Reverse vesicles formed by hydrogen bonded arylamide-derived triammonium cyclophanes and hexaammonium capsule

Article abstract of DOI:10.1039/b914030a

Hydrogen bonded rigid imine-based macrocycles and capsules have been reduced to cyclic triamines and two-layered hexaamines, the triammonium and hexaammonium derivatives of which are revealed to form reverse vesicles in organic liquids of low polarity, wh

Full text of DOI:10.1039/b914030a

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Reverse vesicles formed by hydrogen bonded arylamide-derived
triammonium cyclophanes and hexaammonium capsulew
Xiao-Na Xu, Lu Wang and Zhan-Ting Li*
Received (in Cambridge, UK) 14th July 2009, Accepted 9th September 2009
First published as an Advance Article on the web 25th September 2009
DOI: 10.1039/b914030a
Hydrogen bonded rigid imine-based macrocycles and capsules
have been reduced to cyclic triamines and two-layered hexa-
amines, the triammonium and hexaammonium derivatives of
which are revealed to form reverse vesicles in organic liquids
of low polarity, which are characterized by SEM, AFM,
(HR)TEM, DLS and XRD.
covalent chemistry.5 The key for this approach was that
the intramolecular N–HÁ Á ÁO hydrogen bonds induced the
arylamide segments to adopt a preorganized conformation,6
leading to the exclusive formation of the macrocycles
after the reactions reached equilibrium. Compounds 1a, 1b,
2, 5a, 5b and 6 were thus further prepared from them
(see ESIw).
Vesicles,1,2 microscopic capsules that enclose an aqueous
volume with thin membranes of specific molecules or polymers,
have drawn great attention due to their potential applications
in drug and gene delivery, as nanoreactors, and as artificial cell
membranes.3 Reverse vesicles consist of a solvent core of low
polarity that is surrounded by a reverse membrane shell.4
As the organic counterparts to the ‘‘normal’’ vesicles in
aqueous solution, reverse vesicles may also be potentially
endowed with similar functions. However, examples of this
class of vesicles are quite limited. Moreover, reverse vesicles
have been assembled mainly from aliphatic amphiphiles
in nonpolar hydrocarbons, in which the hydrophobic inter-
action of the polar segments is maximized.4b–h To the best of
our knowledge, there is only one other example that utilizes
dimeric resorcinarenes to form reverse vesicles.4i Herein,
we report a new approach to reverse vesicles, which are based
on the aggregation of hydrogen bonded arylamide-derived
triammonium macrocycles 1a and 1b and hexaammonium
capsule 2.
SEM images showed that in chloroform both 1a and 1b self-
assembled into spherical vesicles (Fig. 1), the average diameter
of which was estimated to be ca. 2.4 (1a) and 6.0 (1b) mm. The
size of the vesicles was decreased with the dilution of the
solution (see ESIw), which was similar to many of the classic
vesicles formed in polar media.7 However, no twins, triplets or
more complicated aggregates were observed within the investi-
gated concentration range, implying that the aliphatic side
chains did not form important van der Waals interactions
across the vesicles. Similar vesicles were also generated in
dichloromethane (Fig. 1b), but not in polar solvents, such as
methanol, acetonitrile or acetone. Moreover, adding methanol
to the chloroform solutions gradually inhibited the formation
of the vesicular structures. The solubility of 1a and 1b in
hydrocarbons was low. However, vesicles could be observed
from the binary solutions (1 : 1, v/v) of chloroform and
n-hexane, cyclohexane and decalin (see ESIw). All these
results supported that a new class of reverse vesicles was
generated.
We previously reported the quantitative synthesis of imine-
based macrocycles 3a and 3b and capsule 4 from precursors
that bear amino and aldehyde units by using the dynamic
State Key Lab of Bioorganic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Lu, Shanghai 200032, China.
E-mail: ztli@mail.sioc.ac.cn; Fax: +86-21-64166128;
Tel: +86-21-54925122
w Electronic supplementary information (ESI) available: Experimental
details, synthesis and characterization, and additional SEM, AFM and
XRD diagrams. See DOI: 10.1039/b914030a
The morphology of the aggregates of 1a and 1b was also
investigated by tapping-mode AFM (Fig. 2, also see ESIw),
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Fig. 3 The intensity-weighted distribution of the vesicles obtained
from the DLS measurements of 1a and 1b from chloroform (0.3 mM)
at 25 1C.
of the vesicles had a monolayer structure. We tentatively
propose that the macrocyclic frameworks stacked to form
cylindrical assemblies, which further aggregated into extended
layers and finally generated the vesicles (Fig. 5), as reported
for the formation of the conventional vesicles formed from
