Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium.

The complexes of Cu(i) and Ag(i) with 1,3,5-triaza-7-phosphadamantane (PTA) are currently studied for their potential clinical use as anticancer agents, given the cytotoxicity they exhibited in vitro towards a panel of several human tumor cell lines. These metallodrugs are prepared in the form of [M(PTA)4]+ (M = Cu+, Ag+) compounds and dissolved in physiological solution for their administration. However, the nature of the species involved in the cytotoxic activity of the compounds is often unknown. In the present work, the thermodynamics of formation of the complexes of Cu(i) and Ag(i) with PTA in aqueous solution is investigated by means of potentiometric, spectrophotometric and microcalorimetric methods. The results show that both metal(i) ions form up to four successive complexes with PTA. The formation of Ag(i) complexes is studied at 298.15 K in 0.1 M NaNO3 whereas the formation of the Cu(i) one is studied in 1 M NaCl, where Cu(i) is stabilized by the formation of three successive chloro-complexes. Therefore, for this latter system, conditional stability constants and thermodynamic data are obtained. To estimate the affinity of Cu(i) for PTA in the absence of chloride, Density Functional Theory (DFT) calculations have been done to obtain the stoichiometry and the relative stability of the possible Cu/PTA/Cl species. Results indicate that one chloride ion is involved in the formation of the first two complexes of Cu(i) ([CuCl(PTA)] and [CuCl(PTA)2]) whereas it is absent in the successive ones ([Cu(PTA)3]+ and [Cu(PTA)4]+). The combination of DFT results and thermodynamic experimental data has been used to estimate the stability constants of the four [Cu(PTA)n]+ (n = 1-4) complexes in an ideal non-complexing medium. The calculated stability constants are higher than the corresponding conditional values and show that PTA prefers Cu(i) to the Ag(i) ion. The approach used here to estimate the hidden role of chloride on the conditional stability constants of Cu(i) complexes may be applied to any Cu(i)/ligand system, provided that the stoichiometry of the species in NaCl solution is known. The speciation for the two systems shows that the [M(PTA)4]+ (M = Cu+, Ag+) complexes present in the metallodrugs are dissociated into lower stoichiometry species when diluted to the micromolar concentration range, typical of the in vitro biological testing. Accordingly, [Cu(PTA)2]+, [Cu(PTA)3]+ and [Ag(PTA)2]+ are predicted to be the species actually involved in the cytotoxic activity of these compounds.

Complexation of uranium(VI) with glutarimidoxioxime: thermodynamic and computational studies.

The complex formation between a cyclic ligand glutarimidoxioxime (denoted as HL(III) in this paper) and UO2(2+) is studied by potentiometry and microcalorimetry. Glutarimidoxioxime (HL(III)), together with glutarimidedioxime (H2L(I)) and glutardiamidoxime (H2L(II)), belongs to a family of amidoxime derivatives with prospective applications as binding agents for the recovery of uranium from seawater. An optimized procedure of synthesis that leads to the preparation of glutarimidoxioxime in the absence of other amidoxime byproducts is described in this paper. Speciation models based on the thermodynamic results from this study indicate that, compared with H2L(I) and H2L(II), HL(III) forms a much weaker complex with UO2(2+), UO2(L(III))(+), and cannot effectively compete with the hydrolysis equilibria of UO2(2+) under neutral or alkaline conditions. DFT computations, taking into account the solvation by including discrete hydration water molecules and bulk solvent effects, were performed to evaluate the structures and energies of the possible isomers of UO2(L(III))(+). Differing from the tridentate or η(2)-coordination modes previously found in the U(vi) complexes with amidoxime-related ligands, a bidentate mode, involving the oxygen of the oxime group and the nitrogen of the imino group, is found to be the most probable mode in UO2(L(III))(+). The bidentate coordination mode seems to be stabilized by the formation of a hydrogen bond between the carbonyl group of HL(III) and a water molecule in the hydration sphere of UO2(2+).

Chemical speciation of uranium(VI) in marine environments: complexation of calcium and magnesium ions with [(UO2 )(CO3 )3 ](4-) and the effect on the extraction of uranium from seawater.

