A self-assembled organic capsule formed from the union of six hexagram-shaped amphiphile molecules

Article abstract of DOI:10.1021/ja804885k

A discrete 2-nm-sized self-assembled organic capsule was formed from the union of six hexagram-shaped amphiphile molecules in aqueous methanol due to the hydrophobic effect, van der Waals forces, and CH-π interactions between the chemical components. A couple of hexa-substituted benzene molecules were encapsulated inside the capsule in both solution and the solid state, as was evidenced by ¹H NMR spectroscopy and single-crystal X-ray analysis. Copyright

Full text of DOI:10.1021/ja804885k

Published on Web 10/08/2008
A Self-Assembled Organic Capsule Formed from the Union of Six
Hexagram-Shaped Amphiphile Molecules
Shuichi Hiraoka,*,†,‡ Koji Harano,† Motoo Shiro,§ and Mitsuhiko Shionoya*,†
Department of Chemistry, Graduate School of Science, The UniVersity of Tokyo, Tokyo 113-0033, Japan,
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science Technology Agency,
Saitama 332-0012, Japan, and Rigaku Co. LTD., Tokyo 196-8666, Japan
Received June 26, 2008; E-mail: shionoya@chem.s.u-tokyo.ac.jp; hiraoka@chem.s.u-tokyo.ac.jp
Self-assembled hollow nanostructures have a great potential for
providing highly functional spaces for molecular recognition,
transport, reaction, and catalysis. A number of excellent examples
of discrete molecular capsules have been reported,1,2 and most are
constructed by directional, noncovalent bonding such as H-bonding1
and metal coordination bonding.2 Another key assembly strategy
is to use amphiphile molecules with hydrophilic and hydrophobic
parts, as seen in a variety of regular aggregates3 such as micelles,
vesicles, and tubes triggered by the hydrophobic effect in aqueous
media. In general, however, the number of components is uncertain
in these aggregates. This is because each building component has
no strict structural information to define a discrete structure due to
the nature of less-directional interactions between the chemical
Figure 1. Crystal structure of 32⊂16. (a) Space-filling models. Each 1 is
shown in a different color. (b) Cylinder model. Hydrogens and 3 are omitted.
(c) Color in 16: red, C; blue, N. Color in 3: green: C, white, H; brown, Br.
was that all the components of the aggregate are chemically
equivalent but each component has a lower C1 symmetry where
all the pyridyl and p-tolyl groups are inequivalent. The ESI-TOF
mass spectrum of 1 in CH3OH showed three prominent signals at
components. Thus, the ensemble of hydrophobic effect and multi-
point weak interactions is critical to define an entire discrete
structure. Herein we present a hexagram-shaped amphiphile (1) with
three hydrophilic pyridyl groups attached to a hydrophobic hexa-
phenyl benzene core. This molecule aggregates in aqueous methanol
to form a box-shaped structure comprised of six molecules of 1.
These six components are assembled by the hydrophobic effect,
van der Waals forces, and CH-π interactions. In addition, the entity
can encapsulate a couple of hexa-substituted benzene molecules
(3) in the hydrophobic interior space (Figure 1).
m/z ) 1235.1, 1638.8, and 2446.6 assignable to [16 ·Na4]4+
,
[16 ·Na3]3+, and [16 ·Na2]2+, respectively (Figure S2), indicating
the formation of a hexameric aggregate.
