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This study proposes a direct-protonation mechanism for the internal protonation of the [1.1.1]cryptand N(C2H4OC2H4)3N as an alternative to the nitrogen-inversion mechanism. The [1.1.1]cryptand is one of the thermodynamically strongest and kinetically slowest bases. The apparent rate constant for internal protonation in [1.1.1]cryptands increases with increasing acidity along with a double sigmoid curve that contains a plateau and a maximum value. Nitrogen inversion for internal protonation is a unimolecular process caused by the umbrella inversion of the amine in the externally monoprotonated and diprotonated cryptands that are generated under different acidic conditions. This mechanism does not explain why the former inversion is slower than the latter. By contrast, direct internal protonation is a bimolecular reaction of the cryptand with various proton carriers. In this mechanism, the externally monoprotonated cryptand carries a proton through the opening between two amines inside the unprotonated cryptand under weakly acidic conditions, and the excess hydronium carries a proton inside the externally monoprotonated cryptand under strongly acidic conditions. The slower rate of the former protonation is due to the formation of less of the intermediate between the cryptand and the externally monoprotonated cryptand. This study found a solution to accelerate the internal protonation rate. The use of proton carriers with strong basicity (e.g. ammonia) suppresses the generation of the externally monoprotonated cryptand and allows rapid internal protonation without strong acids. This predicts that the cryptand can separate triton from tritiated water diluted with ammonia water or ammonium salt solutions by isotopic ion exchange. [ABSTRACT FROM AUTHOR]

In this study, protonation constant values and liquid chromatographic behaviors of hydrophobic cyclizine, chlorcyclizine, hydroxyzine, cinnarizine, cetirizine, meclizine, and buclizine in some water‐organic solvent binary mixtures were examined for the first time using classical and green reverse phase liquid chromatography methods. In the isocratic study, the relationship of the retention time and mobile phase pH in water‐organic solvent binary mixtures containing acetonitrile (45, 50, 55, 60, 65%, v/v), methanol (60, 65, 70, 75%, v/v) and ethanol (45, 50, 55, 56, 59, 60, 62, 65%, v/v) were determined at 37 °C. In the study, XBridge C18 and Gemini NX C18 columns suitable for the chemical properties of basic compounds were used. The obtained liquid chromatographic data were analyzed using the linear solvation energy relationship methodology and the SOLVER program. The aqueous protonation constant values of the investigated compounds were calculated using the linear relationship between the protonation constant data calculated in studied binary mixtures and some macroscopic constant values of the solvents used. The greenness of methods developed using three different solvents was evaluated with the Analytical Greenness Metric Approach, the Green Analytical Procedures Index, and the Green Solvent Selection Tool approaches. [ABSTRACT FROM AUTHOR]

The syntheses of two macrocycles containing original imidazothiadiazole heterocycles are presented. The protonation constants of the ligands have been determined by potentiometry and photophysical measurements. The photophysical properties of the corresponding Tb3+ complexes have been analyzed and the sensitization of the Tb3+ by the heterocyclic moiety demonstrated with modest quantum yields. The corresponding Gd3+ complexes are monohydrated and display higher relaxivities than GdDOTA, which could be explained by the larger size of these complexes. The different substitutions on the heterocycle do not affect strongly the protonation constants of the ligand, the quantum yield, water exchange rate or relaxation properties of the system. [ABSTRACT FROM AUTHOR]

In the present study, we have reported the synthesis of a novel thiophene-based dipodal chelator ligand MPT (N1, N3-bis(3-((E)-thiophen-2-yl)methylene)amino)propyl)malonamide). Further, the physio-chemical properties of as-synthesized ligand was analyzed employing state-of-the-art characterization tools such as 1H NMR, 13C NMR, and IR spectroscopy. In order to calculate the protonation constant for the ligand MPT and formation constants for the ligand MPT with Fe2+ metal ion potentiometric and spectrophotometric analysis were carried out. Further, to analyze the coordination behavior of the ligand MPT with Fe2+ metal ion at room temperature in a highly aqueous medium spectrophotometric analysis was carried out. On the other hand, the theoretical studies for the ligand MPT and its complex with Fe2+ ion were performed employing a semi-empirical method and density functional theory. Further, the structure optimization of the ligand MPT was obtained using the PM6 parameter and B3LYP/6-311(d,p) level for ligand and DGDZVP for metal complex calculations respectively. [ABSTRACT FROM AUTHOR]

In this study, an environmentally friendly analysis of an anti-infective/anthelmintic drug thiabendazole was carried out by liquid chromatography method using ethanol solvent that is not harmful to human health and the environment. Protonation constant values of thiabendazole in 15, 20, 25, and 30% (v/v) ethanol-water binary mixtures at 37 oC were obtained by using the green reverse phase liquid chromatography method. The method is based on a model that relates the chromatographic behavior of the determined analytes to pH. The linear relationship between the solvatochromic parameter ENT and the retention values of the compound was determined depending on the variation of the organic solvent in the mobile phase. The relationship between the calculated ssPKa value and the macroscopic properties of ethanol was investigated. Compatibility was observed between the PKa (wwPKa ) values in the aqueous medium determined by this linear approach. By using the wwPKa value calculated for thiabendazole, the ionization percentages were calculated at different pH (1-12) values with the Henderson-Hasselbalch equation. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is a common antioxidant and its biological activity depends on the conformation and protonation state. We used molecular dynamics, Raman and Raman optical activity (ROA) spectroscopies to investigate GSH structural changes in a broad pH range. Factor analysis of the spectra provided protonation constants (2.05, 3.45, 8.62, 9.41) in good agreement with previously published values. Following the analysis, spectra of differently protonated forms were obtained by extrapolation. The complete deprotonation of the thiol group above pH 11 was clearly visible in the spectra; however, many spectral features did not change much with pH. Experimental spectra at various pH values were decomposed into the simulated ones, which allowed us to study the conformer populations and quality of molecular dynamics (MD). According to this combined ROA/MD analysis conformation of the GSH backbone is affected by the pH changes only in a limited way. The combination of ROA with the computations thus has the potential to improve the MD force field and obtain more accurate populations of the conformer species. The methodology can be used for any molecule, but for a more detailed insight better computational techniques are needed in the future. [ABSTRACT FROM AUTHOR]

Co(II) and Ni(II) complexes of two tri-pyridine-based ligands with two hydroxy and two amide exchangeable protons (TDTA) and with six amide exchangeable protons (TMTP) were investigated for application as paraCEST-based magnetic resonance imaging (MRI) contrast agents. The two hydroxy groups present in the TDTA ligand were found to be passive while the amide group was active towards the CEST process. In the case of the Co(II) and Ni(II) complexes of the TMTP ligand, all three coordinated amide groups participated in the exchange process, and excellent CEST signals were observed. The X-ray structure of the four complexes revealed the seven-coordinate geometry of Co(II) complexes and the six-coordinate geometry of Ni(II) complexes. The presence of amide protons and hydroxy protons in the complexes was detected by the NMR method. The stability of the complexes in solution at high temperatures, in different pH ranges and acidic conditions, in the presence of competing cations, and biologically relevant anions was investigated. Potentiometric titrations were carried out to determine the ligand's protonation constants and the complexes' thermodynamic stability constant at 25.0 °C and I = 0.15 mol L-1 NaClO4. ParaCEST studies of [Co(TMTP)]2+ and [Ni(TMTP)]2+ at variable pH and variable pulse power are highlighted. [ABSTRACT FROM AUTHOR]

