PrepTutorEJDIC

Department of the Interior 内務省 / drill instructor 教練係下士官 / discomfort index

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/20 18:43:30」(JST)

wiki en

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

Characterization of a novel protease from Aeribacillus pallidus strain VP3 with potential biotechnological interest.

Mechri S1, Ben Elhoul Berrouina M1, Omrane Benmrad M1, Zaraî Jaouadi N1, Rekik H1, Moujehed E1, Chebbi A2, Sayadi S2, Chamkha M2, Bejar S1, Jaouadi B3.
International journal of biological macromolecules.Int J Biol Macromol.2017 Jan;94(Pt A):221-232. doi: 10.1016/j.ijbiomac.2016.09.112. Epub 2016 Oct 5.
The present study investigates the purification and physico-chemical characterization of an extracellular protease from the Aeribacillus pallidus strain VP3 previously isolated from a geothermal oil-field (Sfax, Tunisia). The maximum protease activity recorded after 22h of incubation at 45°C was 30
PMID 27720758

Profiling and functional classification of esterases in olive (Olea europaea) pollen during germination.

Rejón JD1, Zienkiewicz A, Rodríguez-García MI, Castro AJ.
Annals of botany.Ann Bot.2012 Oct;110(5):1035-45. doi: 10.1093/aob/mcs174. Epub 2012 Aug 24.
BACKGROUND AND AIMS: A pollen grain contains a number of esterases, many of which are released upon contact with the stigma surface. However, the identity and function of most of these esterases remain unknown. In this work, esterases from olive pollen during its germination were identifided and fun
PMID 22922586

Interactions of phosphororganic agents with water and components of polyelectrolyte membranes.

Lee MT1, Vishnyakov A, Gor GY, Neimark AV.
The journal of physical chemistry. B.J Phys Chem B.2011 Nov 24;115(46):13617-23. doi: 10.1021/jp207469h. Epub 2011 Nov 3.
Interactions of nerve G-agents (sarin and soman) and their simulants DMMP (dimethyl methylphosphonate) and DIFP (diisopropyl fluorophosphate) with water and components of polyelectrolyte membranes are studied using ab initio calculations in conjunction with thermodynamic modeling using the conductor
PMID 21988501

Japanese Journal

25.当院の婦人科細胞診の特徴 : 薬剤性高プロラクチン血症(DIFP)と婦人科細胞診(子宮頸部1)(第42回日本臨床細胞学会秋期大会)

日本臨床細胞学会雑誌 42(Suppl.2), 354, 2003-09-22
NAID 110001222604

チェダーチーズ中の最適pH6.0のプロティナーゼ

西日本畜産学会報 41, 9-13, 1998
NAID 130004185209

気管支喘息患者の気管支肺胞洗浄液上清(BALF)中のカリクレイン様活性物質の同定とその由来に関する研究

岡山医学会雑誌 106(9-10), 1013-1024, 1994-10
NAID 120005817091

Related Pictures

★リンクテーブル★

「DI」

Diisopropyl fluorophosphate
Systematic (IUPAC) name
	bis(propan-2-yl) fluorophosphonate
Identifiers
CAS 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
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 ; Key:MUCZHBLJLSDCSD-UHFFFAOYSA-N ;
Physical data
Melting point	−82 °C (−116 °F)
Boiling point	183 °C (361 °F) 1013 mbar
(verify)