Chiral supramolecular polymers formed by host-guest interactions

Article abstract of DOI:10.1021/ja043289j

α-Cyclodextrin with a p-t-butoxyaminocinnamoylamino group in the 3-position (3-p-^tBocCiNH-α-CD) has been found to form a supramolecular polymer in an aqueous solution. The degree of polymerization of the supramolecular polymer is higher than 15

Full text of DOI:10.1021/ja043289j

Published on Web 02/05/2005
Chiral Supramolecular Polymers Formed by Host-Guest
Interactions
Masahiko Miyauchi, Yoshinori Takashima, Hiroyasu Yamaguchi, and Akira Harada*
Contribution from the Department of Macromolecular Science, Graduate School of Science,
Osaka UniVersity, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan
Received November 8, 2004; E-mail: harada@chem.sci.osaka-u.ac.jp
Abstract: R-Cyclodextrin with a p-t-butoxyaminocinnamoylamino group in the 3-position (3-p-tBocCiNH-
R-CD) has been found to form a supramolecular polymer in an aqueous solution. The degree of
polymerization of the supramolecular polymer is higher than 15 at 20 mM, as proved by VPO (vapor pressure
osmometry) measurements and turbo ion spray TOF MS measurements. The existence of substitution/
substitution interactions between adjacent monomers of the supramolecular polymer have been confirmed
by the observation of positive and negative Cotton bands in circular dichroism spectra. The mechanism for
the induction of the chirality was confirmed using model compounds. The substituents were found to exist
as a left-handed anti configuration in supramolecular polymers. The supramolecular polymer was found to
take a helical structure. The structure of the supramolecular polymer was observed by STM measurements.
Introduction
linear supramolecular polymers, the formation of cyclic oligo-
mers should be avoided. To avoid the formation of cyclic
Supramolecular polymers are ubiquitous in nature, especially
in biological systems. Microtubules, microfilaments, and flagella
are helical supramolecular polymers formed by proteins. In
recent years, much attention has been focused on supramolecular
polymers formed by synthetic molecules because of their unique
structures and properties.1 Supramolecular oligomers formed by
hydrogen bonds were reported for the first time by Lehn et al.2
Supramolecular polymers formed by four hydrogen bonds for
each unit were reported by Meijer et al.3 Furthermore, Meijer
et al. reported chiral supramolecular polymers formed by
hydrogen bonding.4 Rehahn et al. reported supramolecular
polymers formed by metal coordination.5 However, there are
few reports on the formation of supramolecular polymers by
host-guest interactions, although the formation of supramo-
lecular polymers by these interactions is important within
biological systems. To design such supramolecular polymers,
we have to incorporate a host part and a guest part in a single
molecule. Previously, we found and reported that 6-cinnamoyl-
R-cyclodextrin (6-CiO-R-CD) formed supramolecular dimers
and trimers.6 When they were stabilized by attaching bulky
substituents (trinitrophenyl group), a cyclic daisy chain was
obtained, in which a guest part was included in the CD cavity
of the other molecule from its primary hydroxyl side. To obtain
supramolecular structures, a guest part should be attached to
the secondary hydroxyl side. 3-Cinnamoyl CD amide (3-CiNH-
R-CD) was found to form longer supramolecular polymers.7 The
degree of polymerization reached almost to 12 in high concen-
trated aqueous solution (60 mM). However, we could not
observe that the supramolecular polymers were helical. We then
found that 3-p-tBocCiNH-R-CD formed helical supramolecular
polymers in aqueous solutions. We report herein for the first
time the formation of helical supramolecular polymers by a
cyclodextrin-based host-guest system.
Experimental Procedures
1
General. The H NMR spectra were recorded at 400 MHz
on a JEOL GSX-400 spectrometer at 30 °C. Chemical shifts
were referenced to the external standard in the solvent (δ )
1.96 ppm for acetonitrile in D2O). 2-D ROESY NMR and pulsed
gradient NMR experiments (PFG NMR) were obtained with
D2O as the solvent at 60 °C at 500 MHz on a JEOL JNM LA-
500 NMR spectrometer and 600 MHz on a VARIAN-UNITY
PLUS-600 NMR spectrometer, respectively. WETBPPSTE
pulse sequence was applied for PFG NMR measurements, and
the pulsed gradients were increased from 0.30 to 25.0 G cm-1
.
