Sugar-integrated gelators of organic solvents - Their remarkable diversity in gelation ability and aggregate structure

Article abstract of DOI:10.1002/(SICI)1521-3765(19990903)5:9<2722::AID-CHEM2722>3.0.CO;2-N

Five 1-O-methyl-4,6-O-benzylidene derivatives of the monosaccharides D-glucose, D-galactose, and D-mannose were synthesized. The β-isomer of the D-glucose derivative was sparingly soluble in most organic solvents, whereas the α-isomer of the D-mannose derivative was soluble in many organic solvents. The α-isomer of the D-glucose derivative and the α- and β-isomers of the D-galactose derivative acted as versatile gelators of various organic solvents; this indicates that saccharides are useful as potential templates for the molecular design of chiral gelators. In particular, the two D-galactose-based gelators behaved as "excellent gelators". It is very surprising that a change in the configuration of only one carbon atom results in such a drastic change in the solubility and the gelation properties. The possible relationship between the saccharide structure and the gelation properties is discussed on the basis of FT-IR and ¹H NMR spectroscopic data, differential scanning calorimetric (DSC) measurements, scanning electron microscopy (SEM) observations, and computational studies. FT-IR spectroscopy showed that the gelation properties are related to the formation of "moderate" intermolecular hydrogen bonds. The SEM observations showed that the gelators can form various fibrous structures (straight, puckered, and helical). The present study shows that this saccharide family is a potential combinatorial library of organic gelators and more generally, of molecular assembly systems.

Full text of DOI:10.1002/(SICI)1521-3765(19990903)5:9<2722::AID-CHEM2722>3.0.CO;2-N

FULL PAPER
Sugar-Integrated Gelators of Organic SolventsÐTheir Remarkable Diversity
in Gelation Ability and Aggregate Structure
[
a]
[a]
[a]
[b]
Kenji Yoza, Natsuki Amanokura, Yoshiyuki Ono, Tetsuyuki Akao,
[c]
[c]
[a]
[d]
Hideyuki Shinmori, Masayuki Takeuchi, Seiji Shinkai,* and David N. Reinhoudt
Abstract: Five 1-O-methyl-4,6-O-ben-
zylidene derivatives of the monosac-
charides d-glucose, d-galactose, and d-
mannose were synthesized. The b-iso-
mer of the d-glucose derivative was
sparingly soluble in most organic sol-
vents, whereas the a-isomer of the d-
mannose derivative was soluble in many
organic solvents. The a-isomer of the d-
glucose derivative and the a- and b-
isomers of the d-galactose derivative
acted as versatile gelators of various
organic solvents; this indicates that sac-
charides are useful as potential tem-
plates for the molecular design of chiral
gelators. In particular, the two d-galac-
tose-based gelators behaved as ªexcel-
lent gelatorsº. It is very surprising that a
change in the configuration of only one
carbon atom results in such a drastic
change in the solubility and the gelation
properties. The possible relationship
between the saccharide structure and
the gelation properties is discussed on
orimetric (DSC) measurements, scan-
ning electron microscopy (SEM) obser-
vations, and computational studies. FT-
IR spectroscopy showed that the gelat-
ion properties are related to the forma-
tion of ªmoderateº intermolecular hy-
drogen bonds. The SEM observations
showed that the gelators can form var-
ious fibrous structures (straight, puck-
ered, and helical). The present study
shows that this saccharide family is a
potential combinatorial library of organ-
ic gelators and more generally, of mo-
lecular assembly systems.
1
the basis of FT-IR and H NMR spec-
troscopic data, differential scanning cal-
Keywords: hydrogen bonds ´ mo-
lecular assembly ´ organic gels ´
saccharides ´ sol ± gel processes ´
sugars ´ supramolecular chemistry
Introduction
for molecular aggregation: hydrogen-bond-based gelators and
nonhydrogen-bond-based gelators. Typical examples of the
[1±4]
The development of new gelators of organic solvents has
recently received much attention. They not only gelatinize
various organic solvents but also create novel networks with
fibrous superstructures that can be characterized by SEM
pictures of the xerogels.[1±11] The gelators can be classified into
two categories according to the difference in the driving force
former group are aliphatic amide derivatives,
and of the
latter group, cholesterol derivatives.[
6±9]
The superstructures
observed as fibrous aggregates in the organic gels of aliphatic
amide derivatives satisfy the complementarity for intermo-
[5±9]
lecular hydrogen-bond interactions.
