Self-threading of a poly(ethylene glycol) chain in a cyclodextrin-ring: Control of the exchange dynamics by chain length

Article abstract of DOI:10.1021/ja061095t

Poly(ethylene glycol) (PEG)-substituted cyclodextrins (CDs) with different chain lengths have been synthesized. PEG-substituted CDs formed self-threading complexes in aqueous solutions, and the conformational exchange dynamics between self-threading and d

Full text of DOI:10.1021/ja061095t

Published on Web 06/27/2006
Self-Threading of a Poly(ethylene glycol) Chain in a Cyclodextrin-Ring:
Control of the Exchange Dynamics by Chain Length
Youhei Inoue, Masahiko Miyauchi, Hiroki Nakajima, Yoshinori Takashima, Hiroyasu Yamaguchi, and
Akira Harada*
Department of Macromolecular Science, Graduate School of Science, Osaka UniVersity, 1-1 Machikaneyama,
Toyonaka, Osaka, 560-0043, Japan
Received February 15, 2006; E-mail: harada@chem.sci.osaka-u.ac.jp
Scheme 1
Design and control of dynamics of supramolecular complexes
are actively worked on to develop unique and valuable properties
in recent years.1 When a guest part is covalently attached to a cyclic
host, it may form intramolecular or intermolecular complexes.2 We
chose cyclodextrins (CDs) as cyclic hosts, because CDs are able
to form complexes with guest compounds in aqueous solutions.
Although there are some reports on CDs with a small guest forming
intramolecular complexes, which are useful for molecular recogni-
tion sensors,3 an artificial enzyme4 in aqueous solutions, there are
few on polymer-substituted CDs.5 Previously, we reported that
6-hydrocinnamoyl-â-CD (6-HyCiO-â-CD) formed a self-inclusion
complex in aqueous solutions.2e Now, we have synthesized poly-
(ethylene glycol) (PEG)-substituted CDs with different chain lengths
(6-PEG600acid-HyCiO-â-CD from PEG 600 diacid, 6-PEG3000acid-
HyCiO-â-CD from PEG 3000 diacid; Scheme 1).
Mono-6-deoxy-6-(4-aminohydrocinnamoyl)-â-CD (6-AmHyCiO-
â-CD) and 6-PEGacid-HyCiO-â-CDs have also been found to form
intramolecular complexes in aqueous solutions by 1D and 2D NMR
analysis, circular dichroism spectroscopy, and vapor pressure
osmometry (VPO). When 1-adamantane carboxylic acid (AdCA)
was added to aqueous solutions of 6-PEGacid-HyCiO-â-CD as a
competitive guest (Ka ) 105 for â-CD), the substituent (PEG chain
and hydrocinnamoyl part) was found to be exposed to water. The
exchange dynamics of 6-PEGacid-HyCiO-â-CDs were found to be
regulated by their chain lengths.
â-CD, the signals of the aromatic protons largely shifted without
broadening (Figure 1c). The 2D ROESY NMR spectrum showed
no correlation between the aromatic protons of the substituent and
the inner protons of CD, indicating that the substituent was
completely exposed to water by inclusion of AdCA into the CD
cavity (see Supporting Information). The circular dichroism spec-
trum of 6-PEG600acid-HyCiO-â-CD in aqueous solutions shows
an induced positive band around 245 nm, corresponding to the 1La
transition band of the substituent. According to the rules of Harata
Figure 1a shows the partial 1H NMR spectra of 6-PEG600acid-
HyCiO-â-CD in D2O. The signals of the aromatic protons of the
substituent were observed at 7.02 and 7.59 ppm, respectively. The
2D ROESY NMR spectrum of 6-PEG600acid-HyCiO-â-CD shows
the rotational nuclear overhouser effects (ROEs) between the
aromatic protons of the substituent and the inner protons of the
CD, indicating that the aromatic of the substituent is included in
the CD cavity (see Supporting Information). The molecular weight
of 6-PEG600acid-HyCiO-â-CD, measured by VPO, showed about
1900 in aqueous solutions, which is consistent with that of a
monomer. These results indicate that 6-PEG600acid-HyCiO-â-CD
formed a self-inclusion complex in aqueous solutions. 6-PEG3000-
acid-HyCiO-â-CD also was found to form a self-inclusion complex
in aqueous solutions (see Supporting Information).
