Oligoamide duplexes as organogelators

Article abstract of DOI:10.1021/ol100953e

Oligoamide duplexes carrying multiple alkyl side chains were found to serve as gelators for aromatic solvents. The double-stranded backbone was essential for the hierarchical self-assembly of the molecular duplex into fibers of high aspect ratios. The demonstrated gelating abilities may be extended to a large family of analogous H-bonded duplexes having different H-bonding sequences, leading to a unique platform for developing a diverse variety of potential gelators based on a supramolecular and/or a dynamic covalent approach.

Full text of DOI:10.1021/ol100953e

ORGANIC
LETTERS
2010
Vol. 12, No. 13
2958-2961
Oligoamide Duplexes as Organogelators
Ruikai Cao,† Jingjing Zhou,† Wei Wang,† Wen Feng,† Xianghui Li,†
Penghui Zhang,† Pengchi Deng,† Lihua Yuan,*,† and Bing Gong*,‡
College of Chemistry, Key Laboratory for Radiation Physics and Technology of
Ministry of Education, Institute of Nuclear Science and Technology, Analytical & Testing
Center of Sichuan UniVersity, Sichuan UniVersity, Chengdu 610064, Sichuan, China, and
Department of Chemistry, The State UniVersity of New York,
Buffalo, New York 14260
lhyuan@scu.edu.cn; bgong@buffalo.edu
Received April 27, 2010
ABSTRACT
Oligoamide duplexes carrying multiple alkyl side chains were found to serve as gelators for aromatic solvents. The double-stranded backbone
was essential for the hierarchical self-assembly of the molecular duplex into fibers of high aspect ratios. The demonstrated gelating abilities
may be extended to a large family of analogous H-bonded duplexes having different H-bonding sequences, leading to a unique platform for
developing a diverse variety of potential gelators based on a supramolecular and/or a dynamic covalent approach.
Gelation, as a phenomenon frequently observed in nature,
has attracted wide attention due to its fundamental signifi-
cance and potential applications.1,2 Gelators associate into
three-dimensional networks that immobilize the flow of liquid
by trapping solvent molecules. Interest in organic gelators
derives not only from the motivation of developing materials
with applications in fields such as membrane and separation
technology, catalysis, nanotechanology, light-harvesting ma-
terials, dye-sensitized solar cells, etc. but also from the desire
to understand how noncovalent interactions function coop-
eratively to bring about such unique properties. Many
synthetic molecules that assemble into supramolecular
networks via hydrogen bonding, π-π stacking, and solvo-
(3) (a) Wang, R.; Geiger, C.; Chen, L.; Swanson, B.; Whitten, D. G.
J. Am. Chem. Soc. 2000, 122, 2399. (b) Menger, F. M.; Caran, K. L. J. Am.
Chem. Soc. 2000, 122, 11679. (c) Wang, G.; Hamilton, A. D. Chem.sEur.
J. 2002, 8, 1954. (d) van Gorp, J. J.; Vekemans, J. A. J. M.; Meijer, E. W.
J. Am. Chem. Soc. 2002, 124, 14759. (e) George, M.; Weiss, R. G. Langmuir
2003, 19, 1017. (f) Wu¨rthner, F.; Yao, S.; Beginn, U. Angew. Chem., Int.
Ed. 2003, 42, 3247. (g) de Jong, J. J. D.; Lucas, L. N.; Kellog, R. M.; van
Esch, J. H.; Feringa, B. L. Science 2004, 304, 278. (h) Zhan, C.; Gao, P.;
Liu, M. Chem. Commun. 2005, 462. (i) Li, H. F.; Homan, E. A.; Lampkins,
A. J.; Ghiviriga, I.; Castellano, R. K. Org. Lett. 2005, 7, 443. (j) Kishimura,
A.; Yamashita, T.; Aida, T. J. Am. Chem. Soc. 2005, 127, 179. (k) Yoshida,
M.; Fresco, Z. M.; Ohnishi, S.; Frechet, J. M. J. Macromolecules 2005, 38,
334. (l) Park, T.; Zimmerman, S. C. J. Am. Chem. Soc. 2006, 128, 11582.