With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin's low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine–curcumin derivatives is reported. The compounds were fully characterized (1H/13C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells. [ABSTRACT FROM AUTHOR]

Polyarginine (poly-Arg) and arginine-rich peptides have been attracting enormous interest in chemical and cell biology as cell-penetrating peptides capable of direct intracellular penetration. Owing to advances in protein engineering, arginine-rich fragments are often incorporated into multifunctional bioorganic/inorganic core–shell nanoparticles, enabling them the novel unique ability to cross cells and deliver biopharmaceutical cargos. Therefore, understanding the molecular details of the adsorption, packing, and release of poly-Arg onto or from metal nanoparticles is one of the current challenges. In this work, we carry out atomistic molecular dynamics simulations to identify the most favorable location, orientation, and conformation of poly-Arg adsorbed onto a silver nanoparticle (AgNP). Herein, we utilize the constant protonation approach to identify the role of protonation of side chain arginine moieties in the adsorption of poly-Arg to AgNP as a function of pH. The strong adsorption of unprotonated poly-Arg30 onto the quasispherical surface of AgNP with an average diameter of 3.9 nm is primarily governed by multiple interactions of side chain guanidinium (Gdm) moieties, which get stacked and align flat onto the surface. The protonation of the arginine side chain enhances the protein–solvent interactions and promotes the weakening of the protein–nanoparticle binding. The formation of multiple H-bonds between the protonated Arg residues and water molecules favors exposing the charged Gdm+ moieties to the solvent. Protonated poly-Arg30 is found to be partially bound to AgNP due to some weak protein–nanoparticle contacts, maintained by binding of the amide oxygen atoms of the peptide bond. These results suggest that reversible acid–base switching between the arginine protonation states is able to drive the rearrangement of the polyarginine coating around AgNPs, which could be important for a rational design of "intelligent" multifunctional core–shell nanosystems. [ABSTRACT FROM AUTHOR]

In this study, the chromatographic behavior of basic nitrogen in the structure of synthesized compounds containing some benzimidazolium salts (SA‐61, SA‐63, SA‐97) was determined in hydro‐organic mixtures containing polar aprotic acetonitrile and polar protic water. Protonation constant (sspKa) ${{}_{s}{}^{s}{pK}_{a}){\rm \ }}$ values of studied compounds in 40, 45, 50, and 55 % (v/v) acetonitrile‐water binary mixtures at 37 °C were obtained by using the reverse phase liquid chromatography method. The method is based on a model that relates the chromatographic behavior of the determined analytes to pH. The relationship between the calculated sspKa ${{}_{s}{}^{s}{pK}_{a}}$ values and the macroscopic properties of acetonitrile was investigated. The agreement between the pKawwpKa ${\left({}_{w}{}^{w}{pK}_{a}\right)}$ values in the water medium determined by this approach was determined by the t‐test. Using Abraham's solute parameters, the wwpKa ${{}_{w}{}^{w}{pK}_{a}}$ values at 25 °C were also estimated without performing an experimental study. By using the wwpKa ${{}_{w}{}^{w}{pK}_{a}}$ value calculated for each compound, the ionization percentages were calculated at different pH (1–12) values with the Henderson‐Hasselbalch equation. The above‐mentioned compounds were also tested on human lung and liver cancer cell lines using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method for 48 h. One of the compounds (SA‐97) demonstrated antiproliferative effect against both cell lines screened. [ABSTRACT FROM AUTHOR]

A new 15-membered pyridine-based macrocyclic ligand containing one acetate pendant arm (N-carboxymethyl-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene, L1) was synthesized and its Mn(II) complex MnL1 was investigated in the context of MRI contrast agent development. The X-ray molecular structure of MnL1 confirmed a coordination number of seven with an axially compressed pentagonal bipyramidal geometry and one coordination site available for an inner-sphere water molecule. The protonation constants of L1 and the stability constants of Mn(II), Zn(II), Cu(II) and Ca(II) complexes were determined by potentiometry, and revealed higher thermodynamic stabilities in comparison with complexes of 15-pyN3O2, the parent macrocycle without an acetate pendant arm. The MnL1 complex is fully formed at physiological pH 7.4, but it shows fast dissociation kinetics, as followed by relaxometry in the presence of an excess of Zn(II). The short dissociation half-life estimated for physiological pH (ca. 3 minutes) is related to fast spontaneous dissociation of the non-protonated complex. At lower pH values, the proton-assisted dissociation pathway becomes important, while the Zn(II) concentration has no effect on the dissociation rate. 17O NMR and 1H NMRD data indicated the presence of one inner-sphere water molecule with a rather slow exchange (k 298ex = 4.5 × 106 s−1) and provided information about other microscopic parameters governing relaxation. The relaxivity (r1 = 2.45 mM−1 s−1 at 20 MHz, 25 °C) corresponds to typical values for monohydrated Mn(II) chelates. Overall, the acetate pendant arm in L1 has a beneficial effect with respect to 15-pyN3O2 in increasing the thermodynamic stability and kinetic inertness of its Mn(II) complex, but leads to a reduced number of inner-sphere water molecules and thus lower relaxivity. [ABSTRACT FROM AUTHOR]

The protonation constants are one of the most fundamental properties of biological molecules. The determination of the constants of the dipeptide is interesting and necessary for a full understanding of its activities in biological process. In this study, the protonation constants of some aliphatic alanine dipeptides (alanyl-alanine, alanyl-phenylalanine, alanyl-valine, alanyl-leucine, and alanyl-methionine) were studied in water and ethanol–water mixtures (20%ethanol–80%water;40%ethanol–60%water;60%ethanol–40%water, (v/v)) at 25 ± 0.1 °C under nitrogen atmosphere and ionic strength at 0.10 mol L−1 by potentiometry. The constants of the systems were calculated using Best computer program. The effects of the different amino acids bound to the alanine on the acidity of the alanyl dipeptides were investigated. The constants were influenced by changes in solvent composition and their variations were discussed in terms of solvent and structural properties. [ABSTRACT FROM AUTHOR]

A potentiometric investigation has been carried out to disclose the coordination properties of Dacarbazine, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (abbreviated DTIC) with particular transition metal ions (Zn2+, Cu2+, Ni2+ and Co2+). The coordination of DTIC with these metal ions results in several complexes emerging in solution. The aim of this work is to determine the protonation constants of the DTIC and to show the extent of its coordination with (Zn2+, Cu2+, Ni2+ and Co2+), in other words, establish the stability of the complexes formed between the DTIC and these metal ions by the determination of their stability constants. Experimental environments were organized to attain the coordination and measurements in aqueous solutions at 25±0.1 °C and an ionic background of 0.1 mol dm-3 NaCl. The HYPERQUAD computer program was used to determine both the protonation and stability constants for the ligand and metal-ligand complexes respectively. DTIC has five protonation constants that can be obtained under experimental conditions used; 10.54, 20.15, 26.99, 32.02 and 36.01. The results are interpreted in terms of the basicity of the donor atoms and structural composition of the ligand. All the complexes produced in the solution are exhibited in speciation diagrams. [ABSTRACT FROM AUTHOR]