The time separation between pulsed field gradients and their
duration were applied the values of 100 ms and 1.1 ms. FT-IR
measurements were performed on a JASCO FT/IR-410 spec-
trometer. KBr was used as a dispersant. The analytical size
(1) (a) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, 1995. (b)
Ciferri, A. Supramolecular Polymers; Marcel Dekker: New York, 2000.
(2) (a) Lehn, J.-M. AdV. Mater. 1990, 2, 254-257. (b) Gulik-Krzywicki, T.;
Fouquey, C.; Lehn, J.-M. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 163-
167. (c) Lehn, J.-M. Makromol. Chem., Macromol. Symp. 1993, 69, 1-17.
(3) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.; Hirschberg,
J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W. Science 1997,
278, 1601-1604.
(6) (a) Hoshino, T.; Miyauchi, M.; Kawaguchi, Y.; Yamaguchi, H.; Harada,
A. J. Am. Chem. Soc. 2000, 122, 9876-9877. (b) Harada, A.; Kawaguchi,
Y.; Hoshino, T. J. Inclusion Phenom. 2001, 41, 115-121. (c) Harada, A.;
Miyauchi, M.; Hoshino, T. J. Polym. Sci. Part A: Polym. Chem. 2003, 41,
3519-3523. (d) Harada, A. Acc. Chem. Res. 2001, 34, 456-464.
(7) Miyauchi, M.; Kawaguchi, Y.; Harada, A. J. Inclusion Phenom. 2004, 50,
57-62.
(4) (a) Hirschberg, J. H. K. K.; Brunsveld, L.; Ramzi, A.; Vekemans, J. A. J.
M.; Sijbesma, R. P.; Meijer, E. W. Nature 2000, 407, 167-170. (b)
Brunsveld, L.; Folmer, B. J. B.; Meijer E. W.; Sijbesma, R. P. Chem. ReV.
2001, 101, 4071-4097.
(5) Knapp, R.; Schott, A.; Rehahn, M. Macromolecules 1996, 29, 478-480.
9
2984
J. AM. CHEM. SOC. 2005, 127, 2984-2989
10.1021/ja043289j CCC: $30.25 © 2005 American Chemical Society

Cyclodextrin-Based Chiral Supramolecular Polymer
A R T I C L E S
Scheme 1. Synthesis of 3-p-tBocCiNH-R-CD
exclusion chromatography and preparative size exclusion chro-
matography were carried out with TOHSO CCP&8010 system
(column: TSKgel R-2500 and TSKgel R-3000; elution: methanol/
water ) 40:60). Circular dichroism spectra and UV spectra were
recorded on a JASCO J820 spectrometer with 0.1 cm cell at
room temperature. Positive-ion matrix assisted laser desorption
ionization time-of-flight (MALDI-TOF) mass spectrometry
experiments were performed by using a Shimadzu/KRATOS
Axima CFR V2.2.1 mass spectrometer. R-Cyano-4-hydroxy-
cinnamic acid and insulin were used as the standard materials.
Ion spray TOF mass spectrometry experiments were performed
by using an Applied Biosystems QSTAR XL system mass
spectrometer. Vapor pressure osmometry measurements were
carried out by a KNAUER No. A0280 vapor osmometer at 40
°C in water. NaCl aqueous solution and R-CD were used as
standards. Solution viscosities were measured using Ubbelohde
viscometers in a water bath at 30 °C. STM measurements were
taken on a Nanoscope IIIa (Digital Instruments, Santa Barbara,
CA). The sample was prepared by slow evaporation of a dilute
aqueous solution of 3-p-tBocCiNH-R-CD on MoS2 overnight
at room temperature. The STM image was obtained under the
conditions of the sample bias voltage +315 mV, tunneling
current 1.038 nA, and Scan rate 6.1 Hz.
