Quantum Chemical and Physicochemical Studies of Oximes (Prophylactics against and Reactivators of Phosphorylated AChE).

Abstract

The ultimate goal of our interdisciplinary research under this Army contract is to delineate the stereoelectronic and physicochemical requisites for oximes to be effective reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus compounds. This is being done by carrying out theoretical high quality three-dimensional ab-initio quantum chemical calculations on the oximes and from these wave functions generating three-dimensional electrostatic molecular potential contour (EMPC) maps around these oximes as well as experimental determinations of their lipophilicities. In addition to our theoretical work, we have been carrying out experimental determinations of the lipophilicities (their tendency to partition from aqueous to lipid phases) of these oxime reactivators. We have carried out these lipophilicity determinations, first with our microelectrometric technique. It turns out that neither these quaternary oximes nor their deprotonated species are very lipophilic. However, since there have been reports that some oxime reactivators are effective at low concentrations, we have set up and are also using a more sensitive UV spectrophotometric procedure to establish quantitatively and directly just how much of these compounds is partitioning into the lipid phase.

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Document Details

Document Type
Technical Report
Publication Date
Oct 25, 1984
Accession Number
ADA185827

Entities

People

  • Joyce J. Kaufman
  • Walter S. Koski

Organizations

  • Johns Hopkins University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Blood-Brain Barrier
  • Chemical Reactions
  • Chemical Synthesis
  • Chemical Warfare Agents
  • Chemistry
  • Crystal Structure
  • Dihedral Angle
  • Enzyme Inhibitors
  • Ionization
  • Materials
  • Molecular Structure
  • Organic Chemistry
  • Organophosphorus Compounds
  • Poisoning
  • Three Dimensional
  • Wave Functions

Readers

  • Neurotoxicology
  • Quantum Chemistry
  • Systems Analysis and Design

Technology Areas

  • Quantum Computing