Diisopropyl Methylphosphonate Research Articles

Viscosity and density of organophosphorus liquids and their aqueous solutions

Dimethyl methyl phosphonate (DMMP) and diisopropyl methyl phosphonate (DIMP) are surrogates for chemical warfare agents (CWAs). Their density and viscosity need to be known to design and interpret theoretically laboratory tests describing how CWAs interact with contaminated surfaces. Aqueous CWA solutions form when they come in contact with liquid or evaporated water. Quantifying densities and viscosities of such solutions is important for both interpreting relevant laboratory or field tests and designing decontamination and remediation protocols. Here, densities and viscosities of commercially available DMMP and DIMP and their aqueous solutions are measured. The effect of temperature on viscosity of DIMP and DMMP is quantified. Aqueous solutions for both DMMP and DIMP do not behave as ideal. Their viscosities peak at the mole fractions of xDMMP≈0.35 and xDIMP≈0.3. The infrared absorption spectroscopy suggests that this non-ideality is primarily due to the interaction between the P = O groups of the organophosphorus liquids and the hydroxyl groups of water. Those finding will help understanding the structure and designing predictive molecular models for CWAs, their surrogates, and their aqueous solutions. Reported data can also be directly used in simplified models describing the fate of chemical weapon agents and their surrogates in various practical scenarios.

Experimental characterization of the low-temperature thermal decomposition of diisopropyl methylphosphonate (DIMP)

Diisopropyl methylphosphonate (DIMP) is a chemical weapon agent surrogate. Quantifying the rates of thermal decomposition of such compounds is important to enable predictions of spread of respective toxic vapors in different scenarios. An experimental setup is designed and built to quantify the rate of decomposition of DIMP at temperatures of 200–350 °C. Liquid DIMP is fed from a brass evaporator heated to 140 °C and vented with argon. It is mixed with a pre-heated carrier gas (air or nitrogen) in a steel flow reactor. The gas is sampled from the reactor after a certain residence time and sent to a Fourier transform infrared (FTIR) analyzer. Under 350 °C, the thermal decomposition of DIMP in air occurs much faster than in nitrogen. In air, the decomposition of DIMP can be described as the first order reaction with the rate constant kTs-1=107.4±2.5·exp-21.4±6.6kcal/molRT. Despite measuring substantial reduction in the DIMP concentration due to its thermal decomposition, present measurements could not detect the presence of propene and other decomposition products.

Degradation of diisopropyl methylphosphonate in aqueous solutions by ultrasonic irradiation combined with oxidation process

The degradation of diisopropyl methylphosphonate (DIMP) in aqueous solutions was studied using ultrasound irradiation with a fixed frequency of 26.2 kHz, following the first-order kinetic model. The study's primary goal was to determine the influence of the following experimental parameters: the pH (at different values of 2, 7 and 10), the initial concentration of DIMP (at different concentrations: 7, 14, 30, 50, 80 mg/L), the processing time (at different periods: 15, 30, 45, 60, 80, 90 min), and the concentration of the additive CCl4 (at different concentrations: 0.002, 0.004, 0.006, 0.008 mg/L). A DIMP removal efficiency of 98% from aqueous solution was obtained at pH 10 and 0.008 mg/L CCl4, after an ultrasound irradiation time of 45 min, pointing out the influence of the above-mentioned experimental parameters on the DIMP degradation process.

Magnetic and Impedance Analysis of Fe2O3 Nanoparticles for Chemical Warfare Agent Sensing Applications

