A versatile supramolecular hydrogel of nitrilotriacetic acid (NTA) for binding metal ions and magnetorheological response

Article abstract of DOI:10.1039/c1jm10822k

Here we report a novel supramolecular hydrogelator, which contains a nitrilotriacetic acid (NTA) motif, to form a magnetorheological hydrogel upon interacting with nickel particles or holmium ions or to afford a hydrogel as an efficient absorber of metal

Full text of DOI:10.1039/c1jm10822k

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A versatile supramolecular hydrogel of nitrilotriacetic acid (NTA) for binding
metal ions and magnetorheological response†
a
a
a
b
Yue Pan, Yuan Gao, Junfeng Shi, Ling Wang and Bing Xu
ab
*
Received 24th February 2011, Accepted 18th March 2011
DOI: 10.1039/c1jm10822k
ions have been incorporated into polymeric hydrogels for a variety of
applications, including the separation of heavy metal ions.21 In
addition, the concept of metal promoted self-assembly has been
applied to collagen mimetic peptides in the design of supramolecular
structures.22 Encouraged by these developments, particularly the
growing interest of metallogels that can serve as catalytic materials,23
absorbents, and sensors,24 we choose to use nitrilotriacetic acid
(NTA) for generating supramolecular hydrogels to explore the design
principle and scope of metal–ligand interactions in soft materials
because NTA is a well-established ligand for coordinating with metal
ions.
Here we report a novel supramolecular hydrogelator, which contains
a nitrilotriacetic acid (NTA) motif, to form a magnetorheological
hydrogel upon interacting with nickel particles or holmium ions or to
afford a hydrogel as an efficient absorber of metal ions.
This paper describes the synthesis and properties of a molecular
hydrogelator containing nitrilotriacetic acid (NTA). Supramolecular
hydrogels,1,2 a unique type of soft materials that consist of water and
self-assembled3 nanofibers of small molecules, have received
increased attention recently due to their potential applications in
tissue engineering,4 biomaterials,5 wound healing,6 bacterial growth
inhibition,7 and drug delivery.8 Besides the exploration of oligomeric
peptides for making hydrogels as biocompatible and bioactive scaf-
folds for tissue engineering,9 there are developments of supramolec-
ular hydrogels based on small molecules such as amino acids,10,11
carbohydrates,12 antibiotics.13 For example, Hanabusa et al.14 have
shown the versatility of L-lysine as the building block for supramo-
lecular hydrogels, Hamachi and coworkers12 reported the supramo-
lecular hydrogel composed of glycosylated amino acetate, Shimizu
et al.15 reported the hydrogelation of nucleotide bolaamphiphiles,
Adams et al. have investigated the structure–gelation relationship of
several readily accessible dipeptide gelators,16 and Ulijn and Smith
have shown the construction of dynamic library of building blocks of
hydrogelators.11 We also developed supramolecular hydrogels of
complex, bioactive molecules (e.g. vancomycin or taxol).17 These
successful works depend on supramolecular interactions18 as the
driving force to bring the molecules together to form three-dimen-
sional matrices of nanofibers to confine water, which has become
a powerful strategy for generating hydrogels of small molecules.
In most of the supramolecular hydrogels reported, hydrogen
bonding and hydrophobic interactions are responsible for the self-
assembly and hydrogelation. Compared to these driving forces,
another important non-covalent interaction, coordination bonds (i.e.,
metal–ligand interactions), though successfully leading to design and
creation of organogels,19 have received less attention for integrating
with supramolecular hydrogels.20 On the other hand, ligands of metal
NTA, an aminotricarboxylate ligand, forms stable aqueous
complexes with many transition metal ions. Because of the strong
affinity of NTA to metal ions, NTA-attached resin is widely used for
immobilizing nickel ions to separate recombinant proteins that have
six consecutive histidine residues (6ꢀ His).25 These successes indicate
that NTA-based supramolecular hydrogels can act as a useful plat-
form for exploring applications that rely on metal–ligand
coordination.
Using a highly efficient self-assembly motif10,26 and NTA to design
the hydrogelator (9), we obtained a supramolecular hydrogel that can
coordinate with various metal ions. In addition, this supramolecular
hydrogelator exhibits a strong affinity to interact with nickel particles,
which results in a hydrogel that responds to a magnetic force, sug-
gesting that supramolecular hydrogels can integrate with nano-
particles to form a new type of magnetorheological material. These
results demonstrate a facile approach that uses ligands as molecular
building blocks for constructing useful and functional soft materials.
aDepartment of Chemistry, Brandeis University, 415 South Street,
Waltham, MA, USA. E-mail: bxu@brandeis.edu
bDepartment of Chemistry, The Hong Kong University of Science and
Technology, Clear Water Bay, Hong Kong, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1jm10822k
Scheme 1 The synthetic route of the NTA containing hydrogelator.
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Scheme 1 shows the relatively straightforward synthetic route for
making the NTA containing hydrogelator: N-hydroxysuccinimide
(NHS) activated 1 reacts with L-phenylalanine twice in the mix
