Giovanni Micera

EPR and potentiometric reinvestigation of copper(II) complexation with simple oligopeptides and related compounds

Abstract The coordination modes of Cu(II) to Di-, Tri-, and Tetra-glycine and related ligands were investigated, within the entire measurable pH range and over a wide range of ligand excess, by means of electron paramagnetic resonance, electron spectroscopy, and in some cases, pH potentiometry. The results, besides allowing the identification of the complex species involved and the attribution of distinctive spectral data set to the various structures, provide significant insight in relation to: i) the coordination ability of the zwitterionic AH form of simple oligopeptides to yield COO − - or 2COO − -complexes or species with mixed [(NH 2 , CO)(COO − )] or [(NH 2 , N − , COO − )(COO − )] coordination; ii) the influence of the size of the (NH 2 , CO), (NH 2 , N − ), and (N − , COO − ) chelated rings on the stability and structure of the complex species; iii) the bis-complex formation processes taking place with Gly-β-ala, β-Alagly, Tri-, and Tetraglycine.

Ternary complex formation between VO(IV)–picolinic acid or VO(IV)–6-methylpicolinic acid and small blood serum bioligands

In order to assess the role of the low molecular mass bioligands of blood serum in vanadium binding, a study was made of the interactions of the complexes formed in the VO(IV)-picolinic acid and VO(IV)-6-methylpicolinic acid systems with various low molecular mass constituents of blood serum, such as oxalate, lactate, citrate and phosphate. The speciation of VO(IV) in these ternary systems and also in the binary VO(IV)-picolinic acid and VO(IV)-6-methylpicolinic acid systems was studied by pH-potentiometry at 25 degrees C and at an ionic strength I = 0.2 M (KCl). The binding modes of the complexes formed were determined by spectral (electronic absorption and EPR) methods. Picolinic acid and 6-methylpicolinic acid were found to form mono and bis complexes through the pyridine nitrogen and carboxylate oxygen, but the presence of the methyl group in 6-methylpicolinic acid surprisingly decreases the stability of its complexes significantly. The results obtained on the ternary systems reveal that mixed ligand complex formation is favoured in these systems, especially with citrate, and must therefore be taken into account in the speciation description of VO(IV) in blood serum.

Copper(II) complexation by D-glucosamine. Spectroscopic and potentiometric studies

The Cu(II) complex formation equilibria of D- glucosamine were studied in aqueous solution by potentiometric and spectroscopic (ESR, CD, absorption spectra) techniques. All data agree that two major species are formed in the pH region 6–9 involving two D-glucosamine ligand molecules bound to the cupric ion via NH2(CuL2) or NH2 and O− (CuH−2L2). In the latter case deprotonated hydroxyls were found to be very effective coordination sites for Cu(II) giving rise to chelate complexes. On the contrary, no complex formation was observed for the Cu(II) N-acetyl-D-glucosamine system.

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.

Speciation and NMR relaxation studies of VO(IV) complexes with several O-donor containing ligands: oxalate, malonate, maltolate and kojate

Abstract Potentiometric, spectral and 1H NMR relaxation studies are reported on the complex formation of VO(IV) with the bidentate chelating ligands oxalic and malonic acids, of a dicarboxylic nature, and maltol and kojic acid, of the hydroxy-4-pyrone type. Complexes with stochiometries VOA and VOA2 were characterised in aqueous solution. Two main features were established for the complex systems. It was found that five-membered ring chelation favours the cis arrangement in the bis complexes of maltol and kojic acid to a higher extent than in those of oxalic and malonic acids. Moreover, previous investigations of VO(IV) binding to maltol or its analogues did not consider the formation of hydroxo species. Formation of dihydroxo bridged dimeric complexes of stoichiometry (VOAH−1)2 and monomeric hydroxo species VOA2H−1 or VOA2(OH), are now taken into account in order to explain the equilibrium and spectroscopic results. 1H NMR relaxation measurements strongly suggest an equilibrium between the two isomers of the bis complexes.

