A computational protocol to model organophosph(on)ate chemical warfare agents and their simulants

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 – 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 behaviour 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 behaviour and remove the need to use the agents themselves.

Project timeframe

The project ran from 2015 to 2016 and was funded by the US Army Research Office (W911NF-15-1-0624) with in-kind contributions from Defence Science and Technology Laboratory (Dstl), Porton Down.

Project aims

The project sought to determine if computational protocols could be developed, using commercially available software, to accurately predict a) the molecular geometries of chemical warfare agents and b) the receptor molecules with the highest affinities for the agents. The aims would be assessed through the similarities between experimental and calculated infrared spectra and by comparing computational results with experimental data from the Defence Science and Technology Laboratory (Dstl).

Project findings and impact

A protocol was developed to predict the infrared spectra and binding behaviour 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.

GA, GB, GD, GF, VG and VX, together with 11 simulants, were modelled in the gas phase; the G-series was additionally modelled as hydrates. 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. 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. Semiempirical models correctly predicted the different binding strengths of GD stereoisomers with β-cyclodextrin. DFT calculations replicated the much higher experimental affinity that GD has for β-cyclodextrin over all simulants. The results represent the first thorough computational study to predict 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.

Research team

Peter J Cragg

Ian A Gass

Output

Experimental and computational study of the inclusion complexes of β-cyclodextrin with the chemical warfare agent soman (GD) and commonly used simulants, M. R. Sambrook, J. C. Vincent, J. A. Ede, I. A. Gass and Peter J. Cragg, M/S in preparation.

A DFT study of the spectroscopic and binding properties of G-series chemical warfare agents and their commonly used simulants, M. R. Sambrook, I. A. Gass and P. J. Cragg, M/S in preparation.

Partners

Mark Sambrook (Dstl)