Hydrogels composed of organic amphiphiles and α-cyclodextrin: Supramolecular networks of their pseudorotaxanes in aqueous media

Article abstract of DOI:10.1002/chem.200903315

Mixtures of N-alkyl pyridinium compounds [py-N-(CH₂) _n,OC₆H₃3, 5-(OMe)₂] ⁺(X^-) (1bCl: n = 10, X = Cl; 1cBr: n = 12, X = Br) and α-cyclodextrin (α-CD) form supramolecular hydrogel

Full text of DOI:10.1002/chem.200903315

DOI: 10.1002/chem.200903315
Hydrogels Composed of Organic Amphiphiles and a-Cyclodextrin:
Supramolecular Networks of Their Pseudorotaxanes in Aqueous Media
Toshiaki Taira, Yuji Suzaki, and Kohtaro Osakada*[a]
Abstract: Mixtures of N-alkyl pyridini-
um compounds [py-N-(CH2)nOC6H3-
3,5-(OMe)2]+(XÀ) (1bCl: n=10, X=
Cl; 1cBr: n=12, X=Br) and a-cyclo-
dextrin (a-CD) form supramolecular
hydrogels in aqueous media. The con-
centrations of the two components in-
fluences the sol–gel transition tempera-
ture, which ranges from 7 to 678C.
Washing the hydrogel with acetone or
evaporation of water left the xerogel,
and 13C CP/MAS NMR measurements,
powder X-ray diffraction (XRD), and
scanning electron microscopy (SEM)
revealed that the xerogel of 1bCl (or
1cBr) and a-CD was composed of
ROESY 1H NMR measurements sug-
gested intermolecular contact of 3,5-di-
methoxyphenyl and pyridyl end groups
of the axle component. The presence
of the [3]pseudorotaxane is indispensa-
ble for gel formation. Thus, intermolec-
ular interaction between the end
groups of the axle component and that
between a-CDs of the [3]pseudoro-
taxane contribute to formation of the
network. The supramolecular gels were
transformed into sols by adding dena-
turing agents such as urea, C6H3-1,3,5-
pseudorotaxanes with high crystallinity.
1
13C{1H} and H NMR spectra of the gel
revealed the detailed composition of
the components. The gel from 1bCl
and a-CD contains the corresponding
[2]- and [3]pseudorotaxanes, [1b·
CD)]Br and [1b·(a-CD)2]Br, while that
from 1cBr and a-CD consists mainly of
[3]pseudorotaxane [1c·(a-CD)2]Br. 2D
ACHTUNGERTN(NUNG a-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Keywords: cyclodextrins · gels · mi-
celles · rotaxanes · supramolecular
chemistry
(OH)3, and [py-N-nBu] CTHNUGTRNENUG
+A(ClÀ).
Introduction
glycol (PEG, Mw >2000) formed a physical gel in aqueous
media.[10] Low occupancy of a-CDs on long PEG chains is
necessary for aggregation of the polyrotaxanes and forma-
tion of the network structure. Direct bond formation be-
tween a-CDs in the polyrotaxane by condensation with cya-
nuric chloride resulted in a topological gel.[11,12] This new
class of gel exhibits high tensile strength and large swellabil-
ity due to cross-linking a-CDs.
Simple host–guest complexes containing CD also form
gels in water. Gels formed from b-CD and pyridine are com-
posed of their host–guest complex and free pyridine in 1:7
ratio.[13] The host–guest complexes of b-CD with polyaro-
matic hydrocarbons such as chrysene, anthracene, and tri-
phenylene also form gels in DMF/H2O.[14] Self-inclusion
complexes of functionalized b-CDs exist as supramolecular
polymers in water and form hydrogels.[15,16] [2]Rotaxanes
and [4]pseudorotaxanes containing a-CD as the macrocyclic
molecule form light-responsive hydrogels with N,N,N-trime-
thylhexadecan-1-aminium bromide and amphoteric surfac-
tant as gelators.[17]
Polysaccharides are among the important materials in terms
of robust structure, rich functionality, and hydrophilicity.[1,2]
Hydrogels composed of polysaccharides have low toxicity
and potential applications in foods,[3] cosmetics processing
and drug delivery,[4] tissue engineering,[5] and artificial mo-
lecular chaperones and catalysts.[6,7] Cyclodextrins (CDs), a
series of cyclic oligosaccharides consisting of a-1,4-linked
glucopyranose units, form cavities of different sizes depend-
ing on the number of glucose units.[8] Akashi et al. reported
that channel-type aggregates of g-CD form gels in organic
solvents due to microcubic structure.[9] Although native CDs
do not undergo gelation in water, host–guest complexes and
polyrotaxanes of CDs form hydrogels. Harada and Kamachi
reported that the polyrotaxane of a-CDs on polyethylene
[a] T. Taira, Dr. Y. Suzaki, Prof. Dr. K. Osakada
Chemical Resources Laboratory
Tokyo Institute of Technology
4259 Nagastuta, Midori-ku, Yokohama 226-8503 (Japan)
Fax : (+81)45-924-5224
Here we report that pseudorotaxanes, simply obtained by
mixing a-CD and common amphiphiles, form hydrogels
with precisely controlled sol–gel phase transition tempera-
ture, and that [3]pseudorotaxanes play an essential role in
E-mail: kosakada@res.titech.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903315.
6518
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

FULL PAPER
gel formation. Part of this work was reported in a prelimina-
ry form.[18]
10À4 gmLÀ1 (1.6 mm) at 258C on the basis of plots of absorb-
ance at 577 nm versus [1bCl] (Figure 1b). The CMCs of
1aCl and 1cBr were similarly determined to be 3.9 and
0.5 mm, respectively. The emission spectrum of the aqueous
solution containing 1bCl (2.0 mm) and pyrene (5.0 mm)
shows the peak corresponding to pyrene (Figure 2). The
Results
Aggregation of amphiphiles in aqueous solution: Alkyl pyri-
dinium compounds with a 3,5-dimethoxyphenyl group, [py-
N-(CH2)nOC6H3-3,5-(OMe)2]+XÀ (1aCl: n=8, X=Cl; 1bCl:
n=10, X=Cl; 1cBr: n=12, X=Br), were prepared by con-
densation of pyridine with XACHTNUGTRNE(UNG CH2)nOC6H3-3,5-(OMe)2 in
DMF.[19] Exchange of the counteranion of 1bCl yielded [py-
N-(CH2)10OC6H3-3,5-(OMe)2]+XÀ (1bNO3: X=NO3; 1bPF6:
X=PF6; 1bACHTUNGTRENNUNG[PtCl3ACHTUNGTRENNUNG(dmso)]: X=PtCl3ACHTNUGTNER(NUGN dmso), dmso=dimethyl
sulfoxide).
Figure 2. Emission spectrum of 2.0 mm 1bCl and 5.0 mm pyrene (H2O, RT,
lex =333 nm).
ratio of the I1 (375 nm) and the I3 (385 nm) peaks of pyrene
monomer, I3/I1 =0.86, indicates that the pyrene is located in
a nonpolar microenvironment.[22]
We also investigated the micelle-formation process of
1bCl in D2O using 1H NMR spectroscopy (Figure 3). In-
Amphiphilic compounds 1aCl, 1bCl, and 1cBr are expect-
ed to form micelles in aqueous solution.[20] Aggregation of
1bCl and a-CD in aqueous solution has been examined in
the presence of hydrophobic pigments such as Nile red
(lmax =577 nm) and pyrene (lmax =338 nm).[21,22] Dissolution
of 1bCl and Nile red ([Nile red]0 =10 mm) in water leads to
aggregation of 1bCl to form micelles that encapsulate Nile
red molecules in the core. Figure 1a shows absorption spec-
tra of solutions with different concentration of 1bCl (from
3.1ꢁ10À6 to 1.0ꢁ10À2 gmLÀ1). The solution of 1bCl below
6.3ꢁ10À5 gmLÀ1 shows peaks at 526 and 577 nm, but in-
creasing the concentration above 6.4ꢁ10À4 gmLÀ1 causes
significant increase of the peak at 577 nm, which is assigned
to dye encapsulated within micelles. The critical micelle con-
centration (CMC) of 1bCl was determined to be 6.4ꢁ
Figure 3. 1H NMR spectrum of 1bCl (D2O, RT) at a) 5.0 mm, b) 10 mm,
c) 20 mm, d) 30 mm, e) 40 mm, and f) 50 mm.
creasing concentration of 1bCl from 5.0 to 50 mm causes up-
field shifts of the signals. Signal e of para-C6H3-3,5-(OMe)2
at 5.0 mm shows a large shift and overlaps with the signal d
(d=À0.35 ppm) at higher concentration, whereas CH2
peaks close to the pyridinium group show much smaller
changes in peak position (<0.07 ppm). These results indi-
cate that the dimethoxyphenyl groups are located inside the
micelle particle and may interact with aromatic dye or with
each other. Changes in peak positions depending on concen-
tration of 1bCl indicate that 1bCl in the micelle particle un-
dergoes fast exchange with that in solution or with that in
other micelle particles above the NMR timescale. Addition
of a-CD to a micellar solution of 1bCl and pyrene ([1bCl]=
12.3 mm, [pyrene]=10 mm) at 258C decreased absorption de-
pending on the amount of a-CD. Figure 4 shows the de-
Figure 1. a) Absorption spectra of aqueous solutions of Nile red and
1bCl with various concentrations of 1bCl (from 3.1ꢁ10À6 to 1.0ꢁ
10À2 gmLÀ1). b) Plots of absorbance at 577 nm versus concentration of
1bCl.
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6519

