112740-56-4Relevant articles and documents
Sulfur Derivatives of 2-Oxopropanal Oxime as Reactivators of Organophosphate-Inhibited Acetylcholinesterase in Vitro: Synthesis and Structure-Reactivity Relationships
Degorre, Francoise,Kiffer, Daniel,Terrier, Francois
, p. 757 - 763 (2007/10/02)
We have prepared four new oximes, 1b-e, which conform to the general structure RCH2COCH=NOH where R = CH3S, CH3SO, CH3SO2, and (CH3)2S(+), respectively, and have the same E configuration as the parent 2-oxopropanal oxime 1a (R=H, MINA).The pKa values range from 6.54 (1e) to 8.16 (1b), as compared with 8.30 for 1a.Rates of reaction (k1) with 4-nitrophenyl acetate indicate that the oximate anions have a much higher nucleophilicity than common oxyanions of similar basicities: the α effects measured for 1a-e are of the order of 200-250.The abilities of 1b-e to reactivate acetylcholinesterase (AChE) inhibited by organophosphates have been evaluated.In vitro experiments reveal a significant reactivation potency of 1b-e against VX-, sarin-, and paraoxon-inhibited immobilized eel AChE.The highly lipophilic methylthio oxime 1b (log P > 1) is intrinsically (k2) 3 times more reactive than the more basic MINA (log P 1).The sulfonium oxime 1e is a potent reactivator against paraoxon.Interestingly, both 1b and 1e have a low toxicity and they exhibit a significant antidotal effect at a relative low dose against paraoxon in rats.
