User:DiverDave/Aliflurane
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| Names | |||
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| IUPAC name
1-chloro-1,2,2,3-tetrafluoro-3-methoxycyclopropane
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| Identifiers | |||
3D model (JSmol)
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PubChem CID
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| Properties | |||
| C4H3ClF4O | |||
| Molar mass | 178.512633 g/mol | ||
| Hazards | |||
| Occupational safety and health (OHS/OSH): | |||
Main hazards
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Highly flammable Asphyxiant | ||
| NFPA 704 (fire diamond) | |||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Aliflurane (also known as 1-chloro-1,2,2,3-tetrafluoro-3-methoxycyclopropane, 26-P, or compound 56689-41-9) is an experimental inhalational anaesthetic that has never been fully developed for clinical use. It was initially synthesized as an attempt to replace cyclopropane, which presented a hazard in its use due to its extreme reactivity in the presence of enriched oxygen mixtures. When cyclopropane is mixed with oxygen there is a significant risk of explosion.
Medical use
[edit]Physical properties
[edit]Cyclopropanes are a class of organic compounds sharing the common cyclopropane ring, in which one or more hydrogens may be substituted. These compounds are found in biomolecules; for instance, the pyrethrum insecticides (found in certain Chrysanthemum species) contain a cyclopropane ring. Although cyclopropanes are cycloalkanes, they are very reactive due to considerable strain energy and due to double bond character. The bonds between the carbon atoms are considerably weaker than in a typical carbon-carbon bond, yielding reactivity similar to or greater than alkenes. Baeyer strain theory explains why: the angle strain from the 60° angle between the carbon atoms (less than the normal angle of 109.5° for bonds between atoms with sp3 hybridised orbitals) reduces the compound's carbon-carbon bond energy, making it more reactive than other cycloalkanes such as cyclohexane and cyclopentane. The molecule also has torsional strain due to the eclipsed conformation of its hydrogen atoms. It is somewhat stabilized by some pi character in its carbon-carbon bonds, indicated by the Walsh orbital description whereas it is modeled as a three-center-bonded orbital combination of methylene carbenes [citation needed]. Bonding between the carbon centers in aliflurane is generally described by invoking bent bonds.[2]
Because of the strain in the carbon-carbon bonds of cyclopropane, the molecule has an enormous amount of potential energy. A highly reactive molecule, it spontaneously degrades to form linear (non-cyclic) hydrocarbons such as propene. This decomposition is potentially explosive, especially if cyclopropane is liquified or pressurized. Explosions of cyclopropane and oxygen are even more powerful, because the energy released by the formation of propene is compounded by the energy released via the oxidation of the carbon and hydrogen present.
Aliflurane is a halogenated cycloalkane compound with the molecular formula C4H3ClF4O, consisting of three carbon atoms linked to each other to form a ring. Two of these carbon atoms bear halogen atoms, while the third bears a methoxy group, which makes the molecule an ether as well as a cycloalkane.
Pharmacokinetics
[edit]Pharmacodynamics
[edit]In various laboratory animals aliflurane was an effective inhalation anesthetic, causing the loss of the righting reflex, spontaneous motor activity, response to painful stimuli and consciousness. In volunteers the only side effects observed with 0.1-0.6% aliflurane were lightheadedness and tingling of the distal portion of the extremities. Toxic concentrations caused respiratory arrest and cardiovascular depression. Chronic aliflurane administration (.ltoreq.3 times/week for 8 weeks) produced no hematologic, biochemical, histologic, or behavioral changes.[3]
The minimum alveolar concentration (MAC) of aliflurane was measured in ten dogs. A value of 1.84 volumes per cent was determined, which correlates well with predictions based on lipid solubility. Induction of anesthesia and recovery were rapid, as would be anticipated with an agent of relatively low solubility in blood (blood-gas partition coefficient = 1.7). Circulatory responses over a relatively narrow range of aliflurane concentrations (0.8 to 1.4 MAC) remained stable, but the development of tachypnea, irregular ventilatory patterns, and increased muscle tone were frequently encountered during aliflurane anesthesia.[4]