46%. Positive ion MALDI-TOF Mass m/z 1240.25 (M + Na+);
1H NMR (DMSO-d6, 400 MHz): δ 9.47 (s, 1H), 8.07 (d, 1H,
J ) 8.79), 7.52-7.46 (q, 4H, J ) 8.55), 7.31 (d, 1H, J ) 15.63),
6.41 (d, 1H, J ) 15.59), 5.90-5.17 (m, 11H), 4.86-4.64 (m,
6H), 4.52-4.49 (m, 6H), 3.93-3.29 (m, overlaps with HOD),
1.45 (s, 9H). IR (KBr, cm-1): 1702 (vs, νCdO, urethane), 1658
ν
(vs, CdO, amide). Anal. Calcd for C50H76N2O32‚7H2O: C,
44.71; H, 6.75; N, 2.09. Found: C, 44.97; H, 6.63; N, 2.18.
Results and Discussion
Materials. R-CD, tetramethylammonium chloride (TMA),
and NaOH were obtained from Nacalai Tesque, Inc. trans-p-
Aminocinnamic acid was obtained from Tokyo Kasei Kogyo,
CO., Ltd. Di-t-butyl dicarbonate was obtained from Aldrich.
Dimethyl sulfoxide (DMSO)-d6 was obtained from Euriso top.
D2O was purchased from Silantes.
p-t-Butoxycinnamic Acid (p-tBocCiOH). trans-p-Amino-
cinnamic acid (1.63 g, 1.0 × 10-2 mol) in dioxane (10 mL)
was added to 0.5 M NaOH aqueous solution (10 mL). Di-t-
butyl dicarbonate (2.37 g, 1.2 × 10-2 mol) was added to the
solution at 0 °C. The reaction was carried out with stirring for
6 h at 0 °C. Then, to the solution was added citric acid and
ethyl acetate (30 mL). After being extracted three times, the
ethyl acetate was dried with sodium sulfate and evaporated under
vacuum to give 2.80 g of the desired product. (Yield, 98%). 1H
NMR (DMSO-d6, 270 MHz): δ 9.54 (s, 1H), 7.56 (d, 1H, J )
8.78), 7.48 (d, 1H, J ) 8.78), 7.48 (d, 1H, J ) 15.86), 6.36 (d,
1H, J ) 15.86), 1.47 (s, 1H). M.p. 204 °C.
Formation of Supramolecular Polymers. When a guest
group is covalently attached to a CD, the molecule may form
intra-9 or intermolecular complexes10 in aqueous solutions.
Supramolecular polymers would be formed by the formation
of consecutive intermolecular complexes through host-guest
interactions. 3-p-tBocCiNH-R-CD is highly soluble in water.
When the guest part of 3-p-tBocCiNH-R-CD is included in
1
another CD cavity in D2O solution, the H NMR spectra may
show peak shifts. Figure 1a shows the 1H NMR spectra of 3-p-
tBocCiNH-R-CD as a function of concentrations in D2O
solutions. As the concentration of 3-p-tBocCiNH-R-CD in-
creased within the range from 1 to 40 mM, remarkable peak
shifts were observed in the protons of the substitution region.
