Iron-hydroxamic acid complexes

Hydroxamates have been observed in the water in the Bay of Quinte, a eutrophic bay of Lake Ontario, and are believed to be produced by blue-green algae (76). Simpson and Neilands (77) have identified schizokinen, a hydroxamic acid derivative of citric acid as an extracellular product of the blue-green algae, Anabaena sp. However, not all Anabaena produce hydroxamates, Walsby (78) has shown that Anabaena cylindrica releases a large pigmented, peptide-containing material which complexes iron. As yet these peptides have not been examined for ability to complex the actinides. 

The first example of a helical complex with pre-determined chirality was the dinuclear complex [Fe2(rdt)3], where rdtFl2 is the fungal iron chelator rhodotorulic acid, (15), a dihydroxamate siderophore. Several more helical and chiral Fe " " and Fe complexes are documented in the diimine and in the hydroxamate and catechol sections. A doubly looped ( bow tie ) complex has been constructed with the aid of a tris-terimine ligand (Section 5.4.3.5.7). 

The EFF calculations yielded a single Cs-symmetric conformation for each type of ferrichrome analog (Figure 4), both with a A-cis configuration of the hydroxamates about the metal when L-amino acids were used. Taken together with the spectroscopic data, pronounced differences were observed for the conformations of these iron complexes. Inspection of the calculated conformations showed that the backbone amide groups may... 

Novakovic presented a colorimetric method for the determination of procaine hydrochloride, either in its bulk form or in various pharmaceutical formulations [41]. The method utilizes conversion of the drug to a hydroxamic acid, and subsequent complexation with iron. The reaction product is violet in color. 

A large volume of work64 has been published on the determination of stability constants for complexes of hydroxamic acids, e.g. acetohydroxamic acid.65 The stability of 3d transition metal ions (Mn2+ to Zn2+) with salicylhydroxamic and 5-methyl-, 5-chloro-, 5-bromo-, 5-nitro-, 4-chloro-, 4-bromo- and 3-chloro-salicylhydroxamic acids,66 as well as with methyltolylbenzohydroxamic acid,67 has been studied potentiometrically. Stability constants of iron(III) with a number of hydroxamic acids have been determined by redox potential studies.68... 

The presence of any of these functional types may be established chemically by applying the hydroxamic acid test. These compounds react with hydroxyl-amine in the presence of sodium hydroxide to form the sodium salt of the corresponding hydroxamic acid. On acidification and addition of iron(m) chloride solution the magenta coloured iron(m) complex of the hydroxamic acid is formed. 

The present survey will focus on the natural product chemistry, in particular the proof of structure, for a class of compounds which are — or may be reasonably be expected to be — found associated with iron in living tissues. On this point some arbitrary selection has been necessary. Thus a trihydroxamic acid providing six oxygen atoms capable of occupying the six corners of an octahedron having the proper dimension for the iron atom will be found in Nature, at least to some extent, in the complex form. This assumption becomes less likely to be true in the di- and mono-hydroxamic acid series and in other natural products which bind iron less strongly. 

No substances containing only a single hydroxamic acid bond have thus far been isolated from natural materials as the metal complex. They are included here, however, in view of the known affinity of even monohydroxamic acids for iron (2) and also because some are related to higher hydroxamates for which a role in iron metabolism seems assured, l us-arinine, for instance, is both a constituent of ferrirhodin and is produced at high levels in iron deficiency. Although the structures are quite varied they are, for the most part -- like the di- and tri- hydroxamates — derived from the N-hydroxyamino acids. 

Dutta, R. L. Metal complexes of hydroxamic acids. Colored complexes of iron, vanadium and molybdenum with isonicotinohydroxamic acids and their analtyical uses. J. Ind. Chem. Soc. 36, 285 (1959). 

Schwarzenbach, G. and K. Schwarzenbach Hydroxamate complexes, I. The stability of the iron (III) complex of simple hydroxamic acids and ferrioxamine B. Helv. Chim. Acta 46, 1390 (1963). 

Fiala (45) and Fiala and Burk (46) early postulated, by analogy from the visible absorption spectra of iron transferrin and the iron complex of aspergillic acid, that iron was bound in transferrins through a hydroxamic acid-CC>2 complex. This formulation is shown in Fig. 15. Fraenkel-Conrat (48), however, could find no evidence for hydroxylamido groups in chicken ovotransferrin. He also prepared and studied the properties of several hydroxylamido proteins by the chemical introduction of the hydroxylamido groups, and found that their properties were quite different from those of the transferrins. 

Using two cooled bubblers connected in series and charged with ethanol, 0.5-1 L of air was sampled at a flow of 0.3 L/min. The vinyl acetate was converted to N-hydroxyacetamide by the addition of hydroxylamine hydrochloride and sodium hydroxide. After 30 minutes, the hydroxamic acid was complexed with iron by the addition of hydrochloric acid and ferric chloride. The intensity of the color which developed in 10 minutes was compared to the intensities of standards. The lower limit of detection for this method was reported to be 0.3 yg/mL. 

The markedly negative redox potentials of tris-catecholate and tris-hydroxamate iron complexes (Figure 4) may be ascribed to the high stabilities of the iron(III) complexes and the rather low stabilities of their iron(II) analogues. Table 9 details the relevant data (interconnected by a thermochemical cycle earlier applied to amino acid pentacyanoferrate complexes ), and documents the remarkably higher stabilities of tris-catecholate than of tris-hydroxamate complexes of iron(III). 

The hydroxamic acid forms a red-blue complex with iron(III) ion. The unknown must first give a negative test with hydroxylamine at lower temperature (Group 1(f), Alkaline Hydroxamic Acid Test) before trying this test. 

Ferrichrome was the first ligand of this type to be isolated (Figure 47). Ferrichrome is a cyclic peptide with three hydroxamic acid side-chains. It gives a neutral complex with Fe . A number of variations having substituents on the hexapeptide or on the acyl group are also found. The ferrichromes are synthesized by fungi, but they are also used by many bacteria as a source of iron, even though they do not synthesize the siderophore themselves. 

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