In-water truly monodisperse aggregation of gear-shaped amphiphiles based on hydrophobic surface engineering

Article abstract of DOI:10.1021/ja1069135

Exactly six gear-shaped amphiphiles self-assemble into a highly stable, water-soluble, box-shaped capsule, in which indented hydrophobic surfaces of the components mesh with each other like gears. A water-soluble, tetrahedron-shaped capsule was also constructed from four gear-shaped amphiphiles with a template guest. These findings provide a guideline for creating aggregates with a given number of amphiphiles based on hydrophobic surface engineering.

Full text of DOI:10.1021/ja1069135

Published on Web 09/03/2010
In-Water Truly Monodisperse Aggregation of Gear-Shaped Amphiphiles
Based on Hydrophobic Surface Engineering
Shuichi Hiraoka,*,†,‡,| Takashi Nakamura,†,| Motoo Shiro,§ and Mitsuhiko Shionoya*,†
Department of Chemistry, Graduate School of Science, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan, Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science
and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan, and Rigaku Corporation Ltd.,
3-9-12 Matsubaracho, Akishima, Tokyo 196-8666, Japan
Received August 3, 2010; E-mail: chiraoka@mail.ecc.u-tokyo.ac.jp; shionoya@chem.s.u-tokyo.ac.jp
Abstract: Exactly six gear-shaped amphiphiles self-assemble into
a highly stable, water-soluble, box-shaped capsule, in which
indented hydrophobic surfaces of the components mesh with each
other like gears. A water-soluble, tetrahedron-shaped capsule was
also constructed from four gear-shaped amphiphiles with a
template guest. These findings provide a guideline for creating
aggregates with a given number of amphiphiles based on
hydrophobic surface engineering.
Conventional amphiphiles, consisting of a hydrophilic head and
Figure 1. (a) Schematic representation of a gear-shaped amphiphile. (b)
hydrophobic tail(s), form self-aggregates such as micelles and
bilayers in water.1 Much effort has been made to control the
morphology of the resulting aggregates by modification of both
the hydrophobic and hydrophilic parts.2 However, in most cases,
the number of components exhibits a wide distribution. Thus,
dispersion has been recognized as the inherent nature of aggregation
of amphiphiles. A driving force of the aggregation in water is the
hydrophobic effect.3 In other words, hydrophobic parts get together
to minimize the hydrophobic surface areas exposed to water.
Consequently, the stereoscopic complementarity of the hydrophobic
surfaces of amphiphiles is a dominant factor determining the
aggregate structure. It is therefore a challenging task to precisely
design the hydrophobic surfaces of amphiphiles so as to assemble
into an aggregate consisting of a defined number of components.
As pioneering examples of discrete aggregates, dimeric structures4,5
have been constructed by the hydrophobic effect. More recently,
we reported a novel gear-shaped amphiphile (2) having an indented
hydrophobic surface and three hydrophilic parts (Figure 1). The
amphiphiles 2 were found to mesh with each other like gears in a
3:1 mixed solvent of CH3OH and H2O so as to reduce the area of
water-exposed hydrophobic surface to form a monodisperse box-
shaped hexamer6 or a tetrahedron-shaped tetramer.7 Herein we
demonstrate that exactly six gear-shaped amphiphiles, 1·I2, self-
assemble into a box-shaped hexameric capsule with extremely high
stability in water. Furthermore, a tetrahedron-shaped tetrameric
capsule was also constructed from four gear-shaped amphiphiles,
4·I3, and a template guest molecule.
Chemical structures of gear-shaped amphiphiles.
remarkably soluble in water. Furthermore, when two of the three
pyridyl groups of 2 are replaced with pyridinium groups, the
resulting box-shaped aggregate 16 ·I12 should become more stable
due to the electrostatic interactions between positively charged
pyridinium (colored cyan in Figure 2) and electron-rich pyridyl
(colored yellow) nitrogen atoms in the triply stacked aromatic rings.
