Stability Constants Research Articles

Synthesis of Cationic Biphen[4, 5]arenes as Biofilm Disruptors

AbstractSince bacteria in biofilms are inherently resistant to antibiotics and biofilm‐associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium‐functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti‐biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram‐positive S. aureus and Gram‐negative E. coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×104 M−1 for CFZ/WBP4 and (4.98±0.49)×103 M−1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E. coli‐infected mice models, providing a novel supramolecular strategy for combating biofilm‐associated infections.

Effect of calcium and trace metals (Cd, Cu, Mn, Ni, Zn) on root iron uptake in relation to chemical properties of the root-excreted ligands.

Interferences of major cations (Ca2+, Mg2+) and trace metals (TM, i.e. Cd2+, Cu2+, Mn2+, Ni2+ and Zn2+) in root Fe uptakewere evaluated. Root Fe uptake was modelled including the reactions of the root exuded ligand with the soil major and trace cations. Fe uptake was simulated with different ligands representing various affinities for the cations, the latter varying in concentration. The stability constant of Fe complexes (KFeL) does not influence Fe uptake, contrarily to the ligand parameters for Fe-hydroxide dissolution. Fe uptake decreases when KCaL or Ca2+ in solution increases. Presence of TM has nearly no influence on Fe uptake when the TM complexes have low stability constants (KML), as in the case of oxalate and citrate complexes. When ligands have high KML, like EDTA, DFO-B or mugineic acid (MA), TM reduces Fe uptake by 51-55%, and much more in the case of TM contamination. Exudation of Fe ligands with low KML has no negative effect on TM uptake, which can increase if the dissociation rate is high, as for Cu complexes. Ligands with high KML (EDTA, DFO-B, MA) greatly reduce TM uptake, only if their hydrated cations can be absorbed. Calcium does not significantly reduce Fe uptake when Ca-complexes have KCaL < 104. Consequently, ligands like oxalate or MA should be efficient in most soils. TM should perturbate Fe uptake mediated by ligands with high KML such as MA, but not oxalate. Plants exuding phytosiderophores should also absorb TM complexes to avoid micronutrient deficiencies.

Optimization of the stability constants of the ternary system of diclofenac/famotidine/β-cyclodextrin by nonlinear least-squares method using theoretical equations

This study aimed to establish a new method for determining the stability constants of drug/β-cyclodextrin (β-CD) complexes when multiple drugs interacting with each other coexist in the solution of complexation. The basic drug famotidine (FAM) and the acidic drug diclofenac (DIC) were used as model drugs, their solubility decreasing owing to their mutual interaction. The dissolution of both FAM and DIC was characterized by AL-type phase solubility diagrams in the presence of the other’s 1:1 complex with β-CD. When the stability constant was calculated from the slope of the phase solubility diagram using the conventional phase solubility diagram method, it was modified in the presence of the other drug. However, by performing optimization calculations that considered the interactions between the drug/β-CD complex and the drug, drug/β-CD complexes, and drugs, we were able to accurately calculate the stability constant of DIC/β-CD and FAM/β-CD complexes even in the presence of FAM and DIC, respectively. The results of the solubility profile indicated that various molecular species, which are attributed to drug-drug and drug/β-CD interactions, interfere with the values of the dissolution rate constants and saturated concentration in the solubility profiles.

Stability Constants of Nickel(II) Complexes with [2.2.2]Cryptand in Aqueous Ethanol Solutions

Stability Constants of Nickel(II) Complexes with [2.2.2]Cryptand in Aqueous Ethanol Solutions

Formulation of inclusion complex of Abiraterone acetate with 2-Hydroxypropyl-Beta-Cyclodextrin: physiochemical characterization, molecular docking and bioavailability evaluation