(m) Zubarev, E. R.; Sone, E. D.; Stupp, S. I. Chem.sEur. J. 2006, 12,
7313. (n) Pal, A.; Ghosh, Y. K.; Bhattacharya, S. Tetrahedron 2007, 63,
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4991. (p) Fujita, N.; Sakamoto, Y.; Shirakawa, M.; Ojima, M.; Fujii, A.;
Ozaki, M.; Shinkai, S. J. Am. Chem. Soc. 2007, 129, 4134. (q) Li, H.; Estroff,
L. A. J. Am. Chem. Soc. 2007, 129, 5480. (r) Baddeley, C.; Yan, Z.; King,
G.; Woodward, P. M.; Badjic´, J. D. J. Org. Chem. 2007, 72, 7270. (s) Percec,
V.; Peterca, M.; Yurchenko, M. E.; Rudick, J. G.; Heiney, P. A. Chem.sEur.
J. 2008, 14, 909. (t) Moffat, J. R.; David K. Smith, D. K. Chem. Commun.
2009, 316. (u) Du, P.; Wang, G.-T.; Zhao, X.; Li, G.-Y.; Jiang, X.-K.; Li,
Z.-T. Tetrahedron Lett. 2010, 51, 188.
† Sichuan University.
‡ The State University of New York.
(1) (a) Terech, P.; Weiss, R. G. Chem. ReV. 1997, 97, 3133. (b) Estroff,
L. A.; Hamilton, A. D. Chem. ReV. 2004, 104, 1201. (c) Ajayaghosh, A.;
Praveen, V. K. Acc. Chem. Res. 2007, 40, 644. (e) Zang, L.; Che, Y.; Moore,
J. S. Acc. Chem. Res. 2008, 41, 1596. (d) van Esch, J. H. Langmuir 2009,
25, 8392
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Miravet, J. F.; Escuder, B. Chem. Commun. 2005, 5796. (c) Tu, T.;
Assenmacher, W.; Peterlik, H.; Schnakenburg, G.; Do¨tz, K. H. Angew.
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10.1021/ol100953e  2010 American Chemical Society
Published on Web 06/10/2010

phobic effects have been reported as gelators.3 Organic
gelators are developed as “smart” or responsive gel systems
that respond to stimuli such as photoirradiation, electro-
chemistry, solvent polarity and/or pH change. Nevertheless,
the mechanism behind gelation remains elusive.1d Molecules
allowing ready structural modification could afford new
gelators capable of interacting with different solvents. The
availability of new gelators may also lead to valuable insights
into the mechanism of gelation. Herein we report the gelation
of several organic solvents by a series of double-stranded
oligoamides. These duplexes not only offer convenient
structural tunability, but more importantly, can be formed
based on simple mixing of strands having complementary
H-bonding sequences.
H-bonded dimer (duplex) 2a·2a serve as a gelator? Dimer
2a·2a belongs to a family of duplexes consisting of comple-
mentary strands that associate sequence-specifically via
interstrand H-bonds, which have been developed by us as
reliable association units for directing intermolecular as-
sembly.4
A H-bonded duplex like 2a·2a offers three sets of sites
that may allow the tuning of gelating property. For example,
the four interstrand H-bonds ensure the sequence-specific
pairing of two oligoamide strands into a duplex. Compared
to individual strands, a H-bonded duplex is significantly
rigidified, leading to a well-defined, largely flat surface that
should promote further intermolecular association via π-π
stacking interactions. In addition, adjusting the alkyl side
chains and end groups attached to the oligoamide strands
allows properties such as solubility, precipitation, crystal-
lization, and packing of the corresponding molecules and
supermolecules to be varied, which provides a platform for
the systematic exploration of the influence of structures on
gelating ability. It would thus be very attractive if 2a could
gelate solvents since such ability may also be shared by
analogous oligoamides and their H-bonded duplexes, which
may lead to many new gelators.
During our study on H-bond-mediated reactions, it was
found that the metathesis of H-bonded duplex 2a·2a led to
the efficient formation of 1 (Scheme 1). Compound 1 was
Scheme 1. Covalent Cross-Linking of Hydrogen-Bonded 2a·2a
Simple screening indicated that 2a was able to form partial
gels with benzene, toluene, and o-xylene, the same solvents
gelated or partially gelated by 1. In mesitylene, in which 1
was insoluble, partial gelation was induced by 2a. The
modest gelating ability demonstrated by 2a prompted us to
design and prepare strands 2b-f that share the same
backbone with 2a but differ in their side (R) chains and end
(R1 and R2) groups.
then observed to gelate benzene and toluene (Table 1). Unlike
benzene and toluene, o-xylene formed a partial gel, i.e., a
flowing, viscous but gel-like solution, with 1.
