Preparation of loose-fit polyrotaxane composed of β-cyclodextrin and poly(ethylene glycol) derivatives through the slipping-expanding protocol

Article abstract of DOI:10.1246/cl.2010.892

At an elevated temperature, a methylated β-cyclodextrin (β-CD) derivative was self-assembled onto a poly(ethylene glycol) (PEG) chain attached to bulky end groups (slipping), and entrapped through a chemical modification at the end groups (expanding), lea

Full text of DOI:10.1246/cl.2010.892

doi:10.1246/cl.2010.892
892
Published on the web July 14, 2010
Preparation of Loose-fit Polyrotaxane Composed of ¢-Cyclodextrin
and Poly(ethylene glycol) Derivatives through the Slipping-Expanding Protocol
Ryo Katoono,*1,2 Yuichiro Kobayashi,1 and Nobuhiko Yui1,2
1School of Materials Science, Japan Advanced Institute of Science and Technology, Nomi, Ishikawa 923-1292
2JST, CREST, Chiyoda-ku, Tokyo 102-0075
(Received May 31, 2010; CL-100511; E-mail: katoono@jaist.ac.jp)
At an elevated temperature, a methylated ¢-cyclodextrin (¢-CD)
derivative was self-assembled onto a poly(ethylene glycol) (PEG)
chain attached to bulky end groups (slipping), and entrapped through
a chemical modification at the end groups (expanding), leading to an
interlocked species. The preparation of a loose-fit polyrotaxane
composed of ¢-CD and PEG was demonstrated as the slipping-
expanding protocol.
Polyrotaxanes have an interlocked structure in which a number
of cyclic molecules are threaded on a linear polymeric chain capped
with bulky end groups,1 and have been attracting a lot of attention as
a building block to construct nanoarchitectures and to design
functional materials2 since an unprecedented synthetic approach
was discovered in 1992.3a Harada et al. reported successful
preparations of cyclodextrin (CD)-based polyrotaxanes by threading
of a polymeric chain into the CD cavity, followed by endcapping
with bulky molecules.3 The slipping approach is also available to
construct rotaxanes, as reported by Stoddart and other scientists.4,5
We envisaged that an integration of the two above-mentioned
approaches would provide a methodology for constructing poly-
rotaxanes with a variety of combinations of cyclic and linear
components.6 One can imagine a dumbbell-shaped molecule that has
no station for entrapping a ring. When a mismatched ring is selected,
each of the components would prefer an uncomplexed state due to
insufficient energy to overcome the barrier or small gain in enthalpy
upon rotaxanation (Scheme 1a). In such a system, if the temperature
is elevated, rotaxanated species would be formed through a
thermodynamic stabilization in an entropy-driven manner, involving
a change in the states of solvation. Enlargement of the end groups
through a reaction at the elevated temperature would allow the
intermediary complex to be interlocked species, as drawn in
Scheme 1b. It would be of advantage in the construction of a
loose-fit polyrotaxane7 with mismatching in terms of size-adequacy,
for instance, a combination of ¢-CD and PEG. Here we report the
preparation of a loose-fit polyrotaxane composed of ¢-CD and PEG
derivatives through the slipping-expanding protocol, based on the
Scheme 1.
complexation between mismatched components, followed by en-
largement of the end groups. Thus, we designed the dumbbell-shaped
PEG derivative 1 with a 2-propynyl-appended benzoyl group at each
end to entrap cyclic molecules by slipping on-off at an elevated
temperature, and to lock in these molecules by enlargement of the
ends through a 1,3-dipole addition reaction with an azide com-
pound.8 Monoaminated permethylated ¢-CD derivative 29 was
employed as a cyclic molecule with mismatch in size (Scheme 2).
The dumbbell-shaped 1 was prepared by a reaction of PEG
(Mn = 950-1050) bis(2-aminoethyl) ether (PEGBA) and 4-benzyl-
oxy-2-(2-propynyloxy)benzoyl chloride, which was obtained by a
stepwise alkylation of methyl 2,4-dihydroxybenzoate, followed by
hydrolysis, and treatment with thionyl chloride (Scheme S1).12
A preliminary test-mixing of 1 and unmodified ¢-CD in water at
25/60 °C for 3 weeks successfully gave a solid containing 1 and ¢-
CD in a ratio of 1:10, although no precipitate was formed upon
mixing PEGBA and ¢-CD under any conditions, as expected.3c
It seems that ¢-CD was self-assembled onto 1 with the help of
intermolecular hydrogen bonding forming a precipitate.10
Scheme 2.
Chem. Lett. 2010, 39, 892-893
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