Abiraterone acetate is a steroid-based anti-androgen molecule approved in the year of 2011 for the therapy of patients suffering from metastatic prostate cancer. However, its physicochemical properties and therapeutic applications are limited by its lipophilic nature and low aqueous solubility. One of the most favourable and well-established methods of cyclodextrins (CDs) assisted inclusion complex was chosen to elevate the solubility-related pitfalls, chemical stability, and associated bioavailability issues of Abiraterone acetate (ABT). Several preparative methods like grinding, kneading, and freeze-drying were employed to fabricate the inclusion complex of ABT/2-hydroxypropyl-β-cyclodextrin (ABT-HP-β-CD). The freeze-drying assisted inclusion complex showed better physicochemical properties, which were investigated using DSC, TGA, PXRD, ATR-FTIR, FESEM, phase solubility, and molecular docking studies. All the above-said characterization studies performed exhibited the emergence of ABT-HP-β-CD. The inclusion complex existed in the stoichiometric ratio of 1:1 with the calculated stability constant (Ks) of 2385 M−1. The solubility of ABT was enhanced to 39-fold after complexation with HP-β-CD. Moreover, a molecular docking study confirmed that ABT was towards the core of HP-β-CD. The in vivo plasma pharmacokinetic studies demonstrated a higher solubility, absorption rate and 2.25-fold improved bioavailability than the free ABT group. This existing study revealed that HP-β-CD can be a notable molecule to fabricate a feasible and cost-effective inclusion complex for elevating the aqueous solubility, stability and in vivo pharmacokinetics of ABT.

Supercapacitor auto analyser: An automated data analysis software for supercapacitor characterization

High-performance supercapacitors (SCs) with high power, energy, and long-life cycles, are essential for innovating wearable and portable electronics as extensively reported in literature. The Web of Science shows more than 23,000 papers published since 2018 with the topic ‘Supercapacitor’, number that keep growing, from 732 papers per year in 2012 to an average of 4651 papers per year since 2018. However, the establishment of performance metrics on the reported values should be achieved to reduce inconsistencies in their real performances. For that reason, we developed the Supercapacitors Auto Analyser (SCAA) program for SCs data analysis to support the community to establish performance metrics for SC devices, with standard terms, equations, and units. The SCAA generates important graphs with the SCs key properties and electrochemical performance such as capacitance, energy, power, coulombic efficiency (CE), equivalent series resistance (ESR), drop potential (Vdrop), cycling stability, and time constant. These results are calculated from common data generated by potentiostat on SCs characterization such as cyclic voltammetry (CV), galvanostatic charge–discharge (GCD), and electrochemical impedance spectroscopy (EIS). With appropriate inputs, the SCAA provides as many as 50 graphs with accurate normalizations by mass, area, or volume in a few minutes. This automation of data analysis is packed in a software made available to the community in the supplementary materials and website www.scaasoftware.com.

Stability Constants of the Binary Vanadium(III) Complexes with the Aminopolycarboxylic Acids: Nitrilodiaceticpropionic, Nitriloaceticdipropionic, and Nitrilotripopionic Acids Studied by Potentiometric Measurements

Stability Constants of the Binary Vanadium(III) Complexes with the Aminopolycarboxylic Acids: Nitrilodiaceticpropionic, Nitriloaceticdipropionic, and Nitrilotripopionic Acids Studied by Potentiometric Measurements

Dual natural-norm a posteriori error estimators for reduced basis approximations to parametrized linear equations

In this work, the concept of dual natural-norm for parametrized linear equations is used to derive residual-based a posteriori error bounds characterized by a [Formula: see text] stability constant. We translate these error bounds into very effective practical a posteriori error estimators for reduced basis approximations and show how they can be efficiently computed following an offline/ online strategy. We prove that our practical dual natural-norm error estimator outperforms the classical inf–sup based error estimators in the self-adjoint case. Our findings are illustrated on anisotropic Helmholtz equations showing resonant behavior. Numerical results suggest that the proposed error estimator is able to successfully catch the correct order of magnitude of the reduced basis approximation error, thus outperforming the classical inf–sup based error estimator even for non-self-adjoint problems.