To probe the effects of end groups, the gelation of several
aromatic solvents by 2b, 2c, and 2d were examined (Table
1). Oligoamide 2b, which can be regarded as being derived
from 2a by shortening the end groups, could form a partial
gel only with toluene while being insoluble in the other
aromatic solvents. Replacing the end methyl group of 2b
with n-butyl group led to 2c that partially gelated all of the
aromatic solvents tested. Replacing the ethyl group of 2c
with 2-ethylhexyl group resulted in 2d that showed a
significantly expanded gelating ability. In contrast to the
partial gels formed with 2a-c, compound 2d gelated benzene
and toluene, with CGC values of 8.1 and 7.3 mM, respec-
tively. In addition, compound 2d gelated o-xylene with which
1 could only formed a partial gel. Methylene chloride, in
which 1 was insoluble and compounds 2a-c readily dis-
solved, was also gelated by 2d.
Table 1. Gelation Properties and Values of CGCsa
solvent
1
2a 2b 2c
2d
2e
2f
CH2Cl2
benzene
I
S
S
P
S
G19.1,tr
S
S
G6.1,o pG
pG G8.1,o
G11.1,tr G13.5,tr
G11.9,tr G16.5,tr
G17.8,tr G22.0,tr
G12.5,o G12.6,o
pG
G9.8,o
toluene
o-xylene
mesitylene
nitrobenzene
diphenyl ether
G5.4,o pG pG pG G7.3,o
pG
I
pG
pG
P
I
I
I
I
pG G7.4,o
pG
pG
pG
P
P
P
I
G16.7,o
G12.2,o
I
P
a Critical gelation concentrations (CGCs) at room temperature (25 °C)
are given in mM. Abbreviations: G ) gel, pG ) partial gel, I ) insoluble,
S ) soluble, P ) precipitation, tr ) transparent, o ) opaque.
Such an observation led to additional questions. For
example, could 1 gelate other solvents? Could 2a or its
The influence of side (R) chains was then explored by
comparing 2e and 2f with 2d (Table 1). With its n-dodecyl
side chains, compound 2e not only gelated the same solvents
that formed gels with 2d but also resulted in the gelation of
mesitylene and diphenyl ether in which 2d precipitated out
upon cooling. Further increasing the length of the side chains
(4) (a) Gong, B.; Yan, Y.; Zeng, H.; Skrzypczak-Jankunn, E.; Kim,
Y. W.; Zhu, J.; Ickes, H. J. Am. Chem. Soc. 1999, 121, 5607. (b) Zeng, H.;
Miller, R.; Flowers, R. A.; Gong, J. Am. Chem. Soc. 2000, 122, 2635. (c)
Synlett 2001, 5, 582. (d) Yang, X.; Martinovic, S.; Smith, R. D.; Gong, B.
J. Am. Chem. Soc. 2003, 125, 9932. (e) Gong, B. Polym. Int. 2007, 56,
436.
Org. Lett., Vol. 12, No. 13, 2010
2959

led to 2f that turned out to be a “broad-spectrum” gelator
capable of gelating all the aromatic solvents examined.
Comparing the CGC values of 2d (8.1 mM), 2e (11.1 mM),
and 2f (13.5 mM) in benzene indicates that the gelating
efficiencies are inversely related to the length of the side
chains.6 This phenomenon had been observed before.5
Extending the length of side chains probably enhanced the
solubility of the gelators, which weakened intermolecular
aggregation and resulted in higher CGC values.
observations imply that 2d undergoes aggregation at a
concentration far below its CGC for benzene.