A dire need for real-time detection of toxic chemical compounds exists in both civilian and military spheres. In this paper, we demonstrate that inexpensive, commercially available Fe2O3 nanoparticles are capable of selective sensing of chemical warfare agents (CWAs) using frequency-dependent impedance spectroscopy, with additional potential as an orthogonal magnetic sensor. X-ray magnetic circular dichroism analysis shows that Fe2O3 nanoparticles possess moderately lowered moment upon exposure to 2-chloroethyl ethyl sulfide (2-CEES) and diisopropyl methylphosphonate (DIMP) and significantly lowered moment upon exposure to dimethyl methylphosphonate (DMMP) and dimethyl chlorophosphate (DMCP). Associated X-ray absorption spectra confirm a redox reaction in the Fe2O3 nanoparticles due to CWA structural analog exposure, with differentiable energy-dependent features that suggest selective sensing is possible, given the correct method. Impedance spectroscopy performed on samples dosed with DMMP, DMCP, and tabun (GA, chemical warfare nerve agent) showed strong, differentiable, frequency-dependent responses. The frequency profiles provide unique “shift fingerprints” with which high specificity can be determined, even amongst similar analytes. The results suggest that frequency-dependent impedance fingerprinting using commercially available Fe2O3 nanoparticles as a sensor material is a feasible route to selective detection.

Experimental and chemical kinetic modeling study of high-temperature oxidation of diisopropyl methylphosphonate (DIMP) - A sarin simulant

Chemical warfare (CW) agent simulants are used in laboratory experiments to study the combustion characteristics of CW agents due to their high toxicity. A crucial CW agent simulant with a chemical structure similar to the deadly nerve agent Sarin (GB) is diisopropyl methylphosphonate (DIMP), an organophosphate compound (OPC). In this study, the high-temperature oxidation of DIMP is investigated in a shock tube at temperatures between 1440 K and 1710 K and a pressure of 1–2 atm. The carbon monoxide mole fraction time histories near 4.9 µm were obtained using laser absorption spectroscopy. The rate parameters for DIMP's H-abstraction reactions with O, and OH radicals were determined using molecular simulations. The rates of reactions involving smaller phosphorous species were also calculated at the CBS-QB3 level. These reactions along with the isopropanol sub-mechanism from the literature were added to the LLNL model to obtain an improved chemical kinetic mechanism for DIMP. Since isopropanol was a major intermediate in DIMP decomposition, validations were conducted with CO time histories during the oxidation of isopropanol. The new model predicted CO during isopropanol oxidation reasonably well. Both the LLNL model and the model developed in this work could predict CO time histories during DIMP oxidation satisfactorily. To comprehend the CO formation pathways and sensitive reactions during DIMP oxidation, reaction path analysis and sensitivity analysis were also carried out. The reaction mechanism developed here will help in the design, development, and optimization of efficient, effective and secure CW destruction techniques.

Surface Tension of Organophosphorus Compounds: Sarin and its Surrogates

While the production and stockpiling of organophosphorus chemical warfare agents (CWAs), such as sarin, was banned three decades ago, CWAs have remained a threat. New approaches for decontamination and destruction of CWAs require detailed knowledge of their various physicochemical properties. In particular, surface tension is needed to describe the formation and evolution of hazardous aerosols when CWA liquids are dispersed in the air. Due to the extreme toxicity of sarin, most experimental studies are carried out using its surrogates─organophosphorus compounds which, while having similar structures, are much less toxic, e.g., dimethyl methylphosphonate (DMMP) and diisopropyl methylphosphonate (DIMP). However, not only for sarin, but also for its surrogates, literature data on the surface tension are scarce. Here we present experimental measurements and computational predictions of the surface tension of DMMP and DIMP. Classical molecular dynamics simulations using the Transferable Potentials for Phase Equilibria (TraPPE) force field produced an excellent agreement with the experimental results in the temperature range from 3 to 60 °C, validating the predictive capability of TraPPE. Consequently, we applied the TraPPE force field to sarin. Our modeled values for the sarin surface tension cover the range of temperatures from 0 to 85 °C, and the four experimental data points from the literature measured between 20 and 35 °C agree perfectly with our predictions. The temperature-dependent surface tension values for sarin and its surrogates obtained in our study can be used in models predicting the formation and evolution of aerosols made of these chemicals. Furthermore, our results justify the use of the TraPPE force field to derive the thermodynamic properties of other organophosphorus compounds with structures similar to the ones studied here.