This observation
stimulated us to use saccharides as a hydrogen-bond-forming
segment in gelators, because one can then easily introduce a
variety of hydrogen-bond-forming, chiral segments into the
gelators by appropriate selection from a saccharide library. It
is expected, therefore, that many sugar-integrated gelators can
be readily designed by substituting this segment only, leading
eventually to new chiral gelators. However, literature exam-
[
a] Prof. S. Shinkai, Dr. K. Yoza, N. Amanokura, Y. Ono
Chemotransfiguration Project
Japan Science and Technology Corporation
Aikawa, Kurume, Fukuoka 839 ± 0861 (Japan)
Fax : (‡ 81)942399012
e-mail: seijitcm@mbox.nc.kyushu-u.ac.jp
[
[
[
b] Dr. T. Akao
ples of saccharide-containing gelators are very limited in spite
Biotechnology and Food Research Institute
Fukuoka Industrial Technology Center
Aikawa, Kurume, Fukuoka 839-0861 (Japan)
of their high potential.[
8, 12]
In this paper, we report on the
syntheses of the a-isomers of the glucose derivative 1a, the
galactose derivative 2a, and the mannose derivative 3a and
the b-isomers of the glucose derivative 1b and the galactose
derivative 2b and their gelation abilities. We found that the
gelation properties (e.g., gel stability, gel fiber superstructure,
solvent dependence, etc.) are clearly related to the saccharide
structure.[
c] Dr. H. Shinmori, Dr. M. Takeuchi
Department of Chemistry and Biochemistry
Graduate School of Engineering
Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)
d] Prof. D. N. Reinhoudt
Chemotransfiguration Project, Faculty of Chemical Technology
University of Twente, 7500 AE Enschede (The Netherlands)
13]
2
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2
722±2729
Concentration dependence: In
Figure 1, the sol ± gel phase tran-
sition temperatures (T ) of 1a,
gel
2
a, 3a, and 2b in toluene and
diphenyl ether are plotted
against the gelator concentration
in order to compare their gelat-
ion properties. Figure 1 shows
that in both solvents the Tgel
values at the same gelator con-
centration always appear in the
order 2a > 1a > 3a for the a-
isomers, whereas the Tgel values
for 2b are always higher than
those for 2a. Figure 2 shows
similar plots in benzene, carbon
tetrachloride, and water. Again,
a similar trend is observed here;
both in benzene and in carbon
tetrachloride, the Tgel values for
Results and Discussion
2a are higher than those for 1a. Judging from the foregoing
gelation test, one may conclude that the cohesive nature of the
five gelators decreases in the order 1b > 2b > 2a > 1a > 3a.
Gelation test for various organic solvents: The synthesis of 1a
[
14]
has already been reported.
The other gelators were
synthesized in a similar manner by treatment of the corre-
Table 1. Organic solvents tested for gelation by 1a, 1b, 2a, 2b, and 3a.[a]
sponding saccharides with benzaldehyde and ZnCl . The
2
1
1a
1b
2a
2b
3a
products were identified by H NMR and IR spectroscopy and
elemental analyses (see the Experimental Section).
The gelation test was carried out as follows: the gelator
Group I
n-hexane
n-heptane
n-octane
cyclohexane
methylcyclohexane
benzene
toluene
p-xylene
nitrobenzene
carbon tetrachloride
carbon disulfide
diethyl ether
diphenyl ether
ethyl formate
methyl acetate
n-octanol
triethylamine
triethylsilane
tetraethoxysilane
water
G*
P
G*
P
G*
G
G*
G*
S
G*
P
G
G*
S
S
S
S
P
P
P
P
P
P
P
P
P
P
P
P
P
G
P
G
P
P
P
P
P
P
P
G*
G*
G*
G*
G*
G*
G*
G*
S
G*
G*
G*
G*
P
S
G
G
Gp
G*
S
G*
G*
G*
G*
G*
G*
G*
G*
Gp
G*
G*
P
G*
Gp
Gp
G
G
G
G*
G*
G*
G*
G*
P
G*
G*
S
P
G*
P
G
S
(3.0 mg) was mixed with solvent (0.10 mL) in a septum-
capped test tube, and the mixture was heated until the solid
dissolved. The solution was cooled to 258C and left for 1 h. A
ªGº in Table 1 denotes that a gel was formed at this stage.
Some solutions gelled at a gelator concentration below 1.0%
(wt/vol) and are designated ªG*º in Table 1. Solvents in
Group I are those which were gelatinized by some gelators.
Solvents in Group II are those in which all the gelators were
[
15]
either too soluble or precipitated.
From examination of
Table 1, several interesting points can be inferred as charac-
teristic of sugar-integrated gelators. Firstly, among the three
a-isomers, 2a is the best gelator of many organic solvents.
Secondly, comparison of the gelation ability for n-hexane,
cyclohexane, and Group II solvents reveals that 1a is more
cohesive and tends to form a precipitate, whereas 3a is more
soluble than the other two gelators and is frequently unable to
coagulate in solution. Thirdly, the b-isomer of galactose
derivative 2b also acts as an excellent gelator, comparable
with 2a. Finally, the solubility of the b-isomer 1b is generally
inferior to that of the a-isomer 1a as indicated by the
numerous ªPº (P ˆ precipitation) entries for 1b and the ªSº
S
S
S
G*
P
P
S
G
Group II
1,2-dichloroethane
S
S
S
S
S
S
S
S
S
P
P
S
S
S
P
P
P
P
P
P
P
P
P
P
P
P
P
P
S
S
S
P
S
S
S
S
S
P
S
P
S
S
S
S
S
S
S
S
S
S
S
P
P
P
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
dichloromethane
chloroform
ethyl acetate
ethyl malonate
acetone
methyl ethyl ketone
acetonitrile
ethanol
n-propanol
n-butanol
hexanoic acid
acetic anhydride
glycerol
(
S ˆ solution) entriees for 1A.
As seen from the saccharide structures illustrated above,
1
a, 2a, and 3a are epimers that differ only in the carbon
configuration at either C-2 or C-4, whereas 1a ± 1b and 2a ±
b are anomers with one different carbon configuration at
2
C-1. It is surprising that a difference in the carbon config-
uration results in such a marked difference in the solubility or
gelation properties. The possible rationale for the structure-
gelation relationship is discussed below.
[
a] G ˆ gel; G* ˆ gelated even under 1.0 wt/vol%; Gp ˆ partial gel; P ˆ
precipitation; S ˆ solution.
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S. Shinkai et al.
