Recent studies have highlighted the biological significance of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) as a metal chelator. In this work, several techniques were applied for the study of the interaction of 8-HQA with vanadium(IV/V) oxidometal ions at a temperature of T = 298.2 K and an ionic strength of I = 0.20 mol dm(-3) in KCl(aq). The redox behavior of the chemical system was defined, and the stability constants of the formed complexes were determined by H+-ion selective electrode potentiometry and UV-vis spectrophotometric titrations, while nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopies and mass spectrometry provided stoichiometric and structural information. The formation of both oxidovanadium(IV) and dioxidovanadium(V) ML complexes with 8-HQA was observed in aqueous solution, with both complexes being particularly stable in acidic conditions. The dioxidovanadium(V) compound is stable even at neutral pH, but dimeric or tetrameric hydrolytic species are predominant under alkaline conditions. In contrast, oxidovanadium(IV) complexes undergo oxidation as the pH increases. Nevertheless, under strictly anaerobic conditions, the complexation of oxidovanadium(IV) by 8-HQA can also occur at pH > 6.0. The nature of the oxidovanadium(IV) and dioxidovanadium(V) ML complexes, representing the major species formed in solution, was further investigated by DFT calculations

Despite its widespread use in pharmaceuticals, cosmetics, and animal nutrition, the environmental implications of nicotinamide remain largely underexplored. Given its high solubility and prevalent presence in wastewaters, nicotinamide has been proposed as a potential environmental marker and emerging contaminant. This study focuses on the evaluation and modeling of medium and ionic strength effects on the acid-base behavior of nicotinamide in aqueous solution. To this aim, the protonation constants of nicotinamide were determined in aqueous media containing various supporting electrolytes (sodium chloride, tetramethylammonium chloride, tetraethylammonium iodide) at T = 298.15 K and different ionic strengths. The medium and ionic strength dependencies were described through well-established thermodynamic models, including the Extended Debye-H & uuml;ckel equation, the Specific ion Interaction Theory, and the Pitzer approach. Additionally, the Setschenow constant of nicotinamide was determined through distribution measurements between 1-octanol and NaCl(aq) solutions. Furthermore, a critical data analysis was performed to assess the reliability of the proposed models and provided interaction parameters. Overall, this work thoroughly describes the acid-base behavior of nicotinamide in different aqueous media and its distribution between aqueous and organic phases, offering fundamental insights for the assessment of its chemical speciation in real systems, which is crucial for future applications in environmental monitoring and remediation strategies.

Copper radioisotopes constitute a true theranostic family, enabling cancer imaging and therapy with chemically identical metal-based radiopharmaceuticals. Developing chelators that provide copper complexes combining high thermodynamic stability, kinetic inertness, and redox robustness remains a key challenge. Herein, we investigated a cyclen-based chelator with aminoethyl side chains (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(2-ethylamine), DO4N) and its TACN analogue (1,4,7-triazacyclononane-1,4,7-tris(2-ethylamine), NO3N). Both chelators rapidly form Cu2+ complexes with high thermodynamic stability comparable to or exceeding that of their carboxylate counterparts (DOTA and NOTA), with DO4N displaying superior stability. Cu2+ complexes adopt an elongated octahedral (DO4N) or distorted square pyramidal (NO3N) geometry in solution. All macrocyclic amines coordinate the metal, while only one or two side chains participate, leaving additional -NH2 groups available for conjugation to biological vectors. Both ligands are also able to stabilize Cu+ upon reduction. Radiolabeling with [Cu-64]Cu2+ demonstrated superior incorporation by both DO4N and NO3N compared to NODAGA under mild conditions, with DO4N achieving the highest labeling efficiency. Both [Cu-64]Cu2+ complexes remained fully intact in human serum over 24 h. In vivo PET imaging with [Cu-64]Cu-DO4N showed sufficient stability for imaging, with renal clearance dominating early biodistribution. The results indicate that these all-nitrogen macrocycles are highly promising scaffolds for next-generation copper-based theranostic radiopharmaceuticals.

