Microsynthesis, mass spectrometry data and acetylcholinesterase inhibition studies of carbamates related to the OPCW 1.A.16 Scheduled Chemicals

Abstract

The misuse of chemical warfare agents (CWAs) remains a global threat, prompting the Organisation for the Prohibition of Chemical Weapons (OPCW) to expand its list of controlled substances under the Chemical Weapons Convention (CWC), including carbamates -potential acetylcholinesterase inhibitors. As an OPCW Designated Laboratory since 2021, IDQBRN/CTEx aims to develop robust methodologies for CWC verification. This study introduces a comprehensive and safe microscale methodology for synthesizing and purifying monoquaternary carbamates (MQC) - direct precursors of OPCW 1.A.16 chemicals - accompanied by detailed mass spectrometry data (MS, MS/MS, and HRMS). We achieved MQC synthesis using a refined literature procedure, ensuring safety and efficiency in a research setting. Purification was optimized via preparative thin-layer chromatography (TLC) with C18 functionalized silica and acetonitrile as the eluent. Electrospray ionization (ESI) mass spectrometry provided accurate molecular structure determination and fragmentation pathway analysis. Consistent fragmentation patterns across the MQC series revealed systematic mass differences due to methylene unit loss. The distinctive bromine isotope signature (⁷⁹Br and ⁸¹Br) confirmed compound integrity through paired peaks separated by two mass units. These data address to an analytical gap, offering a valuable reference for CWC verification. Finally, we assessed the acetylcholinesterase isoform inhibition by a long-chain carbamate precursor, which in our assays' conditions, led to a moderate inhibition followed by recovering of enzyme activity after 10 min of incubation. We anticipate that these findings will enhance analytical understanding of these CWC-relevant chemicals and improve knowledge on the development of medical countermeasures, bolstering global efforts to detect and deter chemical warfare agent misuse.

Keywords: Acetylcholinesterase; CWC scheduled chemicals; Carbamates; Microsynthesis; Spectral elucidation; Surrogates.