Lead-EDTA chelate

EDTA salts are used for the treatment of heavy metal poisoning. Roosels and Vanderkeel142) were able to extract lead from urine in the presence of EDTA with dithizone by adding calcium to presumably release the lead from EDTA. In view of the fact that the formation constant of the lead-EDTA chelate is 20,000,000 times larger than that of the corresponding calcium chelate, it is doubtful that the calcium actually releases the EDTA from the lead. 

Davis and Christian (D4) have obtained evidence that the formation constant of the lead-APCD chelate is about 5 X KP [Pb(APCD)2]. This compares with a formation constant for the lead-EDTA chelate of 1 X I0 . This 500-fold larger stability for the APCD chelate would indicate that EDTA may not interfere in the extraction if a sufiBdent excess (100- to 1000-fold) of APCD is present. 

Wetai Ion Analysis. We have reported a sensitive trace-metal analysis based upon HPLC separation of p-aminophenyl EDTA chelates and fluorescence detection by postcolumn reaction with fluorescamine (23). An application of the pyridone chemistry already discussed leads to a fluorescent-labeled EDTA (VIII). 

A common form of EDTA used as a preservative is calcium disodium EDTA (CaNa2EDTA). What metals will this form of the sequestrant scavenge effectively The dissolution of the solid will yield calcium ions, sodium ions, and the EDTA anion. Any metal more effectively complexed than calcium will be readily scavenged, including all ions listed in Table 9.1 except silver (Ag+) and magnesium (Mg2+). (In the absence of the calcium counterion, as in the case of the acid form of EDTA, chelation of calcium in the body can occur. In fact, EDTA administered orally is an FDA-approved treatment for calcium deposits in the bloodstream that lead to cardiovascular disease.) Citric acid (Fig. 9.3.3) is another sequestrant of metal ions in foodstuffs. 

Salt and chelate formation with edetate (ethylenediaminetetraacetate, EDTA). A In a solution of calcium disodium salt of EDTA, the sodium and hydrogen ions are chemically and biologically available. B In solutions of calcium disodium edetate, calcium is bound by coordinate-covalent bonds with nitrogens as well as by the usual ionic bonds. C In the lead-edetate chelate, lead is incorporated into five heterocyclic rings. 

Masking can be achieved by precipitation, complex formation, oxidation-reduction, and kinetically. A combination of these techniques may be employed. For example, Cu " can be masked by reduction to Cu(I) with ascorbic acid and by complexation with I . Lead can be precipitated with sulfate when bismuth is to be titrated. Most masking is accomplished by selectively forming a stable, soluble complex. Hydroxide ion complexes aluminum ion [Al(OH)4 or AlOa"] so calcium can be titrated. Fluoride masks Sn(IV) in the titration of Sn(II). Ammonia complexes copper so it cannot be titrated with EDTA using murexide indicator. Metals can be titrated in the presence of Cr(III) because its EDTA chelate, although very stable, forms only slowly. 

Complexometric titrations in the clinical laboratory are limited to those substances that occur in fairly high concentrations since volumetric methods are generally not too sensitive. The most important complexometric titration is the determination of calcium in blood (see Ref. 8). Chelating agents such as. EDTA are used in the treatment of heavy-metal poisoning, for example, when children ingest chipped paint that contains lead. The calcium chelate (as Na2CaY) is administered to prevent complexation and removal of calcium in the bones. Heavy metals such as lead form more stable EDTA chelates than calcium does and will displace the calcium from the EDTA. The chelated lead is then excreted via the kidneys. 

The conditional formation constant for the calcium-EDTA chelate was calculated for pH 10 in Example 9.4 to be 1.8 X 10 °. Calculate the conditional formation constant at pH 3. Compare this with that calculated for lead at pH 3 in Problem 8. Could lead be titrated with EDTA at pH 3 in the presence of calcium ... 

Prepare a spreadsheet for Figure 9.2, log Kj vs. pH for the EDTA chelates of calcium, lead, and mercury. This will require calculating for EDTA and the Kf values for the chelates of calcium, lead, and mercury. Calculate at 0.5 pH intervals. Compare your plot with Figure 9.2. 

A. Calcium EDTA has been used to decrease blood lead concentrations and increase urinary iead excretion in individuais with symptomatic lead intoxication (see p 440) and in asymptomatic persons with high blood lead levels. Although clinical experience associates caicium EDTA chelation with relief of symptoms (particuiarly iead colic) and decreased mortality, controlled clinical trials demonstrating therapeutic efficar are lacking, and treatment recommendations have been largely empiric. 

The calcium salt of EDTA is administered intravenously. In the body, calcium ions of the salt are displaced by heavy-metal ions, such as lead, that bind to the chelate more tightly. The lead-EDTA complex is soluble in body fluids and is excreted in the urine. 

Although studies in animals have shown that administration of vitamin D to vitamin D-deficient rats increased lead absorption, no similar association has been found in children to date. In fact, 1,25-dihydroxy vitamin (1.25-(OH) ) levels in children with high blood lead levels were significantly reduced compared to controls as reported by Rosen et al. (1980). Plasma levels of 1.25-(OH)2 Ds rose to normal values in these children following EDTA chelation therapy, which reduced the children s blood lead levels. Reduced levels of 1.25-dihydroxy vitamin D have been observed in lead-fed rats (Smith et al., 1981). 

Kreppel H, Reichl FX, Szinicz L, Fichtl B, Forth W (1990) Efficacy of various dithiol compounds in acute AS2O3 poisoning in mice. Arch Toxicol 64 387-392 Linz DH, Barrett ET, Pflaumer JE, Keith RE (1992) Neuropsychologic and postural sway improvement after Ca -EDTA chelation for mild lead intoxication. J Occup Med 34 638-641... 

In the treatment of poisoning by lead or other metal ions, higher concentrations of chelant can be safely obtained in humans by administering Na2CaEDTA rather than Na EDTA. The metal ion is bound by displacing small amounts of Ca " that the body can tolerate. Use of Na EDTA would result in calcium chelation and thus serious depletion of calcium in the body fluids (44). Removal of iron in Cooley s anemia is accompHshed by using chelants that are relatively specific for iron (45). 

The extracellular domain of cadherins consists of a variable number of a repeated sequence of about 110 amino acids. This sequence is termed the cadherin repeat and resembles in overall structure, but not in sequence, the Ig like domains. The cadherin repeat is the characteristic motive common to all members of the cadherin superfamily. Classical and desmosomal cadherins contain five cadherin repeats, but as many as 34 repeats have been found in the FAT cadherin (see below). Cadherins are calcium-dependent cell adhesion molecules, which means that removal of Ca2+, e.g., by chelating agents such as EDTA, leads to loss of cadherin function. The Ca2+-binding pockets are made up of amino acids from two consecutive cadherin repeats, which form a characteristic tertiary structure to coordinate a single Ca2+ion [1]. 

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