FULL PAPER
However, we do not consider that this corresponds with a
ªperfectº gel-monomer transition. For example, we observed
the sol ± gel phase transition under an optical microscope.
Although the mobility of the solution system was drastically
increased above the Tgel, small aggregate particles still exist.
One may consider, therefore, that some gelators aggregate
even in the solution phase.
�
1
As shown in Figure 3, plots of log[gelator] against T
gel
afforded straight lines with g(correlation coefficient) >0.97.
The DH values estimated on the basis of Equation 1 are
Figure 1. Plots of
diphenyl ether: 1a/diphenyl ether (*), 1a/toluene (*), 2a/diphenyl ether
), 2a/toluene (
), 3a/diphenyl ether (^), 3a/toluene (^), 2b/diphenyl
Tgel against gelator concentration in toluene and
(
&
&
ether (~), 2b/toluene (~).
Figure 3. Plots of log[gelator] (gelator concentration in moldm 3) against
�
�
1
T
gel. A) (toluene and diphenyl ether system): 1a/toluene (*), 1a/diphenyl
), 2a/diphenyl ether (
ether (*), 2a/toluene ( ), 3a/toluene (^), 3a/
diphenyl ether (^), 2b/toluene (~), 2b/diphenyl ether (~). B) (benzene,
CCl , and water system); 1a/benzene (Â), 1a/CCl
(‡), 2a/benzene (!),
a/CCl ).
(!), 3a/water (&
&
&
Figure 2. Plots of Tgel against gelator concentration in benzene, carbon
tetrachloride, and water: 1a/benzene (*), 1a/CCl
CCl
), 3a/water (^).
(*), 2a/benzene (
), 2a/
&
4
4
4
4
(
&
2
4
‡
Previously, we derived [Eq. (1)] from a Schraderꢁs relation
frequently used for the dissolution of solid compounds in
organic solvents. DH can be determined from the slope of a
summarized in Table 2. The DH values at the melting points
f
as determined by DSC mesurements were 23, 27, 22, 25, and
[
7]
� 1
26 kJmol for 1a, 2a, 3a, 1b, and 2b, respectively. Although
DH
1
log[gelator] ˆ �
Â
‡ constant
(1)
2
:303 R
T
gel
Table 2. DH obtained from [gelator] vs. Tgel plots and DH
f
at the melting
point obtained from DSC measurements.
plot of log[gelator] (with the gelator concentration given in
DH kJmol 1
�
DH
kJmol
� 1
�
3
� 1
f
mol � 1dm ) against T . It is known that the DH values are
gel
Toluene Diphenyl ether Benzene CCl
4
Water
comparable with or slightly larger than the latent heat of
[
a]
1
2
3
a
a
a
43
40
41
33
35
28
±
42
37
ppt
ppt[a]
±
40
45
ppt
ppt
S
23
27
22
25
26
fusion DH values determined from DSC measurements at the
f
[b]
[
7]
melting point of the solid. This might indicate that the DH
values reflect the heat released at the sol ± gel phase transition
temperature. This implies albeit indirectly that the gelator
fibers formed in organic solvents are not so solvated with
[c]
[a]
[a]
22
1b ppt[a]
2b 49
ppt[a] ppt[a]
[
b]
44
±
S
[a] Gelators were precipitated from these solvents. [b] Gelator were
[
7, 16]
solvent molecules.
soluble in these solvents. [c] The correlation coefficient in Figure 3 is 0.97.
2
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Sol±gel Processes
2722±2729
the DH values decrease in the order 2a > 2b > 1b > 1a > 3a,
f
the differences are relatively small. As described later under
the FT-IR measurements, the nOH peak assignable to the free
OH group could not be found for the solid gelator samples.
This means that in the solid state all the OH groups in these
gelators form either intramolecular or intermolecular hydro-
gen bonds. This situation should result in averaged DH values.
f
It is interesting to note, however, that the excellent gelators 2a
and 2b have relatively large DH values, whereas the very
f
[
17]
soluble gelator 3a has a relatively small DH value. Table 2
f
also shows that the DH values are generally larger than the
DHf values and have characteristic solvent dependence.
Firstly, DH values in the hydrocarbon solvents, toluene and
benzene, are generally larger than in oxygen-containing
solvents (diphenyl ether). This implies that diphenyl ether
acts as a hydrogen-bond acceptor and weakens the network
formation based on the intermolecular hydrogen-bond inter-
action. Secondly, 3a ± diphenyl ether and 3a ± water systems
�
1
have small DH values, 28 and 22 kJmol respectively. Gelator
a is relatively soluble in these solvents, and the gel is
3
obtained only in the high concentration region (see Figures 1
and 2). Thus, a small DH value is attributed to the affinity (or
partial dissolution) of the gelator for solvent molecules.
Clearly water is not a favorable solvent for gelation with
sugar-integrated gelators that utilize the intermolecular
hydrogen-bond interaction for network formation. However,
it is rather surprising that water could be gelatinized by 3a.
Thirdly, 2b which is the best of the five gelators tested herein
affords the largest DH values. This finding indicates that the
stable gel formation with high Tgel is related to the formation
of stable, intermolecular hydrogen bonds, as reflected in the
large DH values.
Figure 4. FT-IR spectra at 258C of: A) 1a/toluene system (0.80% (wt/vol))
and B) 2a/toluene system (0.28% (wt/vol)).
