Novel dimeric cholesteryl derivatives and their smart thixotropic gels

Article abstract of DOI:10.1021/la2022819

Three novel LS₂-type dimeric-cholesteryl derivatives (1-3), where S is a steroidal residue and L stands for a linker connecting the two S residues and contains three benzene rings and two amide and two carbamate groups, were designed and prepar

Full text of DOI:10.1021/la2022819

ARTICLE
pubs.acs.org/Langmuir
Novel Dimeric Cholesteryl Derivatives and Their Smart
Thixotropic Gels
Xiaoyu Hou, Di Gao, Junlin Yan, Ying Ma, Kaiqiang Liu, and Yu Fang*
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and
Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China
S Supporting Information
b
ABSTRACT: Three novel LS2-type dimeric-cholesteryl derivatives (1ꢀ3), where S is a
steroidal residue and L stands for a linker connecting the two S residues and contains
three benzene rings and two amide and two carbamate groups, were designed and
prepared. The compounds can gel a wide variety of organic solvents via three different
ways, including mixing at room temperature, a heatingꢀcooling cycle, and ultrasound
treatment. SEM measurements revealed that the structures and the concentrations of
the gelators, the nature of the solvent, and the preparation method employed have a
great effect on the morphologies of the gel networks. It was revealed that 1 is a
supergelator for DMSO (cgc = 0.04% w/v) and that the 1/DMSO gel can be prepared
via any of the three methods mentioned above. Furthermore, the gel possesses excellent
mechanical strength and a very smart thixotropic property. FT-IR and temperature- and
concentration-dependent 1H NMR spectroscopy studies revealed that hydrogen bonding and πꢀπ stacking among the molecules
of 1 are two important driving forces for the physical gelation of DMSO. In addition, XRD analysis confirmed the layered packing
structure of 1 in its DMSO gel.
phase-selective gelation at room temperature21ꢀ23 and gel
1. INTRODUCTION
emulsion and gel film formation,24,25 which are necessities in
Unlike in chemical gels, in which the gelator molecules are
cross-linked via chemical bonds, in particular, covalent bonds, the
gelator molecules in physical gels, particularly those based upon
spilled-oil recovery, water purification, and template prepara-
tion of low-density materials. Actually, molecular gels formed by
other LMMGs with no cholesterol structure may also possess
low-molecular-mass gelators (LMMGs), self-assemble into 3D
smart properties and find important applications.26ꢀ32
network structures via nonchemical bonding interactions, that is,
supramolecular weak interactions such as van der Waals
It is known that most of the LMMG-based supramolecular
gels are prepared via a heatingꢀcooling cycle.19,33ꢀ35 Recently,
other competitive preparation methods have also been devel-
oped, such as light irradiation9 and sonication10 and chemical,
mechanical, or even electronic-/magnetic-field treatment at
room temperature.11,12,25 For example, Zhang36 and Naota10,37
and their co-workers reported, separately, ultrasound-induced
gelation. Their studies demonstrated that the weak noncovalent
interaction between the gelator molecules has been partially
broken, which favors the establishment of a balance between
aggregation and dis-aggregation, a necessity for the gelation of a
system. Moreover, the network structure of the gelator in the gels
can be also controlled by changing the intensity and frequency of
the ultrasound wave employed.38 In fact, the development of
smart, adaptive gels whose properties can be controlled or even
switched by external stimuli has always been appealing, promis-
ing, and challenging.
interactions,1 hydrogen bonding,2 πꢀπ stacking,3 electrostatic
interactions,4 solvophobic interactions,5 coordination interac-
tions,6 and hostꢀguest interactions,7 in suitable solvents. The
weak interaction nature in physical gels causes their formation
and de-formation to be controlled by some physical stimuli,
including heating or cooling, changing pH,8 light irradiation,9
ultrasound treatment,10 proton transfer,11 and the shear force.12
These smart properties may bring about real-life applications of
the LMMG-based physical gels in drug delivery,13 tissue engine-
ering,14 templates,15 sensors,16 the oil industry,17 light-harvesting
materials,9 and dye-sensitized solar cells.18
Among the LMMGs reported, cholesterol-based LMMGs
have attracted a considerable amount of attention because of
their versatility in gelation and diversity of structures. Histori-
cally, these LMMGs have been classified as ALS, A(LS)2, LS, and
LS2 types according to the numbers of aromatic (A) moieties,
and steroids (S), and functionalized linkers (L). The structures of
the LMMGs have been regulated successfully by changing the
components of L or A, and the gelators as gained can gel a range
of solvents including protic/aprotic and polar/nonpolar sol-
vents.19,20 In particular, our group reported several cholesterol-
based LMMGs bearing smart behavior, such as gelation and
Very recently, the structure of benzene was intentionally
introduced into the linkers of cholesterol-based LMMGs in an
Received: June 18, 2011
Revised:
August 24, 2011
Published: August 25, 2011
r
2011 American Chemical Society
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Scheme 1. Schematic Representation of the Synthesis of Compounds 1ꢀ3 and Their Intermediates aꢀc, Respectively
A(LS)2 structure, of which the structures of the compounds were
changed by varying the relative positions of the two linkers on the
benzene ring. It was demonstrated that changes in the positions
of the substrates resulted in great changes in the gelation behav-
iors of the compounds and their gel properties.21 Therefore, it is
of interest to imagine what will happen if another or more
benzene structures were introduced and more variations were
added to the connecting structures between the two cholesterol
units. Accordingly, three novel cholesterol-based LMMGs were
designed and prepared by introducing three benzene rings, two
amide structures, and two carbamate groups into the connecting
structures of a new series of dicholesteryl derivatives. We are
lucky to find that some of the compounds as designed and
prepared possess exceptional gelation and mechanical properties.
