Calculation of chemical equilibria in CaCl<Subscript>2</Subscript>-heparin-sodium adenosinetriphosphate and MgCl<Subscript>2</Subscript>-heparin-sodium adenosinetriphosphate systems in physiological salines

Chemical equilibria in aqueous solutions of disodium adenosinetriphosphate (Na₂H₂ATP), high-molecular-weight heparin (H₄Hep) and Na₂H₂ATP and in MCl₂-H₄Hep-Na₂H₂ATP-H₂O-NaCl (M = Ca²⁺ or Mg²⁺) solutions in the 0.15 M NaCl background were studied using computer simulation and pH titration at 2.3 ≤ pH ≤ 10.5. Formation constants were determined for two protonated ATP species, three protonated complex species of heparin with ATP of equimolar stoichiometry, and mixed-ligand calcium and magnesium complexes with heparin and adenosinetriphosphate. The formation constants for mixed-ligand calcium(II) complexes with heparin are more than two times those of homoligand calcium complexes with heparin. As a result, the Ca²⁺ ion concentration at 6.8 ≤ pH ≤ 7.4 (the pH range of blood plasma stability) decreases from 40 to 100 wt % depending on the ratio of the initial concentrations of CaCl₂, H₄Hep, and Na₂H₂ATP.     

Mixed-ligand complexation of calcium and magnesium ions with heparin and glycine

Chemical equilibria in dilute aqueous solutions containing high-molecular-weight heparin (Na₄hep) and Glycine (HGly), as well as in solutions of the MCl₂-Na₄hep-HGly-H₂O-NaCl system (M = Ca²⁺, Mg²⁺) against the background of 0.15 M NaCl at 37°C, have been studied by mathematical modeling of chemical equilibria on the basis of pH-metric titration data. The model of equilibria of the Na₄hep-HGly-H₂O-NaCl system for the range 2.30 ≤ pH ≤ 10.50 at different ratios of initial heparin and glycine concentrations showed that, in the pH range of blood plasma stability (pH 6.80–7.40), the protonated H H₃hepGly₃⁴⁻ species prevailed. This was supported by UV absorption spectra of heparin and glycine solutions in the presence of 0.15 M NaCl and absorbance dynamics for solutions containing heparin and glycine. The results of modeling equilibria in the five-component MCl₂-Na₄hep-HGly-H₂O-NaCl systems (M = Ca²⁺, Mg²⁺) showed that the Ca²⁺ and Mg²⁺ ions form with heparin and glycine stable protonated mixed-ligand complexes M H₃hepGly₃²⁻. The formation constants of these species are one order of magnitude higher than the formation constants of the homoligand calcium and magnesium with heparin. In the pH range 6.80–7.40, the calcium content decreases depending on the ratio of the initial concentrations of Na₄hep, HGly, and CaCl₂: at the 1 : 3 : 1 ratio, it decreases by a factor of 5.7 owing to the formation of the predominant species CaH₃hepGly₃²⁻, and at equimolar amounts of the reagents (1 : 1 : 1), the calcium content decreases by a factor of 3.5 (the CaH₃hepGly₃²⁻ concentration is three time as low as the NaCahep⁻ concentration).     

Comparative analysis of complex formation of magnesium and calcium ions with low-molecular-weight and unfractionated heparin

The acid-base and complexing properties of Logiparin (a low-molecular-weight variety (LMH) of heparin (H₄L) with magnesium and calcium ions were studied using mathematical modeling of chemical equilibria in aqueous solutions of Logiparin and its solutions with magnesium and calcium ions and pH titration. The heparin concentration was set equal to the concentration of its disaccharide units. The protonated heparin form HL^3? and the most significant heparin complexes of Mg²⁺ and Ca²⁺ were identified; relevant formation constants were estimated. Comparative analysis of the results is carried out against available data on ion complexing with unfractionated (high-molecular-weight) heparin (HMH). The Logiparin complexes of calcium and magnesium ions are inferior to the HMH complexes in both their formation constants in solution and their effect on the decrease in the equilibrium concentration of free calcium ions, a participant of all blood coagulation processes. This distinction creates prerequisites for the lower blood-coagulating activity of Logiparin compared to that of HMH, which is for the first time confirmed in biological experiments with the in vitro administration of the same concentration of HMH or LMH into the blood plasma of laboratory rats.     

