Vesicles and organogels from foldamers: A solvent-modulated self-assembling process

Article abstract of DOI:10.1021/ja801618p

Nonamphiphilic, hydrogen-bonded hydrazide foldamers appended with four or six long flexible chains were revealed to spontaneously assemble to form vesicles in methanol and organogels in aliphatic hydrocarbons. SEM, AFM, TEM, DLS, and fluorescence microscopy were all used to identify the structures of the vesicles. It was proposed that intermolecular π stacking of the folded frameworks and hydrogen bonding of the amide units in the appended chains induced the molecules to produce cylindrical aggregates. In polar methanol, these aggregates packed together to generate one-layered vesicles owing to hydrophobically induced entanglement of the peripheral chains, while in nonpolar hydrocarbons, the peripheral chains entwined across stacked cylinders to form three-dimensional networks and thus immobilize the liquid molecules. Copyright

Full text of DOI:10.1021/ja801618p

Published on Web 05/13/2008
Vesicles and Organogels from Foldamers: A Solvent-Modulated
Self-Assembling Process
Wei Cai, Gui-Tao Wang, Yun-Xiang Xu, Xi-Kui Jiang, and Zhan-Ting Li*
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received March 4, 2008; E-mail: ztli@mail.sioc.ac.cn
Vesicles are important three-dimensional assemblies for studies
in biomimetics, nanomaterials, and drug and gene delivery. Inspired
by the formation of biomembranes from amphiphilic phospholipids,
chemists have developed an ocean of amphiphilic polymers and
surfactants that spontaneously form vesicles of various sizes and
functions.1,2 Examples of vesicles that consist of amphiphilic
dendrimers,3 calixarene,4 cucurbituril,5 fullerene,6 cyclodextrin,7
cyclophane,8 and sexithiophene or p-phenylene vinylene deriva-
Figure 1. SEM images of the sample of (a) 1, (b) 2a, and (c) 2b in methanol
tives9 have also been reported. In contrast, design of nonamphiphilic
(4 mM) on mica surface after the solvent was evaporated.
structures that spontaneously form vesicles has been a great
challenge.10 Herein we report an unprecedented self-assembly of
foldamers,11 which contain no hydrophilic segments but form
vesicles in polar methanol and organogels in nonpolar aliphatic
hydrocarbons.12
We previously reported a class of hydrazide-based foldamers,13
whose planar crescent conformations are stabilized by intramo-
lecular three-center hydrogen bonding.11c–e Since several aromatic
foldamers had been revealed to aggregate via intermolecular π
Figure 2. Fluorescence micrographs of the vesicles of (a) 1, (b) 2a, and
(c) 2b formed in methanol (1 mg/mL).
stacking,14 we envisioned that similar stacking would occur for
foldamers 1 and 2a,b, which might be modulated by intermolecular
hydrogen bonding of the amide units and van der Waals interaction
of the long peripheral aliphatic chains.
AFM also supported the formation of vesicular structures (see
Supporting Information). Compounds 1 and 2a formed isolated
vesicles, whereas vesicles of 2b preferred to further aggregate. The
average diameter of the vesicles is ca. 0.7 µm for all three
molecules, which was notably smaller than that revealed by SEM
but was also revealed to be concentration-dependent.7–9 The ratio
of the diameter and height of the vesicles formed by 1, 2a, and 2b
was estimated to be ca. 7, 16, and 36, indicating important flattening
upon being transferred from solution to mica surface. This result
may be attributed to the removal of solvent molecules from the
hollow spheres and also the high local force applied by the AFM
tip.3b,6
The formation of vesicles in solution was also confirmed by
dynamic light scattering study of the solution of 2a in methanol (5
mM). The average hydrodynamic radium of the vesicles was
observed to be 459 nm. Moreover, the vesicles also displayed a
very narrow size distribution, indicating the formation of well-
equilibrated structures. The hollow feature of the vesicles was
evidenced by fluorescence microscopy images (Figure 2). Although
the nanoscaled light spots could only roughly reflect the size and
shape of the vesicles on the surface, the large difference of the
luminance of the outer rings relative to that of the inner areas of
the spots clearly showed that the vesicles were all centrally hollow
and filled with fluorescence-silent solvent in solution.5,9b The hollow
feature of the vesicles was also confirmed by fluorescent dye
(Rhodamine B) encapsulation experiments.5
At room temperature, compounds 1 and 2a,b all displayed low
solubility in methanol. Upon heating, however, their solubility was
increased considerably (>10 mg/mL). The resulting solution
remained clear for weeks at room temperature, implying that some
kind of assemblies was formed. Figure 1 shows their SEM images
which were obtained on mica surface after the solvent was
evaporated. It can be found that all the compounds self-assembled
into spherical vesicles, the average diameter of which was estimated
to be approximately 1.2 (2a), 3 (1), and 5 (2b) µm, respectively. It
was also revealed that the vesicles could partially combine to
generate twins, triplets, or even multiplets, suggesting that larger
vesicles were formed by the fusion of the smaller ones.3–5 SEM
images of 2a from 2 mM solution were also obtained, which showed
that smaller vesicles were formed, as observed for many of classical
amphiphilic vesicles.7–9
TEM also evidenced the hollow feature of the vesicles. The wall
thickness of vesicles of 2a was estimated to be ca. 3 nm (Figure
3). Similar results were also observed for 1 and 2b. Space-filling
modeling revealed that the folded skeleton of 2 had a diameter of
9
6936 J. AM. CHEM. SOC. 2008, 130, 6936–6937
10.1021/ja801618p CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
dependent, but not in chloroform. These results further supported
π stacking of the oligomers.
In summary, we have shown that nonamphiphilic foldamers self-
assembled to form monolayered vesicles in methanol owing to
cooperative π stacking, hydrogen bonding, and van der Waals
interactions. The fact that 1 and 2b gelated nonpolar hydrocarbons
illustrates that the self-assembly of foldamers can be modulated
through appending additional groups. It is expected that both the
folded segments and peripheral chains can be readily modified.
Thus, the work may open the way for the design of a new generation
of vesicles from nonamphiphilic architectures.
Figure 3. TEM images of the vesicles of 2a (formed in 0.25 mM solution
in methanol) on copper grid covered with Formvar film at different
magnifications.
Acknowledgment. We thank the NBRP (2007CB808000), CAS
(KJCX2-YW-H13), and NSFC (Nos. 20732007, 20621062,
20425208, 20572126, 20672137) for financial support.
Supporting Information Available: Experimental details, spectra
and microscopy images. This material is available free of charge via
the Internet at http://pubs.acs.org.
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