We believe that the present findings may provide additional data
regarding the cholesterol-based gelators, a well-studied class of
LMMGs. This article reports the details.
freeze drying for 12ꢀ24 h. The sample as obtained was attached to a copper
holder by conductive adhesive tape and shielded with gold. It is to be noted
that the morphologies of the xerogels as obtained may not be necessarily the
real structures of the molecular gel networks, from which the xerogels were
obtained. However, it is believed that this kind of measurement does
provide useful information for an understanding of the gel networks.
2.3. Rheological Measurement. Rheological measurements
were carried out with a stress-controlled rheometer (TA Instruments,
AR-G2) equipped with steel-coated parallel-plate geometry (20 mm
diameter). The gap distance was fixed at 1000 μm. A solvent-trapping
device was placed above the plate to avoid evaporation. All measure-
ments were made at room temperature (25 °C).
Stress sweep at a constant angle frequency (6.28 rad sꢀ1) was per-
formed in the 1.0ꢀ6000.0 Pa stress range to determine the linear
viscoelastic region (LVER) of the gel sample. A frequency sweep was
performed in a 1.0ꢀ628.0 rad sꢀ1 angle frequency range at a certain
shear force (500 Pa) within LVER that can bring about small strains in
the tested materials.
A thixotropic study was conducted to examine the recovery behavior
of a supramolecular gel after deformation. This process includes two
steps: (1) Deformation: a constant oscillatory shear stress (6000.0 Pa)
that is enough to destroy the gel is applied to the fresh gel in the sample
holder for 2 min. (2) Modulus recovery in a time sweep: the recovery of
the storage modulus is monitored at 6.28 rad sꢀ1 under a low shear force
(10.0 Pa) placed on the above destroyed gel. The storage modulus G0
and the loss modulus G00 are recorded as functions of time in the re-
covery process.
2. EXPERIMENTAL SECTION
2.1. Gelation Test. A known weight of the potential gelator and a
measured aliquot of liquid were placed into a sealed glass tube (d = 8
mm, v = 0.5 mL), and the system was heated in an oil or water bath until
all solid materials were dissolved completely. Then the solution was
slowly cooled to room temperature in air, and the test tube was inversed
to determine if a gel had formed. When a white or transparent gel is
formed at this stage, it is denoted as G or TG. In some cases, a solution
and gel may coexist within a system, and they are referred to as partial
gels (PG). For the systems in which only solution remained until the end
of the tests, they are referred to as solution (S). The system in which the
potential gelator could not be dissolved even at the boiling point of the
solvent is considered to be an insoluble system (I). For some of the
systems, heating results in the dissolution of the gelators, but cooling
results in their precipitation. These systems are denoted as P. In a few
cases, a viscous solution (VS) was also observed at 2.5% (w/v) gelator.
Molecular gels obtained by simple shaking or sonication at room
temperature are denoted as G (rt) or G*, respectively. The critical
gelation concentration (cgc) refers to the minimum concentration of the
gelator needed for the gelation of the relevant solvent.
A temperature sweep began from 20 °C to 75 °C at 6.28 rad sꢀ1 under
a constant stress (10 Pa) in order to reach the gelꢀsol transition tem-
perature.
The following procedure was used to load the fresh gel sample:
2.0 mL of a solution containing solvent and gelator was heated to 90 °C,
closed using a tight cone, and then cooled to 25 °C. The measurements
started 1 h later after the gels had formed.
2.4. 1H NMR Measurement. The gel sample containing one
gelator and CDCl3 was prepared in an NMR tube, and the chemical
shifts of the sample were detected with a Fourier digital NMR spectro-
meter (Avance, 300 MHz) at a given temperature of between 298 and
318 K or at a given concentration range between 1.0% (w/v) and 2.5%
(w/v) at 298 K.
2.2. SEM Measurement. SEM images of the xerogel were taken on
a Quanta 200 scanning electron microscope (Philips-FEI). The accel-
erating voltage was 15.0 kV, and the emission was 10.0 mA. The xerogel
for the measurement was prepared by freezing the gel formed in a
concerned solvent at a concentration of 2.5% (w/v) in liquid nitrogen and
2.5. FT-IR Measurements. All FT-IR measurements were per-
formed on a Brucher Equinx55 spectrometer in transmittance mode.
