Etelka Farkas

A comparison between the chelating properties of some dihydroxamic acids, desferrioxamine B and acetohydroxamic acid

Abstract The complexes of hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha1) and hexanedioic acid bis(3-hydroxycarbamoyl-propyl)amide (Dha2) with cobalt(II), nickel(II), copper(II), zinc(II), iron(III), calcium(II) and magnesium(II) have been studied by pH-metric and spectrophotometric methods. All the complexes formed with Dha2 are soluble in water, but a very insoluble complex is formed in the copper(II)-Dha1 system. Besides the 1:1 species complexes with 2:3 stoichiometry are also formed in the cobalt(II)-, nickel(II)-, zinc(II)- and iron(III)-containing systems. Dha2 generally forms more stable complexes than those of Dha1 (e.g. log β values for their iron(III) 1:1 complexes are 17.9 and 19.1, respectively). A comparison of the data with those on the complexes of a simple monohydroxamate, (acetohydroxamate, Aha), nonano-dihydroxamate (Dha3) and the natural trihydroxamate-based siderophore, desferrioxamine B (DFB) revealed that the stability sequence of the complexes is generally: DFB>Dha2≥Dha3∼Dha1>Aha. The shorter but more flexible connecting chain of Dha3 results in the ca. same stability of complexes of Dha1 and Dha3. The above sequence, however, did not hold for copper(II) allowing the coordination of at most two hydroxamates and for calcium(II). In this latter case, Dha2, containing the longest connecting chain, formed the most stable complexes.

Coordination modes of hydroxamic acids in copper(II), nickel(II) and zinc(II) mixed-ligand complexes in aqueous solution

The stability constants and coordination modes of the mixed-ligand complexes formed by Cu(II), Ni(II), Zn(II), ethylenediamine (en), 2,2%-bipyridine (bpy), glycinate (Gly), disodium salt of 4,5-dihydroxybenzene 1,3-disulfonate (Tiron), diethylenetriamine (dien) or 2,2%:6,2ƒ-terpyridine (terpy) (ligand B) and acetohydroxamate (Aha), N-methylacetohydroxamate (MeAha) or N-phenylacetohydroxamate (PhAha) (ligand A) were determined in water (25°C, I 0.2 M KCl) by pH-metric, spectrophotometric, EPR and calorimetric methods. Mixed-ligand complexes with typical hydroxamate type chelation mode involving the NHO moiety are formed in all systems. However, further copper(II) induced deprotonation of the NHO moiety of Aha in the presence of en or bpy results in the formation of mixed-ligand complexes with hydroximato chelates at high pH. The results show the favoured coordination of a hydroxamate to metal(II)‐en and especially to a metal(II)‐bpy moiety. If ligand B is Gly, the increase of stability of the mixed-ligand complexes is as expected on statistical basis, whereas the formation of complexes involving O,O-coordinated hydroxamate and O,O-coordinated Tiron is unfavoured. The tridentate coordination of dien or terpy results in five-coordinated mixed-ligand copper(II) complexes in which, most probably, the hydroxamate moiety adopts an equatorial‐axial coordination mode. This quite unstable hydroxamate chelate can not hinder the hydrolysis of the complex above pH 8. Under very basic conditions acetohydroximato moieties (CONO 2 ) displace the rigid terpy ligand from the coordination sphere and complexes, [Cu(AhaH 1)2] 2 involving hydroximato chelates are formed.

Equilibrium studies on copper(II)- and iron(III)-monohydroxamates

Abstract Chelating properties exhibited by a series of monohydroxamic acids toward copper(II) and iron(III) ions were studied by pH-metric, spectrophotometric and EPR methods. The ligands can be divided into three groups: (i) ligands with alkyl substituents either on the hydroxamate carbon atom (acetohydroxamic acid, Aha; propanohydroxamic acid, Pha; and hexanohydroxamic acid, Hha) or on both the carbon and nitrogen atoms (N-methyl-acetohydroxamic acid, MAha; N-isopropyl-acetohydroxamic acid, iPAha) (ii) ligands with aryl substituents (benzohydroxamic acid, Bha; N-phenyl-acetohydroxamic acid, PhAha; and N-phenyl-benzohydroxamic acid, PhBha); (iii) cyclic derivatives (the natural 2,4-dihydroxy-2H-1,4-benzoxazin-3-(4H)-on-glucoside, DIBOA-gl; and 2-hydroxypyridine-N-oxide,PYRha). In addition to the complexes with the well-known hydroxamate type chelate(s), 1:2 species containing one or both of the coordinated ligands in hydroximato ( R C -CONO 2 − ) form, have been found in the copper(II)-Aha and copper(II)-Bha systems. Complex formation with iron(III) starts at a very acidic pH and in the most systems, if the ligand excess is high enough, the 1:3 species solely exists in the pH range ca. 4–8. Hydroxo complexes are generally formed above pH 8–8.5. However, in the cases of iron(III)-iPAha or -Hha, where the ligands have quite large bulky groups, the hydrolysis starts at somewhat lower pH if the metal to ligand ratios are below 1:5 and precipitation starts to form in iron(III)-DIBOA-gl system at ca. pH 5–5.5. In all systems, the stability constants were determined only for the complexes formed below hydrolytic regions. Evaluation of calculated stability constants show that they are determined by a combination of different substituent effects (electronic, resonance and steric effects). The most significant effects are due to substituents on the nitrogen atom in the hydroxamate moieties. The phenyl ring on carbon atom results in somewhat higher stabilities of the complexes.

