In Vitro and In Vivo Studies of Triacetone Triperoxide (TATP) Metabolism in Humans

Purpose Triacetone triperoxide (TATP) is a volatile but powerful explosive that appeals to terrorists due to its ease of synthesis from household items. For this reason, bomb squad, canine (K9) units, and scientists must work with this material to mitigate this threat. However, no information on the metabolism of TATP is available. Methods In vitro experiments using human liver microsomes and recombinant enzymes were performed on TATP and TATP-OH for metabolite identification and enzyme phenotyping. Enzyme kinetics for TATP hydroxylation were also investigated. Urine from laboratory personnel collected before and after working with TATP was analyzed for TATP and its metabolites. Results While experiments with flavin monooxygenases were inconclusive, those with recombinant cytochrome P450s (CYPs) strongly suggested that CYP2B6 was the principle enzyme responsible for TATP hydroxylation. TATP-O-glucuronide was also identified and incubations with recombinant uridine diphosphoglucuronosyltransferases (UGTs) indicated that UGT2B7 catalyzes this reaction. Michaelis–Menten kinetics were determined for TATP hydroxylation, with Km = 1.4 µM and Vmax = 8.7 nmol/min/nmol CYP2B6. TATP-O-glucuronide was present in the urine of all three volunteers after being exposed to TATP vapors showing good in vivo correlation to in vitro data. TATP and TATP-OH were not observed. Conclusions Since scientists working to characterize and detect TATP to prevent terrorist attacks are constantly exposed to this volatile compound, attention should be paid to its metabolism. This paper is the first to elucidate some exposure, metabolism and excretion of TATP in humans and to identify a marker of TATP exposure, TATP-O-glucuronide in urine

Quantification and Aging of the Post-Blast Residue of TNT Landmines

Post-blast residues are potential interferents to chemical detection of landmines. To assess the potential problem related to 2,4,6-trinitrotoluene (TNT), its post-blast residue was identified and quantified. In the first part of this study laboratory-scale samples of TNT (2 g) were detonated in a small-scale explosivity device (SSED) to evaluate the explosive power and collect post-blast residue for chemical analysis. Initiator size was large relative to the TNT charge; thus, issues arose regarding choice of initiator, residue from the initiator, and afterburning of TNT. The second part of this study detonated 75 to 150 g of military-grade TNT (typical of antipersonnel mines) in 55-gal barrels containing various witness materials (metal plates, sand, barrel walls, the atmosphere). The witness materials were analyzed for explosive residue. In a third set of tests, 75-g samples of TNT were detonated over soil (from Fort Leonard Wood or Sandia National Laboratory) in an indoor firing chamber (100 by 4.6 by 2.7 m high). Targeted in these studies were TNT and four explosive-related compounds (ERC): 2,4-dintrotoluene (DNT), 1,3-dinitrobenzene (DNB), 2- and 4-aminodinitrotoluene (2-ADNT and 4-ADNT). The latter two are microbial degradation products of TNT. Post-blast residue was allowed to age in the soils as a function of moisture contents (5 and 10%) in order to quantify the rate of degradation of the principal residues (TNT, DNT, and DNB) and formation of the TNT microbial degradation products (2-ADNT and 4-ADNT). The major distinction between landmine leakage and post-blast residue was not the identity of the species but relative ratios of amounts. In landmine leakage the DNT/TNT ratio was usually greater than 1. In post-blast residue it was on the order of 1 to 1/100th of a percent, and the total amount of pre-blast residue (landmine leakage) was a factor of 1/100 to 1/1000 less than post-blast. In addition, landmine leakage resulted in low DNT/ADNT ratios, usually less than 1, whereas pre-blast residues started with ratios above 20. Because with time DNT decreased and ADNT increased, over a month the ratio decreased by a factor of 2. The rate of TNT degradation in soil observed in this study was much slower than that reported when initial concentrations of TNT were lower. Degradation rates yielded half-lives of 40 and 100 days for 2,4-DNT and TNT, respectively