KBr pellets were obtained by mixing small amounts of the dried gel
samples and anhydrous KBr powder.
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2.6. X-ray Diffraction (XRD) Measurement. Diffraction pat-
terns were obtained on a Japan Rigaku D/max-III diffractometer with
Cu Kα X-rays generated (λ = 1.5418 A) under a voltage of 40 kV and a
current of 40 mA. The scan rate was 0.5°/min.
7.33 (s, 2H, CONH), 7.07ꢀ7.13 (t, 4H, J = 13 Hz, benzene), 5.33
(s, 2H, alkenyl), 4.55ꢀ4.57 (m, 2H, oxy-cyclohexyl), 0.67ꢀ2.34 (m,
86H, cholesteryl protons). FT-IR, vmax/cmꢀ1: 3423 (NH), 2945 (CH),
1738 (CdO, ꢀO), 1644 (CdO, ꢀNH), 1527 (NH, bending), and
1226 (ꢀCꢀO). Anal. Calcd for C34H52N2O2: C, 77.91; H, 9.12; N,
4.78. Found: C, 77.66; H, 9.02; N, 4.83. MS (ESI): m/z calcd for [M +
Na+], 1193.8005; found, 1193.7981.
3. SYNTHESIS OF THREE CHOLESTERYL DERIVATIVES
3.5. Compound 2. Compound b (1.04 g, 2 mmol) and triethyla-
mine (0.29 mL, 2 mmol) were dissolved in 150 mL of THF, and the
mixture was stirred in an iceꢀwater bath. To the solution, 80 mL of a
THF solution of isophthaloyl chloride (0.203 g, 1.0 mmol) was added
dropwise. Then the reaction mixture was stirred at room temperature for
18 h, the reaction mixture was filtered, and the filtrate was evaporated to
dryness. The resulting solid was recrystallized from acetone twice and
then dried in vacuum to give the desired product (2) in 77% yield as a
3.1. Intermediate (a). o-Phenylenediamine (8.64 g, 80 mmol) and
triethylamine (0.58 mL, 4 mmol) were both dissolved in THF (150 mL).
To the solution, 80 mL of a THF solution of cholesteryl chloroformate
(1.8 g, 4 mmol) was added dropwise under stirring in an ice bath. After
the addition, the mixture was stirred at room temperature for 18 h. Then,
the mixture was filtered, and the filtrate was evaporated in vacuum to
dryness, and the residues were dissolved in dichloromethane. The dic-
hloromethane solution was washed with water at least 10 times. The
organic phase was separated and dried by using anhydrous magnesium
sulfate. The dried and purified organic solution was concentrated in
vacuum to dryness. The solid as obtained was recrystallized twice from
methanol, and the desired product (a) was obtained as a white powder in
70% yield with mp 204ꢀ205 °C. 1H NMR (CDCl3/Me4Si, 300 MHz):
δ 7.27ꢀ7.30 (1H, d, J = 8.0 Hz, benzene ring), 6.99ꢀ7.04 (1H, t, J = 15
Hz, benzene ring), 6.80ꢀ6.83 (1H, t, J = 8.2 Hz, benzene ring), 6.77ꢀ
6.79 (1H, d, J = 7.8 Hz, benzene ring), 6.31 (1H, s, CONH), 5.40 (1H, s,
alkenyl), 4.56ꢀ4.63 (1H, m, oxy-cyclohexyl), 3.49 (2H, s, ꢀNH2),
0.68ꢀ2.41 (43H, m, cholesteryl protons). FT-IR, νmax/cmꢀ1: 3394
(NH), 2938 (CH), 1705 (CdO, ꢀO), 1628 (CdO, ꢀNH), 1536 (NH,
bending), and 1254 (ꢀCꢀO). Anal. Calcd for C34H52N2O2: C, 78.41;
H, 10.06; N, 5.38. Found: C, 78.41; H, 10.09; N, 5.02. MS (ESI): m/z
calcd for [M + Na+], 543.3921; found, 543.3926.
3.2. Intermediate (b). The synthesis procedures for intermediate
b are similar to those for intermediate a and produce a powder product
(b) in 35% yield with mp 183ꢀ184 °C. 1H NMR (CDCl3/Me4Si, 300
MHz): δ 7.02ꢀ7.07 (1H, t, J = 16 Hz, benzene), 6.97 (1H, s, benzene
ring), 6.56ꢀ6.59 (1H, d, J = 7.9 Hz, benzene ring), 6.48 (1H, s, CONH),
6.36ꢀ6.39 (1H, d, J = 7.6 Hz, benzene ring), 5.40 (1H, s, alkenyl),
4.58ꢀ4.60 (1H, m, oxy-cyclohexyl), 3.60 (2H, s, ꢀNH2), 0.68ꢀ2.41
(43H, m, cholesteryl protons). FT-IR, νmax/cmꢀ1: 3411 (NH), 2946
(CH), 1728 (CdO, ꢀO), 1635 (CdO, ꢀNH), 1530 (NH, bending),
and 1208(ꢀCꢀO). Anal. Calcd for C34H52N2O2: C, 78.41; H, 10.06; N,
5.38. Found: C, 78.69; H, 9.72; N, 5.33. MS (ESI): m/z calcd for [M +
Na+], 543.3921; found: 543.3929.