Finding the Stability Constants for the Colored Compounds Resulting from The Reaction of Five Food Dyes with the Diazotized Para-Nitro Aniline Reagent at their Natural pH

Finding the Stability Constants for the Colored Compounds Resulting from The Reaction of Five Food Dyes with the Diazotized Para-Nitro Aniline Reagent at their Natural pH

4-Mercaptopyridine-Modified Sensor for the Sensitive Electrochemical Detection of Mercury Ions

As a highly toxic heavy metal ion, mercury ion (Hg2+) pollution has caused serious harm to the environment and human health. In this paper, 4-mercaptopyridine (4-MPY) was selected as the sensing material and decorated on the surface of a gold electrode. Trace Hg2+ could be detected by both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) methods. The proposed sensor displayed a wide detection range from 0.01 μg/L to 500 μg/L with a low limit of detection (LOD) of 0.002 μg/L by EIS measurements. Combined with molecular simulations and electrochemical analyses, the chelating mechanism between Hg2+ and 4-MPY was explored. Through the analysis of binding energy (BE) values and stability constants, 4-MPY showed an excellent selectivity for Hg2+. In the presence of Hg2+, the coordination of Hg2+ with the pyridine nitrogen of 4-MPY was generated at the sensing region, which caused a change in the electrochemical activity of the electrode surface. Due to the strong specific binding capability, the proposed sensor featured excellent selectivity and an anti-interference capability. Furthermore, the practicality of the sensor for Hg2+ detection was validated with the samples of tap water and pond water, which demonstrated its potential application for on-site environmental detection.

Vanadium(IV) and vanadium(V) complexation by succinic acid studied by affinity capillary electrophoresis. Simultaneous injection of two analytes in equilibrium studies

The interaction of V(IV) and V(V) with succinic acid was investigated by affinity capillary electrophoresis (ACE) in aqueous acid solutions at pH values 1.5, 2.0 and 2.4, and different ligand concentrations. V(IV) and V(V) form protonated complexes with succinic acid ligand at this pH range. The logarithms of the stability constants, measured at 0.1 mol L-1 (NaClO4/HClO4) ionic strength and 25 °C, are logβ111=7.4 ± 0.2 and logβ122=14.1 ± 0.5 for V(IV), and logβ111=7.3 ± 0.1 for V(V), respectively. The stability constant values, extrapolated to zero ionic strength with the Davies equation, are logβ°111=8.3 ± 0.2 and logβ°122=15.6 ± 0.5 for V(IV) and logβ°111=7.9 ± 0.1 for V(V). The application of ACE to the simultaneous equilibria of V(IV) and V(V) (injection of two analytes) was also attempted. When the results were compared with those obtained when introducing only one analyte in the capillary, using the traditional version of the method, similar stability constants and precision are obtained. The possibility of studying two analytes simultaneously decreases the time needed for the determination of the constants; this feature is especially valuable when working with hazardous materials or when only small quantities of ligand are available.

68Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake.

Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher in vivo stability constant (log KGaL: 38.5), compared to that of Ga-DOTA (log KGaL: 21.3). Such advantage in stability constant suggests that it may be useful for development of alternative FAPI imaging agents. In this study, previously reported [68Ga]Ga-DOTA-FAPI-02 and -04 were converted to the corresponding [68Ga]Ga-HBED-CC-FAPI-02 and -04 derivatives ([68Ga]Ga-4, [68Ga]Ga-5, [68Ga]Ga-6, and [68Ga]Ga-7). It was found that substituting the DOTA chelating group with HBED-CC led to several unique and desirable tumor-targeting properties: (1) robust, fast, and high yield labeling─readily adaptable to a kit formulation; (2) high stabilities in vitro; (3) excellent FAP binding affinities (IC50 ranging between 4 and 7 nM) and improved cell uptake and retention (in HT1080 (FAP+) cells); and (4) excellent selective in vivo tumor uptake in nude mice bearing U87MG tumor. It appeared that Ga(III) chelation with HBED-CC improved the in vivo kinetics favoring higher tumor uptake and retention compared to the corresponding Ga-DOTA complex. Out of the four tested ligands the new [68Ga]Ga-HBED-CC-FAPI dimer, [68Ga]Ga-6, displayed the best tumor localization properties, and further studies are warranted to demonstrate that it is an alternative FAP imaging agent for cancer patients.

Potentiometric Study of the Dissociation and the Metal Complex-formation Competence of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (Dacarbazine).

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 ºC 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.

