2.3- Dimercaptopropanol Anti-Lewisite

Dimercaptopropanol-1, British anti-Lewisite or dimercaprol Dithiocarbamate... 

A special derivatization reaction is required for lewisite 1, which is so reactive that it cannot be determined by GC/MS in low quantities (e.g. below 10 ng per injection). It has been known for a long time that lewisite 1 reacts with compounds having an a, P-dithiol structure, such as 2,3-dimercaptopropanol-l (British-Anti-Lewisite (BAL) also used for medical treatment). The derivatization reaction can be performed at an analytical level and several examples have been described (29). The reaction product of lewisite 1 with 3,4-dimercaptotoluene, 2-(2-chlorovinyl)-5-methyl-l,3,2-benzodithiarsole (see (1)), is a useful derivative for GC/MS analysis. Its mass spectrum is simple with molecular ion peaks at m/z 290/292 and the base peak at m/z 229 due to the loss of the 2-chlorovinyl group (30). 

Copper toxicity has been observed, althongh it is not a function of dietary overload. Abnormally low levels of ceruloplasmin associated with the genetic disorder, Wilson s disease, lead to excessive deposition of copper in the central nervous system, ocular tissue, liver, and other organs. Severe psychotic symptoms are observed. Urinary excretion of the copper can be achieved with specific chelating agents such as British anti-lewisite (BAL, 2,3-dimercaptopropanol) or penicillamine, orally administered. Symptoms of the disease are reversed as the copper levels return to normal. Reduction of dietary copper nptake by competition with relatively high levels of oral zinc is also effective. ... 

Similar to the mustard agents, exposure prevention is the first line of defense against lewisite. Rapid decontamination is especially relevant to lewisite exposure due to the rapid development of pain (1-2 min) associated with lewisite exposure. Unlike other vesicants, an effective antidote for lewisite toxicity exists in the form of British anti-lewisite (BAL 2,3-dimercaptopropanol) which binds with arsenicals, thereby countering the lewisite-induced damage. Such chelation therapy is associated with notable side effects (e.g. renal effects) and requires carefiil medical management. More effective analogs of BAL have been developed with less significant side effects. 

Treatment for these poisons is the administration of sulfhydryl reagents with adjacent sulfhydryl groups to compete with the dihydrolipoyl residues for binding with the metal ion, which is then excreted in the urine. Indeed, 2,3-dimercaptopropanol (see Figure 17.20) was developed after World War I as an antidote to lewisite, an arsenic-based chemical weapon. This compound was initially called BAL, for British anti-lewisite. 

Abbreviations AA, antimycin BAL, British Anti-Lewisite (2,3-dimercaptopropanol) DCCD, dicyclo-hexylcarbodiimide DTNB, 5,5 -dithiobis(2-nitrobenzoate) oxidoreduction potential relative to the Normal Hydrogen Electrode midpoint oxidoreduction potential E midpoint oxidoreduction potential at pH = x FeS, iron-sulphur (centre or protein) FMN, flavin mononucleotide HMHQQ, 7-( n-heptadecyl)mercapto-6-hydroxy-5,8-quinolinequinone HOQNO, 2-/i-heptyl-4-hydroxyquinoline N-oxide Lb, leghaemoglobin MX, myxothiazol NEM, 7V-ethylmaIeimide pmf, protonmotive force, electrochemical proton gradient Q, ubiquinone Qj i, ubiquinone bound to Complex I SQ, ubise-miquinone SQ , ubisemiquinone anion UHDBT, 5- -undecyl-6-hydroxy-4,7-dioxobenzothiazol. 

Organoarsenicals were used as poison gases in World War I. The most notorious of these was Lewisite (140). During the years before World War II, researchers looked for antidotes and found the compound 2,3-dimercaptopropanol, now commonly known as British Anti-Lewisite or BAL (190). This compound has proven extremely effective in the treatment of lead and mercury poisoning. 

Partial protection was afforded by monothiols, such as cysteine or GSH, when tested against pymvate oxidase (Goldman and Dacre, 1989), which was thought to be one of the prime targets of Lewisite. British anti-lewisite or 2,3-dimercaptopropanol preferentially binds with arsenicals over the thiol rings in proteins to form a nontoxic five-membered stable ring, which reverses the lesion induced by... 

Medical treatment with chelation uses four different agents British Anti-Lewisite (2,3-dimercaptopropanol), edetate calcium disodium, D-penicillamine, and succimer or meso-2,3-dimercaptosuccinic acid (Roper et al. 1993). British Anti-Lewisite is contraindicated in children allergic to peanuts and in glucose-6-phosphate dehydrogenase deficiency D-penicillamine is contraindicated in penicillin allergy (Roper et al. 1993). 

Dimercaptopropanol (dmp. Figure 1, also called British Anti-Lewisite) is thought to be useful for the treatment of toxic side effects arising from gold therapy (29). We report here studies on reactions of dmp with red cells treated with EtaPAuCl or auranofin. 

Dimercaprol (BAL, British anti-Lewisite, 2-3 dimercaptopropanol see p 413) is the chelating agent of second choice if unithiol Is not Immediately available. The starting dose is 3-5 mg/kg by deep intramuscular Injection every 4-6 hours. Lewisite bums to the skin and eyes can be treated with topical inunctions of dimercaprol. 

Organoarsenic compounds have a history not just for good (see Salvarsan above), but also for use as poison gas in World War I. Lewisite (GlGH=GHAsGl2) was tested but luckily never used. Research into possible antidotes led to the development of 2,3-dimercaptopropanol, known as mercaprol or British anti-Lewisite (BAL). This compound to... 

The 2,3-dimercaptopropanol because of this reaction became known as British Anti-Lewisite (BAL). The biological importance of this type of reaction has been discussed by Waters and Stock (363). 

Similar unfavorable constants can be obtained for the other cases. A successful agent in complexing the Hg(II) is BAL (British anti-Lewisite), 2,3-dimercaptopropanol, with potent sulfur ligands for the mercury, and also for arsenic, antimony, bismuth, and gold. It is injected intramuscularly in 10% solution in peanut oil at a dose rate of 3 mg/kg of body weight every 4 hr for two days, and after that at decreasing frequency until recovery. 

The compound 2,3-dimercaptopropanol (HSCH2CHSHCH2OH), commonly known as British Anti-Lewisite (BAL), was developed during World War I as an antidote to arsenic-containing poison gas. (a) If each BAL molecule binds one arsenic (As) atom, how many As atoms can be removed by 1.0 g of BAL (b) BAL can also be used to remove poisonous heavy metals like mercury (Hg) and lead (Pb). If each BAL binds one Hg atom, calculate the mass percent of Hg in a BAL-Hg complex. (An H atom is removed when a BAL molecule binds an Hg atom.)... 

Slater has reported evidence that in heart muscle the oxidation of DPNH2 depends on the presence of a component which has been since referred to as Slater s factor. The evidence is based largely on the effect of BAL (British Anti-Lewisite, 2,3-dimercaptopropanol). Treatment of heart muscle preparations with this substance leads to an irreversible de-... 

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