diisopropylfluorophosphate

ジイソプロピルフルオロリン酸

関

DFP、fluostigmine、isoflurophate

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/21 03:21:28」(JST)

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Diisopropyl fluorophosphate

Systematic (IUPAC) name
bis(propan-2-yl) fluorophosphonate
Identifiers
CAS Number	55-91-4 Y
ATC code	S01EB07 (WHO)
PubChem	CID 5936
DrugBank	DB00677 Y
ChemSpider	5723 Y
UNII	12UHW9R67N Y
KEGG	D00043 Y
ChEBI	CHEBI:17941 Y
ChEMBL	CHEMBL1025 Y
Chemical data
Formula	C6H14FO3P
Molar 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 Y Key:MUCZHBLJLSDCSD-UHFFFAOYSA-N Y
Physical data
Melting point	−82 °C (−116 °F)
Boiling point	183 °C (361 °F) 1013 mbar
(verify)

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

See also

• MAFP (methoxy arachidonoylfluorophosphonate), a mechanistically related inhibitor

References

Using Wikipedia for research

• 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

• Self-Decontaminating Fibrous Materials Reactive toward Chemical Threats.

• Bromberg L1, Su X1, Martis V2, Zhang Y1, Hatton TA1.
• ACS applied materials & interfaces.ACS Appl Mater Interfaces.2016 Jul 13;8(27):17555-64. doi: 10.1021/acsami.6b05241. Epub 2016 Jun 27.
• Polymers that possess highly nucleophilic pyrrolidinopyridine (Pyr) and primary amino (vinylamine, VAm) groups were prepared by free-radical copolymerization of N,N-diallylpyridin-4-amine (DAAP) and N-vinylformamide (NVF) followed by acidic hydrolysis of NVF into VAm. The resulting poly(DAAP-co-VAm-
• PMID 27309383

• Total esterase activity in human saliva: Validation of an automated assay, characterization and behaviour after physical stress.

• Tecles F1,2, Tvarijonaviciute A1,2,3, De Torre C4, Carrillo JM2,5, Rubio M2,5, García M2, Cugat R2, Cerón JJ1,2.
• Scandinavian journal of clinical and laboratory investigation.Scand J Clin Lab Invest.2016 Jul;76(4):324-30. doi: 10.3109/00365513.2016.1163417. Epub 2016 Apr 4.
• Although saliva has esterase activity, this activity has not been characterized or studied in individuals subjected to physical stress. The aim of this report was to develop and validate an automated spectrophotometric assay for total esterase activity measurement in human saliva, as well as to stud
• PMID 27045801

• Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons.

• Gao J1, Naughton SX1, Wulff H1, Singh V1, Beck WD1, Magrane J1, Thomas B1, Kaidery NA1, Hernandez CM1, Terry AV Jr2.
• The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2016 Mar;356(3):645-55. doi: 10.1124/jpet.115.230839. Epub 2015 Dec 30.
• The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this
• PMID 26718240

Japanese Journal

• Analytical approaches to investigate protein-pesticide adducts

• CARTER Wayne G.,TARHONI Mabruka H.,RAY David E.
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 878(17), 1312-1319, 2010-05-15
• NAID 10028036009

• 携帯型7検知セル・アスピレーション方式イオンモビリティスペクトロメーター装置の化学剤検知性能評価

• 岸 慎太郎,關岡 亮二,袖山 真学 [他],志賀 正恩,瀬戸 康雄
• 分析化学 = Japan analyst 59(1), 65-76, 2010-01-05
• … As for interference, the vapors of nerve gas simulants, dimethylmethylphosphonate, trimethylphosphate, triethylphosphate, diisopropylfluorophosphate, blister agent simulants, 2-chloroethylethylsulfide, 1,4-thioxane, 2-mercaptoethanol, and 20 organic solvents within 38 solvents examined were recognized false-positively. …
• NAID 10025980985

• ROLES OF μ-OPIOID RECEPTORS IN DEVELOPMENT OF TOLERANCE TO DIISOPROPYLFLUOROPHOSPHATE (DFP)

• , , [他], ,
• Journal of toxicological sciences 30(1), 43-59, 2005-02-25
• … In the present study, the potential involvement of μ-opioid receptors in mediating the changes of toxic signs and muscarinic receptor binding after administration of irreversible anti-acetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. …
• NAID 130000065384

Related Links

• Diisopropyl fluorophosphate - Wikipedia, the free encyclopedia

InChI=1S/C6H14FO3P/c1-5(2)9-11(7,8)10-6(3)4/h5-6H,1-4H3 Yes Y Key: MUCZHBLJLSDCSD-UHFFFAOYSA-N Yes Y. Physical data. Melt. point, -82 °C (- 116 °F). Boiling point, 183 °C (361 °F) 1013 mbar. N (what is this?) (verify) ...

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関

DFP、diisopropylfluorophosphate、isoflurophate