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Diisopropyl fluorophosphate (DFP, DIFP, diisopropyl phosphorofluoridate) is an oily, colorless liquid with the chemical formula C₆H₁₄FO₃P. It is used in medicine^{[citation needed]} and as an organophosphorus insecticide^{[citation needed]}. It is stable, but undergoes hydrolysis when subjected to moisture, producing hydrofluoric acid. It is known also under names Difluorophate, Diflupyl, Diflurphate, Dyflos, Dyphlos, Fluropryl, Fluostigmine, isofluorophate, isofluorphate, Neoglaucit, PF-3, PF3, T-1703, TL 466, and others.

Uses in medicine

Diisopropyl fluorophosphate is a parasympathomimetic drug irreversible anti-cholinesterase and has been used in ophthalmology as a miotic agent in treatment of chronic glaucoma, as a miotic in veterinary medicine, and as an experimental agent in neuroscience because of its acetylcholinesterase inhibitory properties and ability to induce delayed peripheral neuropathy^{[citation needed]}. It is known as fluostigmine and Dyflos in such uses.

Uses as toxin

Reaction of the DIFP with a serine protease

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.

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 a very potent neurotoxin. Its LD₅₀ in rats is 1.3 mg/kg. It combines with the amino acid serine at the active site of the enzyme acetylcholinesterase,^[1] 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.

Chemistry

Isoflurophate, the di-iso-propyl ester of fluorophosphoric acid, is made by reacting isopropyl alcohol with phosphorus trichloride, forming di-iso-propylphosphite, which is chlorinated and further reacted with sodium fluoride to replace the chlorine atom with fluorine, thus giving isofluorophate.

E.E. Hardy, G.M. Kosoloapoff, U.S. Patent 2,409,039 (1946).

References

^ Millard, C.B.; Kryger, G.; Ordentlich, A.; Greenblatt, H.M.; Harel, M.; Raves, M.L.; Segall, Y.; Barak, D.; Shafferman, A.; Silman, I.; Sussman, J.L (1999). "Crystal structures of phosphylated acetylcholinesterase: Nerve agent reaction products at atomic resolution". Biochemistry 38 (22): 7032–9. doi:10.1021/bi982678l. PMID 10353814.

Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6.
Meiers, P. (2006). "History of the fluorophosphates".

External links

The MEROPS online database for peptidases and their inhibitors: DFP

English Journal

Interaction between substrates suggests a relationship between organophosphorus-sensitive phenylvalerate- and acetylcholine-hydrolyzing activities in chicken brain.

Benabent M1, Vilanova E1, Mangas I1, Sogorb MÁ1, Estévez J2.
Toxicology letters.Toxicol Lett.2014 Oct 15;230(2):132-8. doi: 10.1016/j.toxlet.2014.02.012. Epub 2014 Feb 24.
Organophosphorus compounds (OPs) induce neurotoxic disorders through interactions with well-known target esterases, such as acetylcholinesterase and neuropathy target esterase (NTE). However, OPs interact with other esterases of unknown biological function. In soluble chicken brain fractions, three
PMID 24576786

Theoretical and experimental investigation of photophysical properties of Zn(DFP SAMQ)2.

Valiev RR1, Telminov EN2, Solodova TA2, Ponyavina EN2, Gadirov RM2, Kaplunov MG3, Kopylova TN2.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Jul 15;128:137-40. doi: 10.1016/j.saa.2014.02.157. Epub 2014 Mar 12.
Theoretical calculations and experimental measurements were carried out for the investigation of spectroscopic and photophysical properties of Zn(DFP SAMQ)2 complex. The rate constant of intersystem crossing and the radiative rate constant were calculated using ab initio method. The rate constant of
PMID 24662762

Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats.

Terry AV Jr1, Callahan PM2, Beck WD3, Vandenhuerk L4, Sinha S4, Bouchard K4, Schade R4, Waller JL5.
Neurotoxicology and teratology.Neurotoxicol Teratol.2014 Jul-Aug;44:18-29. doi: 10.1016/j.ntt.2014.04.069. Epub 2014 May 10.
Organophosphate (OP)-based chemicals are used worldwide for many purposes and they have likely saved millions of people from starvation and disease. However, due to their toxicity they can also pose a significant environmental risk. While considerable research has focused on the acute symptoms and l
PMID 24819591

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★リンクテーブル★

リンク元	「イソフルロフェート」「diisopropylfluorophosphate」「fluostigmine」「DFP」

「イソフルロフェート」

Diisopropyl fluorophosphate
Systematic (IUPAC) name
	bis(propan-2-yl) fluorophosphonate
Clinical data
Identifiers
CAS Registry Number	55-91-4
ATC code	S01EB07
PubChem	CID 5936
DrugBank	DB00677
ChemSpider	5723
UNII	12UHW9R67N
KEGG	D00043
ChEBI	CHEBI:17941
ChEMBL	CHEMBL1025
Chemical data
Formula	C6H14FO3P
Molecular mass	184.146 g/mol
	SMILES FP(=O)(OC(C)C)OC(C)C;
	InChI InChI=1S/C6H14FO3P/c1-5(2)9-11(7,8)10-6(3)4/h5-6H,1-4H3 ; Key:MUCZHBLJLSDCSD-UHFFFAOYSA-N ;
Physical data
Melting point	−82 °C (−116 °F)
Boiling point	183 °C (361 °F) 1013 mbar
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