Langmuir 2004, 20, 10413-10418
10413
Nonpolymeric Hydrogelator Derived from
N-(4-Pyridyl)isonicotinamide
D. Krishna Kumar, D. Amilan Jose, Parthasarathi Dastidar,* and Amitava Das*
Analytical Science Discipline, Central Salt & Marine Chemicals Research Institute,
G. B. Marg, Bhavnagar - 364 002, Gujarat, India
Received April 9, 2004. In Final Form: July 14, 2004
A series of pyridyl amides derived from isonicotinic acid, nicotinic acid, and benzoic acid have been
synthesized. Only N-(4-pyridyl)isonicotinamide 1 is found to be an efficient hydrogelator with a minimum
gelator concentration of 0.37 wt %. A wide range of concentrations (0.37-20 wt %) could be used to form
hydrogels. The other amides, namely, N-(3-pyridyl)isonicotinamide 2, N-(2-pyridyl)isonicotinamide 3,
N-(phenyl)isonicotinamide 4, N-(4-pyridyl)nicotinamide 5, N-(3-pyridyl)nicotinamide 6, and N-(4-pyridyl)benzamide 7, did not show any gelation properties. Fourier transform infrared spectroscopy, variable
temperature 1H NMR, single-crystal diffraction and X-ray powder diffraction (XRPD), and scanning electron
microscopy have been used to characterize the gel. Single-crystal diffraction and XRPD studies indicate
that the morph responsible for gel formation is different from that in its bulk solid and xerogel.
Introduction
Hydrogels are an important class of materials that
display many interesting applications1 such as transport
medium for dissolved species as a link between body fluids
and synthetic implants, in drug delivery, in gel electrophoresis, in chemical sensing, as a biointerface, and as
actuators. Classically, hydrogels are made from high
molecular weight natural polymers such as gelatin,2
fibrin,3 and polysaccharide-derived polymers4 and also
from synthetic molecules such as polymers of acrylic acid,
ethylene oxide, vinyl alcohol, and other derivatives.5
Protein polymers6 are also known to form hydrogels, some
of which are environmentally responsive to pH and
temperature.7 However, the preparation of polymer-based
hydrogels often suffers from constraints imposed by their
thermosetting nature and lack of benefits associated with
thermoplastic processing.8 Moreover, many hydrogels of
this class are mechanically weak and do not have adequate
water retention capacity, which limits their usefulness.
* To whom correspondence should be addressed. Fax: +91-2782567562.E-mail: [email protected](P.D.);[email protected]
(A.D.).
(1) (a) Nishikawa, T.; Akiyoshi, K.; Sunamoto, J. J. Am. Chem. Soc.
1996, 118, 6110. (b) Osada, Y.; Gong, J. P. Adv. Mater. 1998, 10, 827.
(c) Novick, S. J.; Dordick, J. S. Chem. Mater. 1998, 10, 955. (d) Ilmain,
F.; Tanaka, T.; Kokufuta, E. Nature 1991, 349, 400. (e) Holtz, J. H.;
Asher, S. A. Nature 1997, 389, 829. (f) Weissman, J. M.; Sunkara, H.
B.; Tse, A. S.; Asher, S. A. Science 1996, 274, 959. (g) Osada, Y., Khokhlov,
A. R., Eds. Polymer Gels and Networks; Marcel Dekker: New York,
2002. (h) Chu, Y. H.; Chen, J. K.; Whitesides, G. M. Anal. Chem. 1993,
65, 1314. (i) Lee, K.; Asher, S. A. J. Am. Chem. Soc. 2000, 122, 9534.
(2) Kavanagh, G. M.; Ross-Murphy, S. B. Prog. Polym. Sci. 1998, 23,
533.
(3) Perka, C.; Spitzer, R. S.; Lindenhayn, K.; Sittinger, M.; Schultz,
O. J. Biomed. Mater. Res. 2000, 49, 305.
(4) Chenite, A.; Chaput, C.; Wang, D.; Combes, C.; Buschmann, M.
D.; Hoemann, C. D.; Leroux, J. C.; Atkinson, B. L.; Binette, F.; Selmani,
A. Biomaterials 2000, 21, 2155.
(5) Peppas, N. A.; Bures, P.; Leobandung, W.; Ichikawa, H. Eur. J.
Pharm. Biopharm. 2000, 50, 27.
(6) (a) Nowak, A. P.; Breedveld, V.; Pakstis, L.; Ozbas, B.; Pine, D.
J.; Pochan, D.; Deming, T. J. Nature 2002, 417, 424. (b) Petka, W. A.;
Harden, J. L.; McGrath, K. P.; Wirtz, D.; Tirrell, D. A. Science 1998,
281, 389. (c) Qu, Y.; Payne, S. C.; Apkarian, R. P.; Conticello, V. P. J.