This research work has two sections. In first section, the equilibrium constant for protonation processes of DL-phenylalanine (K1, and K2) were determined in binary mixed solvents of water–methanol, containing 0, 10, 20, 30, 40, 50, 60, 70, and 80 % (v/v) methanol, at T = 298.15 K and constant ionic strength (0.1 mol.dm-3NaCl). The obtained data (K1, and K2) were analyzed using Kamlet, Abboud, and Taft parameters. In second section, for DLphenylalanine in aqueous solution, the values K1, and K2 were determined at T = (298.15, 303.15, 308.15, 313.15, and 318.15) K and constant ionic strength (0.1 mol.dm-3NaCl). Using these K1, and K2, the thermodynamic properties (changes of enthalpy, ΔH, changes of entropy, ΔS, and changes of Gibbs free energy, ΔG) were calculated for DL-phenylalanine in aqueous solution. In both sections, the values of K1, and K2 were determined using the spectrophotometric and potentiometric methods. This research work has two sections. In first section, the equilibrium constant for protonation processes of DL-phenylalanine (K1, and K2) were determined in binary mixed solvents of water–methanol, containing 0, 10, 20, 30, 40, 50, 60, 70, and 80 % (v/v) methanol, at T = 298.15 K and constant ionic strength (0.1 mol.dm-3NaCl). The obtained data (K1, and K2) were analyzed using Kamlet, Abboud, and Taft parameters. In second section, for DLphenylalanine in aqueous solution, the values K1, and K2 were determined at T = (298.15, 303.15, 308.15, 313.15, and 318.15) K and constant ionic strength (0.1 mol.dm-3NaCl). Using these K1, and K2, the thermodynamic properties (changes of enthalpy, ΔH, changes of entropy, ΔS, and changes of Gibbs free energy, ΔG) were calculated for DL-phenylalanine in aqueous solution. In both sections, the values of K1, and K2 were determined using the spectrophotometric and potentiometric methods. [ABSTRACT FROM AUTHOR]

Morin (MRN), an intriguing bioflavonol, has received increasing interest for its antioxidant properties, as have its metal complexes (Mz+-MRN). Understanding their antioxidant behavior is critical to assess their pharmaceutical, nutraceutical potential, and therapeutic impact in the design of advanced antioxidant drugs. To this end, knowing the speciation of different H+-MRN and Mz+-MRN is pivotal to understand and compare their antioxidant ability. In this work, the protonation constant values of MRN under physiological ionic strength and temperature conditions (I = 0.15 mol L−1 and t = 37 °C), determined by UV–vis spectrophotometric titrations, are introduced. Thus, a reliable speciation model on H+-MRN species in aqueous solution is presented, which exhibits five stable forms depending on pH, supplemented by quantum-mechanical calculations useful to determine the proton affinities of each functional group and corresponding deprotonation order. Furthermore, potentiometry and UV–vis spectrophotometry have been exploited to determine the thermodynamic interaction parameters of MRN with different metal cations (Mg2+, Mn2+, Zn2+, Al3+). The antioxidant ability of H+-MRN and Mz+-MRN has been evaluated by the 2,2′-diphenyl-1-benzopyran-4-one (DPPH) method, and the Zn2+-MRN system has proven to afford the most potent antioxidant effect. Ab initio molecular dynamics simulations of Mz+-MRN species at all possible chelation sites and under explicit water solvation allowed for the fine characterization not only of the metal chelation modalities of MRN in explicit water, but also of the role played by the local water environment around the metal cations. Those microscopic patterns reveal to be informative on the different antioxidant capabilities recorded experimentally. Knowing the speciation of morin (L) (a) and its metal (Mz+)-complexes (b) is decisive to understand their antioxidant ability (c) and, thus, therapeutic potential. Our synergistic experimental and computational approach has identified the most potent antioxidant effect for the Zn2+-morin system. [Display omitted] • Determination of the protonation constants and proton affinities of morin. • Determination of the formation constants of metal-morin complexes. • Ab initio molecular dynamics simulations on metal-morin complexes in liquid water. • Radical-scavenging activity of morin and its complexes. • The Zn2+-morin system shows the most potent antioxidant effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • The pK a values were alternatively determined using the eco-friendly green RPLC methods. • The agreement between theoretical and experimental data is given by the LSER approach. • The ionization behavior of the compounds was determined by RPLC methods. • Aqueous p K a values were calculated for hydro-organic and micellar solvent-free mixtures. In this study, the green reverse-phase liquid chromatography (RPLC) method was used in addition to the traditional RPLC method to determine the ionization/protonation constants (pK a) of the guanine derivatives ganciclovir, valacyclovir, and valganciclovir. The determination of these values was carried out in binary acetonitrile–water mixtures (for the traditional RPLC method), ethanol–water binary mixtures (for the green RPLC method), and in aqueous solution of a micelle-forming surfactant (for pure micellar chromatography). The pK a values s s p K a of the compounds were calculated using the linear solvation energy relationship (LSER) method in the studied hydro-organic and micellar solvent-free mixtures. Moreover, the UV–Vis spectrophotometric method was used to compare the s s p K a values of ganciclovir, valaciclovir, and valganciclovir obtained in a acetonitrile–water medium using another method. The pK a values ​​of the examined compounds in water were calculated using the linear relationship between the s s p K a values ​​determined in hydroorganic mixtures and some macroscopic values ​​of acetonitrile and ethanol. Additionally, w w p K a values ​​were determined in the micellar solvent-free mobile phase. Subsequently, the w w p K a values calculated by these direct and indirect methods were compared and the agreement between them was excellent. By using the w w p K a value calculated for each compound, the ionization percentages were calculated at different pH (1–12) values with the Henderson-Hasselbalch equation. The environmental impact of the RPLC methods used in this study was assessed using the green metrics tools GAPI and AGREE. The result of the investigation was that the environmental suitability of the green methods is satisfactory. [ABSTRACT FROM AUTHOR]

[Display omitted] • The thermodynamic parameters of ammonia protonation were determined at high ionic strengths I = 5–9 (NH 4 NO 3) • The sharp decrease in the entropy of ammonia protonation at high values of ionic strength. • The decrease in entropy with increasing I and T approaches the values characteristic of reactions in the gas phase. • Enthalpy–entropy compensation effect of ammonia protonation. Based on pH-metric measurements, the equilibrium constants for ammonia protonation at 298.15 K and ionic strengths I = 5–9, supported by ammonium nitrate, were calculated. Using direct calorimetric measurements, the enthalpies of this process were determined at 288.15, 298.15 and 303.15 K and I = 5–9 and its full thermodynamic parameters were calculated. The sharp increase in exothermicity and decrease in entropy of this process observed at high ionic strengths are explained by decrease in the contribution of desolvation of reagents in the region of deficiency of solvent molecules and the influence of association of ions of background electrolyte. The obtained thermodynamic characteristics of ammonia protonation clearly indicate that a change in solvation state of reaction participants at high ionic strengths changes the nature of this reaction. [ABSTRACT FROM AUTHOR]

