Columnarly assembled liquid-crystalline peptidic macrocycles unidirectionally orientable over a large area by an electric field

Article abstract of DOI:10.1021/ja203894r

Being inspired by naturally occurring peptidic macrocycles, we developed liquid-crystalline (LC) compounds 1 and 2 that are capable of self-assembling into hexagonal columnar mesophases over a wide temperature range that includes room temperature. Their b

Full text of DOI:10.1021/ja203894r

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Columnarly Assembled Liquid-Crystalline Peptidic Macrocycles
Unidirectionally Orientable over a Large Area by an Electric Field
Kohei Sato, Yoshimitsu Itoh,* and Takuzo Aida*
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
S Supporting Information
b
intermolecular H-bonds, ensuring the columnar assembly of
their macrocyclic cores.
ABSTRACT: Being inspired by naturally occurring pepti-
dic macrocycles, we developed liquid-crystalline (LC) com-
pounds 1 and 2 that are capable of self-assembling into
hexagonal columnar mesophases over a wide temperature
range that includes room temperature. Their bowl-shaped
macrocyclic cores are conformationally robust because of
the presence of internal H-bonds, while the columnar
assembly is ensured by intermolecular H-bonding interac-
tions involving the exocyclic amide units. When an electric
field was applied to their LC films from a direction ortho-
gonal to the film plane, the columns were oriented home-
otropically over a large area.
For the syntheses of 1 and 2,9 L-glutamate-containing cyclic
peptide precursors were prepared according to methods similar
to those reported previously,10 and a gallate-based branched par-
affinic wedge was attached to each glutamate unit. Compounds 1
and 2 thus obtained were unambiguously characterized by their
1H and 13C NMR spectra and MALDIÀTOF mass spectra
(Figures S1ÀS4 in the Supporting Information).9 Compound
1 in C6D12 (2.4 mM) displayed broad 1H NMR signals at 25 °C.
However, when the sample was heated to 70 °C, the spectrum
was entirely sharpened (Figure 2a), and two amide NH signals
appeared at 8.48 and 7.06 ppm. By reference to reported
examples,8 the former NH signal was assigned to the endocyclic
amide protons (NHendo) that are H-bonded to the nitrogen
atoms of the proximal thiazole units within the macrocycle.
Hence, the latter NH signal is most likely due to the exocyclic
amide protons (NHexo). Upon 20-fold dilution of the sample
solution with C6D12, the signal due to the intramolecularly
H-bonded amide NHendo, as expected, did not shift at all
(Figure 2a). In contrast, the NHexo signal displayed a 0.36
ppm upfield shift (Figure 2a). The contrasting behaviors thus
observed upon dilution indicate that the exocyclic amide groups
are H-bonded without interference by the endocyclic amide
units. It is also noteworthy that the amide NHendo signal remained
intact upon the addition of a strongly H-bonding acceptor such as
dimethyl sulfoxide (DMSO) [0.05% (v/v)], whereas that of
NHexo displayed a 0.21 ppm downfield shift (Figure S5a).9 The
high stability of the internal H-bonds suggests that the bowl-
shaped macrocyclic core of 1 is conformationally robust. Sub-
stantially identical 1H NMR spectral profiles were observed for 2
upon dilution with C6D12 (Figure 2b) and addition of DMSO
(Figure S5b).9
embranes with unidirectionally oriented nanopores have
M
attracted long-term attention in various aspects of biolo-
gical and nonbiological permeation phenomena. In particular,
nanoporous organic membranes, which can dynamically change
their pore orientation in response to physical stimuli, not only are
interesting in relation to biomembranes1a but also have the
potential for application to separation technologies.1b Since
liquid-crystalline (LC) molecules are dynamic and possibly can
change their orientation in response to an electric field
(E-field),2,3 several LC materials with columnarly assembled
macrocyclic cores have been developed.4 To date, however, no
such macrocyclic LC molecule has been claimed to be E-field-
responsive. For the realization of E-field-responsive nanoporous
assemblies, we considered that a conformationally rigid, non-
planar macrocycle capable of exerting a large dipole moment
might be a promising structural motif.