Association behaviors of 1·I2 in solution were examined by NMR
spectroscopy. 1H NMR spectra of 1·I2 varied markedly with
solvents. The spectrum in CD3OD showed a simple pattern for
monomeric 1·I2 with C2V symmetry (Figure 2a), whereas that in
D2O was rather complicated (Figure 2b). Several proton signals
were observed with significant upfield shifts compared with those
in CD3OD, suggesting that gear-shaped molecules would mesh with
each other to form an aggregate. The hexameric capsule 16 ·I12
potentially has many structural isomers, depending on the position
of pyridine rings in the triply stacked aromatic rings. Among them,
the most symmetric structure is the one in which every pyridine
ring is placed in the middle of the triply stacked aromatic rings, as
illustrated in Figure 2. In this case, all the six components, 1·I2
with C1 symmetry, are chemically equivalent. In the 1H NMR
spectrum, the signals for three inequivalent methyl groups of p-tolyl
groups i and two inequivalent N-methyl groups j were observed.
This result indicates that a highly symmetric box-shaped capsule
structure was exclusively formed in D2O, which was expected to
be thermodynamically most stable.
The design of 1·I2 is based on the structure of hexameric capsule
26, in which hydrophilic pyridyl nitrogen atoms are put outward
while the indented hydrophobic surface of the hexaphenylbenzene
part is buried deep.6 Replacement of the pyridyl groups of 2 with
N-methylpyridinium groups is expected to make the capsule
The detailed structure of the box-shaped capsule 16 ·I12 was
determined as an inclusion complex [16⊃52]I12 (5 ) 2,4,6-
tribromomesitylene) by X-ray analysis. As a result, it was revealed
that six molecules of 1·I2 mesh with each other to form a box-
shaped capsule (for the encapsulation of 5 in solution, vide infra).
Every pyridine ring (colored yellow in Figure 3c) was placed
between two pyridinium rings (colored cyan), thus establishing the
highly symmetric structure demonstrated by 1H NMR spectroscopy
(Figure 2b).
† The University of Tokyo.
‡ Japan Science and Technology Agency.
§ Rigaku Corporation.
| Present address: Department of Basic Science, Graduate School of Arts and
Sciences, The University of Tokyo.
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Figure 2. 1H NMR spectra of gear-shaped amphiphiles and their aggregates; 500 MHz, 293 K. Color labels in the top-left structure: red, carbon; white,
hydrogen; cyan, N-methyl-3-pyridinium ring; yellow, 3-pyridine ring. A nomenclature for protons in 16 ·I12 is shown in the square frame. (a) 1·I2 in CD3OD,
[12+] ) 3.0 mM. (b) 16 ·I12 in D2O, [12+] ) 3.0 mM. (c) [16⊃52]I12 in D2O, [12+] ) 2.0 mM.
(PFGSE) measurement.8 A log D value (D, in m2 s-1, is the
diffusion coefficient) of -9.90 for 16 ·I12 in D2O was well consistent
with the 2-nm-sized box-shaped capsule.9
Next we investigated the stability of the capsule in solution. Upon
heating a solution of 16 ·I12 in D2O ([12+] ) 3.0 mM) to 353 K, 1H
NMR signals became rather sharper compared with those at 293
K, without any signals for dissociated monomeric 1·I2.8 In contrast,
the hexameric aggregate 26 was mostly dissociated into monomers
Figure 3. Crystal structure of [16⊃52]I12. (a,b) 12+ and 5 are shown by
in a 3:1 mixed solvent of CD3OD and D2O at 333 K. These results
cylinder and space-filling models, respectively. Hydrogen atoms in the
indicate that the water-soluble capsule 16 ·I12 is thermally far more
capsule are omitted for clarity. Color labels in (a): red, carbon in the capsule;
stable than 26, mainly due to the stronger hydrophobic effect in
water than in aqueous methanol. The association property of 1·I2
was also monitored by UV absorption spectrophotometry. A
solution of 1·I2 in CH3OH showed typical absorption bands at 265
and 287 nm for monomeric species. On the other hand, with an
increase in the fraction volume of H2O, their peak absorbance
significantly decreased due to the stacking of the aromatic rings in
the hexameric aggregate 16 ·I12.8 To examine the concentration effect
on the capsule formation, UV absorption of 16 ·I12 in H2O was
measured in the concentration range from 100 down to 1 µM. As
a result, no hypochromism was observed at all in this concentration
blue, nitrogen; green, carbon in 5; brown, bromine. In (b), two molecules
of 5 are omitted, and each molecule is color-coded. (c) Space-filling model.