macrocycles in polar solvents.8a,9 The X-ray diffraction (XRD)
of the dried samples of both 1a and 1b (see ESI) revealed a
broad peak at 0.40 nm and a sharp peak at 1.7 nm, respec-
tively. The former might be attributed to a less compact p
stacking,10 while the latter was close to the size of the cyclic
framework (1.6 nm) and thus supported the monolayer mode
shown in Fig. 5. SEM images of 1b (0.3 mM) showed that
some of the vesicles contained holes (see ESIw), also evidencing
their hollow nature.11
Fig. 1 SEM images of (a) 1a (CHCl3), (b) 1a (CH2Cl2), (c) 1b
(CHCl3) and (d) 2 (CHCl3), obtained by evaporation of the solutions
(3.0 mM) on mica.
which also showed the formation of spherical aggregates.
Cross-section analysis of the typical structures revealed large
ratios of diameter to height (11 and 14, respectively), indi-
cating their flattened shape and the hollow feature of the
original vesicles,8 which were evaporated on the mica surface.
All the samples in dichloromethane also exhibited similar
spherical vesicles (see ESIw).
The formation of vesicles by 1a and 1b in solution was
further confirmed by the dynamic light scattering study
(Fig. 3). The mean hydrodynamic diameters of the vesicles
was 295 and 342 nm, respectively. The number-averaged
distribution of 1b (0.3 mM) was 140–340 nm, which was
narrower than its surface size distributions of 200–900 nm,
determined by SEM and AFM, and 100–700 nm, determined
by TEM. The larger sizes exhibited on the surface may be
attributed to the flattening of the vesicles upon evaporation of
the encapsulated solvent. TEM revealed a clear contrast
between the peripheral and central areas of the spherical
aggregates (Fig. 4), which further supported the hollow
nature. The thickness of the vesicles was estimated to be
ca. 2.0 nm. Considering that the diameter of the macrocyclic
framework is ca. 1.6 nm, this thickness suggested that the wall
To get insight into the mechanism for the formation of the
vesicles, compound 7 was prepared. SEM images showed that
7 did not give rise to vesicular structures in all the above
solvents (Fig. 6), indicating that the cooperative stacking of
the aromatic segments of 1a and 1b played a key role in the
formation of the vesicles. Such stacking should be mainly
driven by the aggregation of the ionic segments in the center of
the cylinder formed by the macrocycles, because in this way,
they could be shielded from the solvent molecules of low
polarity. Several additional experiments supported this
mechanism: when the iodide anion of 1b was exchanged with
nitrate, it still formed vesicles. In contrast, with the larger
perchloride as the anion, the salt did not form vesicles.
Compound 8, which bears three larger ammonium moieties,
also did not generate vesicles (Fig. 6). These results can be
readily rationalized by considering that the large perchlorate
and ammonium units weakened the stacking of the macro-
cycles and in turn the formation of the vesicles. Diluting the
solution of 1b in CDCl3 from 40 mM to 1 mM caused the H-1
and H-2 signals (see the structure) in 1H NMR to shift
downfield by 0.07 ppm. In contrast, no similar shifting
Fig. 2 AFM image of 1b, obtained by evaporation of the solution in
Fig. 4 TEM images of 1a (left) and 1b (right), obtained by evapora-
chloroform (0.3 mM) on mica.
tion the CHCl3 solution (0.3 mM) on copper grids.
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intramolecular stacking was relatively weaker for 9, because it
should had a more flexible conformation owing to the relative
movement of the two macrocycles, which might disable its
ordered stacking and the formation of the vesicles.
In conclusion, we have demonstrated a new approach for
the construction of reverse vesicles. The vesicles formed by 2
may be further used as a model system to study the cross-
membrane transformation of planar aromatic molecules. For
the vesicles formed by macrocyclic salts, one future study will
focus on the modification of the side chains. Vinyl, ethynyl or
azido groups will be introduced. In this way, the macrocycles
may be cross-linked through the metathesis or click reaction to
generate vesicles that are stable in polar media, which may
display new interesting properties due to the electrostatic
repulsion of the ammonium units.
Fig. 5 A schematic illustration for the formation of the mono-layered
vesicles from the tricationic macrocycles.
This work was financially supported by NSFC
(Nos. 20621062, 20672137, 20732007, and 20872167), STCSM
(09XD1405300), and NBRP (2007CB808001).
(o 0.01 ppm) was exhibited for 3b, 5b, 7 or 8. These obser-
vations also revealed that 1b stacked at high concentrations.
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6636 | Chem. Commun., 2009, 6634–6636