K. Osakada et al.
different molar ratios showed a maximum at a molar frac-
tion close to 0.50, which indicates 1:1 complexation of a-CD
and 1cBr to form [1c·ACTHNUGRTENUNG(a-CD)]Br (Figure 5a and bi). The
Figure 4. Absorption spectra of 1bCl and pyrene ([1bCl]=12.3 mm,
[pyrene]=10 mm) in aqueous solutions with various concentrations of a-
CD [from 0 (0 equiv) to 22.1 mm (1.8 equiv)].
Figure 5. Job plots of a) [[1c·
area of d’, b) [[1c·
(a-CD)m]Br] obtained from 1H NMR area of i) d’(*)
(a-CD)]Br] obtained from 1H NMR peak
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(m=1) and ii) d’’ (m=2) The concentrations were obtained by means of
1H NMR area ratios of d, d’, d’(*), and d’’. Sum of the concentrations of
the two components was fixed to 10 mm in all cases.
crease of the absorbance at 338 nm from 0.52 to 0.24 caused
by addition of a-CD. These results are ascribed to the fact
that the encapsulated pyrene in the micelle is released from
the core by ready formation of [2]- and [3]pseudorotaxanes
[1b·
(a-CD)] and [1b·
E
plot obtained from peak d’’ shows a maximum close to a
molar fraction of 0.33 (Figure 5bii), which indicates that
1cBr and a-CD form not only the [2]pseudorotaxane but
complexation of the amphiphile and CD was reported by
many groups,[23] and regarded as complexation controlled by
external stimulus.[20,24]
also [3]pseudorotaxane [1c·ACTHNUTRGEN(UNG a-CD)2]Br.
1H and 13C{1H} NMR spectra and MALDI-TOF mass
Pseudorotaxane formation in solution: Scheme 1 summariz-
es equilibria among the amphiphiles (1aCl, 1bCl, 1cBr) and
spectra of the D2O solution of 1aCl and a-CD indicate the
formation of [2]pseudorotaxane [1a·ACTHNUTRGNEUNG(a-CD)]Cl rather than
the [3]pseudorotaxane. Association constants for formation
of the pseudorotaxanes K1 =[[2]pseudorotaxane]/([N-alkyl
pyridinium] and
G
K2 =[[3]pseudorotaxane]/
([[2]pseudorotaxane]ACHTUNGTERNN[UNG a-CD]) were obtained by comparison
1
of H NMR peak area ratio of the other hydrogen signals.
The van’t Hoff plots of K1 and K2 (Scheme 1) provided ther-
modynamic parameters for formation of [2]pseudorotaxanes
(DH1ꢀ and DS1ꢀ) and [3]pseudorotaxanes (DH2ꢀ and DSꢀ2), re-
spectively, as listed in Table 1. A mixture of 1aCl and a-CD
forms a stable [2]pseudorotaxane with a large equilibrium
constant, K1 =2.8ꢁ103 mÀ1 at 298 K, although [3]pseudoro-
taxane is not observed in the mixtures. Formation of both
[2]- and [3]pseudorotaxanes of a-CD with 1bCl (K1 =5.3ꢁ
102 mÀ1, K2 =30mÀ1) is less favorable than that with 1cBr
(K1 =1.7ꢁ103 mÀ1, K2 =2.1ꢁ102 mÀ1).
The thermodynamic parameters in Table 1 suggest ther-
modynamically favorable pseudorotaxane formation under
enthalpy control. The negative enthalpy change of [2]pseu-
Scheme 1. Formation of [2]- and [3]pseudorotaxanes in aqueous solution.
Isomers of [2]- and [3]pseudorotaxane are omitted.
Table 1. Thermodynamic parameters for formation of [2]pseudorotaxane
(K1, DHꢀ1, DSꢀ1, and DG1ꢀ) and [3]pseudorotaxane (K2, DHꢀ2, DS2ꢀ, and DGꢀ2)
at 298 K.
their [2]- and [3]pseudorotaxanes with a-CD in aqueous
1
media.[25,26] The H NMR spectra of a mixture of the alkyl
Axle K1 (K2)
[mÀ1
DHꢀ1
DSꢀ1
DGꢀ1
pyridinium compound and a-CD at low concentration
(<10 mm) confirmed the presence of pseudorotaxanes. Hy-
drogen atoms in the ortho positions of the aryl group of
G
]
[DHꢀ2]
[kJmolÀ1
[DSꢀ2]
[DGꢀ2]
[kJmolÀ1
]
]
[JKÀ1 molÀ1
]
1aCl 2.8ꢁ103 (À)
1bCl 5.3ꢁ102 (30)
À37(2) [–]
À24(2)
À58(7) [–]
À27(6)
À20(5) [À]
À16(4)
1cBr, [1c·ACHTUNGTRENNUNG(a-CD)]Br, and [1c·ACHTUNGTERN(NUGN a-CD)2]Br give rise to the cor-
[À77(7)]
À19(1)
[À2.3(2)ꢁ102)
À3(3)
[À8(13)]
À18(2)
responding signals at d=5.74, 6.06 (and a minor peak at d=
6.14) and 5.63 ppm, respectively. Job plots of the peak of the
aromatic end group of the mixtures of 1cBr and a-CD with
1cBr 1.7ꢁ103
(2.1ꢁ102)
[À47(5)]
[À1.1(2)ꢁ102]
[À13(10)]
6520
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

Organic Amphiphile/a-Cyclodextrin Hydrogels
FULL PAPER
dorotaxane formation, DHꢀ1, is attributed to the hydrophobic
interaction between a-CD and the axle molecule. The larger
negative value of DHꢀ2 compared to DHꢀ1 suggests a contri-
bution of hydrogen-bonding interactions between OH
groups of two a-CDs in the [3]pseudorotaxane.[27]
The dependence of DSꢀ1 on the chain length of the axle
moiety can be explained by solvation and the bent structure
due to intramolecular p–p interaction of the axle unit (vide
infra).[28] The enthalpy–entropy compensation plot (DH8 vs.
TDS8) for pseudorotaxane formation gave a straight line
with a slope of 1.2(1) and an intercept of 22(3) kJmolÀ1 (see
Supporting Information). These values are larger than those
of the inclusion equilibrium of a-CD with a variety of small
guest molecules;[29] the slope (0.79) and the intercept
(8.0 kJmolÀ1) suggest that pseudorotaxane formation in our
study involves significant conformational change and exten-
sive desolvation due to the large guest molecules. A 2D
1
Figure 7. Photographs. a) Left: 1aCl (50 mm); right: 1aCl (50 mm) and a-
CD (100 mm) (sol). b) Left: 1bCl (50 mm); right: 1bCl (50 mm) and a-
CD (100 mm) (gel). c) Left: 1cBr (50 mm); right: 1cBr (50 mm) and a-
CD (100 mm) (gel).
ROESY H NMR cross-peak of the protons in the 3-posi-
tion of a-CD (H3) and C6H3 proton of [1a·ACTHNUTRGNE(NUG a-CD)]Cl (e’) in-
dicates [2]pseudorotaxane formation in which primary hy-
droxyl groups of a-CD face the C6H3-3,5-(OMe)2 moiety
(Figure 6). The 2D ROESY 1H NMR spectrum of [1b·
ACTHNUTRGNE(UNG a-
CD)]Cl exhibits cross-peaks of NCH2 proton of 1b with H
atoms of a-CD, H5 and H6, that is, a-CD is located on the
Figure 8 depicts the relationship between the gel-to-sol
phase transition temperature Tgel and concentration of the
components. Mixtures of 1bCl and a-CD in water show Tgel
ranging from 78C ([1bCl]=60 mm, [a-CD]=60 mm) to 328C
polymethylene group of [1b·ACHTNUGRTNEUNG
(a-CD)]Cl.[30–32] These solutions
do not form hydrogels under the conditions examined.
Figure 6. 2D ROESY NMR spectrum (D2O, 30 8C) of 1aCl (20 mm) and
a-CD (20 mm).
Figure 8. Phase-transition temperature Tgel at various concentrations of
a) 1bCl and a-CD in H2O, b) 1bCl and a-CD in D2O, and c) 1cBr and a-
CD in H2O.
Gelation of N-alkyl pyridinium and a-CD: Amphiphilic
compounds 1aCl, 1bCl, and 1cBr form micelles in aqueous
solution (vide infra) and do not form hydrogels even at high
concentration. Addition of a-CD (100 mm) to an aqueous
solution containing 50 mm of 1bCl or 1cBr at 608C and cool-
ing it to room temperature yields hydrogels (Figure 7b, c),
while mixtures of a-CD and alkyl pyridinium with a shorter
polymethylene chain (1aCl, n=8) do not form hydrogels
under the same conditions (Figure 7a).
([1bCl]=80 mm, [a-CD]=100 mm), as shown in Figure 8a.
The mixture shows higher Tgel in D2O, ranging from 128C
([1bCl]=50 mm, [a-CD]=50 mm) to 368C ([1bCl]=80 mm,
[a-CD]=100 mm), than in H2O (Figure 8b). The hydrogel
of a mixture of 1cBr and a-CD is thermally more stable
than that of 1bCl and a-CD at the same concentration, and
Tgel attains 678C ([1cBr]=80 mm, [a-CD]=100 mm; Fig-
ure 8c). Table 2 summarizes the effect of the counter ion XÀ
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6521

K. Osakada et al.
Table 2. Gelation properties of N-alkyl pyridinium compounds and CDs
in H2O.
and low-symmetry conformation of the macrocyclic com-
pound (peaks with asterisk in Figure 9a).[33] The xerogel
does not exhibit the corresponding signals, that is, a-CD in
the xerogel adopts a symmetrical cyclic conformation similar
to other host–guest compounds and rotaxanes of a-CD (Fig-
ure 9b, c). These NMR results also indicate that the xerogel
is composed of pseudorotaxanes. The powder X-ray diffrac-
tion (XRD) patterns of the xerogels of 1bCl/a-CD and of
1cBr/a-CD show diffraction peaks at 2q=5.5, 10.98 (Fig-
ure 10a) and 2q=5.7, 11.28 (Figure 10b), respectively. They
System[a]
State[b]
Tgel [8C]
a-CD+1aCl
a-CD+1bCl
a-CD+1bNO3
a-CD+1bPF6
a-CD+1b[PtCl3(dmso)]
a-CD+1cBr
sol
–
gel
gel
insol
sol
gel
sol
32(1), 35(1)[c]
35(1)
–
–
50(1)
–
–
b-CD+1bCl
g-CD+1bCl
sol
[a] [N-alkyl pyridinium]=50 mm, [CD]=100 mm. [b] Gel: gelation, insol:
insoluble, sol: solution. [c] Tgel in D2O.
on gelation of a mixture of 1bX (50 mm) and a-CD
(100 mm). The Tgel of 1bNO3 (358C) is higher than that of
1bCl (328C). Amphiphile 1bPF6 is not soluble in water, and
its mixture with a-CD does not form a hydrogel. Water-in-
soluble 1bACHTUNGTRENNUNG[PtCl3ACHTUNGTRENNUNG(dmso)] dissolves upon addition of a-CD at
608C to give a clear solution of their inclusion complex. b-
CD and g-CD do not gelate 1bCl in water.
A xerogel of 1bCl (1cBr) and a-CD (1:2) was obtained by
slow evaporation of water from the hydrogel or by washing
the hydrogel with acetone. The following results indicate
that the xerogels are composed of pseudorotaxanes of the
above compounds. The MALDI-TOFMS spectrum of the
xerogel of 1bCl/a-CD contains peaks at m/z 1344.6 and
2316.7, which correspond to [2]pseudorotaxane [{py-N-
(CH2)10OC6H3-3,5-(OMe)2}
and [3]pseudorotaxane [{py-N-(CH2)10OC6H3-3,5-(OMe)2}-
(a-CD)2]+ClÀ ([1b·
(a-CD)2]Cl), respectively. The xerogel
A
([1b·ACTHNGUTER(NNUG a-CD)]Cl)
A
ACHTUNGTRENNUNG
obtained from 1cBr and a-CD also shows peaks assigned to
their [2]- and [3]pseudorotaxanes (m/z 1373.4 and 2347.6).
Figure 9 compares the 13C CP/MS NMR spectra of a-CD,
the xerogel of 1cBr/a-CD, and 1cBr. The signals of the alkyl
pyridinium group in the xerogel are broadened significantly
(Figure 9b), if compared with free 1cBr (Figure 9c). The C1
and C4 carbon atoms of free a-CD are observed as multiple
peaks (d=81, 98 ppm) due to the strained glycosidic linkage
Figure 10. X-ray diffraction patterns (CuKa, RT) of xerogels of a) 1bCl
and a-CD, b) 1cBr and a-CD, c) a-CD, d) 1bCl.
can be assigned to {001} and {002} diffraction of the colum-
nar alignment of the a-CD moiety of the pseudorotax-
anes.[34] These diffraction peaks were not observed in the
patterns of a-CD and of 1bCl (Figure 10c, d). Scanning elec-
tron microscopy (SEM) of the xerogel revealed sheetlike
layer morphology, as shown in Figure 11.[35]
Pseudorotaxane formation on hydrogelation: Figure 12
shows changes in the 13C{1H} NMR spectra of 1aCl, 1bCl
and 1cBr upon addition of a-CD in D2O. A solution of a
mixture of 1aCl (2.0ꢁ102 mm) and a-CD (4.0ꢁ102 mm) gives
rise to signals of C3 and C2 due to [2]pseudorotaxane [1a·-
AHCTUNGTREG(NNUN a-CD)]Cl (d=76.5 and 74.4 ppm) (Figure 12a, bottom).
The 13C{1H} NMR spectrum of a mixture of 1bCl (50 mm)
and a-CD (50 mm) exhibits signals assigned to C3, C5, and
C2 of [2]pseudorotaxane [1b·ACTHNUTRGENUGN(a-CD)]Cl at d=76.5, 74.5, and
74.2 ppm, exclusively (Figure 12b, middle). Further addition
of a-CD to the solution leads to hydrogelation, and its spec-
Figure 9. 13C CP/MS NMR spectra (100 Hz, RT) of a) a-CD, b) Xerogel
of 1cBr and a-CD, and c) 1cBr. Peaks with an asterisk are assigned to
C1 and C4 with a conformationally strained glycosidic linkage.
6522
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

