Discrete and well-defined hydrophobic phases confined in self-assembled spherical complexes

Article abstract of DOI:10.1002/anie.200801700

(Figure Presented) Interior design: A 5 nm sized spherical complex, which confines 24 alkyl chains in its interior, provides a localized hydrophobic environment with a uniform size and structure (see picture; shell blue, Pd yellow, O red, C purple, H gray). The hydrophobic phase can solubilize dye molecules, and the hydrophobicity of the complex can be tuned by simply changing the length of the alkyl chains.

Full text of DOI:10.1002/anie.200801700

Communications
DOI: 10.1002/anie.200801700
Host-Guest Chemistry
Discrete and Well-Defined Hydrophobic Phases Confined in
Self-Assembled Spherical Complexes**
Kosuke Suzuki, Junya Iida, Sota Sato, Masaki Kawano, and Makoto Fujita*
Long alkyl chains have a tendency to spontaneously aggre-
gate and form localized hydrophobic environments in polar
media.[1] This tendency has been exploited to prepare a
variety of micelles,[2] vesicles,[3] tubes,[4] core-shell structured
polymers,[5] and dendrimers[6] in which the localized hydro-
phobic environments show interesting properties. These
artificial long alkyl chain systems, as well as biomembranes,[7]
which are bilayered aggregates of long organic phosphates,
are typically structurally dispersed. The structural disparities
result in a distribution of properties. Here we report discrete
and well-defined structures of alkyl chains confined within a
Amphiphilic ligands 1a–c bearing inner alkyl chains and
outer quaternary ammonium groups were designed with the
expectation that, after self-assembly into spheres 2a–c, the
alkyl chains would form a localized hydrophobic phase and
the outer ammonium groups would increase the solubility of
the spheres in polar media, namely DMSO or DMSO/H2O
mixtures. Ligands 1a–c were prepared in six steps from 3,5-
dibromo-4-hydroxybenzene carbaldehyde (see the Support-
ing Information). When ligand 1a (10 mmol) was treated with
Pd(NO3)2 (6 mmol) in deuterated dimethyl sulfoxide for one
hour at 708C, the formation of the [M12L24] spherical complex
2a as a single product was observed by 1H NMR spectroscopy.
The large downfield shifts of the pyridine a and b protons
(Dd = 0.66 and 0.29 ppm, respectively) are ascribed to metal–
pyridine coordination (Figure 2). Spheres 2b and 2c were also
prepared in the same fashion. After anion exchange of nitrate
5 nm spherical coordination shell (Figure 1). The shell frame-
2+
work quantitatively assembles from 12Pd
ions and 24
nonlinear ligands[8,9] and sharply defines the boundary of the
interior hydrophobic region of the long alkyl chains. Fur-
thermore, the nature of hydrophobic interior can be simply
tuned by varying the length of the pendant alkyl chains.
À
À
(NO3 ) for triflate ions (CF3SO3 ), cold-spray ionization mass
spectrometry (CSIMS)[10] clearly confirmed the [M12L24]
composition of 2a–c with molecular weights of 20304,
21313, and 23337 Da, respectively.
Figure 1. Self-assembly of endo-hydrophobic [M12L24] spherical com-
plexes 2a–c.
Figure 2. 1H NMR spectra of a) 1a and b) 2a (500 MHz, [D6]DMSO,
300 K). TMS=tetramethylsilane.
[*] K. Suzuki, J. Iida, Dr. S. Sato, Dr. M. Kawano, Prof. Dr. M. Fujita
Department of Applied Chemistry
School of Engineering
The University of Toyko
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax: (+81)3-5841-7257
E-mail: mfujita@appchem.t.u-tokyo.ac.jp
The rigid shell framework of the [M12L24] complexes was
revealed by X-ray crystallographic analysis of complex 2b.
Single crystals of 2b were obtained by slow vapor diffusion of
ethyl acetate into a solution of 2b in DMSO. Synchrotron X-
ray irradiation with high flux and low divergence provided
high quality data from which the structure of the exterior
shell, with a diameter of 4.7 nm and peripheral cationic
groups (Figure 3a), was clearly identifiable. Only the initial
-OCH2CH2- segment of the alkyl chains could be definitively
[**] This research was supported by the CREST project of the Japan
Science and Technology Agency (JST), for which M.F. is the principal
investigator. This work has been performed under the approval of
the Photon Factory Program Advisory Committee (Proposal No.
2006G284).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200801700.
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Figure 3. Molecular structure of complex 2b. a) The crystal structure of
the shell framework, outer cationic groups, and first -OCH2CH2-
segment of the alkyl chain. The remaining alkyl chains are severely
disordered. b) The combined crystal structure and MD simulation of
disordered side chains.
