Arsen-1,1-dithiolates

Arsen-1,1-dithiolates are less popular than their phosphorus analogs, perhaps due to fear of toxicity and foul smell of the ligands. 

---

Many heavy metals react with dithiol to give coloured precipitates, e.g. bismuth, iron(III), copper, nickel, cobalt, silver, mercury, lead, cadmium, arsenic, etc. molybdate and tungstate also react. Of the various interfering elements, only arsenic distils over with the tin when a mixture is distilled from a medium of concentrated sulphuric acid and concentrated hydrobromic acid in a current of carbon dioxide. If arsenic is present in quantities larger than that of the tin it should be removed. 

Arsenic uptake in rabbit intestine is inhibited by phosphate, casein, and various metal-chelating agents (USEPA 1980). Mice and rabbits are significantly protected against sodium arsenite intoxication by (V-(2,3-dimercaptopropyl)phthalamidic acid (Stine et al. 1984). Conversely, the toxic effects of arsenite are potentiated by excess dithiols, cadmium, and lead, as evidenced by reduced food efficiency and disrupted blood chemistry in rodents (Pershagen and Vahter 1979). 

The relative affinities of various hydroxylic dithiols for arsenite were measured by Zahler and Cleland (33), but proved hard to understand (since seven-membered rings seemed to give the most stable complexes) until Cruse and James (34) showed that an oxygen atom of such a compound acted as a third ligand for arsenic, so that bicyclic complexes were formed. 

This scheme does not link the oxidation of As(III) with methylation and posits that the obligatory substrate for methylation is an As(III)-GSH complex. In a related analysis of AS3 ATT-catalyzed methylation, it has been suggested that As(III) bound to cellular proteins are the substrates for methylation (Naran-mandura, Suzuki and Suzuki, 2006). Because AS3MT can catalyze the methylation of inorganic As(III) in reaction mixtures that do not contain GSH, but do contain dithiol reductants, it is unclear how the presence of GSH can be considered a requirement for AS3 ATT-catal yzed methylation. In cellular environments that contain the dithiol reductants, GSH, and a plethora of proteins that could bind As(III), it is quite possible that multiple reaction pathways may be involved in the production of methylated arsenicals. Further experimental work will be required to identify each of the molecular components of these pathways. 

N-(2,3-Dimercaptopropyl)phthalamidic acid (41, DMPA) has been shown to form relatively stable complexes with cadmium, zinc and mercury312. DMPA has also been shown to enhance faecal and urinary excretion of mercury in mice and arsenic in mice and rabbits. For the decorporation of arsenic, taken in as arsine, the administration of 3-(tolylthio)propane-l, 2-dithiol (42) has been proposed in the USSR313. ... 

The origins of chelation therapy can be traced back to the treatment of First World War soldiers who had suffered from gas attacks that used the arsenic-based toxin, Lewisite. A dithiol, British anti-Lewisite (BAL), was developed to remove the toxic metal. 

Trivalent arsenic forms strong bonds with sulfur, and thiols are therefore used for derivatizing both lewisite and CVAA, forming the same derivative (19). Lewisite reacts with mono and dithiols the reaction with dithiols occurring rapidly at ambient temperature. In a competitive environment, lewisite reacts almost exclusively with dithiols rather than monothiols (35). Three dithiols, 1,2-ethanedithiol, 1,3-propanedithiol and 2,3-dimercaptopropan-l-ol (British Anti-Lewisite, BAL) have been used for biomedical sample analysis of CVAA to form cyclic derivatives (14a, b) and (15). Unlike derivatiza-tion of TDG, CVAA can be derivatized direcdy in an aqueous solution. 2,3-Dimercaptotoluene, which has been used extensively for environmental analysis (19), does not appear to have been used. 

In acute exposure prompt medical attention is critical. The victim should be immediately removed to fresh air and away from the source of exposure. Oxygen should be provided if there is a respiratory distress. Initial therapy should be directed at stopping the ongoing hemolysis by performing exchange transfusion. Currently there is no other treatment to decrease arsine hemolysis however, studies in vitro have shown that some dithiol chelators (meso-2,3-dimercaptosuccinic acid, DMSA 2,3-dimercapto-l-propanesulfonic acid, DMPS and 2,3-butanedithiol) are effective (see Further Reading). This should be followed by aims to restore renal function or compensate for lost renal function (hemodialysis). This process does not remove any formed arsenic from the exposed body. Administration of dimercaprol (British Anti-Lewisite, BAL) has no effect on arsine hemolysis, but it lowers blood arsenic levels resulting from arsine exposure. The use of chelators must be... 

Bonds to Oxygen.—Mossbauer data have been obtained for (Ph2Sb)20 and a series of trialkoxystibines Sb(OR)3, where R = Et, Pr, Bun, or Bu. 756 Cyclic esters, analogous to those discussed above for arsenic, can be obtained with antimony as the central atom by reactions between PhSbCl2 and diols, dithiols, or monothioglycols.757... 

The amplification method for arsenic is based on its extractive separation as molybdoarsenic acid and determination of Mo with Sulphonitrophenol S (e = 4.5 10 ) or zinc dithiol [56]. The molybdoarsenic acid, after extraction into a mixture of butyl acetate and ethanol, is decomposed, then Mo(VI) is reduced to Mo(Ul) in a Jones reducer, and finally Mo is oxidised to Mo(Vl) be means of Fe(Itl). The Fe(ll) produced in this reaction gives a coloured complex with ferrozine. The amplification factor is 36, and e=9.4 10 [57]. 

The dehydration of (/ )-2-hydroxyglutarate to glutaconate has been studied by Buckel and co-workers (229, 2S0), who have found that the syn elimination of ( )-2-hydroxyglutarate requires a prior activation of the enzyme from cell-free extracts of A. fermentans by ATP, NADH, and MgCl2. The enzymic reaction requires a dithiol, acetyl phosphate, and CoASH, as well as strictly anaerobic conditions, because the active enzyme is irreversibly inactivated on contact with oxygen. Evidence was presented that the adenylation of the protein may be a requisite for activation. Based on preliminary EPR studies and the inactivation of the enzymic reaction by hydroxylamine and uncouplers of oxidative phosphorylation (such as azide, arsenate, and 2,4-dinitrophenol), Schweiger and Buckel postulated a radical mechanism for 2-hydroxyglutarate dehydration via the hydroxyl radical (Scheme 53) (229). Hence, the ATP/NADH-dependent ac-... 

---