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

The development of methods to detect chemical warfare agents (CWAs) remains an elusive target for academic and commercial researchers.

While it is possible to design destructive systems that act against a range of CWAs, detecting which specific CWA is present is much harder. As a first step to designing CWA-specific sensors the aim of this project was to develop a robust computational protocol to replicate CWA properties and interactions with potential binding agents.

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.