Color labels: red, carbon; white, hydrogen; cyan, N-methyl-3-pyridinium
ring; yellow, 3-pyridine ring.
All the proton signals of 16 ·I12 were fully characterized by
1H-1H COSY and 1H-1H NOESY measurements.8 Characteristic
chemical shift changes observed for the signals of protons, d2, d1,
e3i, and h2i, which reside in close proximity to the clefts of other
gear-shaped amphiphiles, indicate structural coincidence in solution
and in the solid state. The formation of a monodisperse hexameric
aggregate was also confirmed by pulse-field gradient spin-echo
Figure 4. 1H NMR spectra of 4·I3 and their aggregates; 500 MHz, [43+] ) 2.0 mM, 293 K. A cylinder model denotes the structure of [44⊃6]12+. Color
labels: red, carbon in 43+; white, hydrogen; cyan, N-methyl-3-pyridinium ring; green, carbon in 6. (a) 4·I3 in CD3OD. (b) 4·I3 in D2O. Filled circles, filled
triangles, and open circles denote 46 ·I18, 44 ·I12, and 4·I3, respectively. (c) [44⊃6]I12 in D2O.
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C O M M U N I C A T I O N S
range.8 This indicates that the critical concentration of the capsule
16 ·I12 is considerably lower than 1 µM.
selectively formed by the hydrophobic effect as well as the template
effect. Alternative aggregation structures would be possible based
on the precise design of hydrophobic surface of amphiphiles.
As demonstrated by the crystal structure, the box-shaped
aggregate has a hydrophobic inner space for encapsulating hydro-
phobic molecules. The 0.8 × 0.8 nm inner space of 16 ·I12 is large
enough to accommodate two guest molecules 5. Upon the addition
of 5 to a solution of 16 ·I12 in D2O, though 5 is insoluble in D2O,
two molecules of 5 were encapsulated inside 16 ·I12. A signal for
methyl groups of 5 appeared at δ ) 3.49 ppm, which is downfield
shifted compared with that of free 5 in CD3OD (∆δ ) +0.85 ppm)
(Figure 2c).
Acknowledgment. This work was supported by Grants-in-Aids
from MEXT of Japan and Global COE Program for Chemistry
Innovation.
Supporting Information Available: Experimental details, 1H NMR
and UV spectra, and X-ray structure data in CIF format. This material
is available free of charge via the Internet at http://pubs.acs.org.
References
Formation of the hexameric aggregate depends substantially on
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phiphiles. In the case of amphiphile 3·I with one N-methylpyri-
dinium group, hexameric aggregates with several structural isomers
were formed in aqueous methanol8 but were insoluble in water.
On the other hand, in the case of 4·I3 with three N-methylpyri-
dinium groups, a water-soluble tetrahedron-shaped capsule [44⊃6]I12
was built up from four gear-shaped amphiphiles 4·I3 and a template
guest molecule 6 (Figure 4). A sharp 1H NMR spectrum of [44⊃6]I12
in D2O was consistent with a highly symmetric structure of the
tetrahedron-shaped capsule (Figure 4c, see also the Supporting
Information for a previously reported tetrameric capsule,8 24⊃6).
The tendency of 4·I3 to form a stable tetrameric capsule originates
from its own aggregation behavior. In a 1H NMR spectrum of 4·I3
in D2O, the signals for a tetrameric capsule 44 ·I12 were observed
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among three pyridinium groups of 4·I3.8 That is, different discrete
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In conclusion, the construction of truly monodisperse aggregates
was achieved in pure water using purposefully designed gear-shaped
amphiphiles. The studies of both the solution and the crystal
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water-exposed hydrophobic surfaces, and that the meshing structure
gives rise to extremely high stability in water. Furthermore, the
tetrameric aggregate [44⊃6]I12 with another amphiphile, 4·I3, was
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(8) See the Supporting Information.
(9) No further aggregation of 16 · I12 capsule was observed, probably due to the
electrostatic repulsion that would occur between the positive charges on the
outer surface of the capsules.
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