1
white powder with mp 225ꢀ226 °C. H NMR (CDCl3/Me4Si, 300
MHz): δ 8.69 (s, 2H, CONH), 8.15 (s, 1H, benzene), 7.84ꢀ7.87 (d, J =
7.1 Hz, 2H, benzene), 7.77 (s, 2H, benzene), 7.39ꢀ7.44 (t, 1H, J = 15
Hz, benzene), 7.30ꢀ7.33 (t, 2H, J = 7.1 Hz, benzene), 7.18ꢀ7.21 (d,
2H, J = 7.6 Hz, benzene), 7.12ꢀ7.15 (d, 2H, J = 9.1 Hz, benzene), 6.78
(s, 2H, CONH), 5.36 (s, 2H, alkenyl), 4.51ꢀ4.53 (m, 2H, oxy-
cyclohexyl), 0.68ꢀ2.34 (m, 86H, cholesteryl protons). FT-IR, vmax/cmꢀ1
:
3432 (NH), 2944 (CH), 1730 (CdO, ꢀO), 1616 (CdO, ꢀNH), 1540
(NH, bending), and 1219 (ꢀCꢀO). Anal. Calcd for C34H52N2O2:
C, 77.91; H, 9.12; N, 4.78. Found: C, 77.58; H, 9.09; N, 4.62. MS (ESI):
m/z calcd for [M + Na+], 1193.8005; found, 1193.7987.
3.6. Compound 3. Compound c (1.04 g, 2 mmol) and triethyla-
mine (0.29 mL, 2 mmol) were dissolved in 150 mL of THF, and the
mixture was stirred in an iceꢀwater bath. To the solution, 80 mL of a
THF solution of isophthaloyl chloride (0.203 g, 1.0 mmol) was added
dropwise. Then the reaction mixture was stirred at room temperature for
18 h. After the reaction, the mixture was filtered, and the filtrate was
evaporated to dryness. The resulting solid was washed with hot acetone
five times and then dried in vacuum to give the desired product (3) in
55% yield as a white powder with mp 280ꢀ281 °C. 1H NMR (THF-d8/
Me4Si, 300 MHz): δ 9.57 (s, 2H, CONH), 8.70 (s, 2H, CONH), 8.51
(s, 1H, benzene), 8.09ꢀ8.12 (d, 2H, J = 7.3 Hz, benzene), 7.73ꢀ7.76
(d, 4H, J = 8.3 Hz, benzene), 7.55ꢀ7.60 (t, 1H, J = 15 Hz, benzene),
7.47ꢀ7.50 (d, 4H, J = 8.1 Hz, benzene), 5.44 (s, 2H, alkenyl), 4.56 (m,
2H, oxy-cyclohexyl), 0.77ꢀ2.79 (m, 86H, cholesteryl protons).
FT-IR, vmax/cmꢀ1: 3440 (NH), 2944 (CH), 1704 (CdO, ꢀO), 1647
(CdO, ꢀNH), 1522 (NH, bending), and 1225 (ꢀCꢀO). Anal. Calcd
for C34H52N2O2: C, 77.91; H, 9.12; N, 4.78. Found: C, 77.45; H, 8.87; N,
4.78. MS (ESI): m/z calcd for [M + Na+], 1193.8005; found, 1193.8002.
3.3. Intermediate (c). The synthesis procedures for intermediate c
are similar to those for both a and b and give a powder product in 38%
1
yield with mp 172ꢀ173 °C. H NMR (CDCl3/Me4Si, 300 MHz): δ
7.12ꢀ7.15 (2H, d, J = 6.8 Hz, benzene ring), 6.61ꢀ6.63 (2H, d, J = 8.4
Hz, benzene), 6.46 (1H, s, CONH), 5.39 (1H, s, alkenyl), 4.54ꢀ4.61
(1H, m, oxy-cyclohexyl), 3.42 (2H, s, ꢀNH2), 0.68ꢀ2.40 (43H, m,
cholesteryl protons). FT-IR, νmax/cmꢀ1: 3411 (NH), 2946 (CH), 1728
(CdO, ꢀO), 1635 (CdO, ꢀNH), 1530 (NH, bending), and 1208-
(ꢀCꢀO). Anal. Calcd for C34H52N2O2: C, 78.41; H, 10.06; N, 5.38.
Found: C, 78.49; H, 9.93; N, 4.99. MS (ESI): m/z calcd for [M + Na+],
543.3921; found, 543.3924.