Acid-base properties of cyclodextrins (CDs), persubstituted at C-6 by 3-mercaptopropionic acid, sualphadex (Suα-CD), subetadex (Suβ-CD) and sugammadex (Suγ-CD, the antidote of neuromuscular blocking steroids) were studied by 1H NMR-pH titrations. For each CD, the severe overlap in protonation steps prevented the calculation of macroscopic pKa values using the standard data fitting model. Considering the full symmetry of polycarboxylate structures, we reduced the number of unknown NMR parameters in the "Q-fitting" or the novel "equidistant macroscopic" evaluation approaches. These models already provided pKa values, but some of them proved to be physically unrealistic, deceptively suggesting cooperativity in carboxylate protonations. The latter problem could be circumvented by adapting the microscopic site-binding (cluster expansion) model by Borkovec, which applies pairwise interactivity parameters to quantify the mutual basicity-decreasing effect of carboxylate protonations. Surprisingly, only a single averaged interactivity parameter could be calculated reliably besides the carboxylate 'core' microconstant for each CD derivative. The speciation of protonation isomers hence could not be resolved, but the optimized microscopic basicity parameters could be converted to the following sets of macroscopic pKa values: 3.84, 4.35, 4.81, 5.31, 5.78, 6.28 for Suα-CD; 3.82, 4.31, 4.73, 5.18, 5.64, 6.06, 6.54 for Suβ-CD and 3.83, 4.28, 4.65, 5.03, 5.43, 5.81, 6.18, 6.64 for Suγ-CD. The pH-dependent charge of these compounds can now be accurately calculated, in support of designing new analytical methods to exploit their charge-dependent molecular recognition such as in cyclodextrin-aided chiral capillary electrophoresis. [ABSTRACT FROM AUTHOR]

Dissociation constants of 2-furancarboxylic and 2-furylacrylic acids and stability constants of their complexes with Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Tb3+, Ho3+, Er3+, and Yb3+ ions were determined in aqueous ethanol solution (5 : 1 by volume) by pH-potentiometric titration. It was found that the complex formation occurs in the pH range of 3.0–6.5, the stability constants of complex compounds increasing with increasing values of the protonation constant of the ligands. Solid complex compounds with 2-furancarboxylic and 2-furylacrylic acids of the compositions (С5Н3О3)3Ln·nH2O and (С7Н5О3)3Ln·nH2O (n = 2–4), respectively, have been synthesized. According to IR spectra, Ln3+ ions are coordinated to acids bidentately by the carboxyl groups. The range of thermal stability of the complex compounds has been determined by the TG/DTG/DSC methods. Spectral-luminescent properties of the complex compounds of 2-furancarboxylic acid with Eu3+ and Tb3+ ions have been studied. [ABSTRACT FROM AUTHOR]

Stability and structure of complexes between silver (I) and l-methionine (L) deduced from potentiometric and 1H NMR measurements allow to assume the prevailing of several protonated species. The experimental data are compatible with the formation of the following complexes: AgL, AgL2, AgH2L, AgH1L2, AgH2L2, AgH3L2 and AgH4L2. The coordination sites are obtained by 1H NMR spectra, showing that only the bond between the methylthioether sulfur atom and silver (I) is responsible of the complex stability. The system is studied potentiometrically with silver and glass electrodes at 25 °C and 1.00 mol·dm−3 NaClO4 as ionic medium. Amino acids containing sulfur are few and not extensively studied. In particular, l-methionine, even if it is the most important, enantiomer and their complexes with silver (I) present anticarcinogenic properties, is quite not investigated. In the same experimental conditions, l-methionine protonation constants are determined. The 1H NMR data allow one to assume that, in moderately alkaline solution, silver (I) is bond with six membered chelate rings with sulfur and amino nitrogen, while carboxylic groups are not involved. No polynuclear species are present. The high stability of the complex with ratio 1:2 (silver (I)/l-methionine), involving also two hydrogen ions, predominating in a wide range of hydrogen ion concentration suggests to propose a study for the preparation of an electrode to measure the deprotonated l-methionine concentration. [ABSTRACT FROM AUTHOR]

The copper(ii) complex [Cu(H2L1)2(H2O)2] with (2-hydroxyphenyl)phosphonic acid (H3L1) was synthesized. The composition and structure of the complex were determined by X-ray diffraction, elemental analysis, and IR spectroscopy. Quantum chemical calculations of the structure of the H3L1 molecule were performed by the density functional theory (DFT). The protonation constants of H3L1 and the stability constants of its complexes with Cu2+ in water were determined by potentiometric titration. The cytotoxic properties and the accumulation of the [Cu(H2L1)2(H2O)2] complex in human cervical adenocarcinoma HeLa cells were evaluated for the first time, thereby demonstrating that this complex is promising for further biological studies. [ABSTRACT FROM AUTHOR]

Thermodynamics of the protonation of chelidamic acid (4-oxo-1,4-dihydropyridine-2,6-dicarboxylic acid) was studied using potentiometry and calorimetry in 0.1 mol·L− 1 NaClO4 solution at 298 K under standard pressure (p = 0.1 MPa). There are three successive protonation steps. The protonation constants of each step (log10K) are calculated as 10.74 ± 0.01, 3.22 ± 0.02, and 1.63 ± 0.03. The first two protonation steps are exothermic, while the last step is endothermic. All the protonation steps are mainly driven by entropy. The three protonation states (HL2−, H2L− and H3L) were analyzed using the 1 H NMR spectra and crystal structure. The results confirm that the order of successive protonation sites is the pyridine-N (HL2−), pyridinol-OH (H2L−), and carboxylate oxygen atom (H3L). [ABSTRACT FROM AUTHOR]

Metronidazole (MNZ) is an antibiotic widely used for the treatment of various infectious diseases and as an effective pesticide agent for the cultivation of chickens and fish. Its high resistance to purification processes and biological activity has led to the classification of MNZ as an emerging contaminant. A speciation study, aimed to define the acid-base properties of MNZ and its interaction with Ca2+, commonly present in natural waters, is reported. The protonation constants of MNZ, as well as the formation constant value of Ca2+-MNZ species, were obtained by potentiometric titrations in an aqueous solution, using NaCl as background salt at different ionic strengths (0.15, 0.5, 1 mol L−1) and temperature (15, 25 and 37 °C) conditions. The acid-base behavior and the complexation with Ca2+ were also investigated by 1H NMR and UV-Vis titrations, with results in very good agreement with the potentiometric ones. The dependence of the formation constants on the ionic strength and temperature was also determined. The sequestering ability of MNZ towards Ca2+ was defined by the empirical parameter pL0.5 at different pH and temperature values. The speciation of MNZ simulating sea water conditions was calculated. [ABSTRACT FROM AUTHOR]

