A tutorial on potentiometric data processing. Analysis of software for optimization of protonation constants.

Defining the distribution of the chemical species in a multicomponent system is a task of great importance with applications in many fields. To clarify the identity and the abundance of the species that can be formed by the interaction of the components of a solution, it is fundamental to know the formation constants of those species. The determination of equilibrium constants is mainly performed through the analysis of experimental data obtained by different instrumental techniques. Among them, potentiometry is the elective technique for this purpose. As such, a survey was run within the NECTAR COST Action - Network for Equilibria and Chemical Thermodynamics Advanced Research, to identify the most used software for the analysis of potentiometric data and to highlight their strengths and weaknesses. The features and the calculation processes of each software were analyzed and rationalized, and a simulated titration dataset of a hypothetic hexaprotic acid was processed by each software to compare and discuss the optimized protonation constants. Moreover, further data analysis was also carried out on the original dataset including some systematic errors from different sources, as some calibration parameters, the total analytical concentration of reagents and ionic strength variations during titrations, to evaluate their impact on the refined parameters. Results showed that differences on the protonation constants estimated by the tested software are not significant, while some of the considered systematic errors affect results. Overall, it emerged that software commonly used suffer from many limitations, highlighting the urgency of new dedicated and modern tools. In this context, some guidelines for data generation and treatment are also given.

Deferiprone: new environmental perspectives. Insights into its sequestering ability vs. different metal cations.

Deferiprone, generally, is considered an important chelating agent for Fe3+ overload. From a literature data analysis, a lack of information on the interaction of this molecule toward a series of metal cations emerged, inducing to fill out the topic. The complexing ability of deferiprone toward Ca2+, Mg2+, Cd2+ and Pb2+ was studied by potentiometry and 1H NMR spectroscopy, in KCl aqueous solutions at different ionic strength values (0.1 ≤ I/mol dm-3 ≤ 1.0) and T = 298.15 K. The same speciation model featured by the ML, ML2, ML3 and ML(OH) (M = metal and L = deferiprone or DFP) species was obtained for Cd2+ and Pb2+; the formation constants calculated at infinite dilution are: logTß = 7.23±0.02, 12.47±0.03, 16.70±0.04, and -2.53±0.04, respectively for Cd2+ and 9.91±0.01, 15.99±0.02, 19.93±0.05 and 0.99±0.02 for Pb2+. Only two species, namely ML and ML2, were determined for Ca2+ and Mg2+, whose formation constants at infinite dilution are respectively: 3.72±0.01 and 6.50±0.02, for the first one, 5.31±0.01 and 9.58±0.01, for the second. The ligand sequestering ability and affinity toward M2+ were evaluated by determining the pL0.5 and pM parameters at different pHs and ionic strengths. The results suggest that deferiprone has the best complexing and sequestering ability toward Pb2+, followed by Cd2+, Mg2+ and Ca2+, respectively. 1H NMR studies confirmed the DFP affinity for Cd2+ and Pb2+, and in combination with DFT calculations showed that metal cations are bound to the hydroxo-oxo moiety of the pyridinone ring. The data reported in this study provide information on the possible employment of a small molecule like deferiprone, as a chelating and sequestering agent for Pb2+ accumulation or overload from environmental and biological matrices.

Binary and ternary complexes of epinephrine with alginate and biologically and environmentally relevant metal cations.

The speciation of epinephrine (Eph -) in the presence of alginate (Alg 2-) and two biological and environmental relevant metal cations (Cu2+, UO2 2+) was investigated at T = 298.15K, I = 0.15-1.00 mol dm-3 in NaCl(aq). The formation of binary and ternary complexes was evaluated and, since epinephrine can behave as a zwitterion, the Eph -/Alg 2- interaction was studied by means of DOSY NMR. The dependence of the equilibrium constants on ionic strength was studied using an extended Debye-Hückel type equation and the SIT approach. The effect of temperature was investigated by means of isoperibolic titration calorimetry: the entropic contribution was the driving force for the Cu2+/Eph - complexes formation. The sequestering ability of Eph - and Alg 2- on Cu2+, evaluated by the pL0.5 calculation, increased with pH and ionic strength. The determination of pM parameter showed that Eph - had a higher Cu2+ affinity with respect to Alg 2-. The formation of Eph -/Alg 2- species was also investigated by UV-Vis spectrophotometry and 1H NMR measurements. The ternary Cu2+/Eph -/Alg 2- and Cu2+/UO2 2+/Eph - interactions were also studied. The "extra-stability" calculated for the mixed ternary species confirmed that their formation was thermodynamically favorable.

