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.

Alkali-metal ion coordination in uranyl(VI) poly-peroxo complexes in solution, inorganic analogues to crown-ethers. Part 2. Complex formation in the tetramethyl ammonium-, Li(+)-, Na(+)- and K(+)-uranyl(VI)-peroxide-carbonate systems.

The constitution and equilibrium constants of ternary uranyl(vi) peroxide carbonate complexes [(UO2)p(O2)q(CO3)r](2(p-q-r)) have been determined at 0 °C in 0.50 M MNO3, M = Li, K, and TMA (tetramethyl ammonium), ionic media using potentiometric and spectrophotometric data; (17)O NMR data were used to determine the number of complexes present. The formation of cyclic oligomers, "[(UO2)(O2)(CO3)]n", n = 4, 5, 6, with different stoichiometries depending on the ionic medium used, suggests that Li(+), Na(+), K(+) and TMA ions act as templates for the formation of uranyl peroxide rings where the uranyl-units are linked by µ-η(2)-η(2) bridged peroxide-ions. The templating effect is due to the coordination of the M(+)-ions to the uranyl oxygen atoms, where the coordination of Li(+) results in the formation of Li[(UO2)(O2)(CO3)]4(7-), Na(+) and K(+) in the formation of Na/K[(UO2)(O2)(CO3)]5(9-) complexes, while the large tetramethyl ammonium ion promotes the formation of two oligomers, TMA[(UO2)(O2)(CO3)]5(9-) and TMA[(UO2)(O2)(CO3)]6(11-). The NMR spectra demonstrate that the coordination of Na(+) in the five- and six-membered oligomers is significantly stronger than that of TMA(+); these observations suggest that the templating effect is similar to the one observed in the synthesis of crown-ethers. The NMR experiments also demonstrate that the exchange between TMA[(UO2)(O2)(CO3)]5(9-) and TMA[(UO2)(O2)(CO3)]6(11-) is slow on the (17)O chemical shift time-scale, while the exchange between TMA[(UO2)(O2)(CO3)]6(11-) and Na[(UO2)(O2)(CO3)]6(11-) is fast. There was no indication of the presence of large clusters of the type identified by Burns and Nyman (M. Nyman and P. C. Burns, Chem. Soc. Rev., 2012, 41, 7314-7367) and possible reasons for this and the implications for the synthesis of large clusters are briefly discussed.

Alkali-metal ion coordination in uranyl(VI) poly-peroxide complexes in solution. Part 1: the Li⁺, Na⁺ and K⁺--peroxide-hydroxide systems.

The alkali metal ions Li(+), Na(+) and K(+) have a profound influence on the stoichiometry of the complexes formed in uranyl(VI)-peroxide-hydroxide systems, presumably as a result of a templating effect, resulting in the formation of two complexes, M[(UO2)(O2)(OH)]2(-) where the uranyl units are linked by one peroxide bridge, µ-η(2)-η(2), with the second peroxide coordinated "end-on", η(2), to one of the uranyl groups, and M[(UO2)(O2)(OH)]4(3-), with a four-membered ring of uranyl ions linked by µ-η(2)-η(2) peroxide bridges. The stoichiometry and equilibrium constants for the reactions: M(+) + 2UO2(2+) + 2HO2(-) + 2H2O → M[(UO2)(O2)(OH)]2(-) + 4H(+) (1) and M(+) + 4UO2(2+) + 4HO2(-) + 4H2O → M[(UO2)(O2)(OH)]4(3-) + 8H(+) (2) have been measured at 25 °C in 0.10 M (tetramethyl ammonium/M(+))NO3 ionic media using reaction calorimetry. Both reactions are strongly enthalpy driven with large negative entropies of reaction; the observation that ΔH(2) ≈ 2ΔH(1) suggests that the enthalpy of reaction is approximately the same when peroxide is added in bridging and "end-on" positions. The thermodynamic driving force in the reactions is the formation of strong peroxide bridges and the role of M(+) cations is to provide a pathway with a low activation barrier between the reactants and in this way "guide" them to form peroxide bridged complexes; they play a similar role as in the synthesis of crown-ethers. Quantum chemical (QC) methods were used to determine the structure of the complexes, and to demonstrate how the size of the M(+)-ions affects their coordination geometry. There are several isomers of Na[(UO2)(O2)(OH)]2(-) and QC energy calculations show that the ones with a peroxide bridge are substantially more stable than the ones with hydroxide bridges. There are isomers with different coordination sites for Na(+) and the one with coordination to the peroxide bridge and two uranyl oxygen atoms is the most stable one.