Our next interest moved to the structural change of 6-PEG600acid-
HyCiO-â-CD by external stimulus. In the presence of a half amount
of AdCA in aqueous solutions of 6-PEG600acid-HyCiO-â-CD, the
signals of the aromatic protons were shifted and broadened with
small signals6 (Figure 1b), suggesting that the rate of the formation
of the self-inclusion complex is modestly slow because of its long
chain. Indeed, in the case of 6-AmHyCiO-â-CD with a small
substituent, such broadening was not observed under the same
conditions (see Supporting Information). In the presence of an equal
amount of AdCA in aqueous solutions of 6-PEG600acid-HyCiO-
Figure 1. NMR spectra and proposed structures of 6-PEG600acid-HyCiO-
â-CD in D2O at 30 °C (a) in the absence of AdCA, (b) in the presence of
a half amount of AdCA, and (c) in the presence of an equal amount of
AdCA.
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C O M M U N I C A T I O N S
in the presence of a half amount of AdCA (Figure 3c). From the
variable-temperature NMR measurement, the conformational
exchange rate constants of 6-PEG600acid-HyCiO-â-CD and
6-PEG3000acid-HyCiO-â-CD were estimated to be 382 s-1 and
177 s-1 at 30 °C, respectively (see Supporting Information). It was
revealed that the conformational exchange of 6-PEG600acid-
HyCiO-â-CD was more than twice as fast as that of 6-PEG3000acid-
HyCiO-â-CD. These results indicate that the rate of the self-
threading complex formation depends on the length of the PEG
chain in the substituent.
This is the first report on the self-threading complex of polymer-
substituted CD, and the observation of the difference of self-
threading behavior, depending on polymer chain length. Moreover,
there is a possibility that this self-threading of polymer-substituted
CD leads to novel properties of polymer. The detailed self-threading
behaviors of these complexes are now under investigation.
Figure 2. Circular dichroism spectra of 6-PEG600acid-HyCiO-â-CD in
aqueous solutions (solid line) and in the presence of an equal amount of
AdCA (dashed line).
Acknowledgment. The authors express their special thanks for
the Center of Excellence (21COE) program “Creation of Integrated
EcoChemistry” of Osaka University.
Supporting Information Available: Synthesis and characterization
of 6-AmHyCiO-â-CD, 6-PEG600acid-HyCiO-â-CD, and 6-PEG3000-
acid-HyCiO-â-CD. Variable-temperature measurement. This material
is available free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem.,
Int. Ed. 2000, 39, 3348-3391. (b) Badjic, J. D.; Nelson, A.; Cantrill, S.
J.; Turnbull, W. B.; Stoddart, J. F. Acc. Chem. Res. 2005, 38, 723-732.
(c) Kelly, T. R. Acc. Chem. Res. 2001, 34, 514-522. (e) Collin, J.-P.;
Dietrich-Buchecker, C.; Gavina, P.; Jimenez-Molero, M. C.; Sauvage,
J.-P. Acc. Chem. Res. 2001, 34, 477-487. (f) Harada, A. Acc. Chem.
Res. 2001, 34, 456-464.
(2) (a) Liu, Y.; Flood, A. H.; Stoddart, J. F. J. Am. Chem. Soc. 2004, 126,
9150-9151. (b) Liu, Y.; Flood, A. H.; Moskowitz, R. M.; Stoddart, J. F.
Chem.sEur. J. 2005, 11, 369-385. (c) Hiratani, K.; Kaneyama, M.;
Nagawa, Y.; Koyama, E.; Kanesato, M. J. Am. Chem. Soc. 2004, 126,
13568-13569. (d) Park, J. W.; Lee, S. Y.; Song, H. J.; Park, K. K. J.