Xerogels obtained by freeze-drying the gels of 1 and 2d
with benzene were examined using scanning electron mi-
croscopy (SEM). Rigid fibers were observed for the gel of
1 (Figure 1a). The SEM image of the xerogel of 2d revealed
The reliance of gelation on the presence of the double-
stranded backbone was demonstrated by comparing the
different behavior of 1 and 2d in a mixed solvent containing
CHCl3 and CH3OH (9/1, v/v). It was found that 2d was
soluble in this solvent, while 1 acted as a gelator.6 The
inability of 2d to gelate this mixed solvent can be explained
by the reduced ratio of its H-bonded duplex in a solvent of
enhanced polarity. On the basis of 1H NMR dilution
experiments (25 °C), the dimerization constant of 2d in
CDCl3 was found to be 1.9 × 104 M-1 and that in CDCl3/
CD3OD (100/1, v/v) to be 1.7 × 103 M-1, a difference of
more than 1 order of magnitude.6 It was thus concluded that
the population of H-bonded duplex 2d·2d was significantly
diminished in CHCl3/CH3OH (9/1), a solvent of much higher
Figure 1. SEM images of the free-dried benzene gel formed by
1
polarity than the one used in the H NMR titration experi-
ments.
(a) 1 (average width of fibers ∼3.5 µm, length ∼10-25 µm) and
(b) 2d (average width of fibers ∼2 µm, length >100 µm). TEM
image of the gel from benzene with (c) 1 (average width of fibers
∼60 nm, length >0.6 µm) and (d) 2d (average width of fibers ∼190
nm, length >1.5 µm).
Gelation is contingent upon the aggregation of gelator
1
molecules into supramolecular networks. In CDCl3, the H
NMR spectra of 2d (15 mM) showed well-resolved peaks,
whereas in benzene-d6 (15 mM), poorly resolved signals were
observed.6 The variable-temperature 1H NMR spectra of 2d
in benzene-d6 provided additional evidence for the self-
long fibers (Figure 1b). The formation of fibers suggests that
both 1 and 2d indeed formed extended networks, which is
consistent with and explains the observed gelation of benzene
by these compounds. The formation of long fibers was also
revealed by transmission electron microscopy (TEM) images
(Figure 1c, d). The high aspect ratio of the fibers from SEM
and TME images indicates the highly anisotropic interactions,
which is in line with π-π aromatic stacking interactions
among these molecules and supermolecules.6 Additional
evidence for the presence of a 3D network was provided by
atomic force microscopy (AFM), which revealed bundles of
fibers formed by 2d in benzene.6
The xerogels of 1 and 2d from benzene were also
examined by X-ray diffraction (XRD), which provided
additional insights into the packing of these molecules.6 The
diffraction patterns revealed low angle reflections at 26.7 and
13.0 Å, respectively, for 1 and 28.7 and 15.2 Å for 2d. Given
the different sizes of the end groups of 1 and 2d, these
distances are within the length (∼20 Å) and width (∼12 Å)
revealed by the crystal structure of an H-bonded duplex
having the same backbone.4a The diffractograms of both 1
and 2d contain a peak at 4.1 Å that is within the range of
documented π-π stacking distance.8 These XRD data
confirmed that the H-bonded or covalently cross-linked
duplexes indeed serve as the basic units for assembling into
supramolecular networks. With their large surface areas, the
6
1
assembly process. At 10 °C, the H NMR signals of 2d
nearly disappeared, suggesting strong intermolecular ag-
gregation. Above temperatures above 25 °C, the signals of
aromatic protons became increasingly resolved. At 70 °C,
the otherwise weak and broad signals characteristic of 2d
became well dispersed. Further heating led to no additional
change. These results indicate that the aggregation of 2d is
weakened at elevated temperatures and eventually disrupted.
1
At room temperature, compound 1 also gave distinct H
NMR signals in CDCl3 but had low solubility in benzene-
d6, which again suggested strong intermolecular aggregation.
These observations demonstrate that 1 and 2d aggregate in
benzene with which they form gels.
A large shift of 89 nm was observed in the emission
maxima of the fluorescence spectra of the solution (0.1 mM)
and the gel of 2d in CH2Cl2.6 This observation is consistent
with the parallel, face-to-face packing of the duplexes in the
gel state via π-π stacking interaction. In addition, the
UV-vis spectra of 2d in benzene (10-5 M) contained a broad
peak around 318 nm at 15 °C. As the temperature was raised
from 15 to 70 °C, a new peak appeared at 276 nm with
increasing intensity. This was accompanied by a slight
decrease in the intensity of the peak at 318 nm.6,7 These
(5) Zweep, N.; Hopkinson, A.; Meetsma, A.; Browne, W. R.; Feringa,
B. L.; van Esch, J. H. Langmuir 2009, 25, 8802.
(6) See the Supporting Information for additional data and details.