1H and 13C NMR measurements were carried out to explore anticipated correlations between chemical shifts versus thiolate basicities and redox potentials of cysteamine, homocysteine, penicillamine, and their homodisulfides. All correlations were analyzed and statistically evaluated. The closest correlation was observed for the αCH nuclei concerning 1H and 13C NMR data. Since neither site-specific basicities nor site-specific redox potentials can be directly measured by any means in peptides and proteins containing several thiol and/or disulfide units, these data provide a simple method and predictive power to estimate the aforementioned site-specific physicochemical parameters for analogous sulfur-containing moieties in related biopolymers. [ABSTRACT FROM AUTHOR]

The Zn2+/Ag+-pypo and pysu (pypo = 2-pyridylphosphonate, pysu = 2-pyridylsulfonate) complexes speciation in aqueous solution at I = 0.1 M (KNO3) and 25 °C is described in detail under our experimental synthetic conditions. Protonation and stability constants were determined, and distribution diagrams show protonated and deprotonated complexes formation in the case of Zn2+/Ag+ pypo/pysu binary system, respectively. Moreover, the new complex, {[Zn(H2pypo)2(H2O)2]}n(ClO4)2n·2nH2O, was isolated and its spectral and structural properties were determined. An unusual pypo bidentate coordination mode is described and compared with published ones. [ABSTRACT FROM AUTHOR]

Three new Schiff bases (1a–3a) were synthesized as the starting compounds with the reaction of 5-(2-nitrophenyl)-2-furfural and 2-hydroxy-5-X aniline (X: H, Cl, Me, respectively). Afterwards, the asymmetric diimine ligands (1b–3b) were obtained by a two-step method as follows: nitro group of the starting Schiff bases was reduced into their amino derivative in solution and were reacted with 2-hydroxy-1-naphthaldehyde. Ni(II) complexes of the diimines (1c–3c) were then synthesized. The starting Schiff bases, asymmetric diimines and their complexes were characterized by elemental analyses, IR, LC-MS, TGA, UV-vis, 1H and 13C-NMR, conductivity and magnetic measurements. Square planar geometry was proposed for the complexes. The protonation constants of all the Schiff bases and the stability constants of the complexes were determined potentiometrically in 50% ethanol-water solution (1:1, v/v) at 25 °C and 0.5 M KCl ionic strength. [ABSTRACT FROM AUTHOR]

A series of thiosemicarbazone (TSCN) compounds including ((E)-2-((E)-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (TSC1), (E)-N-ethyl-2-((E)-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (TSC2), and (E)-N-phenyl-2-((E)-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide) (TSC3) were synthesized and fully characterized by diverse spectroscopies, such as X-ray single-crystal, infrared, mass, proton nuclear magnetic resonance, and ultraviolet-visible. Potentiometric measurements, molecular modeling, and biological and antitumor activity screening were studied. The thermodynamics and protonation constants of TSC1 as a representative of the synthesized TSCs were calculated and discussed. The solution speciation of different species was studied with pH. The molecular parameters of the optimized structures were calculated and discussed. The X-ray single crystals of TSC2 and TSC3 were established. Considering the antimicrobial activities and correlating structure-activity relationship of the synthesized compounds, the TSC1 molecule was considered a promising candidate as an antifungal agent against Candida albicans. Thus, it would be extremely helpful in the field of medicinal chemistry, particularly as an antimicrobial agent. The results are of significance to the chemistry of antimicrobial agents. [ABSTRACT FROM AUTHOR]

L-alanine and β-alanine are important biological molecules and have zwitterion structure. In this study, L-alanine and β-alanine's microscopic protonation constants and thermodynamic parameters (enthalpy, entropy, and free energy changes) for the proton--ligand systems of L-alanine methyl ester, β-alanine and β-alanine methyl ester have been determined at 5; 20; 35 °C, in ACN-water (25% ACN and 50% ACN (v/v)) mixtures at constant ionic strength of 0.1000 mol L-1 NaClO4 by potentiometric method. The results shown that, L-alanine and β-alanine's microscopic protonation constants generally tend to decrease with temperature rise and their protonation reactions in ACN-water mixtures generally favor enthalpy-driven. [ABSTRACT FROM AUTHOR]

The imidazole motif is widely encountered in biomolecules, and its biological role, for instance, as a proton relay, is often linked to its ability to form hydrogen bonds with water molecules. The detailed characterization of the hydration pattern of imidazole and of its changes upon protonation is thus of high interest. Here, we combine neutron scattering experiments with force field simulations to provide an unprecedented characterization of the neutral and protonated imidazole solvation at the atomistic level. We show that neutron diffraction data can be used to assess the quality of the imidazole force field in molecular simulations. Simulations using the CHARMM general force field for imidazole are in excellent agreement with the experimental neutron scattering data and we use them to provide an atomic scale interpretation of the neutron scattering patterns. Upon protonation, we clearly identify the signature of the reorganization in the hydration pattern caused by the change from one H-bond donor and one H-bond acceptor group for imidazole to two H-bond donor groups for imidazolium. We also point the limits of the experiment, which are rather insensitive to details of the H-bond geometry at the deprotonated nitrogen of imidazole and further complement the description of the hydration structure with ab initio molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

[Display omitted] • This work deal with study of the structure, keto-enol, spectral and chelation properties of three β-diketones with pyrrole, pyrazole, and pyridine rings. • The formation constants for the sixteen rare earth complexes, dissociation and protonation constants have been determined in an aqueous solution. • Quantum-chemical simulations were performed with using DFT and TD-DFT. Aqueous equilibria of three substituted perfluorinated 1,3-diketones with pyrrole, pyrazole, and pyridine rings have been extensively studied in aqueous solutions. Thermodynamic characteristics of dissociation, protonation, and chelation processes have been investigated by UV–Vis spectroscopy using non-linear regression analysis. Acid-base parameters were discovered in the acidity range from highly acidic media (C(HCl) = 10 M) to alkaline pH region. Dissociation constants (pK a) have been determined in glycine-HCl, phosphate-citrate, and TRIS-HCl buffered media. Protonation activities were studied by the Cox-Yates approach in concentrated hydrochloric acid solutions. First formation constants of ML complex species with trivalent ions of Sc3+, Y3+, La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Dy3+, Tb3+, Ho3+, Er3+, Tm3+, Yb3+, and Lu3+ have been obtained in the pH within 3.0–5.6 (I = 0.5 M, NaCl). True stability constants have been calculated using determined acid-base parameters considering side reactions. The "True" formation constants lie from 3.7 to 6.9 logarithmic units and have a linear relationship with the ionic (Coulomb) potential of metals. DFT and TD-DFT simulations have been performed for the modeling of the data obtained. [ABSTRACT FROM AUTHOR]

