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Novel Anisotropic Supramolecular Hydrogel with High Stability over
a Wide pH Range†
Fan Zhao,‡,§ Yuan Gao,‡ Junfeng Shi,‡ Hayley M. Browdy,‡ and Bing Xu*,‡
‡Department of Chemistry and §Quantitative Biology Program, Brandeis University, 415 South Street,
Waltham, Massachusetts 02454, United States
Received October 4, 2010. Revised Manuscript Received November 4, 2010
The hydrolysis of the carboxylic ester bond, by a base or catalyzed by an enzyme under weak basic conditions, serves
as the only path to obtain a novel anisotropic supramolecular hydrogel that is stable over a wide pH range. This result
not only expands the molecular scope of supramolecular hydrogelators but also illustrates the design principles for
creating pH-stable supramolecular soft materials.
Supramolecular hydrogels, resulting from the self-assembly of
certain small organic molecules (i.e., hydrogelators) driven by
noncovalent interactions, have emerged as a type of versatile soft
material and have found applications in many areas.1 Because of
their inherent and excellent biocompatibility and biodegradabil-
ity, supramolecular hydrogels have shown promise in becoming a
useful alternative to polymeric hydrogels.2 For example, su-
pramolecular hydrogels are being explored to serve as scaffolds
for regenerative medicine,3 wound healing,4 biomineralization,5
vehicles for controlled drug release,6 matrices for protein micro-
arrays,7 a low-cost platform for screening enzyme inhibitors or
enzyme detection,8 and components for enzyme mimetics.9
Forming a hydrogel is the first step in developing supramole-
cular hydrogels as useful soft materials. There are several different
ways to generate supramolecular hydrogels. A commonly used
method involves dissolving hydrogelators into an aqueous solu-
tionand changing the temperature, pH, orionicstrength to initiate
molecular self-assembly in water, resulting in hydrogelation.1
This kind of approach, which works well for most hydrogelators,
has some inherent disadvantages for certain hydrogelators, for
example, a hydrogelator with exceedingly low solubility (or unusually
high hydrophobicity) or having the potential to form precipitates
instead of a hydrogel as a result of the change in temperature,
ionic strength, or pH. These molecules have the potential to self-
assemble in water despite their poor aqueous solubility. One
approach is to dissolve them in a polar organic solvent and then
mix this solution with water to form nanostructures or hydrogels.
For example, in work on the self-assembly or hydrogelation of
NH2-Phe-Phe-COOH,10 Fmoc-Phe-Phe,11 Fmoc-Phe(F5),12
GSH-pyrene,13 and NH3þ-Phe-Phe-CO-NH2,14 an organic sol-
vent (usually 1,1,1,3,3,3-hexafluoro-2-propanol or DMSO) is
always necessary to assist the dissolution of these compounds.
Despite its effectiveness, this approach inevitably brings small
amount of organic solvent into the hydrogels, which changes, if
not completely disturbs, the biocompatibility or rheological
behavior of the resulting hydrogels.
To explore new methods for making hydrogels, we and others
have been developing new ways to induce hydrogelation via
chemical or enzymatic conversion. For example, the phosphor-
ylation of tyrosine residues on hydrogelators offers precursors
that are soluble at physiological pH. Then a phosphatase can
hydrolyze the phosphoric monoester and convert the precursors
to less soluble but amphiphilic hydrogelators, which self-assemble
in water to form supramolecular nanofibers and result in hydro-
gels.15 Besides the route of dephosphorylation, other chemical or
enzymatic paths should also be suitable for the generation of
supramolecular hydrogels, which have been less explored.16
In this work, we explored the paths for generating the hydrogel
of a small molecule (2). Because of its high hydrophobicity, neither
the change in pH nor the change in temperature creates the hydro-
gel of 2. However, a simple chemical modification of 2 offered
† Part of the Supramolecular Chemistry at Interfaces special issue.
*Corresponding author. Tel: 1-781-736-5201. Fax: 1-781-736-2516. E-mail:
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1510 DOI: 10.1021/la103982e
Published on Web 12/08/2010
Langmuir 2011, 27(4), 1510–1512