(8) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int.
Ed. 2003, 42, 1210.
(7) George, S. J.; Ajayaghosh, A. Chem.sEur. J. 2005, 11, 3217
.
2960
Org. Lett., Vol. 12, No. 13, 2010

duplexes associate into 1D networks via π-π stacking
interaction. The 1D networks pack further into fibers via van
der Waals interaction between the alkyl side chains and end
groups of the duplexes, which leads to the formation, further
association and entanglement of the fibers, and therefore the
observed gelation of solvent molecules.6
Having demonstrated the correlation between the double-
stranded backbone and the gelation of organic solvents, it
was reasoned that gelators with altered capabilities might
be obtained by pairing two different strands. Such a duplex
may consist of two different strands that (1) have the same
H-bonding sequence but differ in their side chains and end
group; or (2) consist of two strands having different,
complementary H-bonding sequences and the same or
different side chains and end groups. In this work, the first
possibility was probed by mixing 2b, which is insoluble in
benzene at room temperature, and 2f, which forms a
transparent gel with benzene with a CGC of 13.5 mM (Figure
2). It was found that the presence of both 2b and 2f in
of 2b, the CGC value of 2f changed to 9.3 mM, a
concentration that is too low for pure 2f to gelate benzene.
Although additional details remain to be elucidated, this
example serves to demonstrate an encouraging first step for
developing duplex gelators by pairing different strands.
In summary, oligoamide duplexes have been observed to
serve as organogelators. Varying the side chains and end
groups of the oligoamides has resulted in gelators with
expanded and altered gelating abilities. Evidence from NMR,
SEM, TEM, AFM, fluorescence, UV-vis, and XRD dem-
onstrated the aggregation of the duplexes into fibrous
networks. Noncovalent forces such as π-π stacking and van
der Waals interactions should be the cause of the formation
of fibrillar aggregates that lead to gelation.6 These duplexes
offer multiple levels of tunability including convenient
structural modification as well as rapid, straightforward
recombination based on the simple mixing of complementary
strands.4 Therefore, such a double-stranded system represents
a platform allowing the diversity of potential gelators to be
systematically expanded. Furthermore, duplexes cross-linked
via dynamic covalent bonds9 may lead to gelators for polar
solvents including water. The dynamic formation of the
duplexes foretells the prospect of identifying gelators of
desired properties based on a supramolecular and/or dynamic
covalent combinatorial approach. The corresponding studies
are being carried out, results from which will be reported in
due course.
Acknowledgment. The National Natural Science Founda-
tion of China (20874062) and the National Science Founda-
tion (CHE-0701540), SRF for ROCS, and Ms. Xinyuan
Zhang of the Analytical Center of Sichuan University are
acknowledged for support and technical assistance.
Supporting Information Available: Synthesis, analytical
data, gelation procedures, NMR and mass spectra, TEM and
additional SEM images, XRD results, AFM, fluorescence,
UV/vis spectra, and a model of the assemblies of the
duplexes. This material is available free of charge via the
Internet at http://pubs.acs.org.
Figure 2. Photos of (a) a solution of compound 2f in benzene at
9.3 mM, (b) a transparent gel formed by 2f in benzene at 13.5
mM, and (c) an opaque gel formed by a 1:1 mixture of 2b and 2f
in benzene at 9.3 mM, at room temperature.
benzene led to significant changes of gelation properties for
both strands. Specifically, heating a 1:1 mixture of 2b and
2f in benzene led to a clear solution that turned into a stable
gel upon cooling to room temperature. The resultant gel,
being opaque, had no similarity to the transparent gel induced
by 2f alone in benzene. Besides, in the presence of 1 equiv
OL100953E
(9) (a) Roland, J. T.; Guan, Z. J. Am. Chem. Soc. 2004, 126, 14328. (b)
Yang, X. W.; Gong, B. Angew. Chem., Int. Ed. 2005, 44, 1352. (c) Li,
M. F.; Yamato, K.; Ferguson, J. S.; Gong, B. J. Am. Chem. Soc. 2006,
128, 16528. (d) Li, M.; Yamato, K.; Ferguson, J. S.; Singarapu, K. K.;
Szyperski, T.; Gong, B. J. Am. Chem. Soc. 2008, 130, 491.
Org. Lett., Vol. 12, No. 13, 2010
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