Orthogonal Self-Assembly of Low Molecular Weight Hydrogelators and Surfactants

Article abstract of DOI:10.1021/ja036954h

The concurrent self-assembly of new 1,3,5-trisamide-cyclohexane-based low molecular weight hydrogelators and various surfactants in water leads to the formation of self-assembled fibrillar networks with encapsulated micelles. This prototype system present

Full text of DOI:10.1021/ja036954h

Published on Web 10/31/2003
Orthogonal Self-Assembly of Low Molecular Weight Hydrogelators and
Surfactants
Andre´ Heeres,† Cornelia van der Pol,† Marc Stuart,‡ Arianna Friggeri,† Ben L. Feringa,*,‡ and
Jan van Esch*,‡
BioMaDe Technology Foundation, Nijenborgh 4, 9747 AG Groningen, The Netherlands, and Laboratory of Organic
Chemistry, Stratingh Institute, UniVersity of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Received June 28, 2003; E-mail: esch@chem.rug.nl
Chart 1
The self-assembly of partially incompatible molecular compo-
nents leading to (micro-) phase separation comprises a powerful
approach toward the fabrication of complex nanoarchitectures and
new materials and plays an essential role in nature, for example,
in protein folding and the formation of biological membranes.1-3
Phase-separated systems are so far usually based on the immiscibil-
ity of block-copolymer segments4 or fluorinated compounds with
hydrocarbons,5 and this toolbox has only very recently been
extended by low molecular weight organogels in liquid crystalline
phases.2b Here, we report on the concurrent self-assembly of new
low molecular weight hydrogelators6,7 and various surfactants in
Table 1. Gelation of Water by 1-3 in the Presence of
Surfactantsa
water, leading to self-assembled fibrillar networks with encapsulated
micelles. This prototype system presents an example of orthogonal
self-assembly, that is, the independent formation of two different
supramolecular structures, each with their own characteristics that
coexist within a single system.
anionic (SDS)
cationic (CTAB)
nonionic (OG)
<cmc
(4.6)c
>cmc
(13.6)c
<cmc
(0.5)c
>cmc
(2.2)c
<cmc
(6.8)c
>cmc
(34)c
gelatorb
1
2
3
G
G
G
G
G
G
p
G
G
p
G
G
G
G
G
G
G
G
Recent progress in the design of low molecular weight gelators
has emphasized the importance of self-complementary and highly
anisotropic interactions for the gelation ability.6b,8-10 In the present
work, we employed the 1,3,5-trisamide cyclohexane11 moiety
because it can self-assemble into 1D arrays stabilized by six
hydrogen bonds. We have extended this moiety with hydrophobic
amino acids to shield the amide groups from competitive interac-
tions with water and have thereby enforced the anisotropic self-
assembly of the gelator molecules in water due to the concurrent
action of hydrogen bonding and hydrophobic effects. A similar
combination of interactions stabilizes secondary protein structures,
which are stable in the presence of weakly interacting surfactants
and lipids.3
Compounds 1-3 are examples of gelators12 (Chart 1) that fulfill
these requirements and are easily prepared by coupling of the
corresponding (C-derivatized) amino acids with 1,3,5-tris(carbamoyl
chloride)cyclohexane. Compounds 1-3 all form thermoreversible
gels in water at very low concentrations.13,14 The very low critical
gelation concentrations (cgc) and the high gel-sol phase transition
temperatures (TGS) of the gels clearly indicate that self-assembly
of 1-3 is driven by strong intermolecular interactions. FTIR
spectroscopy of xerogels and of hydrogels of 1 showed amide I
vibrations typical for hydrogen-bonded amides at almost the same
position of 1639 and 1635 cm-1, respectively.15 This indicates that
the amide moieties participate in a similar hydrogen-bonded network
in hydrogels and their corresponding xerogels. Hydrogels of 1-3
tolerate NaCl concentrations up to at least 100 mM and are stable
for at least 3 months. Transmission electron microscopy (TEM and
cryo-TEM) of the gels in water revealed that 1-3 self-assemble
into elongated fibers (diameters for 1, 20-150 nm; 2, 10-50 nm;
a SDS, sodium dodecyl sulfate (cmc ) 8.1 mM); CTAB, cetyltrimethy-
lammonium bromide (cmc ) 0.9 mM); OG, n-octyl-â-D-glucopyranoside
(cmc ) 25 mM); G, gel; p, precipitation. b [1] ) 16 mM, [2] ) 13 mM,
[3] ) 11 mM. c Concentration of surfactant in mM.
3, 10-200 nm), which in turn form an entangled fibrillar network,
thereby immobilizing the solvent.
The compatibility of hydrogel formation by 1-3 with various
types of surfactants was investigated by dissolving 1-3 in sur-
factant solutions below and above the critical micelle concentration
(cmc)16 at T > TGS and by subsequently examining the samples
for gelation after they had been cooled to room temperature (Table
1). Gels of 1 are formed in combination with nonionic (OG) or
anionic (SDS) surfactants either by temperature-induced gelation
or by the lowering of the pH from 7 to 3.5,13 but with cationic
CTAB immediate precipitation occurred, due to salt formation. Most
interestingly, cryo-TEM showed no significant differences between
hydrogels of 1 alone and in the presence of OG (Figure 1), and
furthermore the melting temperatures of hydrogels of 1 are not
changed by the presence of OG up to concentrations well above
the cmc (35 mM). The gelation behavior of the nonionic gelators
2 and 3 is even more tolerant toward the presence of surfactants,
and transparent gels are obtained in the presence of SDS, CTAB,
or OG below and well above the cmc of the surfactants. These
results clearly indicate that the self-assembly of 1-3 leading to
the gelation of water is not markedly affected by the presence of
surfactants or surfactant assemblies, except when strong interactions
between surfactant and gelator are possible, like electrostatic
interactions between acidic gelator 1 and the cationic surfactant
CTAB.
† BioMaDe Technology Foundation.
‡ University of Groningen.
9
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J. AM. CHEM. SOC. 2003, 125, 14252-14253
10.1021/ja036954h CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
speculate that the orthogonal self-assembly of our hydrogelators
and surfactants is due to their different molecular architectures as
well as the in part different driving forces for self-assembly, that
is, hydrogen bonding and hydrophobic effects versus hydrophobic
effects alone, respectively. The straightforward design of 1,3,5-
trisamide-cyclohexane-based gelators and the thermoreversibility
and pH-sensitivity13 of the hydrogels make them ideal model
systems to investigate the factors controlling self-assembly and
phase separation in gelator-surfactant systems and employ them
as cytoskeleton mimics in liposomes.
Supporting Information Available: Experimental details on the
preparation and characterization of 1-3, and cryo-TEM (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
Figure 1. Cryo-TEM of a hydrogel of 1 (3.3 mM) in the presence of 33
mM of OG, that is, well above the cmc of OG. For a cryo-TEM of a gel
of 1 without surfactant, see the Supporting Information. The scale bar is
300 nm.
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The results presented here show that self-assembly of 1 and of
OG are orthogonal processes, leading to the independent formation
of a fibrillar network with encapsulated micelles, and the compa-
rable gelation behavior and molecular architecture with 1 form a
clear indication that 2 and 3 with surfactants behave similarly. We
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