The order of the DH values is solvent dependent. Generally
speaking however, the order is 2b > 1a ꢀ 2a > 3a. This order
is roughly coincident with the DH values and also supports
f
� 1
Table 3. nOH bands (cm ) of the gels prepared from the toluene solutions.
the view that the gel fibers are not so solvated with solvent
molecules, but are composed of aggregates of solid-like
particles.
�
Concentration
(wt/vol)%]
Free OH [cm 1][a]
Hydrogen-bonded
OH [cm ]
�
1 [a]
[
1
2
3
1b
2b
a
a
a
0.60
0.26
0.60
0.40 (ppt)
0.15
3577(sh)
3573(sh)
3577(sh)
3577(sh)
3588(sh)
3328(br), 3389(br)
3314(sh), 3429(sh), 3475(sh)
3235(br), 3350(br)
3220(br), 3377(br)
3280(sh), 3373(sh), 3440(sh)
Intermolecular hydrogen-bond interactions as detected by
FT-IR spectroscopy: In the FT-IR spectra, the n peak of the
[b]
OH
�
1
free OH group (at around 3600 cm ) was not found for solid
samples of the five gelators. This indicates that all the OH
groups form either intermolecular or intramolecular hydro-
gen bonds. On the other hand, the gel solutions exhibited two
[
a] sh ˆ sharp peak; brˆ broad peak. [b] The sample is the solution
containing the precipitate.
�
1
peaks at 3220 ± 3475 and 3573 ± 3588 cm in the nOH region,
which could be assigned to hydrogen-bonded OH and free
OH groups, respectively. Typical FT-IR spectra are shown in
Figure 4. The 1a ± toluene system shows two broad peaks
This might mean that the hydrogen-bond interaction in these
systems is more ordered, with a high degree of complemen-
tartiy between the hydrogen-bond-forming OH groups. It is
important to note that 2a and 2b, which show the three sharp
nOH peaks, are excellent gelators. These findings lead us to
conclude that in these systems the complementarity of the OH
groups is the primary factor in controlling organic gel stability.
Figure 5 shows that the peak intensity ratio (R) of hydro-
gen-bonded OH to free OH abruptly increases at the sol ± gel
phase transition concentration. For excellent gelators such as
2a and 2b, the nOH peaks for hydrogen-bonded OH groups
appear even at low gelator concentrations [ca. 0.1 ± 0.2% (wt/
vol)], whereas those for 1a and 3a appear only at high gelator
�
1
around 3328 and 3389 cm in addition to a nOH peak at
�
1
3
577 cm for free OH groups. The 1b ± toluene and 3a ± tol-
uene systems exhibit similar broad nOH peaks for the hydro-
gen-bonded OH groups. The appearance of the broad peaks
suggests that the hydrogen-bonded network in these systems
is relatively disordered. On the other hand, in the 2a ± toluene
system there are three sharp peaks at 3314, 3429, and
�
1
� 1
3
475 cm in addition to a peak at 3573 cm for free OH
groups. The 2b ± toluene system was similar to the 2a ± to-
luene system, in giving rise to three sharp nOH peaks, Table 3.
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S. Shinkai et al.
FULL PAPER
Figure 5. Plots of the peak intensity ratio R of hydrogen bonded to free
OH groups as a function of gelator concentration in toluene at 208C. There
are two major peaks for hydrogen-bonded OH groups; the filled points
�
1
were obtained from the intensities at nOH ˆ 3220 ± 3314 cm , whereas the
Figure 6. Plots of dOH the OH group chemical shift and d1/2 the half-height
peak width of the PhCH methine proton peak against temperature; [1a] ˆ
�
1
open points were obtained from those at nOH ˆ 3350 ± 3429 cm ; (*,*) 1a,
(
,
& &
) 2a, (^,^) 3a, and (~,~) 2b. The arrows indicate the sol ± gel transition
[
2a] ˆ [3a] ˆ 2.0% (wt/vol) in [D
8
]toluene. There are two peaks for the OH
temperature of i) 1a, ii) 2a, iii) 3a, and iv) 2b.
groups: (*,*) 1a, (
&
,
&
) 2a, (^,^) 3a; d1/2 (*) 1a, (
) 2a, (^) 3a, (~) 2b. The
&
arrows indicate the sol ± gel transition temperature of i) 1a, ii) 2a, iii) 3a,
and iv) 2b.
concentrations [ca. 0.5% (wt/vol)]. In particular, the value of
R for 3a increases very gradually with increasing 3a concen-
tration. This means that 3a is very soluble in toluene and the
gel fibers are created gradually under the disadvantageous
condition by which an equilibrium of monomeric 3a with
aggregated 3a favours monomeric 3a . It is not yet clear what
structural factor governs the magnitude of the R value. If this
measure could be correlated with the complementarity of the
intermolecular hydrogen bonds, 2b would be expected to have
one of the highest R values as in fact it does (Figure 5). How-
ever, 1a is significantly inferior to 2a in its gelation ability, but
of the PhCH methine proton is nearly constant above the Tgel
,
while it increases with falling temperature below the Tgel. The
results imply that the mobility of gelator molecules is
significantly suppressed in the gel phase, whereas it is
comparable with that of the homogeneous solution in the
sol phase. On the other hand, plots of dOH (chemical shift of
the OH groups) against temperature for 1a, 2a, and 3a show
that the chemical shifts have their maximum downfield values
at the Tgel. In general, the formation of strong hydrogen bonds
[
18]
[20, 21]
it has an R value comparable with 2a.
It is likely therefore,
with OH groups induces a downfield shift of dOH
.