4. RESULTS AND DISCUSSION
4.1. Design of the Gelators. It has been demonstrated in
previous work that some A(LS)2-type gelators gel some organic
solvents efficiently (<1% w/v) at room temperature and their
gelation behavior can be adjusted by changing the spatial
structure of the linker with a benzene ring.21 As demonstrated
already, cholesteryl derivatives possessing aromatic structures
have a strong tendency to self-aggregate in various solvents via
the van der Waals interaction between the cholesteryl units and
πꢀπ stacking between the aromatic rings, which are the reasons
that explain why A(LS)2-type compounds are efficient gelators.
For the present study, another two benzene rings were purposely
introduced into the linker in different ways (Scheme 1). With
reference to the structures of 1ꢀ3, it is seen that with the
exception of the three benzene structures, each of the linkers
contains two amide structures and two carbamate groups, which
were introduced in order to provide more hydrogen bonding
3.4. Compound 1. Compound a (1.04 g, 2 mmol) and triethyla-
mine (0.29 mL, 2 mmol) were dissolved in 150 mL of THF, and the
mixture was stirred at room temperature. To the solution, 80 mL of a
THF solution of isophthaloyl chloride (0.203 g, 1.0 mmol) was added
dropwise. After the addition, the mixture was stirred at 65 °C for 6 h.
Then the reaction mixture was filtered, and the filtrate was evaporated to
dryness. The resulting solid was washed with hot acetone five times and
then dried in vacuum to give the desired product (1) in 55% yield as a
1
white powder with mp 212ꢀ213 °C. H NMR (CDCl3/Me4Si, 300
MHz): δ 9.27 (s, 2H, CONH), 8.50 (s, 1H, benzene), 8.09ꢀ8.12 (d, 2H,
J = 7.7 Hz, benzene), 7.55ꢀ7.60 (t, 1H, J = 15 Hz, benzene), 7.50ꢀ7.53
(d, 2H, J = 6.3 Hz, benzene), 7.39ꢀ7.41 (d, 2H, J = 7.4 Hz, benzene),
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sites. It was believed that these designs may guarantee the
adaptive and versatile aggregation and dis-aggregation behaviors,
which are the bases of forming supramolecular gels, of the new
cholesteryl derivatives.
4.2. Gelation Behavior of the Compounds. The gelation
behavior of 1ꢀ3 in 34 organic solvents at a concentration of 2.5%
(w/v) was tested, and the results are shown in Table 1. An
examination of the table reveals that the three compounds are
more versatile and efficient gelators if compared to compounds
with similar structures but fewer benzene ring in the linkers.21
Compound 1 gels or partially gels 18 protic/aprotic or polar/
nonpolar organic solvents, such as alcohols, xylene, and DMF.
Compounds 2 and 3 show similar gelation properties and gel or
partially gel 24 and 17 of the solvents tested, respectively.
In addition to the number and type of solvents gelled, for a
given gelator, the cgc is also an important parameter that shows
its gelling ability. The cgc values of the gel systems are also listed
in Table 1. It can be seen that the cgc values of 1 in DMSO and 3
in DMF are both close to 0.04% (w/v), which is significantly
lower than 0.1% (w/v), a well recognized standard for supergela-
tion.39 Interestingly, only via a heatingꢀcooling cycle can com-
pound 3 gel CCl4 (2.5% w/v). In contrast, both heatingꢀcooling
treatment and ultrasound treatment can result in gelation of the
system of 2/CCl4 (2.5% w/v). For 1, however, a concentration of
2.5% w/v is not great enough to gel the solvent but results in only
a viscous solution. Similar phenomena were also seen in other
solvents, such as benzene, toluene, DMF, DMSO, ethanol, ether,
TEA, and CHCl3. Moreover, the 1/DMSO gel forms easily via
any of the three methods discussed above.
4.3. Morphology Studies. Figure 1 shows the SEM images of
the xerogels of gels of 1, 2, or 3 in DMSO or cyclohexane. With
reference to the images, it is seen that 1ꢀ3 aggregated into
loosely packed network structures with various morphologies
in both DMSO and cyclohexane. For example, the xerogel of 3 in
DMSO at the concentration studied is characterized by a
coralloid morphology. At the same concentration, 1, however,
aggregated mainly into skin-like structures with fitful holes inside,
and the aggregates of 2 in the solvent possess a cottonlike
morphology interwove with numerous regular fibers. Similarly,
the structures of the aggregates of the three gelators in cyclohexane
are also different from each other. Considering the fact that the
Table 1. Gelation Behavior of Compounds 1ꢀ3 in Various
Solvents (2.5% w/v)a
solvents
1
2
3
solvents
1
2
3
CH2Cl2
Gb
S
2.5 2.5
Gb 2.5(rt)
Gb 2.5(TG) 1-propanol PG PG
methanol
ethanol
I
I
Gb
Gb
I
CHCl3
CCl4
I
VS
I
benzene
toluene
xylene
PG(rt) Gb 2.5(TG) 1-butanol
PG(rt) TGb 2.5(TG) 1-pentanol PG 0.31 0.36
PG 0.36b 0.28
PG(rt) PG 2.5G
1-hexanol 0.50 0.33 0.20
1-heptanol 0.50 0.40 0.20
acetone
I
P
I
cyclohexane 2.5
2.5 2.5
1-octanol
0.83 0.4 0.14(TG)
THF
S
Gb
S
S
1- nonanol 0.42 0.50 0.20
1-decanol 0.36 0.33 0.17
DMF
DMSO
VS 0.04
0.04 (rt) 2.5 2.5
n-pentane
n-hexane
I
P
I
I
I
I
mineral ether I
I
I
I
P
kerosene
ether
VS
I
0.25(TG) n-heptane
I
I
Gb
Gb
S
PG
Gb
S
I
n-octane
n-nonane
n-decane
I
2.5
TEA
I
I
PG VS
pyridine
S
I
P
I
I
I
acetonitrile
I
Gb
ethyl acetate I
Gb
aG, gel; TG, transparent gel; PG, partial gel; S, solution; I, insoluble; P,
precipitate; VS, viscous solution; Gb, gels formed via sonication; G(rt), gels
formed at room temperature and the numerals within the Table stand for
the critical gelation concentrations (cgc) of the systems in w/v.
