The marked toxicity of esters of
monofluorophosphoric acid was discovered in 1932, when
Willy Lange and his PhD student Gerda von Krueger prepared the methyl, ethyl, n-propyl, and n-butyl esters and incidentally experienced their toxic effects. Another homologue of this series of esters, diisopropyl fluorophosphate, was developed by British scientist
Bernard Charles Saunders. On his search for compounds to be used as
chemical warfare agents, Saunders was inspired by the report by Lange and Krueger and decided to prepare the new homologue which he labeled PF-3. It was much less effective as a chemical weapon than the G series agents. It was often mixed with
mustard gas, forming a more effective mixture with significantly lower melting point, resulting in an agent suitable for use in cold weather. Image:Crystal structure of Herpes Simplex Virus Protease-Inhibitor (DFP) complex.jpg|thumb|right|250px|alt=Protease-Inhibitor Complex.|Crystal structure of Herpes Simplex Virus Protease/Inhibitor (DFP) complex. The active site serine (yellow) has undergone phosphonylation resulting in irreversible inhibition. Rendered from PDB 1AT3. In military research, due to its physical and chemical similarities and comparatively low toxicity, it is used as a simulant of
G-agents (
GA,
GB,
GD, and
GF). Diisopropyl fluorophosphate is used in civilian laboratories to mimic lethal nerve gas exposure or organophosphate toxicities. It has also been used to develop a rodent model of
Gulf War Syndrome. Diisopropyl fluorophosphate is a very potent
neurotoxin. Its in rats is 6 mg/kg (oral). It combines with the
amino acid serine at the active site of the enzyme
acetylcholinesterase, an enzyme that deactivates the
neurotransmitter acetylcholine. Neurotransmitters are needed to continue the passage of
nerve impulses from one
neuron to another across the
synapse. Once the impulse has been transmitted, acetylcholinesterase functions to deactivate the acetylcholine almost immediately by breaking it down. If the enzyme is inhibited, acetylcholine accumulates and nerve impulses cannot be stopped, causing prolonged muscle contraction.
Paralysis occurs and
death may result since the
respiratory muscles are affected. DFP also inhibits some
proteases. It is a useful additive for protein or cell isolation procedure. Diisopropyl fluorophosphate (DFP) was a nerve gas developed by the German during the
Second World War. DFP irreversibly binds with the enzymes containing serine at the active site, e g. Serine proteases, acetylcholine esterase. ==Production==