893
through a simple enlargement of the ends (Table 1, Entry 5). Also, an
expanding reaction at room temperature failed to hold a ring even
after maintaining the system at 60 °C for 7 days (Table 1, Entry 6).
These results are interesting in terms of controlling the content of
cyclic molecules in a CD-based polyrotaxane. In some cases, especially
for polymeric chains with large molecular weights, self-assembly of
cyclic molecules onto a long polymeric chain can lay down in the
course of threading to give a partially covered pseudopolyrotaxane as a
solid, which is not always arbitrarily controlled by mixing conditions
such as ratios, concentrations, temperatures, and others.
In conclusion, we demonstrated a synthetic approach, the
slipping-expanding protocol, for the construction of a loose-fit
polyrotaxane, based on the complexation between mismatched
components of ¢-CD and PEG derivatives, followed by enlargement
of the ends of PEG through a chemical modification. The protocol, in
principle, would be applied to a wide variety of polyrotaxane
preparations. When the ¢-CD derivative is linked by a spacer, self-
assembly of the linked derivative onto the dumbbell-shaped PEG at
an elevated temperature would be also interesting in terms of
designing a novel class of thermoresponsive materials, which is in
progress and will be reported soon.
The authors thank Associate Prof. Akio Ohta (Kanazawa
University) and Dr. Issey Osaka (JAIST) for their help in character-
ization (elemental analysis and mass spectroscopy) of the new
componds.12
Figure 1. 1H NMR spectra (400 MHz) of (a) dumbbell 4, (b) ring 2, and
(c) polyrotaxane 3 (Entry 3), measured in CDCl3 at room temperatrue.
References and Note
1
2
3
4
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Table 1. Conditions for slipping, the number (m) of 2 in 3, determined by
1H NMR, and yields of 3a
Entry
Temp/°C
Time/day
m
Yield of 3/%
1
2
3
4
5
6
60
60
60
60
rt
3
7
14
21
14
7
1.0
2.5
3.4
3.6
®
17
14
14
14
<1
<1
60
®
aConcentrations of 1 and 2 were constant ([1] = 6 © 10¹2 M and
[2] = 7 © 10¹1 M). Mixing at lower concentrations ([1] < 3 ©10¹2 M
and [2] < 4 © 10¹1 M) failed to give 3. The yields of 3 were calculated
based on 1 with an assumption that the repeating distribution of an
ethylene glycol unit in 1 (averaged n = 24) was invariable. Conditions
for the expanding reaction are as follows: BnN3 (10 equiv), CuSO4
(0.8 equiv), and (+)-ascorbic acid (2 equiv), for 3 h at the same
temperature as in the slipping process (Entries 1-5) and rt (Entry 6).
5
6
7
8
Mixing of 1 and 2 in water at 25/60 °C led to no change in
appearance due to high water-solubility of 2,11 thus the transparent
solution was subjected to the expanding reaction in one pot after a
period of slipping to give loose-fit polyrotaxanes 3 in 14-17% yield,
which was successfully isolated in pure form by silica gel column
chromatography and gel permeation chromatography due to the
differences in Rf value (0.44 for 3, 0.36 for 4, and 0.09 for 2, eluted
with 10% MeOH/CH2Cl2 on SiO2) and retention time (see
experimental section and Figure S1).12 The ¢-CD derivative 2 was
found in association with a PEG component in the 1H NMR spectrum
of 3 exhibiting a simple integration of each component (Figure 1).
The content of 2 in a series of 3 was increased with time for slipping
(Table 1, Entries 1-4). Isolation of polyrotaxanes 3 can support the
slipping and entrapping of 2 onto 1 in water at 60 °C. It is noted that
the slipping and expanding reaction at room temperature did not lead
to a sufficient amount of rotaxane, but gave a dumbbell 4 in 88% yield
9
I. W. Muderawan, T. T. Ong, T. C. Lee, D. J. Young, C. B. Ching, S. C. Ng,
Tetrahedron Lett. 2005, 46, 7905.
10 K. A. Udachin, L. D. Wilson, J. A. Ripmeester, J. Am. Chem. Soc. 2000,
122, 12375.
11 The 1H NMR spectrum of 1 itself ([1] = 3.2 © 10¹2 M) measured in D2O at
room temperature showed broadened resonances, whose intensity was
remarkably increased at 60 °C, although the solution remained turbid in
appearance at both temperatures due to the hydrophobic inherence in 1. No
difference was found in the spectra of 2 itself ([2] = 3.5 © 10¹1 M)
measured in D2O at both temperatures, exhibiting sharpened resonances.
Upon mixing of them in D2O, significant downfield shifts were induced for
the protons of terminal group in 1, which were observed at both
temperatures. The intensity of the resonances was unchanged in the two
spectra measured at room temperature and 60 °C, unlike in the case of 1
itself.
12 Supporting Information is available electronically on the CSJ-Journal Web
site, http://www.csj.jp/journals/chem-lett/index.html.
Chem. Lett. 2010, 39, 892-893
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/