Erprobung eines neuen Antidot-Prinzips bei experimenteller DFP-Vergiftung

Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)bis(pyridinium chloride) in aqueous phosphate buffers

“…When approximately 95% decomposition had been achieved, the solvent was removed under reduced pressure (room temperature) and the residue was resolubilized in a minimum of methanol, applied to a short column of silica gel (8 X 0.6 cm), and eluted with CHCl3/MeOH (3:1). The product crystallized slowly on evaporating the solvent: mp 191-193 °C; NMR 5.59 (s, 2 H, methylene), 6.07 (s, 2 H, methylene), 6.30 (d, 1 H, A-ring proton), 6.40 (m, 1 H, A-ring proton), 7.44 (m, 1 H, A-ring proton), 4-Carbamoyl-7V-(methoxymethyl)pyridinium Chloride (XIV). Chloromethyl methyl ether, 100 gL, dissolved in 3 mL of acetone was added dropwise to an ice-cold stirred solution of isonicotinamide, 0.1 g (0.819 mmol), dissolved in 12 mL of acetone.…”

“…This product, intermediate 1, had a retention time (relative to HI-6 = 1.0) of 0.48 which was different from any of the anticipated monopyridine ring products. A subsequent 2 H, J = 7 Hz) 8.43 (d, 2 H, J = 7 Hz) 8.97 (d, 2 H, J = 6.4 Hz), 5.96 (s, 2 H) 8.30 (d, 2 H, J = 6.5 Hz), 3.53 (s, methoxy group) 6.37 (s, 2 H) 6.32 (s, 2 H) 5.51 (s, 2 H) 3.50 (s, methoxy) 8.78 (d, 1 H, «7 = 6 Hz), 8.48 1 H, J = 6 Hz), 7.92 (d of d, 1 H) 7.49 (d, 1 H, J = 6 Hz), 7.37 (d of d, 1 H) 6.33 (d of d, 1 H, J = 6 Hz), 6.24 (d, 1 H, J = 6 Hz) 8.53 (s, 1 H) reinvestigation of the crude decomposition profiles using the gBondapak column provided a superior resolution of products with shorter retention times and revealed the presence of a second decomposition intermediate (intermediate 2, RRT = 0.13, Figure 4) in addition to intermediate 1 (RRT = 0.38, Figure 4).…”

“…There is a continuing interest in bis(pyridinium) aldoximes in terms of their ability to reactivate the enzyme acetylcholinesterase (AChE) which has been inhibited by organophosphorus esters or carbamates (1)(2)(3)(4). Pyridinium aldoximes, with an oxamino group ortho or para to a quaternary N, have been demonstrated to react with organophosphorus compounds (5,6) and carbamates in vitro to yield rapidly decomposing products. Provided that the methine hydrogen of the oximino group is sufficiently acidic, decomposition of the phosphorylated or carbamylated oxime is rapid and the adduct shows little tendency to act as a transfer agent and rephosphorylate (carbamylate) the liberated enzyme (7,8).…”

“…The chemical stability and abiotic fate of HI-6 have not been fully studied. This product was demonstrated (18) to decompose to isonicotinic acid and to isonicotinamide in aqueous buffers (pH [2][3][4][5][6][7][8][9]. Two additional products were not identified.…”

“…Given the preponderance of monopyridine ring products it was suggested that HI-6 may be decomposed via routes which are appreciably different from those of other bis(pyridinium) aldoximes as reported by . An earlier study (23) indicated that the aldoxime group of HS-6 (II) was decomposed to the corresponding aldehyde in acidic solutions (pH 2-3), and to the corresponding amide or hydroxy derivative in less acidic buffers (pH [4][5][6][7][8][9].…”