A calorimetric study of the hydrolysis and peroxide complex formation of the uranyl(VI) ion.

The enthalpies of reaction for the formation of uranyl(vi) hydroxide {[(UO2)2(OH)2](2+), [(UO2)3(OH)4](2+), [(UO2)3(OH)5](+), [(UO2)3(OH)6](aq), [(UO2)3(OH)7](-), [(UO2)3(OH)8](2-), [(UO2)(OH)3](-), [(UO2)(OH)4](2-)} and peroxide complexes {[UO2(O2)(OH)](-) and [(UO2)2(O2)2(OH)](-)} have been determined from calorimetric titrations at 25 °C in a 0.100 M tetramethyl ammonium nitrate ionic medium. The hydroxide data have been used to test the consistency of the extensive thermodynamic database published by the Nuclear Energy Agency (I. Grenthe, J. Fuger, R. J. M. Konings, R. J. Lemire, A. B. Mueller, C. Nguyen-Trung and H. Wanner, Chemical Thermodynamics of Uranium, North-Holland, Amsterdam, 1992 and R. Guillaumont, T. Fanghänel, J. Fuger, I. Grenthe, V. Neck, D. J. Palmer and M. R. Rand, Update on the Chemical Thermodynamics of Uranium, Neptunium, Plutonium, Americium and Technetium, Elsevier, Amsterdam, 2003). A brief discussion is given about a possible structural relationship between the trinuclear complexes [(UO2)3(OH)n](6-n), n = 4-8.

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.

Chemical equilibria in the UO2(2+)-H2O2-F-/OH- systems and possible solution precursors for the formation of [Na6(OH2)8]@[UO2(O2)F]24(18-) and [Na6(OH2)8]@[UO2(O2)OH]24(18-) clusters.

The focus of this study is on the relationship between uranyl(VI) poly-peroxo clusters in the solid state and their possible precursors in solution. For this purpose, the complex formation in the ternary U(VI)-H2O2-F(-) system has been studied by potentiometric titrations, measuring p[H(+)] and p[F(-)], revealing that significant amounts of ternary uranyl(VI)-peroxide-fluoride complexes are formed. Based on the analysis of these data we find that there are two models consistent with structure data and previous speciation in the uranyl(VI)-peroxide-carbonate system (Dalton. Trans., 2012, 41, 11635-11641). One model contains ternary complexes (UO2)4(O2)4F(-) and (UO2)4(O2)4F2(2-) and the other (UO2)4(O2)4F(-) and (UO2)5(O2)5F3(3-); we have chosen the second model as the one most consistent with available information. We suggest that (UO2)4(O2)4F(-) is a building block in the U-24 cluster, [Na6(OH2)8]@[UO2(O2)F]24(18-) identified in a single-crystal X-ray diffraction study of the solid phase that slowly precipitates from the slightly acidic test solutions. At p[H(+)] ≈ 9.5, a new solid phase is formed that contains the cluster [Na6(OH2)8]@[UO2(O2)OH]24(18-), also identified from an X-ray structure. Both structures contain η(2)-η(2) bridging peroxide and η(2) bridging fluoride or hydroxide ions, respectively. As fluoride bridges are unknown in solution coordination chemistry, it is unlikely that the U-24 fluoride cluster is formed in solution. We suggest that both the solid state fluoride and hydroxide clusters are formed in the crystallization from smaller precursors identified in solution. The study illustrates the importance of accurate control of the solution chemistry when preparing poly-peroxo-metallate clusters and also that the mechanism of their formation is still an open field of research.

New tris-3,4-HOPO lanthanide complexes as potential imaging probes: complex stability and magnetic properties.

