2,3-димеркапто-1-пропанол

Описание

Dimercaprol (INN) or British anti - Lewisite (abbreviated BAL), is a compound developed by British biochemists at Oxford University during World War II . It was developed secretly as an antidote for lewisite, the now - obsolete arsenic - based chemical warfare agent . Today, it is used medically in treatment of arsenic, mercury , gold, lead, antimony, and other toxic metal poisoning . In addition , it has in the past been used for the treatment of Wilson's disease, a genetic disorder in which the body tends to retain copper.

Химические свойства

colourless oily liquid with a typically offensive mercaptan smell

Использование

2,3-Dimercapto-1-propanol has been used in synthesizing novel (2-substituted phenyl-1,3-dithiolan-4-yl) methanol (PDTM) derivatives, which are potent tyrosinase inhibitors. It can also be considered for developing new drugs against AIDS due to its ability to inhibit HIV-1 tat activity.

Определение

ChEBI: A dithiol that is propane-1,2-dithiol in which one of the methyl hydrogens is replaced by a hydroxy group. a chelating agent originally developed during World War II as an experimental antidote against the arsenic-based poison gas Lewisite, it has been use clinically since 1949 for the treatment of poisoning by arsenic, mercury and gold. It can also be used for treatment of poisoning by antimony, bismuth and possibly thallium, and (with sodium calcium edetate) in cases of acute leaad poisoning. Administrati n is by (painful) intramuscular injection of a suspension of dimercaprol in peanut oil, typically every 4 hours for 2-10 days depending on the toxicity. In the past, dimercaprol was also used for the treatment of Wilson's disease, a severely debilitating g netic disorder in which the body tends to retain copper, with resultant liver and brain injury.

Биологические функции

Arsenic and some other heavy metals act by chemically reacting with adjacent thiol residues on metabolic enzymes, creating a chelate complex that inhibits the affected enzyme's activity. Dimercaprol competes with the thiol groups for binding the metal ion, which is then excreted in the urine .
Dimercaprol is itself toxic, with a narrow therapeutic range and a tendency to concentrate arsenic in some organs. Other drawbacks include the need to administer it by painful intramuscular injection. Serious side effects include nephrotoxicity and hypertension.
Dimercaprol has been found to form stable chelates in vivo with many other toxic metals including inorganic mercury, antimony, bismuth, cadmium, chromium, cobalt, gold, and nickel. However, it is not necessarily the treatment of choice for toxicity to these metals. Dimercaprol has been used as an adjunct in the treatment of the acute encephalopathy of lead toxicity. It is a potentially toxic drug, and its use may be accompanied by multiple side effects. Although treatment with dimercaprol will increase the excretion of cadmium, there is a concomitant increase in renal cadmium concentration, so that its use in case of cadmium toxicity is to be avoided. It does, however, remove inorganic mercury from the kidneys; but is not useful in the treatment of alkylmercury or phenyl mercury toxicity. Dimercaprol also enhances the toxicity of selenium and tellurium, so it is not to be used to remove these elements from the body.

Общее описание

Clear colorless viscous liquid with a pungent offensive odor of mercaptans. Used as a medicine and an antidote to the chemical warfare agent LEWISITE.

Реакции воздуха и воды

Moderately soluble in water with decomposition [Hawley].

Профиль реактивности

2,3-Dimercapto-1-propanol forms highly stable chelates with a variety of metal ions. Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid.

Пожароопасность

2,3-Dimercapto-1-propanol is probably combustible.

Фармацевтические приложения

Dimercaprol (BAL) is a chelating agent used as an antidote for arsenic, antimony, bismuth, gold and mercury poisoning. It has the chemical name 2,3-dimercapto-1-propanol and is a clear, colourless or slightly yellow liquid.

Клиническое использование

2,3-Dimercapto-1-propanol, BAL, or dithioglycerol is afoul-smelling, colorless liquid. It is soluble in water (1:20)and alcohol. It was developed by the British during WorldWar II as an antidote for “Lewisite,” hence the name Britishanti-Lewisite or BAL. Dimercaprol is effective topicallyand systematically as an antidote for poisoning caused byarsenic, antimony, mercury, gold, and lead. It can, therefore,also be used to treat arsenic and antimony toxicity associatedwith overdose or accidental ingestion of organoarsenicalsor organoantimonials.The antidotal properties of BAL are associated with theproperty of heavy metals to react with sulfhydryl (SH)groups in proteins (e.g., the enzyme pyruvate oxidase) andinterfere with their normal function. 1,2-Dithiol compoundssuch as BAL compete effectively with such proteins for themetal by reversibly forming metal ring compounds.These are relatively nontoxic, metabolically conjugated(as glucuronides), and rapidly excreted.BAL may be applied topically as an ointment or injectedintramuscularly as a 5% or 10% solution in peanut oil.

Профиль безопасности

Poison via ingestion, intramuscular, parenteral, intraperitoneal, and intravenous routes. Experimental teratogenic effects. Human systemic effects by intramuscular route: hemorrhage and dermatitis. Human blood and systemic skin effects by intramuscular route. It causes redness and swelling when applied locally to the skin, but does not produce blisters or ulcers. Intensely irritating to eyes and mucous membranes. Systemic symptoms are caused by injection. When heated to decomposition, it emits toxic fumes of SO,. Used as an antidote to arsenic, gold, and mercury poisoning.

Экологическая судьба

BAL is believed to compete with tissue sulfhydryl groups and interferes with cellular respiration. It also competes with metallic cofactors of metabolic enzyme systems and increases capillary permeability. Metabolic degradation and excretion are essentially complete within 4 h. BAL not excreted as dimercaprol– metal complex is quickly metabolized by the liver and excreted as an inactive product in the urine. Because it is a lipophilic drug, it penetrates rapidly the intracellular spaces. The highest concentrations are found in the liver, kidneys, brain, and small intestine. Due to its lipophilic characteristic, the complexes formed with mercury and other metals may be redistributed into sensitive cells in the brain following dimercaprol treatment.

Методы очистки

Precipitate BAL as the Hg mercaptide [see Bj.berg Chem Ber 75 13 1942], regenerate with H2S, and distil it under a vacuum [Rosenblatt & Jean Anal Chem 951 1955]. It is an antidote for heavy metal (As, Hg, Au etc) poisoning. [Beilstein 1 IV 2770.]