Collect. Czech. Chem. Commun. 1998, 63, 1021-1030

Hydrates of Quaternary Ammonium Aldehydes as Potential Reactivators of Sarin-Inhibited Acetylcholinesterase

Jiří Cabala, František Hamplb, František Liškab, Jiří Patočkaa, František Riedlb and Kateřina Ševčíkováb

a Department of Toxicology, J. E. Purkyně Military Medical Academy, 500 01 Hradec Králové, Czech Republic
b Department of Organic Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6, Czech Republic


Synthesis of 2- (5a), 3- (5b) and 4-formyl-1-methylpyridinium iodides (5c) and (2,2-dihydroxyethyl)trimethylammonium chloride (6a) is described. In aqueous solution aldehydes 5 exist predominantly as hydrates - geminal diols 7. The ability of the geminal diols 6a and 7 to reactivate acetylcholinesterase inhibited by isopropyl methylfluorophosphonate (Sarin) was tested in vitro. Although compounds 6a and 7 exhibit an affinity towards the acetylcholinesterase bonding site comparable with that of the natural substrate acetylcholine, their reactivation ability was negligible. Second-order rate constants for cleavage of 4-nitrophenyl diphenyl phosphate (PNPDPP) with anions of the studied geminal diols were measured in order to determine their nucleophilicity.

Keywords: Acetylcholinesterase; Organophosphorus inhibitors; Reactivators of phosphonylated acetylcholinesterase; Pyridinium salts; Sarin; Phosphonates.