Iron chelators formation constants

Ail of the kinetic tests were conducted by using the same batch of tubing obtained from an operational northeastern U.S. drum boiler. The tubes were machined to a constant OD (3.34 cm) and length (4.74 cm) with a total surface area of 102.8 cm. The interior surfaces were coated with about 1 g of oxide and 50 mg of Cu. The composition of the scale as determined by x-ray diffraction and the chemical composition of the boiler tube are shown in Table 2. In each of the dissolution tests, two AISI 1010 carbon steel coupons in a PTFE mount were added to give a total wetted surface area of 190 cm. The chelating agents tested were obtained from commercial sources and were used without further purification. The chelants and their iron formation constants are described in Table 3. 

Iron(II), concentration formation constant of chelates, 5 717t... 

To enhance iron excretion, intensive chelation therapy is used. The most successful drug is desferrioxamine B, a powerful Fe3+-chelator produced by the microbe Streptomyces pilosus,6 The formation constant for the Fe(III) complex, called ferrioxamine B, is 103afi. Used in conjunction with ascorbic acid—vitamin C, a reducing agent that reduces Fe3+ to the more soluble Fe2+— desferrioxamine clears several grams of iron per year from an overloaded patient. The ferrioxamine complex is excreted in the urine. 

In the presence of hydrogen sulfide produced by anaerobic bacterial activity, particularly sulfate reducers, conditions are created whereby sulfides of copper and zinc could be formed. The partition of these metals between the sulfide phase and the organic phase depends on the relation between the stability constants of the complexes and the solubility product of the sulfides of these metals. Elements with small solubility products of their sulfides and low stability constants of their chelates would be expected to go into the sulfide phase when hydrogen sulfide is present. Copper is typical of such elements. Chalcocite has a solubility product of about 10" ° and covellite about 10"44, whereas the most stable chelates of copper have stability constants of about 10" Consequently, copper could be expected to be accumulated as the sulfide. Zinc sulfide has a much larger solubility product however, the stability of its chelates is lower. From the fact that zinc appears to be completely associated with the inorganic fraction of coal, it can be assumed that the relation between the solubility product of any of its sulfides and its chelates favors formation of the sulfide. Iron could be expected to follow a similar pattern. 

Fig. 14.12 Formation constants at 25 °C for 1 1 chelates of ions with various aminepoly-carboxylate ions (ida, iminodiacetate nta, nitrilo-triacetate , /V-hydroxy-ethylethylenediaminetri-acetate edta, ethylene-diaminetetraacetate cdta, irons-1.2-cyclohexane-diaminetetraacetate dtpa. dicthylenetriaminepenta-acetate). [From Moeller, T. J. Chem. Educ. 1970, 47, 417-430. Reproduced with permission.]...

The chelate effect of DFB causes the formation constant to be greater than that of the monomeric acetohydroxamic acid by two orders of magnitude. Table 1. Other naturally occurring iron chelators, called siderochromes, include various modifications of DFB, ferrichrome (II), rhodotorulic acid (III) and enter-obactin (IV), all of which possess high formation constants... 

A polymer (P-DHB) (XI) based on catechol, the active functional group of enterobactin, was recently synthesised by the reaction of polyvinyl amine with the ethyl ester of 2,3-dihy-droxybenzoic acid (DHB). Only about one third of the amine groups was found to be substituted with DHB units. The formation constant of the iron(III) complex (log K = 40) is the same as that reported for the simple dimethyl amide of DHB and so there does not appear to be any appreciable chelate effect. 

Comparison of the complex-formation constants for bofli 1 1 (57 and 58) and 1 2 (such as 59) species ° with those obtained for the respective copper(II) complexes with parent amino acids revealed that the fructosyl moiety provides for an additional chelate effect in D-fructose-a-amino acids and as a consequence, a significant increase in the complex stability. In the absence of an anchoring chelating group, such as a-carboxylate, the D-finctosamine structure is not a good copper(II) chelator, and Cu(n) expectably does not form stable complexes with the carbohydrate in A -d-Iructose-L-lysine peptides. Although it would be expected that iron(III) complexes with D-finctose-amino acids in aqueous solutions, no related thermodynamic equilibrium studies have been done so far for this important redox-active metal. 

Lactoferrin is a glycoprotein found in mammalian milk that tightly binds two ferric ions producing an iron complex more physically and chemically stable than the uncomplexed protein. Bovine lactoferrin inhibited oxidation in com oil-in-water emulsions and lecithin liposome systems (Table 10.8). At the same molar concentration, lactoferrin was less effective than EDTA in inhibiting hydroperoxide formation in a com oil emulsion. This lower antioxidant activity of lactoferrin may be explained by its partial iron saturation and lower affinity for ferric ions. The formation constant for ferric-EDTA is 1.3 x 10 compared to 10 ° for the ferric-lactoferrin complex. Lactoferrin was a better iron chelator in the liposome than in the emulsion systems. Inhibition in liposomes with iron-lactoferrin mixtures was in the order 1 2 > 1 1 > 2 1. This order suggested that lactoferrin also chelated metal impurities as well as added iron to inhibit lipid oxidation. Lactoferrin did not inhibit the copper-catalysed... 

Finally, control by a chelating agent, EDTA, seems logical. A derivation indicated that the predicted rate ratios would be 10. The predicted rate ratio was improved using formation constants for protonated species for iron, but not manganese, and the chelation approach was not pursued further (19). 

A comparison of values for bi- (n = 3) and hexadentate (n = 1) chelators can be misleading. For example, log P of deferiprone is 35.9 but the log of the third stepwise formation constant given by log(P /p2) is only 9.7 (Motekaitis and Martell 1991). Also, this definition of stability constant does not take into account the different acidities of the ligands and the ability of iron to compete for them with proton. Protonation of the ligand and hydrolysis of the metal, as well as competition with other metals and ligands in biological systems, complicate the interpretation of stability constants. Therefore, in comparing the stability of iron chelates it is useful to introduce the additional terms iTeff and pM. Martell has defined an effective stability constant for Fe complexes based on competition for the... 

Formation of L-lysinehydroxamato-iron(III) complexes occurs by an interchange mechanism formation and dissociation (acid-catalyzed) are significantly affected by charge repulsion (the ligand is H3N+(CH2)4CH(NH3 )CONHOH (335). Rate constants for complex formation between Feaq and two synthetic chelators of the dicatecholsper-midine family are, at 450 and 500M-1s-1 (336), similar to that for desferrioxamine. 

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