(The peak shifts of the tBoc part were also observed, but those
data are shown in Figure S2). This result indicates that 3-p-
tBocCiNH-R-CD forms intermolecular complexes in D2O solu-
tions. In particular, the peak e drastically shifted upfield about
0.35 ppm at 40 mM (Figure 1b). The data were analyzed
quantitatively with double reciprocal plots. This result indicates
that the consecutive inclusion of 3-p-tBocCiNH-R-CD gives rise
Mono-3-deoxy-amino-r-CD (3-NH2-r-CD). This compound
was prepared according to the literature previously reported.8
3-p-tBocCiNH-r-CD. To a solution of 3-NH2-R-CD (591.0
mg, 6.08 × 10-4 mol) in 50 mL of DMF was added p-t-
BocCiOH (548.0 mg, 2.08 × 10-3 mol). After the solution was
cooled below 0 °C, N,N′-dicyclohexyl carbodiimide (171.0 mg,
8.29 × 10-4 mol) and 1-hydroxybenzotriazole (112.0 mg,
8.29 × 10-4 mol) was added. The resulting mixture was stirred
at room temperature for 5 days. After the removal of insoluble
materials by filtration, we poured the filtrate into acetone (1 L)
and then collected and washed the precipitate with acetone. The
crude product was purified by preparative reversed phase
chromatography (elution: water/methanol )100:0 to 50:50).
After the concentration of the solution containing 40% of
methanol under vacuum, the residue was separated with
preparative size-exclusion chromatography (Scheme 1). Yield,
(9) For example: (a) Hamasaki, K.; Ikeda, H.; Nakamura, A.; Ueno, A.; Toda,
F.; Suzuki, I.; Osa, T. J. Am. Chem. Soc. 1993, 115, 5035-5040. (b) Ueno,
A.; Minato, S.; Suzuki, I.; Fukushima, M.; Ohkubo, M.; Osa, T.; Hamada,
F.; Murai, K. Chem. Lett. 1990, 605-608. (c) Corradini, R.; Dossena, A.;
Marchelli, R.; Panagia, A.; Sartor, G.; Saviano, M.; Lombardi, A.; Pavone,
V. Chem.sEur. J. 1996, 2, 373-381. (d) Corradini, R.; Dossena, A.;
Galaverna, G.; Marchelli, R.; Panagia, A.; Sartor, G. J. Org. Chem. 1997,
62, 6283-6289. (e) Wang, Y.; Ikeda, T.; Ikeda, H.; Ueno, A.; Toda, F.
Bull. Chem. Soc. Jpn. 1994, 67, 1598-1607. (f) Miyauchi, M.; Harada, A.
J. Am. Chem. Soc. 2004, 126, 11418-11419.
(10) For example: (a) Tong, L.-H.; Hou, Z.-J.; Inoue, Y.; Tai, A. J. Chem.
Soc., Perkin Trans. 2, 1992, 1253-1257. (b) Zanotti-Gerosa, A.; Solari,
E.; Giannini, L.; Floriani, C.; Chiesi-Villa, A.; Rizzoli, C. Chem. Commun.
1996, 119-120. (c) Yamaguchi, N.; Nagvekar, D. S.; Gibson, H. W. Angew.
Chem., Int. Ed. Engl. 1998, 37, 2361-2364. (d) Bu¨gler, J.; Sommerdijk,
N. A. J. M.; Visser, A. J. W. G.; van Hoek, A.; Nolte, R. J. M.; Engbersen,
J. F. J.; Reinhoudt, D. N. J. Am. Chem. Soc. 1999, 121, 28-33. (e) Mirzoian,
A.; Kaifer, A. E. Chem. Commun. 1999, 1603-1604. (f) McAlpine, S. R.;
Garcia-Garibay, M. A. J. Am. Chem. Soc. 1998, 120, 4269-4275. (g) Onagi,
H.; Easton, C. J.; Lincoln, S. F. Org. Lett. 2001, 3, 1041-1044. (h) Kaneda,
T.; Yamada, T.; Fujimoto, T.; Sakata, Y. Chem. Lett. 2001, 1264-1265.
(i) Liu, Y.; You, C.-C.; Zhang, M.; Weng, L.-H.; Wada, T.; Inoue, Y. Org.
Lett. 2000, 2, 2761-2763.
(8) (a) Takahashi, K.; Hattori, K.; Toda, F. Tetrahedron Lett. 1984, 25, 3331-
3334. (b) Ikeda, H.; Nagano, Y.; Du, Y.-q.; Ikeda, T.; Toda, F. Tetrahedron
Lett. 1990, 31, 5045-5048.
9
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A R T I C L E S
Miyauchi et al.