The ionization/protonation (pKa) constant, which is a physicochemical parameter that directly affects the pharmacokinetic properties of a drug such as absorption, distribution, metabolism, and excretion (ADME), is currently determined by analytical methods. The effect of pH of the mobile phase on the chromatographic behavior of 1-(2-methylbenzonitrile)-3-benzylbenzimidazolium bromide (2) which its synthesis, fully characterization, and antiproliferative activity properties were studied previously, and the protonation constant (pKa) value were determined in this study. The pKa value of compound 2, benzimidazolium salt, was determined by the reverse-phase liquidchromatographic (RPLC) method at 25 °C. ss pka values were evaluated using retention time (tR) in acetonitrile-water binary mixtures with acetonitrile (ACN) percentages of 40%, 45%, 50% and 55% (v/v). The aqueous pKa wwpkavalue of the synthesized compound was calculated from the sspka value using the macroscopic parameters (dielectric constant and mole fraction) which play an important role in the solvent properties. Obtained wwpka values were found to be 11.290 and 11.241, respectively. In addition, the degree of ionization of the related compound was calculated using the wwpka values. [ABSTRACT FROM AUTHOR]

We report the synthesis of the macrocyclic ligands 3,9-PC2AMH (2,2′-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,9-diyl)diacetamide) and 3,9-PC2AMtBu (2,2′-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,9-diyl)bis(N-tert-butyl)acetamide) which contain a pyclen platform functionalized with acetamide or tert-butylacetamide pendant arms at positions 3 and 9 of the macrocyclic unit. The corresponding Co(II) and Ni(II) complexes were prepared, isolated and characterised as potential paramagnetic chemical exchange saturation transfer (paraCEST) agents. The X-ray structures of the Ni(II) complexes reveal six-coordination of the ligands to the metal ion. The Co(II) complex with 3,9-PC2AMtBu shows a similar six-coordinate structure in the solid state, while the Co(II) complex with 3,9-PC2AMH contains a seven-coordinate metal ion, seventh coordination being completed by the presence of an inner-sphere water molecule. The structure of the Co(II) complexes was investigated using 1H NMR spectroscopy and computational methods. The complexes present a seven-coordinate structure in solution, as demonstrated by the analysis of the paramagnetic shifts using density functional theory. Ligand protonation constants and stability constants of the complexes with 3,9-PC2AMH were determined using potentiometric titrations (I = 0,15 M NaCl). The Co(II) complex was found to be more stable than the Ni(II) analogue (log KCoL = 14.46(5) and log KNiL = 13.15(3)). However, the Ni(II) and Co(II) complexes display similar rate constants characterizing the proton-assisted dissociation mechanism. The presence of highly shifted 1H NMR signals due to the amide protons in slow exchange with bulk water results in sizeable CEST signals, which are observed at +67 and +15 ppm for the Co(II) complex with 3,9-PC2AMH and +42 and +7 ppm for the Ni(II) analogue at 25 °C. [ABSTRACT FROM AUTHOR]

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A new tris-(2-aminoethyl)amine (TREN) capped tripodal Schiff base ligand has been developed by mimicking structural features of a natural siderophore, Bacillibactin, by substituting the catechol units with salicylaldehyde and employing amino acid as a spacer. Synthesis of the ligand N-[2-[bis[2-[[2-[(2-hydroxyphenyl)methylamino]acetyl] amino]ethyl]amino]ethyl]-2-[(2-hydroxyphenyl)methylamino]acetamide(TRENglySAL) includes condensation of salicylaldehyde and amino acid (glycine) followed by an in-situ reduction of the produced Schiff base, followed by further condensation with TREN. The complexation behavior of the ligand with Fe(III) has been investigated by potentiometric and UV-Vis spectrophotometric method at temperature 25±1oC and 0.1 M ionic strength. Seven protonation constants were obtained of the ligand: three each for secondary amine and phenolic protons and one for tertiary nitrogen of capping TREN moiety. The formation constants (log β11n) of different complex species MLH3, MLH2, MLH, ML and MLH-1 are found to be 35.15, 32.09, 27.91, 25.32 and 17.32 respectively. These results indicate that the ligand is an excellent iron-binding chelator. Significant electronic spectral variations during complex formation at higher pH also provide a scope for the ligand to act as an optical pH sensor towards Fe (III) metal ion in biological systems. Structures of the ligand and metal complexes are proposed through experimental findings along with the theoretical semi-empirical PM3 calculation. The theoretical spectroscopic results are found to be comparable with the experimental finding.

Rigid derivatives of the acyclic ligand PDTA4− (H4PDTA = propylenediamine-N,N,N′,N′-tetraacetic acid) were prepared by functionalization of a 1,3-diaminocyclobutyl spacer. The new ligands contain either four acetate groups attached to the central scaffold (H4L1) or incorporate pyridyl (H2L2) or propylamide (H2L3) units replacing two of the carboxylate groups. The ligand protonation constants and the stability constants of their Mn2+ complexes were determined using potentiometric and spectrophotometric titrations. The stability of the [Mn(L1)]2− complex was found to be significantly higher than that of the flexible [Mn(PDTA)]2− derivative (log KMnL = 10.78 and 10.01, respectively). A detailed study of the 1H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles and 17O NMR measurements evidence that the [Mn(L1)]2− and [Mn(L2)] complexes display a hydration equilibrium in solution involving a seven-coordinate species with an inner-sphere water molecule and a six-coordinate species that lacks a coordinated water molecule. As a result the 1H relaxivities of these complexes are somewhat lower than that of [Mn(EDTA)]2− and related systems. The introduction of propylamide groups in [Mn(L3)] shifts the hydration equilibrium to the seven-coordinate species, which results in a 1H relaxivity (r1p = 3.7 mM−1 s−1 at 22 MHz and 25 °C) exceeding that of [Mn(EDTA)]2− (r1p = 3.3 mM−1 s−1 at 22 MHz and 25 °C). The parameters that control the relaxivities in this family of complexes were determined by simultaneous fitting of the experimental 1H NMRD and 17O NMR data (transverse relaxation rates and chemical shifts), with the aid of computational studies performed at the DFT and CASSCF/NEVPT2 levels. These studies provide detailed insight of the parameters that control the efficiency of these relaxation agents at the molecular level. [ABSTRACT FROM AUTHOR]

Conformationally flexible ligands of appropriate size and denticity can wrap to a metal ion with high stability. In this perspective, a new tripodal siderophore‐mimic hexadentate chelator, N‐[3,5‐bis[(1‐hydroxy‐6‐oxo‐pyridine‐2‐carbonyl)amino]cyclohexyl]‐1‐hydroxy‐6‐oxo‐pyridine‐2‐carboxamide, (TACH‐1,2‐HOPO), which contains three 1,2‐hydroxypyridinone units attached to a cyclohexane ring through amide linkage at 1,3 and 5 positions, has been designed and synthesized. The characterization of the ligand was carried out through various techniques like FT‐IR, 1H NMR, 13C NMR, ESI‐MS, and electronic spectroscopy. In an aqueous medium, the solution thermodynamics and photophysical properties of the chelator and its La3+, Gd3+, and Lu3+ complexes were determined experimentally as well as theoretically. The pKa values for the ligand were found to be 8.40, 5.74, and 5.39. Formation of lanthanide complexes of type MLH3, MLH2, MLH, ML, and ML.(H2O)x (x=1,2 and 3) was perceived, and the log βmlh for various partially and fully protonated and hydrated lanthanide complexes are reported. Theoretical calculations by DFT supported the experimental results. The experimentally determined protonation constants gave the same trend of ΔG0 values obtained by DFT; also, the theoretically calculated FT‐IR, 1H, 13C NMR, electronic, and excitation spectral data are in covenant with experimental findings. The bonding behavior between the lanthanide ions and the TACH‐1,2‐HOPO explicated by implication of NBO, Morokuma Ziegler energy decomposition analysis (ETS‐NOCV), propose the Ln−L bonds are less covalent with the trend Lu>Gd>La. [ABSTRACT FROM AUTHOR]