Am. Chem. Soc. 2000, 122, 5014.
(7) (a) Lee, J.; Macosko, C. W.; Urry, D. W. Macromolecules 2001, 34,
4114. (b) McMillan, R. A.; Conticello, V. P. Macromolecules 2000, 33,
4809.
(8) Shah, K. R. In Polymeric Materials Encyclopedia; Salamone, J.
C., Ed.; CRC Press: Boca Raton, FL, 1996; p 3092.
On the other hand, nonpolymeric self-assembly driven
hydrogels derived from small molecules have attracted
attention because of the amenability to tuning the gel
properties by changing the chemical functionality, preparation conditions such as the pH and temperature, and
composition of the aqueous solution. However, in contrast
to their low molecular mass organic gelators (LMOGs),9
the examples of nonpolymeric hydrogels are indeed
limited.10 This is due to the fact that LMOGs are often
insoluble or poorly soluble in water as well as they display
high crystallinity in water. Moreover, structural requirement for a molecule to be a hydrogelator is quite critical.
It is believed that the careful balance between hydrophobic
interactions and hydrogen bonding in water is required
to achieve the essential three-dimensional elastic networks
of these small gelator molecules within which the water
molecules get immobilized. To achieve such a balance, it
is important to have a hydrophobic moiety and multiple
hydrogen bonding sites in the potential gelator molecules.
Moreover, solubility in water is also an important point
to be considered.
We noticed in the Cambridge Crystallographic Database11 that mainly two types of hydrogen bonding patterns
are present in pyridyl amides. Both are hydrogen bonded
one-dimensional polymeric networks, which is believed
to be one of the prerequisites for a molecule to become a
potential gelator:9e one through a typical N-H‚‚‚O synthon
involving the amide moiety and the other through a
N-H‚‚‚N synthon involving the amide and pyridine ring
nitrogen. If the amide functionality is flanked by two
pyridine moieties, in either case, the network may be
(9) (a) Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133. (b) Abdallah,
D. J.; Weiss, R. G. Adv. Mater. 2000, 12, 1237. (c) Prost, J.; Rondelez,
F. Nature 1991, 350, 11. (d) Grownwald, O.; Shinkai, S. Curr. Opin.
Colloid Interface Sci. 2002, 7, 148. (e) van Esch, J.; Feringa, B. L. Angew.
Chem. 2000, 112, 2351; Angew. Chem., Int. Ed. 2000, 39, 2263. (f)
Grownwald, O.; Shinkai, S. Chem.sEur. J. 2000, 7, 4328. (g) Tiller, J.
C. Angew. Chem., Int. Ed. 2003, 42, 3072. (h) Menger, F. M.; Peresypkin,
A. V. J. Am. Chem. Soc. 2003, 125, 5340. (i) Menger, F. M.; Yamasaki,
Y.; Catlin, K. K.; Nishimi, T. Angew. Chem., Int. Ed. Engl. 1995, 34,
585. (j) Kölbel, M.; Menger, F. M. Chem. Commun. 2001, 275. (k) Heeres,
A.; van der Pol, C.; Stuart, M.; Friggeri, A.; Feringa, B. L.; van Esch,
J. J. Am. Chem. Soc. 2003, 125, 14252.
(10) Estroff, L. A.; Hamilton, A. D. Chem. Rev. 2004, 104, 1201 and
references therein.
(11) Allen, F. H.; Kennard, O. Chem. Des. Automat. News 1993, 8,
3137 (CSD version 5.24, Nov 2002).
10.1021/la049097j CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/23/2004
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Langmuir, Vol. 20, No. 24, 2004
Kumar et al.
Chart 1
Figure 1. Plot of Tgel (gel-sol dissociation temperature in °C)
versus gelator concentration (wt %, w/v) of 1.
Chart 2
Figure 2. DSC curves of the aqueous gel of 1 (10 wt %). Heating
and cooling rate: 5 °C/min.
envisaged as one-dimensional wherein pyridine ring
nitrogen atoms are also available for further hydrogen
bonding (Chart 1).
Because hydrophobicity (due to the heterocyclic aromatic ring), the plausible one-dimensional hydrogen
bonded network (either motif A or B, Chart 1), and the
expected solubility in water due to pyridine moieties are
present in this class of molecules, we have synthesized a
series of pyridyl amides as possible hydrogelators (Chart
2). Out of seven amides (1-7), only N-(4-pyridyl)isonicotinamide 1 is found to be an efficient hydrogelator, and
this paper describes its gelation behavior and structure.