Figure 1. 1H NMR spectra (400 MHz) of 3-p-tBocCiNH-R-CD at various concentrations in D2O (a) and plots of ∆δ (a-e) as a function of concentra-
tions (b).
Figure 2. 500 MHz 2-D ROESY NMR spectrum of 3-p-tBocCiNH-R-CD in D2O.
to the formation of supramolecular polymers with an increase
in the concentration.
Figure 2 shows the 2-D ROESY NMR spectrum of 3-p-
tBocCiNH-R-CD in D2O solution. Rotational nuclear overhauser
effects (ROEs) can be obviously observed between the sub-
stituent parts (b-d) and the inner protons of the CD part (the
NOEs for a are also observed, and the data is shown in Figure
t
S3), which indicates that the Boc part is deeply included in
another CD cavity.
It is difficult to estimate the size of supramolecular polymers
by NMR measurements because the formation and dissociation
of intermolecular complexes formed by 3-p-tBocCiNH-R-CD
are too fast on the NMR time scale. Figure 3 shows the results
of VPO measurements of 3-p-tBocCiNH-R-CD and native R-CD
at various concentrations at 40 °C in H2O. Although R-CD
showed no concentration dependence on the molecular weight
(MW), the MW of 3-p-tBocCiNH-R-CD increased as the
Figure 3. Effects of the concentrations on the molecular weight of 3-p-
tBocCiNH-R-CD (O) and R-CD (0) observed by VPO in water at 40 °C.
of NMR measurements in Figure 1, the peak shift of 3-p-
tBocCiNH-R-CD is remarkable in the range up to 10 mM. In
concentration increased from 0.5 to 15 mM. From the results
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Cyclodextrin-Based Chiral Supramolecular Polymer
A R T I C L E S
Figure 4. Plots of diffusion coefficients (D) of 3-p-tBocCiNH-R-CD
obtained by PFG NMR measurements as a function of concentrations at
30 °C.
the concentration range from 15 to 40 mM, the molecular
weights are slightly increased from 16 000 to 20 000, which is
also in good agreement with the NMR data. These results
indicate that 3-p-tBocCiNH-R-CD forms water-soluble su-
pramolecular polymers at higher concentrations.
The self-diffusion coefficients of 3-p-tBocCiNH-R-CD are
also determined by the utilization of a pulsed field gradient
(PFG) NMR measurement in D2O solutions.11 According to the
Figure 5. Positive turbo ion spray TOF mass spectra of 3-p-tBocCiNH-
R-CD with AcONH4 in the range of 0-18 000 (a) and 3200-18 000 (b).
Stejskal and Tanner’s reports,12 when ln I/I versus g2 was
0
plotted, where I and g are the echo intensity and (pulsed)
gradient strength, respectively, the slope of the line is given by
D/(∆-δ/3)γ2δ2 (Figure S6). Here, δ, γ, and ∆ are the duration,
gyromagnetic ratio, and time interval, respectively, between the
magnetic field gradient pulses. Figure 4 shows the plots of the
diffusion coefficients derived from the attenuation of proton
signals of 3-p-tBocCiNH-R-CD (D) in D2O solutions as a
function of concentrations. The diffusion coefficients decreased
with an increase in the concentration (5.0 mM: 2.65 × 10-6
cm s-1 and 40 mM: 1.57 × 10-6 cm s-1). The results show
that the sizes of intermolecular complexes formed by 3-p-
tBocCiNH-R-CD increased with an increase in the concentration
in D2O solutions.
Turbo ion spray TOF mass spectrum provides direct evidence
supporting the formation of supramolecular polymers. Figure
5 shows the representative positive turbo ion spray-TOF mass
spectra of 3-p-tBocCiNH-R-CD with AcONH4 at 10 mM in
aqueous solutions. The signals can clearly be assigned as the
supramolecular polymers. The number average molecular weight
of the polymer was up to 18 000 formed by 3-p-tBocCiNH-R-
CD. The intervals of signals correspond to the molecular weight
of 3-p-tBocCiNH-R-CD. These data are in good agreement with
the VPO data.
