Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C₆H₁₄FO₃P. It is used in medicine and as an organophosphorus

insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...

. It is stable, but undergoes hydrolysis when subjected to moisture.

Uses in medicine

Diisopropyl fluorophosphate is a parasympathomimetic drug irreversible anti-cholinesterase and has been used in ophthalmology as a

miotic Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

agent in treatment of chronic glaucoma, as a miotic in veterinary medicine, and as an experimental agent in neuroscience because of its

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...

inhibitory properties and ability to induce delayed peripheral neuropathy.

Uses as toxin

The marked toxicity of esters of

monofluorophosphoric acid Fluorophosphoric acid is the inorganic compound with the formula H2PO3F. It is a colorless viscous liquid that solidified to a glass upon cooling. Preparation Fluorophosphoric acid is produced commercially by treating phosphorus pentoxide wit ...

was discovered in 1932, when

Willy Lange Willy or Willie is a masculine, male given name, often a diminutive form of William (given name), William or Wilhelm (name), Wilhelm, and occasionally a nickname. It may refer to: People Given name or nickname * Willie Aames (born 1960), American ...

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 Bernard ('' Bernhard'') is a French and West Germanic masculine given name. It is also a surname. The name is attested from at least the 9th century. West Germanic ''Bernhard'' is composed from the two elements ''bern'' "bear" and ''hard'' "bra ...

. On his search for compounds to be used as

chemical warfare Chemical warfare (CW) involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from nuclear warfare, biological warfare and radiological warfare, which together make up CBRN, the military acronym ...

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 Mustard gas or sulfur mustard is a chemical compound belonging to a family of cytotoxic and blister agents known as mustard agents. The name ''mustard gas'' is technically incorrect: the substance, when dispersed, is often not actually a gas, b ...

, forming a more effective mixture with significantly lower melting point, resulting in an agent suitable for use in cold weather. In military research, due to its physical and chemical similarities and comparatively low toxicity, it is used as a simulant of

G-agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that ...

s ( 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 Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

. Its in rats is 6 mg/kg (oral). It combines with the amino acid

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

at the active site of the enzyme

, an enzyme that deactivates the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

. Neurotransmitters are needed to continue the passage of nerve impulses from one neuron to another across the

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

. 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 Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

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) Is 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

Isoflurophate, the diisopropyl ester of fluorophosphoric acid, is made by reacting isopropyl alcohol with phosphorus trichloride, forming diisopropylphosphite, which is chlorinated and further reacted with sodium fluoride to replace the chlorine atom with fluorine, thus giving diisopropyl fluorophosphate. : DIFP synthesis

Biochemistry

DIPF is a diagnostic test for the presence of the active site Ser in serine proteases. The toxin, along with other neurotoxins is inactivated by the enzyme paraoxonase, which is present in widely varying levels in humans.

Society and culture

It is marketed under many brand names including Difluorophate, Diflupyl, Diflurphate, Dyflos, Dyphlos, Fluropryl, Fluostigmine, Neoglaucit.

Uses in medicine

Uses as toxin

Production

Biochemistry

Society and culture

See also