Results and Discussion
All the amides 1-7 are sparingly soluble in water at
room temperature. However, upon heating at ∼90 °C, all
of them become soluble in water. On cooling to 25 °C, only
1 gives a translucent gel (which does not show any physical
deformity upon inversion of the test tube), and the others
do not produce a gel. The amide 1 turns out to be a highly
efficient gelator of water. The minimum gelator concentration (MGC) of 1 is found to be 0.37 wt %, meaning that
one molecule of the gelator is able to rigidify ∼3030
molecules of water. To estimate the thermal stability of
the gel, a plot of the gel-sol dissociation temperature
(Tgel)22 versus gelator concentration is examined.
Figure 1 clearly indicates that, with the increase in
gelator concentration, Tgel increases, which means that
the aggregation of the gelator molecules during gelation
is driven by strong supramolecular interactions. It is
interesting to note that the gelator is highly soluble in
water upon heating, and it is possible to form a thermoreversible gel even at 20 wt % (Tgel ) 79 °C).
The gelation behavior of 1 is quite pH sensitive. The pH
of the aqueous solution of 1 is found to be 7.7 at the MGC.
When the pH is changed to 5.0 using 1% AcOH (v/v), it
fails to form gel. On the other hand, when gelation
experiments are performed at pH 8-11 using NaHCO3,
a gel is formed. These results clearly indicate that the
free pyridine nitrogen atoms might be contributing toward
Figure 3. SEM of the xerogel of 1: (a) 0.37 wt % (bar ) 20 µm);
(b) 20 wt % (bar ) 10 µm).
the required self-assembly of the gelator molecules through
possible hydrogen bonding. To provide further support to
this hypothesis, a monohydrochloride salt 8 of the gelator
1 has been synthesized (Chart 2), and it also turns out to
be a nongelator. This indicates that both the ring nitrogen
atoms of the gelator 1 must be free from protonation to
form a gel.
A 10.0 wt % gel of 1 shows an endothermic phase
transition from gel to sol at 81 °C whereas in the
corresponding cooling cycle, the exothermic phase transition from sol to gel appears at 44 °C in a differential
scanning calorimetry (DSC) experiment (Figure 2).
Observation under a low resolution optical microscope
equipped with a cross polar reveals that the typical fibrous
nature of the gel (0.5 wt %) and the fibers, often radiating
from central points, is optically birefringent displaying
its crystalline nature.
To see the morphology of the fibers in more detail,
scanning electron microscopy (SEM) pictures at the MGC
are recorded. Figure 3a depicts the SEM picture of the
xerogel of 1 at the MGC. The morphology of the fibers
appears to have tape architecture. The widths of the tapes
range from 0.57 to 5.7 µm. Because 1 is able to form a
thermo-reversible gel even at a very high concentration
such as 20 wt %, SEM is also recorded to see the
morphology of the fibers at this concentration. Figure 3b
displays the SEM of the xerogel of 1 at 20 wt %. In this
Nonpolymeric Hydrogelator
Figure 4. 1H NMR spectra of the aqueous gel of 1 in D2O at
various temperatures.
case, the morphology of the fibers is also found to be of
tape type and the widths range from 1.65 to 5.5 µm. Fibers
in both the cases form a complicated three-dimensional
network. Understandably, the solvent water molecules
are immobilized in such a three-dimensional network of
fibers, resulting into gel formation.
Fourier transform infrared (FT-IR) spectroscopy of the
bulk solid, xerogel, and crystals (grown from EtOH) of 1
appears to be virtually identical, meaning that the internal
structure of the gelator molecule in the bulk solid is
identical to its xerogel as well as crystals grown from
EtOH. The amide I band in these cases appears at 1688
cm-1. Interestingly, the amide I band in the gel state (D2O)
appears at 1672 cm-1. The 16 cm-1 shift of the CdO
stretching may be attributed to further hydrogen bonding
either involving CdO and solvent water molecules or
rearranged self-assembly of the gelator molecules.
To provide further insights into the self-assembly
process during gelation, 1H NMR (D2O) experiments have
been performed on an aqueous 0.9 wt % gel of 1 at various
temperatures. Thus, at 25 °C, the Ha and Hd protons
appear at δ 8.77 and 8.53 respectively, whereas Hb and
Hc appear at 7.87-7.82. At 65 °C the corresponding signals
are obtained at δ 9.45 (Ha), 9.22 (Hb), and 8.53-8.39 (Hb
and Hc). Therefore, all the aromatic protons have been
gradually shifted downfield while heating the sample from
25 to 65 °C (Figure 4). This observation may be attributed
to the ordered self-assembly of the gelator molecule in the
gel state probably through π-π stacking interactions.12
Although both hydrogen bonding and hydrophobic
interactions play an important role in the gelation process
of the hydrogel, it is considered worthwhile to study the
hydrogen bonding interactions in these compounds in their
crystalline state to address the important structural
issue: what, if any, is the relationship between the
molecular packing of the bulk crystals of a compound and
its gelation behavior.9a Fortunately, X-ray quality crystals
of all the amides except 6 can be grown. The structure of
4-pyridyl benzamide 7 is already available in the literature.13 The single-crystal structure of the monohydrochloride salt 8 of the gelator 1 is also investigated to
compare the corresponding supramolecular assemblies
of the protonated 8 and nonprotonated form 1. Figure 5
depicts the supramolecular assemblies of the corresponding molecules (1-5 and 8) in their crystal structures. While
1, 4, and 5 display a one-dimensional hydrogen bonded
(12) Jung, J. H.; Shinkai, S.; Shimizu, T. Chem.sEur. J. 2002, 8,
2684.
