Supramolecular hydrogel formed by glucoheptonamide of l-lysine: simple preparation and excellent hydrogelation ability

Article abstract of DOI:10.1016/j.tet.2007.02.065

We describe the simple preparation of new l-lysine derivatives with a gluconic or glucoheptonic group, their hydrogelation properties, and the thermal and mechanical properties of the supramolecular hydrogels. The l-lysine derivatives with a gluconic group have no hydrogelation ability, while the l-lysine-glucoheptonamide derivatives functioned as hydrogelators. Their hydrogelation abilities increased with the decreasing length of the spacer between the l-lysine segment and the glucoheptonic group. The compound, which has no spacer, formed a supramolecular hydrogel at 0.05 wt % in pure water. The thermal stability and high mechanical strength of the supramolecular hydrogels based on this compound significantly depended on the aqueous solutions. Electron microscopy and FTIR studies demonstrated?that the hydrogelators created a three-dimensional network through hydrogen bonding and hydrophobic interactions in the supramolecular hydrogel. In addition, it was found that hydrophobic interactions played an important role in the thermal stability of the supramolecular hydrogel.

Full text of DOI:10.1016/j.tet.2007.02.065

Tetrahedron 63 (2007) 7302–7308
Supramolecular hydrogel formed by glucoheptonamide of
L-lysine: simple preparation and excellent hydrogelation ability
*
Masahiro Suzuki, Sanae Owa, Hirofusa Shirai and Kenji Hanabusa
*
Graduate School of Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan
Received 16 October 2006; revised 5 February 2007; accepted 9 February 2007
Available online 20 February 2007
Abstract—We describe the simple preparation of new L-lysine derivatives with a gluconic or glucoheptonic group, their hydrogelation prop-
erties, and the thermal and mechanical properties of the supramolecular hydrogels. The L-lysine derivatives with a gluconic group have no
hydrogelation ability, while the L-lysine-glucoheptonamide derivatives functioned as hydrogelators. Their hydrogelation abilities increased
with the decreasing length of the spacer between the L-lysine segment and the glucoheptonic group. The compound, which has no spacer,
formed a supramolecular hydrogel at 0.05 wt % in pure water. The thermal stability and high mechanical strength of the supramolecular
hydrogels based on this compound significantly depended on the aqueous solutions. Electron microscopy and FTIR studies demonstrated that
the hydrogelators created a three-dimensional network through hydrogen bonding and hydrophobic interactions in the supramolecular hydro-
gel. In addition, it was found that hydrophobic interactions played an important role in the thermal stability of the supramolecular hydrogel.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
hydrogelators based on L-lysine, L-valine, and L-isoleucine
function as excellent hydrogelators that can form hydrogels
below 0.5 wt %. Another strategy for hydrogelators is
the introduction of nonionic water-soluble functional groups
9
,22–26
Over recent years, low-molecular weight hydrogelators
have become an area of considerable interest, involving
the development of low-molecular weight organogela-
such as sugars, nucleotides, hydroxyl groups, and aldon-
amides.
1
–21
1–3,5,14,27–35
tors.
In a supramolecular gel, gelators self-assemble
In this paper, we describe a new class
of hydrogelators based on L-lysine derivatized with aldon-
amide.
into nano-scale supramolecular polymers with the monomer
units being linked via noncovalent interactions such as hy-
drogen bonding, van der Waals, p–p stacking, coordination,
and electrostatic interactions. Therefore, the supramolecular
polymers show polymeric properties in solution and in the
bulk. Because of the reversible dynamic conversion from
supramolecular polymers to monomers by external stimuli
such as temperature, pH, ionic strengths, light, and electric-
ity, gelators are useful as new soft materials alternative to
conventional polymers. Based on the gelation behavior of
organic solvents by an organogelator, many hydrogelators
2. Results and discussion
3
6
The synthetic procedures are illustrated in Scheme 1. The
amino group of amino acids (6-amino-1-hexanoic acid or
12-amino-1-dodecanoic acid) was protected with a benzyl-
oxycarbonyl group, and then the amino-protected amino
acids were converted into the acid chlorides using oxalyl
chloride in dry dichloromethane. After reaction of the acid
6
–21
have subsequently been reported.
The molecular struc-
3
9
tures of hydrogelators are designed based on those of orga-
nogelators. The important points for the conversion of
organogelators into hydrogelators are: (i) to be water-soluble
and (ii) to keep the self-assembling properties of organo-
gelators intact. One of the simplest strategies is the intro-
duction of charges into the terminus of organogelators.
According to this strategy, we have developed L-amino
acid-based hydrogelators with a positively or negatively
charged terminal group; in particular, the positively charged
chlorides with N -lauroyl-L-lysine ethyl ester, the amino
group-terminated L-lysine derivatives were obtained by
deprotection using Pd/C. Finally, compounds 1 and 2 were
obtained by the reaction with D-(+)-glucono-1,5-lactone or
D-glucoheptono-1,4-lactone in methanol. Compounds 3a
3
and 3b were simply prepared from N -lauroyl-L-lysine ethyl
esters and lactones in methanol.