Figure 4. UV/Vis absorption spectra of nile red (3) dissolved in the
hydrophobic cores of 2a–c (84 mm) in DMSO/H2O (1:1).
copy (538 nm, see the Supporting Information). The concen-
trations of displaced 3 were calculated, and it was estimated
that spheres 2a–c contained 2, 10, and 12 molecules of 3 per
complex, respectively.
located because of severe disorder of the remainder of the
alkyl side chains. Therefore, the disordered alkyl chain
segments were modeled separately and attached to the crystal
structure of the shell. Simulated annealing by molecular
dynamics (MD) calculations (100 iterations from 2000 K to
300 K) gave an optimized structure. The combined crystal
structure and MD simulation show that the cavity of the
spherical complex is filled with 24 flexible C12H25 chains,
thereby forming a localized hydrophobic pocket with a
uniform shape and size (Figure 2b).[11]
Complexes 2a–c provide a 5 nm hydrophobic phase
localized and isolated from the polar solvent that should be
able to solubilize hydrophobic guests. The well-known hydro-
phobic dye, nile red (3),[12,13] was examined as a guest because
its poor solubility in aqueous solvents and its solvatochro-
matic nature make it suitable for estimating the polarity and
hydrophobicity of the local environment.[14] An excess of 3
was suspended in solutions of 2a–c in DMSO and the
resulting solutions were then diluted with water to increase
the solvent polarity (DMSO/H2O 1:1).[15] Residual 3 was
removed by filtration. Free 3 is sparingly soluble in DMSO/
H2O (1:1) and thus solutions of 3 showed only a very weak
UV/Vis absorption. In contrast, 3 shows enhanced solubility
in solutions of 2a–c in DMSO/H2O (1:1; Figure 4).
The solubility and solvatochromatic behavior of 3 clearly
show that the properties of the hydrophobic interiors of 2a–c
vary with the length of the alkyl chains. The solubility of 3 is
enhanced in the order 2a < 2b < 2c, which indicates that
more molecules of 3 are trapped in hosts that have a greater
hydrocarbon density. The solvatochromism of 3, which shows
bathochromic shifts in nonpolar media, also directly reflects
the concurrent reduction in the polarity of the complexes. The
maximum absorption wavelength (lmax) of included 3 under-
went a bathochromic shift in the order of 2a < 2b < 2c (576,
555, and 552nm, respectively), in good agreement with the
expected solvatochromism of 3.
In summary, we have prepared well-defined spherical
complexes containing 24 interior alkyl chains. The aggregated
alkyl chains form approximately 5 nm sized “hydrocarbon
droplets” that provide a localized hydrophobic environment.
These discrete hydrophobic phases completely differ from
previously studied, ill-defined long alkyl chain aggregates in
that 1) the shape and size are uniform and can be analyzed by
crystallographic methods and 2) the hydrophobic nature can
be precisely tuned by simply changing the length of the alkyl
chains. New properties and functions of solutes can be
developed within such “designer” hydrophobic environments.
Experimental Section
Inclusion of 3 in spheres 2a–c: A solution of 3 in DMSO (16 mm,
0.19 mL) was added to solutions of 2a in DMSO (0.23 mm, 0.56 mL).
The resulting DMSO solutions (0.75 mL) were diluted with water
(0.75 mL) to increase the solvent polarity, and stirred for 1 h at 48C.
After excess 3 was removed by filtration, the filtrates were analyzed
by UV/Vis absorption (Figure 3). The same procedure was performed
for 2b and 2c.
Calculation of the number of molecules of 3 within the spheres
2a–c: The solutions of 3 with 2a–c (DMSO/H2O 1:1, 0.1 mL) were
diluted 20-fold with CH3CN (1.9 mL). As 3 was observed at the same
maximum absorption wavelength as that of free 3 (538 nm; see
Figure S8 in the Supporting Information), 3 appeared to have been
expelled from the spheres into the bulk solvent. The concentration of
expelled 3 was calculated from the absorbance at 538 nm by using the
calibration curve of 3 (see Figure S9 in the Supporting Information),
and calculated to be 0.82( 3), 6.6 (3 + 2a), 43 (3 + 2b), and 52 mm (3 +
2c). From the concentration of 2a–c (4.2 mm), the number of
molecules of 3 encapsulated in 2a–c was estimated to be 2, 10, and
12molecules per sphere, respectively.
Received: April 11, 2008
Trapped 3 is expelled from the core of 2a–c into the bulk
solvent when the polarity of the solvent is reduced by diluting
with CH3CN, a less polar solvent. In a CH3CN/DMSO/H2O
mixture (38:1:1), only free 3 is observed by UV/Vis spectros-
Keywords: cage compounds · hydrophobic effect ·
nanostructures · self-assembly · solvatochromism
.
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