(13) Noveron, J. C.; Lah, M. S.; Del Sesto, R. E.; Arif, A. M.; Miller,
J. S.; Stang, P. J. J. Am. Chem. Soc. 2002, 124, 6613.
Langmuir, Vol. 20, No. 24, 2004 10415
network through the N-H‚‚‚N (in 1), N-H‚‚‚O (in 4), and
both N-H‚‚‚N and N-H‚‚‚O (in 5) hydrogen bonds,
participation of water molecules in the crystal lattice of
2 makes the network three-dimensional. On the other
hand, the molecules in the crystal structure of 4 are
assembled mainly through dispersion force into a twodimensional sheet structure wherein the individual
molecules appear to be assembled via very weak NH‚‚‚N hydrogen bonding. The crystal structure of 713 also
displays a one-dimensional hydrogen bonded polymeric
network through N-H‚‚‚N interactions involving amide
and pyridine ring nitrogen atoms. It is believed, on the
basis of single-crystal structures of some organogelators,14,15 that the one-dimensional hydrogen bonded
network may induce the one-dimensional growth of the
gel fibril, whereas the growth perpendicular to the fibril
axis is slower because of interaction with the solvent
molecules, and, therefore, molecules that tend to form
one-dimensional hydrogen bonded network have a better
chance of showing gelation properties. Although the
gelation ability of 1 and nongelling behavior of 2 and 3
can be easily correlated with their corresponding crystal
structures (one-dimensional network for 1, three-dimensional network for 2, and two-dimensional network for 3),
the nongelling behavior of 4, 5, and 7 cannot be correlated
with the hydrogen bonding network (all one-dimensional)
observed in their corresponding crystal structures. Thus,
the present findings from the crystals structures of the
compounds studied here indicate that the supramolecular
process of aggregating the gelator molecules to form a gel
fibril is much more complicated than the simplistic view
stated above. However, it may be noted here that the main
differences in the molecular structures of these amides
arise due to the fact that, in gelator 1, the ring nitrogen
atoms are linearly oriented, whereas in others (2, 3, and
5) the relative positions of the ring nitrogen atoms are not
linear and there is only one ring nitrogen atom present
in 4 and 7. Therefore, the relative orientation and the
number of ring nitrogen atoms seem to be important for
gel fibril formation.
Because the monoprotonated form 8 of the gelator is a
nongelator, it is considered worthwhile to investigate its
single-crystal structure. In 8, the monoprotonated molecules are self-assembled through N-H‚‚‚N hydrogen
bonding involving protonated ring nitrogen atoms with
the nonprotonated counterpart to form a one-dimensional
hydrogen bonded network. Counterion Cl- and water of
crystallization are found to form a bridge between two
such one-dimensional hydrogen bonded chains of the
monoprotonated amides resulting in an overall onedimensional tape type of network (Figure 5f). Therefore,
none of the pyridine ring nitrogen atoms are available for
further hydrogen bonding in 8, which is in contrast to its
parent unprotonated structure (in 1) wherein one of the
pyridine ring nitrogen is available for further hydrogen
bonding.
The crystalline morph of the gel fibril needs not
necessarily be the same as that in the corresponding
xerogel because morphological transformation might take
place during solvent removal for xerogel preparation or
it might be initiated by some nucleation events induced
by the small amount of soluble gelator molecules present
in the bulk liquid in the gel state. To probe whether such
(14) (a) Luboradzki, R.; Gronwald, O.; Ikeda, M.; Shinkai, S.;
Reinhoudt, D. N. Tetrahedron 2000, 56, 9595. (b) Tamaru, S.-I.;
Luboradzki, R.; Shinkai, S. Chem. Lett. 2001, 336.
(15) (a) Ballabh, A.; Trivedi, D. R.; Dastidar, P. Chem. Mater. 2003,
15, 2136. (b) Trivedi, D. R.; Ballabh, A.; Dastidar, P. Chem. Mater.
2003, 15, 3971.