There is a growing interest in the development of new medical diagnostic tools with higher sensibility and less damage for the patient body, namely on imaging reporters for the management of diseases and optimization of treatment strategies. This article examines the properties of a new class of lanthanide complexes with a tripodal tris-3-hydroxy-4-pyridinone (tris-3,4-HOPO) ligand - NTP(PrHP)(3). Among the studies herein performed, major relevance is given to the thermodynamic stability of the complexes with a series of Ln(3+) ions (Ln = La, Pr, Gd, Er, Lu) and to the magnetic relaxation properties of the Gd(3+) complex. This hexadentate ligand enables the formation of (1 : 1) Ln(3+) complexes with high thermodynamic stability following the usual trend, while the Gd-chelates show improved relaxivity (higher hydration number), as compared with the commercially available Gd-based contrast agents (CAs); transmetallation of the Gd(3+)-L complex with Zn(2+) proved to be thermodynamically and kinetically disfavored. Therefore, NTP(PrHP)(3) emerges as part of a recently proposed new generation of CAs with prospective imaging sensibility gains.

Energetics and structure of uranium(VI)-acetate complexes in dimethyl sulfoxide.

The thermodynamics of the complexation between uranium(VI) and acetate in dimethyl sulfoxide (DMSO) was studied at 298 K in an ionic medium of 0.1 mol dm(-3) tetrabutyl ammonium perchlorate. The results show that the uranyl ion forms three strong successive mononuclear complexes with acetate. The complexes, both enthalpically and entropically stabilized, are significantly more stable in DMSO than in water. This feature can be ascribed to the weak solvation of acetate in DMSO. The thermodynamic parameters for the formation of the uranium(VI) complexes with acetate in DMSO are compared with those with ethylenediamine in the same solvent. The difference between the two ligand systems reveals that, for the complexation reactions involving charge neutralization, the reorganization of the solvent gives a very important contribution to the overall complexation energetics. The coordination mode of acetate in the uranyl complexes and the changes of the solvation sphere of UO(2)(2+) upon complexation were investigated by FT-IR spectroscopy in DMSO and in acetonitrile/DMSO mixtures. In addition, DFT calculations were performed to provide an accurate description of the complexation at the molecular level. The experimental and calculated results suggest that acetate is solely bidentate to UO(2)(2+) in the 1:1 and 1:3 complexes but mono- and bidentate in the 1:2 complexes. The DFT calculations also indicate that the medium effects must always be taken into account in order to gain accurate information on the complex formation in solution. In fact, the relative stability of the reaction products changes markedly when the DFT calculations are carried out in vacuum or in DMSO solution.

Chemical equilibria in the uranyl(VI)-peroxide-carbonate system; identification of precursors for the formation of poly-peroxometallates.

The focus of this study is on the identification of precursors in solution that might act as building blocks when solid uranyl(VI) poly-peroxometallate clusters containing peroxide and hydroxide bridges are formed. The precursors could be identified by using carbonate as an auxiliary ligand that prevented the formation of large clusters, such as the ones found in solids of fullerene type. Using data from potentiometric and NMR ((17)O and (13)C) experiments we identified the following complexes and determined their equilibrium constants: (UO(2))(2)(O(2))(CO(3))(4)(6-), UO(2)(O(2))CO(3)(2-), UO(2)(O(2))(CO(3))(2)(4-), (UO(2))(2)(O(2))(CO(3))(2)(2-), (UO(2))(2)(O(2))(2)(CO(3))(2-) and [UO(2)(O(2))(CO(3))](5)(10-). The NMR spectra of the pentamer show that all uranyl and carbonate sites are equivalent, which is only consistent with a ring structure built from uranyl units linked by peroxide bridges with the carbonate coordinated "outside" the ring; this proposed structure is very similar to [UO(2)(O(2))(oxalate)](5)(10-) identified by Burns et al. (J. Am. Chem. Soc., 2009, 131, 16648; Inorg. Chem., 2012, 51, 2403) in K(10)[UO(2)(O(2))(oxalate)](5)·(H(2)O)(13); similar ring structures where oxalate or carbonate has been replaced by hydroxide are important structure elements in solid poly-peroxometallate complexes. The equivalent uranyl sites in (UO(2))(2)(O(2))(2)(CO(3))(2-) suggest that the uranyl-units are linked by the carbonate ion and not by peroxide.

Chemical equilibria in the binary and ternary uranyl(VI)-hydroxide-peroxide systems.