Differential scanning calorimetry (DSC) analysis of 1 on
second heating showed an LC mesophase over the temperature
range from À12 to 77 °C (Figure S6a).9 Polarized optical
microscopy (POM) at 75 °C displayed a fan texture, which is
characteristic of hexagonal columnar (Colh) LC materials
(Figure S7a).9 X-ray diffraction (XRD) analysis of 1 at the same
temperature showed diffraction peaks with d spacings of 35.2,
20.6, and 17.6 Å, which were indexed as the (100), (110), and
(200) diffractions of a Colh assembly with an intercolumnar
distance of 40.6 Å (Figure 2c). Likewise, compound 2 self-as-
sembled into a columnar LC material. Notably, the temperature
Here we report that peptidic macrocycles 1 and 2 (Figure 1)
self-assemble into columnar LC mesophases over a rather wide
temperature range that includes room temperature. Further-
more, unprecedentedly, their columns can be oriented uniformly
over a large area upon application of an E-field. By coincidence,
we were fascinated by the structures of a series of naturally
occurring peptidic macrocycles isolated from the marine organ-
ism Lissoclinum.5À7 With the help of internal H-bonds,8 these
macrocyclic peptides adopt a highly robust, bowl-shaped con-
formation capable of exerting a large dipole moment. Being
inspired by such structural features, we developed compounds 1
and 2 (Figure 1), whose macrocyclic cores bear branched par-
affinic wedges attached via polar amide spacers. We expected that
these exocyclic amide groups in 1 and 2 might selectively form
Received: April 27, 2011
Published: May 31, 2011
r
2011 American Chemical Society
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Figure 1. Molecular structures and phase transition diagrams (temper-
atures in °C) of LC macrocyclic oligopeptide derivatives 1 and 2. Their
core units are bowl-shaped (see the schematic illustrations) and self-
assemble columnarly with a hexagonal geometry (numerical values
represent intercolumnar distances). The estimated pore diameters for
1 and 2 are 4.0 and 5.7 Å, respectively.
range of its LC mesophase (À14 to 95 °C; Figure S6b)9 was
wider than that of 1. POM and XRD profiles indicated that the
LC material from 2 adopts a Colh geometry (Figure S7b and
Figure 2d).9 As expected, its intercolumnar distance (41.6 Å) was
larger than that of 1 (Figure 2d). On the basis of these dimensional
aspects, the molecular models shown in Figure 1 are expected for
the columnarly assembled 1 and 2, wherein the branched par-
affinic wedges that wrap around the stacked columns most likely
adopt a fan shape.
Figure 2. (a, b) 1H NMR spectra of (a) 1 and (b) 2 at 70 °C in C6D12 at
2.4 mM (blue) and 0.12 mM (red). Signals A and B represent phenyl and
thiazole protons, respectively. (c, d) XRD patterns of (c) 1 at 75 °C and
(d) 2 at 93 °C. (e, f) Wavenumbers (cmÀ1) of the NHendo and NHexo
stretching vibrations in the FT-IR spectral profiles of (e) 1 on heating
from 50 to 110 °C and (f) 2 on heating from 60 to 120 °C. (g, h) POM
images of (g) 1 at 75 °C and (h) 2 at 93 °C, sandwiched by glass plates
(5 μm separation) partially coated with ITO electrodes. A rectangular-
shaped 1.0 Hz AC voltage (120 V peak-to-peak) was applied to the
samples. Scale bars represent 200 μm.
