Detecting a peroxide-based explosive via molecular gelation

Article abstract of DOI:10.1039/c2cc33486k

A convenient and portable triacetone triperoxide (TATP) sensor was developed utilizing a thiol-to-disulfide oxidation to trigger a solution-to-gel phase transition. Using this method, TATP can be detected visually without any instrumentation.

Full text of DOI:10.1039/c2cc33486k

View Online / Journal Homepage
Dynamic Article Links
ChemComm
Cite this: DOI: 10.1039/c2cc33486k
www.rsc.org/chemcomm
COMMUNICATION
Detecting a peroxide-based explosive via molecular gelationw
Jing Chen, Weiwei Wu and Anne J. McNeil*
Received 14th May 2012, Accepted 26th May 2012
DOI: 10.1039/c2cc33486k
A convenient and portable triacetone triperoxide (TATP) sensor
was developed utilizing a thiol-to-disulfide oxidation to trigger a
solution-to-gel phase transition. Using this method, TATP can
be detected visually without any instrumentation.
as well as the rate of the chemical reaction. To date, we have
developed gelation-based sensors for nitric oxide,6a Hg2+
ions,6b and several proteases.6c
A gelation-based sensor requires three components: (1) a
non-gelling reactant, (2) a gelling product, and (3) an analyte-
mediated chemical reaction to convert the reactant into product.
We initially selected L-cysteine derivative 1 (a nongelator) as the
reactant because of the known peroxide-induced thiol-to-disulfide
reaction as well as the reported gelation ability of disulfide 2
(eqn (1)).7 These disulfide-based gelators were first reported
in 18928 and were more recently studied by Menger7 and
Bradley.9,10 Disulfide 2 has one of the lowest critical gel
concentrations (cgc) known for small molecules (0.25 mM in
25/75 DMSO/H2O), and it forms gels in a variety of organic
solvents. A low cgc is important for sensing because in many
cases the analyte is a stoichiometric reagent in the chemical
transformation. As a result, sensors based on gelators with
lower cgcs will detect lower analyte concentrations.
The continued safety of civilian and military personnel requires
methods for on-site explosives detection. Existing methods range
from those based on high-end instrumentation, which provide
both accuracy and sensitivity, to those without instrumentation,
which are portable but less accurate and less sensitive.1 The ideal
method depends on the location, method of sampling, and sense
of urgency.
Triacetone triperoxide (TATP) is a peroxide-based explosive
that is easily accessible due to its facile synthesis from readily
available reagents (acetone, hydrogen peroxide, and acid). As a
consequence, several recent terrorist plots have used TATP.2
Portable TATP sensors have been developed and a few are
commercialized.3 Several of these methods rely on spectrometers
to detect changes in absorption or emission spectra of dyes, and
most methods involve time-intensive sample pre-treatment to
convert TATP into more reactive components. Suslick and
co-workers recently reported a colorimetric array-based sensor
for detecting TATP vapors that utilizes an in-line acid catalyst for
decomposition and a flatbed scanner for analysis.4 The system has
both a fast response time and the ability to discriminate TATP
from other common oxidants. Several methods based on visual
detection have also been reported. For example, Finney and
Malashikhin detected TATP based on an increase in fluorescence
of a dye (with UV illumination) that is observable with the
naked eye.5 We describe herein an alternative instrument-free
approach, in which the presence of TATP triggers a solution-
to-gel phase transition.
ð1Þ
Thiol 1 and disulfide 2 were synthesized from commercially
available L-cysteine methyl ester (ESIw). No reaction was
observed when thiol 1 was treated directly with TATP. To
generate a stronger oxidant, p-toluenesulfonic acid (TsOH)
was used to presumably generate H2O2 (and acetone) in situ
from the degradation of TATP.11 When TATP is added to a
mixture of 1 and TsOH in MeOH, a stable gel is formed within
30 min (Fig. 1). It is important to note that no gel was
observed without TATP, indicating a negligible background
rate of oxidation (ESIw).12 Based on these promising initial
results, the system was further optimized to develop a gelation-
based sensor with an even lower detection limit and faster
response time.