2-Hydroxy-5-methoxyphenylphosphonic acid (H3L1) and the complex [Cu(H2L1)2(H2O)2] were synthesized and characterized by IR spectroscopy, thermogravimetry, and X-ray diffraction analysis. The polyhedron of the copper atom is an axially elongated square bipyramid with oxygen atoms of phenolic and of monodeprotonated phosphonic groups at the base and oxygen atoms of water molecules at the vertices. The protonation constants of the H3L1 acid and the stability constants of its Cu2+ complexes in water were determined by potentiometric titration. The protonation constants of the acid in water are significantly influenced by the intramolecular hydrogen bond and the methoxy group. The H3L1 acid forms complexes CuL‒ and CuL24‒ with Cu2+ in water. [ABSTRACT FROM AUTHOR]

Acid–base, spectral and complexing properties, as well as keto–enol tautomerism of the para-fluorinated derivative of benzoyl-trifluoroacetone have been investigated. Thermodynamic parameters were studied by UV–vis spectroscopy, NMR, and quantum-chemical modeling. Dissociation constants (pKa) were obtained in the citric-phosphate buffer (pH 2.0–7.0) for various ionic strengths. The protonation constant (pKH) was determined in concentrated HCl solution by the non-linear Cox–Yeates method. 1H-,13C-, and 19F-NMR spectra demonstrate the enolization of the studied ligand in a non-polar solvent. Study of aqueous complexation with rare-earth metals (Sc(III), Y(III), La(III), and trivalent lanthanides, except Pm) have been performed in acetate and glycine–HCl buffer media. The formation of mono-complex species and their conditional stability constants were computed through mathematic modeling of spectrophotometric data. Using the obtained acid–base parameters and taking into account the side reactions, sixteen "true" formation constants were determined. The "true" (thermodynamic) stability constants lie in the range of 4.8–12.0 logarithmic units. Thermodynamic and spectral characteristics have been reproduced by DFT simulations using several density functionals. [ABSTRACT FROM AUTHOR]

The excited-state relaxation of retinal protonated Schiff bases (PSBs) is an important test case for biological applications of time-dependent (TD) density-functional theory (DFT). While well-known shortcomings of approximate TD-DFT might seem discouraging for application to PSB relaxation, progress continues to be made in the development of new functionals and of criteria allowing problematic excitations to be identified within the framework of TD-DFT itself. Furthermore, experimental and theoretical ab initio advances have recently lead to a revised understanding of retinal PSB photochemistry, calling for a reappraisal of the performance of TD-DFT in describing this prototypical photoactive system. Here, we re-investigate the performance of functionals in (TD-)DFT calculations in light of these new benchmark results, which we extend to larger PSB models. We focus on the ability of the functionals to describe primarily the early skeletal relaxation of the chromophore and investigate how far along the out-of-plane pathways these functionals are able to describe the subsequent rotation around formal single and double bonds. Conventional global hybrid and range-separated hybrid functionals are investigated as the presence of Hartree-Fock exchange reduces problems with charge-transfer excitations as determined by the Peach-Benfield-Helgaker-Tozer criterion and by comparison with multi-reference perturbation theory results. While we confirm that most functionals cannot render the complex photobehavior of the retinal PSB, do we also observe that LC-BLYP gives the best description of the initial part of the photoreaction. [ABSTRACT FROM AUTHOR]

Hydroxypyridones (HOPOs) are an important class of chelating compounds. They bind strongly to hard metal ions such as Fe(III). Here we present the solid‐phase synthesis of peptides containing 1,2‐HOPO moieties linked through a carboxylic acid placed at position 4 of the ring. A total of four ligands were studied, two bidentate and two hexadentate. The latter were synthesized by both stepwise and convergent strategies. The ligands and their complexes were characterized from the physico‐chemical perspective. The pKa values for all ligands showed their total deprotonation at pH lower than the physiological pH. The formation constant of the Fe(III) complex (log β) ranged from 23.66, corresponding to ligand A, to 27.63, corresponding to ligand C. The pFe3+ at pH=7.4 revealed that ligands B and C had a strong iron affinity (26.91 and 28.58, respectively), thereby making them suitable for further study in therapeutic applications. [ABSTRACT FROM AUTHOR]

Knowledge of the protonation constants of α-amino acids is important, interesting and necessary for complete understanding of the physiochemical behavior of the acids. The acid–base chemistry of zwitterionic compounds such as α-amino acids has been characterized in terms of the macroscopic constants; K1, K2; the microscopic constants; k11, k12, k21, k22 and the tautomeric constant; kz. The compounds may exist in four different microforms; a cation, zwitterion (dipolarion), neutral species and anion. In this study, both to demonstrate whether the predominant species are zwitterion or the neutral form and to predict the change of dipolar form to neutral form ratio in dioxane–water mixtures, the macroscopic protonation constants of the α-amino acids, glycine, DL-alanine, DL-valine, L-leucine, DL-phenylalanine and L-serine, and their esters, were determined potentiometrically using a combined pH electrode system calibrated as the concentration of hydrogen ion and later the microscopic and tautomeric constants of the amino acids were calculated in dioxane–water mixtures (20, 40, and 60% dioxane (v/v)). Titrations were performed at 25.0 ± 0.1 °C and the ionic strength of the medium was maintained at 0.10 mol·dm−3 using sodium chloride. The protonation constants were influenced by changes in solvent composition and the effects of solvent composition on the protonation constants are discussed. Also, the variation of microscopic constants and the ratio of zwitterionic form to neutral form are discussed on the basis of solute–solvent interactions of amino acids in dioxane–water mixtures. [ABSTRACT FROM AUTHOR]

Coumarins comprise a large class of natural-based and synthetic compounds containing a 2Hchromen-2-one ring. Derivatives with hydroxy groups are able to donate a H˙, exhibiting antioxidant activities similar to phenols and quinones. In this work, 3-(pyridin-2-yl)coumarins with and without hydroxy group/s were prepared and their antioxidant ability and inhibition activity towards lipoxygenase enzymes were studied. The studied derivatives have shown potent lipoxygenase activities with IC50 in the μM range, with the radical scavenging properties tuneable according to the number and position of the hydroxy groups. The study of the protonation constants of the 3-(pyridin-2-yl)coumarins, carried out in aqueous solutions, helped in evaluating the absorption and the potential biological properties of the molecules, strongly affected by their protonation state and charge. The antioxidant properties and the way of enzymatic inhibition of the studied 3-(pyridin-2-yl)coumarins are discussed on the basis of the calculated specific thermochemical descriptors and molecular docking. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Five software used to optimize log K from potentiometric data are critically evaluated. • A simulated titration dataset of a hexaprotic acid was processed by five software. • The impact on log K of systematic errors occurring during titrations is evaluated. • The impact on log K of ionic strength variations occurring during titrations is evaluated. • Guidelines for data acquisition and treatment are given. [ABSTRACT FROM AUTHOR]