Figure 6. Circular dichroism spectra of p-tBocCiOH with R-CD (blue line),
3-p-tBocCiNH-R-CD at 0.25 mM (green line), and 3-p-tBocCiNH-R-CD
+ native R-CD (brown line) in water (a); schematic structure of p-tBoc-
CiOH-R-CD complex (b); monomeric structure of 3-p-tBocCiNH-R-CD (c);
and heterodimeric structure of 3-p-tBocCiNH-R-CD + native R-CD
complexes (d).
We could not observe cycle formation in this system, although
6-CiO-R-CD formed a cyclic trimer and dimer, and 6-CiNH-
R-CD formed a cyclic dimer. The guest part of 3-CiNH-R-CD
is attached to dC(3)sNH2 of R-CD directly by amide bond,
so that the direction of the guest part relative to R-CD is rather
fixed so as not to form cyclic dimers. The insertion of the guest
part from the secondary OH side of CD is thought to be
disfavored.
complex of p-t-BocCiOH with R-CD in water. The spectrum
shows an induced positive band around 250-380 nm, corre-
sponding to the 1La transition band of p-t-BocCiOH. The
observed positive circular dichroism bands in 220-380 nm can
be assigned to the bands induced by the inclusion of p-tBocCiOH
with R-CD. According to the theoretical treatment by Kodaka
et al.,13 a positive Cotton band is produced by the electronic
transition moment being nearly parallel to the molecular axis
Circular Dichroism Spectra of 3-p-tBocCiNH-r-CD. Figure
6a (blue line) shows the circular dichroism spectrum of the
(11) Stilbs, P. Prog. NMR Spectrosc. 1987, 19, 1-45.
(12) Stejskal, E. O.; Tanner, J. E. J. Chem. Phys. 1965, 42, 288-292.
9
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A R T I C L E S
Miyauchi et al.
Figure 7. Circular dichroism spectra of 3-p-tBocCiNH-R-CD at the
concentration range from 0.1, 0.25, 0.38, 0.5, 0.75, 1.0, and 1.5 mM in
water.
Figure 8. Schematic structures and signs of the observed Cotton bands of
(2S,4S)-2,4-anti-hexanediol bis-p-methoxycinnamates (a), (2R,4R)-2,4-anti-
pentanediol bis-p-methoxycinnamates (b), and 3-p-tBocCiNH-R-CD (c).
of R-CD. The result of the induced circular dichroism indicates
an axial inclusion in which the 1La axis of p-tBocCiOH is parallel
to the axis of R-CD (Figure 6b).14 The circular dichroism
spectrum of 3-p-tBocCiNH-R-CD at 0.25 mM is also shown in
Figure 6a (green line). The observed negative Cotton band at
323 nm indicates that the p-tBocCi part exists parallel to its
own CD axis in monomeric structure without the formation of
supramolecular complexes since the concentration (0.25 mM)
is too low to form intermolecular complexes in aqueous
solutions (Figure 6c). Interestingly, when an excess amount of
R-CD was added to this solution of 3-p-tBocCiNH-R-CD, the
negative Cotton band shifted to 311 nm with some weakening
in the intensity (Figure 6a, brown line). This result indicates
that the tBocCi part is incorporated into the native R-CD cavity
in a slantwise state to form 3-p-tBocCiNH-R-CD-native R-CD
heterodimer (Figure 6d).
Figure 9. Plots of the observed Cotton band intensities as a function of
concentrations.