Gel-based sensors provide an unambiguous visual change in
the material’s physical properties and, in contrast to colorimetric
and fluorescent sensors, there is no interference from opaque or
colored samples. The detection process typically involves an
analyte-triggered chemical reaction, which converts a nongelator
into a gelator, followed by gel formation. Response times can vary
from seconds to minutes depending on the analyte concentration
Department of Chemistry and Macromolecular Science and
Engineering Program, University of Michigan, 930 North University
Avenue, Ann Arbor, Michigan 48109-1055, USA.
E-mail: ajmcneil@umich.edu
w Electronic supplementary information (ESI) available: Experimental
details, spectroscopic data. See DOI: 10.1039/c2cc33486k
Fig. 1 A gel forms within 30 min of adding TATP (2.5 mg) to a vial
containing thiol 1 (36 mM) and TsOH (1.3 M) in MeOH.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.

View Online
One approach to lowering the detection limit is to modify
the structure of disulfide 2 to identify an alternative gelator
with a lower cgc in MeOH (ESIw). (Note that the cgc of 2 is
4.6 mM in MeOH.) Because of the largely unpredictable
relationship between structure and gelation ability,13 several
approaches were investigated. For example, previous studies
of peptide- and disulfide-based gelators have shown improve-
ments in cgc with halogen substitution and attributed these
results to increased hydrophobicity.9,14 In this case, however,
halogenated disulfides 3a and 4a exhibited higher cgcs (6.5 mM
and 25 mM, respectively) than disulfide 2 while both 3b and 4b
were nongelators. Disulfides with electron-donating substituents at
the same position were synthesized to compare to the halogenated
derivatives but none of these compounds (3c–3e) formed gels
under these conditions. Because p-stacking was suggested to be
important in the self-assembly of these disulfide-based gelators,7
compounds 5a–5b and 6a–6b were synthesized and screened for
gelation. Extending the linker length in 5a led to a nongelator, as
did changing the point of attachment (6a) and extending the
aromatic unit (6b). In contrast, using the larger linker (5b) led to a
gelator, albeit with a higher cgc (8.5 mM). Because intermolecular
H-bonding is also suggested to drive the self-assembly of these
disulfides,7 a glycine residue was inserted between the naphthyl
and amide residues (7). This amino acid-based compound did not
form a gel under these conditions. Overall, these results highlight
the challenges involved in the design and discovery of new
gelators.13 In total, three new gelators were discovered through
these efforts.15 Among all the compounds synthesized, the
original disulfide (2) remained the best gelator for the TATP
sensor because it had the lowest cgc in MeOH. Thus, further
optimizations were performed using disulfide 2.
TATP degradation (by increasing the [TsOH]) will increase the
oxidation and gelation rate. However, a background reaction
involving esterification of the amide in 2 became significant at
higher TsOH concentrations (ESIw). The optimized TsOH
concentration was empirically determined to be 36 equivalents
relative to thiol 1 (ESIw).17
To lower the detection limit, we investigated the impact of
decreasing the reaction volume. A decrease in reaction volume
will decrease the quantity of TATP required to form a gel
based on the reaction stoichiometry. For example, while 20 mg
of TATP is required to gel a 4 mL solution of 1 (36 mM in
MeOH), only 2 mg of TATP is required to gel a 0.4 mL of the
same solution. A further decrease in detection limit can be
obtained by decreasing the diameter of the container because
the yield stress of a gel is inversely proportional to the
container diameter (with constant volume).18 Therefore, when
using the vial inversion test, smaller containers will require less
gelator to form stable gels. This effect can be attributed to a
relative increase in the surface area between the container
and the gel. As evidence, the amount of 2 needed to gel 0.5 mL
of MeOH decreased from 4.6 mM (1.3 mg) in a 13 mm inner
diameter vial to 2.0 mM (0.5 mg) in 4.6 mm inner diameter vial.
