M.Cândida T.A. Vaz

Bis-(N-hydroxy-iminodiacetate)vanadate(IV), a synthetic model of ‘amavadin’

The vanadium(IV) octaco-ordinated complex (NH4+)[N(CH3)4+][V(HIDA)2](HIDA =N-hydroxy-iminodiacetate), whose anion is a likely model for the natural compound ‘amavadin,’ has been prepared and its crystal and molecular structures have been determined by X-ray crystallography; this is the first example of an octaco-ordinated vanadium(IV) complex with just N and O donor atoms.

The thermodynamics of complex formation of cyclic tetra-aza-tetracetic acids

Enthalpy changes for the complexation of alkaline-earth and transition metals with three cyclic tetra-aza-tetracetic acids (cDOTA, cTRITA and cTETA) were obtained by continuous titration calorimetry. From these values and free energy data, the entropy changes for the same reactions were derived. The results show that these complexes are stabilised by both favourable enthalpy and entropy changes, except those of Mg2+ and those of Sr2+ and Ba2+ with cTETA. Generally, the entropy changes for the reactions of the alkaline-earth metals are higher than for the reactions of the non cyclic polyaminocarboxylic acids, but for the reactions of the transition metals the entropy changes are comparable for the cyclic and non cyclic ligands. These results are discussed in terms of a model of ‘cage’ coordination of the metals. The enthalpy changes decrease with the increase in size of the tetra-aza ring (except in the case of Cu2+) but no specific cavity size effect is noticeable. Consideration of the temperature-dependent and temperature-independent contributions to ΔH supports the idea that the number of coordinated nitrogen atoms and carboxylate groups vary along the series.

Siderophore analogues. Chelating properties of a new cyclic diazadihydroxamic acid

Abstract A new cyclic diaza-dihydroxamic acid, 1,4-diazacycloheptane- N, N ′-bis( N -methyl-acetohydroxamic acid) (DACHDMAHA) has been synthesized and studied. This paper is the second one devoted to finding synthetic ferric sequestering agents suitable for mimicking chemical and biological properties of the naturally occurring rhodotorulic acid. This ligand, having the hydroxamate arms bound to a seven-membered ring diamine, presents some biological activity, as was previously found for the corresponding six-membered compound (PIPDMAHA). Stability constants with iron(III) and iron(II) as well as with copper(II) and copper(I) have been determined by potentiometry, spectrophotometry and cyclic voltammetpy, this latter technique being also useful for the interpretation of the electrochemical reaction and the determination of the rate constant of dissociation of iron(II) complexes. Comparing the complexes obtained with DACHDMAHA and PIPDMAHA it has been noticed that the complexes with the first ligand are more stable and that the rate constant of dissociation of the iron(II) complex is higher, showing that this ligand has more of the characteristics of a siderophore.

Siderophore analogues. Synthesis and chelating properties of a new macrocyclic trishydroxamate ligand

A new iron(III)-specific ligand, 1,5,9-triazacyclododecane-N,N′,N″-tris(N-methylacetohydroxamic acid) H3L, containing three hydroxamic acid groups as pendant arms on a macrocyclic triamine backbone, has been synthesized and characterized. Its acid–base and chelating properties with iron(III) and copper(II) ions have been studied by potentiometric and spectrophotometric techniques. The mechanism of electron transfer as well as the kinetics of dissociation and stability constants of reduced species, which are thought to be important in the biological activity of this siderophore analogue, have been studied by voltammetric methods. This ligand has proved to be biologically active and its properties were compared with ferrichrome and ferrioxamine B.

MICROSCOPIC ACID-BASE EQUILIBRIA OF A SYNTHETIC HYDROXAMATE SIDEROPHORE ANALOG, PIPERAZINE-1,4-BIS(N-METHYLACETOHYDROXAMIC ACID)

The protonation behavior of the cyclic diaminodihydroxamate ligand, piperazine-1,4-bis(N-methylacetohydroxamic acid) (H2L1), has been studied at both the macroscopic and the microscopic level. Potentiometric and 1H NMR techniques have been used for the study of this ligand as well as several model compounds: N-methylchloroacetohydroxamic acid, glycinehydroxamic acid and piperidino(N-methylacetohydroxamic acid). Molecular modeling calculations have also been performed to predict the most stable conformations and to estimate relevant contributions to the overall protonation process. The results of the protonation microconstants show that the N-donors in H2L1 are much less basic than the O-donors. The protonated amine moieties release most of their protons in the acid region while the deprotonation of the hydroxamate moieties starts only above pH 5. The theoretical modeling calculations show the effect of electrostatic interactions and internal hydrogen bonds on the interactivity of the basic sites throughout the protonation process.