Study on the effects of cefotaxime on intracellular Ca^2＋ in human peripheral lymphocytes by fluoremetry

Characteristic of Fura-2-Ca~(2 )interaction was studied based on the fluorescence technique.The apparent dissociation constants(K_d)of the Fura-2-Ca~(2 )complex were determined at different temperature.The effect of cefotaxime(CEFA)on intracellular Ca~(2 )concentration([Ca~(2 )]_i)was discussed by using a ratiometric fluorescence dye Fura-2 as a probe.The basal[Ca~(2 )]_i in resting humanperipheral lymphocytes was 100 7 nmol/L but after treatment with cefotaxime,the changes of[Ca~(2 )]_i were observed in differentconditions.In the concentration range of 1-30 μmol/L of cefotaxime[Ca~(2 )]_i increased,as a result of releasing intracellular Ca2 stores.Higher concentration of cefotaxime(50-500 μmol/L)stimulated to decrease of[Ca~(2 )]_i.     

Quantitative parameters for the sequestering capacity of polyacrylates towards alkaline earth metal ions

The complex formation constants of polyacrylic (PAA) ligands (1.4≤log N≤2.4, N=number of monomer units) with calcium and magnesium ions were determined in different ionic media at different ionic strengths, 0≤I≤1 mol l⁻¹, at t=25 °C. Experimental pH-metric data in the presence of Ca²⁺ or Mg²⁺ were firstly analysed in terms of apparent protonation constants, log K^H*, using the “three parameter model” proposed by Högfeldt; differences in log K^H*, determined in different ionic media, were interpreted in terms of complex species formation. The only species present in the system M-PAA (M=Ca²⁺ or Mg²⁺) is ML₂: attempts to find species of different stoichiometry were unsuccessful. The stability dependence of this species on ionic strength, on the degree of neutralisation (α) and on PAA molecular weight is discussed using empirical equations. The formation constant, log β₂, is significantly higher for Ca²⁺ than for Mg²⁺: at I=0.1 mol l⁻¹ (NaCl), log N=1.8 and α=0.5, log β₂^Ca=4.43 and log β₂^Mg=4.24. The formation of polyacrylate-alkaline earth metal complexes is discussed in the light of sequestering effects in natural waters.     

Ca2+- and Mg2+-doped covalent organic frameworks exhibiting high hydrogen and acetylene storage

A multiscale theoretical investigation has been performed to study the hydrogen and acetylene storage in Ca²⁺- and Mg²⁺-doped COFs (COF-105 and COF-108). The first-principles calculations show that the Ca²⁺ and Mg²⁺ can be immobilized at the COFs surfaces, and the doped Ca and Mg cations can adsorb five H₂ molecules and three C₂H₂ molecules with ideal binding energies. The Grand Canonical Monte Carlo (GCMC) simulations were carried out to obtain the hydrogen and acetylene uptakes of Ca²⁺- and Mg²⁺-doped COFs at room temperature in the different pressure ranges. Our results demonstrate that, at T = 298 K and p = 100 bar, the total gravimetric uptakes of H₂ in Ca²⁺-doped COF-105 and COF-108 reach 6.78 and 6.54 wt%, respectively, and a higher uptakes of 7.14 and 7.27 wt% have been reached for Mg²⁺-doped COF-105 and COF-108, respectively. At T = 298 K and p = 1 bar, the acetylene uptakes of Ca²⁺-doped COF-105, Ca²⁺-doped COF-108, Mg²⁺-doped COF-105, and Mg²⁺-doped COF-108 are 406.42, 366.24, 308.07, and 319.88 cm³/g (corresponding to the excess uptakes of 358.37, 316.38, 236.7109, and 245.42 cm³/g), respectively. The Ca²⁺-doped COF-105 displays a highest acetylene storage capacity among all materials reported. The Ca²⁺- and Mg²⁺-doped COFs can be very practical hydrogen or acetylene storage medium in the future.     