We tried to obtain a single crystal of the aggregate from a saturated
solution of 1 in aqueous methanol, but a suitable crystal was not
obtained.6 However, a single crystal suitable for X-ray analysis was
obtained in the presence of tribromomesitylene (3).7 In the inclusion
complex 32⊂16, six hexagram-shaped ligands 1 assemble to form a
box-shaped hexameric capsule, which encapsulates a couple of the
guest 3 stacked face to face (Figure 1). The hexagram-shaped molecules
in 32⊂16 lost their original C3 symmetry of 1 because the pyridyl and
p-tolyl groups in 1 became inequivalent. This is consistent with the
symmetry of the solution structure observed in the 1H NMR spectrum
of the inclusion complex in aqueous methanol. The methyl groups of
1 are in close proximity to the pyridyl and p-phenylene groups of the
neighboring molecules. This result is in good accordance with the
observation that the proton signals of the methyl groups, Hi, in the
aggregate were shifted to higher field. A pair of 3 appears to move
about freely in the hydrophobic space of 16 as the guest molecules
were disordered in the X-ray analysis (Figure 1 shows only one of the
three possible structures). This agrees with the result that the sym-
metries of 16 and the encapsulated 3 in solution are independent of
each other as shown by the 1H NMR study.
The formation of the hexameric aggregate depends heavily on
the structure of the hexagram-shaped amphiphile. 2, in which three
methyl groups of 1 are hydrogen-modified, exists as a monomer in
aqueous methanol regardless of the solvent composition (Figure
S10). Furthermore, the X-ray analysis of a single crystal obtained
from an aqueous methanol solution of 2 established not a hexameric
capsule but a multilayered structure (Figure S9). These results
indicate that van der Waals forces and/or CH-π interactions
between the methyl groups and the adjacent aromatic rings help to
stabilize the discrete capsule structure of 16 to a great extent.
Recently, we have reported octahedron-shaped metallo-capsules,
[M618]12+, constructed from six transition metal ions M2+ (M: Mn,
Fe, Co, Ni, Pd, Pt, Cu, Zn, Cd, and Hg) and eight metal ligands
(1) having three 3-pyridyl groups,2j and found that the [Hg618]12+
capsule is interconvertible with a [Hg614]12+ cage by changing the
ratio of ligand to metal.2k We found that this molecule aggregates
1
to form a discrete structure in aqueous methanol solution. The H
NMR spectrum of 1 in CD3OD showed simple signals indicating
the C3 symmetric monomer (Figure 2a), whereas that in a mixed
solvent of D2O/CD3OD ) 25:75 (v/v) was rather complicated and
some of signals appeared in an upper field region (Figure 2d).4,5
These results indicated that the aggregation in aqueous methanol
was induced by the hydrophobic effect. It should be noted that three
separate signals with the same integral values were observed for
three methyl groups (Hi). The (H, H) COSY spectrum of 1 in a
mixed solvent of D2O/CD3OD ) 25:75 (v/v) displayed 36 signals
in the aromatic region, which contain 12 pyridyl and 24 p-phenylene
1
protons (Figure 2f). The H DOSY measurement of the solution
showed that all the signals have the same log D values of -9.91
(D ) 1.2 × 10-10 m2 s-1) (Figure S4), indicating the existence of
a single component. These results raised two possibilities. The first
one was that the solution includes the same amount of three
chemically inequivalent 1 with C3 symmetry. The second possibility
† The University of Tokyo.
‡ PRESTO.
§ Rigaku Co. LTD.
9
14368 J. AM. CHEM. SOC. 2008, 130, 14368–14369
10.1021/ja804885k CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
1
Figure 2. (a-d) H NMR spectra (500 MHz, 293 K, [1] ) 2.0 mM) in a mixed solvent of D2O and CD3OD in various ratios (D2O/CD3OD ) X:Y). X:Y
) (a) 0:100; (b) 5:95; (c) 15:85; (d) 25:75; (e) 1H NMR spectra of 32⊂16 (500 MHz, D2O/CD3OD ) 25:75 (v/v), 293 K, [1] ) 2.0 mM). (f) (H-H) COSY
NMR spectrum of 16 (500 MHz, D2O/CD3OD ) 25:75 (v/v), 293 K, [1] ) 2.0 mM). Small red letters denote proton signals for the pyridyl groups a-d.