Closer Look at Adsorption of Sarin and Simulants on Metal–Organic Frameworks

The development of effective protection against exposure to chemical warfare agents (CWAs), such as sarin, relies on studies of its adsorption on the capturing materials and seeking candidates capable of adsorbing large amounts of sarin gas. Many metal-organic frameworks (MOFs) are promising materials for the effective capture and degradation of sarin and simulant substances. Among the simulants capable of mimicking thermodynamic properties of the agent, not all of them have been investigated on the ability to act similarly in the adsorption process, in particular, whether the agent and a simulant have similar mechanisms of binding to the MOF surface. Molecular simulation studies not only provide a safe way to investigate the aforementioned processes but can also help reveal the mechanisms of interactions between the adsorbents and the adsorbing compounds at the molecular level. We performed Monte Carlo simulations of the adsorption of sarin and three simulants, dimethyl methylphosphonate (DMMP), diisopropyl methylphosphonate (DIMP), and diisopropyl fluorophosphate (DIFP), on selected MOFs that have previously shown strong capabilities to adsorb sarin. On the basis of the calculated adsorption isotherms, enthalpy of adsorption, and radial distribution functions, we revealed common mechanisms among the particularly efficient adsorbents as well as the ability of simulants to mimic them. The findings can help in selecting a suitable simulant compound to study CWA adsorption on MOFs and guide further synthesis of efficient MOFs for the capture of organophosphorus compounds.

Removal of diisopropyl methyl phosphonate (DIMP) from heated metal oxide surfaces.

Diisopropyl methyl phosphonate (DIMP) is an organophosphorus compound used as a surrogate of sarin, a chemical weapon agent. Thermal decomposition of DIMP and similar liquids may be affected by added inorganic solids. Understanding such effects is needed to guide decontamination and environmental mitigation work. Here, liquid DIMP mixed with powders of γ-Al2O3 or SiO2, was heated to 350°C in a thermogravimetric analyzer while observing effluent gas using a mass spectrometer. For both powders, evaporation of DIMP occurred between 50 and 200°C, followed by a second mass loss step up to 350°C. The amount of DIMP evaporated in the first step varied; however, the size of the second, mass loss step was consistent between experiments for each solid used. For γ-alumina, 2-propanol and propene were released below the DIMP boiling point and mostly propene at higher temperatures. Calcining alumina prior to exposure to DIMP reduced the release of 2-propanol. For silica, the second mass loss step was smaller and only propene was released. Powders exposed to DIMP and recovered at different temperatures showed FTIR peaks corresponding to the individual bond vibrations of DIMP. At higher temperatures, only the P-CH 3 stretching vibration was observed.

Dual-technique assay for the analysis of organophosphorus compounds for environmental and chemical defense applications

Forensic and environmental sciences often rely on chromatographic separations coupled to mass spectrometry to detect contaminants in complex matrices. However, these methods require lengthy analysis times and sample preparation that is not suitable for analysis in the field. In this work, two analytical methods were combined that are known for their potential for portable analysis. The ambient ionization technique, paper spray mass spectrometry (paper spray-MS) was coupled to paper-based surface enhanced Raman spectroscopy (pSERS) to detect toxic organophosphorus molecules from the same substrate, with a total analysis time of less than five minutes. The coupling of these techniques presents a potential for portable Raman screening followed by MS confirmation in a field-forward laboratory. A cartridge insert was designed and 3D printed to facilitate the sample collection and analysis for PS-MS and pSERS. Three chemical warfare agent simulants: dimethyl methylphosphonate (DMMP), diethyl phosphoramidate (DEPA), and diisopropyl methylphosphonate (DIMP) were included in the method due to having similar chemistries to G- and V-series chemical warfare agents (CWAs). Organophosphorus pesticides, malathion and dichlorvos, with similar mechanisms of action to the CWAs, were also included in the method. Because CWAs quickly degrade in the environment, the CWA hydrolysis products, ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), pinacolyl methylphosphonic acid (PinMPA), methylphosphonic acid (MPA), 2-Diethylaminoethanethiol (EDA), and 2-Diisopropylaminoethanethiol (IDA) were also studied. A mixture of the analytes was used to create calibration curves using the dual-polarity, PS-MS method with sub-ng to low ng limits of detection. A dilution series, spanning 3 orders of magnitude, was made using pSERS, also with low ng limits of detection. These experiments show the potential and feasibility for PS-MS coupled to pSERS to be used to rapidly, screen and confirm the presence of organophosphorus molecules, in complex matrices, with portable instrumentation.

