A computational protocol to model organophosph(on)ate chemical warfare agents and their simulants
Abstract
The manufacture of chemical warfare agents (CWAs) is banned under the 1993 Chemical Weapons Convention. Nevertheless, significant stockpiles still exist in the US, Israel, North Korea, Syria and Russia, and there is evidence of their use in Iraq (1987), Japan (1995) and Syria (2013). In the event of deliberate or accidental release it is essential to detect and destroy these highly toxic materials. Many methods of detection have been developed, however, they can only be tested using simulants Ð molecules with much lower toxicity than the CWAs but otherwise similar properties. These detection methods often work well with simulants but behave very differently with the CWAs. If accurate computer models can be developed, then the behavior of both simulants and CWAs can be predicted. Comparisons can then be made between experimental and computational simulant data. If these correlate then computer predictions concerning CWAs should also be an accurate representation of their real behavior and remove the need to use the agents themselves. The project sought to determine if computational protocols could be developed, using commercially available software, which would accurately predict a) the molecular geometries of chemical warfare agents and b) the receptor molecules with the highest affinities for the agents. The first aim would be assessed through the similarities between experimental and calculated infrared spectra. The second aim would be assessed by comparing computational results with experimental data from the Defence Science and Technology Laboratory (DSTL), Porton Down, UK. A protocol was developed to predict the infrared spectra and binding behavior of organophosph(on)ates. GB (sarin) was used to benchmark the method through gas phase simulations with progressively more sophisticated models. Computed spectra were compared with examples in the literature and those provided by DSTL. Density functional theory using the EDF2 functional and diffuse 6-311++G** basis set was found to give the closest match. Using the same method and functional the 6-31G (2df, 2p) basis set was found to be superior when hydrated GB was modeled. GA, GB, GD, GF, VG and VX, together with 11 simulants, were modeled using the gas phase protocol; the G-series was additionally modeled using the protocol for hydrates. The gas phase simulations were in good agreement with calculated asymmetric P-O-R stretches in the literature and more accurate for the P=O stretches. The hydrated simulations exhibited shifts for the P-O-R and P=O bond stretches as would be expected from the effects of hydrogen bonding to water. The shift to lower wave numbers for the P=O stretch on organophosphonates was also consistent with literature data. Binding of CWAs and simulants to cyclodextrins was investigated at semiempirical and ab initio levels of theory. Semiempirical (PM6) models were able to correctly predict the different binding strengths of GD stereoisomers with §-cyclodextrin. Higher level calculations were able to replicate the much higher experimental affinity that GD has for §-cyclodextrin over all simulants. Investigation of §-cyclodextrinásimulant complexes for which experimental data were not available suggested that DIFP is the best simulant to mimic the binding behavior of GD. The results represent the first thorough computational study that predicts infrared spectra and cyclodextrin-binding affinities of CWAs and simulants. The computational method developed during this project will have applications in the design of molecular sensors for CWAs.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1510624
Entities
People
- Peter J Cragg
Organizations
- Army Contracting Command
- United States Army
- University of Brighton