Environmental behaviour of a pesticide metabolite, the AMPA. Sequestration of Ca2+, Mg2+, Cu2+, Zn2+ and Al3.

The chelating and sequestering ability of a glyphosate metabolite, the aminomethylphosphonic acid (AMPA) towards bi- and trivalent metal cations, such as Ca2+, Mg2+, Zn2+, Cu2+ and Al3+, were investigated in aqueous solutions of NaCl, in an ionic strength range of 0.1 ≤ I/mol dm-3 ≤ 1.0 and at constant temperature of T = 298.15 ± 0.15 K. The investigations on the acid-base properties and complexing ability were performed, by means of potentiometry, in conditions of different cM:cAMPA molar ratios and pH values. The formation of insoluble species was experimentally observed in the Mn+/AMPA2- systems, and the solid phases were characterized by means of X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM) and InfraRed Attenuated Total Reflection spectroscopy (IR-ATR). The dependence on ionic strength of the stability constants of the Mn+/AMPA2- complexes species, determined at different ionic strengths, was modelled by the Debye-Hückel type equation. The sequestering ability of AMPA toward the investigated metal cations was evaluated by pL0.5 parameter.

Indole-3-acetic acid correlates with monocyte-to-high-density lipoprotein (HDL) ratio (MHR) in chronic kidney disease patients.

PURPOSE: Indole-3-acetic acid is a protein-bound indolic uremic toxin deriving from tryptophan metabolism. Increased levels are associated with higher thrombotic risk and both cardiovascular and all-cause mortality. An emerging biomarker of cardiovascular disease is the monocyte-to-high-density lipoprotein ratio (MHR). The main purpose of this study was to investigate the association of indole-3-acetic acid with MHR and other markers of cardiovascular risk in patients with chronic kidney disease (CKD). METHODS: We enrolled 61 non-dialysis CKD patients and 6 dialysis patients. Indole-3-acetic acid levels were measured with ELISA technique. RESULTS: In the whole cohort of 67 patients, indole-3-acetic acid was directly related to Ca × P (ρ = 0.256; P = 0.0365) and MHR (ρ = 0.321; P = 0.0082). In the 40 patients with previous cardiovascular events, indole-3-acetic acid correlated with uric acid (r = 0.3952; P = 0.0116) and MHR (ρ = 0.380; P = 0.0157). MHR was related with fibrinogen (ρ = 0.426; P = 0.0010), arterial hypertension (ρ = 0.274; P = 0.0251), C-reactive protein (ρ = 0.332; P = 0.0061), gender (ρ = - 0.375; P = 0.0017; 0 = male, 1 = female), and CKD stage (ρ = 0.260; P = 0.0337). A multiple regression analysis suggested that indole-3-acetic acid might be an independent predictor of MHR. CONCLUSION: This study shows a significant association between indole-3-acetic acid and MHR. Prospective studies are required to evaluate if decreasing indole-3-acetic acid concentrations may reduce MHR levels and cardiovascular events and improve clinical outcomes.

Caffeic Acid/Eu(III) Complexes: Solution Equilibrium Studies, Structure Characterization and Biological Activity.

Caffeic acid (CFA) is one of the various natural antioxidants and chemoprotective agents occurring in the human diet. In addition, its metal complexes play fundamental roles in biological systems. Nevertheless, research on the properties of CFA with lanthanide metals is very scarce, and little to no chemical or biological information is known about these particular systems. Most of their properties, including their biological activity and environmental impact, strictly depend on their structure, stability, and solution behaviour. In this work, a multi-analytical-technique approach was used to study these relationships for the Eu(III)/CFA complex. The synthesized metal complex was studied by FT-IR, FT-Raman, elemental, and thermal (TGA) analysis. In order to examine the chemical speciation of the Eu(III)/CFA system in an aqueous solution, several independent potentiometric and spectrophotometric UV-Vis titrations were performed at different M:L (metal:ligand) and pH ratios. The general molecular formula of the synthesized metal complex in the solid state was [Eu(CFA)3(H2O)3]∙2H2O (M:L ratio 1:3), while in aqueous solution the 1:1 species were observed at the optimum pH of 6 ≤ pH ≤ 10, ([Eu(CFA)] and [Eu(CFA)(OH)]-). These results were confirmed by 1H-NMR experiments and electrospray-ionization mass spectrometry (ESI-MS). To evaluate the interaction of Eu(III)/CFA and CFA alone with cell membranes, electrophoretic mobility assays were used. Various antioxidant tests have shown that Eu(III)/CFA exhibits lower antioxidant activity than the free CFA ligand. In addition, the antimicrobial properties of Eu(III)/CFA and CFA against Escherichia coli, Bacillus subtilis and Candida albicans were investigated by evaluation of the minimum inhibitory concentration (MIC). Eu(III)/CFA shows higher antibacterial activity against bacteria compared to CFA, which can be explained by the highly probable increased lipophilicity of the Eu(III) complex.