Hence,
that the R value reflects mainly the structure of the solid-like
gel fibers, whereas the gelation ability is related not only to
the fiber structure but also to the solubility of gelators or their
affinity for solvent molecules. This difference may cause the
disagreement between the gelation ability and the R value.
The foregoing FT-IR spectroscopic data consistently sup-
port the view that the gel network in the present system is
primarily stabilized by intermolecular hydrogen bonding.
Judging from the plots in Figure 5, the molecular coagulation
tendency decreases in the order: 2b > 2a > 1a > 3a. This
order coincides with that estimated from the gelation test
the hydrogen bonds with the OH groups are strengthened
with lowering of the medium temperature from the sol phase
to the Tgel region. This change is explicable in terms of
intermolecular aggregation near the gel region. In contrast, it
is difficult to explain why the hydrogen bonds are gradually
weakened as the medium temperature falls in the gel phase.
Presumably, in the Tgel region the formation of the ªsoft gelº is
predominantly governed by the intermolecular hydrogen-
bond interaction, but at temperatures much lower than Tgel,
the formation of the crystal-like ªhard gelº [
7, 16]
is governed
not only by the intermolecular hydrogen-bond interaction but
also by other intermolecular forces such as p ± p interactions,
van der Waals interactions, etc.[ In cases in which the latter
forces cannot harmonize with the hydrogen-bond interaction
because of steric mismatching, the hydrogen bonds may be
weakened with decreasing medium temperature. In any event,
(vide supra).
10]
1
Temperature-dependent H NMR spectra: It is to be expected
that the molecular motion of gelators drastically changes at
the sol ± gel phase transition temperature Tgel. This change can
be conveniently monitored by the line-broadening effect in
the 1H NMR spectrum. In fact, such a phenomenon has
1
it is clear that H NMR spectroscopy is a potential tool for
studying the formation of organic gels.
[
19]
already been reported for a related gel system. We have
1
measured the H NMR spectra of 1a, 2a, 3a [each at 2.0%
SEM observations of xerogels: In order to obtain visual
insights into the aggregation mode, we have prepared dry
samples of organic gel fibers for SEM studies.[ Figure 7 (a
(
wt/vol)], and 2b [0.50% (wt/vol)] in [D ]toluene at 25 ±
8
22]
838C. As shown in Figure 6, the half-height peak width d1/2
2
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Chem. Eur. J. 1999, 5, No. 9

Sol±gel Processes
2722±2729
Figure 8. Energy-minimized structures of 1a, 2a, 3a, 1b, and 2b in their
C1 forms predicted on the basis of MM3 calculations.
It is known that the physical properties of certain gelators
are affected by epimeric effects.[ In the present system, the
solubility of 1b is the lowest of the five saccharide-based
gelators tested herein (Table 1). Two features of this com-
pound are that the molecular structure is relatively ªflatº,
because of the b-configuration of the 1-OMe group, and two
unmodified OH groups occupy the sterically less crowded
equatorial position. These steric characteristics should facil-
itate intermolecular aggregation, which occurs through the
stacking of pyranose rings and hydrogen-bond interaction
among the OH groups. In contrast, the solubility of 3a is the
highest of the five saccharide-based gelators tested here
(Table 1). Two relevant features of this compound are that the
molecular structure is l-configured, because of the a-config-
uration of the 1-OMe group, and one of the two unmodified
OH groups occupies the sterically more crowded axial
position. In fact, of the five gelators, only 3a has an axial
OH group. These steric characteristics should suppress the
intermolecular aggregation tendency and eventually enhance
the solubility. Gelator 1a, which has an a-1-OMe group and
two equatorial OH groups, has intermediate solubility and
gelation properties between 1b and 3a (Table 1).
So why do 2a and 2b, prepared from d-galactose, possess
such excellent gelation ability? Based on the above discus-
sion, it is beyond doubt that the primary reason is related to
their axial 4-OR substituent, which forces 2a and 2b to adopt
an l-configuration. As seen in Figure 8, the pyranose rings are
almost perpendicular to the benzene rings, an orientation that
hinders intermolecular aggregation. But they have two
equatorial OH groups which favor intermolecular aggrega-
tion. These two opposing effects within the same gelator
molecule should create excellent gelation properties. As a
principle for the molecular design of gelators, therefore, one
may propose that they will produce a precipitate if the
intermolecular aggregation forces are too strong, whereas the
6b]
Figure 7. SEM pictures of 1a, 2a, 3a, and 2b: a) 1a prepared from carbon
tetrachloride [0.5% (wt/vol)], b) 2a prepared from carbon tetrachloride
[
0.5% (wt/vol)], c) 3a prepared from toluene [3.0% (wt/vol)], d) 2b
prepared from benzene [1.0% (wt/vol)], and e) 3a prepared from water
3.0% (wt/vol)].
[
and b) shows typical pictures obtained from xerogels of 1a or
a in carbon tetrachloride. It is clear that the gelators form a
2
three-dimensional network with 50 ± 200 nm puckered fibrils.
On the other hand, the fibrils obtained from the gel of 3a with
toluene and of 2b with benzene are more linear (Figure 7, c
and d). Interestingly, the fibrils obtained from the aqueous gel
of 3a show a regular left-handed helical structure, Figure 7e.
Presumably, in an aqueous system the balance between
hydrogen-bond interaction and hydrophobic interaction is
different from that in organic media. This problem is currently
under investigation to clarify a possible relationship between
the gelator structure and the aggregate morphology.