Organic Amphiphile/a-Cyclodextrin Hydrogels
FULL PAPER
(20 mm) in D2O. 13C{1H} NMR signals of both [2]- and[3]-
pseudorotaxanes are observed (Figure 12c, middle). Further
addition of a-CD converts [1c·ACTHNUTRGENN(GU a-CD)]Br to [1c·CAHTUNGTERN(NUGN a-CD)2]Br,
giving a mixture of the [3]pseudorotaxane and free a-CD
(Figure 12c, bottom).
Figure 13 compares the H NMR spectra of 1cBr and mix-
1
tures of 1cBr and a-CD ([1cBr]=20 mm, [a-CD]=10–
195 mm). The solution containing 1cBr (20 mm) and a-CD
(10 mm) shows signals of 1cBr as well as a set of peaks due
Figure 11. SEM image of xerogels of a) 1bCl/a-CD, b) 1cBr/a-CD.
to [1c·ACTHNURTGNEU(GN a-CD)]Br at d=8.39 (a’), 7.91 (b’), 6.10 (e’), 6.06 (d’)
and 1.94 ppm (f’) (Figure 13ii). These peaks are at different
positions than those of 1cBr (d=8.42 (a), 7.49 (b), 5.79 (d),
5.74 (e), 1.75 ppm (f)). Further addition of a-CD ([1cBr]=
20 mm, [a-CD]=20–30 mm) increases the amount of [1c·
ACHTUNGTRENNUNG(a-
CD)]Br and generates [3]pseudorotaxane [1c·(a-CD)2]Br
AHCTUNGTRENNUNG
with a new set of signals at d=8.47 (a’’), 7.99 (b’’), 6.17 (e’’),
5.63 (d’’), and 1.85 ppm (f’’). Small signals at d=6.14 [d’(*)],
6.11 [e’(*)] and 1.87 ppm [f’(*)] may be attributed to an
isomer of [1c·ACTHUNTGRNEUNG(a-CD)]Br with different orientation of the a-
CD on the alkylene group.
1
Figure 13v–x show the H NMR spectra at higher concen-
trations of a-CD ([a-CD]ꢁ40 mm), and the D2O solution
turned to hydrogel under these conditions. The signals of
the NMR spectra correspond to molecules entrapped in the
space in the gel network. The molecules of 1cBr contained
in the network may not show the clear sharp NMR signals
due to restricted molecular motion and much longer relaxa-
tion time of the nuclei. Signals of the NCH2CH2 hydrogen
Figure 12. 13C{1H} NMR spectra (D2O, RT) of a) a-CD (top) and a mix-
ture of 1aCl (2.0ꢁ102 mm) and a-CD (4.0ꢁ102 mm) (bottom). b) a-CD
(top), a mixture of 1bCl (50 mm) and a-CD (50 mm) (middle), and a mix-
ture of 1bCl (50 mm) and a-CD (1.0ꢁ102 mm) (gel) (bottom). c) a-CD
(top), a mixture of 1cBr (20 mm) and a-CD (20 mm) (gel) (middle), and
a mixture of 1cBr (20 mm) and a-CD (90 mm) (gel) (bottom). (*: a-CD,
^
&: [2]pseudorotaxane, : [3]pseudorotaxane).
atoms of [1c·
1.74–2.00 ppm as two broadened signals, although they se-
verely overlap with the signals of [1c·(a-CD)]Br [f’ and
f’(*)]. They indicate the existence of isomers of [1c·(a-
ACHTUNGTERNN(UNG a-CD)2]Br [f’’ and f’’(*)] are observed at d=
trum contains C3 signals of [3]pseudorotaxane [1b·ACTHNUTRGNEUNG(a-
CD)2]Cl (d=76.7 ppm; Figure 12b, bottom). A mixture of
1cBr and a-CD forms hydrogel even at low concentration
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Figure 13. 1H NMR spectra (D2O, 25 8C) of i) 1cBr (20 mm), ii) a mixture of 1cBr and a-CD ([1cBr]0 =20 mm, [a-CD]0 =10 mm), iii) a mixture of 1cBr
and a-CD ([1cBr]0 =20 mm, [a-CD]0 =20 mm), iv) a mixture of 1cBr and a-CD ([1cBr]0 =20 mm, [a-CD]0 =30 mm), v) a mixture of 1cBr and a-CD
([1cBr]0 =20 mm, [a-CD]0 =40 mm) (Gel), vi) a mixture of 1cBr and a-CD ([1cBr]0 =20 mm, [a-CD]0 =50 mm) (gel), vii) a mixture of 1cBr and a-CD
([1cBr]0 =20 mm, [a-CD]0 =65 mm) (gel), viii) a mixture of 1cBr and a-CD ([1cBr]0 =20 mm, [a-CD]0 =85 mm) (gel), ix) a mixture of 1cBr and a-CD
([1cBr]0 =20 mm, [a-CD]0 =115 mm) (gel), and x) a mixture of 1cBr and a-CD ([1cBr]0 =20 mm, [a-CD]0 =195 mm) (gel).
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6523

K. Osakada et al.
CD)2]Br with regard to orientation of two a-CDs.[27,30,31] Fig-
ure 13viii–x ([a-CD]ꢁ85 mm) contain almost negligible sig-
nals of [1c·ACHTUNGTRENNUNG(a-CD)]Br and large signals of [3]pseudorotaxane
[1c·ACHTUNGTRENNUNG(a-CD)2]Br. Since [3]pseudorotaxane [1c·CATHGNUTREN(NGNU a-CD)2]Br dis-
solved within the gel network undergoes exchange with the
rotaxanes contained in the network, the gel network is prob-
ably composed mainly of the [3]pseudorotaxane. Mixtures
1
of 1bCl and a-CD in D2O also show H NMR signals of [2]-
and [3]pseudorotaxanes [1b·
ACHUTGTNRENN(GU a-CD)]Cl and [1b·ACHTUGNTREN(NUGN a-
CD)2]Cl.[18]
Figure 15. Plots of lnKd versus 1/T for a) 1cBr·
CD) and ii) 1bCl·(a-CD)2.
ACHUTGTNRNE(NGU a-CD)2 and b) i) 1bCl·ACHTUNGTRENNUNG(a-
Figure 14 plots concentrations of the compounds existing
in solution and gel as a function of temperature. The mix-
ture ([1cBr]=20 mm, [a-CD]=1.0ꢁ102 mm) in D2O forms a
AHCTUNGTRENNUNG
Gelation of [1c·
CAHUTTGNRENN(GU a-CD)2]Br(sol) and dissolution of [1c·ACHTUNGTRENNUNG(a-
CD)2]Br(gel) occur reversibly. Temperature dependence of
Kd2, which was estimated to be [1cBr·ACHTNUGRTNEUNG(a-CD)2(sol)], gave
DHꢀd2 =45(2) kJmolÀ1, DSdꢀ2 =1.1(1)ꢁ102 JKÀ1 molÀ1 and
DGꢀd2 =12(3) kJmolÀ1 (Figure 15a). Equilibrium constant
Kd1 was also equal to [1bCl·ACTHUNGRTNEUNG(a-CD)(sol)], and the thermody-
namic parameters were obtained from the van’t Hoff plots
(Figure 15b), giving DHꢀd1 =37(3) kJmolÀ1, DSdꢀ1 =93(9)
JKÀ1 molÀ1, and DGdꢀ1 =10(5) kJmolÀ1. Dissolution of the
[3]pseudorotaxane in gel occurs with thermodynamic param-
eters DHꢀd2 =57(4) kJmolÀ1, DSdꢀ2 =1.5(1)ꢁ102 JKÀ1 molÀ1,
and DGꢀd2 =13(7) kJmolÀ1 (Figure 15bii).
Figure 14. Temperature-dependent change of a) [[1c·
and [[1c·(a-CD)2]Br(sol)] (*), b) [[1b·(a-CD)m]Cl(gel)] (&) (m=1, 2), and
[[1b·(a-CD)]Cl(sol)] (~), and [[1b·(a-CD)2]Cl(sol)] (*). Concentration of
ACHTUGNERTN(NUGN a-CD)2]Br(gel)] (&)
N
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
Chemical response of hydrogel: Figure 16 summarizes for-
mation of hydrogel from 1bCl and a-CD and transformation
to sol induced by addition of guest molecules. The hydrogel
composed of 1bCl and a-CD ([1bCl]=50 mm, [a-CD]=
100 mm, Tgel =328C, Figure 16i, ii) is turned into low-viscosi-
ty suspension by addition of an excess of NaCl (500 mm)
(Figure 16ii, iii). Gel-to-sol phase transition is caused by ad-
dition of 200 mm of urea or phloroglucinol (Figure 16iv, v).
Addition of C6H3-1,3,5-(OH)3 (200 mm) to a D2O solution
the compounds in gel was estimated from that in solution.
1
hydrogel at 58C (278 K) showing broadened H NMR sig-
nals assigned to [1c·
water in hydrogel with on concentration of 2.6 mm. Raising
the temperature increases the amount of [1cBr·(a-CD)2(sol)
and decreases that of [1c·(a-CD)2]Br(gel)] (concentration of
[1c·(a-CD)2]Br incorporated into the hydrogel network), as
shown in Figure 14a. The H NMR signals of [1c·
ACHTUNGNERTN(NUG a-CD)2]Br(sol) dissolved in entrapped
U
]
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
1
1
(a-CD)]Br
of 1bCl and a-CD did not change the H NMR and the 2D
or 1cBr are not observed in the range 278–323 K. Hydrogel
formed from 1bCl and a-CD ([1bCl]=50 mm, [a-CD]=1.0ꢁ
102 mm) contains [1b·
ACHTNUTRGENN(GU a-CD)]Cl and [1b·ACHTUNGTERN(NUGN a-CD)2]Cl, whose
concentration varies depending on temperature (Fig-
ure 14b).
Equilibria of [2]- and [3]pseudorotaxanes in the gel and in
aqueous solution are shown in Scheme 2:[14,36–38] The [2]- and
[3]pseudorotaxanes are equilibrated in solution, as shown in
Schemes 1 and 2. The dissolution equilibrium constants Kd1
and Kd2 can be defined as Kd1 =[[2]pseudorotaxane(sol)] and
Kd2 =[[3]pseudorotaxane(sol)] by assuming activity of the gel
to be unity, which allows estimation of thermodynamic pa-
rameters for gelation and dissolution, DHꢀd and DSdꢀ from the
plots of lnKd versus 1/T. Figure 15 plots lnKd against 1/T.
Figure 16. Illustration and photograph of thermally and chemically re-
sponsive properties of hydrogel of 1bCl and a-CD ([1bCl]=50 mm, [a-
CD]=100 mm).
Scheme 2. Equilibria of [2]- and [3]pseudorotaxanes.
6524
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