Thermodynamic Solution Properties of a Biodegradable Chelant (L-glutamic-N,N-diacetic Acid, L-GLDA) and Its Sequestering Ability toward Cd2.

The thermodynamics of the interaction of L-glutamic-N,N-diacetic acid (GLDA) with protons was studied potentiometrically at different temperatures, ionic strengths and ionic media. Four protonation constants and corresponding enthalpy changes occurred at infinite dilution together with temperature and ionic strength coefficients. The medium effect was also interpreted in terms of the formation of weak complexes between the ligand and the cations of supporting electrolytes, resulting in a greater tendency of GLDA to chemically interact with Na+ rather than K+ and, in turn, (CH3)4N+. Formation constants of GLDA with Cd2+ were determined in NaCl(aq) at different ionic strength values. Five complex species were found, namely CdL2-, CdHL-, CdH2L0(aq), Cd2L0(aq), and Cd(OH)L3-, whose formation constant values at infinite dilution were log ß = 12.68, 17.61, 20.76, 17.52, and 1.77, respectively. All the species results were relevant in the pH range of natural waters, although the Cd2L0(aq) was observed only for CCd ≥ CGLDA and concentrations of >0.1 mmol dm-3. The sequestering ability of GLDA toward Cd2+, evaluated by means of pL0.5, was maximum at pH~10, whereas the presence of a chloride containing a supporting electrolyte exerted a negative effect. Among new generation biodegradable ligands, GLDA was the most efficient in Cd2+ sequestration.

Bifunctional 3-Hydroxy-4-Pyridinones as Potential Selective Iron(III) Chelators: Solution Studies and Comparison with Other Metals of Biological and Environmental Relevance.

The binding ability of five bifunctional 3-hydroxy-4-pyridinones towards Cu2+ and Fe3+ was studied by means of potentiometric and UV-Vis spectrophotometric measurements carried out at I = 0.15 mol L-1 in NaCl(aq),T = 298.15 K and 310.15 K. The data treatments allowed us to determine speciation schemes featured by metal-ligand species with different stoichiometry and stability, owing to the various functional groups present in the 3-hydroxy-4-pyridinones structures, which could potentially participate in the metal complexation, and in the Cu2+ and Fe3+ behaviour in aqueous solution. Furthermore, the sequestering ability and metal chelating affinity of the ligands were investigated by the determination of pL0.5 and pM parameters at different pH conditions. Finally, a comparison between the Cu2+ and Fe3+/3-hydroxy-4-pyridinones data herein presented with those already reported in the literature on the interaction of Zn2+ and Al3+ with the same ligands showed that, from the thermodynamic point of view, the 3-hydroxy-4-pyridinones are particularly selective towards Fe3+ and could therefore be considered promising iron-chelating agents, also avoiding the possibility of competition, and eventually the depletion, of essential metal cations of biological and environmental relevance, such as Cu2+ and Zn2+.

The Effect of Metal Cations on the Aqueous Behavior of Dopamine. Thermodynamic Investigation of the Binary and Ternary Interactions with Cd2+, Cu2+ and UO22+ in NaCl at Different Ionic Strengths and Temperatures.