Using all of these optimized conditions, a simple one-pot
method was developed. Specifically, 1 (36 mM), TsOH (1.3 M),
and TATP (1.5 mg) were pre-mixed and then transferred to a
small tube, where gelation was observed within 8 min (Fig. 2).12
Note that faster response times can be obtained with higher
concentrations of TATP. For example, gelation occurs within
2 min when 12 mg of TATP is added (ESIw). Overall, this
method is convenient and simple to use and interpret.
Similar to most portable TATP sensors, this gel-based
sensor is also sensitive to other hydrogen-based peroxides
and strong oxidants such as bleach, Cr3+, Cr6+ and peracetic
acid (ESIw). Fortunately, none of these oxidants have a similar
white powder appearance to TATP and can therefore be
distinguished. In addition, oxidants with similar white powder
formulations, such as potassium iodide, potassium chlorate
and benzoyl peroxide do not trigger gelation even under acidic
conditions (ESIw).
In summary, a convenient and portable gel-based sensor for
detecting mg quantities of solid TATP was developed. Given that
hundreds of grams of TATP are used in improvised explosive
devices, milligram-sized samples should be readily accessible. The
sensor is based on a TATP-triggered gelation via a thiol-to-disulfide
oxidation reaction. Although modifying the original structure
To decrease the response time, the TATP degradation and
thiol oxidation reaction rates were independently optimized.
Rate studies were first performed on the TsOH-mediated
decomposition of TATP. As noted above, the main decomposition
products have been suggested to be H2O2 and acetone.11 To
provide support for this proposal, the degradation reaction was
performed in the presence of 2,4-dinitrophenyl hydrazine, which
should react with any acetone present to form a hydrazone.16
Approximately 30% of the expected acetone was trapped as the
hydrazone (ESIw). Based on the mechanism of acetone formation,
this result suggests that H2O2 is also generated during this reaction.
Rate studies revealed a fractional order (0.7) dependence on
[TsOH] for the TATP degradation (ESIw). Rate studies were then
performed on the H2O2-mediated oxidation of thiol 1, which
revealed an approximate first-order dependence on [H2O2] (ESIw).
Combined, these results suggest that increasing the rate of
Fig. 2 Gel formation is observed within 8 min of mixing 1 (36 mM),
TsOH (1.3 M), and TATP (1.5 mg) in MeOH.
c
Chem. Commun.
This journal is The Royal Society of Chemistry 2012

View Online
did not produce a better gelator, optimizing the oxidation and
gelation rates, as well as the reaction volume and container
size, improved both the detection limit and response time.
Overall, we believe that this sensor is complementary to the
traditional colorimetric and fluorescent approaches used in
TATP detection, with the added advantages of unambiguous
signal read-out and no instrumentation needed.
8 (a) K. Brenzinger, Z. Phys. Chem., 1892, 16, 552–588; (b) See also:
R. A. Gortner and W. F. Hoffman, J. Am. Chem. Soc., 1921, 43,
2199–2202(c) C. G. L. Wolf and E. K. Rideal, Biochem. J., 1922,
16, 548–555.
9 M. Matteucci, G. Bhalay and M. Bradley, J. Pept. Sci., 2004, 10,
318–325.
10 For examples of other disulfide-based gelators, see: (a) L. Milanesi,
C. A. Hunter, N. Tzokova, J. P. Waltho and S. Tomas, Chem.–
Eur. J., 2011, 17, 9753–9761; (b) R. P. Lyon and W. M. Atkins,
J. Am. Chem. Soc., 2001, 123, 4408–4413.
11 D. Armitt, P. Zimmermann and S. Ellis-Steinborner, Rapid Commun.
Mass Spectrom., 2008, 22, 950–958.
We thank the Office of Naval Research (N00014-09-1-0848)
and 3M for support of this work. A. J. M. thanks the Alfred P.
Sloan Foundation for a research fellowship.
12 Although thiol 1 is stable for months under ambient conditions in
the solid state, it slowly undergoes oxidation to disulfide 2 in
MeOH (e.g., 35% conversion after 21 days). When TsOH is
present, a competing esterification reaction occurs (see ESIw).
