Study of Efficacy of Reactivator HI-6 in Reactivation of Immobilized Acetylcholinesterase, Inhibited by Organophosphorus Chemical Warfare Agents of the “G” Series

Abstract

Reactivation with bis quaternary aldoxime HI-6, chemical formula 1-(2-hydroxyamino-methylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride of immobilized enzyme acetylcholinesterase inhibited by nerve agent type "G" was studied. This aldoxime is effective in reactivation of sarin-inhibited acetylcholinesterase. Substantially lower reactivation potency was observed with cyclosarin-inhibited enzyme and almost no effect was found for that acetylcholinesterase is the enzyme complex. HI 6 is completely ineffective towards the soman-inhibited enzyme: After a 2-minute inhibition of the enzyme with soman no ability to define reactivator the inhibited enzymes and complexes.

Novichok Nerve Agents as Inhibitors of Acetylcholinesterase—In Silico Study of Their Non-Covalent Binding Affinity

“…There are reports on the analysis of these compounds using theoretical and spectroscopic methods [ 9 , 10 , 13 , 15 , 16 ], and scarce in vitro research [ 17 ], yet there is, to the best of our knowledge, no information about any extensive in silico examinations of Novichoks’ mechanism of action and their potential reactivators. In reactivating the enzyme from OPNAs, several oxime-based compounds [ 18 , 19 , 20 , 21 , 22 ] as well as several engineered OPNA-degrading enzymes [ 14 ] are effective, and purely theoretical studies were conducted (e.g., [ 23 , 24 ]). Regarding Novichoks however, there is a lack of both QM and molecular mechanics (MM) investigations of Novichok–AChE interactions, including the noncovalent ones; yet, obviously, the noncovalent interplay between the ligand and the enzyme contributes to and facilitates the irreversible phosphonylation of the AChE catalytic-triad serine e.g., by adjusting the ligand electron density distribution therefore stabilizing the ligand in the enzyme active centre gorge and making it thus more susceptible to nucleophilic enzyme attack.…”