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Compounds containing an oxime functional group, such as 2-PAM and obidoxime, are used in the treatment of poisoning with organophosphorus compounds. These oximes reactivate the enzyme acetylcholinesterase, which has been inhibited by the OPC.

However, some organophosphorus compounds are resistant to re-activation by oximes such as 2-PAM and obidoxime for reasons not related to denaturation of the enzyme (aging), but are responsive to some other oximes. For instance, methylfluorophosphonylcholine and related compounds such as GV are more susceptible to treatment by HI-6 than to obidoxime. Why?

Both of these compounds have fluorine act as a leaving group and have an amino-chain that would occupy the anionic site of the enzyme, so I presume that their resistance to reactivation by older oximes has to do with steric effects, though I have not been able to find research confirming or denying this. Nevertheless, why are some oxime compounds, especially the larger ones such as HI-6 and Hlo-7, better reactivators of AChE than others, especially if some OPCs' resistance to reactivation actually is due to steric effects?

References

  1. Kassa, J.; Bajgar, J. Therapeutic Efficacy of Obidoxime or HI-6 with Atropine against Intoxication with Some Nerve Agents in Mice. Acta Medica (Hradec Kralove) 1996, 39 (1), 27–30. PMID: 9106387.
  2. Worek, F.; Thiermann, H.; Szinicz, L. Reactivation and Aging Kinetics of Human Acetylcholinesterase Inhibited by Organophosphonylcholines. Arch Toxicol 2004, 78 (4), 212–217. DOI: 10.1007/s00204-003-0533-0.
  3. Fredriksson, T.; Tibbling, G. Reversal of Effects on the Rat Nerve-Diaphragm Preparation Produced by Methylfluorophosphorylcholines. Biochemical Pharmacology 1959, 2 (1), 63–64. DOI: 10.1016/0006-2952(59)90058-9.
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