Organic Amphiphile/a-Cyclodextrin Hydrogels
FULL PAPER
1
1
ROESY H NMR spectra. The 2D ROESY H NMR spec-
trum of the solution containing 1bCl (50 mm), a-CD
(100 mm), and C6H3-1,3,5-(OH)3 (200 mm) shows an ROE
correlation between NCH2 and C6H3 protons of [2]- and
[3]pseudorotaxanes of 1bCl and a-CD, which indicates that
the pseudorotaxane structure and interpseudorotaxane inter-
action between C6H3-3,5-(OMe)2 and the pyridyl moiety are
Discussion
Figure 17 summarizes a plausible gelation mechanism. Com-
pound 1bCl forms micelles above the CMC (Figure 17i).
Addition of a-CD to the micellar solution of 1bCl forms
[2]pseudorotaxane [1b·ACTHUNRGTNE(NUG a-CD)]Cl. It does not form micelles
due to less significant intermolecular interaction of the alkyl
chains complexed with a-CD than those without the pseu-
dorotaxane structure (Figure 17ii). Further reaction of a-CD
with [2]pseudorotaxane leads to formation of [3]pseudoro-
also maintained in the sol. Addition of [py-N-nBu] CTHNUGTRNENUG
+A(ClÀ)
(200 mm) to the hydrogel leads to gel-to-sol phase transition
(Figure 16v, vi). The results suggest that interaction of cat-
ionic [py-N-nBu]
(ClÀ) with the electron-rich C6H3-3,5-
taxane [1b·
ACHUTNGTERNG(NU a-CD)2]Cl. The thus-formed [1b·ACHTUNTGERN(NUGN a-CD)2]Cl and
(OMe)2 group of the rotaxanes degrades the supramolecular
[1b·(a-CD)]Cl aggregate to form supramolecular polymer A
ACHTUNGTRENNUNG
polymers of the pseudorotaxanes.[39]
through attractive interaction between C6H3-3,5-(OMe)2 and
pyridyl moieties, which is observed by ROESY experiments
(Figure 17iii). Further aggregation of A results in hydrogela-
tion (Figure 17iv). Evaporation of water from the hydrogel
yields a xerogel composed of [1b·ACHTNUTRGNEUNG(a-CD)m]Cl (m=1,2) (Fig-
ure 17v). The solid state is maintained by hydrogen bonds
between a-CDs and channel-type packing yielding the layer
morphology, which are observed by XRD and SEM analysis.
This hydrogen bonding between a-CDs and formation of
microcrystals may be important for cross-linking of supra-
molecular polymer A in the hydrogel (Figure 17v). Addition
of urea, C6H3-1,3,5-(OH)3, or [py-N-nBu] CTHNUGTRNENUG
+A(ClÀ) to the hy-
drogel causes transition of gel to sol. C6H3-1,3,5-(OH)3
cleaves the cross-links of the gel network, in which the pseu-
dorotaxane remains as the supramolecular polymer. Stack-
ing of [py-N-nBu] CTHNUGTRENUNGN 3CAHTUNGTERN(NUNG OMe)2 groups leads to
+A(ClÀ) with C6H
degradation of the supramolecular polymer and results in
phase transition to sol.
Figure 18 summarizes the energy diagram of the hydroge-
lation of 1cBr and a-CD. Although each step involves a
negative change of entropy due to multicomponent com-
plexation, formation of hydrogel is a thermodynamically fa-
vorable reaction (DG(total) =À43(15) kJmolÀ1) under enthal-
py control. The [3]pseudorotaxane shows a dual function as
the monomer of A and as the cross-linker, which are essen-
tial for hydrogelation. The mixture of a-CD and 1aCl (n=
8) does not form a hydrogel because the alkyl chain is not
long enough for [3]pseudorotaxane formation. Supramolec-
Figure 17. Plausible mechanism for formation of the supramolecular hy-
drogel.
Figure 18. Energy diagram of hydrogelation of 1cBr and a-CD.
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6525

