title: Stability studies of bis(pyridiniumaldoxime) reactivators of organophosphate-inhibited acetylcholinesterase.
abstract: Relative stability studies of three organophosphate-inhibited acetylcholinesterase reactivators, 1-(2-hydroximinomethyl-1-pyridinium)-3-(4-carbamoyl-1-pyridinium)- 2-oxapropane dichloride (HI-6), 1,1'-methylenebis(4-hydroximinomethylpyridinium) dichloride (MMB-4), and 1,1'-trimethylenebis(4-hydroximinomethylpyridinium) dibromide (TMB-4) were carried out by semiquantitative TLC and NMR methods. TMB-4 appears to be the most, and HI-6 the least stable of the three compounds. The extent of hydrolysis of HI-6, MMB-4, and TMB-4 in 0.05 M, pH 7 phosphate buffer was approximately 50, 25, and less than 1%, respectively, after 20 d at room temperature. The hydrolysis products of HI-6 were identified by NMR and MS (electron impact) as 2-pyridinealdoxime, picolinamide, and isonicotinamide, whereas that of MMB-4 was identified as 4-pyridinealdoxime. The stability of these reactivators decreases with increasing pH. TMB-4 was stable under both neutral and basic conditions at room temperature. Deuterium exchange of the methylene protons of MMB-4 in D2O and of the protons at the 2- and 6-positions of the pyridinium ring of TMB-4 in NaOD/D2O were observed.
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002801:Cholinesterase Reactivators / Q000032:analysis*; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011220:Pralidoxime Compounds / Q000032:analysis*
chemical_list: D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds; D000110:Acetylcholinesterase