As mentioned above, we have reported some positively
charged L-lysine hydrogelators; especially, N -(11-pyridi-
a
3
nium undecanoyl)-N -dodecaonyl-L-lysine ethyl ester bro-
mide (A) is an excellent hydrogelator that can form
*
Corresponding authors. Tel.: +81 268 21 5415; fax: +81 268 21 5608;
e-mail: msuzuki@giptc.shinshu-u.ac.jp
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.065

M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
7303
O
OH OH
H
H
N
n
D-(+)-Glucono-1,5-lactone
C11H23
N
OH
N
H
MeOH
H
N
H
N
n
O
O
O
OH OH
C11H23
O
O
O
NH2
1
a: n = 11; 2a: n = 5
O
O
O
O
n = 5 or 11
O
OH OH
H
N
H
n
C11H23
N
D-glucoheptono-1,4-lactone
MeOH
N
H
OH
O
OH OH OH
O
1b: n = 11; 2b: n = 5
OH OH
H
N
H
N
D-(+)-Glucono-1,5-lactone
MeOH
C11H23
OH
O
O
OH OH
H
O
O
C11H23
N
NH2
3a
O
O
O
OH OH OH
H
H
N
D-glucoheptono-1,4-lactone
MeOH
C11H23
N
OH
O
O
OH OH
O
O
3b
Scheme 1. Synthetic procedure for L-lysine aldonamide derivatives.
ꢀ
1
9,23
a hydrogel at 3 g L (Fig. 1).
In contrast, compound B
3a precipitated after dissolution in water. This is attributed
to the lack of hydrophilicity of the gluconic head group,
which leads to the unsuitable hydrophilic–hydrophobic bal-
ance. On the other hand, compounds 1b–3b, possessing
a glucoheptonic group (six hydroxyl groups), functioned
as hydrogelators. Surprisingly, 3b was an excellent hydro-
had no hydrogelation ability. Based on this hydrogelator,
we prepared compounds 1a and 1b, which had a nonionic
and hydrophilic group at the terminal, and examined their
hydrogelation abilities. Compound 1a was water-insoluble
and did not act as a hydrogelator, while 1b formed a hydrogel
at 15 g L . It is noteworthy that the increase in number of
only one hydroxyl group brings about water-solubility and
hydrogelation ability. Compared with compound A, the
hydrogelation ability of 1b was relatively low because its
hydrophilic–hydrophobic balance was unsuitable. For com-
pounds 1a–3a, possessing a gluconic group (five hydroxyl
groups), these compounds did not function as hydrogelators;
compounds 1a and 2a were water-insoluble and compound
ꢀ
1
ꢀ1
gelator that formed a transparent hydrogel at 0.5 g L cor-
responding to one gelator molecule immobilizing more than
62,000 water molecules (for hydrogelator A, ca. 12,600
water molecules were immobilized)
9
,23
(Table 1).
For the positively charged L-lysine-based hydrogelator sys-
tem, the hydrogelation ability was lost when the length of
the alkylene spacers between the L-lysine segment and
H
N
H
+
N
N
Br
-
O
O
O
O
O
O
A
Br-
N+
H
N
H
N
O
O
B
Figure 1. Positively charged L-lysine derivatives.
ꢁ
Table 1. Hydrogelation properties of 1–3 in pure water at 25 C
1
a
2a
3a
1b
15
2b
3b
a
a
a
Pure water
H
Insoluble
—
Insoluble
—
Precipitate
—
5
7520
0.5
62,670
b
2
O molecules
2820
a
ꢀ1
Minimum gel concentration necessary for hydrogelation (MGC, g L ).
The number of water molecules that is immobilized by one gelator molecule.
b

7304
M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
pyridinium group decreased; indeed, compound B did not
function as a hydrogelator. In the present case, the hydro-
gelation ability decreased with the increasing number of car-
bons in the alkylene spacer between the L-lysine segment
and the glucoheptonic group (i.e., increase in hydrophobic-
ity). This is ascribed to a difference in hydrophilicity of
the terminal group; probably, the glucoheptonic group has
less hydrophilicity than the positively charged pyridinum.
Table 3. Hydrogelation properties of 1b–3b in aqueous solutions containing
ꢁ
a,b
acids and salts at 25 C
c
Saline HCl H SO H PO CH CO H NaCl KCl MgCl CaCl2
2
4
3
4
3
2
2
1
2
b Ins
b 3
Ins Ins
Ins
5
0.8
2
5
1
Ins Ins Ins
Ins
P
4
4
4
3
2
8
2
8
2
8
3
3b 3
a
Values denote MGC.
Acids and salts are 1.0 M.
Saline contains 8.6 g L
b
c
ꢀ1
ꢀ1
(ca. 0.147 M) NaCl, 0.3 g L
(ca.