10416
Langmuir, Vol. 20, No. 24, 2004
Kumar et al.
Figure 5. Association modes of the molecules through hydrogen bonds and other nonbonded interactions as obtained in their
corresponding single-crystal structures. (a) One-dimensional network through the N-H‚‚‚N hydrogen bond in 1; (b) water-mediated
three-dimensional hydrogen bonding network in 2; (c) two-dimensional layer arising from the dispersion force and one-dimensional
network through weak N-H‚‚‚N interactions in 3; (d) one-dimensional network through weak N-H‚‚‚O interactions in 4; (e)
one-dimensional network arising from an unusual alternating N-H‚‚‚O and N-H‚‚‚N hydrogen bonding in 5; (f) one-dimensional
tape architecture involving N-H‚‚‚N, N-H‚‚‚Cl-, and O-H‚‚‚Cl- interactions in 8.
Scheme 1. Schematic Representation of the
Molecular Association in the Xerogel Fibrils of 1 As
Concluded from XRPD Experiments
Figure 6. XRPD patterns at various conditions of 1.
a transformation is indeed taking place, the simulated
powder diffraction pattern obtained from single-crystal
X-ray diffraction data and X-ray powder diffraction
(XRPD) of the bulk solid, xerogel, and gel of 1 are compared
(Figure 6). XRPD of the gel is recorded using a highly
concentrated solution of 1 (20 wt %) because the patterns
below 20 wt % are highly masked by the scattering of
water. It is clear from Figure 6 that the simulated, bulk
solid and xerogel XRPD patterns are virtually super-
imposable, meaning that the single-crystal structure of 1
truly represents the molecular packing in its bulk solid
and gel fibers of the xerogel. Therefore, the aggregation
mode of the molecules in xerogel fibrils is established
(Scheme 1). However, the XRPD pattern of the gel is found
to be different. Therefore, it appears that the morph
responsible for hydrogel formation is quite different from
that present in the xerogel or bulk solid.
Because solubility and crystallinity may have a significant impact on gelation, solubility of all the compounds
in water at 25 °C has been measured. Most of the
Nonpolymeric Hydrogelator
Langmuir, Vol. 20, No. 24, 2004 10417
Table 1. Crystallographic Parameters for 1-5 and 8
crystal data
empirical
formula
FW
crystal size
(mm), color
crystal system
space group
a, Å
b, Å
c, Å
r/0
β/0
γ/0
volume, Å-3
Z
Dcalc
F(000)
µ Mo KR (mm-1)
temperature (K)
observed reflections [I > 2σ(I)]
parameters
refined
goodness of fit
final R1 on
observed data
final wR2 on
observed data
1
2
3
4
5
8
C11H9N3O
C11H11N3O2
C11H9N3O
C12H10N2O
C22H18N6O2
C22H22Cl2N6O3
199.21
0.31 × 0.21 × 0.17,
colorless
orthorhombic
Pbcn
14.169(7)
8.920(6)
15.709(13)
90.00
90.00
90.00
1985(2)
8
1.333
832
0.090
293(2)
822
217.23
0.56 × 0.33 × 0.18,
pale yellow
orthorhombic
Pbca
24.983(11)
12.394(5)
7.039(3)
90.00
90.00
90.00
2179.6(16)
8
1.324
912
0.094
293(2)
859
199.21
0.67 × 0.43 × 0.19,
colorless
monoclinic
P21/n
8.3652(8)
13.5971(13)
8.7826(9)
90.00
102.248(2)
90.00
976.22(17)
4
1.355
416
0.092
293(2)
1722
198.22
0.55 × 0.34 × 0.11,
pale yellow
triclinic
P1
h
5.3406(7)
7.8247(10)
12.1855(15)
74.337(2)
79.174(2)
89.913(2)
480.93(11)
2
1.369
208
0.090
293(2)
1877
398.42
0.34 × 0.26 × 0.23,
colorless
triclinic
P1h
8.703(6)
10.393(4)
12.564(5)
95.37(3)
108.00(5)
112.87(6)
965.8(9)
2
1.370
416
0.093
293(2)
1877
489.35
0.74 × 0.59 × 0.29,
colorless
triclinic
P1
h
8.6136(9)
11.5406(12)
11.9548(12)
80.317(2)
75.454(2)
85.618(2)
1133.2(2)
2
1.434
508
0.324
293(2)
3780
173
189
172
176
343
386
0.931
0.0412
1.149
0.0715
1.043
0.0536
1.086
0.0452
0.997
0.0420
1.063
0.0435
0.0956
0.1908
0.1333
0.1213
0.0988
0.1216
