VX fate on common matrices: evaporation versus degradation.

A study of the volatilization rate of the nerve agent VX (O-ethyl S-2-(N,N-diisopropylamino)ethyl methylphosphonothiolate) from various urban matrices in a specially designed climatic chamber (model system) is described. The performance of the model system combined with the analytical procedure produced profiles of vapor concentration obtained from samples of VX dispersed as small droplets on the surfaces of the matrices. The results indicated that the bitumen-containing surfaces such as asphalt blocks and bitumen sheets conserve VX and slow-release part of it over a long period of time. No complete mass balance could be obtained for these surfaces. Influence of environmental and experimental parameters as well as the efficacy of decontamination procedure were also measured. From smooth surface tiles a fast release of VX was measured and almost a complete mass balance was obtained, which characterizes the behavior of inert surfaces. Experiments carried out on concrete blocks showed fast decay of the concentration profile along with a very poor reconstruction of the initial quantity of VX, implying that this matrix degraded VX actively due to its multiple basic catalytic sites. To complement this study, solid-state NMR measurements were compared to add data concerning agent-fate within the matrices.

Long-term evaluation of the fate of sulfur mustard on dry and humid soils, asphalt, and concrete.

The long-term fate of the blister agent sulfur mustard (HD, bis(2-chloroethyl)sulfide) was determined in a variety of commercial and natural matrices. HD was found to be extremely stable in dry matrices for over a year. The addition of 5% water to the matrices induced slow degradation of HD, which lasted several months. The major degradation product in sands and asphalt was found to be a sulfonium salt, S[CH(2)CH(2)S(+)(CH(2)CH(2)OH)(2)](2) (H-2TG). Red loam soil, which has not been examined before, exhibited strong interaction with HD, both in dry form and in the presence of water. Humid red loam soil gave rise to unique oxidative degradation products. On humid concrete HD degraded to a complex mixture of products, including vinyls. This may be attributed to the basic sites incorporated in concrete.

Degradation of sulfur mustard on KF/Al2O3 supports: insights into the products and the reactions mechanisms.

The degradation of the warfare agent sulfur mustard (HD) adsorbed onto KF/Al(2)O(3) sorbents is described. These processes were explored by MAS NMR, using (13)C-labeled sulfur mustard (HD*) and LC-MS techniques. Our study on the detoxification of this blister agent showed the formation of nontoxic substitution and less-toxic elimination products (t(1/2) = 3.5-355 h). Interestingly, the reaction rates were found to be affected by MAS conditions, i.e., by a centrifugation effect. The products and the mechanisms of these processes are discussed.

The role of AChE active site gorge in determining stereoselectivity of charged and noncharged VX enantiomers.

The reactivity of human acetylcholinesterase (HuAChE) toward the chemical warfare agent VX [O-ethyl S-[2-(diisopropylamino)ethyl] methyl-phosphonothioate] and its stereoselectivity toward the P(S)-enantiomer were investigated by examining the reactivity of HuAChE and its mutant derivatives toward purified enantiomers of VX and its noncharged isostere nc-VX [O-ethyl S-(3-isopropyl-4-methyl-pentyl) methylphosphonothioate]. Stereoselectivity of the wild-type HuAChE toward VX(S) is manifested by a 115-fold higher bimolecular rate constant (1.4 x 10(8) min(-1) M(-1)) as compared to that of VX(R). HuAChE was also 12,500-fold more reactive toward VX(S) than toward nc-VX(S), demonstrating the significance of the polar interactions of the ammonium substituent to their overall affinity toward VX. Indeed, substitution of the cation-binding subsite residue Trp86 by alanine resulted in a decrease of three orders of magnitude in HuAChE reactivity toward both VX enantiomers, with only a marginal effect on the reactivity toward the enantiomers of nc-VX. These results demonstrate that accommodation of the charged moieties of both VX enantiomers depends predominantly on interactions with the aromatic moiety of Trp86. Yet, these interactions seem to limit the stereoselectivity toward the P(S)-enantiomer, which for charged methylphosphonates is much lower than for the noncharged analogs, like sarin or soman. Marked decrease in stereoselectivity toward VX(S) was observed following replacements of Phe295 at the acyl pocket (F295A and F295A/F297A). Replacement of the peripheral anionic site (PAS) residue Asp74 by asparagine (D74N) practically abolished stereoselectivity toward VX(S) (a 130-fold decrease), while substitution which retained the negative charge at position 74 (D74E) had no effect. The results from kinetic studies and molecular simulations suggest that the differential reactivity toward the VX enantiomers originates predominantly from a different orientation of the charged leaving group with respect to residue Asp74. Such different orientations of the charged leaving group in the HuAChE adducts of the VX enantiomers seem to be a consequence of intramolecular interactions with the bulky phosphorus alkoxy group.