Figure 7 shows the circular dichroism spectra of 3-p-
tBocCiNH-R-CD at concentrations ranging from 0.1 to 1.5 mM
in water because the upper limit of the concentration detectable
by the circular dichroism spectra is 1.5 mM. The induced
circular dichroism bands in 3-p-tBocCiNH-R-CD at higher than
0.25 mM are extremely different from those of the complex of
p-tBocCiOH with R-CD and 3-p-tBocCiNH-R-CD at lower
concentrations. As the concentration increased, the observed
negative Cotton band around 323 nm at 0.25 mM is gradually
separated to form a negative and a positive band, which shifted
to 327 and 288 nm, respectively. Nakanishi et al. previously
reported that the (2S,4S)-2,4-anti-hexanediol bis-p-methoxy-
cinnamates gave rise to the splitting positive and negative Cotton
bands around 322 and 283 nm, respectively, in the 1La transition
(Figure 8a).15 (2R,4R)-2,4-anti-Pentanediol-bis-p-methoxycin-
namates also showed the splitting Cotton bands with the opposite
signs (Figure 8b). These observations show the existence of the
pairwise exciton-coupling interactions (cinnamate/cinnamate
interactions) in the compound and the rotational configuration
effects on the sign of induced circular dichroism bands.
According to this paper, the rotational configurations of cin-
namates attached to a compound such as a polymer could be
distinguished. This method is also applicable to the supramo-
lecular polymer system possessing cinnamate groups. The
splitting Cotton bands shown in Figure 7 also indicate the
existence of substitution/substitution interactions between the
adjacent 3-p-tBocCiNH-R-CD units. Additionally, the substitu-
tion part of 3-p-tBocCiNH-R-CD can be assigned to the
existence of the left-handed anti configuration (Figure 8c). These
data indicate the formation of helical supramolecular polymer
constructed by 3-p-tBocCiNH-R-CD in aqueous solution.
The plots of the observed circular dichroism are shown in
Figure 9. The observed intensities (ellipticity, θ) obviously
increased with nonlinearity as the concentration increased. These
data indicate that 3-p-tBocCiNH-R-CD forms the left-handed
helical supramolecular polymer cooperatively.
Figure 10 shows the circular dichroism spectrum of 1.5 mM
aqueous solution of 3-p-tBocCiNH-R-CD with additions of
excess amounts of R-CD (0.1 to 48 mM). The positive (288
nm) and negative (327 nm) Cotton bands originally observed
at 1.5 mM were gradually decreased to unite into one negative
Cotton effect band around 320 nm, indicating the disappearance
of the substitution/substitution transition. The native R-CD
competitively inhibited the formation of intermolecular com-
plexes formed by 3-p-tBocCiNH-R-CD to bear a 3-p-tBocCiNH-
R-CD-native R-CD heterodimer. The ultimate observed negative
Cotton band is compatible with the slantwise inclusion of the
tBocCi part with native R-CD, as shown in Figure 6d.
(13) (a) Kodaka, M.; Fukaya, T. Bull. Chem. Soc. Jpn. 1989, 62, 1154-1157.
(b) Kodaka, M. J. Am. Chem. Soc. 1993, 115, 3702-3705.
(14) For CiOH-R-CD complex: Uekama, K.; Otagiri, M.; Kanie, Y.; Tanaka,
S.; Ikeda, K. Chem. Pharm. Bull. 1975, 23, 1421-1430.
(15) (a) Wiesler, W. T.; Nakanishi, K. J. Am. Chem. Soc. 1989, 111, 9205-
9213. (b) Zhao, N.; Zhou, P.; Berova, N.; Nakanishi, K. Chirality 1995, 7,
636-651. (c) Berova, N.; Nakanishi, K.; Woody, R. W. Circular Dichroism,
Principles and Applications, 2nd ed; Wiley-VCH: New York, Chichester,
Weinheim, Brisbane, Singapore, Toronto, 2000.
Viscosity Measurements of Supramolecular Polymer So-
lutions. To obtain the physical evidence of formation of the
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Cyclodextrin-Based Chiral Supramolecular Polymer
A R T I C L E S
Figure 10. Circular dichroism spectra of 3-p-tBocCiNH-R-CD (1.5 mM)
on addition of R-CD (1.0, 6.0, 12, 24, and 48 mM) in water.
Figure 12. STM image of the 3-p-tBocCiNH-R-CD prepared from its
concentrated aqueous solution on MoS2 substrate.