Forensic analysis of the deuterium/hydrogen isotopic ratios of the nerve agent sarin, its reaction by-product diisopropyl methylphosphonate and their precursors by 2H SNIF-NMR

The Deuterium/Hydrogen (D/H) isotope ratios of sarin (5), diisopropyl methylphosphonate (3) and their precursors Isopropanol (1), methylphosphonic acid dichloride (2) and methylphosphonic acid difluoride (4) were measured by the 2H SNIF-NMR technique. The D/H isotope ratios of 1 show a large variation. It is shown, that the formation of 3 by reaction of 1 with 2, the fluorination of 2 to form 4 and the reaction of 4 with 1 to form 5, the D/H isotope ratios of the methyl and isopropyl moieties in 3, 4 and 5 are not significantly changed compared to 1 and 2.

High-temperature pyrolysis experiments and chemical kinetics of diisopropyl methylphosphonate (DIMP), a simulant for Sarin

Due to the high toxicity of chemical warfare (CW) agents, laboratory experiments are carried out using CW surrogates. Diisopropyl Methylphosphonate (DIMP), an organophosphate compound (OPC), is a crucial CW surrogate that has a chemical structure similar to the deadly nerve agent Sarin (GB). In this work, high-temperature pyrolysis of DIMP is conducted in a shock tube within a temperature range of 1400 - 1800 K at near 1 atm pressure. Laser absorption spectroscopy was used to obtain carbon monoxide mole fraction time-histories during high-temperature pyrolysis for DIMP. In order to predict the CO mole fraction time-histories during DIMP pyrolysis, a reaction mechanism was developed using the Lawrence Livermore National Lab (LLNL)’s OPC mechanism. Several important reactions of DIMP and its important intermediates during pyrolysis were studied at the CBS-QB3 level of theory, and corresponding reaction rates were determined using transition state theory. The reactions related to methyl phosphonic acid (MPA) and methyl(oxo)phosphoniumolate (MOPO) were added from literature and by analogies with similar compounds. Thermochemical properties of crucial species involved in DIMP pyrolysis were calculated using the CBS-QB3 composite method and were updated in the model. A reaction mechanism was compiled for DIMP pyrolysis using these rates. Two versions of this mechanism (‘Model A’ and ‘Model B’) were generated to understand the significance of new reactions in predicting CO mole fraction time histories. Significant improvement in the prediction of CO was observed compared to the LLNL model with either of these mechanisms. A reaction path analysis was conducted to understand the formation pathways of CO during DIMP pyrolysis. Finally, sensitivity analysis was performed to get insights into important reactions leading to CO formation. It was found that the H-abstraction from MOPO by methyl radical plays an important role in CO formation.

Part-per-Trillion Trace Selective Gas Detection Using Frequency Locked Whispering-Gallery Mode Microtoroids.

