Arsenic metal chelators

Oxidation Trivalent arsenic citric acid or EDTA Potassium permanganate depending on chelating agent, metal chelate is either strongly sorbed to soil or is highly mobile and can be flumbed usinj water or dilute acid solutions. Oxidizes trivalent arsenic to pentavalent... 

Alkaline phosphatases [AP, orthophosphoric-monoester phosphorylase (alkaline optimum) EC 3.1.3.1] represent a large family of almost ubiquitous isoenzymes found in organisms from bacteria to animals. In mammals, there are two forms of AP, one form present in a variety of tissues and another form found only in the intestines. They share common attributes in that the phosphatase activity is optimal at pH 8-10, is activated by the presence of divalent cations, and is inhibited by cysteine, cyanides, arsenate, various metal chelators, and phosphate ions. Most conjugates created with AP utilize the form isolated from calf intestine. 

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 heavy-metal chelating properties of thiols were taken advantage of in the design of dimercaprol ( British Anti-Lewisite, BAL) as counter poison of the arsenical war gas lewisite (Figure 20.43). Today dimercaprol is used to treat poisoning by compounds of gold, mercury, antimony and arsenic. The toxic nature of the heavy metals is masked and chelate is stable enough to be excreted as such in the urine. 

Many inhibitors may be present in biological samples or in buffers currently used for EIA. Pi is a competitive inhibitor of the enzyme and forms an intermediate with the enzyme which is indistinguishable from the intermediate formed during catalysis of the hydrolysis of phosphate esters (Caswell and Caplow, 1980). The K, (i.e. the for Pi) is lower than the for the substrate, typically KijK, = 0.3, i.e. a lower concentration of Pi than of the substrate is required to half-saturate the enzyme. Arsenate is a stronger competitive inhibitor than Pi, whereas phosphonates are weaker. Metal chelating products (EDTA, cysteine, thioglycolic acid) are also important inhibitors. Many amino acids show a mixed competitive or uncompetitive inhibition (Fernley, 1971). 

Dimercaprol, a metal-chelating agent (30 mg/kg IM), is used to treat severe arsenic or gold poisoning. 

EDTA (ethylenediaminetetraacetic acid) forms stable metal chelates with a number of metal ions. Using this reagent as a complexing- agent, arsenic, bismuth, and selenium can be determined without any interference in the presence of nickel and cobalt. The cobalt-EDTA chelate is stable in 5 M HCl solution, whereas the corresponding bismuth complex is not. The influence of copper on the determination of arsenic can also be eliminated with EDTA, but not in the determination of selenium. Thiourea has been used to eliminate the influence of copper in the determination of antimony and sodium oxalate to eliminate the influence of copper and nickel in the determination of tin. An addition of thiosemicarbazide and 1,10-phenanthro-line reduces the interference of copper, nickel, platinum, and palladium in the determination of arsenic. 

SIA (4-Hydroxy-3,5-Dimethoxy-Cinnamic Acid) (Fig. 63.2) is a phenylpropanoid compound found in various herbal materials and high-bran cereals. It has been reported that sinapic acid has antioxidant efficacy as a metal chelator due to the orientation of functional groups. Administration of sinapic acid exhibited significant reversal of arsenic-induced toxicity in hepatic tissue [68]. 

As discussed, metal chelators are administered to increase the excretion of arsenic but, unfortunately, the... 

CHjSH CHSH-CHjOH. Usually obtained as an oil, m.p. 77 C. Developed as an antidote to poisoning by organic arsenicals by external application, it is of use in poisoning by Hg, Cu, Zn, Cd but not Pb. It acts by forming a chelate with the metal and so removing it from the system. 

Dimercaprol (BAL, British Anti-Lewisite) was developed in World War 11 as an antidote against vesicant organic arsenicals (B). It is able to chelate various metal ions. Dimercaprol forms a liquid, rapidly decomposing substance that is given intramuscularly in an oily vehicle. A related compound, both in terms of structure and activity, is di-mercaptopropanesulfonic acid, whose sodium salt is suitable for oral administration. Shivering, fever, and skin reactions are potential adverse effects. 

Tolerance to heavy metals, specifically mercury and cadmium, has been associated with the induction of kidney metallothionein, a protein rich in sulfhydryl groups which protects by chelation (102). The synthetic antidote dimercaprol, introduced after World War I for arsenic-containing gases, works by a similar mechanism (103). 

---