Metal-chelating agents

Liquid-liquid extractions using ammonium pyrrolidine dithiocarbamate (APDC) as a metal chelating agent are commonly encountered in the analysis of metal ions in aqueous samples. The sample and APDC are mixed together, and the resulting metal-ligand complexes are extracted into methyl isobutyl ketone before analysis. 

Amidocarbonylation converts aldehydes into amido-substituted amino acids, which have many important industrial applications ranging from pharmaceuticals to detergents and metal-chelating agents.588 Two catalyst systems have been developed, a cobalt-based system and, more recently a palladium-based system. In the cobalt system, alkenes can be used as the starting material, thus conducting alkene-hydroformylation, formation of hemi-amidal and carbonylation in one pot as... 

Proteins modified with 2-iminothiolane are subject to disulfide formation upon sulfhydryl oxidation. This can cause unwanted conjugation, potentially precipitating the protein. The addition of a metal-chelating agent such as EDTA (0.01-0.1M) will prevent metal-catalyzed oxidation and maintain sulfhydryl stability. In the presence of some serum proteins (i.e., BSA) a 0.1M concentration of EDTA may be necessary to prevent metal-catalyzed oxidation, presumably due to the high contamination of iron from hemolyzed blood. 

Elution of the bound antibody-enzyme conjugate occurs by only a slight shift in pH to acidic conditions or through the inclusion of a metal-chelating agent like EDTA or imidazole in the binding buffer. Either method of elution is mild compared to most immunoaffinity separation techniques (discussed in the previous section). Thus, purification of the antibody-enzyme complex can be done without damage to the activity of either component. 

Certain bifunctional metal chelating agents have been used to investigate protein interactions by virtue of their ability to generate reactive oxygen species that affects protein structure in the immediate vicinity of their modification site. The following sections discuss two applications of such chelate labels, one of which cleaves peptide bonds while the other one causes covalent crosslinks to occur between interacting protein structures. 

The heavy metals copper, manganese, cobalt and zinc were omitted individually and in combination from MS and B5 media to determine the effect on antibody stability in solution [63]. When IgG, antibody was added to these modified media in experiments similar to the one represented in Figure 2.2, only the B5 medium without Mn showed a significant improvement in antibody retention relative to normal culture media. Nevertheless, protein losses were considerable as only about 30% of the added antibody could be detected in the Mn-free medium after about 5 h. The beneficial effect of removing Mn was lost when all four heavy metals, Cu, Mn, Co and Zn, were omitted simultaneously. The reason for these results is unclear. Addition of the metal chelating agent ethylenediaminetetraacetate (EDTA) had a negligible effect on antibody retention in both MS and B5 media [63]. 

Metals Chelating agent Solvent Detection limit (bg/1) Reference... 

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). 

This enzyme [EC 3.4.13.3] (also referred to as Xaa-His dipeptidase, X-His dipeptidase, aminoacylhistidine dipeptidase, and homocarnosinase), is a zinc-dependent dipeptidase that catalyzes the hydrolysis of Xaa-His dipeptides. Carnosine, homocarnosine, and anserine are preferred substrates for this mammalian cytosolic enzyme. Other aminoacylhistidine dipeptides are weaker substrates (including homoanserine). The enzyme is activated by thiols and inhibited by metal-chelating agents. O. W. Griffith (1986) Ann. Rev. Biochem. 55, 855. 

Pharmacology Succimer is an orally active, heavy metal chelating agent it forms water soluble chelates and, consequently, increases the urinary excretion of lead. Pharmacokinetics In a study in healthy adult volunteers, after a single dose of 16, 32, or 48 mg/kg, absorption was rapid but variable, with peak blood levels between 1 and 2 hours. Approximately 49% of the dose was excreted 39% in the feces, 9% in the urine, and 1 % as carbon dioxide from the lungs. Because fecal excretion probably represented nonabsorbed drug, most of the absorbed drug was excreted by the kidneys. The apparent elimination half-life was about 2 days. 

Also, some distillate fuel stabilizers contain metal chelating agents. The purpose of this is to help prevent the metal-catalyzed oxidation of fuel components. However, if a distillate fuel containing a chelating agent is stored in a tank or transferred through lines which are rusted, the stabilizer may act to chelate iron. As a result of this, the fuel containing the stabilizer appears dark. 

Repulsive electrostatic interactions seem to determine (82CPB3442) the conformation of the formyl group in 1,2,3,6-tetrahydropyridines 72 the conformation represented is of higher energy, but is favored in the presence of metal chelating agents. 

Other reports concerning chemically modified amino acid as metal chelating agents used for the carbonic anhydrase active site model reconstruction are in close agreement with the small contribution of Zn(II) binding to the proton chemical shift variation discussed above. NMR experiments carried out in DMSO-rfg, at 300 K, and the observed... 

Paramagnetic metal chelating agent in NMRI Transport across the blood brain barrier... 

Inventory Concentrated process chemistry Low or high pH Organic compounds Dissolved metals Compl exed metals Chelating agents Reducing... 

In 1976, Marion Bradford introduced the first Coomassie dye-based reagent for the rapid colorimetric detection and quantitation of total protein. The Coomassie dye (Bradford) protein assay reagents have the advantage of being compatible with most salts, solvents, buffers, thiols, reducing substances, and metal chelating agents encountered in protein samples. 

Love D, Dow WC, Himmelsbach RJ, Watson AD, Rocklage SM WO 91/05672 Multi-site metal chelating agents... 

We will not go in depth into the subject of antioxidants (12), which is more a part of preformulation than a stress test, but the autoxidation mechanism does suggest that oxidation can be inhibited by peroxy radical scavengers (chain-breaking antioxidants) like phenol antioxidants, by heavy metal chelating agents, and by peroxide inactivating substances (preventive antioxidants). 

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