Computational studies: The above-mentioned results consis-
tently support the view that the slight difference in the
saccharide configuration is largely reflected by the solubility,
the gelation ability, and the superstructure of the gel fibers.
What is the origin of these differences? Although the gel fiber
structure is not necessarily the same as that obtained from the
[
5]
single-crystal X-ray studies, X-ray crystallography should
give some useful information. Unfortunately, these gelators
tend to grow as needles and single crystals suitable for X-ray
analysis have not been isolated so far. Thus, in order to obtain
some insight into the difference in the solubility (which is
eventually related to the gelation ability), we undertook some
computational studies with MM3. The energy-minimized
structures in their C1 forms are illustrated in Figure 8.
Chem. Eur. J. 1999, 5, No. 9
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2727

S. Shinkai et al.
FULL PAPER
gelators will be solubilized in solution if the intermolecular
forces are too weak. In addition, galactose-based 2a and 2b
have an additional structural characteristic that the other
gelators do not possess. In cyclohexane derivatives the bulky
substituent tends to occupy the equatorial position. This
stereochemical requirement should also be valid for the
pyranose ring. This is achieved by ring inversion of the C1
structure to the 1C structure, forcing the axial 1-OMe into an
equatorial position. In 1a, 1b, and 3a, however, both the
solvents. In the present system, these parameters tend to
appear in the order: 1b (too cohesive) > 1a, 2a, 2b (moder-
ately cohesive; suitable for gelation) > 3b (less cohesive; too
soluble). We believe that such a convenient synthetic route
and remarkable diversity in the gelation ability and the gel
fiber structure (including the creation of the helical structure)
can hardly be attained in a more simple fashion than with
saccharide templates. More concisely, the present paper has
shown the high potential of saccharide-based molecules for
gel formation. We believe that the saccharide library provided
by nature can be applied further, in particular to the design of
molecular assemblies, such as macrocycles, DNA mimics,
monolayers, bilayer membranes, liquid crystals, etc.
4
-OR and 5-CH OR groups occupy an equatorial position, so
2
that inversion to the 1C structure would force them into the
trans-axial position. This process is unrealistic because the
4
-OR and 5-CH OR groups form a 1,3-dioxane ring. In other
2
words, the C1 structure in Figure 8 is the only possible
conformation. In contrast, the 4-OR and 5-CH OR groups in
2
2
a and 2b occupy the axial and equatorial positions,
Experimental Section
respectively. Hence inversion of the pyranose ring is possible
to give structure 1C; in this conformation the 1-OMe group
can move to the less crowded equatorial position (Figure 9).
Methyl-4,6-O-benzylidene-a-d-glucopyranoside (1a): Compound 1a was
synthesized according to the method described in the literature.[
14]
A
mixture of benzaldehyde (5.0 mL, 49.5 mmol) and methyl-a-d-glucopyr-
anoside (2.0 g, 10.3 mmol) was stirred with zinc chloride (1.50 g, 11.0 mmol)
under a nitrogen atmosphere. The reaction was continued at room
temperature for 6 h. After the reaction mixture was added to water
(
50 mL), the product thus precipitated was collected by filtration. The
precipitate was washed with water and n-hexane and then reprecipitated by
chloroform/n-hexane: yield (2.27 g, 78%) (calculated from methyl-a-d-
1
glucopyranoside). M.p. 165.4 ± 166.88C; H NMR (300 MHz, CDCl
3
, 258C,
TMS): d ˆ 2.46 (brs, 1H; OH), 2.95 (brs, 1H; OH), 3.45 (s, 3H; OMe),
.48 ± 4.31 (m, 6H; sugar�CH (H2 ± 6)), 4.77 (d, 1H; sugar�H (H1)), 5.52
s, 1H; Ph�CH), 7.35 ± 7.38 (m, 3H; m,p-Ph�H), 7.45 ± 7.51 (m, 2H; o-
3
(
�
1
Ph�H); IR (KBr): nÄ ˆ 3650 ± 3100 (OH), 1030 cm (C�O�C); C14
282.3): calcd C 59.57, H 6.43; found C 58.21, H 6.55; C14 ´ 0.4H
requires C 58.07, H 6.56.
18 6
H O
(
H
18
O
6
2
O
Methyl-4,6-O-benzylidene-a-d-galactopyranoside (2a): Compound 2a was
synthesized by means of a method similar to that used for 1a:[ yield
13]
(
1
1
1.12 g, 39%) (calculated from methyl-a-d-galactopyranoside). M.p.
68.9 ± 170.58C; 1H NMR (300 MHz, CDCl
H; OH), 2.52 (brs, 1H; OH), 3.46 (s, 3H; OMe), 3.70 ± 4.31 (m, 6H;
, 258C, TMS): d ˆ 2.30 (brs,
3
sugar�CH (H2 ± 6)), 4.93 (d, 1H; sugar�H (H1)), 5.55 (s, 1H; Ph�CH),
Figure 9. Energy-minimized structures of 2a and 2b in their 1C forms
predicted on the basis of MM3 calculations.
7.36 ± 7.38 (m, 3H; m,p-Ph�CH), 7.48 ± 7.52 (m, 2H; o-Ph�H); IR (KBr):
�
1
nÄ ˆ 3640 ± 3100 (OH), 1030 cm (C�O�C); C H O (282.3): calcd C 59.57,
14
18
6
H 6.43; found C 58.09, H 6.35; C14
18 6 2
H O ´ 0.4H O requires C 58.07, H 6.56.