Org. Chem. 2005, 70, 9505-9513. (e) Harada, A.; Kawaguchi, Y.;
Hoshino, T. J. Inclusion Phenom. Macrocyclic Chem. 2001, 41, 115-
121. (f) Hoshino, T.; Miyauchi, M.; Kawaguchi, Y.; Yamaguchi, H.;
Harada, A. J. Am. Chem. Soc. 2000, 122, 9876-9877. (g) Miyauchi, M.;
Harada, A. J. Am. Chem. Soc. 2004, 126, 11418-11419. (h) Miyauchi,
M.; Hoshino, T.; Yamaguchi, H.; Kamitori, S.; Harada, A. J. Am. Chem.
Soc. 2005, 127, 2034-2035. (i) Miyauchi, M.; Takashima, Y.; Yamaguchi,
H.; Harada, A. J. Am. Chem. Soc. 2005, 127, 2984-2989.
(3) (a) Ueno, A.; Kuwabara, T.; Nakamura, A.; Toda, F. Nature 1992, 356,
136-137. (b) Ikunaga, T.; Ikeda, H.; Ueno, A. Chem.sEur. J. 1999, 356,
136-137. (c) Bugler, J.; Engbersen, J. F. J.; Reinhoudt, D. N. J. Org.
Chem. 1998, 63, 5339-5344. (d) Ikeda, H.; Nakamura, M.; Ise, N.;
Oguma, N.; Nakamura, A.; Ikeda, T.; Toda, F.; Ueno, A. J. Am. Chem.
Soc. 1996, 118, 10980-10988. (e) Corradini, R.; Dossena, A.; Galaverna,
G.; Marchelli, R.; Panagia, A.; Sartor, G. J. Org. Chem. 1997, 62, 6283-
6289.
Figure 3. NMR spectra of the aromatic protons of the substituted CDs
and conformational exchange rates in the presence of a half amount of AdCA
at 30 °C.
(4) (a) Easton, C. J.; Lincoln S. F. Modified Cyclodextrins; Imperial College
Press: London, 1999. (b) D’Souza, V. T.; Bender, M. L. Acc. Chem. Res.
1987, 20, 146-152. (c) Breslow, R.; Dong, S. D. Chem. ReV. 1998, 98,
1997-2012.
and Uedaira,7 the substituent is included in its CD cavity and is
parallel to the axis of CD. On the contrary, the circular dichroism
spectrum of 6-PEG600acid-HyCiO-â-CD with AdCA showed an
induced negative band in the same wavelength region. According
to the theoretical treatment by Kodaka,8 the exposed substitution
part in water exists nearly parallel to its CD axis (Figure 2).
6-PEG3000acid-HyCiO-â-CD with a longer PEG chain showed
similar results to 6-PEG600acid-HyCiO-â-CD. In contrast, the
NMR spectrum in the presence of a half amount of AdCA is quite
different from that of 6-PEG600acid-HyCiO-â-CD. The signals of
the aromatic protons of 6-PEG3000acid-HyCiO-â-CD were split
(5) (a) Caliceti, P.; Salmaso, S.; Semenzato, A.; Carofiglio, T.; Fornasier,
R.; Fermeglia, M.; Ferrone, M.; Pricl, S. Bioconjugate Chem. 2003, 14,
899-908. (b) Kakuchi, T.; Narumi, A.; Miura, Y.; Matsuya, S.; Sugimoto,
N.; Satoh, T.; Kaga, H. Macromolecules 2003, 36, 3909-3913.
(6) It was found that the broad signals came from the species that participate
in conformational exchange because these signals coalesced; in contrast,
the small signals came from the species that did not participate in
conformational exchange because these signals did not coalesce in the
variable-temperature NMR measurement (see Supporting Information).
(7) Harata, K.; Uedaira, H. Bull. Chem. Soc. Jpn. 1975, 48, 375-378.
(8) Kodaka, M. J. Phys. Chem. A 1998, 102, 8101-8103.
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