ꢀ
3
ꢀ1
ꢀ3
The hydrogelation abilities of 1b–3b were examined in
aqueous solutions of various pHs, which were adjusted by
HCl (pH¼0–6) or NaOH (pH¼8–14) and the results are
listed in Table 2. Although 1b was insoluble in aqueous so-
lutions with the high concentrations of HCl (>0.01 M) and
NaOH (>0.001 M), it formed a hydrogel in aqueous solu-
tions with pH¼2–10. Compound 2b gelled aqueous solu-
tions with pH¼0–10. Compound 3b formed a hydrogel in
4.02ꢃ10 M) KCl and 0.33 g L (ca. 2.97ꢃ10 M) CaCl . Ins: insol-
2
uble and P: precipitate after dissolution.
for pure water and acid solutions, while giving translucent
hydrogels for inorganic salt solutions. It is well-known that
a supramolecular gel is often formed by self-assembled
1
–5
nanofibers.
The superstructures created by the gelators
ꢀ
1
aqueous solutions of pH¼0–12 below 4 g L , while it
was not able to form a hydrogel with high concentrations
of alkali (pHꢂ13). The hydrogels prepared from alkali solu-
tions of pH¼9–12 had a short lifetime and collapsed within
in the hydrogels were observed using a transmission electron
microscope (TEM). Figure 2 shows the photographs of hy-
drogels and TEM images of their dried gels prepared from
pure water gel, saline gel, and NaCl gel based on 3b. The
pure water gel was transparent, while the saline and NaCl
gels were translucent. The TEM images demonstrate
a three-dimensional network formed by the entangling
self-assembled nanofibers of the hydrogelators. The average
diameters of self-assembled nanofibers are about 10–50 nm
for the pure water gel, 30–100 nm for saline gel, and 60–
150 nm for 1 M NaCl gel. These results correspond with
the aspects of hydrogels; the nanofibers in the transparent
2
weeks; especially, the hydrogel of pH¼12 based on 3b col-
lapsed one day later. The FTIR spectrum of the precipitate
showed that the IR peak of the ester group was no longer
observed. This fact implies that the collapse of hydrogels
formed by alkali solutions is caused by hydrolysis of the es-
ter group. In contrast, the hydrogels prepared from aqueous
solutions of pH¼1–8 have very long lifetimes and are stable
for more than half a year. Similar results were obtained using
other acids such as sulfuric acid, phosphoric acid, and acetic
acid. Therefore, 2b and 3b form an acid-resistant hydrogel.
2
3
hydrogel are smaller to those in the translucent hydrogels.
The evidence for the intermolecular interactions between the
gelator molecules in the gel state was provided by FTIR
analysis. As shown in Figure 3A, the FTIR spectrum of
Table 3 lists the hydrogelation properties of 1b–3b in aque-
ous solutions containing 1 M acids and salts. Although 1b
was insoluble in saline and aqueous solutions containing
ꢁ
the D O gel (at 25 C) showed the typical peaks at
2
ꢀ
1
ꢀ1
1
acid solution at 2 g L . It is noteworthy that the MGC value
M inorganic acids and salts, it formed a hydrogel in acetic
1632 cm and at 1677 cm . Such a characteristic IR spec-
trum demonstrates that the self-assembled nanofibers are
formed through an intermolecular hydrogen bonding inter-
action between the amide groups and have an antiparallel
ꢀ1
is greater than that in pure water. Except for the CaCl solu-
2
tion, 2b formed a hydrogel in all the aqueous solutions and
their MGC values were barely affected by the addition of in-
organic salts and acids. In the presence of inorganic salts,
however, the hydrogelation ability tends to slightly decrease.
In contrast, inorganic salts and acids influenced the hydro-
gelation ability of 3b. The MGC values increased in the pres-
ence of these additives; especially, the MGC values for HCl
3
7,38
b-sheet arrangement.
The CD spectrum of the D O gel
2
showed a negative peak at 202 nm and shoulder at 216 nm.
This CD result supports the IR data. In addition, the absorp-
tion bands of antisymmetric (n ) and symmetric (n ) C–H
as
s
ꢀ1
stretching vibrations were observed at 2920 cm (n C–
as
H) and 2850 cm (n C–H), and in the IR region arising
s
ꢀ
1
and CaCl solutions are 8 times larger than those for pure
2
from the amide A and hydroxyl group, the IR peak appeared
.
ꢀ
1 36
ꢁ
IR spectrum and CD spectrum drastically changed; the
water. In summary, compound 3b can form a hydrogel con-
taining a high concentration of ions such as protons, alkali
at 3400 cm
On the other hand, at 80 C (solution), the
ꢀ
1
ꢀ1
long wavenumber shifts of nC–H (2920 cm /2925 cm
ꢀ1
ions, alkali earth metal ions, and anions below 0.5 g L of
the gelator, it is an excellent hydrogelator.
