Clear, colourless, heavy, nonflammable liquid organic compound with a pleasant etherlike odour, chemical formula CHCl3. It was the first substance successfully used as a surgical anesthetic (1847); being somewhat toxic, it has been increasingly displaced by other substances for this purpose. It has some industrial uses, primarily as a solvent.
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In 1847, the Edinburgh obstetrician James Young Simpson first used chloroform for general anesthesia during childbirth. The use of chloroform during surgery expanded rapidly thereafter in Europe. In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century; however, it was quickly abandoned in favor of ether upon discovery of its toxicity, especially its tendency to cause fatal cardiac arrhythmia analogous to what is now termed "sudden sniffer's death". Ether is still the preferred anesthetic in some developing nations due to its high therapeutic index (~1.5-2.2) and low price. Trichloroethylene, a halogenated aliphatic hydrocarbon related to chloroform, was proposed as a safer alternative, though it too was later found to be carcinogenic.
Chloroform undergoes further chlorination to give CCl4:
The output of this process is a mixture of the four chloromethanes: chloromethane, dichloromethane, chloroform (trichloromethane), and carbon tetrachloride, which are then separated by distillation.
Chloroform was first produced industrially by the reaction of acetone (or ethanol) with sodium hypochlorite or calcium hypochlorite, known as the haloform reaction. The chloroform can be removed from the attendant acetate salts (or formate salts if ethanol is the starting material) by distillation. This reaction is still used for the production of bromoform and iodoform. The haloform process is obsolete for the production of ordinary chloroform. It is, however, used to produce deuterated material industrially. Deuterochloroform may be prepared by the reaction of sodium deuteroxide with chloral hydrate, or from ordinary chloroform.
The precise mechanism by which chloroform produces anesthesia is not certain. This is due, in part, to the fact that the mechanism of anesthesia itself is uncertain. There are two main theories of how drugs produce anesthesia. The Meyer-Overton theory states that anesthetics dissolve in cellular membranes, causing structural distortion of the membranes. The distortion may reduce the conduction of a nerve impulse along a nerve cell. This theory is based on the observation that the potency of most anesthetic drugs is correlated with their solubility in oil. As an alternative to the Meyer-Overton theory, it has been proposed that anesthetics interact with specific proteins. Examples of proteins that may be altered by binding of an anesthetic are neurotransmitter receptors and ion channels. Anesthetics may change the conformation (structure) of the protein. Other theories include actions at the interface between proteins and lipids.
One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channels in nerve cells. A paper by Patel et al. published in Nature Neuroscience (May 1999, Volume 2, Number 5, pp. 422-426) shows that chloroform activates potassium channels. This can lead to hyperpolarization of membranes. Hyperpolarization of a nerve cell membrane makes it less excitable. When this occurs presynaptically, it will decrease the release of neurotransmitters. When this effect occurs postsynaptically, it reduces the response to a neurotransimitter.
In general, most anesthetics enhance inhibitory neurotransmission in the brain. Many of them do this by increasing the actions of the primary inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Chloroform may also act by increasing GABA neurotransmission.
Animal studies have shown that miscarriages occur in rats and mice that have breathed air containing 30 to 300 ppm of chloroform during pregnancy and also in rats that have ingested chloroform during pregnancy. Offspring of rats and mice that breathed chloroform during pregnancy have a higher incidence of birth defects, and abnormal sperm have been found in male mice that have breathed air containing 400 ppm chloroform for a few days. The effect of chloroform on reproduction in humans is unknown.
The National Toxicology Program's eleventh report on carcinogens implicates it as reasonably anticipated to be a human carcinogen, a designation equivalent to International Agency for Research on Cancer class 2A. It has been most readily associated with hepatocellular carcinoma. Caution is mandated during its handling in order to minimize unnecessary exposure; safer alternatives, such as dichloromethane, have resulted in a substantial reduction of its use as a solvent.
During prolonged storage hazardous amounts of phosgene can accumulate in the presence of oxygen and ultraviolet light. To prevent accidents, commercial chloroform is stabilized with ethanol or amylene, but samples that have been recovered or dried no longer contain any stabilizer and caution must be taken. Suspicious bottles should be tested for phosgene. Filter-paper strips, wetted with 5% diphenylamine, 5% dimethylaminobenzaldehyde, and then dried, turn yellow in phosgene vapor.
Commonly used in DNA extractions and generally in conjunction with phenol to form a biolayer with extraction buffer (tris etc). DNA will form in the supernatant while protein and non soluble cell materials will precipitate between the buffer chloroform layers.