Homemade explosives

In the last 2 decades a number of explosives, not traditionally employed by traditional military, have found use in terrorist hands. This chapter will discuss a few of the new detection targets

Decomposition of a multi-peroxidic compound: Triacetone triperoxide (TATP)

The thermal decomposition of triacetone triperoxide (TATP) was investigated over the temperature range 151 to 230°C and found to be first order out to a high degree of conversion. Arrhenius parameters were calculated: activation energy, 151 kJ/mol and pre-exponential factor, 3.75 × 1013 s-1. Under all conditions the principle decomposition products were acetone (about 2 mole per mole TATP in the gas-phase and 2.5-2.6 mole per mole in condensed-phase) and carbon dioxide. Minor products included some ascribed to reactions of methyl radical: ethane, methanol, 2-butanone, ethyl acetate; these increased at high temperature. Methyl acetate and acetic acid were also formed in the decomposition of neat TATP; the former was more evident in the gas-phase decompositions (151°C and 230°C) and the latter in the condensed-phase decompositions (151°C). The decomposition of TATP in condensed-phase or in hydrogen-donating solvents enhanced acetone production, suppressed CO2 production, and slightly increased the rate constant (a factor of 2-3). All observations were interpreted in terms of decomposition pathways initiated by O-O homolysis

A new polymorph of HMTD

While exploring the synthesis pathway of HMTD, an unexpected new route for preparing HMTD was found through the reaction of formaldehyde, hydrogen peroxide, and ammonium hydroxide. The recovered HMTD was characterized by Raman spectroscopy and powder x-ray diffraction and found to be a different crystal structure. This HMTD is believed to be the result of a different conformation of the HMTD, only previously predicted by computational methods and through the use of specialized NMR reagents

Developing small-scale tests to predict explosivity

Materials which release significant heat upon decomposition are energetic materials. Some of these are also explosives. Seeking a correlation with detonability of large quantities of energetic materials, four laboratory tests were used. The characteristics considered indicative of detonability were ability to fragment a metal casing, when initiated by a detonator, and ability to produce large quantities of gas and heat. The best developed of these tests is differential scanning calorimetry. It has already been pioneered by other researchers. A limitation of this study is that large-scale detonability remains unknown for a number of materials examined; thus, it is difficult to sufficiently evaluate the success of the small-scale analyses. © 2010 Akadémiai Kiadó, Budapest, Hungary

Thermal decomposition of high-nitrogen energetic compounds - Dihydrazido-S-tetrazine salts

The thermal stabilities of 3,6-dihydrazido-1,2,4,5-tetrazine (Hz2Tz) and its salts with diperchlorate [Hz2Tz(HClO4)2], dinitrate [Hz2Tz(HNO3)2], bisdintramidate [Hz2Tz(HDN)2], and bisdinitroimidazolate [Hz2TzBim] have been examined and compared to other 3,6-disubstituted tetrazines. The neutral tetrazines exhibited two principal modes of decomposition: elimination of N2 from the tetrazine ring followed by cleavage of the remaining N-N bond, and loss of the substituent group, in some cases assisted by proton transfer. The salts Hz2TzX2 undergo reversible equilibrium with the parent Hz2Tz and HX, thus, in several cases the decomposition rate of the parent tetrazine and the salt are essentially identical. © 2002 Elsevier Science B.V. All rights reserved

Decomposition of azo- and hydrazo-linked bis triazines

In a search for novel energetic materials, azo-linked bis triazines were pursued. Herein the thermal decomposition of 14 simple triazines and 16 hydrazo- or azo-linked bis triazines were studied using mass spectrometry, permanent gas evolution, and differential scanning calorimetry. At temperatures far above the melting/decomposition point, decomposition was complete. Lower temperatures provided insight into the stability of the functional groups pendant to the triazine rings. Decomposition gases were identified by chromatography; they indicated little degradation of the triazine rings. The s-triazine ring system appears very stable, resisting decomposition up to 550C while its substituents undergo relatively isolated chemistry