Table 2. Hydrogen Bonding Parameters of 1-5 and 8
D-H‚‚‚A
1
N(9)-H(9)‚‚‚N(1)
2
N(9)-H(9)‚‚‚O(16)
O(16)-H(16A)‚‚‚N(1)
O(16)-H(16B)‚‚‚N(14)
3
N(9)-H(9)‚‚‚N(1)
4
N(9)-H(9)‚‚‚O(8)
5
N(9′)-H(9′)‚‚‚O(8)
N(9)-H(9)‚‚‚N(13′)
8
N(9)-H(9)‚‚‚Cl(1)
N(13)-H(13)‚‚‚N(1)
O(16)-H(17A)‚‚‚Cl(1)
O(16)-H(17B)‚‚‚Cl(1′)
N(9′)-H(9′)‚‚‚Cl(1′)
N(13′)-H(13′)‚‚‚N(1′)
∠D-H‚‚‚A
D-H
H‚‚‚A
D‚‚‚A
symmetry operation for A
0.89(3)
2.06(3)
2.953(3)
174(3)
-x + 0.5, y - 0.5, z
0.91(3)
1.14(7)
0.77(5)
1.99(4)
1.76(7)
2.09(5)
2.885(4)
2.887(5)
2.819(4)
169(3)
171(5)
159(5)
-x, -y + 0.5, z + 0.5
-x + 0.5, y - 0.5, z
-x, -y + 1, -z + 1
0.82(2
2.57(2)
3.3913(19)
172.1(17)
x + 0.5, -y + 0.5, z + 0.5
0.862(17)
2.337(17)
3.1522(15)
157.7(13)
x + 1, y, z
0.83(2)
0.85(2)
2.18(2)
2.11(2)
3.001(3)
2.956(4)
173(2)
169.6(19)
x, y, z
x + 1, y + 1, z
0.84(2)
0.92(2)
0.90(3)
0.82(3)
0.84(2)
0.94(3)
2.47(2)
1.88(3)
2.31(3)
2.40(3)
2.43(2
1.85(3)
3.2926(16)
2.7893(19)
3.200(2)
3.213(2)
3.2640(16)
2.7752(19)
164.5(19)
168(2)
171(3)
174(3)
169.9(18)
167(2)
x, y, z
x, y, z + 1
-x + 1, -y + 1, -z + 1
-x + 1, -y + 1, -z + 1
x + 1, y, z
x, y, z - 1
nongelator amides 2, 3, 5, and 6 are found to be more
soluble than the gelator 1, and monoprotonated amide 8
is found to be extremely soluble in water. On the other
hand, 4 and 7 have solubility comparable to that of 1
(Supporting Information). Less solubility of 1 probably
helps the molecules aggregate in required superstructures
during gel formation. The fact that 4 and 7 are nongelator
despite having solubility comparable to that of 1 may be
because of the fact that in both the compounds, there is
only one ring nitrogen atom in contrast to the gelator
molecule 1.
free from protonation to form a gel. Gel formation is
observed in a wide range of gelator concentrations (0.3620 wt %, w/v), which leaves room to play with the physical
property of the gel. Variable-temperature 1H NMR
experiments reveal that in the gel state the gelator
molecules are quite ordered in nature probably through
π-π stacking interactions. Both FT-IR and XRPD experiments indicate that the superstructure of the fibril in the
gel state is different from that in its bulk solid or xerogel
state.
Conclusions
Materials and Physical Measurements. All chemicals are
commercially available (Aldrich) and used without further
purification. Microanalyses are performed on a Perkin-Elmer
elemental analyzer 2400, Series II. FT-IR and NMR spectra were
recorded using Perkin-Elmer Spectrum GX and 200 MHz Bruker
Avance DPX200 spectrometers, respectively. Powder X-ray patterns are recorded on an XPERT Philips (Cu KR radiation)
diffractometer. SEM is performed on a LEO 1430VP. DSC
analyses are performed on a Mettler Toledo DSC 822e.
General Methods of Syntheses. All amides 2-7 are
synthesized by the standard reaction between the corresponding
The present example, that is, N-(4-pyridyl)isonicotinamide 1, definitely represents an efficient hydrogelator
with remarkably low molecular weight. Nongelling behavior of related amides (2-7) indicates that the number
of ring nitrogen atoms and their relative position are
important for gel formation. The fact that 1 does not form
a gel either at pH 5.0 or in its monoprotonated form 8
clearly shows that both the ring nitrogen atoms must be
Experimental Section
10418
Langmuir, Vol. 20, No. 24, 2004
acid and amine in the presence of Et3N. 1 is synthesized by
following the reported procedure.16 The monohydrochloride salt
8 of the gelator is prepared by excluding the bicarbonate-washing
step from the synthetic procedure of the gelator.