Solution speciation and spectral studies on oxovanadium(IV) complexes of pyridinecarboxylic acids

Abstract Complex formation between oxovanadium(IV) and several pyridinecarboxylic acids (picolinic acid, 3-hydroxypicolinic acid and 2-hydroxynicotinic acid) was studied in aqueous solution by pH-potentiometric and spectroscopic (electron paramagnetic resonance and electronic absorption) techniques. The results demonstrated that picolinic acid forms mono and bis complexes with the VO(IV) ion, coordinated through the pyridine nitrogen and the carboxylate group. The pyridine nitrogen is also involved in the complexation of VO(IV) by 3-hydroxypicolinic acid and 2-hydroxynicotinic acid in the acidic pH range, but as the pH is increased deprotonation of the phenolic hydroxy group occurs and complexes with salicylate-type (COO − ,O − )-coordination are formed. In the VO(IV)–3-hydroxypicolinic acid system, the ligand coordinates to the metal ion in a tridentate fashion via the (N,COO − ,O − ) donor set, forming a tetrameric complex (VOA) 4 in the pH range 6–8.

Oxovanadium(IV) complexes of citric and tartaric acids in aqueous solution

Abstract The complex-formation processes taking place in the systems containing VO(IV) and d-, l-, dl- or meso -tartaric acid or citric acid in aqueous solution were re-examined by combined use of pH potentiometry and spectroscopic (EPR and electronic absorption) methods. The results allowed a full characterization of the dinuclear species existing in the VO(IV)— d-, l- and dl -tartrate systems and indicated a different complexation behaviour in the corresponding meso -tartrate system. As its conformation is unfavourable for dimer formation, the meso ligand yields predominantly cyclic trinuclear species, one of them exhibiting distinctive EPR features. In the VO(IV)-citrate system, dinuclear species with structures different from those of the VO(IV) tartrates are suggested.

Formation of D-glucosamine complexes with Cu(II), Ni(II) and Co(II) ions

Abstract The potentiometric and spectroscopic results for Cu(II), Ni(II) and Co(II) ion complexes with D- glucosamine and the polarographic results for Cu(II)- D-glucosamine systems are discussed. Cu(II) and Ni(II) form two major complex species, i.e.: ML2 and ML2H−2. Co(II) forms only the latter complex in which two D-glucosamine molecules are chelating to metal ion via {NH2, O−} donor sets. The values of stability constants obtained by two different programs (F.I.C.S. and SUPERQUAD) as well as those calculated from polarography for Cu(II) complexes are similar for the major species. The correlation of the potentiometric results with those obtained from spectroscopy and polarography seems to be necessary for reasonable description of the systems studied.

Interaction of Insulin-Enhancing Vanadium Compounds with Human Serum holo-Transferrin

The interaction of VO(2+) ion and four insulin-enhancing compounds, [VO(ma)2], [VO(dhp)2], [VO(acac)2], and cis-[VO(pic)2(H2O)], where Hma, Hdhp, Hacac, and Hpic are maltol, 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, acetylacetone, and picolinic acid, with holo-transferrin (holo-hTf) was studied through the combined application of electron paramagnetic resonance (EPR) and density functional theory (DFT) methods. Since in holo-hTf all of the specific binding sites of transferrin are saturated by Fe(3+) ions, VO(2+) can interact with surface sites (here named sites C), probably via the coordination of His-N, Asp-COO(-), and Glu-COO(-) donors. In the ternary systems with the insulin-enhancing compounds, mixed species are observed with Hma, Hdhp, and Hpic with the formation of VOL2(holo-hTf), explained through the interaction of cis-[VOL2(H2O)] (L = ma, dhp) or cis-[VOL2(OH)](-) (L = pic) with an accessible His residue that replaces the monodentate H2O or OH(-) ligand. The residues of His-289, His-349, His-473, and His-606 seem the most probable candidates for the complexation of the cis-VOL2 moiety. The lack of a ternary complex with Hacac was attributed to the square-pyramidal structure of [VO(acac)2], which does not possess equatorial sites that can be replaced by the surface His-N. Since holo-transferrin is recognized by the transferrin receptor, the formation of ternary complexes between VO(2+) ion, a ligand L(-), and holo-hTf may be a way to transport vanadium compounds inside the cells.