K. Osakada et al.
trifluoroacetate). Elemental analysis was carried out with
a LECO
ular polymer A is formed by attractive inter-rotaxane inter-
action between the pyridinium and C6H3-3,5-(OMe)2 groups,
while it is aggregated by hydrogen bonding between CD
molecules.[40,41] Similar cation–p interaction is well known
and observed in biological systems.[42] Tsuzuki et al. calculat-
ed the interaction energy of the complex of N-methylpyridi-
nium and benzene as À9.36 kcalmolÀ1.[43] Fossey et al. re-
ported intramolecular interactions between N-methyl pyridi-
nium and benzene by NOE and fluorescence spectrosco-
py.[44]
CHNS-932 CHNS or Yanaco MT-5 CHN autorecorder at the Center for
Advanced Materials Analysis, Technical Department, Tokyo Institute of
Technology. The absorption spectra were recorded with a Jasco V-530
UV/Vis spectrometer. The samples were stored at a temperature of 258C
in a Jasco EHC-477 Peltier-type thermostated cell holder prior to mea-
surement. Xerogels were analyzed by scanning electron microscopy
(SEM, HITACHI S-5200) at 30 kV. X-ray diffraction (XRD) analyses
were carried out with a Rigaku RINT2000.
À
G
G
ACHTUNGRTEN(NUNG 1bPF6): An aqueous solution
(10.0 mL) of 1bCl (1.0 g, 2.5 mmol) was poured into an aqueous solution
(10.0 mL) of NH4PF6 (2.0 g, 12.5 mmol), and the solution was stirred for
21 h at room temperature. The solid product that separated from the mix-
ture was collected by filtration and washed with water to yield 1bPF6 as a
À1
~
white solid (1.1 g, 2.1 mmol, 84%). IR (KBr disk, RT): n=839, 558 cm
;
Conclusion
1H NMR (400 MHz, [D6]DMSO, RT): d=1.20–1.42 (12H, CH2), 1.65 (m,
2H; OCH2CH2), 1.90 (m, 2H; NCH2CH2), 3.68 (s, 6H; OCH3), 3.88 (t,
3J
(3H; C6H3), 8.14 (t, J
1H; C5H5N), 9.06 ppm (d, 3J
AHCTUNGTRENNUNG
(H,H)=6 Hz, 2H; OCH2), 4.57 (t, 3J
ACHUTGTNRENUNG ACHUTGNTERN(NUGN H,H)=7 Hz, 2H; NCH2), 6.05
We have described facile multicomponent hydrogelation of
a-CDs and N-alkyl pyridiniums [py-N-(CH2)nOC6H3-3,5-
(OMe)2]+XÀ. Reaction of 1bCl (or 1cBr) with a-CD in
aqueous solution forms [2]- and [3]pseudorotaxanes as an
equilibrium mixture, while the reaction of 1aCl and a-CD
does not give [3]pseudorotaxane but [2]pseudorotaxane.
[3]Pseudorotaxanes composed of 1bCl (or 1cBr) and a-CDs
aggregate to form supramolecular polymers, followed by en-
tanglement to form three-dimensional networks which im-
mobilize water on the macroscale. Amphiphilic compounds
1bCl and 1cBr form micelles in aqueous solution above
their CMCs. During the course of gel formation, solutions of
1bCl (or 1cBr) undergo degradation of the micelle aggrega-
tion and afford [3]pseudorotaxanes. They may exist as indi-
vidual molecules or species and/or supramolecular polymers,
which are re-aggregated as the network polymer to form the
supramolecular hydrogels. Hydrogel formation was induced
by formation of the [3]pseudorotaxane. This unique supra-
molecular transformation of amphiphiles may provide a new
method to control aggregation and functions of these soft
materials. Easy construction of supramolecular hydrogels
from simple components may provide a new bottom-up ap-
proach to the design of biodegradable hydrogels and deliv-
ery matrices for drugs.
3
3
N
ACHTUNGTRENUN(NG H,H)=8 Hz,
(100 MHz, [D6]DMSO, RT): d=25.4 (CH2), 25.5 (CH2), 28.3 (CH2), 28.7
(3C; CH2), 28.9 (CH2), 30.7 (CH2), 55.1 (OCH3), 60.8 (NCH2), 67.4
(OCH2), 92.7 (C6H3), 93.1 (C6H3), 128.0 (C5H5N), 144.5 (C5H5N), 145.3
(C5H5N), 160.4 (C6H3), 161.0 ppm (C6H3); MS (FAB): m/z calcd for
C23H34NO3: 372 [MÀPF6]+; found 372; elemental analysis calcd (%) for
C23H34F6NO3P·0.5H2O (517.5): C 52.47, H 6.70, N 2.66; found: C 52.62,
H 6.54, N 2.72.
À
G
G
ACHTUNGTREN(NUNG 1bNO3): AgNO3 (204 mg,
1.2 mmol) was added to an aqueous solution (10.0 mL) containing 1bCl
(0.50 g, 1.2 mmol), and the mixture was stirred for 15 h at room tempera-
ture in the dark. The formed AgCl was removed by filtration and the
product was extracted with acetone (10.0 mL). Evaporation of the sol-
vent under reduced pressure yielded 1bNO3 as a white solid (468 mg,
1.1 mmol, 92%). 1H NMR (400 MHz, [D6]DMSO, RT): d=1.19–1.42
(12H; CH2), 1.65 (m, 2H; OCH2CH2), 1.90 (m, 2H; NCH2CH2), 3.68 (s,
3
3
6H; OCH3), 3.88 (t, J
2H; NCH2), 6.05 (3H; C6H3), 8.15 (t, 3J
(t, 3J(H,H)=7 Hz, 1H; C5H5N), 9.09 ppm (d, 3J
ACHTUNGTRENNUNG
N
ACHTUNGTRENUN(NG H,H)=7 Hz,
AHCTUNGTRENNUNG
U
C5H5N); 13C{1H} NMR (100 MHz, [D6]DMSO, RT): d=25.4 (CH2), 25.5
(CH2), 28.4 (CH2), 28.7 (3C; CH2), 28.9 (CH2), 30.7 (CH2), 55.1 (OCH3),
60.8 (NCH2), 67.4 (OCH2), 92.7 (C6H3), 93.1 (C6H3), 128.0 (C5H5N),
144.6 (C5H5N), 145.3 (C5H5N), 160.4 (C6H3), 161.0 ppm (C6H3); elemental
analysis calcd (%) for C23H34N2O6·0.5H2O (517.5): C 62.28, H 7.95, N
6.32; found: C 62.38, H 8.21, N 6.41.
A
E
E
G
(1bACTHNGUERTNNU[G PtCl3ACHTUNGTRENNUNG(dmso)]):
A
CHTUNGTRENNUNG
the solution was stirred for 24 h at room temperature. The formed precip-
itate was collected by filtration and washed with H2O, EtOH, and Et2O
Experimental Section
to yield 1bACTHUNRGTENNUG[PtCl3ACHTUNGTREN(NGUN dmso)] as a yellow solid (0.70 g, 1.0 mmol, 83%).
1H NMR (300 MHz, [D6]DMSO, RT): d=1.18–1.42 (12H; CH2), 1.64 (br,
2H; OCH2CH2), 1.90 (br, 2H; NCH2CH2), 2.53 (s, 6H; SCH3), 3.67 (s,
Materials and methods: [py-N-(CH2)8OC6H3-3,5-(OMe)2]+ClÀ (1aCl),
[py-N-(CH2)10OC6H3-3,5-(OMe)2]+ClÀ (1bCl), and [py-N-(CH2)12OC6H3-
3,5-(OMe)2]+BrÀ (1cBr) were prepared according to the literature
method.[18] Other chemicals were commercially available. NMR spectra
(1H, 13C{1H}) ware recorded on Varian MERCURY300, Jeol EX-400, and
Jeol JNM La-500 spectrometers. 13C CP/MAS NMR spectra were record-
ed on a JEOL JNM La-500. Sodium 3-(trimethylsilyl)-1-propanesulfonate
(DSS) and sodium 3-(trimethylsilyl)-1-propionate (TSP) were used as an
external standards in the 13C{1H} NMR measurements in D2O. 2D
ROESY spectra were recorded on a JEOL JNM La-500 spectrometer
(500 MHz). The parameters used were spin-rock mixing time of 400 ms,
PD=1.2 s, and eight scans. The temperature was kept at 303 K during
measurement. Fast atom bombardment mass spectra (FABMS) were ob-
tained with a JEOL JMS-700 spectrometer (2-nitrophenyl n-octyl ether
(NPOE) or 3-nitrobenzyl alcohol (NBA) matrix). Matrix assisted laser
desorption ionization time of flight mass spectra (MALDI-TOFMS) were
obtained with a Shimadzu AXIMA-CFR Plus spectrometer (matrix: 2-
hydroxy-5-methoxybenzoic acid (super DHB); cationization agent: silver
3
3
6H; OCH3), 3.87 (t, J
2H; NCH2), 6.04 (3H; C6H3), 8.16 (t, 3J
(t, 3J(H,H)=7 Hz, 1H; C5H5N), 9.09 ppm (d, 3J
ACHTUNGTRENNUNG
N
ACHTUNGTRENUN(NG H,H)=7 Hz,
AHCTUNGTRENNUNG
U
C5H5N); 13C{1H} NMR (75.5 MHz, [D6]DMSO, RT): d=25.4 (CH2), 25.5
(CH2), 28.4 (CH2), 28.6 (CH2), 28.7 (2C; CH2), 28.9 (CH2), 30.8 (CH2),
40.3 (SCH3), 55.1 (OCH3), 60.8 (NCH2), 67.4 (OCH2), 92.7 (C6H3), 93.1
(C6H3), 128.1 (C5H5N), 144.7 (C5H5N), 145.5 (C5H5N), 160.5 (C6H3),
161.1 ppm (C6H3); elemental analysis calcd (%) for C25H40Cl3NO4PtS
(517.5): C 39.92, H 5.36, N 1.86, S 4.26, Cl, 14.14; found: C 39.59, H 5.12,
N 1.94, S 4.12, Cl 14.45.
[2]Pseudorotaxane of 1aCl and a-CD ([1a·ACTHNUTRGNE(UNG a-CD)]Cl): 1aCl (53 mg,
0.14 mmol) and a-CD (272 mg, 0.28 mmol) were charged to a NMR tube.
After addition of D2O (0.70 mL) to the mixture, the 1H NMR spectrum
was recorded. The solution contained [1a·ACTHNUTRGNE(UNG a-CD)]Cl and free a-CD.
1H NMR (400 MHz, D2O, RT): d=1.09–1.51 (8H; CH2), 1.63 (br, 2H;
OCH2CH2), 2.00 (br, 2H; NCH2CH2), 4.91 (br, 6H; H1-a-CD), 5.83
6526
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