ꢀ
1
ꢀ1
ꢀ1
and 2850 cm /2855 cm ) and amide A (3400 cm /
ꢀ
1
ꢀ1
3
increase in the absorbance at 1655 cm , disappearance of
446 cm ), decrease in absorbance at 1632 cm
and
ꢀ
1
Compound 3b formed transparent or translucent hydrogels
in these aqueous solutions, e.g., giving transparent hydrogels
ꢀ
1
the IR peak at 1677 cm , and no observation of the CD
ꢁ
a,b
Table 2. Hydrogelation properties of 1b–3b in aqueous solutions with various pHs at 25 C
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
2
3
b
b
b
Ins
4
4
Ins
8
1
5
10
0.5
15
10
0.5
15
10
0.5
15
10
0.5
15
3
0.5
15
5
0.5
15
10
0.5
15
10
2
15
10
2
S
P
2
Ins
P
3
Ins
S
S
Ins
S
S
a
ꢀ1
Values denote minimum gel concentration (MGC, g L ).
Aqueous solutions with various pHs were adjusted by HCl or NaOH: pH¼0–6 by HCl, pH¼8–10 by NaOH, and pH¼7 is pure water. Ins: insoluble, P: pre-
b
cipitate after dissolution, and S: solution.

M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
7305
ꢀ1
ꢀ1
ꢀ1
Figure 2. Photographs of hydrogels and TEM images of their dried gels. (A) pure water (0.5 g L ); (B) saline (3 g L ); and (C) 1 M NaCl (2 g L ) of 3b.
Scale bars are 200 nm.
ꢁ
ꢁ
ꢀ1
Figure 3. FTIR (A) and CD (B) spectra of D
2
O gel (25 C, solid line) and D
2
O solution (80 C, dashed line) of 3b (5 g L ).
ꢀ
1
peak. Therefore, the nanofibers are formed through hydro-
phobic interaction and the intermolecular hydrogen bonding
with an antiparallel b-sheet arrangement, and then a three-
dimensional network is created by entanglement of the
nanofibers, which leads to hydrogelation.
Here, the IR spectra observed in this region (3400 cm –
3440 cm ) were likely conjugated by some spectra, e.g.,
ꢀ1
nO–H (in gelator and of H O in D O), nN–H, etc, and the
2
Tgel was 65 C under the experimental conditions
2
ꢁ
ꢀ
1
(10 g L ). The temperature dependences of the IR peaks
of the amide groups were slightly different from those of
the alkyl group. In the region of 3400 cm –3440 cm ,
ꢀ
ꢁ
1
ꢀ1
In order to obtain further information on the hydrogelation
mechanism, we measured the FTIR spectra at various tem-
peratures. Figure 4 shows the temperature dependences of
the IR peak of the amide A and hydroxyl group region
ꢁ
the drastic changes were observed at 35 C–45 C and
ꢁ
ꢁ
63 C–65 C. The absorbances of the amide I changed at
ꢁ
ꢁ
60 C–65 C. In contrast, the IR bands of the nC–H changed
ꢁ
ꢁ
(
1
A), n C–H (B) as well as n C–H (C), and absorbances at
at 65 C–70 C. These facts let us to propose the mechanism
of the gel–sol transition as follows: the hydrogen bonding
as
s
ꢀ ꢀ1
677 cm (D) and 1632 cm (E) in the D O gel of 3b.
2
1
ꢀ ꢀ1
2
O gel based on 3b (5 g L ). (A) IR peak appearing in 3400–3440 cm , (B)
1
1
Figure 4. Temperature dependences of IR peaks obtained from VT–IR spectra of D
IR peak arising from nasC–H, (C) IR peak arising from n C–H, (D) absorbance at 1677 cm , and (E) absorbance at 1632 cm . Tgel is 65 C.
ꢀ
ꢀ1
ꢁ
s

7306
M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
interactions of hydroxyl groups and amide groups are broken
at 35 C–45 C and at 63 C–65 C, respectively, and around
The thermodynamic analysis for the gel–sol transition was
carried out using a van’t Hoff relationship. From the rela-
ꢁ
5 C, the gel state should be maintained by only hydro-
ꢁ
ꢁ
ꢁ
40
ꢁ
6
tionship between Tgel and MGC, the gel–sol transition
enthalpy (DHgel) was determined from the slope of ln[3b]
ꢁ
phobic interaction. Over 65 C, the hydrophobic interaction
is broken, leading to the destruction of the hydrogel.
ꢀ
1
versus (Tgel) . For all hydrogels, the plots gave a linear re-
lationship. The DHgel values increased in the order of pure
water gel<saline gel<1 M NaCl gel. This order reflects
the concentration of inorganic salts in the aqueous solutions
and size of the nanofibers. Because the DHgel values are rel-
ative to the strength of intermolecular interactions (mainly
hydrophobic interaction) in the nanofiber, the highest DHgel
value in 1 M NaCl solution of compound 3b is caused by the
strong intermolecular interactions.