Complex formation between some metals and a quinolone family member (ciprofloxacin)

Abstract Some metal [Ca(II), Co(II), Ni(II), Cu(II), Zn(II), Al(III) and Fe(III)] complexes of the quinolone family member (ciprofloxacin = cf) were studied by potentiometric and spectroscopic methods in solution. The results of EPR and polarographic methods are also included. The titration curves for the metal ion-ciprofloxacin were evaluated by assuming all possible models. It was found that a lot of protonated complexes are formed before precipitation in the systems studied. The UV-vis results in the Cu(II)-cf system showed that in the more acidic region a 1:1 complex is favoured, whereas a 1:2 complex prevailed at higher pH values. The coordination of the second ligand is somewhat more favoured than that of the first ligand, and it seems probable that the 1:1 complex is more distorted. Some ternary complexes [Cu(II)-cf-2,2′-bipyridyl, -glycine and -tyrosine] were studied as well. From the ΔlogK value, it was deduced that the formation of the mixed ligand complex in the system Cu(II)-cf-2,2′-bipyridyl is favoured due to back-coordination.

Metal-binding Ability of Desferrioxamine B

The metal complex formation properties of the naturally-occurring hydroxamate-type siderophore Desferrioxamine B is surveyed with special emphasis on its solution speciation. The most likely binding-modes of the complexes formed with this ambidentate ligand are also evaluated. A brief survey of the implications of metal chelation in the therapeutic role of DFB in the treatment of metal overloads is also given.

Copper(II), nickel(II), zinc(II), and molybdenum(VI) complexes of desferrioxamine B in aqueous solution

Abstract Based on pH-metric, spectrophotometric, and EPR measurements, stability constants and bonding modes are reported for the complexes formed in aqueous solutions of the copper(II)-, nickel(II)-, zinc(II)-, and molybdenum(VI)-desferrioxamine B (DFA) systems. Besides the totally deprotonated species, several protonated mononuclear complexes were found in the copper(II)-, nickel(II)-, and zinc(II)-DFA systems, and also the dinuclear species [Cu 2 AH] 2+ . All three hydroxamate groups are able to coordinate to nickel(II) and zinc(II), but only two of them to the copper(II). Molybdenum(VI) yields only one complex species, [MoO 2 (H 2 DFA)] + . This species, which exists below pH 7, involves two hydroxamate groups coordinated to the metal ion. DFA completely prevents the formation of polyoxomolybdates below pH 7, but MoO 4 2− and free DFA exist above this pH.

Metal complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid and benzohydroxamic acid. Crystal and molecular structure of [Cu(phen)2(Cl)]Cl H2Sha, a model for a peroxidase-inhibitor complex.

Stability constants of iron(III), copper(II), nickel(II) and zinc(II) complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid (HAha) and benzohydroxamic acid (HBha) have been determined at 25.0 degrees C, I=0.2 mol dm(-3) KCl in aqueous solution. The complex stability order, iron(III) >> copper(II) > nickel(II) approximately = zinc(II) was observed whilst complexes of H2Sha were found to be more stable than those of the other two ligands. In the preparation of ternary metal ion complexes of these ligands and 1,10-phenanthroline (phen) the crystalline complex [Cu(phen)2(Cl)]Cl x H2Sha was obtained and its crystal structure determined. This complex is a model for hydroxamate-peroxidase inhibitor interactions.

X-Ray and potentiometric studies on a pentanuclear copper(II) complex with β-alaninehydroxamic acid

Potentiometric and X-ray studies on the system copper(II)–L-β-alaninehydroxamic acid have shown the formation of a very stable pentanuclear complex [Cu5A4H–4]2+ at pH around 4. In this species all donor atoms of the aminohydroxamic acid are involved in the metal ion co-ordination. Four peripheral metal ions form an almost planar structure and the central metal ion is 0.4 A above this plane. There are twelve five- and six-membered chelate rings with different conformations. The X-ray structure results support earlier suggestions based on potentiometric and spectroscopic data for the formation of oligomeric structures at relatively low pH.

Studies on transition-metal–peptide complexes. Part 9. Copper(II) complexes of tripeptides containing histidine

Copper(II) complexes of the histidine-containing tripeptides glyclyl-L-histidylglycine (GlyHisGly), glycylglycyl-L-histidine (GlyGlyHis), and L-pyroglutamyl-L-histidyl-L-prolinamide (trf), and the dipeptide L-pyroglutamyl-L-histidine methyl ester (pghme), have been studied by pH-metric and spectrophotometric methods. It was found that, similarly as for glycyl-L-histidine (GlyHis), GlyHisGly forms a complex [CuAH–1], but bis complexes are also formed in low concentration. For GlyGlyHis, only the highly stable species [CuAH–2]– is formed. A complex [CuAH–2]– is also formed with trf and pghme which indicates that the prolinamide side-chain in trf does not take part in the co-ordination. The sequence of deprotonation of the N1H group of the imidazole side-chain is as follows: GlyHisGly > GlyHis > pghme > trf > GlyGlyHis.

Thermodynamic study of the parent and mixed complexes of aspartic acid, glutamic acid and glycine with copper(II)

Abstract The equilibrium constants and in part the ΔH and ΔS data for the parent and mixed complexes copper(II)-aspartic acid, copper(II)-glutamic acid, copper(II)-aspartic acid-glycine, copper(II)-glutamic acid-glycine and copper(II)-aspartic acid-glutamic acid were determined pH-metrically and calorimetrically. Protonated complexes are formed in significant concentration in the copper(II)-aspartic acid and copper(II)-glutamic acid systems. The thermodynamic data led to the assumption that in the CuA complex of aspartic acid the β-carboxyl group of the ligand also forms a bond with the metal. The glutamic acid is bound “glycine-like” to the copper(II). There is an appreciable stabilization in the copper(II)-aspartic acid-glycine mixed complex, while in the copper(II)-glutamic acid-glycine system the stability of the mixed complex agrees with the statistical value. The above statements are supported by the dependence of the stability constants on the ionic strength.