueous solution under the
same conditions. The radius of gyration of the aggregates,
Rg = 78 nm, was obtained from the gradient of the angular
dependence of the SLS signal. The ratio Rg/RH is 1.25, which is
evidence of the formation of cylindrical aggregates.[10]
We present herein the formation of helical strands from
the self-assembly of a dumbbell-shaped molecule based on a
conjugated rod segment in aqueous solution and reversible
transformation between helical strands and nanocages trig-
gered by the addition of aromatic guest molecules
(Scheme 1). The dumbbell-shaped molecule 1 consists of a
hexa-para-phenylene rod and aliphatic polyether dendrons
based on a tetrahedral core, which are covalently linked at
both ends of the rod segment. To synthesize 1, aromatic
tetrahedral cores containing three oligoether dendrons were
prepared according to procedures described previously
(Scheme 2).[5] The final dumbbell-shaped molecules were
synthesized by using a palladium-catalyzed homocoupling
1
reaction. The resulting compound was characterized by H
and 13C NMR spectroscopies, elemental analysis, and
MALDI-TOF mass spectrometry, the data of which were in
full agreement with the structures presented.
[*] Dr. J.-H. Ryu, H.-J. Kim, Z. Huang, E. Lee, Prof. M. Lee
Center for Supramolecular Nano-Assembly and
Department of Chemistry
Yonsei University
Shinchon 134, Seoul 120-749 (Republic of Korea)
Fax: (+82)2-393-6096
E-mail: mslee@yonsei.ac.kr
[**] This work was supported by the Creative Research Initiative
Program of the Ministry of Science and Technology, Korea. H.J.K.,
E.L., and Z.H. thank the Seoul Science Fellowship Program.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Scheme 2. Synthesis of the dumbbell molecule 1. DHP: dihydropyran, THP: tetrahydropyran, Ts: para-toluenesulfonyl, TMS: trimethylsilyl.
Further evidence of the formation of cylindrical aggre-
gates was provided by transmission electron microscopy
(TEM; Figure 1). The micrographs, which were negatively
the same direction to avoid steric hindrance between the
bulky dendritic wedges. Consequently, this stacking of the
aromatic rod segments leads to helical objects comprising
hydrophobic aromatic cores surrounded by hydrophilic
dendritic segments that are exposed to the aqueous environ-
ment. This formation process is similar to that of other helical
structures of self-assembling molecules that are based on a
conjugated rod block.[3,7,11]
Remarkably, these cylindrical objects transformed into
spherical objects on adding three equivalents of 4-bromo-
nitrobenzene (Scheme 1) to an aqueous solution of 1.
CONTIN analysis of the correlation functions in DLS experi-
ments of the resulting solution showed RH to be 70 nm and the
SLS results showed Rg to be 73 nm. Thus, the radius of
gyration of the mixture solution is nearly identical to the
hydrodynamic radius. The measured diameter exceeds the
extended molecular length (approximately 10 nm) by a factor
of about 14, which also strongly suggests that these aggregates
are capsulelike entities rather than simple micelles.[12] In
contrast to the results derived for 1, the gradient of the slope
of the angular dependence of the apparent diffusion coef-
ficient (Dapp) was approximately zero (Figure 2a), which
suggests that the self-assembled architecture is spherical.[13]
The formation of spherical objects was further confirmed by
TEM (Figure 2b), which revealed the presence of spherical
objects with an average diameter of about 140 nm. This is in
good agreement with the results obtained by DLS and SLS
experiments. Atomic force microscopy (AFM) measurements
showed that the spherical objects consist of a unilamellar
membrane.[14]
Figure 1. a) TEM image of 1 with negative staining. b) Magnified
image; the inset shows the density profile.
stained with a 2wt% aqueous solution of uranyl acetate,
show helical objects with a uniform diameter of about 10 nm
and a pitch length of 3.6 nm. When the extended molecular
length (9.8 nm in a CPK model) is taken into consideration,
the image indicates that the diameter of the elementary
cylindrical objects corresponds to one molecular length.