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop-)] with cadmium(II), copper(II) and uranyl(VI) were studied in NaCl(aq) at different ionic strengths (0 ≤ I/mol dm-3 ≤ 1.0) and temperatures (288.15 ≤ T/K ≤ 318.15). From the elaboration of the experimental data, it was found that the speciation models are featured by species of different stoichiometry and stability. In particular for cadmium, the formation of only MLH, ML and ML2 (M = Cd2+; L = dopamine) species was obtained. For uranyl(VI) (UO22+), the speciation scheme is influenced by the use of UO2(acetate)2 salt as a chemical; in this case, the formation of ML2, MLOH and the ternary MLAc (Ac = acetate) species in a wide pH range was observed. The most complex speciation model was obtained for the interaction of Cu2+ with dopamine; in this case we observed the formation of the following species: ML2, M2L, M2L2, M2L2(OH)2, M2LOH and ML2OH. These speciation models were determined at each ionic strength and temperature investigated. As a further contribution to this kind of investigation, the ternary interactions of dopamine with UO22+/Cd2+ and UO22+/Cu2+ were investigated at I = 0.15 mol dm-3 and T = 298.15K. These systems have different speciation models, with the MM'L and M2M'L2OH [M = UO22+; M' = Cd2+ or Cu2+, L = dopamine] common species; the species of the mixed Cd2+ containing system have a higher stability with respect the Cu2+ containing one. The dependence on the ionic strength of complex formation constants was modelled by using both an extended Debye-Hückel equation that included the Van't Hoff term for the calculation of the formation enthalpy change values and the Specific Ion Interaction Theory (SIT). The results highlighted that, in general, the entropy is the driving force of the process. The quantification of the effective sequestering ability of dopamine towards the studied cations was evaluated by using a Boltzmann-type equation and the calculation of pL0.5 parameter. The sequestering ability was quantified at different ionic strengths, temperatures and pHs, and this resulted, in general, that the pL0.5 trend was always: UO22+ > Cu2+ > Cd2+.

The Solution Behavior of Dopamine in the Presence of Mono and Divalent Cations: A Thermodynamic Investigation in Different Experimental Conditions.

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop-)] with methylmercury(II) (CH3Hg+), magnesium(II), calcium(II), and tin(II) were studied in NaCl(aq) at different ionic strengths and temperatures. Different speciation models were obtained, mainly characterized by mononuclear species. Only for Sn2+ we observed the formation of binuclear complexes (M2L2 and M2LOH (charge omitted for simplicity); M = Sn2+, L = Dop-). For CH3Hg+, the speciation model reported the ternary MLCl (M = CH3Hg+) complex. The dependence on the ionic strength of complex formation constants was modeled by using both an extended Debye-Hückel equation that included the Van't Hoff term for the calculation of enthalpy change values of the formation and the Specific Ion Interaction Theory (SIT). The results highlighted that, in general, the entropy is the driving force of the process. The sequestering ability of dopamine towards the investigated cations was evaluated using the calculation of pL0.5 parameter. The sequestering ability trend resulted to be: Sn2+ > CH3Hg+ > Ca2+ > Mg2+. For example, at I = 0.15 mol dm-3, T = 298.15 K and pH = 7.4, pL0.5 = 3.46, 2.63, 1.15, and 2.27 for Sn2+, CH3Hg+, Ca2+ and Mg2+ (pH = 9.5 for Mg2+), respectively. For the Ca2+/Dop- system, the precipitates collected at the end of the potentiometric titrations were analyzed by thermogravimetry (TGA). The thermogravimetric calculations highlighted the formation of solid with stoichiometry dependent on the different metal:ligand ratios and concentrations of the starting solutions.

Critical Reappraisal of Methods for Measuring Urine Saturation with Calcium Salts.

Background: Metabolic and physicochemical evaluation is recommended to manage the condition of patients with nephrolithiasis. The estimation of the saturation state (ß values) is often included in the diagnostic work-up, and it is preferably performed through calculations. The free concentrations of constituent ions are estimated by considering the main ionic soluble complexes. It is contended that this approach is liable to an overestimation of ß values because some complexes may be overlooked. A recent report found that ß values could be significantly lowered upon the addition of new and so far neglected complexes, [Ca(PO4)Cit]4- and [Ca2H2(PO4)2]. The aim of this work was to assess whether these complexes can be relevant to explaining the chemistry of urine. Methods: The Ca-phosphate-citrate aqueous system was investigated by potentiometric titrations. The stability constants of the parent binary complexes [Cacit]- and [CaPO4]-, and the coordination tendency of PO43- toward [Ca(cit)]- to form the ternary complex, were estimated. ßCaOx and ßCaHPO4 were then calculated on 5 natural urines by chemical models, including or not including the [CaPO4]- and [Ca(PO4)cit]4- species. Results: Species distribution diagrams show that the [Ca(PO4)cit]4- species was only noticeable at pH > 8.5 and below 10% of the total calcium. ß values estimated on natural urine were slightly lowered by the formation of [CaPO4]- species, whereas [Ca(PO4)cit]4- results were irrelevant. Conclusions: While [CaPO4]- species have an impact on saturation levels at higher pHs, the existence of ternary complex and of the dimer is rejected.