Solvent influence upon complex formation between benzo-15-crown-5 and Mg2+, Ca2+ and Sr2+ cations in some pure and binary mixed solvents using conductometric method

The complexation reactions between Mg²⁺, Ca²⁺ and Sr²⁺ cations with the macrocyclic ligand, benzo-15-crown-5 (B15C5), in pure acetonitrile, water, methanol and tetrahydrofuran and also in acetonitrile–water (AN–H₂O) and in methanol–tetrahydrofuran (MeOH–THF) binary mixtures have been studied at different temperatures using conductometric method. The conductance data show that the stoichiometry of the complexes in most cases is 1:1 [ML]. But in the case of Ca²⁺ cation a 1:2 [ML₂] complex is formed in pure THF, which shows that the stoichiometry of the complexes may be changed by the nature of the medium. The values of stability constants of complexes, which were obtained from conductometric data, show that the stability of complexes is affected by the nature and composition of the binary mixed solvents and a non-linear behavior was observed for variation of logK_f of the complexes versus the composition of the solvent systems. The results show that the selectivity order of B15C5 for the metal cations in two AN–H₂O binary solutions (mol% AN = 25.71 and 50.94) at 25 °C is: Mg²⁺ > Sr²⁺ > Ca²⁺. The values of thermodynamic parameters (ΔH _c ⁰ , ΔS _c ⁰ ) for formation of complexes were obtained from temperature dependence of stability constants of complexes using the van’t Hoff plots. The results show that the values and also the sign of these parameters are influenced by the nature and also the composition of the binary mixed solvents.     

Solution Equilibria of Ternary Systems Involving Nickel(II) Ion,Picolinic Acid,and the Amino Acids Histidine,Cysteine, Aspartic and Glutamic Acids

Solution equilibria of the ternary systems Ni(II)–picolinic acid (Hpic) and the amino acids aspartic acid (H₂asp), glutamic acid (H₂glu), cysteine (H₂cys) and histidine (Hhis), where the amino acids are denoted as H _i L, have been studied pH-metrically. The formation constants of the resulting mixed ligand complexes have been determined at 25 °C using a ionic strength 1.0 mol·dm^?3 NaCl. In the Ni(II)–Hpic–H₂asp and Ni(II)–Hpic–H₂glu systems, the complexes [Ni(pic)H₂L]⁺, Ni(pic)HL, [Ni(pic)L]^? and [Ni(pic)L(OH)]^2? were detected. In the Ni(II)–Hpic–H₂cys system the complexes [Ni(pic)H₂L]⁺ and [Ni(pic)L]^? are present. Additionally, in the Ni(II)–Hpic–Hhis system the species [Ni(Hpic)HL]²⁺, Ni(pic)L and [Ni(pic)L(OH)]^? were identified. The species distribution diagrams as functions of pH are briefly discussed.     

Calculations of chemical equilibria in Tb(NO3)3-H2O, Tb(NO3)3-heparin-H2O, and CaCl2-Tb(NO3)3-heparin-H2O systems in physiological saline solution

Chemical equilibria in the heterogeneous system Tb(NO₃)₃-H₂O, physiological saline solutions containing terbium nitrate, and unfractionated heparin ((H₄L) Tb(NO₃)₃-H₄L-H₂O-NaCl), and solutions containing calcium chloride, terbium nitrate, and unfractionated heparin (CaCl₂-Tb(NO₃)₃-H₄L-H₂O-NaCl) were studied by mathematical modeling and pH titration. A physicochemical model was designed for two-phase equilibria in the system Tb(NO₃)₃-H₂O, which consists of an aqueous solution and a solid phase of precipitated terbium hydroxide. Formation constants were calculated for terbium hydroxide ions Tb(OH) _i ^(3?i)+ (i = 1, 2, 3) in an aqueous phase, and a correlation was found between the amount of precipitated Tb(OH) ₃ ⁱ and pH. The four-component solution Tb(NO₃)₃-H₄L-H₂O-NaCl in the range 2.3 ≤ pH ≤ 10.4 is homogeneous; as a result of its investigation, the formation constants were ascertained for significant terbium complexes with heparin: TbL, TbHL ₂ ⁴ , and Tb(OH)₂L^3?. Chemical equilibria in the five-component solution CaCl₂-Tb(NO₃)₃-H₄L-H₂O-NaCl were modeled proceeding from the models developed for equilibria in the four-component solution subsystems Tb(NO₃)₃-H₄L-H₂O-NaCl and CaCl₂-H₄L-H₂O-NaCl. The modeling showed that the Tb³⁺ ion is an efficient competitive complex former to the Ca²⁺ ion, which forms complexes with heparin, and decreases tenfold the concentration of the major complex NaCaL at 6.8 ≤ pH ≤ 7.4 (the pH range of blood plasma stability).     