Methyl-4,6-O-benzylidene-a-d-mannopyranoside (3a): Compound 3a was
synthesized by means of a method similar to that used for 1a and was
This structural variation may improve the ability of 2a and 2b
to form a complementary hydrogen-bond network in their
aggregates and prevent precipitation or crystallization.[
Judging from the three above-mentioned charactistics, the l-
configuration, the presence of unique OH groups, and
interconversion between the C1 and the 1C forms, we can
conclude that d-galactose serves as the best template for
designing excellent gelators of organic solvents.
purified by column chromatography (silica gel, CHCl /MeOH 30:1 (v/v);
3
23]
R
f
ˆ 0.14). This product was reprecipitated by chloroform/n-hexane: yield
(
190 mg, 7%) (calculated from methyl-a-d-mannopyranoside). M.p.
1
1
31.1 ± 133.78C; H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 2.78 ± 2.82
(
4
m, 2H; OH), 3.39 (s, 3H; OMe), 3.77 ± 4.30 (m, 6H; sugar�CH (H2 ± 6)),
.73 (s, 1H; sugar H (H1)), 5.56 (s, 1H; Ph CH), 7.36 ± 7.39 (m, 3H; m,p-
�
�
Ph�H), 7.47 ± 7.51 (m, 2H; o-Ph�H); IR (KBr): n ˆ 3650 ± 3000 (OH),
�
1
1
5
020 cm (C�O�C); C14
H
18
O
6
(282.3): calcd C 59.57, H 6.43; found C
requires C 54.82, H 5.90.
4.89, H 5.94; C14 ´ 0.25CHCl
H
18
O
6
3
Methyl-4,6-O-benzylidene-b-d-glucopyranoside (1b): Compound 1b was
synthesized by means of a method similar to that used for 1a: yield (1.61 g,
5
5%) (calculated from methyl-b-d-glucopyranoside). M.p. 174 ± 1758C;
Conclusions
1
H NMR (300 MHz, CDCl
.39 ± 4.35 (m, 10H; OMe, and sugar�CH (H1 ± 6)), 5.54 (s, 1H; Ph�CH),
.26 ± 7.39 (m, 3H; m,p-Ph�H), 7.48 ± 7.51 (m, 2H; o-Ph�H); IR (KBr): nÄ ˆ
3700 ± 3200 (OH), 1030 cm� 1 (C�O�C); C H O (282.3): calcd C 59.57, H
3
, 258C, TMS): d ˆ 2.72 ± 2.87 (q, 2H; OH),
3
7
The present study has demonstrated that saccharides serve as
promising templates for the molecular design of new gelators
with different gelation properties and different three-dimen-
sional network structures. Surprisingly, we have found that the
gelation ability is drastically changed by a slight change in the
saccharide configuration. The gelation ability is predictable to
14
18
6
6.43; found C 59.36, H 6.49.
Methyl-4,6-O-benzylidene-b-d-galactopyranoside (2b): Compound 2b was
synthesized by means of a method similar to that used for 2a: yield (1.02 g,
3
5%) (calculated from methyl-b-d-glucopyranoside). M.p. 180.7 ± 182.98C;
1
H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 2.55 ± 2.59 (q, 2H; OH),
some extent from physical parameters, such as n from FT-IR,
�
�
OH
3.49 ± 4.38 (m, 10H; OMe, and sugar CH (H1 ± 6)), 5.56 (s, 1H; Ph CH),
7.26 ± 7.37 (m, 3H; m,p-Ph�H), 7.49 ± 7.52 (m, 2H; o-Ph�H); IR (KBr): nÄ ˆ
1
dOH from H NMR, DH from DSC, and solubility in organic
f
2
728
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0947-6539/99/0509-2728 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 9

Sol±gel Processes
2722±2729
�
1
3
6
700 ± 3200 (OH), 1030 cm (C�O�C); C14
H
18
O
6
(282.3): calcd C 59.57, H
[6] a) P. Terech, I. Fuman, R. G. Weiss, J. Phys. Chem. 1995, 99, 9558, and
references therein; b) P. Terech, J. J. Allegraud, C. M. Garner,
Langmuir 1998, 14, 3991.
.43; found C 59.23, H 6.48.
Gelation test: A gelator (3.0 mg) was mixed with solvent (0.10 mL) in a
septum-capped sample tube and heated in an oil bath until the solid was
dissolved. Then, the solution was cooled to 258C and left for 1 h. If a stable
gel was observed, it was classified as G in Table 1. When the gel was
obtained from a solution at a concentration even lower than 1.0% (wt/vol),
it was designated G*.
[
7] K. Murata, M. Aoki, T. Suzuki, T. Hanada, H. Kawabata, T. Komori, F.
Ohseto, K. Ueda, S. Shinkai, J. Am. Chem. Soc. 1994, 116, 6664, and
references therein.
[
[
8] T. D. James, K. Murata, T. Hanada, K. Ueda, S. Shinkai, Chem. Lett.
1
994, 273.
9] S. W. Jeong, K. Murata, S. Shinkai, Supramol. Sci. 1996, 3, 83.
Gel-sol phase transition temperatures: A test tube containing the gel was
inverted in a thermostatted oil bath. The temperature was raised at a rate of
8Cmin . Here, the Tgel was defined as the temperature at which the gel
[
10] T. Brotin, R. Utermolen, F. Fagles, H. Bouas-Laurent, J.-P. Desvergne,
J. Chem. Soc. Chem. Commun. 1991, 416.
�
1
2
[
11] a) J. van Esch, S. de Feyter, R. M. Kellogg, F. de Schryver, B. L.