Three 2-thiophenecarboxylate (Tio2c) complexes with different central atoms Ag(I), Zn(II) and Ga(III), [Ag(Tio2c)]2 (AgTio2c), {[Zn2(Tio2c)4]2}n (ZnTio2c) and [Ga(Tio2c)3]·H2O (GaTio2c), were synthesized and elemental, spectral and thermal analyses were used for their characterization. The AgTio2c and ZnTio2c single crystal structures confirmed the most common bidentate bridging coordination mode with typical strong argentophilic interactions in the case of AgTio2c complex. Complexes' stability in biological test stock solution were confirmed by 1H NMR spectroscopy. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constants of four complex species, [Zn(Tio2c)]+ (log β110 = 2.06 ± 0.04), [Zn(Tio2c)(OH)] (log β11-1 = -5.0 ± 0.1), [Zn(Tio2c)(OH)2]- (log β11-2 = -12.9 ± 0.4) and [Zn(Tio2c)2(OH)2]2- (log β12-2 = -8.54 ± 0.04) with low abundance in aqueous solution. Theoretical estimation of the complex species in aqueous solution indicates a rather monodentate Tio2c coordination mode in the [Zn(Tio2c)]+ species, while the hydroxido complex species prefer a rather bidentate O,O'-bond of the carboxylate. Antimicrobial and anticancer bioassays clearly confirmed the highest biological activity (toxicity) of the AgTio2c complex. The activity of ZnTio2c was slightly higher (or the same) compared to GaTio2c. The HSA (human serum albumin) binding behaviour of the AgTio2c, ZnTio2c and GaTio2c complexes was investigated using fluorescence spectroscopy and results revealed that the calculated Kb values were in the order of 104 M-1.

Ethylenediaminetetraacetic acid (EDTA) is, so far, the most known and widely used chelating agent. It is well known to form very stable mononuclear complexes with several metal ions in aqueous solution. However, its multidentate nature opens the possibility to simultaneously bind more than one cation forming polynuclear species, rarely observed for EDTA, but common for its analogues like, e.g., DTPA and TTHA. If formed, these species could significantly affect the speciation of both EDTA and metal ions in solution. As such, in this work we report the result of a potentiometric investigation on the chemical speciation of three model systems, namely: Sn2+/Zn2+/EDTA, Sn2+/Fe2+/EDTA and Zn2+/Fe3+/EDTA, at T = 298.15 K and I = 0.15 mol⋅dm‒3 (in NaNO3(aq) or NaClO4(aq)), as a proof of concept that simple and mixed polynuclear species can be also formed by EDTA. In fact, experimental data analysis evidenced the formation of not only the simple Sn2(EDTA), Zn2(EDTA) and [Fe2(EDTA)]2+ species, but also the mixed SnZn(EDTA), SnFe(EDTA) and [ZnFe(EDTA)]+. The formation of latter species was then analyzed in terms of thermodynamic extra stability with respect to simple species, and their influence on the speciation of EDTA and the investigated cations was evaluated. Furthermore, quantum mechanical calculations were also performed for a better insight on the binding mode of EDTA when forming dinuclear species, and to support the evidence concerning the extra stability of mixed ones. We could conclude that, when forming dinuclear species, EDTA behaves as a tridentate ligand, binding cations through two carboxylates and one amino group (MIDA-like mode).