Organic Amphiphile/a-Cyclodextrin Hydrogels
FULL PAPER
(2H; C6H3), 6.04 (s, 1H; C6H3), 7.94 (m, 2H; C5H5N), 8.42 (m, 1H;
C5H5N), 8.77 ppm (m, 2H; C5H5N) (peak of NCH2, OCH2, OCH3, H2–6
of a-CD overlapped with the signals of solvent and free a-CD); 13C{1H}
NMR (100 MHz, D2O, RT): d=28.9 (CH2), 29.4 (CH2), 32.1 (CH2), 32.3
(CH2), 32.7 (CH2), 33.9 (CH2), 58.1 (OCH3), 62.3 (C6-a-CD), 64.5
(NCH2), 71.3 (OCH2), 74.2 (C2-a-CD), 74.6 (C5-a-CD), 76.5 (C3-a-CD),
83.7 (C4-a-CD), 95.2 (C6H3), 96.2 (C6H3), 104.6 (C1-a-CD), 131.0
(C5H5N), 146.6 (C5H5N), 148.4 (C5H5N), 162.7 (C6H3), 163.9 ppm (C6H3)
1H NMR data of [1c·
in the a-CD face the C6H3-3,5-(OMe)2 moiety (500 MHz, D2O, RT): d=
ACHTUNGTREN(NUNG a-CD)]Br showed that the primary hydroxyl groups
3
3
6.06 (dd, J
ortho-C6H3); other signals of the isomers of [1c·
tinguished from each other due to severe overlap; d=1.51 (m, 2H;
A
ACHTUNGTREN(NUNG H,H)=2 Hz, 2H;
AHCTUNGTRENNUNG
3
OCH2CH2), 1.92 (m, 2H; NCH2CH2), 3.49 (dd, J
CD), 3.52 (dd, 3J(H,H)=9 Hz, 6H; H4-a-CD), 3.59 (dd, 3J
10 Hz, 6H; H5-a-CD), 3.64 (s, 6H; OCH3), 3.75 (dd, 3J
(H,H)=9, 9 Hz,
6H; H3-a-CD), 4.48 (t, 3J(H,H)=7 Hz, 2H; NCH2), 4.90 (d, 3J
(H,H)=
3 Hz, 6H; H1-a-CD), 7.89 (t, 3J(H,H)=7 Hz, 2H; C5H5N), 8.37 (t, 3J-
(H,H)=7 Hz, 1H; C5H5N), 8.70 ppm (d, 3J
(H,H)=6 Hz, 2H; C5H5N);
1H NMR data of [1c·
(a-CD)2]Br (500 MHz, D2O, RT): d=0.92–1.54
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1
1
(assignment was supported by H–1H COSY, H–13C COSY, and ROESY
A
ACHTUNGTRENNUNG
spectroscopy in D2O.); MS (MALDI-TOF): m/z calcd for C57H90NO33
:
AHCTUNGTRENNUNG
1316.5 [MÀCl]+; found 1315.1.
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
[2]- and [3]pseudorotaxanes of 1bCl and a-CD ([1b·ACTHNUGRTENUNG(a-CD)]Cl and [1b·-
ACHTUNGTRENNUNG
(a-CD)2]Cl): Compound 1bCl (28.6 mg, 7.01ꢁ10À2 mmol) and a-CD
(18H; CH2), 1.78–1.96 (2H; NCH2CH2), 4.48 (br, 2H; NCH2), 5.63 (s,
2H; ortho-C6H3), 6.17 (s, 1H; para-C6H3), 7.99 (br, 2H; C5H5N), 8.47 (br,
1H; C5H5N), 8.75 ppm (br, 2H; C5H5N); the signals of OCH2, OCH3,
(61.3 mg, 6.31ꢁ10À2 mmol) were dissolved in D2O (1.40 mL). Part of the
1
solution was transferred to an NMR tube and H and 13C{1H} NMR spec-
and a-CD of [1c·
ACHTUNGTRENNUNG
trum were recorded. The resulting mixture showed signals of 1bCl
free a-CD; 13C{1H} NMR data of [1c·
AHCTUNGTRENNUNG
(11.1 mm, 22%); [1b·
in the a-CD are close proximity to the C6H3-3,5-(OMe)2 moiety
(32.9 mm, 66%); and isomers of [1b·(a-CD)]Cl (5.1 mm, 10%) and [1b·
ACHTUNGTRENNUNG(a-CD)]Cl, in which the secondary hydroxyl groups
d=28.4 (CH2), 29.4 (CH2), 31.7 (2CH2), 32.2 (CH2), 33.3 (CH2), 33.4
(CH2), 33.6 (CH2), 33.7 (CH2), 34.1 (CH2), 58.4 (OCH3), 62.4 (C6-a-CD),
64.8 (NCH2), 70.8 (OCH2), 74.5 (C2-a-CD), 74.8 (C5-a-CD), 76.7 (C3-a-
CD), 84.1 (C4-a-CD), 96.3 (C6H3), 96.8 (C6H3), 105.0 (C1-a-CD), 131.1
(C5H5N), 147.0 (C5H5N), 148.4 (C5H5N), 163.0 (C6H3), 164.1 ppm (C6H3);
AHCTUNGTRENNUNG
(a-CD)2]Cl (0.9 mm, 2%), while signals of free a-CD was not observed.
Further addition of a-CD (68.1 mg, 7.01ꢁ10À2 mmol) to the solution at
608C and cooling to room temperature gave a hydrogel. 1H and 13C{1H}
13C{1H} NMR data of [1c·
ACHTNUTRGNEUG(N a-CD)2]Br (125 MHz, D2O, RT): d=29.7
NMR spectra of the gel showed the presence of [1b·ACHTNUGTRENNUG(a-CD)]Cl, [1b·ACHTUNTGREN(NUGN a-
(CH2), 29.9 (CH2), 33.2 (CH2), 33.8 (CH2), 33.9 (CH2), 34.1 (CH2), 34.6
(CH2), 34.7 (CH2), 35.0 (CH2), 35.4 (CH2), 58.5 (OCH3), 62.4 (C6-a-CD),
62.9 (C6’-a-CD), 64.7 (NCH2), 71.6 (OCH2), 75.1 (C2-a-CD), 74.8 (C5-a-
CD), 76.7 (C3-a-CD), 83.4 (C4-a-CD), 94.9 (C6H3), 96.4 (C6H3), 105.3
(C1-a-CD), 105.4 (C1’-a-CD), 131.3 (C5H5N), 147.1 (C5H5N), 148.9
(C5H5N), 162.7 (C6H3), 164.5 ppm (C6H3); signals of C2’-, C3’-, C4’-, and
C5’-a-CD were significantly overlapped with the signal of free a-CD. The
assignment was supported by 1H–1H COSY, 1H–13C COSY, and ROESY
CD)2]Cl, and free a-CD. The concentrations of the compounds were de-
termined from the peak area ratio of the ortho-C6H3 proton. 1H NMR
data of [1b·ACHTUNGTRENNUNG(a-CD)]Cl showed that the secondary hydroxyl groups in the
a-CD face the C6H3-3,5-(OMe)2 moiety (400 MHz, D2O, RT): d=1.95
(m, 2H; NCH2CH2), 5.97 (s, 2H; ortho-C6H3), 6.07 (s, 1H; para-C6H3);
1H NMR data of [1b·
ACHTUNGTRENNUNG(a-CD)]Cl showed that the primary hydroxyl groups
in the a-CD face the C6H3-3,5-(OMe)2 moiety (400 MHz, D2O, RT): d=
1.84 (m, 2H; NCH2CH2), 6.05 (s, 1H; para-C6H3), 6.13 (s, 2H; ortho-
C6H3); 1H NMR data of [1b·
ACHTUNGTRENNUNG
spectroscopy in D2O); MS (MALDI-TOF) data of [1c·ACHTNUTRGNE(NUG a-CD)]Br: m/z
calcd for C61H98NO33: 1372.6 [MÀBr]+; found 1373.4; MS (MALDI-
TOF) data of [1c·CATHUNGTRNE(GUN a-CD)2]Br: m/z calcd for C97H158NO63: 2344.9
A
ACHTUNGTRENNUNG
[MÀBr]+; found 2347.6.
AHCTUNGTRENNUNG
Thermodynamic parameters of [2]- and [3]pseudorotaxane and hydrogel
formation
AHCTUNGTRENNUNG
Formation of [1a·
ACHUTGTNRENNUG(a-CD)]Cl: The equilibrium constants for [1a·ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
CD)]Cl formation (K1 =[[1a·AHCTUNRTGEG(NUNN a-CD)]Cl]/ACHTUTGNRENNUG[1aCl]ACUTHNGTRENNUNG
31.9 (CH2), 32.2 (CH2), 32.7 (CH2), 33.4 (CH2), 33.6 (2C; CH2), 58.1
(OCH3), 62.2 (C6-a-CD), 64.4 (NCH2), 70.6 (OCH2), 74.2 (C2-a-CD),
74.5 (C5-a-CD), 76.5 (C3-a-CD), 83.7 (C4-a-CD), 95.7 (C6H3), 96.5
(C6H3), 104.6 (C1-a-CD), 130.8 (C5H5N), 146.6 (C5H5N), 148.1 (C5H5N),
by means of 1H NMR spectroscopy. 1aCl (5.3 mg, 1.4ꢁ10À2 mmol) and
a-CD (6.8 mg, 7.0ꢁ10À3 mmol) were charged to a NMR tube. After addi-
1
tion of D2O (1.40 mL) to the mixture, H NMR spectra were recorded at
various temperatures (303, 313, 323, 333, and 343 K). The concentration
162.5 (C6H3), 163.7 ppm (C6H3); 13C{1H} NMR data of [1b·
ACTHNUTRGNEU(GN a-CD)2]Cl
of the 1aCl and [1a·ACTHNUTRGNEU(GN a-CD)]Cl at each temperatures were obtained by
(100 MHz, D2O, RT): d=62.5 (a-CD), 63.1 (a-CD), 75.3 (a-CD), 76.7
(a-CD), 83.0 (a-CD), 84.2 ppm (a-CD); other signals significantly over-
comparison of 1H NMR peak area ratio of the signals d and d’. Plotting
the natural logarithm of K1 against reciprocal absolute temperature gave
straight lines (R2 =0.99), which provide DH1ꢀ and DSꢀ1.
lapped with signals of [1b·
ACHTUNGTRENUN(NG a-CD)]Cl and free a-CD. The assignment was
supported by 1H–1H COSY, 1H–13C COSY, and ROESY spectroscopy in
Formation of [1b·
A
ACHTUNGTRENNUNG(a-
D2O); MS (MALDI-TOF) data of [1b·ACTHUNTGRNEUNG(a-CD)]Cl: m/z calcd for
C61H98NO33: 1344.6 [MÀCl]+; found 1344.6; MS (MALDI-TOF) data of
CD)]Cl formation (K1 =[[1b·AHCTNUGTRENNNUG
in a similar way. 1bCl (2.9 mg, 7.0ꢁ10À3 mmol) and a-CD (3.4 mg, 3.5ꢁ
[1b·
2316.7.
[2]- and [3]pseudorotaxanes of 1cBr and a-CD ([1c·ACHTNUGTRNEUN(G a-CD)]Br and [1c·-
(a-CD)2]Cl: m/z calcd for C97H158NO63
:
2316.9 [MÀCl]+; found
10À3 mmol) were charged to
a NMR tube. After addition of D2O
1
(0.70 mL) to the mixture, H NMR spectra were recorded at various tem-
peratures (308, 313, 333, 343, and 353 K). At each temperature, the sig-
nals of [1b·ACHTNUTRGENNG(U a-CD)2]Cl were not observed. Plotting the natural logarithm
ACHTUNGTRENNUNG
(a-CD)2]Br): 1cBr (6.7 mg, 1.4ꢁ10À2 mmol) and a-CD (13.6 mg, 1.40ꢁ
10À2 mmol) were charged to an NMR tube. After addition of D2O
(0.70 mL) to the mixture at room temperature, the 1H NMR spectrum of
of the K1 against reciprocal absolute temperature gave straight lines
(R2 =0.98), which provide DH1ꢀ and DSꢀ1.
the resulting mixture contained signals of 1cBr (6.5 mm, 32%), [1c·
CD)]Br, in which the secondary hydroxy groups in the a-CD are in close
proximity to the C6H3-3,5-(OMe)2 moiety (7.7 mm, 39%), [1c·(a-CD)]Br,
in which the primary hydroxy groups in the a-CD are close to the C6H3-
3,5-(OMe)2 moiety (1.4 mm, 7%), and [1c·(a-CD)2]Br (4.4 mm, 22%).
Further addition of a-CD (47.7 mg, 4.91ꢁ10À2 mmol) to the solution led
to formation of [1c·
(a-CD)2]Br as major component. 1H and 13C{1H}
NMR spectra of the solution showed the existence of [1c·(a-CD)2]Br and
free a-CD. The concentration of the compounds was determined from
the peak area ratio of the ortho-C6H3 proton. 1H NMR data of [1c·
(a-
CD)]Br showed that the secondary hydroxyl groups in the a-CD face the
C6H3-3,5-(OMe)2 moiety (500 MHz, D2O, RT): d=6.04 (d, 3J
(H,H)=
(H,H)=2, 2 Hz, 1H; para-C6H3);
ACHTUNGERTN(NUNG a-
Formation of [1b·
CD)2]Cl formation (K2 =[[1b·
determined in similar way. 1bCl (20.4 mg, 0.05 mmol) and a-CD
G
ACHTUNGTRENNUNG(a-
A
E
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
a
(97.3 mg, 0.10 mmol) were charged to a NMR tube. After addition of
D2O (0.70 mL) in the presence of NEt4Cl (5.0 mm) to the mixture,
1H NMR spectra were recorded at various temperatures (308, 311, 313,
318, 323, and 328 K). At each temperature, the signals of 1bCl were not
observed. Plotting the natural logarithm of the K2 against reciprocal ab-
solute temperature gave straight lines (R2 =0.97), which provide DH2ꢀ and
DSꢀ2.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
T
Formation of [1c·
A
ACHTUNGTRENNUNG(a-
2 Hz, 2H; ortho-C6H3), 6.08 (dd, 3J
A
CD)]Br formation (K1 =[[1c·
A
R
ACHTUNGTRENNUNG
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6527