In healthy human volunteers aliflurane (<2%) inhalation produced excitment or a very light stage of surgical anesthesia. Aliflurane (4%) produced deeper anesthesia ranging to stage 3 plane 3. Respiratory effort decreased but was easily assisted. Blood gases were near normal and no cardiovascular or electrocardiographic alterations were observed. Anesthesia was discontinued after 50 to 80 minutes and volunteers recovered within 15-20 min, depending on the length and depth of anesthesia. Mild nausea was the only observable side effect.[5]
Aliflurane produces complete amnesia when breathed at a typical anesthetic concentration of 1-3%. This may be accompanied by a slight tachypnea, increase in motor tone and continuous eye movements. As with other general anesthetics, it may cause airway obstruction which may require the use of an airway adjunct such as an oral airway, nasal airway, laryngeal mask airway or tracheal intubation. There may be a modest decline in blood pressure, accompanied by a compensatory increase in heart rate. Peak excretion of metabolites occurs within 24 hours, during which time there may be a mild leukocytosis.[6]
Biodegradation and toxicity
[edit]Biodegradation of volatile anesthetics can lead to the production of toxic metabolites which can cause hepatic necrosis and renal failure.[7][8] In a study published in 1979, Holaday et al studied the biotransformation of aliflurane in ten healthy young male volunteers.[9] They found that approximately 1% of the absorbed dose appears to converted to measurable metabolites (some combination of fluoride ion and various organic fluorine compounds) and excreted in the urine. This compares favorably with methoxyflurane (41% of absorbed dose is excreted as urinary metabolites), halothane (12-25% of absorbed dose is excreted as urinary metabolites), fluroxene (10% of absorbed dose is excreted as urinary metabolites), and enflurane (2.4% of absorbed dose is excreted as urinary metabolites). The authors concluded that aliflurane is more resistant to biotransformation than those agents.[9]
History
[edit]At room temperature, liquified cyclopropane can self-detonate. To guard against this, the liquid is shipped in cylinders filled with tungsten wool, which prevents high-speed collisions between molecules and vastly improves stability. Pipes to carry cyclopropane must likewise be of small diameter, or else filled with unreactive metal or glass wool to prevent explosions. Even if these precautions are followed, cyclopropane is dangerous to manufacture and handle. This was the rationale for the development of aliflurane, a far more stable compound. Aliflurane was first synthesized in (year) by (chemist).[10]
Notes
[edit]References
[edit]- ^ Merck Index, 11th Edition, 2755.
- ^ Eric V. Anslyn and Dennis A. Dougherty. Modern Physical Organic Chemistry. 2006. pages 850-852
- ^ Borgstedt HH, Steen SN, Clifton JF, De Ciutiis VL (1976). [http://www.lookchem.com/cas-566/56689-41-9.html "Aliflurane: a new inhalation anesthetic agent"]. International Research Communications System Medical Science: Library Compendium. 4 (11): 504.
{{cite journal}}: Check|url=value (help)CS1 maint: multiple names: authors list (link) - ^ Munson ES, Schick LM, Chapin JC, Kushins LG, Navarro AA (1979). "Determination of the minimum alveolar concentration (MAC) of aliflurane in dogs" (PDF). Anesthesiology. 51 (6): 545–7. PMID 42331.
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{{cite journal}}: Check|url=value (help)CS1 maint: multiple names: authors list (link) - ^ Kaushik, S (1995). "New drugs in anaesthesia". In Kaushik, S (ed.). Anaesthesia:Concepts and Management (1st ed.). New Delhi: Jaypee Brothers Medical Publishers Ltd. pp. 117–128. ISBN 81-7179-406-8.
- ^ Cousins MJ, Mazze RI (1973). "Methoxyflurane nephrotoxicity: a study of dose response in man (abstract)". Journal of the American Medical Association. 225 (13): 1611–6. doi:10.1001/jama.1973.03220410023005. PMID 4740737.
- ^ Brown BR, Sipes IG (1977). "Biotransformation and hepatotoxicity of halothane". Biochemical Pharmacology. 26 (22): 2091–4. PMID 337973.
- ^ a b Holaday DA, Jardines MC, Greenwood WH (1979). "Uptake and biotransformation of aliflurane (1-chloro-2-methoxy-1,2,3,3-tetrafluorocyclopropane, compound 26-p) in man" (PDF). Anesthesiology. 51 (6): 548–50. PMID 42332.
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Further reading
[edit]- Halsey MJ (1981). "Investigations on isoflurane, sevoflurane and other experimental anaesthetics". British Journal of Anaesthesia. 53 (Suppl 1): 43S–47S. PMID 7016154.
External links
[edit][[Category:General anesthetics]] [[Category:Cycloalkanes]]