13 Although the rational design of gelators remains a challenge, some
of the key factors relevant to gelation are being uncovered. For
recent examples, see: (a) H. Xu, J. Song, T. Tian and R. Feng, Soft
Matter, 2012, 8, 3478–3486; (b) M. Raynal and L. Bouteiller,
Chem. Commun., 2011, 47, 8271–8273; (c) M. L. Muro-Small,
J. Chen and A. J. McNeil, Langmuir, 2011, 27, 13248–13253;
(d) J. Chen, J. W. Kampf and A. J. McNeil, Langmuir, 2010, 26,
13076–13080; (e) A. R. Hirst and D. K. Smith, Langmuir, 2004, 20,
10851–10857.
14 For recent examples of halogenated peptide-based gelators, see:
(a) D. M. Ryan, S. B. Anderson and B. L. Nilsson, Soft Matter,
2010, 6, 3220–3231; (b) D. M. Ryan, S. B. Anderson,
F. T. Senguen, R. E. Youngman and B. L Nilsson, Soft Matter,
2010, 6, 475–479.
15 Elucidating the origin of these structure-property relationships was
difficult because X-ray quality single-crystals could not be obtained
for any of these compounds.
Notes and references
1 For recent reviews, see: (a) Y. Salinas, R. Martı
M. D. Marcos, F. Sancenon, A. M. Costero, M. Parra and
S. Gil, Chem. Soc. Rev., 2012, 41, 1261–1296; (b) M. Makinen,
nez-Manez,
´ ´
´
¨
M. Nousiainen and M. Sillanpaa, Mass Spectrom. Rev., 2011, 30,
¨
¨
940–973; (c) M. E. Germain and M. J. Knapp, Chem. Soc.
Rev., 2009, 38, 2543–2555; (d) S. Singh, J. Hazard. Mater., 2007,
144, 15–28; (e) D. S. Moore, Rev. Sci. Instrum., 2004, 75,
2499–2512.
2 M. Jacoby, Chem. Eng. News, 2009, 87(22), 10–13.
3 For reviews on sensing peroxide-based explosives, see: (a) R. M. Burks
and D. S. Hage, Anal. Bioanal. Chem., 2009, 395, 301–313;
(b) R. Schulte-Ladbeck, M. Vogel and U. Karst, Anal. Bioanal.
Chem., 2006, 386, 559–565.
4 H. Lin and K. S. Suslick, J. Am. Chem. Soc., 2010, 132,
15519–15521. See also: H. Lin, M. Jang and K. S. Suslick,
J. Am. Chem. Soc., 2011, 133, 16786–16789.
5 S. Malashikhin and N. S. Finney, J. Am. Chem. Soc., 2008, 130,
12846–12847.
16 For
a recent review, see: (a) S. Uchiyama, Y. Inaba and
6 (a) J. Chen and A. J. McNeil, J. Am. Chem. Soc., 2008, 130,
16496–16497; (b) K. N. King and A. J. McNeil, Chem. Commun.,
2010, 46, 3511–3513; (c) S. C. Bremmer, J. Chen, A. J. McNeil and
M. B. Soellner, Chem. Commun., 2012, 48, 5482–5484.
7 (a) F. M. Menger and K. L. Caran, J. Am. Chem. Soc., 2000, 122,
11679–11691; (b) F. M. Menger, Y. Yamasaki, K. K. Catlin and
T. Nishimi, Angew. Chem., Int. Ed. Engl., 1995, 34, 585–586;
(c) F. M. Menger and K. S. Venkatasubban, J. Org. Chem.,
1978, 43, 3413–3414.
N. Kunugita, J. Chromatogr., B, 2011, 879, 1282–1289; (b) See
also: C. F. H. Allen, J. Am. Chem. Soc., 1930, 52, 2955–2959;
(c) O. L. Brady, J. Chem. Soc., 1931, 756–759.
17 Under these conditions, disulfide 2 undergoes esterification over
the course of 3 d (see ESIw).
18 S. R. Raghavan and B. H. Cipriano, Gel Formation: Phase Diagrams
Using Tabletop Rheology and Calorimetry, In Molecular Gels:
Materials with Self-Assembled Fibrillar Networks, ed. R. G. Weiss
and P. Terech, Springer, The Netherlands, 2006, pp. 241–252.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.