Synthesis, self-assembly and characterization of a new glucoside-type hydrogel having a Schiff base on the aglycon

Article abstract of DOI:10.1016/j.carres.2004.03.012

A new hydrogel based on a substituted phenyl glucoside with a Schiff base in the aglycon was synthesized, and the self-assembling characteristics was studied. FTIR spectra, UV-vis absorption spectra and X-ray diffraction (XRD) revealed that π-π interactions between the Schiff base moieties, hydrogen bonds, and the interdigitated interactions between hydrophobic chains had effects on the formation of the self-assembling hydrogel. Scanning electron microscopic (SEM) and transmission electron microscopic (TEM) observation showed that the three-dimensional hydrogel network was constructed from nanotubes with inner diameters of ca. 75nm and wall of ca. 20nm.

Full text of DOI:10.1016/j.carres.2004.03.012

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1311–1316
Synthesis, self-assembly and characterization of a new glucoside-type
hydrogel having a Schiff base on the aglycon
Chunyan Bao, Ran Lu,* Ming Jin, Pengchong Xue, Changhui Tan, Yingying Zhao
and Guofa Liu
College of Chemistry, Department of Organic Chemistry, Jilin University, 119 Jiefang Road, Changchun 130023, PR China
Received 25 December 2003; accepted 15 March 2004
Available online 10 April 2004
Abstract—A new hydrogel based on a substituted phenyl glucoside with a Schiff base in the aglycon was synthesized, and the self-
assembling characteristics was studied. FTIR spectra, UV–vis absorption spectra and X-ray diffraction (XRD) revealed that p–p
interactions between the Schiff base moieties, hydrogen bonds, and the interdigitated interactions between hydrophobic chains had
effects on the formation of the self-assembling hydrogel. Scanning electron microscopic (SEM) and transmission electron micro-
scopic (TEM) observation showed that the three-dimensional hydrogel network was constructed from nanotubes with inner
diameters of ca. 75 nm and wall of ca. 20 nm.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Sugar derivative; Glucoside; Hydrogel; Self-assembly; Nanotubes
1. Introduction
organogelators are difficult to dissolve in water on
account of their low solubility or insolubility. Therefore,
only a limited number of hydrogels composed of such
aggregates have been reported, but hydrogels have
attracted extensive interest because of their applications
for tissue engineering and the development of new
materials that reversibly respond to various external
stimuli.18
Recently, Shinkai and co-workers6;7 have reported a
series of hydrogels comprised of the derivatives of glu-
cose. The mechanism for the formation of the self-
assembled structure of those hydrogels have also been
extensively discussed. It was found that the hydrogen
bonding between the hydroxyl groups of the sugar
moiety and the amide groups stabilized the aggregates
and determined the overall morphologies. The main
morphologies of the hydrogels thus obtained were fibers
and twisted ribbons, while only a few tubular structures
have been reported.
Gels derived from low-molecular-mass compounds have
attracted considerable interest in recent years on account
of their unique features and potential applications for
new organic soft materials,1 template synthesis,2 drug
delivery,3 separations and biomimetics.4 Compounds
with wide structural diversities concluding carbohy-
drates, amino acids, ureas, and cholesterols have been
summarized5 and reported6–15 to gelatinize organic
liquids efficiently. These organogels or hydrogels can
self-assemble into nanoscale superstructures such as
fibers, rods, ribbons, and tubes. The supramolecular gels
are based on the spontaneous, thermoreversible self-
assembly of low-molecular-weight molecules under
nonequilibrium conditions. Noncovalent interactions
give rise to the formation of superstructures, which
subsequently entrain and immobilize the solvent inside
the interstices of a three-dimensioned network.16;17 Most
Hollow tubular structure of nanoscale dimensions
may offer a variety of applications in chemistry, bio-
chemistry, and material science. In this work, we syn-
* Corresponding author. Fax: +86-431-8949334; e-mail: luran@mail.
jlu.edu.cn
thesized a new compound a phenyl b-D-glucopyranoside
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.03.012