In order to elucidate the excellent hydrogelation ability and
thermal stability, some measurements were carried out. Gel
strength is one of the important factors in the applications of
hydrogels. In the present study, the gel strengths were eval-
uated as the power necessary to sink a cylindrical bar
(
10 mm in diameter) 4 mm deep in the hydrogels. As listed
in Table 4, among three hydrogels, the pure water gel showed
the largest gel strength and the value was 35 kPa. It is likely
that the gel strength is connected with the rigidity of self-
assembled nanofibers; namely, the gel strength of a hydrogel
having a three-dimensional network formed by rigid nano-
3. Conclusion
3
9
fibers is large. As shown in Figure 2, the sizes of nanofibers
are the order of pure water gel<saline gel<1 M NaCl gel,
while the gel strengths show the inverted order (pure water
gel>saline gel>NaCl gel). Compound 3b would form the
narrower nanofibers and a more effective interpenetrated
network, which leads to the large gel strength.
In this paper, we revealed the easy synthesis and hydrogela-
tion property of new L-lysine-based hydrogelators with glu-
coheptonamide. All L-lysine derivatives with a gluconic
group have no hydrogelation ability, while the L-lysine
derivatives of glucoheptonamide function as hydrogelators.
The hydrogelation ability significantly depends on the length
of spacer between the L-lysine segment and glucoheptonic
group and increases with decreasing length. Especially,
compound 3b, which has no spacer, functions as a super hy-
drogelator that forms a hydrogel at 0.05 wt % in pure water,
which corresponds to the immobilization of more than
62,000 water molecules per gelator molecule. The hydrogels
based on 3b have thermal stability and high mechanical
strength. The FTIR studies demonstrate that the hydrogel
is formed by the creation of a three-dimensional network
through hydrogen bonding and hydrophobic interactions;
particularly, the hydrophobic interaction plays an important
role in the thermal stability of the hydrogel.
Figure 5 shows the gel–sol transition temperatures (T ) of
gel
pure water gel, saline gel, and 1 M NaCl gel based on 3b
as a function of the gelator concentrations. For the pure
ꢁ
water gel, the Tgel values sharply increased to 65 C with
ꢀ1
the increasing concentration of 3b up to 5 g L , and over
5 C, 3b was not able to gel pure water even at 50 g L
ꢁ
ꢀ1
.
6
The saline gel and 1 M NaCl gel had thermal stabilities
and were maintained at 70 C; 20 g L for saline gel and
ꢁ
0 g L for NaCl gel. These results indicate that 3b forms
ꢀ1
ꢀ1
1
thermally stable hydrogel in various aqueous solutions. It
is noteworthy that the pure water gel formed by 3b at
ꢁ
ꢀ
1
5
g L has the highest Tgel (65 C).
a
4. Experimental
4.1. General
Table 4. Physical parameters for hydrogels based on 3b
b
Pure water
Saline
NaCl 1 M
ꢁ
T
gel ( C)
DHgel (kJ mol
Gel strength (kPa)
65
81.5
35.4
60
99.3
24.7
65
107.2
20.9
ꢀ1
3
)
4.1.1. Materials. N -Lauroyl-L-lysine was obtained form
Ajimonoto Co., Inc. The ethyl ester of N -lauroyl-L-lysine
was prepared according to the literature. The other chemi-
3
9
a
ꢀ1
.
[
3b]¼5 g L
b
ꢀ1
ꢀ1
(ca. 0.147 M) NaCl, 0.3 g L
cals were of the highest commercial grade available and
used without further purification. All solvents used in the
syntheses were purified, dried, or freshly distilled as required.
Saline contains 8.6 g L
4
(ca.
.02ꢃ10ꢀ M) KCl, and 0.33 g L (ca. 2.97ꢃ10 M) CaCl
3
ꢀ1
ꢀ3
2
.
4
1
4
.1.2. Typical synthetic procedure. To a stirring metha-
nol suspension (20 mL) of D-glucono-1,5-lactone or D-glu-
coheptono-1,4-lactone (20 mmol), a methanol solution
(50 mL) of amino acid derivatives with an amino group at
the terminal (20 mmol) was carefully added dropwise at
ꢁ
5
0 C. The reaction was continued for another 6 h. The reac-
tion mixture was cooled to room temperature and then fil-
tered to remove traces of unreacted lactone. The filtrate
was evaporated to dryness. The crude solid was purified
twice by recrystallization from methanol. The compounds
1
a–3a and 1b–3b were obtained as white solids.
a
N -(12-Gluconamide-1-dodecanoyl)-N -
3
4.1.2.1.
lauroyl-L-lysine ethyl ester (1a). Yield 93%. Mp¼
Figure 5. Dependence of Tgel on concentration of 3b (A) and van’t Hoff
plots (B) for pure water gel (C), saline gel (-), and 1 M NaCl gel (:).