Quantitative Study of the Interaction between ATP and Aromatic Amines in Aqueous Solution

The interaction between adenosine-5??-triphosphate (ATP) and some aromatic amines (L), namely 1,2-phenylenediamine, 2-(2,4-diaminophenoxy)ethanol, 4-N-(2-hydroxyethyl)2,4-diaminoanisole, 4,5-diamino-1-N-(2-hydroxyethyl)pyrazole and 1,3-bis(2,4-diaminophenoxy) propane, was studied at T=298.15 K and I=0.06 mol?L^?1 in NaCl aqueous solution. For all of the investigated systems, the formation of [(ATP)(L)H _i ]^(i?4) species (i=1 to n+2; n=maximum protonation degree of the amine) with high yields (60?C80?%) were found. The ionic strength and temperature dependences of the complex formation constants were studied using semiempirical equations. The sequestering ability of the aromatic amines toward ATP was defined by calculating the pL₅₀ parameter (the total ligand concentration, as ?log₁₀ C _L, able to bind 50?% of ATP). The dependence of pL₅₀ on pH, ionic strength and temperature is reported. Moreover, it was found that the overall formation constants are reasonably linearly dependent on the number of protons in the complex species. Comparison with the stability of the species of analogous systems, such as ATP?Caliphatic amines and pyrophosphate?Caliphatic amines, is reported. For all these systems a fairly linear dependence was found of the formation constants on the basicity of the amines.     

Complexing ability of pesticides and related compounds. Formation and stability in aqueous solution of H+ , Li+, Na+, K+, Mg2+ and Ca2+ phenoxyacetate complexes at different temperatures and ionic strengths

The formation constants of Li⁺, N⁺, K⁺, Mg²⁺ and Ca²⁺ phenoxyacetate complexes were determined potentiometrically using an (H⁺)-glass electrode at 10, 25, 37 and 45°C, at several ionic strengths, in the range 0.04?I? 0.9 mol 1^?1. Simple empirical equations for the dependence of the formation constants on ionic strength were derived. From the temperature coefficients, estimates of ΔH^o and ΔS^o were obtained.     

Study of Complex Formation between N-Phenylaza-15-Crown-5 with Mg2+, Ca2+, Ag+ and Cd2+ Metal Cations in Some Binary Mixed Aqueous and Non-aqueous Solvents using the Conductometric Method

The complexation reactions between Mg²⁺, Ca²⁺, Ag⁺ and Cd²⁺ metal cations with N-phenylaza-15-crown-5 (Ph-N15C5) were studied in acetonitrile (AN)–methanol (MeOH), methanol (MeOH)–water (H₂O) and propanol (PrOH)–water (H₂O) binary mixtures at different temperatures using the conductometric method. The conductance data show that the stochiometry of all of the complexes with Mg²⁺, Ca²⁺, Ag⁺ and Cd²⁺ cations is 1:1 (L:M). The stability of the complexes is sensitive to the solvent composition and a non-linear behaviour was observed for variation of log K _f of the complexes versus the composition of the binary mixed solvents. The selectivity order of Ph-N15C5 for the metal cations in neat MeOH is Ag⁺>Cd²⁺>Ca²⁺>Mg²⁺, but in the case of neat AN is Ca²⁺>Cd²⁺>Mg²⁺>Ag⁺. The values of thermodynamic parameters (ΔH _c ^o , ΔS _c ^o ) for formation of Ph-N15C5–Mg²⁺, Ph-N15C5–Ca²⁺, Ph-N15C5–Ag⁺ and Ph-N15C5–Cd²⁺ complexes were obtained from temperature dependence of stability constants and the results show that the thermodynamics of complexation reactions is affected by the nature and composition of the mixed solvents.     