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C. Bao et al. / Carbohydrate Research 339 (2004) 1311–1316
OAc
O
OAc
O
AcO
AcO
PTC
AcO
AcO
HO
CHO
+
O
CHO
OAc
Br
OAc
(3)
OAc
O
H2N
AcO
(3)
(2)
O
O
AcO
N
OAc
(2)
(1)
OH
O
HO
HO
NaOCH3
CH OH
/
3
N
OH
Scheme 1. The synthesis route and structure of compound 1.
with a Schiff base component on the aglycon (compound
1, as shown in Scheme 1). Compound 1 was designed as
an aqueous gelator to self-assemble into tubular struc-
ture. Here, the introduction of conjugated Schiff base
units into the glucose derivative replaced the traditional
amide groups and serves to increase the rigidity of the
molecule, which should be favorable for the molecules
to pack into cylindrical structure via p–p interactions.
FTIR spectra, UV–vis absorption, and X-ray diffraction
(XRD) confirmed that the intermolecular hydrogen
bonding, p–p stacking, and interdigitated interactions of
hydrophobic chains had an effect on the process of
aggregation. Transmission electron microscopy (TEM)
and scanning electron microscopy (SEM) gave the
tubular morphologies of the hydrogel thus obtained.
4
3
2
1
0
A
B
200
300
400
500
600
700
800
Wavelength (nm)
Figure 1. UV–vis absorption spectra: (A) Compound 1 in water in the
sol phase [0.05 (wt/vol) %], and (B) compound 1 in water in the
hydrogel phase [0.2 (wt/vol) %].
2. Results and discussion
Hydrogen-bonding-directed self-assembly is a well-
studied mechanism for superstructure formation with
amphiphiles in an arranged system. In compound 1, p–p
interaction between the Schiff base units may play an
important role in directing the formation of the hydro-
gel, except for the hydrogen bonds between hydroxyl
groups. To research the driving forces and mechanism
for the self-organization of hydrogel 1 that came from
compound 1, FTIR and UV–vis spectra were measured.
In FTIR spectra (not shown), the absorption of mas
(CH2) and ms (CH2) stretching vibration for alkylene
chains were 2921 and 2851 cmꢀ1, respectively, suggesting
an all-trans conformation of the hydrogel.19 Further-
more, the appearance of the OH vibration peak at
3412 cmꢀ1 confirmed the presence of the intermolecular
hydrogen bonding in the glucose.20 In the UV–vis
absorption spectra (as shown in Fig. 1), the kmax for the
Schiff base unit of compound 1 in water appeared at
261 nm in the sol phase and at 267 nm in the hydrogel
phase. This slight but significant red shift phenomena in
the gel phase suggested that the chromophores of the
Schiff base assembled into the J-type aggregation mode
via p–p stacking.21 Therefore, the p–p stacking between
the Schiff base moieties was favored, and J-type aggre-
gation took place.
To reveal how the molecules packed to the tubular
self-assemblies, XRD was investigated (as shown in Fig.
2) for the xerogel obtained from water by a freezing
method. The small-angle diffraction comes from the
characteristic lattice repeat, that is, the long-range
ordering of the hydrogel, whereas the wide-angle region
is indicative of hydrocarbon chain packing, that is, the
short-range ordering. In Figure 2, the small-angle dif-
fraction pattern of the xerogel showed a series of sharp
reflection peaks, indicating the layered organization.
The long d-spacing of the aggregation obtained by the
XRD method was about 4.08, 2.02, and 1.34 nm, which
are almost exactly 1:0.5:0.33, and the distance was
smaller than twice the extended molecular length of
compound 1 (2.5 nm by CPK molecular modeling), but
larger than the length of one molecule. It suggested that

C. Bao et al. / Carbohydrate Research 339 (2004) 1311–1316
1313
structures were obtained. The nanotubes of the self-
assembled hydrogel had tens of micrometers of length,
inner diameters of ca. 75 nm and wall of ca. 20 nm. And
the entangled tubes created a three-dimensional network
structure, which indicated that the hydrogel is formed
by the entrapment of water (solvent) molecules into the
space of the three-dimensional networks. The mecha-
nism of the nanotube formation can be speculated upon
the above results (as shown in Fig. 5). The wall of the
nanotube is packed by ca. five lipid interdigitated
bilayers, and the packed bilayers encircle to form a
nanotube.
25000
20000
15000
10000
5000
0
3000
2000
1000
0
d=4.08 nm
10
15
20
25
30
d=2.02 nm
d=1.34 nm
0
1
2
3
4
5
6
7
3. Conclusions
2θ (degree)
Figure 2. The small-angle XRD pattern of xerogel prepared from
hydrogel 1 and wide-angle diffraction (inset).
In this paper, a new kind of hydrogel, a phenyl glycoside
with a Schiff base derivatized aglycon, was synthesized,
and the characterization of hydrogel was discussed. Dif-
ferent from the usual hydrogel of glucoamides, the main
driving forces for the self-assembly are not only hydrogen
bonding, but also p–p interactions between the Schiff base
moieties. UV–vis absorption spectra confirmed the
interaction of the Schiff base units that could assemble
into a J-aggregation via p–p stacking in the hydrogel
phase. The XRD pattern revealed three ordered reflection
peaks with a long period of 4.08 nm, which suggested a
highly ordered bilayered packing with an interdigitated
hydrophobic chain. SEMand TEMrevealed the tubular
morphologies of the self-assembled hydrogel with inner
diameters of ca. 75 nm and wall of ca. 20 nm that was
stacked by ca. five lipid interdigitated bilayers.
the self-assembled compound 1 form a bilayer struc-
ture with interdigitated lipid chains by a hydrophobic
interaction. On the other hand, the diffraction of the
wide-angle region also gave a series of sharp peaks,
supporting the view that long alkyl chain groups pre-
sumably were packed into highly ordered layer packing
through the interdigitated hydrophobic interaction.22
On the basis of XRD, FTIR, and UV–vis results, the
hydrogel was found to be stabilized by combination of
the hydrogen bonding, p–p interactions, and hydro-
phobic forces. Therefore, a possible self-assembling
mode of the hydrogel based on the bilayered arrange-
ment can be obtained upon the above results (as shown
in Fig. 3).
4. Experimental
Figure 4a–e showed the pictures of polarized light
microscopy, TEM, and SEM of the hydrogel, and a
tubular structure and some slightly coiled tubular
4.1. Measurements
1H NMR spectra were determined with Varian-300 EX
and JEOL JNM-500EX instruments. Electrospray ion-
ization mass spectra (ESIMS, positive-ion mode) were
obtained using a Hitachi M-250 mass spectrometer.
UV–vis absorption spectra were recorded with a Shi-
madzu UV-2201 UV–vis spectrophotometer. Fourier-
transform infrared (FTIR) spectra were measured at
room temperature on a Nicolet Impact 410 FTIR
spectrometer. X-ray diffraction (XRD) patterns were
obtained on a Japan Rigaku D/max-cA. XRD equipped
with graphite monochromatized CuKa radiation
O
O
O
N
N
N
ꢀ
(k ¼ 1:5418 A), employing a scanning rate of 0.02°/s in
N
N
the 2h range from 0.7° to 10° and 0.05°/s in the 2h range
from 10° to 50°. The measured sample was prepared by
casting the hydrogel on silicon and dried at room tem-
perature. Scanning electron microscopy (SEM) was
taken with a Japan Hitachi model X-650 San electron
microscope. The sample for these measurements was pre-
pared in a 0.5-mL bottle and frozen in liquid nitrogen.
N
O
O
O
Figure 3. The possible molecular self-assembling packing mode for the
hydrogel 1.