ꢁ
ꢁ
ꢀ1
120 C–122 C. IR (KBr): 3322, 1733, 1640, 1542 cm .

M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
7307
1
ꢀ1
1
H NMR (400 MHz, DMSO-d , TMS): 0.85 (t, J¼6.6 Hz,
3401, 3316, 1739, 1643, 1547 cm . H NMR (400 MHz,
6
3
1
2
2
3
1
H), 1.15–1.27 (m, 40H; alkyl), 1.33–1.46 (m, 8H), 1.52–
.71 (m, 2H), 2.02 (t, J¼7.3 Hz, 2H), 3.02 (q, J¼6.1 Hz,
H), 3.02–3.08 (m, 2H), 3.30–3.39 (m, 1H), 3.45–3.48 (m,
H), 3.53–3.56 (m, 1H), 3.66–3.67 (m, 1H), 3.85 (br, 1H),
.92 (t, J¼5.8 Hz, 1H), 4.02–4.11 (m, 1H), 4.12–4.17 (m,
H), 4.28 (br, 1H), 4.36 (d, J¼6.3 Hz, 1H), 4.43 (t,
DMSO-d , TMS): 0.88 (t, J¼6.6 Hz, 3H), 1.25–1.31 (m,
6
21H; alkyl), 1.48–1.56 (m, 2H), 1.58–1.62 (m, 2H), 1.70–
1.88 (m, 2H), 2.14 (t, J¼7.3 Hz, 2H), 3.17 (q, J¼6.0 Hz,
2H), 3.54 (br, 1H), 2.70–3.82 (m, 7H), 4.16–4.21 (m, 3H),
4.30 (d, J¼3.6 Hz, 1H), 4.50–4.55 (m, 1H), 6.71 (t, J¼
5.3 Hz, 1H), 7.50 (d, J¼8.1 Hz, 1H). Elemental Anal. Calcd
for C H N O (534.68): C, 58.40; H, 9.43; N, 5.24. Found:
J¼5.6 Hz, 1H), 4.84 (d, J¼4.1 Hz, 1H), 5.48 (d, J¼6.1 Hz,
2
6 50 2 9
1
(
H), 7.72 (t, J¼5.3 Hz, 1H), 7.84 (t, J¼5.8 Hz, 1H), 8.10
d, J¼7.4 Hz, 1H). Elemental Anal. Calcd for
C H N O (732.00): C, 62.35; H, 10.05; N, 5.74. Found:
C, 58.55; H, 9.89; N, 5.25.
a
N -Glucoheptonamide-N -lauroyl-L-lysine
3
4.1.2.6.
3
8 73 3 10
ꢁ
ꢁ
KBr): 3446, 3392, 3349, 3305, 1734, 1682, 1644,
C, 62.58; H, 10.33; N, 5.77.
ethyl ester (3b). Yield 95%. Mp¼114 C–116 C. IR
(
1549 cm . H NMR (400 MHz, DMSO-d , TMS): 0.86
a
.1.2.2. N -(6-Gluconamide-1-hexanoyl)-N -lauroyl-
3
ꢀ1
1
4
6
ꢁ
ꢁ
H NMR
L-lysine ethyl ester (2a). Yield 89%. Mp¼153 C–154 C.
(t, J¼6.6 Hz, 3H), 1.19 (t, J¼7.1 Hz, 3H), 1.23 (br, 18H;
alkyl), 1.33–1.38 (m, 2H), 1.42–1.50 (m, 2H), 1.60–1.75
(m, 2H), 2.02 (t, J¼7.3 Hz, 2H), 2.96–2.99 (m, 2H), 3.31
(br, 2H), 3.34–3.39 (m, 1H), 3.44–3.49 (m, 2H), 3.87–3.89
(m, 1H), 3.98 (t, J¼6.6 Hz, 1H), 4.06–4.12 (m, 2H), 4.21–
4.25 (m, 1H), 4.28–4.30 (m, 2H), 4.42–4.45 (m, 2H), 4.66
(d, J¼4.8 Hz, 1H), 5.43 (d, J¼6.6 Hz, 1H), 7.69 (t, J¼
5.6 Hz, 1H), 7.99 (d, J¼7.6 Hz, 1H). Elemental Anal. Calcd
for C H N O (564.71): C, 57.43; H, 9.28; N, 4.96.
ꢀ
1
1
IR (KBr): 3327, 1731, 1644, 1544 cm
(
.