In this work, the coordination properties of 8-hydroxyquinoline-2-carboxylic acid (8-HQA, LH2) toward Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ are discussed. Stability constants for Mn2+, Co2+, and Ni2+/8-HQA systems were determined by ISE-H+ (glass electrode) potentiometry, and those of Cu2+ and Zn2+/8-HQA by ultraviolet-visible (UV-vis) spectrophotometry, in KCl(aq) at I = 0.2 mol dm-3 and T = 298.2 K. For all systems, three species are formed: MLH+, ML, and ML2 2-. 8-HQA proved a good sequestering agent of M2+ over a wide pH range, as also shown by the calculated pL0.5 values. The stability of the formed metal complexes follows the expected Irving-Williams trend, especially concerning the ML2 2- species, with log β120: 12.45 ± 0.01 (Mn2+) < 13.45 (Fe2+) < 15.90 ± 0.04 (Co2+) < 17.17 ± 0.05 (Ni2+) < 20.64 ± 0.03 (Cu2+) > 18.78 ± 0.02 (Zn2+). This trend is inversely correlated to the M-N bond length determined by quantum mechanical calculations. These studies, together with voltammetry and electron paramagnetic resonance spectroscopy, allowed us to derive information about the coordination modes, structure, and nature of the formed species. Results support the formation of ML2 2- complexes over possible ML-(OH)-, with 8-HQA acting as tridentate in all formed species, including the protonated MLH+.

The definition of reliable equilibrium constants is an essential step in speciation studies, as the uncertainty and the consistency of the estimated values concur to define the reliability of the speciation model. It is therefore necessary to evaluate the uncertainty contribution of all factors involved at each step of the data acquisition procedure and to be aware about the consequences of systematic errors on the best-estimated values of experimentally measured equilibrium constants. In this work, a series of computer-generated H+-ion selective electrode titration curves simulating the alkalimetric titration of equimolar mixtures of Zn2+-EDTA in aqueous solutions have been processed by different equilibrium data fitting software. Hence, the uncertainties of the refined stability constants of the Zn2+-EDTA complexes could be derived, while excluding the experimental variability that intrinsically affects all practical experiments. The sensitivity of a given chemical system to different data processing strategies and to possible errors in the input data was evaluated. The systematic errors considered relate to the potential reading, the concentration of the titrant and solution components, and ionic strength variations during titrations. The outcomes highlight how unsuitable decisions taken at the stage of nonlinear least squares fitting of the data can affect the results and underline that the main error contribution is related to the measurement of the glass-electrode potential. The processing of simulated data sets can be a useful tool to alert the researchers to the sensitivity of a given chemical system to different strategies and to possible errors in the input data.

In the human body, bacteria coexist symbiotically under normal conditions. However, radiation can disrupt this balance, causing microbiota dysbiosis. This is particularly observed in cancer patients undergoing radiation therapy. Recent research highlights microbiota-derived metabolites as critical signalling molecules or metabolic precursors, with shown radioprotective effects. Among these, 8-hydroxyquinoline-2-carboxylic acid (8-HQA), a tryptophan metabolite from the kynurenic acid pathway, has been studied for its chelation properties and radioprotective effects. Previous studies indicated the potential of 8-HQA for the complexation of cations, such as Ga3+, to affect the bacterial metabolism. These results lead us to a deeper evaluation of the possible action on 8-HQA and its Ga3+ metal complexes on microbiota exposed to ionizing radiation. Inactivation kinetics studies by ionizing radiation of individual and co-culture bacterial isolates from human microbiota were performed. The preliminary results indicated a radioprotective effect of Ga3+/8-HQA complex on Actinomyces viscosus and a potential preservation effect against gut microbiota species. Co-culture experiment provided a new perspective, revealing a potential symbiotic effect among oral cavity bacteria with increased survival rates under certain conditions compared to individual assays. This study further advances the assessment of the radioresistance of human microbiota bacteria in a tryptophan metabolite and its Ga3+ complexes, contributing to a better understanding of bacterial inactivation patterns in the context of radiotherapy.

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.

Chemical speciation studies, i.e., the study of the distribution of an element or compound among its various species in a system of interest, are of fundamental importance. Chemical speciation investigations can be performed mainly by either the direct measurement of the chemical species by different analytical techniques, or by chemical modeling through equilibrium thermodynamic data, based on the use of stability constants (and other thermodynamic parameters) of the formed species. For these purposes, a series of techniques can be used. As soon as the complexity of the systems of interest increases, the need for more detailed information arises. As such, a multi-technique approach is essential to derive complementary data to define a chemical system. In this tutorial review we analyzed the most common instrumental techniques employed for chemical speciation studies and equilibrium data analysis. The main advantages and disadvantages of potentiometry, voltammetry, coulometry, UV-vis spectrophotometry, spectrofluorimetry, NMR, EPR, ITC, HRMS and quantum mechanical calculations, together with brief mention to other less common techniques, are discussed together with a series of practical examples of their application. The main aim of this tutorial review is to provide a practical guide to all scientists interested in the field.

