Chemical weapons’ detection requires good analytical data

Chemical weapons, and their precursors, were banned by the Chemical Weapons Convention, which has been signed and ratified by nearly all the countries in the world. However, the illegal use of chemical weapons, whether by state agencies or terrorist organisations, remains a threat. Chemical weapons were used by Iraqi forces in the 1980s against Iranian forces and Kurdish civilians. Some chemical weapons, such as chlorine gas, are believed to have been used in recent years in the Syrian civil war.

Current databases include mass spectra of the more common chemical warfare agents; however, more work needs to be carried out on rarer agents. The so-called ‘Novichok’ agents are a range of highly toxic nerve agents developed in the Soviet Union in the 1970s and 1980s. The literature on their spectral properties is sparse.

The detection of chemical weapons may involve samples in which they are present at extremely low levels. Mass spectrometry is generally used for identification, typically GC/MS or LC/MS. Even with these techniques, identification may be difficult in situations where the molecular ion is weak or isomeric compounds could be present. It is important to recognise typical fragmentation pathways in order to reliably identify the compounds.

GC/MS and LC-MS/MS used for ‘Novichok’ agent detection

The Iranian researchers synthesised five ‘Novichok’ agents, along with four deuterated analogues. They were all O-alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidate compounds (i.e. molecules with the typical nerve agent phosphorus group coupled to N,N,N’N’-tetramethylguanidine). The O-alkyl group was varied, with the methoxy, ethoxy, isopropoxy, phenoxy, and 2,6-dimethylphenoxy derivatives being prepared. The syntheses were carried out on a micro-scale in order to minimize exposure.

The synthesised nerve agents were examined using GC/MS, using a 40–280°C GC ramp, an electron ionisation (EI) source and a mass selective detector (MSD). The compounds all showed a good to moderate molecular ion. The other main ions were identified with the help of the mass spectra from the deuterated analogues. The fragmentation was mostly as might be expected; for example, for the methoxy analogue the base peak involved loss of a dimethylamino group and the phosphorus methyl group. For the phenoxy compound, the base peak was that from the loss of a dimethylamino group; the authors propose an intramolecular reaction involving attack from the ortho position of the phenoxy group on the central ‘guanidine’ carbon, leading to the loss of the dimethylamino group and formation of a stable sigma complex. Some evidence for this mechanism is provided by the spectrum of the 2,6-dimethylphenoxy derivative, where the corresponding peak is far weaker, presumably because the ortho positions are blocked by the methyl groups. A distinctive McLafferty-type rearrangement, with the loss of an alkene from the alkoxy group, was seen with derivatives where this was possible, such as ethoxy and isopropoxy, but not in methoxy and phenoxy derivatives, where such a rearrangement could not occur.

The compounds were examined by LC-MS/MS, using an electrospray ionisation (ESI) source and a quadrupole tandem mass spectrometer. The HPLC used an aqueous acetonitrile gradient system, with 20 mM formic acid. In general the ESI spectra were similar to the EI spectra. The facile loss of a dimethylamino group with the phenoxy derivative was again noted.

New additions to chemical weapons database

The authors succeeded in synthesising and obtaining detailed mass spectral data on a series of unusual nerve agents. The data have been added to the Organisation for the Prohibition of Chemical Weapons’ Central Analytical Database (OCAD). It is important that such databases are as comprehensive as possible so that unusual chemical weapons can be unambiguously detected. The task of ridding the world of all chemical weapons requires a great deal of painstaking work, but the ultimate goal is surely something of which we should all approve.

Author(s)

Ryan De Vooght-Johnson