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

organophosphorus Organophosphorus compounds are organic compounds containing phosphorus. They are used primarily in pest control as an alternative to chlorinated hydrocarbons that persist in the environment. Some organophosphorus compounds are highly effective in ...

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 Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...

as a

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

agent in treatment of chronic

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

, 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 An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...

properties and ability to induce delayed peripheral neuropathy.

Uses as toxin

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 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-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 Gulf War syndrome or Gulf War illness is a chronic and multi-symptomatic disorder affecting military veterans of both sides of the 1990–1991 Persian Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue ...

. 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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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 impulse An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, c ...

s from one

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

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 Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

may result since the

respiratory muscles The muscles of respiration are the muscles that contribute to inhalation and exhalation, by aiding in the expansion and contraction of the thoracic cavity. The diaphragm and, to a lesser extent, the intercostal muscles drive respiration during q ...

are affected. DFP also inhibits some

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

s. 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 Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the simple ...

with

phosphorus trichloride Phosphorus trichloride is an inorganic compound with the chemical formula PCl3. A colorless liquid when pure, it is an important industrial chemical, being used for the manufacture of phosphites and other organophosphorus compounds. It is toxic a ...

, forming diisopropylphosphite, which is chlorinated and further reacted with

sodium fluoride Sodium fluoride (NaF) is an inorganic compound with the formula . It is used in trace amounts in the fluoridation of drinking water, in toothpaste, in metallurgy, and as a flux. It is a colorless or white solid that is readily soluble in water. I ...

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 Paraoxonases are a family of mammalian enzymes with aryldialkylphosphatase activity. There are three paraoxonase isozymes, which were originally discovered for their involvement in the hydrolysis of organophosphates. Research has indicated the ...

, 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