Towards a rational design of materials for the removal of environmentally relevant cations: polymer inclusion membranes (PIMs) and surface-modified PIMs for Sn2+ sequestration in aqueous solution.

This work is focused on the design and preparation of polymer inclusion membranes (PIMs) for potential applications for stannous cation sequestration from water. For this purpose, the membranes have been synthesized employing two polymeric matrices, namely, polyvinylchloride (PVC) and cellulose triacetate (CTA), properly enriched with different plasticizers. The novelty here proposed relies on the modification of the cited PIMs by selected extractants expected to interact with the target cation in the membrane bulk or onto its surface, as well as in the evaluation of their performances in the sequestration of tin(II) in solution through chemometric tools. The composition of both the membrane and the solution for each trial was selected by means of a D-Optimal Experimental Design. The samples such prepared were characterized by means of TG-DTA, DSC, and static contact angles investigations; their mechanical properties were studied in terms of tensile strength and elastic modulus, whereas their morphology was checked by SEM. The sequestering ability of the PIMs toward stannous cation was studied by means of kinetic and isotherm experiments using DP-ASV. The presence of tin in the membranes after the sequestration tests was ascertained by µ-ED-XRF mapping on selected samples.

8-Hydroxyquinoline-2-Carboxylic Acid as Possible Molybdophore: A Multi-Technique Approach to Define Its Chemical Speciation, Coordination and Sequestering Ability in Aqueous Solution.

8-hydroxyquinoline-2-carboxylic acid (8-HQA) has been found in high concentrations (0.5-5.0 mmol·dm-3) in the gut of Noctuid larvae (and in a few other lepidopterans), in which it is proposed to act as a siderophore. Since it is known that many natural siderophores are also involved in the uptake and metabolism of other essential elements than iron, this study reports some results on the investigation of 8-HQA interactions with molybdate (MoO42-, i.e., the main molybdenum form in aqueous environments), in order to understand the possible role of this ligand as molybdophore. A multi-technique approach has been adopted, in order to derive a comprehensive set of information necessary to assess the chemical speciation of the 8-HQA/MoO42- system, as well as the coordination behavior and the sequestering ability of 8-HQA towards molybdate. Chemical speciation studies have been performed in KCl(aq) at I = 0.2 mol·dm-3 and T = 298.15 K by ISE-H+ (glass electrode) potentiometric and UV/Vis spectrophotometric titrations. CV (Cyclic Voltammetry), DP-ASV (Differential Pulse-Anodic Stripping Voltammetry), ESI-MS experiments and quantum mechanical calculations have been also performed to derive information about the nature and possible structure of species formed. These results are also compared with those reported for the 8-HQA/Fe3+ system in terms of chemical speciation and sequestering ability of 8-HQA.

RAS inhibition modulates kynurenine levels in a CKD population with and without type 2 diabetes mellitus.

Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus, mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO), and few studies have investigated its potential link with proteinuria. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk, but whether these drugs influence kynurenine levels in humans is unknown. We evaluated serum tryptophan and kynurenine in patients suffering from CKD with or without type 2 diabetes mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Of 72 adult patients enrolled, 55 were receiving RASis, whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography); kynurenine was measured using an enzyme-linked immunosorbent assay kit; IDO activity (%) was calculated with the formula (kynurenine/tryptophan) × 100. Kynurenine levels were significantly lower in the group under RASis compared to the untreated group (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P = 0.0378). In patients not receiving RASis, kynurenine was inversely related to estimated glomerular filtration rate (eGFR) (r = - 0.4862; P = 0.0478) and directly related to both proteinuria (ρ = 0.493; P = 0.0444) and albuminuria (ρ = 0.542; P = 0.0247). IDO activity was higher in patients with history of cardiovascular disease compared to patients with no such history, and it negatively correlated with eGFR (ρ = - 0.554; P = 0.0210) in the same group. These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

Understanding the Solution Behavior of Epinephrine in the Presence of Toxic Cations: A Thermodynamic Investigation in Different Experimental Conditions.