Figure 1. SEM images of the xerogels of 1ꢀ3 in different solvents (2.5% w/v). (a) 1/DMSO, (b) 2/DMSO, (c) 3/DMSO, (d) 1/cyclohexane, (e)
2/cyclohexane, and (f) 3/cyclohexane.
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Figure 2. SEM images of the xerogels of 1 in DMSO (2.5% w/v) obtained by different preparation methods: (a) shaking at room temperature,
(b) sonication, and (c) the heatingꢀcooling cycle.
Figure 3. Evolution of G0 as a function of the applied shear stress. The
samples used are the gels of 1, 2, or 3 in DMSO (2.5% w/v).
Figure 4. Evolution of G0 as a function of the applied shear stress at
different concentrations of 1 in DMSO.
nature of the solvent and the concentration of each gelator
have been fixed, the notable difference in the morphologies of
via three different ways, that is, simple shaking, sonication at
room temperature, or heating first and then cooling. The SEM
images of the gel networks (xerogels) are shown in Figure 2. It
can be seen that the morphology of the gel networks formed
via sonication possesses the characteristics of both the one pre-
pared via physical shaking (fine fibers) and the other prepared via
a heatingꢀcooling cycle (mainly skinlike structures). Similar
observation can be also found in the 1/benzene gel system (cf.
Figure S3, Supporting Information). This additional experiment
suggests that the network structures of a gel could be affected by
either static factors such as the structures of gelators and the
nature of the solvents concerned or dynamic factors such as the
preparation method employed. Of course, it should be safe to
anticipate that the property of a gel is dependent not only on its
chemical compositions but also on how it is prepared.
4.4. Rheological Behaviors. The rheological behaviors of gels
are important for their real-life applications.41 To explore the
effect of the spatial structures of the linkers of the compounds
studied upon the mechanical properties of their gels, the rheolo-
gical properties of the gels of 1ꢀ3 in DMSO (2.5% w/v) were
examined. Their storage modulus G0, associated with energy
storage, and loss modulus G00, associated with a loss of energy,
were measured as functions of shear stress at room temperature,
and the results are shown in Figure 3. With reference to the
figure, it is seen that at the stress values before their sharp
decreases, the values for 1/DMSO are 2 or 3 orders of magnitude
exponentially greater than those for gels 2/DMSO and 3/DMSO.
Furthermore, the yield stress of 1/DMSO reaches 3414.0 Pa, a
the gelators in each set of experiment can be attributed only to the
small difference in the structures of the linkers, that is, the
difference in the substitute positions. As for the aggregation ability
of the compounds, it is clear that the variation in the structures of
the linkers does alter this ability very much, as indicated by the fact
that the cgc values of the gelators with respect to the two solvents
are different from each other, suggesting that the aggregates (the
xerogels) of the gelators in each set of gel systems may be in
different aggregation stages. This explains why the morphologies
of the xerogels are different from each other because of the
concentration dependence nature of the network structure of a
gel as revealed by the results shown in Figure S1 (cf. Supporting
Information), which are the results of SEM studies of the system of
1/DMSO. With reference to the figure, it is clearly seen that the
morphology of the xerogel changes along with the change in the
concentration of the gelator in the system. Furthermore, molecular
dynamics modeling reveals that the conformations of the three
compounds in vacuum are very different from each other (cf.
Figure S2, Supporting Information),40 suggesting that their spatial
packing (aggregating) modes must be very different from each
other. Upon the basis of the above discussions, it may be con-
cluded that a small change in the spatial structure of the linker of a
dimeric-cholesteryl derivative can produce a dramatic effect on the
aggregation behavior of the compound in the solvent.
Actually, the network structure of a gel depends not only upon
the structure of the gelator and the nature of the solvent to be
gelled but also the method employed for the preparation of the
gel. To clarify this statement, the gel of 1/DMSO was prepared
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Figure 5. Eight cycles of deformation and recovery by stress sweep and
time sweep. The sample is 1/DMSO gel (2.5% w/v).