K. Osakada et al.
in a similar way. 1cBr (3.4 mg, 7.0ꢁ10À3 mmol) and a-CD (3.4 mg, 3.5ꢁ
Acknowledgements
10À3 mmol) were charged to
a NMR tube. After addition of D2O
(0.70 mL) to the mixture, H NMR spectra were recorded at various tem-
peratures (323, 333, 338, and 343 K). At each temperature, the signals of
1
We thank our colleagues in the Chemical Resources Laboratory of
Tokyo Institute of Technology for their technical support and discussions;
Dr. Yoshiyuki Nakamura for 13C CP/MAS NMR measurements, Dr.
Masato Koizumi of the Center for Advanced Materials Analysis, Techni-
cal Department, Tokyo Institute of Technology for MALDI-TOF MS
measurements, Dr. Daling Lu for scanning electron microscopy (SEM)
measurements, and Tomohito Ide for theoretical calculation of the inter-
action energy of the model complex. This work was supported by a
Grant-in-Aid for Scientific Research for Young Scientists from the Minis-
try of Education, Culture, Sports, Science and Technology, Japan
(19750044), and by the Global COE program “Education and Research
Center for Emergence of New Molecular Chemistry”. T.T. acknowledges
the scholarship by the Japan Society for the Promotion of Science.
[1c·ACHTUNGTRENNUNG(a-CD)2]Br were not observed. Plotting the natural logarithm of K1
against reciprocal absolute temperature gave straight lines (R2 =0.99),
which provide DHꢀ1 and DSꢀ1, respectively.
Formation of [1c·ACHTUNGTRENNUNG(a-CD)2]Br: The equilibrium constants for [1c·ACHTNUGTRENNUNG
CD)2]Br formation (K2 =[[1c·CATHNUGTRNE(NGNU a-CD)2]Br]/ACTHUNGTREN[NUGN [1c·ACHTUNGTRENN(GUN a-CD)]Br]ACHTUNGTRENNNUG
determined by similar may. 1cBr (1.7 mg, 3.5ꢁ10À3 mmol) and a-CD
(6.8 mg, 7.0ꢁ10À3 mmol) were charged to a NMR tube. After addition of
1
D2O (0.70 mL) to the mixture, H NMR spectra were recorded at various
temperatures (303, 308, 313, 318, 323, and 328 K). At each temperature,
the signals of 1cBr were not observed. Plotting the natural logarithm of
K2 against reciprocal absolute temperature gave straight lines (R2 =0.95),
which provide DHꢀ2 and DSꢀ2, respectively.
Dissolution of hydrogel of 1cBr and a-CD: Compound 1cBr (6.7 mg,
1.4ꢁ10À2 mmol) and a-CD (68.1 mg, 7.0ꢁ10À2 mmol) were charged to a
NMR tube. After addition of D2O (0.70 mL) in the presence of NBu4Br
(5.0 mm) to the mixture, 1H NMR spectra were recorded at various tem-
peratures (278, 283, 288, 293, 298, 301, 303, 305, and 308 K). From the
known concentration of internal standard and initial concentration of
[1] R. L. Whistler, C. L. Smart, Polysaccharide Chemistry, Academic
Press, New York, 1953.
[2] a) K. Akiyoshi, S. Deguchi, N. Moriguchi, S. Yamaguchi, J. Sunamo-
to, Macromolecules 1993, 26, 3062–3068; b) N. Morimoto, F. M.
Winnik, K. Akiyoshi, Langmuir 2007, 23, 217–223.
1cBr, the concentration of [1c·
CD)2]Br](Sol)) and that of the gel phase ([[1c·
lated, respectively. At each temperature, the signals of 1cBr and [[1c·
CD)]Br were not observed. Plotting the natural logarithm of Kd (=[[1c·-
ACHTUNGTRENNUNG(a-CD)2]Br](sol)) against reciprocal absolute temperature gave straight
lines (R2 =0.99), which provide DHdꢀ and DSꢀd.
N
ACHTUNGERTN(NUNG a-
[3] W. Pilnik, F. M. Rombouts, Carbohydr. Res. 1985, 142, 93–105.
[4] N. A. Peppas, J. Z. Hilt, A. Khademhosseini, R. Langer, Adv. Mater.
2006, 18, 1345–1360.
[5] a) J. L. Drury, D. J. Mooney, Biomaterials 2003, 24, 4337–4351; b) S.
Ladet, L. David, A. Domard, Nature 2008, 452, 76–80.
[6] a) Y. Nomura, M. Ikeda, N. Yamaguchi, Y. Aoyama, K. Akiyoshi,
FEBS Lett. 2003, 553, 271–276; b) Y. Nomura, Y. Sasaki, M. Takagi,
T. Narita, Y. Aoyama, K. Akiyoshi, Biomacromolecules 2005, 6,
447–452.
[7] a) R. Valentin, K. Molvinger, F. Quignard, D. Brunel, New J. Chem.
2003, 27, 1690–1692; b) E. Guibal, Prog. Polym. Sci. 2005, 30, 71–
109; c) D. J. Macquarrie, J. J. E. Hardy, Ind. Eng. Chem. Res. 2005,
44, 8499–8520; d) M. Chtchigrovsky, A. Primo, P. Gonzalez, K. Mol-
vinger, M. Robitzer, F. Quignard, F. Taran, Angew. Chem. 2009, 121,
6030–6034; Angew. Chem. Int. Ed. 2009, 48, 5916–5920.
[8] a) K. Harata, Chem. Rev. 1998, 98, 1803–1827; b) H.-J. Schneider, F.
Hacket, V. Rꢂdiger, Chem. Rev. 1998, 98, 1755–1785; c) W. Saenger,
J. Jacob, K. Gessler, T. Steiner, D. Hoffmann, H. Sanbe, K. Koizumi,
S. M. Smith, T. Takaha, Chem. Rev. 1998, 98, 1787–1802.
[9] T. Kida, Y. Marui, K. Miyawaki, E. Kato, M. Akashi, Chem.
Commun. 2009, 3889–3891.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Dissolution of hydrogel of 1bCl and a-CD: Compound 1bCl (20.4 mg,
5.00ꢁ10À2 mmol) and a-CD (97.3 mg, 1.00ꢁ10À1 mmol) were charged to
a NMR tube. After addition of D2O (1.00 mL) in the presence of NEt4Cl
(5.0 mm) to the mixture, 1H NMR spectra were recorded at various tem-
peratures (293, 296, 289, 303, and 305 K). From the known concentration
of internal standard and initial concentration of 1bCl, the concentration
of 1bCl·
were calculated, respectively. Kd1 and Kd2 were estimated to be [[1b·
CD)]Cl](sol) and [[1b·(a-CD)2]Cl](sol), respectively. At each temperature,
ACHTUNGTRENNUNG(a-CD) and 1bCl·ACTHUNGTRENNNUG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
the signals of 1bCl were not observed. Plotting the natural logarithm of
Kd1 (or Kd2) against reciprocal absolute temperature gave straight lines
for each compounds (R2 =0.99), which provide DHdꢀ and DSꢀd.
Gelation criterion and determination of sol/gel phase-transition tempera-
tures Tgel
[10] J. Li, A. Harada, M. Kamachi, Polym. J. 1994, 26, 1019–1026.
[11] a) Y. Okumura, K. Ito, Adv. Mater. 2001, 13, 485–487; b) K. Ito,
Polym. J. 2007, 39, 489–499; c) J. Araki, K. Ito, Soft Matter 2007, 3,
1456–1473.
[12] T. Oku, Y. Furusho, T. Takata, Angew. Chem. 2004, 116, 984–987;
Angew. Chem. Int. Ed. 2004, 43, 966–969.
[13] C. de Rango, P. Charpin, J. Navaza, N. Keller, I. Nicolis, F. Villain,
A. W. Coleman, J. Am. Chem. Soc. 1992, 114, 5475–5476.
[14] D. Rizkov, S. Mizrahi, J. Gun, R. Hoffman, A. Melman, O. Lev,
Langmuir 2008, 24, 11902–11910.
[15] a) W. Deng, H. Yamaguchi, Y. Takashima, A. Harada, Angew.
Chem. 2007, 119, 5236–5239; Angew. Chem. Int. Ed. 2007, 46, 5144–
5147; b) W. Deng, H. Yamaguchi, Y. Takashima, A. Harada, Chem.
Asian J. 2008, 3, 687–695; c) A. Harada, Y. Takashima, H. Yamagu-
chi, Chem. Soc. Rev. 2009, 38, 875–882.
Gelation criterion: Stability to inversion of a test tube was used as a gen-
eral criterion for gel formation.[35] N-Alkyl pyridinium, a-CD, and the
solvent were put in a septum-capped glass tube (internal diameter/length
18 mm/40 mm) and heated at 608C until the solid dissolved. The solution
was cooled to room temperature or 08C in an ice–water bath. If the gel
existed stably, it was classified as a hydrogel. If the sample was a solution,
it was classified as a sol.
Gel-to-sol phase transition temperature (Tgel): We determined Tgel by two
methods: stability to inversion of a test tube and the spectroscopic tur-
bidity method.[36] In the former method, a glass tube containing gel was
immersed upside-down in a thermostatted bath. In the latter, we pre-
pared the gel in a 10 mm optical cell and measured the transmittance at
600 nm where the N-alkyl pyridinium and a-CD do not absorb. Gradual-
ly increasing the temperature of the gel leads to gel-to-sol phase transi-
tion with no absorption at 600 nm, and this temperature was regarded as
[16] a) A. Miyawaki, Y. Takashima, H. Yamaguchi, A. Harada, Chem.
Lett. 2007, 36, 828–829; b) A. Miyawaki, Y. Takashima, H. Yamagu-
chi, A. Harada, Tetrahedron 2008, 64, 8355–8361.
Tgel
.
Reaction of gel with phloroglucinol: Compound 1bCl (20.4 mg, 5.0ꢁ
10À2 mmol), a-CD (97.3 mg, 1.0ꢁ10À1 mmol), and phloroglucinol
(25.2 mg, 0.200 mmol) were charged to a glass tube. After addition of
D2O (1.00 mL), the mixture was heated at 608C until the solid had dis-
solved. The solution was cooled to room temperature, and did not form a
hydrogel. Part of the solution was transferred to an NMR tube and
1H NMR and 2D ROESY spectra were recorded.
[17] a) L. Zhu, X. Ma, F. Ji, Q. Wang, H. Tian, Chem. Eur. J. 2007, 13,
9216–9222; b) X. Ma, Q. Wang, D. Qu, Y. Xu, F. Ji, H. Tian, Adv.
Funct. Mater. 2007, 17, 829–837.
[18] T. Taira, Y. Suzaki, K. Osakada, Chem. Commun. 2009, 7027–7029.
[19] a) Y. Suzaki, T. Taira, K. Osakada, Dalton Trans. 2006, 5345–5351;
b) Y. Suzaki, T. Taira, K. Osakada, Transition Met. Chem. 2007, 32,
753–756.
6528
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6518 – 6529

