Diisopropyl fluorophosphate
 | |
 | |
| Clinical data | |
|---|---|
| ATC code | |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| ECHA InfoCard | 100.000.225 |
| Chemical and physical data | |
| Formula | C6H14FO3P |
| Molar mass | 184.146 g/mol |
| 3D model (JSmol) | |
| 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
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.
_complex.jpg)
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.[1][2][3] It has also been used to develop a rodent model of Gulf War Syndrome.[4]
Diisopropyl fluorophosphate is a very potent neurotoxin. Its LD50 in rats is 6 mg/kg (oral). It combines with the amino acid serine at the active site of the enzyme acetylcholinesterase,[5] 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
- Sarin (isopropyl methylphosphonofluridate), a related phosphofluridate
References
- ↑ Deshpande, Laxmikant S.; Carter, Dawn S.; Blair, Robert E.; DeLorenzo, Robert J. (2010-08-01). "Development of a prolonged calcium plateau in hippocampal neurons in rats surviving status epilepticus induced by the organophosphate diisopropylfluorophosphate". Toxicological Sciences: An Official Journal of the Society of Toxicology. 116 (2): 623–631. ISSN 1096-0929. PMC 2905411
. PMID 20498005. doi:10.1093/toxsci/kfq157. - ↑ Pessah, Isaac N.; Rogawski, Michael A.; Tancredi, Daniel J.; Wulff, Heike; Zolkowska, Dorota; Bruun, Donald A.; Hammock, Bruce D.; Lein, Pamela J. (2016-08-01). "Models to identify treatments for the acute and persistent effects of seizure-inducing chemical threat agents". Annals of the New York Academy of Sciences. 1378 (1): 124–136. ISSN 1749-6632. PMC 5063690 . PMID 27467073. doi:10.1111/nyas.13137.
- ↑ Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio; Davis, John M.; Auta, James (2011-03-01). "Acute imidazenil treatment after the onset of DFP-induced seizure is more effective and longer lasting than midazolam at preventing seizure activity and brain neuropathology". Toxicological Sciences: An Official Journal of the Society of Toxicology. 120 (1): 136–145. ISSN 1096-0929. PMID 21097996. doi:10.1093/toxsci/kfq356.
- ↑ Phillips, Kristin F.; Deshpande, Laxmikant S. (2016-01-01). "Repeated low-dose organophosphate DFP exposure leads to the development of depression and cognitive impairment in a rat model of Gulf War Illness". Neurotoxicology. 52: 127–133. ISSN 1872-9711. PMID 26619911. doi:10.1016/j.neuro.2015.11.014.
- ↑ 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. PMID 10353814. doi:10.1021/bi982678l.
- Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6.
- Meiers, P. (2006). "History of the fluorophosphates".