1
Figure 6. Temperature-dependent H NMR spectra of 1 in CDCl3
(2.0% w/v).
maximum value reported for LMMGs-based supramolecular gels
until now, but in contrast, the values for the other two gels are only
10.8 and 3.69 Pa, respectively. The remarkable differences in the
yield stresses of the three gels are great signatures for showing the
tremendous effect of a small change in the spatial structure of the
gelator with the cholesteryl unit, benzene ring, amide structure,
and carbamate group as their key structures.
Moreover, as expected, the mechanical property of a gel is also
gelator-concentration-dependent. As shown in Figure 4, the
value of G0 for 1/DMSO increased from 457.5 to 1.85 ꢁ 105
Pa with an increase in the gelator concentration from 0.1 to 2.5%
(w/v), and at the same time, the yield stress increased from 29.27
to 3414.0 Pa, clearly indicating that the mechanical performance
of a gel of 1/DMSO at a gelator concentration of only 0.1%
(w/v) is competitive with those of 2/DMSO and 3/DMSO at a
concentration of 2.5% (w/v), indicating again the importance of
the spatial structure of the linker to the properties of the gels
formed by LS2-type gelators.
Figure 7. XRD profile of the xerogel of 1/DMSO recorded at room
temperature.
To seek out the tolerance of the gel of 1/DMSO (2.5% w/v) to
external forces, angle frequency sweeps were conducted at a
shear stress of 500.0 Pa within its LVER. The result is shown in
Figure S4 (cf. Supporting Information). It is seen that with the
angle frequency increased from 1.0 to 628 rad sꢀ1, the values of
the storage modulus (G0) of the sample are always greater than
those of the loss modulus (G00), suggesting no phase separation
or phase transition during the sweep process. Furthermore, both
G0 and G00 remained relatively stable within the whole frequency
regime sweep, indicating that the gel possesses good tolerance to
external forces.
More interestingly, the 1/DMSO gel possesses excellent
thixotropic properties, as demonstrated by a result of shakingꢀ
flowing and standingꢀgelling that was observed in a simple route
shaking test. A more serious test was conducted to verify the
preliminary observation, and the result is shown in Figure S5 (cf.
Supporting Information). With reference to the figure, it is seen
that at t = 0, the end of the shearing treatment and the start of
monitoring the gel recovery, the system (viscous solution) recov-
ered its elasticity instantly, as indicated by the fact that the value of
G0 is larger than that of G00, a very smart thixotropic property as
expected. Moreover, the thixotropic process can be repeated
several times, as illustrated by the results shown in Figure 5.
Rheological measurements are also a reliable method for
measuring the solꢀgel phase-transition temperature (Tgel) of
the gels, which may provide important information about the
thermostability of the gels under study. In the present work, the
1/DMSO (2.5% w/v) gel was specifically chosen for conducting
temperature-dependent rheological measurements. The result as
obtained is shown in Figure S6 (cf. Supporting Information).
Reference to the figure reveals that both G0 and G00 of the gel
remain almost constant during the measurement, provided that
the temperature of the gel is below a critical value, 65 °C, which
should be the Tgel of the system characterizing its solꢀgel phase
transition.
1
4.5. Hydrogen Bonding and πꢀπ Stacking. H NMR spec-
troscopy is a powerful tool for examining the hydrogen bonding and
πꢀπ stacking within an LMMG-based gel.42 Accordingly, tem-
1
perature- and concentration-dependent H NMR measurements
for the solution of 1 in CDCl3 were performed, and the 1H NMR
traces are shown in Figure 6. It is seen that change in temperature
results in a gradual upfield or downfield shift of the peak of NꢀH
protons and those of the aromatic protons of the gelator, respec-
tively. A further examination of the traces reveals that the chemical
shifts of the two sets of NꢀH protons appeared at 9.26, 9.20, and
9.14 and at 7.31, 7.20, and 7.12, respectively. In contrast, the
chemical shifts of the aromatic protons appeared at 7.49 and 7.52
at 298 K, respectively, and then fused together as a single peak
appearing at 7.58 at 308 K and finally shifted to 7.58 with a shoulder
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Figure 8. Structural model of the assembly of 1 in its DMSO gel, where a stands for the conformation of the aggregate of two molecules of 1 and b stands
for that of 12 molecules of the compound.
appearing at 7.64 at a temperature of 318 K. These results
demonstrate clearly that the amide structures and carbamate
groups of the gelators may have played important roles in the
characterizing the stretching vibration of the ester CdO group and
the bending vibration of the NH group of the gelator tend to be
syncretized rather than alienated, a phenomenon observed in the
spectrum of 1/benzene, suggesting that hydrogen bond formation
in this system might be different from that in the 1/DMSO system.