Superscripts (A-C) indicate the protons in the same pyridine ring. Blue capital letters denote 12 coupling pairs for the phenylene and p-tolyl protons (e-f
and g-h, respectively).
1
The H NMR titration study verified that a couple of the guest 3
were encapsulated in the box-shaped capsule 16 in solution (Figure
S11), which is consistent with the crystal structure. Upon addition of
2 equiv of 3 to an aqueous methanol solution of the capsule 16, the
1H NMR signals for the capsule became sharpened (Figure 2e). This
should be due to the formation of an inclusion complex 32⊂16.
Note Added after ASAP Publication. Production errors in the
definition of M in the second paragraph and the notation for the
inclusion complex were corrected on October 29, 2008.
Supporting Information Available: Synthetic procedures, NMR
spectra, mass spectra, and crystal structures. This material is available
free of charge via the Internet at http://pubs.acs.org.
In the presence of excess 3, proton signals of free 3 appeared
separately, at δ ) 2.63 ppm, indicating that the inclusion/release
of the guest molecules is relatively slow compared with the NMR
time scale. The signals for encapsulated 3 were observed in the
lower field region (∆δ ) 0.87 ppm) compared to those of free 3.8
This is best explained by the deshielding of the neighboring
aromatic rings in 16. Indeed, an (H, H) NOESY spectrum of the
inclusion complex showed two cross peaks between the signals of
1 and 3 (Figure S7), indicating that both are close to each other as
References
(1) (a) Rebek, J., Jr. Angew. Chem., Int. Ed. 2005, 44, 2068. (b) Lu¨tzen, A.
Angew. Chem., Int. Ed. 2005, 44, 1000. (c) Kobayashi, K.; Shirasaka, T.;
Yamaguchi, K.; Sakamoto, S.; Horn, E.; Furukawa, N. Chem. Commun. 2000,
41. (d) Purse, B. W.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 2005, 102,
10777. (e) Shimizu, S.; Kiuchi, T.; Pan, N. Angew. Chem., Int. Ed. 2007,
46, 6442. (f) Baillargeon, P.; Dory, Y. L. J. Am. Chem. Soc. 2008, 130,
5640.
(2) (a) Dalgarno, S. J.; Power, N. P.; Atwood, J. L. Coord. Chem. ReV. 2008,
252, 825. (b) Fiedler, D.; Bergman, R. G.; Raymond, K. N. Angew. Chem.,
Int. Ed. 2004, 43, 6748. (c) Pluth, M. D.; Bergman, R. G.; Raymond, K. N.
Science 2007, 316, 85. (d) Yoshizawa, M.; Tamura, M.; Fujita, M. Science
2006, 312, 251. (e) Sato, S.; Iida, J.; Suzuki, K.; Kawano, M.; Ozeki, T.;
Fujita, M. Science 2006, 313, 1273. (f) Yamanaka, M.; Yamada, Y.; Sei,
Y.; Yamaguchi, K.; Kobayashi, K. J. Am. Chem. Soc. 2006, 128, 1531. (g)
Haino, T.; Kobayashi, M.; Fukazawa, Y. Chem. Eur. J. 2006, 12, 3310. (h)
Ikeda, A.; Udzu, H.; Zhong, Z.; Shinkai, S.; Sakamoto, S.; Yamaguchi, K.
J. Am. Chem. Soc. 2001, 123, 3872. (i) Hiraoka, S.; Harano, K.; Shiro, M.;
Shionoya, M. Angew. Chem., Int. Ed. 2005, 44, 2727. (j) Hiraoka, S.; Harano,
K.; Shiro, M.; Ozawa, Y.; Yasuda, N.; Toriumi, K.; Shionoya, M. Angew.
Chem., Int. Ed. 2006, 45, 6488. (k) Harano, K.; Hiraoka, S.; Shionoya, M.