400 MHz, DMSO-d , TMS): 0.85 (t, J¼6.6 Hz, 3H), 1.15–
6
1
2
3
.35 (m, 24H; alkyl), 1.35–1.50 (m, 8H), 1.51–1.69 (m,
H), 2.02 (t, J¼7.3 Hz, 2H), 2.10 (t, J¼7.3 Hz, 2H), 2.91–
.02 (m, 2H), 3.05–3.09 (m, 2H), 3.34–3.40 (m, 1H), 3.48
(
4
br, 2H), 3.55–3.61 (m, 1H), 3.90 (br, 1H), 3.97 (t, J¼
.3 Hz, 1H), 4.03–4.10 (m, 1H), 4.11–4.17 (m, 1H), 4.31 (t,
J¼5.6 Hz, 1H), 4.37 (d, J¼4.4 Hz, 1H), 4.45 (d, J¼4.5 Hz,
H), 4.51 (d, J¼4.5 Hz, 1H), 5.32 (d, J¼4.8 Hz, 1H), 7.58
2
7 52 2 10
1
(
1
5
Found: C, 57.64; H, 9.49; N, 4.98.
t, J¼5.8 Hz, 1H), 7.71 (t, J¼5.6 Hz, 1H), 8.08 (d, J¼7.3 Hz,
H). Elemental Anal. Calcd for C H N O (647.84): C,
3
4.1.3. Apparatus for measurements. The elemental analy-
ses were performed using a Perkin–Elmer series II CHNS/O
analyzer 2400. The FTIR spectra were recorded on a JASCO
FS-420 spectrometer. The TEM observations were carried
out using a JEOL JEM-2010 electron microscope at
2 61 3 10
9.33; H, 9.49; N, 6.49. Found: C, 59.77; H, 9.71; N, 6.52.
a
3
.1.2.3. N -(12-Glucoheptonamide-1-dodecanoyl)-N -
4
lauroyl-L-lysine ethyl ester (1b). Yield 91%. Mp¼
ꢁ
ꢁ
ꢀ1
1
1
17 C–119 C. IR (KBr): 3311, 1740, 1639, 1546 cm
.
200 kV. The H NMR spectra were measured using a Bruker
1
H NMR (400 MHz, DMSO-d , TMS): 0.85 (t, J¼6.6 Hz,
AVANCE 400 spectrometer. The gel strengths of the hydro-
gels were measured using a Sun Science Sun Rheo Meter
CR-500DX. The circular dichroism spectra were measured
using a JASCO Circular Dichroism J-600 spectrometer.
6
3
H), 1.15–1.27 (m, 40H; alkyl), 1.34–1.48 (m, 8H), 1.53–
.73 (m, 2H), 2.02 (t, J¼7.3 Hz, 2H), 3.00 (q, J¼6.3 Hz,
H), 3.04–3.10 (m, 2H), 3.31–3.39 (m, 1H), 3.45–3.48 (m,
H), 3.55–3.58 (m, 1H), 3.66–3.67 (m, 1H), 3.85 (br, 1H),
.92 (t, J¼5.8 Hz, 1H), 4.02–4.11 (m, 2H), 4.12–4.17 (m,
H), 4.28 (br, 1H), 4.36 (d, J¼6.3 Hz, 1H), 4.43 (t, J¼
.6 Hz, 2H), 4.81 (d, J¼4.1 Hz, 1H), 5.45 (d, J¼6.1 Hz,
H), 7.71 (t, J¼5.3 Hz, 1H), 7.81 (t, J¼5.8 Hz, 1H), 8.06
1
2
2
3
1
5
1
4.1.4. Gelation test. A mixture of a weighed gelator in
solvent (1 mL) in a sealed test tube was heated until a clear
solution appeared. After allowing the solutions to stand at
25 C for 6 h, the state of the solution was evaluated by
the ‘test tube inversion’ method.
ꢁ
(
d, J¼7.4 Hz, 1H). Elemental Anal. Calcd for
C H N O (762.03): C, 61.47; H, 9.92; N, 5.51. Found:
3
9 75 3 11
C, 61.49; H, 9.99; N, 5.53.
4.1.5. Transmission electron microscope (TEM). The
samples were prepared as follows: aqueous solutions of
the gelators were added dropwise onto a collodion- and car-
bon-coated 400 mesh copper grid. The grids were then dried
under vacuum for 24 h. The dried samples were stored in
a sealed bottle containing osmic oxide in acetone overnight.
a
N -(6-Glucoheptonamide-1-hexanoyl)-N -
3
4
.1.2.4.
