Dm. Maxwell et al., OXIME-INDUCED REACTIVATION OF CARBOXYLESTERASE INHIBITED BY ORGANOPHOSPHORUS COMPOUNDS, Chemical research in toxicology, 7(3), 1994, pp. 428-433
A structure-activity analysis of the ability of oximes to reactivate r
at plasma carboxylesterase (CaE) that was inhibited by organophosphoru
s (OP) compounds revealed that uncharged oximes, such as 2,3-butanedio
ne monoxime (diacetylmonoxime) or monoisonitrosoacetone, were better r
eactivators than cationic oximes. Cationic oximes that are excellent r
eactivators of OP-inhibited acetylcholinesterase, such as pyridine-2-a
ldoxime or the bis-pyridine aldoximes, HI-6 and TMB-4, produced poor r
eactivation of OP-inhibited CaE. The best uncharged reactivator was 2,
3-butanedione monoxime, which produced complete reactivation at 0.3 mM
in 2 h of CaE that was inhibited by phosphinates, alkoxy-containing p
hosphates, and alkoxy-containing phosphonates. Complete reactivation o
f CaE could be achieved even after inhibition by phosphonates with hig
hly branched alkoxy groups, such as sarin and soman, that undergo rapi
d aging with acetylcholinesterase. CaE that was inhibited by phosphona
tes or phosphates that contained aryloxy groups were reactivated to a
lesser extent. The cause of this decreased reactivation appears to be
an oxime-induced aging reaction that competes with the reactivation re
action. This oxime-induced aging reaction is accelerated by electron-w
ithdrawing substituents on the aryloxy groups of phosphonates and by t
he presence of multiple aryloxy groups on phosphates. Thus, reactivati
on and aging of OP-inhibited CaE differ from the same processes for OP
-inhibited acetylcholinesterase in both their oxime specificity and in
hibitor specificity and, presumably, in their underlying mechanisms.