solvent of acetone and water to afford 6, which reacts with NTA to
give the desired product (9) in 45% overall yield.
Compound 9, itself, forms a pH responsive hydrogel (gel I in
Fig. 1) at pH ¼ 5 and the concentration of 0.9 wt%. The CD spectra
of gel I (Fig. S1†) indicate that b-sheet like structures dominate the
hydrogel, as evidenced by negative bands at about 210 nm and
positive bands at 195 nm. The transmission electron micrograph
(TEM) (Fig. 2A) reveals that the molecules of 9 self-assemble to form
nanofibers that further entangle into networks for encapsulating
a large volume of water molecules to form the hydrogel. The average
widths of the nanofibers are about 20 to 40 nm and lengths longer
than microns.
Fig. 2 Transmission electron micrograph (TEM) images of (A) gel I, (B)
Because of the ability of NTA to coordinate with metal ions, we
examine theinteractionsbetween 9 and several representative metal
ions or particles. As shown in Fig. 1, 9 can form hydrogels in the
presence of transition and lanthanide metal ions (e.g., Cu2+, Ni2+,
Ho3+), and these hydrogels are stable at room temperature for
several months.
gel III, (C) gel V, and (D) gel VIII.
the solution of 9 (0.4 mL, 0.9 wt%, pH 9). Because of the high
paramagnetism of holmium ions, a small magnet is able to attract the
hydrogel if the hydrogel floats on chloroform as a small sphere
(Fig. S2 in the ESI†).
The addition of CuSO4 (15 mL, 0.5 M) into the solution of 9
(0.4 mL, 0.9 wt%, pH 9) results in a light blue hydrogel (Fig. 1, gel III)
within 1 minute when the mole ratio of Cu2+ to Nap-FF–NTA is
about 3 : 2. This is a typical process for the gelation of hydrogelator
(9) with those representative metal ions. Similarly, after being added
with 10 mL NiCl2 (0.5 M), the solution of 9 turns into a light green
hydrogel within several seconds (Fig. 1, gel V). In this hydrogel, the
mole ratio of Ni2+ to 9 is about 1 : 1. The addition of HCl solution
(1.0 M) to gel V causes precipitates, which dissolve well in acetone.
The evaporation of acetone allows the recovery of the Nap-FF–
NTA, which can afford gel I and gel V again. Besides transition metal
ions, lanthanide metal ions also complex with NTA to form
a hydrogel. As shown in Fig. 1, a light pink hydrogel, gel IV, forms
within 5 minutes after the addition of 30 mL Ho(NO3)3 (0.5 M) into
As shown in Fig. 1, gel V collapses and gradually forms
a suspension after the addition of 0.5 mL imidazole (0.2 M) (Fig. 1,
VI) while gel I is stable under the same treatment (Fig. 1, VII). The
addition of imidazole to gel V results in the disruption of gel
formation since imidazole competes with NTA to coordinate with
Ni2+. This result suggests that the interaction of Ni2+ ions with Nap-
FF–NTA (hydrogelator 9–Ni complexation) plays an essential role in
formation of the metallogels.
Besides the addition of the metal ions to the solution of 9 results in
the hydrogelation, metal nanoparticles also lead to the hydrogelation
of 9. After 2 mg Raneyꢀ nickel were added to the solution of
hydrogelator 9 (0.9 wt%, pH ¼ 8, 0.4 mL) at room temperature, it
would form a black gel after 8 hours (Fig. 1, gel VIII). As shown in
Fig. 1, we can attract gel VIII by a magnet easily. This gel is thermally
reversible, and a simple heating/cooling procedure would regenerate
the magnetic hydrogel. We can repeat this cycle many times.
Although there are many reports on magnetorheological polymeric
gels (e.g., ferrogels),27 magnetic supramolecular hydrogels are less
explored.28 This result suggests that supramolecular hydrogels can
avoid phase separation of the nanofibers and the nanoparticles, thus
offering a new alternative to develop magnetorheological materials.
According to the TEM images of the gels (Fig. 2B and C), the
metal ions (Cu2+ and Ni2+) would induce 9 to self-assemble into
nanofibers of various sizes (with the diameters from 30 nm to 40 nm).
As shown in the TEM image (Fig. 2D), the Raneyꢀ nickel particles
distribute along the nanofibers, indicating strong interactions
between the nickel particles and hydrogelator 9. The higher magni-
fication TEM image (Fig. S3 in the ESI†) clearly shows that all the
particles attach to the nanofibers. Since the particle sizes range from
about 50 nm to 310 nm in diameter, this result suggests that the
formation of the hydrogel tolerates the nanoparticles with different
sizes.
Fig. 1 Optical images of (I) the hydrogel of 9 (0.4 mL, 0.9 wt%, pH 5);
(II) the solution of 9 (0.9 wt%, pH 9); (III) the hydrogel made of 9 (0.9 wt
%) and 15 mL 0.5 M CuSO4; (IV) the hydrogel made of 9 (0.9 wt%) and
30 mL 0.5 M Ho(NO3)3; (V) the hydrogel made of 9 (0.9 wt%) and 10 mL
0.5 M NiCl2; (VI) gel V treated with 0.5 mL imidazole (0.2 M); (VII) gel I
treated with 0.5 mL imidazole (0.2 M); (VIII) 0.9 wt% of 9 with 2 mg
Raneyꢀ nickel; (IX) after gel VIII attracted by a magnet.
As shown in Fig. 3, the storage moduli (G0) of all the gel samples
are larger than their loss moduli, indicating that the materials behave
elastic-like. The G0 of gel III and gel V are about 3254 Pa and 2092 Pa
while that of gel I is about 51 Pa, suggesting that the metal–ligand
interactions of 9 and metal ions are much stronger than the
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The authors acknowledge the financial support from start-up grant
from Brandeis University and RGC (Hong Kong). We also thank
Prof. Nikolaus Grigorieff and Dr Chen Xu for the assistance on the
use of Brandeis EM facility.
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