Analytical Data. 1: mp 196 °C. Anal. Calcd for C11H9N3O:
C, 66.32; H, 4.55; N, 21.09. Found: C, 65.86; H, 4.85; N, 21.02.
1H NMR (MeOD): 8.75 (d, J ) 6 Hz, 2H), 8.49 (d, J ) 8 Hz, 2H),
7.92-7.83 (m, 4H). FT-IR (KBr, cm-1): 3303w, 3238w, 3154m,
3056w, 2998w, 2958m, 2881m, 2815m, 2741w, 2454w, 1960m,
1870w, 1811w, 1688vs, 1619m, 1592vs, 1556m, 1524vs, 1487s,
1413s, 1330s, 1305vs, 1261m, 1227w, 1207m, 1124m, 1094w,
1062s, 991m, 860s, 825s, 756s, 719m, 689m, 660w, 593s, 542s,
507s.
2: mp 162-164 °C. Anal. Calcd for C11H11N3O2 (molecular
formula includes one molecule of H2O): C, 60.82; H, 5.10; N,
19.34. Found: C, 60.65; H, 4.80; N, 18.27. 1H NMR (MeOD):
8.912 (s, 1H), 8.767 (d, J ) 4.6 Hz, 3H), 8.352-8.258 (m, 3H),
7.927 (d, J ) 5 Hz, 3H), 7.501-7.438 (m, 1H). FT-IR (KBr, cm-1):
3310m, 3194w, 3130w, 3105w, 3069w, 3048w, 3015w, 2918w,
2855w, 2360w, 2284w, 1974m, 1923w, 1872w, 1849w, 1680vs,
1623s, 1589s, 1555vs, 1480s, 1427vs, 1329w, 1307vs, 1242w,
1220m, 1137m, 1103w, 1067w, 1052m, 1023m, 999s, 971w, 938m,
895m, 854m, 840m, 813s, 790w, 756s, 701vs, 666w, 629s, 594m,
522s, 491w, 421w, 406m.
3: mp 136-138 °C. Anal. Calcd for C11H9N3O: C, 66.32; H,
4.55; N, 21.09. Found: C, 65.62; H, 4.29; N, 20.36. 1H NMR
(MeOD): 8.748 (s, 2H), 8.363 (s, 1H), 8.245 (d, J ) 8.2 Hz, 1H),
7.902-7.801 (m, 3H), 7.208-7.153 (m, 1H). FT-IR (KBr, cm-1):
3294w, 3199w, 3155w, 3047m, 3002w, 2900w, 1987w, 1957w,
1911w, 1870w, 1839w, 1732w, 1679vs, 1604w, 1592w, 1577s,
1557m, 1535vs, 1495s, 1460m, 1431vs, 1339m, 1308vs, 1262m,
1238m, 1227m, 1147s, 1121m, 1104w, 1088w, 1065s, 991s, 968w,
957w, 894m, 873m, 848m, 781vs, 749s, 690s, 622m, 597s, 520s,
468w, 421w, 406m.
4: mp 186-188 °C. Anal. Calcd for C12H10N2O: C, 72.71; H,
5.08; N, 14.13. Found: C, 72.80; H, 4.59; N, 22.32. 1H NMR
(MeOD): δ 8.745 (d, J ) 5 Hz, 2H), 7.898 (d, J ) 4.6 Hz, 2H),
7.727 (d, J ) 8 Hz, 2H), 7.415-7.339 (m, 2H), 7.210-7.139 (m,
1H). FT-IR (KBr, cm-1): 3342vs, 3128w, 3076w, 3060w, 3044m,
2790w, 2649w, 1943w, 1770w, 1657vs, 1601s, 1532vs, 1492m,
1442vs, 1407s, 1325s, 1266s, 1215m, 1177m, 1157w, 1119w,
1066m, 1031m, 1002w, 986m, 961w, 909m, 889m, 847m, 820m,
750vs, 712m, 690s, 650s, 585m, 507s, 429w.
5: mp 186-188 °C. Anal. Calcd for C11H9N3O: C, 66.32; H,
4.55; N, 21.09. Found: C, 65.77; H, 4.78; N, 22.93. 1H NMR
(MeOD): 9.10 (s, 1H), 8.76 (d, 1H), 8.47-8.36 (m, 3H),7.85 (d,
J ) 4 Hz, 2H), 7.64-7.58 (m, 1H). FT-IR (KBr, cm-1): 3308m,
3276m, 3186m, 3154w, 3037w, 2981w, 2949w, 2887w, 2817w,
1951w, 1795w, 1734w, 1694s, 1658s, 1615w, 1592vs, 1533s,
1513vs, 1439w, 1419vs, 1339vs, 1315s, 1219s, 1215s, 1193m,
1132w, 1115m, 1096m, 1066w, 1024m, 997m, 968m, 940w, 894w,
850m, 829s, 741m, 711s, 663m, 622m, 584s, 536s, 500m, 407m.