Feringa, Chem. Eur. J. 1997, 3, 1238; b) R. Oda, I. Huc, S. J. Candau,
Angew. Chem. 1998, 110, 2835; Angew. Chem. Int. Ed. 1998, 37, 2689.
12] S. Yamasaki, H. Tsutsumi, Bull. Chem. Soc. Jpn. 1996, 69, 561, and
references therein.
disappears.
SEM observations: An Hitachi S-900S scanning electron microscope was
used for taking the SEM pictures. The thin gel was prepared in a sample
tube and frozen in liquid nitrogen. The frozen specimen was dried under
vacuum for 3 ± 5 h. The dry sample thus obtained was shielded by gold. The
accelerating voltage was 5 kV and the emission current was 10 mA.
[
[
13] K. Yoza, Y. Ono, K. Yoshihara, T. Akao, H. Shinmori, M. Takeuchi, S.
Shinkai, D. N. Reinhoudt, Chem. Commun. 1998, 907.
Apparatus for spectroscopy measurements: 1H NMR spectra were
measured with a Bruker ARX300 apparatus. IR spectra were obtained in
NaCl cells with a Shimazu FT-IR8100 spectrometer.
[14] M. Svaan, T. Anthonsen, Acta. Chem. Scand. Ser. B 1986, 40, 119.
[15] The following solvents were also tested: m-cresol, tetrahydrofuran,
dioxane, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl
sulfoxide, 1-methyl-2-pyrrolidone, methanol, benzyl alcohol, acetic
acid, n-propylamine, diethylamine, aniline, pyridine, and 2,2,2-tri-
fluoroethanol, but all the five gelators were too soluble in these
solvents and gels were not formed.
Computational methods: Energy minimization was carried out by a MM3
program with AccuModel1.0 (Microsimulation L. A. Systems Inc.) with a
Macintosh computer.
[
16] The same idea was also proposed by Weiss et al. on the basis of the
spectroscopic data in Ref. [5] and R. Mukkamala, R. G. Weiss, J.
Chem. Soc. Chem. Commun. 1995, 375.
[
1] a) K. Hanabusa, K. Okui, T. Koyama, H. Shirai, J. Chem. Soc. Chem.
Commun. 1992, 1371, and references therein; b) K. Hanabusa, M.
Yamada, M. Kimura, H. Shirai, Angew. Chem. 1996, 108, 2086; Angew.
Chem. Int. Ed. Engl. 1996, 35, 1949; c) K. Hanabusa, K. Shimura, K.
Hirose, M. Kimura, H. Shirai, Chem. Lett. 1996, 885; d) K. Hanabusa,
A. Kawakami, M. Kimura, H. Shirai, Chem. Lett. 1997, 191; e) T. Kato,
G. Kondo, K. Hanabusa, Chem. Lett. 1998, 193; f) Y. Hishikawa, K.
Sada, R. Watanabe, M. Miyata, K. Hanabusa, Chem. Lett. 1998, 795.
2] E. J. de Vries, R. M. Kellogg, J. Chem. Soc. Chem. Commun. 1993,
[17] A similar correlation between the DH and the gelator solubility was
found in a related system. See N. Amanokura, K. Yoza, H. Shinmori,
S. Shinkai, D. N. Reinhoudt, J. Chem. Soc. Perkin Trans. 2 1998, 2585.
[18] In a preliminary communication,[13] the explanation of this figure
(plots of R against gelator concentration) is partially confused.
[19] M. Aoki, K. Nakashima, H. Kawabata, S. Tsutsui, S. Shinkai, J. Chem.
Soc. Perkin Trans. 2 1993, 347.
[20] N. Inamoto, Hamme Rule, Maruzen, Tokyo, 1983, p. 90.
[21] K. Araki, K. Iwamoto, S. Shinkai, T. Matsuda, Bull. Chem. Soc. Jpn.
1990, 63, 3480.
[
[
238.
3] M. Takafuki, H. Ihara, C. Hirayama, H. Hachisako, K. Yamada, Liq.
Cryst. 1995, 18, 97.
[22] For the preparation of dry samples for SEM observations, see ref. [7]
and S. W. Jeong, S. Shinkai, Nanotechnology 1997, 8, 179.
[23] We estimated the heat of formation for C1 ± 2a and 1C ± 2a by
[
[
4] J.-E. S. Sobna, F. Fages, Chem. Commun. 1997, 327.
5] a) E. Otsuni, P. Kamaras, R. G. Weiss, Angew. Chem. 1996, 108, 1423;
Angew. Chem. Int. Ed. Engl. 1996, 35, 1324, and references therein;
b) P. Terech, R. G. Weiss, Chem. Rev. 1997, 97, 3133; c) Y-C. Lin, B.
Kachar, R. G. Weiss, J. Am. Chem. Soc. 1989, 111, 5542; d) I. Furman,
R. G. Weiss, Langmuir 1993, 9, 2084; e) L. Lu, R. G. Weiss, Langmuir
MOPAC PM3. However, the energy difference was not significant
enough to alter their relative stability (� 900 and � 875 kJmol� 1
respectively).
1995, 11, 3630; f) L. Lu, R. G. Weiss, Chem. Commun. 1996, 2029.
Received: December 21, 1998 [F1501]
Chem. Eur. J. 1999, 5, No. 9
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0947-6539/99/0509-2729 $ 17.50+.50/0
2729