Synthesis, fluorescence and biodistribution of a bone-targeted near-infrared conjugate.

Enhanced imaging of early-stage bone abnormalities, such as primary tumors or metastases is highly required as the widely-used bone scan frequently lacks the desired sensitivity. Near IR (NIR) fluorescence imaging affords high contrast and enhanced sensitivity, as body tissue expresses minimal autofluorescence at NIR range (600-1200 nm). Indocyanine green (ICG), a biocompatible NIR dye, is widely used in the imaging of various organs, such as liver, heart and blood circulation. We report the preparation and in-vivo testing of a bone-targeting ICG derivative, in comparison to the parent molecule(s). Since ICG itself is chemically unreactive, and could not form conjugates, we prepared two novel ICG conjugatable derivatives. The overall ICG structure was maintained while only a replacement of one or two sulfonate groups with carboxylic acids resulted in new linkers for covalent binding to biomolecules. These derivatives were evaluated for their fluorescence and biodistribution in comparison to ICG and were found to be comparable. One of the novel ICG-derivatives was conjugated to a bone-targeting moiety and this new compound was found to bind to growing regions of the skeleton, and emit fluorescence for as long as two weeks in young mice.

Efficient heterogeneous and environmentally friendly degradation of nerve agents on a tungsten-based POM.

Common (chemical warfare agent) CWA decontaminants exhibit harsh and corrosive characteristics, and are harmful to the environment. In the course of our quest for active sorbents as efficient decontaminants, Keggin-type polyoxometalate (POM) (NH(4))(3)PW(12)O(40) was tested for oxidative degradation of CWAs. Although oxidation did not take place, sarin (GB) and VX were smoothly decontaminated to non-toxic products within 1 and 10 days, respectively. Degradation was carried out directly on the powder, eliminating the need for solvents. Mustard gas (HD), whose degradation is highly dependent on oxidation, was not decontaminated by this POM. Solid state MAS NMR ((31)P and (13)C) was utilized both for POM characterization and for decontamination studies monitoring.

31P MAS NMR: a useful tool for the evaluation of VX natural weathering in various urban matrixes.

The fate of chemical warfare agent VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) in various urban matrixes was monitored utilizing 31P MAS NMR. Chosen matrixes represent buildings, roads, pavement, and earth found in urban environments. In view of the high toxicity of VX, solid state NMR afforded a fairly safe experimental mode, omitting any chance for evaporation. Moreover, due to the nondestructive nature of these experiments, measurements could be repeated over and over using the same samples. Degradation rates of VX were obtained and compared to provide a list of relative reactivity toward VX: concrete >> desert sand > beach sand > asphalt approximately to bitumen sheet. Chemical interactions between VX, its degradation products, and the matrixes were often expressed by widening of the peaks to the extent that mass balance could not be achieved. It is noteworthy that these experiments were usually carried out on crushed or milled specimens, allowing high reactivity and rapid reactions.

Stereoselectivity toward VX is determined by interactions with residues of the acyl pocket as well as of the peripheral anionic site of AChE.

The origins of human acetylcholinesterase (HuAChE) reactivity toward the lethal chemical warfare agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) and its stereoselectivity toward the P(S)-VX enantiomer (VX(S)) were investigated by examining the reactivity of HuAChE and its mutant derivatives toward purified enantiomers of VX and its noncharged isostere O-ethyl S-(3-isopropyl-4-methylpentyl) methylphosphonothioate (nc-VX) as well as echothiophate and its noncharged analogue. Reactivity of wild-type HuAChE toward VX(S) was 115-fold higher than that toward VX(R), with bimolecular rate constants of 1.4 x 10(8) and 1.2 x 10(6) min(-1) M(-1). HuAChE was also 12500-fold more reactive toward VX(S) than toward nc-VX(S). Substitution of the cation binding subsite residue Trp86 with alanine resulted in a 3 order of magnitude decrease in HuAChE reactivity toward both VX enantiomers, while this replacement had an only marginal effect on the reactivity toward the enantiomers of nc-VX and the noncharged echothiophate. These results attest to the critical role played by Trp86 in accommodating the charged moieties of both VX enantiomers. A marked decrease in stereoselectivity toward VX(S) was observed following replacements of Phe295 at the acyl pocket (F295A and F295A/F297A). Replacement of the peripheral anionic site (PAS) residue Asp74 with asparagine (D74N) practically abolished stereoselectivity toward VX(S) (130-fold decrease), while a substitution which retains the negative charge at position 74 (D74E) had no effect. The results from kinetic studies and molecular simulations suggest that the differential reactivity toward the VX enantiomers is mainly a result of a different interaction of the charged leaving group with Asp74.