6: mp 182-184 °C. Anal. Calcd for C11H9N3O: C, 66.32; H,
4.55; N, 21.09. Found: C, 65.22; H, 4.84; N, 22.13. 1H NMR
(MeOD): 9.116 (s, 1H), 8.904 (s, 1H), 8.753 (d, J ) 4.6 Hz, 1H),
8.396-8.248 (m, 3H), 7.628-7.421 (m, 2H). FT-IR (KBr, cm-1):
3286w, 3243m, 3184m, 3122w, 3104w, 3068m, 3047w, 3005w,
2955w, 2895w, 2831w, 2661w, 1980w, 1956w, 1941w, 1771w,
1732w, 1679vs, 1609s, 1587vs, 1547vs, 1484s, 1472m, 1428s,
(16) Gardner, T. S.; Wenis, E.; Lee, J. J. Org. Chem. 1954, 19, 753.
Kumar et al.
1331s, 1291vs, 1238m, 1190m, 1134m, 1114s, 1040m, 1022s,
969w, 929m, 886m, 842m, 816s, 712m, 701s, 628s, 597w, 521w,
470m, 416m.
8: mp >300 °C. Anal Calcd for C22H22Cl2N6O3: C, 52.08; H,
4.77; N, 16.56. Found: C, 52.82; H, 5.44; N, 15.22. 1H NMR
(MeOD): 8.826-8.675 (m, 4H), 8.318 (d, J ) 7.2 Hz, 2H), 7.9757.946 (m, 2H). FT-IR (KBr, cm-1): 3688w, 3409m, 3202w, 3084m,
3040w, 3018m, 2924w, 2814m, 2504w, 2125w, 2029w, 1961w,
1697vs, 1639vs, 1588vs, 1509vs, 1421m, 1398w, 1326s, 1299s,
1274m, 1254w, 1226w, 1194s, 1117m, 1102w, 1068m, 1052m,
1010s, 978m, 891m, 875w, 847s, 830m, 756s, 716w, 695vs, 649w,
579m, 530s, 442w.
Single-Crystal X-ray Diffraction. X-ray quality single
crystal of 1 is obtained from MeOH, 5, and 8 from water at room
temperature. Crystals of 2-4 are obtained from a water/MeOH
mixture.
Diffraction data for 3, 4, and 8 are collected using Mo KR (λ
) 0.7107 Å) radiation on a SMART APEX diffractometer equipped
with charge-coupled device area detector. Data for other crystals
1, 2, and 5 are collected using Mo KR (λ ) 0.7107 Å) radiation
on a CAD-4 diffractometer. Data collection, data reduction, and
structure solution/refinement are carried out using the software
package of SMART APEX for 3, 4, and 8 whereas the corresponding calculations are performed for the data collected on
CAD-4 using CAD4-PC,17 NRCVAX,18 and SHELX97.19 Graphics
are generated using PLATON20 and MERCURY 1.1.1.21
All structures are solved by direct methods and refined in a
routine manner. In all cases, nonhydrogen atoms are treated
anisotropically. Whenever possible, the hydrogen atoms are
located on a difference Fourier map and refined. In other cases,
the hydrogen atoms are geometrically fixed. The crystallographic
parameters are listed in Table 1. The hydrogen bonding
parameters are given in Table 2.
Acknowledgment. We thank all the reviewers for
their valuable comments and suggestions. Department of
Science and Technology and Ministry of Environment and
Forests, New Delhi, is thankfully acknowledged for
financial support. Dr. P. K. Ghosh is thanked for his
support.
Supporting Information Available: Solubility data
of 1-8 and ORTEP diagrams of 1-5 and 8 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
LA049097J
(17) CAD-4 Software, version 5.0; Enraf-Nonius: Delft, 1989.
(18) Gabe, I.; Page, Y. L.; Charland, I. P.; Lee, F. L.; While, P. S. J.
Appl. Crystallogr. 1989, 22, 384.
(19) Sheldrick, G. M. SHELEXL-97, A program for crystal structure
solution and refinement; University of Göttingen: Göttingen, Germany,
1993.
(20) Spek, A. L. PLATON-97; University of Utrecht: Utrecht, The
Netherlands, 1997.
(21) Mercury 1.1.1 Supplied with Cambridge Structural Database;
CCDC: Cambridge, U.K., 2001-2002.
(22) Tgel was measured by the drop ball method. A custom-made
glass ball weighing 0.19 g was placed on the gel surface, and the gel
was heated gradually in an oil bath. The temperature at which the ball
fell into the bottom of the test tube was recorded as the gel dissociation
temperature (Tgel).