Metronidazole (MNZ) is an antibiotic widely used for the treatment of various infectious diseases and as an effective pesticide agent for the cultivation of chickens and fish. Its high resistance to purification processes and biological activity has led to the classification of MNZ as an emerging contaminant. A speciation study, aimed to define the acid-base properties of MNZ and its interaction with Ca2+, commonly present in natural waters, is reported. The protonation constants of MNZ, as well as the formation constant value of Ca2+-MNZ species, were obtained by potentiometric titrations in an aqueous solution, using NaCl as background salt at different ionic strengths (0.15, 0.5, 1 mol L−1) and temperature (15, 25 and 37 °C) conditions. The acid-base behavior and the complexation with Ca2+ were also investigated by 1H NMR and UV-Vis titrations, with results in very good agreement with the potentiometric ones. The dependence of the formation constants on the ionic strength and temperature was also determined. The sequestering ability of MNZ towards Ca2+ was defined by the empirical parameter pL0.5 at different pH and temperature values. The speciation of MNZ simulating sea water conditions was calculated.

In the frame of a systematic study on the sequestering ability of natural antioxidants towards metal cations, the complexation of coumarin-3-carboxilic acid (HCCA) with neodymium(III) and dioxouranium(VI) (uranyl, UO22+), and overall stability constants of the resulting complexes, were evaluated from the pH-potentiometric titration data at 37 °C and in an aqueous solution (i.e., 0.16 mol/L NaClO4). The graphic representation of the complex's concentration curves is given by the distribution diagrams, which provide a depiction of all the species present in the solution in the selected pH ranges. The protonation constant of HCCA was also determined to evaluate the competition of the ligand for the metal cations and H+. The ligand-to-metal concentration ratio was varied between 1 and 10, and the hydrogen ion concentration was decreased stepwise until the incipient precipitation of a basic salt of the metal, which occurred at different values depending on the specific metal cation and the ligand to metal ratio. Speciation profiles obtained by potentiometric titrations and supported by UV-Vis data show that a complexation occurs at a ligand-to-Nd(III) and to –UO22+ ratio of 1:1 and 2:1, with different degrees of deprotonation: Nd(OH)(CCA)+, UO2(OH)(CCA), UO2(OH)2(CCA)−, and Nd(OH)(CCA)2, UO2(CCA)2 and (UO2)2(OH)2(CCA)2. [ABSTRACT FROM AUTHOR]

The solubility of folic acid was determined at 25 °C in 1.00 mol dm−3 and in 0.15 mol dm−3 NaCl (physiological solution) spectrophotometrically by measuring the absorbance of saturated solution at different hydrogen ion concentrations. Five protonation constants of folate were determined both from the dependence of the solubility on the hydrogen ion concentration as well as from potentiometric titrations carried out in the presence of solid folic acid and in alkaline solution, in which folate is relatively soluble. Corresponding to the protonation constants, nuclear magnetic resonance and florescence spectra were also obtained at different hydrogen ion concentrations to determine the protonation positions in acid, neutral and alkaline solutions. An approach through circular dichroism was also applied to study the eventual polymerization of folate in alkaline solution. [ABSTRACT FROM AUTHOR]

Stable solutions of gold nanoparticles with an average diameter of 13 nm and CAu = 5×10–4 M were obtained by the reduction of HAuCl4 with an equivalent amount of sodium sulfite at 80–100 °C in the presence of 2% PEG 6000 as a stabilizer: AuCl4– + 3/2 SO32– + 3/2 H2O → Au0 + 3/2 SO42– + 3 H+ + 4 Cl–. The resulting solutions of nanoparticles do not contain additional components capable of complexation, redox, and acid-based interactions. The effect of additives of thiourea, cysteine, thiomalate, and glutathione at various pH on the stability of such solutions to the aggregation has been studied. It was shown that the values of the protonation constants and charges of species of a thiol-containing component are not the only factors determining stability. Using thiomalate (HTM2–) as an example, it was shown also that at pH 7–8, the chemisorption is not followed by the release of H+ ions into the solution. [ABSTRACT FROM AUTHOR]

The protonation constants of streptozocin (K) were determined in binary mixtures of a combination of potentiometric and spectrophotometric methods at 25°C and constant ionic strength (0.1 mol dm–3 sodium perchlorate). The protonation constants were analyzed using the Kamlet, Abboud, and Taft (KAT) parameters. A very good linear relationship between water and methanol containing mixtures (0, 10, 20, 30, 40, 45, 50, 60, 70, and 80 vol %) using correlation of the protonation constants (on the logarithmic scale) was obtained. Dual-parameter correlation of versus π* (dipolarity/polarizability) and α (hydrogen-bond donor acidity) and π* and β (hydrogen-bond acceptor basicity) as well as α (hydrogen-bond donor acidity) and β (hydrogen-bond acceptor basicity) and multi-parameter correlation π* (dipolarity/polarizability), α (hydrogen-bond donor acidity), and β (hydrogen-bond acceptor basicity) also gives suitable results in different aqueous organic solvent mixtures. Finally, the results are discussed in terms of the effect of the solvent on the equilibrium constants. [ABSTRACT FROM AUTHOR]

We have undertaken a thorough investigation on pH-responsive optical and redox switching behaviors of our recently reported trans form of bis-tridentate Ru(II) luminophores, [(H2pbbzim)Ru(tpy-pvp-X)]2+ where X = H, Me, Cl, NO2, and Ph. The complexes possess two benzimidazole protons in their second coordination sphere, which became acidic upon coordinating influence of Ru2+ and could be successively deprotonated with the increase of pH. The effect of pH on photophysical and electrochemical behaviours of the complexes was thoroughly studied. Substantial quenching of emission together with the red-shift of both absorption (color change) and emission bands is noticed for all complexes upon dissociation of NH protons. Absorption vs. pH data were employed for determination of ground-state pKa values, while excited-state pKa (pKa*) values were estimated by employing the Förster cycle based equation. The electronic nature of X induces a small but finite effect on the pKa values and a linear correlation is found by plotting pKavs. Hammett σp parameters of X. Proton-coupled electrochemical behaviours were investigated within the pH range of 1–10. From the E1/2vs. pH plot, acid dissociation constants in different protonation states of the complexes were estimated in both Ru2+ and Ru3+ states. Compared with their protonated forms which exhibit reversible oxidation within 0.91–0.95 V, the oxidation potential of the doubly deprotonated forms shifted remarkably to the cathodic region (0.61–0.66 V). In essence, the present complexes act as potential pH-responsive colorimetric, emission and redox switches. [ABSTRACT FROM AUTHOR]