The reason might be attributed to the structural differences in the
two solvents, that is, DMSO is active in hydrogen bond formation
but benzene is inactive in the process.22,44
4.6. Molecular Packing. The XRD technique is employed to
investigate the molecular packing of 1 in the powder state and in
its DMSO gel network.45 As shown in Figure 7, the XRD trace of
1 in DMSO is characterized by four reflection peaks, which
correspond to spacing (d) values of 4.90, 2.45, 1.62, and 1.22 nm,
respectively, almost exactly following the ratio of 1:1/2:1/3:1/4,
indicating clearly that the molecules of 1 possess a layered
packing in the gel networks. Furthermore, the interlayer distance
is about 4.90 nm, which is just the calculated length of one unit
containing two molecules of the compound (Figure 8a).40 The
powder of 1 from THF also shows four sharp reflection peaks (cf.
Figure S9, Supporting Information), and the spacings (d) are
4.85, 2.40, 1.61, and 1.14 nm, respectively, almost following the
ratio of 1:1/2:1/3:1/4, which is strong evidence of a layered
structure of the powder of 1 from its THF solution. Accordingly,
a possible packing model of 1 in its DMSO gel and its powder
state was proposed and is shown in Figure 8b.
formation of the gel via the formation of hydrogen bonds, very
1
likely ꢀCdO
HꢀNꢀ. The shift in the H NMR signals of
3 3 3 3
the benzene structure of the linker provides direct evidence of the
contribution of πꢀπ stacking to the formation of the gel. However,
it is to be noted that the chemical shift information obtained via the
variation in temperature could be a result of either a change in intra-
or intermolecular hydrogen bonding and/or a change in intra- or
intermolecular πꢀπ stacking. Therefore, additional experiment
must be conducted to make sure that the intermolecular interaction
is the main reason for changes in the chemical shifts of the
corresponding structures. Thus, the 1H NMR spectra of the same
system were recorded as a function of the concentration of the
gelator at 298 K, and the results are shown in Figure S7 (cf.
Supporting Information). It is seen that decreases in the concentra-
tion of the gelator results in a result similar to that obtained by
increasing the temperature, suggesting that intermolecular hydro-
gen- bonding and intermolecular πꢀπstacking are the main driving
forces for the formation of the gel networks. This tentative
conclusion is further supported by the results from FT-IR measure-
ments.
FT-IR spectroscopy is another powerful tool for studying
hydrogen bond formation during the self-assembly of gelators in
solvents.43 In the present study, the FT-IR spectra of two gels of 1
in DMSO and benzene and that of a solution of 1 in THF were
recorded, and the results are shown in Figure S8 (cf. Supporting
Information; a, b, and b0). It was believed that THF is a good
solvent for 1, and the compound in this solvent exists in a
molecular state rather than an aggregated state. With reference to
the spectrum of the 1/THF solution, it can be seen that the four
bands of 1 corresponding to the stretching vibrations of NH,
amide CdO groups, ester CdOgroups, and the bendingvibration
ofNH appeared at 3317, 1730, 1662, and 1531 cmꢀ1, respectively.
Upon the gelation of 1 in benzene, the bands shifted to 3215,
1740, 1641, and 1525 cmꢀ1, respectively, which is further
evidence of the formation of hydrogen bonds in the gel networks.
But for the gel system of 1/DMSO, the changes in the FT-IR
spectrum are very different if compared to those for 1/benzene. For
this gel system, the two peaks appearing at 1730 and 1662 cmꢀ1
5. SUMMARY
Three novel dimeric cholesterol-based LMMGs with three
benzene rings and two amide and two carbamate groups in the
linkers were prepared, and their gelation behaviors were tested in
various organic solvents. In addition to the nature of the solvents
tested, the gelation behaviors of the compounds and the struc-
tures of the gel networks are strongly dependent upon the spatial
structures of the linkers of the dimeric cholesteryl deriva-
tives and the preparation processes of the gels. Interestingly,
compound 1 is a supergelator of DMSO with 0.04% (w/v) as its
cgc. The gel of 1/DMSO containing 2.5% (w/v) of the gelator
possesses excellent mechanical strength, good tolerance to
external forces, and smart thixotropic properties. Temperature-
and concentration-dependent 1H NMR and FT-IR spectroscopy
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studies demonstrated that hydrogen bonding and πꢀπ stacking
are two important driving forces in gel network formation. XRD
analysis revealed that the molecules of 1 aggregated into a layered
structure in its DMSO gel and into a powder state in its THF
solution.
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’ AUTHOR INFORMATION
(30) Pal, A.; Basit, H.; Sen, S.; Aswal, V. K.; Bhattacharyax, S.
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(31) Basit, H.; Pal, A.; Sen, S.; Bhattacharya, S. Chem.—Eur. J. 2008,
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Corresponding Author
*E-mail: yfang@snnu.edu.cn. Tel: +86 29 85310081. Fax:
+86 29 85310097.
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’ ACKNOWLEDGMENT
We thank the Natural Science Foundation of China (20902055,
20927001, and 91027017) and the 13115 Project of Shaanxi
Province (2010ZDKG-89) for financial support. This work is also
supported by “Program for Changjiang Scholars and Innovative
Research Team in University” of China (IRT1070).
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