The interactions of Ca(2+) and Mg(2+) with [UO2 (CO3 )3 ](4-) were studied by calcium ion selective electrode potentiometry and spectrophotometry. The stability constants of ternary Ca-UO2 -CO3 and Mg-UO2 -CO3 complexes were determined with calcium ion selective electrode potentiometry and optical absorption spectrophotometry, respectively. The enthalpies of complexation for two successive complexes, [CaUO2 (CO3 )3 ](2-) and [Ca2 UO2 (CO3 )3 ](aq), were determined for the first time by microcalorimetry. The data help to revise the speciation of uranium(VI) species under seawater conditions. In contrast to the previously accepted assumption that the highly negatively charged [UO2 (CO3 )3 ](4-) is the dominant species, the revised speciation indicates that the dominant aqueous uranium(VI) species under seawater conditions is the neutral [Ca2 UO2 (CO3 )3 ](aq). The results have a significant impact on the strategies for developing efficient sorption processes to extract uranium from seawater.

The relationship between electrospray ionization behavior and cytotoxic activity of [M(I)(P)4](+)-type complexes (M = Cu, Ag and Au; P = tertiary phosphine).

RATIONALE: To try to find a correlation between the antiproliferative activity of a series of [M(I)(P)4](+) complexes (M = Cu, Ag and Au; P = tertiary phosphine) and their stability at micromolar concentration under mass spectrometric conditions. METHODS: [M(I)(P)4](+) complexes were investigated by positive ion electrospray ionization mass spectrometry with multiple collisional experiments using an ion trap mass spectrometer. RESULTS: The displacement of P from native [M(I)(P)4](+), previously described for the copper derivative, is common for the triad complexes leading to the formation of [M(P)3](+) and [M(P)2](+) adducts. Further dissociation of [M(P)2](+) depends on the nature of the metal (Cu ~ Ag > Au). More labile [Cu(P)2](+) and [Ag(P)2](+) are more cytotoxic against HCT-15 human colon carcinoma cells compared to less labile [Au(P)2](+) species. CONCLUSIONS: The dissociation of P ligand(s) from the [M(I)(P)4](+) complexes is the driving force for the triggering of the antiproliferative activity. The more favored is the displacement of P from the [M(P)2](+) active form, the more favored is in turn the possibility for the metal to interact with biological substrates related to cancer proliferation.

Interaction of d(10) metal ions with thioether ligands: a thermodynamic and theoretical study.

Thermodynamic parameters of complex formation between d(10) metal ions, such as Zn(2+), Cd(2+), Hg(2+) and Ag(+), and the macrocyclic thioether 1,4,7-trithiacyclononane ([9]AneS3) or the monodentate diethylsulfide (Et(2)S), in acetonitrile (AN) at 298.15 K, were studied by a systematic methodology including potentiometry, calorimetry and polarography. [9]AneS3 is able to form complexes with all the target cations, Et(2)S only reacts with Hg(2+) and Ag(+). Mononuclear ML(j) (j = 1, 2) complexes are formed with all the metal ions investigated, where the affinity order is Hg(2+) > Ag(+) > Cd(2+) ≈ Zn(2+) when L = [9]AneS3 and Hg(2+) > Ag(+) when L = Et(2)S. Enthalpy and entropy values are generally negative, as a consequence of both metal ion interactions with neutral ligands, the reagents' loss of degrees of freedom and the release of solvating molecules. DFT calculations on the complexes formed with [9]AneS3 in vacuum and in AN are also carried out, to correlate experimental and theoretical thermodynamic values and to highlight the interplay between the direct metal-thioether interaction and the solvation effects. Trends obtained for the stability constants and enthalpies of the 1 : 1 and 1 : 2 complexes in solvent well reproduce the experimental ones for all the divalent metal ion complexes with [9]AneS3 and indicate the release of 3 AN molecules in the formation of each consecutive octahedral complex. In addition, calculated and experimental values for Ag(+) complex formation in solution suggest that in AgL(2) species [9]AneS3 ligands are not both tridentate.

Interaction of thorium(IV) with nitrate in aqueous solution: medium effect or weak complexation?

Microcalorimetric titrations were performed to study the Th(IV)/nitrate interaction in aqueous solution. The results show the formation of a weak mononuclear complex of Th(IV) with nitrate and allow the determination of the complexation thermodynamic parameters at 298 K and ionic strength 1.0 mol dm(-3). The reaction is endothermic and entropy driven. Data and comparison with similar actinide(IV) complexes allow to confirm the inner-sphere nature of the Th(NO(3))(3+) complex.