Pyridinium 4-aldoximes

In the search of antidotes for these cholinesterase inhibitors, oximates as well as hydrox-ylamines and hydroxamates have become paramount, since these are 100- or greater-fold more reactive under mild conditions than the common base, hydroxide Structures of commonly studied oximes including pyridinium aldoximes are given in Scheme 4. The pyridinium moiety confers advantages of solubility as well as in lowering the oxime pTsTa. thus effecting higher reactivity under milder conditions of pH. 

Sidell, F.R., Groff, W.A. (1971). Intramuscular and intravenous administration of small doses of 2-pyridinium aldoxime methochloride to man. J. Pharm. Sci. 60 1224-8. 

Csermely, T., Petroianu, G., Kuca, K., Furesz, J., Darvas, F., Gulyas, Z., Laufer, R., Kalasz, H. (2007). TLC of quaternary pyridinium aldoximes, antidotes of organophosphoras esterase inhibitors JPC 20 39-42. 

Petroianu, G.A., Kalasz, H. (2007). Comparison of the ability of pyridinium aldoximes to reactivate human RBC cholinesterases inhibited by ethyl- and methyl-paraoxon. Curr. Org. Chem. 11 1624-34. 

The thermal polymer was inhibited by diisopropyl iluorophosphate (DFP Table V). The extent of inhibition was dependent upon the length of preincubation of polymer with DFP (20 mg of polymer per micromole of DFP) and was, e.g., 80% after 6 hoiurs of preincubation. The inhibition by DFP could be 80% reversed by 0.1 il/ 1,3-bis(iV-pyridinium aldoxime)propane. The authors conclude that the inhibition, reactivation, and Michaelis-Menten data obtained are indicative of enzyme-like properties. 

Calculated Heats of Formation (AHf) and Ionization Potentials of Some Tertiary and Quaternary Pyridinium Aldoximes... 

Besides specific proton catalysis, general acid catalysis by oximes may contribute to the advanced degradation of concentrated pyridinium aldoxime solutions. In fact, addition of 2-PAM to HI 6 accelerated not only the cleavage of the aminal-acetal bridge of the latter (Eyer et al, 1988), but also isonicotinamide deamination (Korte and Shih, 1993). Due to this molecular canibalism , concentrated solutions of HI 6 and HLd 7 seem to be condemned to increased degradation and cannot be stockpiled in dissolved form. 

Table 3. Shelf-lives of pyridinium aldoximes at 25°C (10% decomposition)...

In a patient who had received obidoxime for 12 days and died 15 days after parathion poisoning, obidoxime concentrations in cartilage were 100-fold higher than in plasma (unpublished). These data indicate that the chondroitin sulfate-rich tissues may represent the deep compartment from which pyridinium aldoximes are slowly released. 

When l-[14C]methyl-pyridinium aldoxime iodide or radioactive pralidoxime [14C]-labelled in the oxime group was parenterally administrated to rats, 90% of the radioactivity was recovered in urine and 6% in the faeces, irrespective of the position of the label. About 90% of the urinary radioactivity was associated with intact pralidoxime. In addition, some 5% of the dose was excreted as l-methyl-2-pyridone, indicating some cyanogenesis (Enandcret al., 1962). In humans, the l-methyl-2-cyanopyridinium ion was detected in urine of male volunteers without significantly increased urinary thiocyanate. Since 90% of pralidoxime chloride, 5 mg kg 1 IV, was recovered from urine, cyanide formation is probably of no toxicological concern (Garrigue etal., 1990). 

Korte WD and Shih ML (1993). Degradation of three related bis(pyridinium)aldoximes in aqueous solutions at high concentrations Examples of unexpectedly rapid amide group hydrolysis. J Pharm Sci, 82, 782-786. 

Ramachandran, B.V., The influence of DFP, atropine and pyridinium aldoximes on the rate of clearance of diisopropyl phosphate (Df P) from the mouse circulatory system, Biochem. Pharmacol., 16, 2061, 1967. 

H12. Hobbiger, F., and Vojvodic, Z., The reactivation by pyridinium aldoximes of phosphorylated acetylcholinesterase in the central nervous system. Biochem. Pharmacol. 16, 455-462 (1967). 

Comparison of the ability of pyridinium aldoximes to reactivate human red blood cell cholinesterases inhibited by ethyl- and methyl-paraoxon 07COC1624. 

Pyridinium aldoximes N-llnked to C-1 or C-6 of hexoses or to a 3-carbon aglycone unit of a glycoside have been synthesized as potential antidotes of organophosphate poisoning thus the N -... 

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