Organic Amphiphile/a-Cyclodextrin Hydrogels
FULL PAPER
[20] a) Y. Suzaki, T. Taira, D. Takeuchi, K. Osakada, Org. Lett. 2007, 9,
887–890; b) Y. Suzaki, T. Taira, K. Osakada, M. Horie, Dalton
Trans. 2008, 4823–4833.
[21] a) C. Forder, C. S. Patrickios, S. P. Armes, N. C. Billingham, Macro-
molecules 1996, 29, 8160–8169; b) D. Takeuchi, A. Inoue, F. Ishi-
maru, K. Osakada, J. Polym. Sci. Part A: Polym. Chem. 2009, 47,
959–972.
[32] a-CD may undergo weak interaction with C6H3-3,5-(OMe)2. For ex-
amples of complexation of a-CD with C6H5OMe, see: a) I. B. Golo-
vanov, S. M. Zhenodarova, I. G. Tsygankova, Russ. J. Gen. Chem.
2006, 76, 267–271; b) E. Estrada, I. Perdomo-Lꢃpez, J. J. Torres-
Labandeira, J. Chem. Inf. Comput. Sci. 2001, 41, 1561; c) Q.-X. Guo,
S.-H. Luo, Y.-C. Liu, J. Inclusion Phenom. Mol. Recognit. Chem.
1998, 30, 173–182.
[22] a) K. Kalyanasundaram, J. K. Thomas, J. Am. Chem. Soc. 1977, 99,
2039–2044; b) C. B. Roxlo, H. W. Deckman, B. Abeles, Phys. Rev.
Lett. 1986, 57, 2462–2465.
[33] a) P. C. Manor, W. Saenger, J. Am. Chem. Soc. 1974, 96, 3630–3639;
b) M. J. Gidley, S. M. Bociek, J. Am. Chem. Soc. 1988, 110, 3820–
3829.
[23] a) T. Okubo, H. Kitano, N. Ise, J. Phys. Chem. 1976, 80, 2661–2664;
b) A. Diaz, P. A. Quintela, J. M. Schuette, A. E. Kaifer, J. Phys.
Chem. 1988, 92, 3537–3542; c) E. Junquera, E. Aicart, G. Tardajos,
J. Phys. Chem. 1992, 96, 4533–4537; d) A. Toki, H. Yonemura, T.
Matsuo, Bull. Chem. Soc. Jpn. 1993, 66, 3382–3386; e) G. M. Nic-
olle, A. E. Merbach, Chem. Commun. 2004, 854–855; f) E. Mileo, P.
Franchi, R. Gotti, C. Bendazzoli, E. Mezzina, M. Lucarini, Chem.
Commun. 2008, 1311–1313.
[24] a) C. Park, I. H. Lee, S. Lee, Y. Song, M. Rhue, C. Kim, Proc. Natl.
Acad. Sci. USA 2006, 103, 1199–1203; b) Y. Wang, N. Ma, Z. Wang,
X. Zhang, Angew. Chem. 2007, 119, 2881–2884; Angew. Chem. Int.
Ed. 2007, 46, 2823–2826; c) J. Zou, F. Tao, M. Jiang, Langmuir
2007, 23, 12791–12794; d) Y. Wang, H. Xu, X. Zhang, Adv. Mater.
2009, 21, 2849–2864.
[25] a) T. Taira, Y. Suzaki, K. Osakada, Chem. Lett. 2008, 37, 182–183;
b) T. Taira, Y. Suzaki, K. Osakada, Chem. Asian J. 2008, 3, 895–902.
[26] The pseudorotaxanes in this study may be alternatively termed
“semirotaxanes”, since supramolecule with a stopper at one end of
the axle component are sometimes classified into a subdivision of
pseudorotaxanes; a) R. S. Wylie, D. H. Macartney, J. Am. Chem.
Soc. 1992, 114, 3136–3138; b) J.-P. Collin, P. GaviÇa, J.-P. Sauvage,
New J. Chem. 1997, 21, 525–528; c) C. Seel, A. H. Parham, O. Safar-
owsky, G. M. Hꢂbner, F. Vçgtle, J. Org. Chem. 1999, 64, 7236–7242.
We prefer to refer to the present supramolecules as “pseudorotax-
anes” to avoid confusion and because “pseudorotaxane” is em-
ployed more commonly in reports on this area.
[34] a) A. Harada, M. Kamachi, Macromolecules 1990, 23, 2821–2823;
b) I. N. Topchieva, A. E. Tonelli, I. G. Panova, E. V. Matuchina,
F. A. Kalashnikov, V. I. Gerasimov, C. C. Rusa, M. Rusa, M. A.
Hunt, Langmuir 2004, 20, 9036–9043.
[35] a) Y. He, P. Fu, X, Shen, H. Gao, Micron 2008, 39, 495–516; b) P.
Jara, L. Barrientos, B. Herrera, I. Sobrados, J. Chil. Chem. Soc.
2008, 53, 1474–1476.
[36] a) J. E. Eldridge, J. D. Ferry, J. Phys. Chem. 1954, 58, 992–995; b) A.
Takahashi, M. Sakai, T. Kato, Polym. J. 1980, 12, 335–341.
[37] K. Murata, M. Aoki, T. Suzuki, T. Harada, H. Kawabata, T. Komori,
F. Ohseto, K. Ueda, S. Shinkai, J. Am. Chem. Soc. 1994, 116, 6664–
6676.
´
´
´
ˇ ´
´
´
[38] a) J. Makarevic, M. Jokic, B. Peric, V. Tomisic, B. Kojic-Prodic, M.
ˇ
´
´
´
Zinic, Chem. Eur. J. 2001, 7, 3328–3341; b) J. Makarevic, M. Jokic,
ˇ
ˇ
´
´
´
´
Z. Raza, Z. Stefanic, B. Kojic-Prodic, M. Zinic, Chem. Eur. J. 2003,
9, 5567–5580; c) D. Rizkov, J. Gun, O. Lev, R. Sicsic, A. Melman,
Langmuir 2005, 21, 12130–121388.
[39] The equilibrium constant of the reaction of [py-N-nBu]
a-CD was estimated by Benesi–Hildebrand plot to be 21(1) mÀ1
which is much smaller than those of [1ba-CD)]Cl and [1b·(a-
CD)2]Cl. The effect of complexation of [py-N-nBu]
+A(ClÀ) and a-CD
CHTUNGTRENNUNG
+A(ClÀ) and
,
ACHTUNGTRENNUNG
CTHUNGTRENNUNG
was considerably less significant for the phase transition.
[40] Pseudorotaxanes with channel-type arrangement generally show
high crystallinity, which makes the complexes separate from aqueous
solutions.
[3]Pseudorotaxanes
[4,4’-bpy-N-(CH2)10OC6H3-3,5-
(OMe)2·A CHUTNGTRENNUNG
G
3 A
[27] For examples of stereoselective synthesis of cyclodextrin[3]rotax-
anes, see: a) A. G. Cheetham, T. D. W. Claridge, H. L. Anderson,
Org. Biomol. Chem. 2007, 5, 457–462; b) H. W. Daniell, E. J. F.
Klotz, B. Odell, T. D. W. Claridge, H. L. Anderson, Angew. Chem.
2007, 119, 6969–6972; Angew. Chem. Int. Ed. 2007, 46, 6845–6848;
c) S. Tsuda, J. Terao, Y. Tanaka, T. Maekawa, N. Kambe, Tetrahe-
dron Lett. 2009, 50, 1146–1150.
crystalline solids, which have a similar structure to 1bCl, which sug-
gests that terminal aromatic moiety of axle molecules have signifi-
cant importance for formation of A.[25,41] See also: D.-R. Yei, S.-W.
Kuo, H.-K. Fu, F.-C. Chang, Polymer 2005, 46, 741–750.
[41] Interaction energy of the complex of [py-N-Me]+ and C6H3-1,3,5-
(OMe)3 is calculated to be À19.0 kcalmolÀ1 (DG=À6.93 kcalmolÀ1).
See Supporting Information.
[28] a) H. Saito, H. Yonemura, H. Nakamura, T. Matsuo, Chem. Lett.
1990, 19, 535–538; b) H. Yonemura, M. Kasahara, H. Saito, H. Na-
kamura, T. Matsuo, J. Phys. Chem. 1992, 96, 5765–5770; c) M. Hari-
haran, P. P. Neelakandan, D. Ramaiah, J. Phys. Chem. B 2007, 111,
11940–11947.
[29] M. V. Rekharsky, Y. Inoue, Chem. Rev. 1998, 98, 1875–1917.
[30] Kinetically controlled unidirectional pseudorotaxane formation of
a-CD and N-alkyl pyridinium compounds: a) T. Oshikiri, Y. Taka-
shima, H. Yamaguchi, A. Harada, J. Am. Chem. Soc. 2005, 127,
12186–12187; b) T. Oshikiri, Y. Takashima, H. Yamaguchi, A.
Harada, Chem. Eur. J. 2007, 13, 7091–7098; c) H. Yamaguchi, T.
Oshikiri, A. Harada, J. Phys. Condens. Matter 2006, 18, S1809-S1816.
[31] For examples of isomerization of pseudorotaxanes containing a-CD
and N-alkyl pyridinium compounds: a) D. H. Macartney, J. Chem.
Soc. Perkin Trans. 2 1996, 2775–2778; b) J. W. Park, H. J. Song, Org.
Lett. 2004, 6, 4869–4872; c) J. W. Park, H. J. Song, Y. J. Cho, K. K.
Park, J. Phys. Chem. C 2007, 111, 18605–18614.
[42] a) H. Ritter, F. Koch-Nolte, V. E. Marquez, G. E. Schulz, Biochem-
istry 2003, 42, 10155–10162; b) D. T. Major, J. Gao, J. Am. Chem.
Soc. 2006, 128, 16345–16357; c) S. Yamamoto-Katayama, M.
Ariyoshi, K. Ishihara, T. Hirano, H. Jingami, K. Morikawa, J. Mol.
Biol. 2002, 316, 711–723; d) B. F. Eichman, E. J. OꢄRourke, J. P.
Radicella, T. Ellenberger, EMBO J. 2003, 22, 4898–4909.
[43] S. Tsuzuki, M. Mikami, S. Yamada, J. Am. Chem. Soc. 2007, 129,
8656–8662.
[44] a) I. Richter, J. Minari, P. Axe, J. P. Lowe, T. D. James, K. Sakurai,
S. D. Bull, J. S. Fossey, Chem. Commun. 2008, 1082–1084; b) I.
Richter, M. R. Warren, J. Minari, S. A. Elfeky, W. Chen, M. F.
Mahon, P. R. Raithby, T. D. James, K. Sakurai, S. J. Teat, S. D. Bull,
J. S. Fossey, Chem. Asian J. 2009, 4, 194–198.
Received: December 3, 2009
Published online: April 21, 2010
Chem. Eur. J. 2010, 16, 6518 – 6529
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6529