lauroyl-L-lysine ethyl ester (2b). Yield 88%. Mp¼
ꢁ
ꢁ
ꢀ1
1
50 C–153 C. IR (KBr): 3314, 1723, 1639, 1559 cm .
1
H NMR (400 MHz, DMSO-d , TMS): 0.85 (t, J¼6.8 Hz,
6
3
H), 1.15–1.27 (m, 24H; alkyl), 1.35–1.52 (m, 8H), 1.53–
.66 (m, 2H), 2.02 (t, J¼7.1 Hz, 2H), 2.10 (t, J¼7.4 Hz,
H), 3.00 (q, J¼6.3 Hz, 2H), 3.07 (q, J¼7.1 Hz, 2H),
.34–3.38 (m, 1H), 3.43–3.51 (br, 2H), 3.53–3.61 (m, 1H),
.66–3.69 (m, 1H), 3.84–3.87 (m, 1H), 3.92 (t, J¼6.3 Hz,
H), 4.03–4.10 (m, 2H), 4.11–4.17 (m, 1H), 4.28 (t,
1
2
3
3
1
4.1.6. Gel strength. Samples were prepared as follows:
a mixture of a weighed gelator in water (2 mL) in a sealed
sample tube (15 mm in diameter) was heated until a clear so-
lution appeared. The resulting solution was allowed to stand
ꢁ
at 25 C for 6 h. The gel strength was evaluated as the force
J¼5.8 Hz, 1H), 4.37 (d, J¼6.6 Hz, 1H), 4.43 (q, J¼2.1 Hz,
H), 4.81 (d, J¼6.8 Hz, 1H), 5.49 (d, J¼6.6 Hz, 1H), 7.71
t, J¼5.6 Hz, 1H), 7.82 (t, J¼5.8 Hz, 1H), 8.08 (d,
J¼7.6 Hz, 1H). Elemental Anal. Calcd for C H N O
necessary to sink a cylinder bar (10 mm in diameter) 4 mm
deep in the gel.
2
(
4.1.7. FTIR study. The FTIR spectroscopy was performed
using the spectroscopic cell with a CaF window and 50 mm
spacers operating at a 2 cm resolution with 32 scans.
3
3 63 3 11
(
677.87): C, 58.47; H, 9.37; N, 6.20. Found: C, 58.79; H,
.59; N, 6.24.
2
ꢀ
1
9
a
3
.1.2.5. N -Gluconamide-N -lauroyl-L-lysine ethyl
4
4.1.8. Temperature-controlled FTIR study. An automatic
temperature-control cell unit (Specac Inc., P/N 20,730) with
ꢁ
ꢁ
ester (3a). Yield 95%. Mp¼125 C–127 C. IR (KBr):

7308
M. Suzuki et al. / Tetrahedron 63 (2007) 7302–7308
a vacuum-tight liquid cell (Specac Inc., P/N 20,502, path
length 50 mm) fitted with CaF windows was used to mea-
sure the IR spectra at different temperatures.
15. Heeres, A.;vanderPol, C.;Stuart, M.;Friggeri,A.;Feringa, B.L.;
van Esch, J. J. Am. Chem. Soc. 2003, 125, 14252–14253.
16. Kiyonaka, S.; Sada, K.; Yoshimura, I.; Shinkai, S.; Kato, N.;
Hamachi, I. Nat. Mater. 2004, 3, 58–64.
2
4
for the D O gel at 25 C and the solution state at 80 C of 3b.
.1.9. Circular dichroism. The CD spectra were measured
ꢁ
17. Bhuniya, S.; Park, S. M.; Kim, B. H. Org. Lett. 2005, 7, 1741–
1744.
ꢁ
2
1
8. Karinaga, R.; Jeong, Y.; Shinkai, S.; Kaneko, J.; Sakurai, K.
Langmuir 2005, 21, 9398–9401.
Acknowledgements
19. Srivastave, A.; Ghorai, S.; Bhattacharjya, A.; Bhattacharya, S.
J. Org. Chem. 2005, 70, 6574–6582.
This work was supported by a Grant-in-aid for the 21st
century COE Program and a Grant-in-aid for Exploratory
Research (No. 17655049) by Ministry of Education, Sports,
Culture, Science, and Technology of Japan and by To-
kuyama Science Foundation.
20. K €o hler, K.; Meister, A.; F €o rster, G.; Dobner, B.; Drescher, S.;
Ziethe, F.; Richer, W.; Steiniger, F.; Drechsler, M.; Hause,
G.; Blume, A. Soft Matter 2006, 2, 77–86.
21. Yang, Z.; Liang, G.; Xu, B. Chem. Commun. 2006, 738–740.
22. Suzuki, M.; Yumoto, M.; Kimura, M.; Shirai, H.; Hanabusa, K.
Chem. Lett. 2004, 33, 1496–1497.
2
3. Suzuki, M.; Yumoto, M.; Kimura, M.; Shirai, H.; Hanabusa, K.
Chem.—Eur. J. 2003, 9, 348–354.
Supplementary data
2
4. Suzuki, M.; Owa, S.; Yumoto, M.; Kimura, M.; Shirai, H.;
Hanabusa, K. Tetrahedron Lett. 2004, 45, 5399–5402.
25. Suzuki, M.; Owa, S.; Kimura, M.; Kurose, A.; Shirai, H.;
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.02.065.
Hanabusa, K. Tetrahedron Lett. 2005, 46, 303–306.
6. Suzuki, M.; Nanbu, M.; Yumoto, M.; Shirai, H.; Hanabusa, K.
New J. Chem. 2005, 29, 1439–1444.
7. Shimizu, T.; Masuda, M.; Minamikawa, H. Chem. Rev. 2005,
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