A Thermodynamic Study Between 18-Crown-6 with Mg2+, Ca2+, Sr2+and Ba2+ Cations in Water–Methanol and Water–Ethanol Binary Mixtures Using The Conductometric Method

The complexation reactions between Mg²⁺, Ca²⁺, Sr²⁺ and Ba²⁺ cations with the macrocyclic ligand, 18-Crown-6 (l8C6) in water–methanol (MeOH) binary systems as well as the complexation reactions between Ca²⁺ and Sr²⁺ cations with 18C6 in water–ethanol (EtOH) binary mixtures have been studied at different temperatures using conductometric method. The conductance data show that the stoichiometry of all the complexes is 1:1. It was found that the stability of 18C6 complexes with Mg²⁺, Ca²⁺, Sr²⁺ and Ba²⁺ cations is sensitive to solvent composition and in all cases, a non-linear behaviour was observed for the variation of log K _f of the complexes versus the composition of the mixed solvents. In some cases, the stability order is changed with changing the composition of the mixed solvents. The selectivity order of 18C6 for the metal cations in pure methanol is: Ba²⁺ > Sr²⁺ > Ca²⁺ > Mg²⁺. The values of thermodynamic parameters (Δ H _c ° and Δ S _c °) for formation of 18C6–Mg²⁺, 18C6–Ca²⁺, 18C6–Sr²⁺ and 18C6–Ba²⁺complexes were obtained from temperature dependence of the stability constants. The obtained results show that the values of (Δ H _c ° and Δ S _c °) for formation of these complexes are quite sensitive to the nature and composition of the mixed solvent, but they do not vary monotonically with the solvent composition.This revised version was published online in July 2005 with a corrected issue number.     

Interaction of Phosphate with Iron(III) in Acidic Medium,Equilibrium and Kinetic Studies

Equilibrium reactions of iron(III) with phosphate were studied spectrophotometrically by UV-Vis in the pH range of ～ 1.0-2.20. The STAR-94 Program was used to determine the number of absorbing species as well as the stoichiometries and formation constants of the complex species. Some literature values were further confirmed and new values of different stoichiometries were obtained. The kinetics and mechanism of Fe(III) with phosphate were studied in acidic medium. The reactive phosphate species were found to be only H₃PO₄ and H₂PO^? ₄ and for Fe(III) were only Fe³⁺, FeOH²⁺ and Fe(OH)⁺ ₂. The observed rate constants were pH as well as T_phos (total concentration of phosphate) dependent, i.e. K_obs,i = A _i + B _i T_phos + C _i T² _phos (at a given pH).     

Palladium complexes with biological ligands—I. Equilibrium and reaction mechanism of Pd(II) complexes with ethionine

An equilibrium study has been carried out on the interaction of ethionine(eth) with Pd(II) in aqueous solution at I = 0.16 M (Cl⁻ and 25°C using potentiometic methods. It has been concluded that five complex species exist in the pH range 2.8–4.8. these species are: PdCl₃(Eth0H⁰₂, PdCl₂(Eth)⁻, PdClOH(Eth)⁻, Pd(Eth)₂(H)²⁺₂ and Pd(Eth)⁰₂. In addition, the stopped-flow method has been used to study the reaction kinetics of Pd(II) with Eth. Three kinetic steps were observed in the pH range 1–5.5. These steps are dependent on the total concentration of Eth (T_Eth) as well as the pH of the medium. The observed pseudo-first order rate constants for the three reaction kinetic steps at constant pH are expressed empirically by kⁱ_obs = m_i + m′_iT_Eth. The parameters m_i and m′_i are pH-dependent. It has been concluded that PdCl²⁻₄ and PdCl₂OH²⁻ species play an important role in the complex formation reactions with Eth. The data were interpreted in terms of the complex species obtained from the equilibrium study. cis-trans substitution reactions have been suggested to account for some kinetic steps.     