The composition and equilibrium constants of the complexes formed in the binary U(VI)-hydroxide and the ternary U(VI)-hydroxide-peroxide systems have been studied using potentiometric and spectrophotometric data at 25 °C in a 0.100 M tetramethylammonium nitrate medium. The data for the binary U(VI) hydroxide complexes were in good agreement with previous studies. In the ternary system two complexes were identified, [UO(2)(OH)(O(2))](-) and [(UO(2))(2)(OH)(O(2))(2)](-). Under our experimental conditions the former is predominant over a broad p[H(+)] region from 9.5 to 11.5, while the second is found in significant amounts at p[H(+)] < 10.5. The formation of the ternary peroxide complexes results in a strong increase in the molar absorptivity of the test solutions. The absorption spectrum for [(UO(2))(2)(OH)(O(2))(2)](-) was resolved into two components with peaks at 353 and 308 nm with molar absorptivity of 16200 and 20300 M(-1) cm(-1), respectively, suggesting that the electronic transitions are dipole allowed. The molar absorptivity of [(UO(2))(OH)(O(2))](-) at the same wave lengths are significantly lower, but still about one to two orders of magnitude larger than the values for UO(2)(2+)(aq) and the binary uranyl(VI) hydroxide complexes. It is of interest to note that [(UO(2))(OH)(O(2))](-) might be the building block in cluster compounds such as [UO(2)(OH)(O(2))](60)(60-) studied by Burns et al. (P. C. Burns, K. A. Kubatko, G. Sigmon, B. J. Fryer, J. E. Gagnon, M. R. Antonio and L. Soderholm, Angew. Chem. 2005, 117, 2173-2177). Speciation calculations using the known equilibrium constants for the U(vi) hydroxide and peroxide complexes show that the latter are important in alkaline solutions even at very low total concentrations of peroxide, suggesting that they may be involved when the uranium minerals Studtite and meta-Studtite are formed by α-radiolysis of water. Radiolysis will be much larger in repositories for spent nuclear fuel where hydrogen peroxide might contribute both to the corrosion of the fuel and to transport of uranium in a ground water system.

Hydrolysis of plutonium(VI) at variable temperatures (283-343 K).

The hydrolysis of Pu(VI) was studied at variable temperatures (283-343 K) by potentiometry, microcalorimetry, and spectrophotometry. Three hydrolysis reactions, mPuO(2)(2+) + nH(2)O=(PuO(2))(m)(OH)(n) (2m-n)( +) + nH(+)), in which (n,m)=(1,1), (2,2), and (5,3), were invoked to describe the potentiometric and calorimetric data. The equilibrium constants (*ß(n,m)) were determined by potentiometry at 283, 298, 313, 328, and 343 K. As the temperature was increased from 283 to 343 K, *ß(1,1), *ß(2,2), and *ß(5,3), increased by 1, 1.5, and 4 orders of magnitude, respectively. The enhancement of hydrolysis at elevated temperatures is mainly due to the significant increase of the degree of ionization of water as the temperature increases. Measurements by microcalorimetry indicate that the three hydrolysis reactions are all endothermic at 298.15 K, with enthalpies of (35.0±3.4) kJ mol(-1), (65.4±1.0) kJ mol(-1), and (127.7±1.7) kJ mol(-1) for ΔH(1,1), ΔH(2,2), and ΔH(5,3), respectively. The hydrolysis constants at infinite dilution have been obtained with the Specific Ion Interaction approach. The applicability of three approaches for estimating the equilibrium constants at different temperatures, including the constant enthalpy approach, the DQUANT equation, and the Ryzhenko-Bryzgalin model, were evaluated with the data from this work.

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.

Thermodynamics of the complexation of uranium(vi) with oxalate in aqueous solution at 10-70 degrees C.