Rapid detection of toxic and hazardous gases at trace concentrations plays a vital role in industrial, battlefield, and laboratory scenarios. Of interest are both sensitive as well as highly selective sensors. Whispering-gallery mode (WGM) microresonator-based biochemical sensors are among the most sensitive sensors in existence due to their long photon confinement times. One main concern with these devices, however, is their selectivity toward specific classes of target analytes. Here, we employ frequency locked WGM microtoroid optical resonators covalently modified with various polymer coatings to selectively detect the chemical warfare agent surrogate diisopropyl methylphosphonate (DIMP) as well as the toxic industrial chemicals formaldehyde and ammonia at parts-per-trillion concentrations (304, 434, and 117 ppt, respectively). This is 1-2 orders of magnitude better than previously reported, depending on the target, except for pristine graphene and pristine carbon nanotube sensors, which demonstrate similar detection levels but in vacuum and without selectivity. Selective polymer coatings include polyethylene glycol for DIMP sensing, accessed by the modification of commercially available materials, and 3-(triethoxysilyl) propyl-terminated polyvinyl acetate (PVAc) for ammonia sensing. Notably, we developed for the first time an efficient one-pot procedure to access 3-(triethoxysilyl) propyl-terminated PVAc that utilizes cobalt-mediated living radical polymerization and a nitroxyl polymer-terminating agent. Alkaline hydrolysis of PVAc coatings to form polyvinyl alcohol coatings directly bound to the microtoroid proved to be reliable and reproducible, leading to WGM sensors capable of the rapid and selective detection of formaldehyde vapors. The selectivity of these three polymer coatings as sensing media was predicted, in part, based on their functional group content and known reactivity patterns with the target analytes. Furthermore, we demonstrate that microtoroids coated with a mixture of polymers can serve as an all-in-one sensor that can detect multiple agents. We anticipate that our results will facilitate rapid early detection of chemical agents, as well as their surrogates and precursors.

Direct measurement of reaction rate for decomposition of diisopropyl methylphosphonate at high temperature using shock tube and laser absorption

AbstractDiisopropyl methylphosphonate (DIMP) is an organophosphorus compound used as a simulant for the chemical weapon Sarin. One of the means of destruction of Sarin is incineration at high temperature, which requires a clear understanding of the high‐temperature reaction kinetics of Sarin. In this work, we study the reaction rate for thermal decomposition of DIMP in the temperature range of 762–1059 K at a pressure near 1 atm. Test conditions are carefully chosen to minimize interferences from other reactions and intermediates formed during the decomposition process. The experimental rates obtained have been fitted for the Arrhenius rate expression to get the rate parameters of the reaction r1, DIMP (C7H17O3P) = IMP (C4H11O3P) + propene (C3H6) as The rate obtained in this work extended the temperature range of previous measurements (up to 800 K) and can be used in reaction kinetic models for combustion of DIMP.

Emission Spectra of Hydrocarbon Flames Doped with Phosphorus-Containing Compounds

Phosphorus-containing compounds, including organophosphorus substances, are valuable laboratory flame additives for understanding the combustion behavior of sarin. Chemiluminescence features of excited intermediate species are useful markers of combustion, but an effective chemiluminescence-based combustion diagnostic for phosphorus-based compounds is yet to be developed. In this study, chemiluminescence spectra of atmospheric-pressure flames doped with three phosphorus-containing compounds, namely, dimethyl methylphosphonate, diisopropyl methylphosphonate, and phosphoric acid (), were obtained in two flame configurations, namely, spherically expanding flames and piloted liquid-spray flames. The spectra are compared with those obtained from undoped flames fueled by methane and methanol, respectively. Spectra were recorded for the wavelength range of 200–800 nm and for three equivalence ratios (, 1.0, 1.2) of spherical flames. For both flame configurations, the intensity of the doped flame emission increased relative to the neat flames by over an order of magnitude, but no clear spectral features besides a broad, featureless continuum emission could be identified. No significant difference was observed between the spectra of the spray flames doped with and with diisopropyl methylphosphonate. The observance of a continuum emission for all the doped flames is attributed to blackbody emission, likely resulting from high-temperature soot particles in the flame originating from condensed, phosphorus-containing combustion products. However, unique, narrow chemiluminescence features specific to phosphorus combustion could not be identified at this time.

High-Temperature Decomposition of Diisopropyl Methylphosphonate on Alumina: Mechanistic Predictions from Ab Initio Molecular Dynamics

The enhanced degradation of organophosphorous-based chemical warfare agents (CWAs) on metal-oxide surfaces holds immense promise for neutralization efforts; however, the underlying mechanisms in this process remain poorly understood. We utilize large-scale quantum calculations for the first time to probe the high-temperature degradation of diisopropyl methylphosphonate (DIMP), a nerve agent simulant. Our Born-Oppenheimer molecular dynamics (BOMD) calculations show that the $\gamma$-Al$_2$O$_3$ surface shows immense promise for quickly adsorbing and destroying CWAs. We find that the alumina surface quickly adsorbs DIMP at all temperatures, and subsequent decomposition of DIMP proceeds via a propene elimination. Our BOMD calculations are complemented with metadynamics simulations to produce free energy paths, which show that the activation barrier decreases with temperature and DIMP readily decomposes on $\gamma$-Al$_2$O$_3$. Our first-principle BOMD and metadynamics simulations provide crucial diagnostics for sarin decomposition models and mechanistic information for examining CWA decomposition reactions on other candidate metal oxide surfaces.