On the basis of these results, we consider that 1 self-
assembles into cylindrical micelles in which the rods are
aligned perpendicular to the cylinder axis. However, the rod
segments stack on top of each other with mutual rotation in
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Communications
Figure 3. a) Emission spectra of 1 (0.01 wt% aqueous solution, excited
at 332 nm) with the addition of 4-bromonitrobenzene. The inset shows
the emission intensity at 420 nm (E) as a function of the molar ratio
bromonitrobenzene:1 (r). b) CD spectra of 1 with the addition of
bromonitrobenzene (increase in molar ratio from 0 to 1).
guest molecules are effectively intercalated between the rod
segments.[18]
Consistent with the intensity changes in the emission
spectra, the CD intensity decreases rapidly upon addition of
up to one equivalent of the guest molecule to give a very small
CD signal, which infers the depletion of the twisted arrange-
ment of the rod segments (Figure 3b). Upon removal of the
guest molecule by extraction with n-hexane, the CD spectrum
fully recovered, thus indicating that this structural trans-
formation is reversible.[19] These results demonstrate that the
addition of guest molecules into the solution of 1 forces the
twisted arrangement of the rod segments into a parallel
arrangement that leads to the formation of a capsulelike
structure.
In summary, the results described herein demonstrate that
the dumbbell-shaped molecules based on a hexa-p-phenylene
rod and bulky dendritic segments self-assemble into well-
defined left-handed helical cylinders with a diameter of
approximately the length of one molecule and a pitch of
3.6 nm. Interestingly, the helical structure transforms into a
capsulelike structure on addition of guest molecules. This
reversible transformation between helical strands and nano-
cages in response to the addition of guest molecules is
attributed to the intercalation of aromatic substrates within
the rod segments and subsequent packing change of the rod
segments from a twisted to a parallel arrangement to allow
more space for guest molecules. This dynamic structural
variation triggered by external stimuli may find useful
applications in many areas including the development of
responsive supramolecular materials.
Figure 2. a) Angular dependence of Dapp (q is the scattering vector);
b) TEM image for the spherical capsules with negative staining;
c) emission spectra of calcein measured at 258C (weak emission) and
calcein measured at 608C (strong emission) of an aqueous solution of
1 (0.01 wt%) containing three equivalents of 4-bromonitrobenzene;
d) release of calcein from the capsule as a function of time.
Further evidence for the formation of hollow capsules was
provided by the encapsulation of the fluorescence dye
calcein.[15] Calcein, a hydrophilic fluorescent guest, was
encapsulated at a sufficiently high, self-quenching concen-
tration, and free calcein was removed by filtration over a
Sephadex column. Release of calcein into solution from the
inside of the capsules was accompanied by an increase in
fluorescence emission (Figure 2c).[16] As shown in Figure 2d,
no leakage of entrapped calcein was observed over periods of
60 min. Heating the calcein-loaded vesicular solution to 608C
resulted in the rapid and complete release of encapsulated
calcein, thus demonstrating that the dye molecules are
effectively enveloped within the interior of a capsule.[17]
These results show that addition of guest molecules to a
solution of 1 leads to the transformation of the helical
nanofibers into hollow capsulelike structures.
This unique structural variation on the addition of guest
molecules can be rationalized by considering the packing
arrangement of the rod segments. With amphiphilic molecular
dumbbells in aqueous media, aromatic guest molecules are
intercalated between the rod segments through intermolec-
ular interactions, including hydrophobic and p–p interactions.
As a result, this intercalation of the guest molecules drives the
twisted packing arrangement of the rod segments into a
parallel arrangement, which allows more space for guest
molecules while maintaining uniform density of the dendron
dumbbell ends. This parallel arrangement of the rod segments
is responsible for the formation of a cagelike structure.
Intercalation of the aromatic substrates within the rod
segments was confirmed with 4-bromonitrobenzene as a
guest molecule in an aqueous solution of 1 by fluorescence
spectroscopy (Figure 3). Upon addition of the guest mole-
cules, the fluorescence intensity of the aqueous rod–coil
solution of 1 was suppressed, thus demonstrating that the
Received: March 13, 2006
Revised: May 25, 2006
Published online: July 12, 2006
Keywords: host–guest systems · intercalation · nanostructures ·
.
nanotechnology · scanning probe microscopy
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