A new iron(III) ion sequestering ligand: synthesis, solution chemistry and electrochemistry

A new cyclic diaminodihydroxamic ligand, piperazine-1,4-bis(N-methylacetohydroxamic acid)(H2L2), presenting a reasonable analogy with the naturally occurring siderophore rhodotorulic acid (H2L1), has been prepared through an easy two-step process. This ligand, which has proved to be biologically active, forms a very stable complex [Fe2L23]. The ligand and its iron and copper complexes have been characterized by potentiometric and spectrophotometric techniques. The mechanism of electron transfer in the complexes has been studied by voltammetric methods, and the kinetics of dissociation of the iron(II) complex, which might be of crucial importance in the biological activity of this siderophore analogue, was also investigated.

The thermodynamics of complex formation between uramildiacetic acid and the alkaline-earth metals

Abstract Values for the thermodynamic functions (enthalpy and entropy changes) were determined for the complexation reactions of alkaline-earth metals by uramildiacetic acid (UDA) and for the complexation reactions of beryllium by nitrilotriacetic acid (NITA) and 1.2-diaminoethanetetracetic acid (EDTA) using the temperature coefficient method. For the reactions of uramildiacetic acid both enthalpy and entropy changes are favourable and may be correlated with the “effective” ion radii of the metals; the complexes seem to retain coordinated water molecules and to have a coordination number which exceeds the possibilities of the ligand. However, in the case of the beryllium complex, the values obtained suggest a different structure, possibly tetrahedral and more pronounced covalent interactions. These values contrast with those determined in the cases of the reactions of beryllium with NITA and EDTA, for which the entropy changes are higher and favourable and the enthalpy changes unfavourable, as happens with the complexation reactions of magnesium by the same ligands.

Protonation of diaza cyclic complexones: 1H NMR, calorimetric and molecular mechanics studies

A detailed study of the sequences of protonation of three normal- and medium-ring cyclic diamino-carboxylate ligands (PIPDA, DACHDA and DACODA) has been carried out by 1H NMR spectroscopy. Theoretical molecular mechanics calculations were carried out to predict the most stable conformations of their monoprotonated forms (HL–) and to estimate relevant bond lengths and contributions to overall energy.Determinations of the enthalpy changes were made by microcalorimetry, to confirm and relate the conclusions of these studies to the thermodynamic functions of the reactions of protonation.The results suggest that a strong NH ⋯ N hydrogen bond (bond length 2.02 A) is formed in monoprotonated 15-diazacycloctane-N,N′- diacetate (DACODA), the ring of which adopts a boat conformation, whereas monoprotonated 1,4-diazacycloeptane-N,N′-diacetate (DACHDA) adopts a semi-chair, and piprazine-N,N′-diacetate (PIPDA) adopts a trans-chair conformation for which NH ⋯ N hydrogen bonds are not possible. The doubly protonated species (H2L) of these ligands seems to have both protons involved in intramolecular NH ⋯2OC– bonds tothe acetate groups.Hydrogen bonding and differences in ring inductive effects may explain the large discrepancies in the values of the protonation constants of the three ligands.

Thermodynamic studies on mixed complexes-I Complexes of uramildiacetic acid and of nitrilotriacetic acid with transition metals and glycine

Abstract Values for the thermodynamic functions (enthalpy and entropy changes) were determined for the formation of mixed complexes of transition metals with uramildiacetic acid (UDA) and nitrilotriacetic acid (NTA) as “primary” ligand and glycine as secondary ligand, using the temperature coefficient method. The mixed complexes are stabilized by the enthalpy changes in the reaction of MX with L; entropy changes are unfavourable to complex formation. There results were interpreted in terms of the covalent and electrostatic contributions of the metal-nitrogen and metal-carboxylate interactions as well as of structural modifications in the complexes to the overall enthalpy changes. The results obtained were complemented by a spectrophotometric study of the complexes formed by cobalt, copper and nickel.