Modeling and simulation of external electric field application for diisopropyl methylphosphonate sensing through B12N12 fullerene

The external electric field can effectually enhance the electronic and optical features of low dimensional systems. Hence, the corresponding atomic structure and adsorption feature changes of a B12N12 fullerene under different applied external electric fields for dimethyl methylphosphonate (DMMP) detection were evaluated. The adsorption of DMMP on the B12N12 surface has been calculated using density functional theory (DFT) and time dependent density functional theory (TDDFT) by the PBE (Perdew-Burke-Ernzerhof) functional to study the effects of the parallel (EX) and transverse (EY) external electric fields on the structural and optoelectronic features of the pure fullerene. Through the analysis of the binding energy it is found that B12N12 fullerenes, in the presence of a parallel external electric field (EX = 0.15 a.u.), are energetically favored when compared to B12N12 fullerenes in the presence of a transverse external electric field (EY = 0.15 a.u.). The results demonstrate that a transverse external electric field ranging from 0.005 a.u. to 0.015 a.u. could enhance the DMMP sensitivity of the B12N12 fullerene (with a significant reduction of energy band gap), which potentially could aid in the development of a room temperature DMMP gas sensor. The adsorption and desorption of DMMP could be controlled by external electric field too, which has the potential for applications in itself, relative to DMMP collection and storage.

Force Fields for Molecular Modeling of Sarin and its Simulants: DMMP and DIMP.

Even three decades after signing the Chemical Weapons Convention, organophosphorus chemical warfare agents (CWAs), such as sarin, remain a threat. The development of novel methods for the detection of CWAs, protection from CWAs, and CWA decontamination motivates research on their physicochemical properties. Due to the extreme toxicity of sarin, most of the experimental studies are carried out using less toxic simulant compounds. In addition to experimental studies of sarin simulants, both sarin and simulants can be studied using in silico experiments-molecular simulations. The results of classical molecular modeling of the compounds and their agreement with experimental data rely on the force field used to describe the system. In recent years, there have been several force fields proposed for sarin and its most common simulant dimethyl methylphosphonate (DMMP). However, other simulants frequently used in experiments received less attention from the molecular simulation perspective, for example, to date, there is no force field and no simulation data for diisopropyl methylphosphonate (DIMP). Here, we compare the literature force fields for sarin and DMMP, focusing specifically on the vapor-liquid equilibrium for the pure species. We carried out Monte Carlo and molecular dynamics simulations using the existing literature force fields from which we predicted the liquid densities and vapor pressures developing the entire binodal curves. We compared the predictions to the experimental data and showed that the TraPPE-UA force field outperformed the other force fields. Thus, we extended TraPPE-UA for DIMP, utilized this force field in molecular simulations, and predicted the liquid densities and vapor pressures for a range of temperatures (binodal curve), which agreed well with the published experimental data. From the binodal, we calculated the critical properties of DIMP and demonstrated that these parameters can be used in the Peng-Robinson equation of state for this compound.

