Other Synthetic Chelators

PoNKA and coworkers (Ponka et al. 1979) discovered that condensation of pyridoxal with isonicotinoyl hydrazide produced a potent Fe chelator. 

Acknowledgements. Work on cellular iron uptake and removal in the author s laboratory is supported by grants from the Medical Research Council of Canada and the Heart and Stroke Foundation of Ontario. 

Adamson lYR, Sienko A, Tenenbein M (1993) Pulmonary toxicity of deferoxamine in iron-poisoned mice. Toxicol Appl Pharmacol 120 13-19 Aisen P (1992) Entry of iron into cells a new role for the transferrin receptor in modulating iron release from transferrin. Ann Neurol 32 S62-S68 Aksoy M, Birdwood GFB (eds) (1985) Hypertransfusion and iron chelation in thalassemia. Huber, Berne 

Al-Refaie FN, Wickens DG, Wonke B, Kontoghiorghes GJ, Hoffbrand AV (1992) Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and LI. Br J Haematol 82 431-436 Alfrey AC, Froment DH, Hammond WS (1989) Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. Kidney Int 36 753-759 

Aust SD, Chignell CF, Bray TM, Kalyanaraman B, Mason RP (1993) Free radicals in toxicology. Toxicol Appl Pharmacol 120 168-178 

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Reactions of the Hydroxyl Group. The hydroxyl proton of hydroxybenzaldehydes is acidic and reacts with alkahes to form salts. The lithium, sodium, potassium, and copper salts of sahcylaldehyde exist as chelates. The cobalt salt is the most simple oxygen-carrying synthetic chelate compound (33). The stabiUty constants of numerous sahcylaldehyde—metal ion coordination compounds have been measured (34). Both sahcylaldehyde and 4-hydroxybenzaldehyde are readily converted to the corresponding anisaldehyde by reaction with a methyl hahde, methyl sulfate (35—37), or methyl carbonate (38). The reaction shown produces -anisaldehyde [123-11-5] in 93.3% yield. Other ethers can also be made by the use of the appropriate reagent. 

Treeby M., Marschner H., Romheld V. Mobilisation of iron and other micronutrient cations from a calcareous soil by plant borne, microbial and synthetic chelators. Plant Soil 1989 114 217-226. 

At present, many natural and synthetic chelators have been studied as potential pharmacological agents for the treatment of iron or copper overload under various pathophysiological conditions. (The chelating activity of flavonoids was already discussed above and the application of chelators in thalassemia and some other pathologies is considered in Chapter 31.) There are specific thermodynamic demands to chelators to be efficient antioxidants [369], We will consider just several chelators of potential therapeutic importance. 

Three methods for trace metal preconcentration were examined liquid-liquid extraction aided by a chelating agent, concentration on a synthetic chelating resin and reductive precipitation with NaBTLt. The latter method gave 1000-fold preconcentration factors with total recovery of Pb and other elements17. Preconcentration of nanogram amounts of lead can be carried out with a resin incorporating quinolin-8-ol (3)18. Enhancement factors of 50-100 can be achieved by such preconcentration procedures followed by determination in a FLA (flow injection analysis) system limits of detection are a few pg Pb/L19. 

For synthesizing tris-chelates (or bis-tridentate chelates) the ideal source material is RuC13 3 H20 simply because of its availability. Hypophosphite reduction in the presence of the ligand provides a fairly general, rapid synthetic technique. While there will always be questions of purity for compounds prepared by this route, it is a valuable method for the initial synthesis of a compound to determine general properties before exploring other synthetic routes. 

The perspective of use of cryosynthesis procedures for obtaining other metal chelates is of high interest. Thus, synthetic reactions (3.234) with use of nitrogen-containing chelating ligands were carried out [541] ... 

Figure 1-35. Formula ofrepeat unit of PTO fibre, showing possible chelated form. 1.8.6 Other synthetic fibres...

The attachment of iron chelating ligands to polymers is an alternative means of modifying bioavailability. DFB has been covalently bonded to poly(acrolein) and other synthetic polymers and shown to have some potential for use in extracorporeal detoxification of acute iron overloaded plasma (57). Poly(N-methacryl-oyl-6-alanine hydroxamic acid), a polydentate polymer obtained by derivatization of poly(acrylic acid) with pendant hydroxamic acid groups, has shown significant iron chelation activity in vivo (58), a result which is possibly related to the longer retention of polymeric species in the circulatory system. 

The chemical properties of heterometallic alkoxides are in general similar to their homometal counterparts (i) hydrolysis, (ii) alcoholysis, (iii) trans-esterification reactions, (iv) reactivity with carboxylic acids and enolic forms of chelating ligands such as /3-diketones/j6-ketoesters. The hydrolytic reactions are now widely employed for the preparation of homogeneous mixed metal-oxide ceramic materials and the rest have found wide applications for the synthesis of a variety of novel metallo-organic derivatives (sometimes unique), which are not often available through any other synthetic route. ... 

Alloxan (1003) has been observed in the mucus associated with dysentery and it was the very first pyrimidine made synthetically when Brugnatelli oxidized uric acid in 1818. Alloxan has an interesting diabetogenic action which appears to be associated with removal of essential zinc from insulin by chelation. Such permanent diabetes may be induced in fish, dogs, cats, sheep, some birds, monkeys and other creatures, but not in man, owls or guinea-pigs certain pyrimidines related to alloxan show some such activity. 

Some of these compounds could be considered as dietary additives, but various other terms, including pesticides, can also be used. They can have beneficial effects on the environment and this aspect will be discussed later. The ionophore monensin, which is an alicyclic polyether (Figure 1), is a secondary metabolite of Streptomyces and aids the prevention of coccidiosis in poultry. Monensin is used as a growth promoter in cattle and also to decrease methane production, but it is toxic to equine animals. " Its ability to act as an ionophore is dependent on its cyclic chelating effect on metal ions. ° The hormones bovine somatotropin (BST) and porcine somatotropin (PST), both of which are polypeptides, occur naturally in lactating cattle and pigs, respectively, but can also be produced synthetically using recombinant DNA methods and administered to such animals in order to increase milk yields and lean meat production. "... 

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