The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga3+ has been investigated by ISEH+ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl(aq) at I = 0.2 mol dm-3 and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]+, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)2]- and [Ga(8-HQA)2]- species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]- and [Ga(EDTA)(OH)]2- in the above conditions. Due to the relevance of Ga3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm-3 ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization - Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga3+/8-HQA complexes were also performed, identifying [Ga(8-HQA)2]- as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga3+/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga3+/8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga3+/8-HQA complex. Nevertheless, Ga3+/8-HQA complex highlighted potential anti-inflammatory properties.

The acid-base properties of 2-hydroxyquinoline (2-HQ), 4-hydroxyquinoline (4-HQ), 6-hydroxyquinoline (6-HQ), and 8-hydroxyquinoline (8-HQ) were investigated in this work by UV–Vis spectrophotometry, ISE-H+ potentiometry (glass electrode) and Isothermal Titration Calorimetry (ITC) in KCl(aq) at I = 0.2 mol·dm−3, and T = 298.15 K. Potentiometric titrations were also performed at different temperatures (288.15 ≤ T/K ≤ 318.15) to derive, together with direct ITC measurements, the corresponding protonation enthalpy and entropy changes. The analysis of the results obtained using various techniques allowed for a comprehensive characterization of the thermodynamic profile and chemical speciation of the studied hydroxyquinolines. Most importantly, it enabled the evaluation of how the position of the hydroxyl group influences the stability and driving forces involved in the protonation/deprotonation processes of both the quinolinic nitrogen and the hydroxyl groups on the pyridine or benzene ring of the hydroxyquinolines.

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The protonation constants of quinaldic acid (QA), 8-hydroxyquinoline (8-HQ) and 8-hydroxyquinoline-2-carboxylic acid (8-HQA) were determined potentiometrically in KCl(aq) at I = 0.2 mol dm(-3) at different temperatures (288.15 <= T/K <= 318.15). Their temperature dependence was modeled by the van't Hoff equation, which allowed the calculation of other thermodynamic parameters, such as Delta H-0 and Delta S-0. Protonation enthalpy changes were also experimentally determined by isothermal titration calorimetry (ITC) at T = 298.15 K in the same medium and ionic strength conditions. From the obtained results, it emerged that all stepwise protonation reactions for the three ligands are exothermic, with protonation constants decreasing with increasing temperature. Then, thermodynamic protonation parameters obtained by both approaches were critically analyzed and compared, evidencing that protonation enthalpy changes obtained experimentally by direct calorimetry are more accurate than those derived by the van't Hoff equation. However, the latter approach proved useful to evidence possible variability of this thermodynamic parameter with temperature, thus allowing the eventual calculation of the corresponding Delta C-P. Furthermore, on the basis of both the analysis of the obtained parameters and the results of detailed 1D and 2D H-1 NMR studies, it was possible to unequivocally determine the protonation sequence of the different functional groups of 8-HQA (as well as QA and 8-HQ): from basic to acidic pH, the first group to undergo protonation is the phenolate, followed by the quinolinic nitrogen and, finally, by the carboxylate.

