Detection of nerve agent via perturbation of supramolecular gel formation

Article abstract of DOI:10.1039/c3cc44841j

The formation of tren-based tris-urea supramolecular gels in organic solvents is perturbed by the presence of the nerve agent soman providing a new method of sensing the presence of organophosphorus warfare agents.

Full text of DOI:10.1039/c3cc44841j

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Detection of nerve agent via perturbation of
supramolecular gel formation†
Jennifer R. Hiscock,a Francesca Piana,a Mark R. Sambrook,b Neil J. Wells,a
Alistair J. Clark,a Jack C. Vincent,b Nathalie Busschaert,a Richard C. D. Browna and
Philip A. Gale*a
Cite this: Chem. Commun., 2013,
49, 9119
Received 27th June 2013,
Accepted 21st August 2013
DOI: 10.1039/c3cc44841j
www.rsc.org/chemcomm
The formation of tren-based tris-urea supramolecular gels in organic OP-based nerve agent simulant so providing a new paradigm
solvents is perturbed by the presence of the nerve agent soman for nerve agent detection.
providing a new method of sensing the presence of organophosphorus
warfare agents.
We prepared a series of bis- and tris-urea compounds of known
gelators 1–312a,13 and compound 4. Bis-ureas 1 and 3 have previously
been shown to gelate toluene, xylene, tetralin and octanol in
There has been significant interest and research effort devoted to the quantities of less than 10 mg mLÀ1 13
Compound 2 has been
.
design and synthesis of supramolecular gel systems.1 Stimuli shown to gelate xylene, toluene, tetralin and also benzene,
responsive supramolecular gels are of particular interest for their dichloromethane and dichloroethane in quantities less than
potential role as sensors.2 For example, hydrogen-bonded gels or equal to 10 mg mLÀ1 12a We studied the gel formation properties
.
containing urea groups have been shown by Escuder, Miravet and of compound 4 by dissolving quantities of gelator into 1 mL of
co-workers to be sensitive to the presence of neutral phenolic guests solvent by heating the sample and then allowing the sample to cool
with catechol disrupting the gel’s hydrogen bonding network.3 to room temperature. An inversion test14 was then conducted to
In seminal work, Steed and co-workers have shown that anions ascertain if a gel had formed. If no solution remained then the
can disrupt the structures of gels4 and have used this approach formation of a gel was deemed successful. Gelation was observed
to dissolve crystal growth media and recover new polymorphs with tetralin (5 mg mLÀ1), toluene (5 mg mLÀ1), cyclohexanone
of pharmaceutical interest.5
Our work on developing new motifs for oxo-anion complexa- was observed with 2-octanol, hexane, ethanol or water.
tion6 and particularly for phosphates7 led us to explore whether
A scanning electron microscopy (SEM) image of the xerogel
(15 mg mLÀ1), and ethyl acetate (15 mg mLÀ1) however no gelation
similar motifs could be used for organophosphorus (OP) based formed in toluene by compound 4 is shown in Fig. 1. This
nerve agent (NA) sequestration8 and catalysis.9 In a similar shows that the toluene xerogel forms a branching fibrillar
fashion we wished to explore whether we could employ the network structure.
formation of hydrogen bonded NA complexes to disrupt a gel
network and perturb a sol–gel transition which could be used to
sense OPs. Our group and others have explored the use of the
tripodal tren scaffold in anion complexation10 and transport.11
Tris-(2-aminoethyl)amine (tren) based tris-ureas have been
shown to gelate organic solvents12 and to have a high affinity
for phosphates in non-aqueous media.10 We therefore decided
to examine whether the structure of tren-based organogels and
We studied the effect of the nerve agent simulant, dimethyl
related systems would be disrupted by the presence of a neutral methylphosphonate (DMMP), on gels formed by compounds 1–4.
We found that in some cases the simulant would disrupt the
a Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
E-mail: philip.gale@soton.ac.uk; Fax: +44 (0)23 8059 6805;
Tel: +44 (0)23 8059 3332
b Detection Department, Dstl Porton Down, Salisbury, SP4 0JQ, UK.
E-mail: msambrook@dstl.gov.uk; Tel: +44 (0)1980 613306
† Electronic supplementary information (ESI) available: Synthesis and character-
isation information for compound 4 and further details on gel formation studies.
See DOI: 10.1039/c3cc44841j
structure of the gel resulting in a gel–sol transition. However
we found a high degree of variability in the time required for
this transition to occur. Therefore as an alternative, and more
quantifiable approach to study the response of these systems to
DMMP, the formation of gels from precursor amines and
isocyanates in the absence or presence of varying amounts of
DMMP was studied at room temperature (20–21 1C).
c
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form was then noted. A partial gel is a mixture that contains
both gel and solution. The experiments with gels which did
show perturbation of formation time in the presence of DMMP
were repeated, and the time taken to form the gel in these cases
was shown to be reproducible. NMR experiments showed that
no reaction occurred between either the amine (tren) or hexyl-
isocyanate and the simulant. Additionally, there was no obser-
vable change in the rate of urea formation upon addition of
DMMP (see ESI†).
Several different relationships between gelator (structure
and concentration), solvent and DMMP concentration were
observed to affect the time required for gel formation. The