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C. Bao et al. / Carbohydrate Research 339 (2004) 1311–1316
Figure 4. The morphological pictures of hydrogel 1 [0.2 (wt/vol) %]: (a) polarized light microscopy, (b and c) TEM, and (d and e) SEM.
4.2. Materials
ca.20 nm
2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl bromide was
prepared according to the standard literature proce-
ca.75 nm
1
dures23 and identified by FTIR and H NMR spectral
evidence. The completed process of the synthesis is
shown in Scheme 1.
4.3. Synthesis
Figure 5. The aggregation model of the tubular hydrogel 1.
4.3.1. Synthesis of p-formylphenyl (2,3,4,6-tetra-O-acet-
yl)-b-D-glucopyranoside (3). The method of phase-
The frozen specimens were evaporated by a vacuum
pump, and then the dry samples were coated by gold.
Transmission electron microscopy (TEM) was taken
with a Hitachi modes H600A-2 apparatus by wiping the
gel onto a 200-mesh copper grid, followed by naturally
evaporating the solvent.
transfer catalysis was applied in this synthesis. Tetra-
butylammonium bromide (Aldrich) (1.2898 g, 4 mmol)
was dissolved in 1:1 water–chloroform (20 mL), and the
mixture was stirred and heated to 40 °C. 2,3,4,6-Tetra-
O-acetyl-a-
D-glucopyranosyl bromide (8.22 g, 0.02 mol)
was dissolved in CHCl3 (15 mL, designated as solution

C. Bao et al. / Carbohydrate Research 339 (2004) 1311–1316
1315
A) and p-hydroxylbenzaldehyde (Aldrich) (2.44 g,
4.4. Formation of hydrogel
0.02 mol) was dissolved in water (20 mL) containing
6.9 g of K2CO3 (designated as solution B). Then solu-
tions A and B were simultaneously dropped into the
above mixture, and the system was heated to 60 °C and
stirred vigorously. After 6 h, the organic phase was
separated and washed with NaOH (10 mL, 5%) three
times. The solution thus obtained was dried with anhyd
Na2SO4. The solvent was evaporated under reduced
pressure and the solid was recrystallized in ethanol. The
white crystalline product (5.0 g, 55%) was collected and
dried in a vacuum: mp 142–143 °C; FTIR: 2963.5,
Compound 1 (1 mg) and 0.5 mL of water containing a
trace amount of EtOH (0.05 mL) were put in a septum-
capped sample tube and heated until the solid was dis-
solved. The solution was cooled at room temperature
for 5 h and the gel was formed.
Acknowledgements
The authors acknowledge the National Nature Science
Foundation of China (NNSFC) for financial support of
this work.
1
2746.8, 1750.5, 1737.6, 1692.6, 1601.0, 1222.3 cmꢀ1. H
NMR (CDCl3, 300 MHz): d 9.933 (s, 1H, CHO), 7.861
(d, 2H, ArH), 7.106 (d, 2H, ArH), 5.157–5.343 (m, 4H,
CH), 4.159–4.331 (m, 2H, CH), 3.926–3.961 (m, 1H,
CH), 2.081 (s, 3H, CH3CO), 2.070 (s, 3H, CH3CO),
2.067 (s, 3H, CH3CO), 2.052 (s, 3H, CH3CO). ESIMS:
Calcd for C21H24O11 m=z 452.13; found m=z 453.1
[M+H].
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1642.8, 1606.4 cmꢀ1. H NMR (DMSO-d6, 500 MHz): d
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