We confirmed that the columnar assembly of 1 and 2 is indeed
ensured by intermolecular H-bonding interactions involving
their exocyclic amide groups (Figure 2a,b). For example, in
FT-IR spectroscopy at 25 °C, compound 2 showed stretching
vibrations due to amide CO (overlapped COendo and COexo),
NHexo, and NHendo at 1663, 3316, and 3390 cmÀ1, respectively,
which are typical of those of H-bonded amide groups. When 2
was heated to allow its LC-to-isotropic (Iso) phase transition, the
vibrational band due to NHexo shifted discontinuously toward
higher wavenumber, indicating that the H-bonds were weakened
upon heating. In sharp contrast, the vibrational band due to
NHendo remained intact during the phase transition (Figure 2f).
Thus, not only in solution (see above) but also in the LC state,
the endocyclic amide groups of 2 did not hamper the H-bonding
interactions of the exocyclic amide units. Although the spectral
change profile of 1 associated with the LC-to-Iso phase transition
was similar to that of 2, the band shift of NHexo was not as explicit
as that of 2 (Figure 2e). This observation is in accord with the fact
that the clearing temperature of the LC mesophase of 1 (Figure 1)
was lower than that of 2 (see above).
Quite interestingly, we found that upon application of an E-field,
the LC columns of both 1 and 2 undergo large-area unidirec-
tional orientation (Figure 2g,h). For investigating the E-field
responsiveness, we prepared a sandwich-type cell with two
parallel-oriented glass plates (5 μm separation) partially coated
with indium tin oxide (ITO) electrodes. Next, a 1 Hz square-wave
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AC voltage (120 V peak-to-peak) was applied to film samples of
these molecules during incubation in the cell at a temperature
just below the LC-to-Iso phase transition. At 75 °C, the film
sample of 1, for example, started to lose its characteristic birefringent
texture in the E-field-exposed area sandwiched by the ITO elec-
trodes (Figure 2g). In 3 h, this area became entirely nonbire-
fringent, indicating that the LC columns of 1 were oriented home-
otropically relative to the electrodes.11 In contrast, other areas
without the E-field (i.e., sandwiched by an ITO electrode and a
glass plate) remained birefringent. Meanwhile, heating the LC
sample of 1 to induce its LC-to-Iso phase transition followed by
cooling to 75 °C without the E-field resulted in the development
of a birefringent texture over the entire sample. All of these
observations demonstrate that the homeotropic orientation of
the columns was driven by application of the E-field. It is also
noteworthy that even after the E-field was switched off, the large-
area unidirectional columnar orientation was maintained through-
outan observation period of half a year. The same was true for LC
compound 2 (Figure 2h). As for the origin of the observed E-field
responsiveness, we consider that compounds 1 and 2 interact
with the applied E-field in a dipolar fashion. It should be noted
that these compounds carry not only multiple amide units but
also bowl-shaped cores that are capable of exerting a large dipole
moment.
In conclusion, we have developed peptides 1 and 2 as the first
E-field-orientable macrocyclic LC molecules that self-assemble
into columnar structures. Upon application of an E-field, the LC
columns are oriented homeotropically over a large area. Further-
more, as long as the materials are kept in their LC mesophase
temperature range, this large-area unidirectional orientation,
once developed, is maintained even without the E-field. If free-
standing membranes are available from these oriented LC films,
one can envisage selective transport of molecules and ions across
the membranes.1 Hence, the design of cross-linkable versions of
these molecules is one of the interesting challenges worthy of
further investigation.
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’ ASSOCIATED CONTENT
S
Supporting Information. Synthesis and characterization
b
details and POM, XRD, DSC, and FT-IR spectral data for 1 and
2. This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
itoh@macro.t.u-tokyo.ac.jp; aida@macro.t.u-tokyo.ac.jp
’ ACKNOWLEDGMENT
The present work was supported by the Japan Society for the
Promotion of Science (JSPS) through its “Funding Program for
World-Leading Innovative R&D on Science and Technology
(FIRST Program)”. K.S. thanks JSPS for a Young Scientist
Fellowship.
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Rev. 2011, 40, 2453–2474. (b) Baker, L. A.; Bird, S. P. Nat. Nanotechnol.
2008, 3, 73–74.
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