The protonation reactions of oxalate (ox) and the complex formation of uranium(vi) with oxalate in 1.05 mol kg(-1) NaClO(4) were studied at variable temperatures (10-70 degrees C). Three U(vi)/ox complexes (UO(2)ox(j)((2-2j)+) with j = 1, 2, 3) were identified in this temperature range. The formation constants and the molar enthalpies of complexation were determined by spectrophotometry and calorimetry. The complexation of uranium(vi) with oxalate ion is exothermic at lower temperatures (10-40 degrees C) and becomes endothermic at higher temperatures (55-70 degrees C). In spite of this, the free energy of complexation becomes more negative at higher temperatures due to increasingly more positive entropy of complexation that exceeds the increase of the enthalpy of complexation. The thermodynamic parameters at different temperatures, in conjunction with the literature data for other dicarboxylic acids, provide insight into the relative strength of U(vi) complexes with a series of dicarboxylic acids (oxalic, malonic and oxydiacetic) and rationalization for the highest stability of U(vi)/oxalate complexes in the series. The data reported in this study are of importance in predicting the migration of uranium(vi) in geological environments in the case of failure of the engineering barriers, which protect waste repositories.

Complexation of thorium(IV) with acetate at variable temperatures.

The complexation between Th(IV) and acetate in 1.05 mol kg(-1) NaClO4 was studied at variable temperatures (10, 25, 40, 55 and 70 degrees C). The formation constants of five successive complexes, Th(Ac)j(4-j)+ where Ac = CH3COO- and j = 1-5, and the molar enthalpies of complexation were determined by potentiometry and calorimetry. Extended X-ray absorption fine structure spectroscopy (EXAFS) provided additional information on the complexes in solution. The effect of temperature on the stability of the complexes is discussed in terms of the electrostatic model.

Hydrolysis of uranium(VI) at variable temperatures (10-85 degrees C).

The hydrolysis of uranium(VI) in tetraethylammonium perchlorate (0.10 mol dm(-3) at 25 degrees C) was studied at variable temperatures (10-85 degrees C). The hydrolysis constants (*beta(n,m)) and enthalpy of hydrolysis (Delta H(n,m)) for the reaction mUO(2)(2+) + nH(2)O = (UO(2))(m)(OH)(n)((2m-n))+) + nH(+) were determined by titration potentiometry and calorimetry. The hydrolysis constants, *beta(1,1), *beta(2,2), and *beta(5,3), increased by 2-5 orders of magnitude as the temperature was increased from 10 to 85 degrees C. The enthalpies of hydrolysis, Delta H(2,2) and Delta H(5,3), also varied: Delta H(2,2) became more endothermic while Delta H(5,3) became less endothermic as the temperature was increased. The heat capacities of hydrolysis, Delta C(p(2,2)) and Delta C(p(5,3)), were calculated to be (152 +/- 43) J K(-1) mol(-1) and -(229 +/- 34) J K(-1) mol(-1), respectively. UV/Vis absorption spectra supported the trend that hydrolysis of U(VI) was enhanced at elevated temperatures. Time-resolved laser-induced fluorescence spectroscopy provided additional information on the hydrolyzed species at different temperatures. Approximation approaches to predict the effect of temperature were tested with the data from this study.

Complexation of uranium(VI) and samarium(III) with oxydiacetic acid: temperature effect and coordination modes.

The complexation of uranium(VI) and samarium(III) with oxydiacetate (ODA) in 1.05 mol kg(-1) NaClO(4) is studied at variable temperatures (25-70 degrees C). Three U(VI)/ODA complexes (UO(2)L, UO(2)L(2)(2-), and UO(2)HL(2)(-)) and three Sm(III)/ODA complexes (SmL(j)((3-2)(j)+) with j = 1, 2, 3) are identified in this temperature range. The formation constants and the molar enthalpies of complexation are determined by potentiometry and calorimetry. The complexation of uranium(VI) and samarium(III) with oxydiacetate becomes more endothermic at higher temperatures. However, the complexes become stronger due to increasingly more positive entropy of complexation at higher temperatures that exceeds the increase in the enthalpy of complexation. The values of the heat capacity of complexation (Delta C(p) degrees in J K(-1) mol(-1)) are 95 +/- 6, 297 +/- 14, and 162 +/- 19 for UO(2)L, UO(2)L(2)(2-), and UO(2)HL(2)(-), and 142 +/- 6, 198 +/- 14, and 157 +/- 19 for SmL(+), SmL(2)(-), and SmL(3)(3-), respectively. The thermodynamic parameters, in conjunction with the structural information from spectroscopy, help to identify the coordination modes in the uranium oxydiacetate complexes. The effect of temperature on the thermodynamics of the complexation is discussed in terms of the electrostatic model and the change in the solvent structure.