H2O2: a Ca2+ or Mg2+‐sensing function in statin passive diffusion

In a previous paper Guillaume's group demonstrated that magnesium (Mg²⁺ concentration range 0.00–2.60 mm ) increased the passive diffusion of statins and thus played a role in their potential toxicity. In order to confirm an increase in this passive diffusion by divalent salt cations, the role of calcium chloride (CaCl₂) on the statin–immobilized artificial membrane (IAM) association was studied. It was demonstrated that calcium supplementation (Ca²⁺ concentration range 0.00–3.25 mm ) increases the statin passive diffusion. In addition, it was shown that the Ca²⁺ effect on the statin–IAM association is higher than that of Mg²⁺. These results show that Ca²⁺ enhances the passive diffusion of drugs into biological membranes and thus their potential toxicity. Also, addition of H₂O₂ to the medium showed a hyperbolic response for the statin passive diffusion and this effect was enhanced for the highest Ca²⁺ or Mg²⁺ concentrations in the medium. H₂O₂ is likely to interact with the polar head groups of the IAM through dipole–dipole interactions. The conformational changes in H₂O₂–IAM result in a higher degree of exposure of hydrophobic areas, thus explaining why the binding of pravastatin, which showed the lowest logP value, was less affected by H₂O₂. This result shows the significant contribution of H₂O₂ and thus the oxidative stress on the statin passive diffusion. Much of the sensitivity derives from the action of Ca²⁺ or Mg²⁺, in turn supported the idea that H₂O₂ may serve a Ca²⁺ or Mg²⁺ sensing function in statin passive diffusion Copyright © 2015 John Wiley & Sons, Ltd.     

Study on the equilibrium in the M(CH3COO)2 ? CH3OH ? H2O system (M  Mg2+, Ca2+, Ba2+) at 25°C

The complex formation and dehydration processes in the system M(CH₃COO)₂? CH₃OH? H₂O have been studied by the methods of the physico-chemical analysis at 25°C; (M = Mg²⁺, Ca²⁺ and Ba²⁺). In the Mg(CH₃COO)₂? CH₃OH? H₂O system. methanol was found to behave as a solvent in which complex formation reactions take place, including also methanolation of Mg²⁺. The fields of equilibrium existence of two new compounds have been found: Mg(CH₃COO)₂ · 3H₂O · CH₃OH and Mg(CH₃COO)₂ · 1,5 CH₃OH. In the systems M(CH₃COO)₂? CH₃OH? H₂O (M = Ca²⁺, Ba²⁺), methanol was found to react as a dehydrating reagent.     

A thermodynamic study of the complexation reaction of beryllium(II), magnesium(II) and calcium(II) with 3-hydroxy-2-naphtoic acid

The thermodynamic stability constants and thermodynamic parameters for the complexation reaction of Be²⁺, Mg²⁺ and Ca²⁺ with 3-hydroxy-2-naphthoic acid have been determined pH metrically in a 70% v/v dioxane-water medium in the presence of potassium nitrate. The study showed the formation 1:1 and 1:2 complexes of Be²⁺, Mg²⁺ and 1:1 complex of Ca²⁺ with 3-hydroxy-2-naphthoic acid. The order of overall stability is Be²⁺>Mg²⁺>Ca²⁺.     

Transport of selenite through a solid supported liquid membrane using sodium diethyldithiocarbamate,Na(DDTC), as carrier between hydrochloric acid solutions

The complex formation between Se(IV) and Na(DDTC) has been exploited to carry out the transport of selenite through an SSLM. The differences of solubilities of the related complex in aqueous and in organic kerosene solution along with the additional effect of H₂O₂ have provided the conditions for such transport.In this case, the study reveals that transport of selenite is effectively facilitated by DDTC. It has been determined that the concentration of HCl in the stripping solution has an optimum value around 2.0 M. The presence of H₂O₂ in the stripping solution is necessary to accomplish the mass transfer of selenite. The role of this reagent has been investigated.The transport has shown to be selective for Se(IV) and Cu²⁺ in the presence of Mg²⁺, Fe³⁺ and Ca²⁺     

Extraction of microamounts of calcium,strontium and barium into nitrobenzene by using hydrogen dicarbollylcobaltate in the presence of dibenzo-18-crown-6

Extraction of microamounts of calcium, strontium and barium by a nitrobenzene solution of hydrogen dicarbollylcobaltate (H⁺B⁻) in the presence of dibenzo-18-crown-6 (DB18C6, L) has been investigated. The equilibrium data have been explained assuming that the complexes HL⁺, ML²⁺, ML₂²⁺ and MHL₂³⁺ (M²⁺ = Ca²⁺, Sr²⁺, Ba²⁺) are extracted into the organic phase. The values of extraction and stability constants of the species in nitrobenzene saturated with water have been determined.