The interactions of epinephrine ((R)-(-)-3,4-dihydroxy-α-(methylaminomethyl)benzyl alcohol; Eph-) with different toxic cations (methylmercury(II): CH3Hg+; dimethyltin(IV): (CH3)2Sn2+; dioxouranium(VI): UO22+) were studied in NaClaq at different ionic strengths and at T = 298.15 K (T = 310.15 K for (CH3)2Sn2+). The enthalpy changes for the protonation of epinephrine and its complex formation with UO22+ were also determined using isoperibolic titration calorimetry: HHL = -39 ± 1 kJ mol-1, HH2L = -67 ± 1 kJ mol-1 (overall reaction), HML = -26 ± 4 kJ mol-1, and HM2L2(OH)2 = 39 ± 2 kJ mol-1. The results were that UO22+ complexation by Eph- was an entropy-driven process. The dependence on the ionic strength of protonation and the complex formation constants was modeled using the extended Debye-Hückel, specific ion interaction theory (SIT), and Pitzer approaches. The sequestering ability of adrenaline toward the investigated cations was evaluated using the calculation of pL0.5 parameters. The sequestering ability trend resulted in the following: UO22+ >> (CH3)2Sn2+ > CH3Hg+. For example, at I = 0.15 mol dm-3 and pH = 7.4 (pH = 9.5 for CH3Hg+), pL0.5 = 7.68, 5.64, and 2.40 for UO22+, (CH3)2Sn2+, and CH3Hg+, respectively. Here, the pH is with respect to ionic strength in terms of sequestration.

Speciation Studies of Bifunctional 3-Hydroxy-4-Pyridinone Ligands in the Presence of Zn2+ at Different Ionic Strengths and Temperatures.

The acid-base properties of two bifunctional 3-hydroxy-4-pyridinone ligands and their chelating capacity towards Zn2+, an essential bio-metal cation, were investigated in NaCl aqueous solutions by potentiometric, UV-Vis spectrophotometric, and 1H NMR spectroscopic titrations, carried out at 0.15 ≤ I/mol -1 ≤ 1.00 and 288.15 ≤ T/K ≤ 310.15. A study at I = 0.15 mol L-1 and T = 298.15 K was also performed for other three Zn2+/Lz- systems, with ligands belonging to the same family of compounds. The processing of experimental data allowed the determination of protonation and stability constants, which showed accordance with the data obtained from the different analytical techniques used, and with those reported in the literature for the same class of compounds. ESI-MS spectrometric measurements provided support for the formation of the different Zn2+/ligand species, while computational molecular simulations allowed information to be gained on the metal-ligand coordination. The dependence on ionic strength and the temperature of equilibrium constants were investigated by means of the extended Debye-Hückel model, the classical specific ion interaction theory, and the van't Hoff equations, respectively.

Exploring various ligand classes for the efficient sequestration of stannous cations in the environment.

Metal pollution, coming from both natural and anthropogenic sources, has become one of the most serious environmental problems. Various strategies have been tested with the aim of removing heavy metals from environment. In this contribution, containing a robust experimental work together with a critical literature analysis, the sequestering ability of a variety of ligands towards Sn2+ cation will be evaluated in the conditions of several natural fluids, i.e. sea water, fresh water, human blood plasma, urine and saliva. 13 structural and 11 thermodynamic descriptors will be selected for a total of thirty-eight molecules belonging to different classes (carboxylic acids, amines, amino acids, phosphonates, polyelectrolytes etc. …). For the filling of those missing data relative to the 11 thermodynamic descriptors, different strategies will be adopted, including simple correlations and Nipals algorithm. The evaluation of the sequestering ability of the ligands is assessed in terms of estimation of pL0.5 (total concentration of ligand required to bind the 50% of metal in solution), an empirical parameter that takes into account all the side reactions in solutions and does not depend on the speciation scheme. Partial least square calculations were performed to model the pL0.5 and to determine its correlation with the abovementioned descriptors. The possibility to design and build up new tailor-made molecules capable of effectively sequester Sn2+ in various conditions is crucial for practical applications in biosphere, hydrosphere and lithosphere.

Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: synthesis, solution equilibrium studies and in vivo evaluation.

