Iron complexing agents

FIA was used to optimise sampling from a tablet dissolution apparatus in order to determine the rate of release of iron (II) from a sustained release formulation. The dissolution medium was automatically sampled at 30-minute intervals and the 100/rl aliquots of medium were mixed with the iron complexing agent ferrozine, diluted and then passed into a spectrophotometric detector. The system was microprocessor controlled thus enabling unattended sampling of the dissolution medium for a prolonged period."... 

In order to prevent the reduction between iron(II) and formaldoxime occurring, another iron complexing agent (potassium cyanide) was used in the presence of a reductant (ascorbic acid) that reduces iron(III) to iron(II). Aluminium, titanium, uranium, molybdenum and chromium also form light-coloured complexes that normally do not interfere in the determination of manganese in water or plant material by this method. If the aluminium or titanium concentrations are higher than 40 ppm an additional masking flow of tartrate is recommended [31]. 

Direct Titrations. The most convenient and simplest manner is the measured addition of a standard chelon solution to the sample solution (brought to the proper conditions of pH, buffer, etc.) until the metal ion is stoichiometrically chelated. Auxiliary complexing agents such as citrate, tartrate, or triethanolamine are added, if necessary, to prevent the precipitation of metal hydroxides or basic salts at the optimum pH for titration. Eor example, tartrate is added in the direct titration of lead. If a pH range of 9 to 10 is suitable, a buffer of ammonia and ammonium chloride is often added in relatively concentrated form, both to adjust the pH and to supply ammonia as an auxiliary complexing agent for those metal ions which form ammine complexes. A few metals, notably iron(III), bismuth, and thorium, are titrated in acid solution. 

Variamine blue (C.I. 37255). The end point in an EDTA titration may sometimes be detected by changes in redox potential, and hence by the use of appropriate redox indicators. An excellent example is variamine blue (4-methoxy-4 -aminodiphenylamine), which may be employed in the complexometric titration of iron(III). When a mixture of iron(II) and (III) is titrated with EDTA the latter disappears first. As soon as an amount of the complexing agent equivalent to the concentration of iron(III) has been added, pFe(III) increases abruptly and consequently there is a sudden decrease in the redox potential (compare Section 2.33) the end point can therefore be detected either potentiometrically or with a redox indicator (10.91). The stability constant of the iron(III) complex FeY- (EDTA = Na2H2Y) is about 1025 and that of the iron(II) complex FeY2 - is 1014 approximate calculations show that the change of redox potential is about 600 millivolts at pH = 2 and that this will be almost independent of the concentration of iron(II) present. The jump in redox potential will also be obtained if no iron(II) salt is actually added, since the extremely minute amount of iron(II) necessary is always present in any pure iron(III) salt. 

Iron can be controlled with certain complexing agents, in particular glucono-5-lactone, citric acid, ethylenediaminetetraacetic acid, nitrilotriacetic acid, hydroxyethylethylene diaminetriacetic acid, hydroxyethyliminodiacetic acid, and the salts from the aforementioned compounds. These compounds must be added together with nitrogen-containing compounds such as hydroxylamine salts or hydrazine salts [486,643,1815]. 

Figure 17-26. Complexing agents for iron control glucono-6-lactone, nitrilotriacetic acid, hydroxyethylene diaminetetraacetic acid, and ethylenediaminetetraacetic acid.

This was significant in the preparation of l,2-dimethyl-3-hydroxy-4-pyridone, employed clinically as an iron chelating agent. The aminoreductone is obtained by reaction of methylamine with maltol. Traces of metal within the system readily form highly colored complexes with reactant or product and these are difficult to remove. With the CMR, the preparation was achieved in 65 % yield without the need for decolorizing charcoal and the product was crystallized by collecting the effluent in acetone (Scheme 2.10) [22]. 

---