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Synthesis and characterization of novel oxime antidotes for organophosphorus poisoning

In attempt to find new, more potent antidotes against organophosphorus poisoning [1], series of novel, quaternary imidazole-2-aldoxime based compounds have been prepared. N-alkylation of commercially available imidazole was carried out with benzyl bromide in THF with sodium hydride as a base. N-benzylimidazole was converted to 2-carbaldehyde derivative by the reaction with n-butyllithium and DMF [2]. N-benzylimidazole-2-aldoxime was synthesized using hydroxylamine hydrochloride in solution and without solvent in mechanochemical reaction [3]. Quaternization of N-benzylimidazole-2-aldoxime with methyl iodide and benzyl bromides substituted with fluorine atoms and trifluoromethyl groups resulted in the desired novel quaternary compounds [1, 4]. Structures of compounds were deduced from FTIR, ATR, one- and two-dimensional NMR spectra. Furthermore, molecular modelling was used to predict the most probable orientations of compounds within the active site of the enzyme to determine the potency to reactivate phosphorylated human plasma butyrylcholinesterase (BChE). The optimized geometries for complexes of all prepared oximes with BChE have been proposed. Structural characteristics of an efficient oxime reactivator, differences in orientation and relative energies will be presented and discussed.

imidazole-2-aldoxime compounds ; organophosphorus poisoning ; antidotes

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