Oxime-Induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds
Abstract
A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus (OP) compounds revealed that uncharged oximes, such as diacetylmonoxime or monoisonitrosoacetone, were better reactivators than cationic oximes. Cationic oximes that are excellent reactivators of OP-inhibited acetylcholinesteraser such as pyridinium-2-aldoxime or the bis-pyridinium oximes, HI-6 and TMB-4, produced poor reactivation of OP-inhibited CaE. The best uncharged reactivator was diacetylmonoxime which produced complete reactivation at 0.3 mM in 2 hr of CaE that was inhibited by organophosphinates, alkoxy-containing phosphates, and alkoxy-containing phosphonates. Complete reactivation of CaE could be achieved even after inhibition by phosphonates with highly branched alkoxy groups, such as sarin and soman, that undergo rapid aging with acetylcholinesterase. CaE that was inhibited by phosphonates or phosphates that contained aryloxy groups were reactivated to a lower extent. The cause of this decreased reactivation appears to be an oxime-induced aging reaction that competes with the reactivation reaction. This oxime-induced aging reaction is accelerated by electron- withdrawing substituents on the aryloxy groups of phosphonates and by the presence of multiple aryloxy groups on phosphates. Thus, reactivation and aging of OP-inhibited CaE differ from the same processes for OP-inhibited acetylcholinesterase in both their oxime specificity and inhibitor specificity and, presumably, in their underlying mechanisms.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008837
Entities
People
- Claire N. Lieske
- Donald M. Maxwell
- Karen M. Brecht
Organizations
- United States Army Medical Research Institute of Chemical Defense