The decisive role of pericyclic reactions in the thermal decomposition of organophosphorus compounds

The understanding of the thermal decomposition chemistry of chemical warfare nerve agents is largely limited by the scarcity of kinetic data. Because of the high toxicity of these molecules, experimental determination of their chemical properties is very difficult. In the present work, a comprehensive detailed kinetic model for the decomposition of sarin and some simulants, i.e. di-isopropyl methyl phosphonate (DIMP), diethyl methylphosphonate (DEMP), and triethyl phosphate (TEP) were developed, containing possible molecular and radical pathways. The importance of unimolecular pericyclic decomposition led to evaluate precisely the rate constants of these reactions with high level theoretical calculations. The QCISD(T)/cc-PV∞QZ//B2PLYPD3/6–311+G(2d,d,p) level of theory was selected after a benchmark. The contribution of hindered rotors was included with the 1D-HR-U approach. Tunneling was taken into account for H-atom transfer. Transition state theory was used to calculate high-pressure limit rate constants and pressure dependent rate constants were calculated using Master Equation modeling. The model was validated against experimental pyrolysis and oxidation experimental data available in literature. Flux analyses showed that whatever the conditions are, the first step of decomposition of the studied phosphorus compounds are pericyclic eliminations leading to successive decompositions, whereas bond-breaking or H-atom abstraction remain negligible, even at high temperature.

Follicular pathway role in chemical warfare simulants percutaneous penetration.

Chemical warfare (CW) exposure could be fatal to military and civilians through skin contamination. Our work and others focus on investigating stratum corneum reservoir with less regards to skin appendageal routes including hair follicles. Here, C-14 CW simulants (CWS) with specific activity of 0.1 mCi/ml were tested on abdominal and scalp human cadaver skin using flow-through diffusion system. Quantitative analysis of simulants in skin compartments were performed using scintillation counter. Scalp permeation of dipropylene glycol monomethyl ether (DPGME), diisopropyl methylphosphonate (DIMP) and methyl salicylate (MeS) exceed abdominal skin by 8%, 15%, and 6% (p value < 0.05) of applied dose, respectively. DPGME and DIMP (most hydrophilic) showed earlier permeation peak time (Tmax) through scalp skin at 2 and 4 h, respectively, comparing with 6 h with abdominal skin. The percentage of applied dose of DPGME and DIMP retained in human skin membrane (SC, epidermis, and viable dermis) showed no statistically significant difference between tested abdominal and scalp skin samples (p value >0.05). The percentage of applied dose of MeS in scalp showed higher partitioning in stratum corneum and viable epidermis than abdominal skin (p value <0.05). In conclusion, human scalp showed greater total skin absorption than abdominal skin. This work points to a qualitative importance of high follicular density body regions in percutaneous penetration and suggests that transfollicular pathway might have a significant role in early stage permeation of chemical warfare simulants. However, the difference noticed here between scalp and abdominal skin could be attributed to regional variability in anatomy, physiology, and barrier characteristics.

Binding of Organophosphorus Nerve Agents and Their Simulants to Metal Salts.

Nerve agents (NAs) pose a great threat to society because they are easy to produce and are deadly in nature, which makes developing methods to detect, adsorb, and destroy them crucial. To enable the development of these methods, we report the use of first principles electronic structure calculations to understand the binding properties of NAs and NA simulants on metal salt surfaces. We report calculated Gibbs free binding energies (GBE) for four NAs (tabun (GA), sarin (GB), soman (GD), and venomous X (VX)) and five NA simulants (dimethyl methylphosphonate (DMMP), dimethyl chlorophosphate (DMCP), trimethyl phosphate (TMP), methyl dichlorophosphate (MDCP), and di-isopropyl methylphosphonate (DIMP)) on metal perchlorate and metal nitrate salts using density functional theory. Our results indicate a general trend in the binding strength of NAs and NA simulants to metal salt surfaces: MDCP < DMCP < GA < GD ≈ GB < TMP < VX ≈ DMMP < DIMP. Based on their binding properties on salt surfaces, we identify the most effective simulant for each of the studied NAs as follows: DMCP for GA, TMP for GB and GD, and DMMP for VX. To illustrate the utility of the binding energies calculated in our study, we address the design of NA sensors based on the competitive binding of NAs and liquid crystalline compounds on metal salts. We compare our results with previous experimental findings and provide a list of promising combinations of liquid crystal and metal salt systems to selectively and sensitively detect NAs. Our study highlights the great value of computational chemistry for designing selective and sensitive NA sensors while minimizing the number of very dangerous experiments involving NAs.