This paper reports the results on the study of a set of synthesized bifunctional 3-hydroxy-4-pyridinones chelators as potential aluminium sequestering agents. They were N-functionalized with alkyl-amino, -carboxylic and -(amino-carboxylic) groups, envisaging the improvement of the Al3+ sequestering capacity, in comparison with the marketed chelating drug deferiprone. The main focus of this work was given to the assessment of their binding ability towards Al3+, which was studied by potentiometric and UV-Vis spectrophotometric measurements carried out at T = 298.15 K. The speciation models were characterized by AlpLqHr(3p+r-qz) species with different stoichiometry. Depending on ligand side-chain structures and on their thermodynamic properties, different trends of stability was found. Furthermore, the sequestering ability of the ligands towards Al3+ was investigated by the calculation of pL0.5 values at different experimental conditions. These results clearly indicate that the presence of amino-carboxylic groups in the ligands increases the sequestering ability towards Al3+. The in silico evaluation of pharmacokinetic descriptors indicated no violation to the Lipinski's rule and drug-likeness properties. Furthermore, the in vivo bioassays on a model of metal-overload mice showed for three investigated ligands a higher metal-sequestering capacity than for the chelating drug deferiprone, thus suggesting their potential interest as Al-chelating drug candidates.

Understanding the bioavailability and sequestration of different metal cations in the presence of a biodegradable chelant MGDA in biological fluids and natural waters.

Thermodynamic information about the metal-ligand interaction between Fe3+, Zn2+, Cu2+ and Sn2+, and a biodegradable ligand as MGDA is reported. The speciation scheme was obtained by means of potentiometric measurements and isothermal titration calorimetry (to determine enthalpy changes) in NaCl medium. The formation of the ML and MLOH species was evidenced for all the metal cations, and for Fe3+ also the ML2 and ML(OH)2 were found. The relative stability, for the ML species, follows the order: Sn2+ > Fe3+ > Cu2+ > Zn2+. Stability constants and enthalpy changes were obtained at different ionic strengths, and data were modeled using the Debye-Hückel and SIT approaches to obtain data in a standard state. At infinite dilution, the enthalpy changes are largely negative for Cu2+ (-34.1 kJ mol-1) and Sn2+ (-16.6 kJ mol-1), slightly negative for Fe3+ (-3.3 kJ mol-1) and positive for Zn2+ (8.7 kJ mol-1). In all cases, the entropic contribution to the stability is predominant. The sequestering ability of MGDA was evaluated determining the pL0.5 values in different conditions. Comparing the data reported in this work and literature ones, some empirical relationships were obtained with predictive purpose. For example, using 11 data in the test set we have: log K (M/MGDA) ± 0.1 = 1.13 + 0.84·log K (M/NTA) Case studies were built up in the conditions of seawater, fresh water and urine to study the possible use of MGDA towards the metal cations here studied. Some considerations were also done in the light of the ocean acidification.

Potentiometric, UV and 1H NMR study on the interaction of penicillin derivatives with Zn(II) in aqueous solution.

The interaction of Zn(II) with ampicillin [(2S,5R,6R)-6-([(2R)-2-amino-2-phenylacetyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2- carboxylic acid] and amoxicillin [(2S,5R,6R)-6-{[(2R)-2-amino-2-(4-hydroxyphenyl)-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-24-carboxylic acid] in NaCl aqueous solution at different ionic strengths and at t=25°C was investigated by potentiometric, UV and 1H NMR techniques. Fairly similar speciation models were obtained for the two systems. At I=0.15molL-1, two different sets of measurements, at low and high concentrations, were carried out. For the Zn2+-amoxicillin system, the Zn2L2(OH)2 species was obtained in the set of measurements at high concentration. The spectrophotometric and 1H NMR results thus obtained are fully consistent with the speciation models found from potentiometric investigations, confirming the formation as well as the relative stability of the complex species. The dependence of the stability constants on the ionic strength was modeled by means of the Debye-Hückel and SIT (Specific ion Interaction Theory) approaches, and the parameter that accounts for the variation of the stability constants with the ionic strength and the specific ion interaction parameters were determined for all the ionic species. The sequestering ability of the ligands towards Zn2+ was evaluated by determining the pL0.5 parameter at different ionic strengths. It resulted that the sequestering ability of ampicillin is higher of ~0.5 order of magnitude with respect to amoxicillin.