lower the concentration of the gelator the longer it takes for the
gel network to form in the presence of DMMP. The addition of
DMMP in the gel precursor solution in most cases extends the
time required for the gel to form, with higher concentrations
of DMMP leading to increasingly delayed gel formation. This
is presumed to be a result of the hydrogen bond accepting
DMMP interacting with the hydrogen bond donating groups of
the urea functionality thus perturbing the formation of the
hydrogen bond network in the gel matrix, along with increased
solvent polarity. A combination of low gelator concentration
and high concentrations of simulant leads to the longest
gelation times. The full results can be found in the ESI.†
The results obtained with compounds 1 and 3 were similar
and showed that the addition of simulant to the gelator solutions
did not perturb the formation of the gel significantly under any
conditions tested (see ESI†). Immediate gel formation in the
presence of simulant appears to be a function of the bis-urea
structure as the gel formation of the tris-urea analogue 2 was
perturbed to a much greater extent by the addition of DMMP with
gel formation at 10 mg mLÀ1 being delayed by over 3 minutes in
toluene in the presence of 0.1 mL DMMP.
Gel formation by tris-urea compound 4 was perturbed to a
greater extent by the presence of DMMP than compound 2. The
most successful set of conditions for perturbing gel formation
by the systems studied was found to be the formation of a gel from
the precursors to compound 4 (5 mg mLÀ1) in toluene. In this case
full gel formation was delayed by four minutes upon the addition of
0.01 mL of DMMP to 1 mL of the gel precursor solutions. Upon
addition of 0.1 mL DMMP under the same conditions gel
formation did not occur at all. Thus at this concentration of
simulant (approximately 100 equivalents of simulant to gelator)
there is a clear ON-OFF response in the absence vs. presence of
DMMP. Gel formation in toluene proved to be perturbed more
readily that that in tetralin (see ESI†).
Fig. 1 SEM image of the xerogel formed by compound 4 and toluene after
drying from a sample prepared from 15 mg mLÀ1 of gelator.
The urea based gelators (1–4) were formed in situ, in a
similar fashion to systems explored by Hanabusa and others.15
Solutions of the appropriate amine and either benzyl or hexyl-
isocyanate were mixed in 0.5 mL aliquots at appropriate con-
centrations to produce 1 mL of 20, 15, 10 and 5 mg mLÀ1 gels
containing compounds 1–4. The samples were sealed, allowed
to stand and inverted at 30 second intervals until a gel had
formed. A gel was deemed to have fully formed when, upon
inversion no solution remained. In most cases the gel formed
within thirty seconds or not at all. The starting point (t = 0) for the
experiment was taken at the point when the two solutions were
mixed together and all experiments were halted after 10 minutes
(see ESI†).
To test the effects of the presence of nerve agent simulant on
the time taken for gel formation to occur DMMP was added to
either the amine or isocyanate solution in 0.1, 0.05, 0.025 or
0.01 mL quantities (it was found that the systems behaved
identically whichever precursor the simulant was added to). The
amounts of gelator formed and phosphonate added are given in
Table 1 – by taking the ratio of these values the equivalents of
phosphonate:gelator may be calculated for the experiments
presented here. An equal volume of the second precursor
solution was then added to the mixture containing the simulant
and the first precursor. The vial was then sealed and inverted at
various times and the time taken for a full gel or partial gel to
Table 1 Amount of gelator (mmol) and added phosphonate (mmol)
The results that we observe may be due to two competing
effects. The first is a solvent effect; with the addition of the
larger amounts of phosphonate the polarity of the solution will
be altered substantially resulting in inhibition of gel formation.
However at lower concentrations of phosphonate, a complexation
mechanism may occur in which guest species bind to the urea
groups so inhibiting gel formation.
These experiments were used to find the optimum system
for testing with nerve agent. Consequently the formation of gels
from the precursors to compound 4 and toluene were tested in the
presence of the nerve agent pinacolyl methylphosphonofluoridate
Amount of gelator in 1 mL of gel (mmol)
Gelator
20 mg
15 mg
10 mg
5 mg
1
2
3
4
0.052
0.037
0.047
0.038
0.039
0.027
0.035
0.028
0.026
0.018
0.024
0.019
0.013
0.009
0.012
0.009
Amount of phosphonate added (mmol)
Phosphonate
0.100 mL
0.050 mL
0.025 mL
0.010 mL
DMMP
GD
0.923
—
0.461
—
0.231
0.140
0.092
0.056
c
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A*STAR (ARAP Programme) for a post-graduate scholarship
(NB). PAG thanks the Royal Society and the Wolfson Founda-
tion for a Royal Society Wolfson Research Merit Award.
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Fig. 2 The time required for complete/partial gel formation (1 mL) by com-
pound 4 in toluene in the presence of GD (0.010 mL/0.025 mL). Gelation
experiments were first observed after 0.5 min.
(soman, GD). GD was found to behave similarly to the DMMP
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for sensing nerve agents that functions via the suppression of a
sol–gel phase change. We are continuing to study the interaction
of gelators with organophosphorus nerve agents at room tem-
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