Lists of Chemical Warfare Agents and Precursors from International Nonproliferation Frameworks: Structural Annotation and Chemical Fingerprint Analysis

• Published in: Journal of chemical information and modeling 2020-10, Vol.60 (10), p.4804-4816
• Main Authors: Costanzi, Stefano, Slavick, Charlotte K, Hutcheson, Brent O, Koblentz, Gregory D, Cupitt, Richard T
• Format: Article
• Language: English
• Subjects: Agent Orange; Analytical chemistry; Annotations; Biological & chemical weapons; Chemical fingerprinting; Chemical Information; Chemical warfare; Chemical Warfare Agents - toxicity; Chemical weapons; Chemists; Lists; Precursors; Schedules; Websites
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.0c00896

To support efforts to stem the proliferation of chemical weapons (CWs), we have curated and structurally annotated CW-control lists from three key international nonproliferation frameworks: the Chemical Weapons Convention (CWC), the Australia Group (AG), and the Wassenaar Arrangement. The curated lists are available as web tables at the Costanzi Research website (https://costanziresearch.com/cw-control-lists/). The annotations include manually curated 2D structural images, which provide a means to appreciate at a glance the similarities and differences between different entries, as well as downloadable 2D structures, in two different formats and three different structural identifiers, namely, simplified molecular-input line-entry system, standard InChI, and standard InChIKey, which are intended to provide a platform for cheminformatics analyses. The tables also include links to National Center for Biotechnology Information’s PubChem and National Institute of Standards and Technology’s Chemistry WebBook cards, hence providing prompt access to a wealth of physicochemical, analytical chemistry, and toxicological information. To showcase the importance of structural annotations, we discuss a discrepancy in a CW-control list covering the defoliant Agent Orange, which we identified through our curation process, and propose a solution to address it. Moreover, we present the results of chemical fingerprinting analyses, through which we clustered the entries of the three CW-control lists under study into structurally related groups and studied the overlaps between the three lists. As an application of this study, we examine the recent updates of CWC Schedule 1 and the AG precursors list, highlighting the relationships between the two amendments and proposing the possible addition of further chemicals. Our research is intended to facilitate the communication between scientific advisors and policymakers as well as the work of chemists and cheminformaticians involved in the CW nonproliferation field. Ultimately, we seek to provide tools to bolster the control of CWs and support the global efforts to rid the world of this category of weapons.