J. Am. Chem. Soc. 2007, 129, 5300.
1
was observed in the crystal structure. A H DOSY measurement
1
showed that the H signals for 3 showed a log D value of -9.88
(D ) 1.3 × 10-10 m2 s-1), which is identical to that of 16 (Figure
S5). These results demonstrate that a couple of the guest molecules
3 are encapsulated in 16 in solution. Other benzene derivatives were
also tested for the encapsulation in the capsule (Figure S12). As a
result, hexamethylbenzene, mesitylene, and hexafluorobenzene were
encapsulated into 16, while a larger hexabromobenzene and a
smaller 1,3,5-trichlorobenzene were not. These results indicate that
a high size and shape selectivity observed in the molecular
recognition should arise not only from a hydrophobic effect but
also from van der Waals forces that work between 16 and the guest
molecules.
(3) (a) Ryu, J.-H.; Hong, D.-J.; Lee, M. Chem. Commun. 2008, 1043. (b)
Shimizu, T.; Masuda, M.; Minamikawa, H. Chem. ReV. 2005, 105, 1401.
(c) Isobe, H.; Homma, T.; Nakamura, E. Proc. Natl. Acad. Sci. U.S.A. 2007,
104, 14895. (d) Hill, J. P.; Jin, W.; Kosaka, A.; Fukushima, T.; Ichihara,
H.; Shimomura, T.; Ito, K.; Hashizume, T.; Ishii, N.; Aida, T. Science 2004,
304, 1481. (e) Yamamoto, Y.; Fukushima, T.; Suna, Y.; Ishii, N.; Saeki,
A.; Seki, S.; Tagawa, S.; Taniguchi, M.; Kawai, T.; Aida, T. Science 2006,
314, 1761. (f) Kishimura, A.; Koide, A.; Osada, K.; Yamasaki, Y.; Kataoka,
K. Angew. Chem., Int. Ed. 2007, 46, 6085.
In conclusion, a self-assembled organic capsule was formed from
the union of six hexagram-shaped amphiphile molecules 1 in
aqueous methanol due to the hydrophobic effect, van der Waals
forces, and CH-π interactions. Such an integration of noncovalent
weak interactions between multiple chemical components is critical
in maintaining well-defined discrete self-assembled structures of
large molecules, as seen in many biological events in Nature. The
present study would provide a new roadmap to more complex and
larger self-assembled molecules and molecular systems by means
of not only directional but also directionless binding forces.
(4) The critical concentration of the capsule formation was determined to be
∼1 mM by a variable-concentration 1H NMR experiment.
(5) When the fraction of water is set over 30%, the capsule gradually precipitated
due to its lower solubility.
(6) A single crystal of box-shaped 16 was obtained from a saturated solution of
1 in CH3CN. This aggregate contains a hexameric CH3CN cluster inside
which may act as a template, whereas 1 exists as a monomer in both dilute
CH3CN and aqueous CH3CN solutions (Figure S8).
(7) Crystallographic data for 32⊂16: C386H348Br6N18O22, M ) 6070.53, T ) 93.1
j
K, trigonal, R3, Z ) 3, a ) 23.8917(6), b ) 23.8971(6), c ) 50.1378(12)
Å, R ) 90.0000°, ꢀ ) 90.0000°, γ ) 120.0000°, V ) 24796.3(11) Å3, R )
0.1545, wR ) 0.4376, GOF ) 1.484. Material details for the crystal structure
are available free of charge from the Cambridge Crystallographic Data Centre
under Deposition No. CCDC 692402.
(8) Three 1H NMR signals were separately observed in a 1:2:6 integral ratio
for the methyl groups of a pair of 3 in the capsule. This is probably because
a pair of the guest molecules tumbles in the cavity in a somewhat restricted
way to make these signals inequivalent.
Acknowledgment. We thank A. Sato of JASCO International
Co., LTD. for measuring the FT mass spectrum of the capsule 16.
This work was supported by Grants-in-Aids from MEXT of Japan
and Global COE Program for Chemistry Innovation.
JA804885K
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