A new, open-source, practical, modern and multi-platform Python application for concentrations calculation (PyES - Python Equilibrium Species) was developed by re-writing and implementing the ES4, a freeware computer program originally written using the BASIC programming language. Currently PyES has two working modes, i.e., titration simulation and species distribution, and it can handle both precipitation and solution equilibria. Noteworthy, PyES is actually the only open-source software able to perform calculations at variable ionic strength, taking into account the dependence of the stability constants on it, and to take into account the error propagation to estimate the uncertainties in the calculated concentrations using those of the formation constants, solubility products and components concentrations. Various tests were performed to verify the reliability of PyES with very satisfying results. Moreover, PyES is user friendly and compatible with existing operative systems. The data analysis results can be visualized in a graphical presentation and can be easily exported as .xlsx or .csv files. PyES and the corresponding source code are available for download at htt ps://github.com/Kastakin/PyES.

Caffeic (CFA) and p-coumaric (p-CA) acids are biologically active compounds commonly found in plants and food of plant origin. Metal complexes of these acids exhibit diverse bioactivity, sometimes even higher than the free ligands. Lanthanide (Ln) complexes with organic ligands also attract the attention of researchers, due to their potential application as novel potential biologically active agents. The aim of the present study was the evaluation of the interactions of CFA and p-CA with representative lanthanides (Ln3+ = Eu3+, Gd3+, and Dy3+) in aqueous solution. Potentiometric, spectrophotometric, and 1H NMR techniques were used to study the acid-base behavior of CFA and p-CA, as well as their complexing ability towards Ln3+ cations, over a wide range of pH values (2 <= pH <= 8), in KCl(aq) at I = 0.2 mol dm-3 and T = 298.15 +/- 0.1 K. The evaluation of the sequestering ability of both ligands towards the studied lanthanides, by means of pM and pL0.5 parameters, show that CFA is a better chelating agent.

Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2-carboxylic acid, were synthesized and their composition was confirmed using elemental, spectral, thermal and structural ana-lyses. The {[Ag(Py2c)1}n (AgPy2c, Py2c = pyrrole-2-carboxylate) and {[Ag(Fu2c)1}n (AgFu2c, Fu2c = furan-2-carboxylate) solubility and stability in biological test stock solution were confirmed by 1H NMR spectroscopy. The X-ray analysis has enabled us to determine typical argentophilic interactions and bridging carboxylate co-ordination mode of both ligands. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constant of only one species, i.e., the ML (M = Ag+, L = Fu2c ), log & beta;ML = 0.59 & PLUSMN; 0.04. Anti-microbial and anticancer tests were performed against selected microorganisms and cell lines with new silver(I) complexes and compared with AgSD (silver(I) sulfadiazine) and cisplatin. From their microbial toxicity point of view, selectivity was determined against lactobacilli (AgPy2c is 8x more effective against S. aureus and E. coli and AgFu2c is 8x more effective against E. coli and 4x against S. aureus). AgFu2c significant anticancer activity was determined against Jurkat cell lines (IC50 = 8.00 & mu;M) and was similar to cisPt (IC50 = 6.3 & mu;M) similarly to its selectivity (SI (AgFu2c) = 7.3, SI (cisPt) = 6.4, SI = selectivity index). In addition, cell cycle arrest was observed already in the Sub-G0 phase during a flow cytometry experiment. To evaluate the AgPy2c and AgFu2c bioavailability we also discuss their Lipinski's Rule of Five.

Rare earth elements (REEs) have been increasingly exploited for crucial new technologies, and their massive use in the past decades has significantly increased their environmental concentrations. In this article, we have tried to answer the question as to whether or not the wide use of REEs, including nanoparticles, in agriculture and medicine may pose a health risk to the population through diet. For this reason, information on their biological role and potential toxicity to living organisms has been summarised. The fate of REEs in the aquatic and terrestrial environment, such as surface water, soil, soil-plant systems and animals, was described. Particular emphasis was placed on their uptake by plants and animals, translocation between species and thus their entrance into the human food chain. For a better understanding of REEs bioavailability and toxicity, their physicochemical properties, such as e.g. solubility, oxidation state, chemical form, and coordination with ligands are discussed. Data on the estimated daily intake and the presence of REEs in the human body were also compiled. In our concluding remarks we identified gaps in knowledge about the impact of REEs on the population through diet and predicted future research needs in this area.

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.