In the fight against chemical weapons, information is power. That’s why researchers are hopeful that a new database of chemical warfare agents (CWAs), including molecular structures and other key details, will help efforts to clamp down on these deadly compounds (J. Chem. Inf. Model. 2020, DOI: 10.1021/acs.jcim.0c00896). “We built these tables to facilitate communication between chemists and policymakers,” says Stefano Costanzi, a chemist at American University who led the work.
Chemical weapons, and the CWAs they contain, are controlled by three main international frameworks. The Chemical Weapons Convention (CWC), which came into force in 1997, imposes a blanket ban on the use of any toxic chemical as a weapon. In parallel, a forum known as the Australia Group coordinates export regulations for precursors of CWAs, along with dual-use materials like chlorine that have legitimate applications but may also be used as weapons. The Wassenaar Arrangement, which is dedicated to arms control and includes CWAs, completes the triumvirate.
The frameworks each maintain lists of CWAs or their precursors, identified using text-only descriptions: their name and a registry number set by CAS, a division of the American Chemical Society (ACS publishes C&EN). Some entries cover entire families of molecules. There is some overlap among the lists, but also a lot of divergence. Unlike the CWC, for example, the Wassenaar Arrangement includes riot control agents and defoliants.This can make it challenging to keep track of the compounds covered by each framework. Chemicals often have many synonyms that are not included in the lists, and different stereoisomers or salts of the same CWA tend to have different CAS numbers, even though they pose essentially the same security threat.
To clarify the picture, Costanzi’s team has organized the chemicals from all of the lists into an online database and added a wealth of other useful information for each entry, including molecular structures and computer-readable identifiers that describe compounds’ structures in strings of characters, such as SMILES (simplified molecular-input line-entry system) and InChI (the International Chemical Identifier) entries. The entries also link to 3-D models of the molecules, and to physical and chemical data provided by the US National Institute of Health’s PubChem database and the US National Institute of Standards and Technology.All this information is already publicly available, but it can be time-consuming to find, says Carlos G. Fraga, a chemical weapons expert at the Pacific Northwest National Laboratory (PNNL), who was not involved in the work. “As a scientist who works in this field, having one place to find all this information is fantastic,” he says.
The science advisory board of the Organization for the Prohibition of Chemical Weapons (OPCW), the CWC’s watchdog agency, had also suggested that control lists would benefit from this kind of annotation, adds Jonathan E. Forman, who was the science policy advisor to OPCW from 2013 until earlier this year and is now at PNNL.
Costanzi says that the changing nature of the chemical weapons threat makes it increasingly important to have this kind of overarching view of CWAs and their precursors. When the CWC came into force, it focused on chemicals manufactured on a large scale that could be used as weapons of mass destruction. But now, a wider variety of chemical agents are being used on a much smaller scale for targeted assassinations. In 2018, for example, the Novichok nerve agent A-234 was used in the attempted murder of Sergei Skripal and his daughter in the UK. And in August, Russian opposition leader Alexei Navalny was poisoned with a Novichok agent.
After the Skripal affair, the CWC was revised—for the first time in its history— to include various Novichoks and carbamate agents, a change that came into force in June. Some of these revisions prompted changes to the Australia Group’s precursors list, although these only cover a subset of Novichok agents. Costanzi’s team showed that the new databae could be used to generate diagrams that clearly show the relationships among older CWAs, the new additions, and their precursors, across the three control frameworks.
Costanzi now plans to use the database to build a more powerful one that could automatically identify variants of CWAs, based on a structural search. He suggests that chemical manufacturers and shipping companies that handle CWA precursors and dual-use compounds could use the system to assess whether a chemical of interest is covered by the main international frameworks.