Conclusions
We have investigated the formation of cyclodextrin-based
supramolecular polymers formed in an aqueous solution and in
a solid state. R-Cyclodextrin with a p-t-butoxyaminocinnamo-
ylamino group in the 3-position forms a supramolecular polymer
of higher than a 15 mer, which was proved by VPO measure-
ments and turbo ion spray TOF MS measurements in aqueous
solution. The existence of substitution/substitution interactions
shown among the adjacent monomers of the supramolecular
polymer are proved by the observation of positive and negative
Cotton bands in circular dichroism spectra. The mechanism for
the induction of the chirality was also confirmed with model
compounds. The substitution part of 3-p-tBocCiNH-R-CD is
incorporated into a CD cavity of an adjacent monomer in a
slantwise state. The substituents exist as a left-handed anti
configuration in supramolecular polymers. This is the first
observation of CD-based helical supramolecular polymers
formed in aqueous solutions. The formation of a helical
supramolecular polymer with some cooperativity is shown by
the increasing intensities of Cotton effect peaks with increase
in the concentrations. These results remind us that microtubules,
microfilaments, and flagella are helical supramolecular polymers
formed by host-guest cooperative interactions in the biological
system. We could also achieve the visualization of the supramo-
lecular polymers by using STM measurements under ambient
conditions. The length of the supramolecular polymer is
observed more than 20 nm, and the helical structure is also
confirmed on the substrate.
Figure 11. Reduced viscosity of 3-p-tBocCiNH-R-CD (b) and native R-CD
(2) as a function of the concentrations in aqueous solutions.
supramolecular polymer, the viscosity titration of 3-p-tBocCiNH-
R-CD was performed in aqueous solution.16 Figure 11 shows
the reduced viscosity of 3-p-tBocCiNH-R-CD and native R-CD
aqueous solution, respectively, as a function of concentrations.
Although the native R-CD solution showed a slight increase in
the viscosity, the 3-p-tBocCiNH-R-CD solution showed large
concentration dependence. In particular, for the two highest
concentrations, the 3-p-tBocCiNH-R-CD solution showed a
much higher viscosity than the R-CD solution. These results
obviously indicate that the formation of the supramolecular
polymer affects the viscosity of the aqueous solution.
STM Measurement of Supramolecular Polymers Con-
structed by 3-p-tBocCiNH-r-CD. STM measurement was
carried out to investigate the detailed structure of the 3-p-
tBocCiNH-R-CD in solid state under ambient conditions. Figure
12 shows a typical 3-D STM image of the 3-p-tBocCiNH-R-
CD prepared from its aqueous solutions (5.0 × 10-9 M). The
image shows clearly a long chain with a helical structure,
corresponding to the supramolecular polymer constructed by
3-p-tBocCiNH-R-CD (>20 nm). It is difficult to discuss the
period of the helicity because the supramolecular structures of
the samples concentrated on a substrate are not necessarily
consistent with the helical structure in an aqueous solution.
However, the height of an object obviously corresponds to that
of a CD ring in the 3-p-tBocCiNH-R-CD (∼2 nm).
Acknowledgment. This work was supported by a Grant in-
Aid No. S14103015 for Scientific Research from the Ministry
of Education, Culture, Sports, Science and Technology, Japan.
M.M. is a research fellow of the Japan Society for the Promotion
of Science, 2003-2005. We also thank Applied Biosystems for
support of turbo ion spray-TOF MS measurements.
Supporting Information Available: 1H NMR spectra, 2-D
ROESY NMR spectra, circular dichroism spectra, diffusion
coefficients, and relative viscosity of 3-p-tBocCiNH-R-CD. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(16) (a) Sandier, A.; Brown, W.; Mays, H.; Amiel, C. Langmuir 2000, 16, 1634-
1642. (b) Blomberg, E.; Kumpulainen, A.; David, C.; Amiel, C. Langmuir
2004, 20, 10449-10454.
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J. AM. CHEM. SOC. VOL. 127, NO. 9, 2005 2989