Green synthesis and characterization of new carbothioamide complexes; cyclic voltammetry and DNA/methyl green assay supported by silico ways versus DNA-polymerase

Three novel complexes with the formulae of [Ni(L)2(H2O)2], [Zn(HL)2(OAc)2] and [UO2(L)2].2H2O were synthesized from simple thiosemicarbazide derivative. The ligand in such bis-form binds either as mononegative bidentate or neutral bindentate mode. The NS donors were the binding centers towards all central atoms inside an octahedral geometry. This geometry was supported by 3A2g→3T1g(P,υ3) and 3A2g→3T1g(F,υ2) transitions that assigned from the bands in UV–Vis spectrum of Ni(II) complex. All structures were optimized under DFT method by using B3LYP/6-31G (d) basis set to estimate valuable quantum data. The charges of N11 (-0.197790) and S14 (-0.067486) donors describe their sufficient nucleophilicity for coordination. Cyclic voltammograms of Ni+2 were studied in presence of the ligand to measure the shift in redox peak that affected by the Ni2+-ligand covalency. The elevated stability constants (βML) and Gibbs free energies (ΔG) suggest the successive building to stable complex in solution. The antimicrobial screening showed an excellent inhibition role from the ligand towards the tested bacteria. Moreover, the genotoxicity of the new compounds was assessed using DNA/ methyl green assay. The ligand exhibited the best decay for the green color results from DNA/ methyl green solution. This in vitro investigation was strengthened by silico ways among that the interaction with DNA-polymerase proteins (1bpy, 5szt and 1zqa). A drug with code number MolPort-002–822-252 has high similarity to our ligand in its binding with DNA beside a low Root Mean Square Deviation value (RMSD = 0.266). Further, the ligand interacted perfectly to DG 6(T) residue in 1bpy protein via H-donor bond and the scoring energy value of the docking pose was excellent (S = −6.1512 kcal/mol). The BOILED-Egg indicates the ability of the ligand to absorb in brain barrier. While, there is no ability for such compound to absorb in gastrointestinal tract. Additionally, the ligand doesn't play as a substrate of P-gp protein, which is considered favorable for protecting tissues and organisms.

Selective Complexation and Separation of Uranium(VI) from Thorium(IV) with New Tetradentate N,O-Hybrid Diamide Ligands: Synthesis, Extraction, Spectroscopy, and Crystallographic Studies.

An unmet challenge in the thorium-uranium fuel cycle is the efficient separation of uranium from thorium. Herein, two new tetradentate N,O-hybrid ligands, N,N'-diethyl-N,N'-di-p-tolyl-2,2'-bipyridine-6,6'-dicarboxamide (Et-Tol-BPDA) and N,N'-diethyl-N,N'-di-p-tolyl-2,2'-bipyrimidine-4,4'-dicarboxamide (Et-Tol-BPymDA), comprising a bipyridine or bipyrimidine core and amide moieties were designed and synthesized for selectively complexing and separating U(VI) from Th(IV). The high U(VI)/Th(IV) extraction selectivity was achieved by Et-Tol-BPDA (SFU/Th = 33 at 3 M HNO3) and Et-Tol-BPymDA (SFU/Th = 73 at 3 M HNO3) in nitric acid solutions. The extraction process for U(VI) or Th(IV) with these two ligands primarily proceeded through the solvation mechanism, as evidenced by slope analyses. Thermodynamic studies for the extraction of U(VI) and Th(IV) revealed a spontaneous process. Results from UV-vis spectroscopic titration and slope analyses demonstrated that U(VI) and Th(IV) each form a 1:1 complex with the two ligands both in the monophasic organic solution and the biphasic extraction system. The stability constants of the 1:1 complexes of Et-Tol-BPDA or Et-Tol-BPymDA with U(VI) were found to be larger than those with Th(IV), which coincide well with the high U(VI)/Th(IV) extraction selectivity. The solid-state structures of Et-Tol-BPDA, Et-Tol-BPymDA, and 1:1 complexes of the two ligands with U(VI) or Th(IV) were analyzed by X-ray diffraction technique. The results from this work implicate the potential of bipyridine- and bipyrimidine-derived diamide ligands for uranium/thorium separation.

Pyrrolidine-Derived Phenanthroline Diamides: An Influence of Fluorine Atoms on the Coordination of Lu(III) and Some Other f-Elements and Their Solvent Extraction.

Three pyrrolidine-derived phenanthroline diamides were studied as ligands for lutetium trinitrate. The structural features of the complexes have been studied using various spectral methods and X-ray. The presence of halogen atoms in the structure of phenanthroline ligands has a significant impact on both the coordination number of lutetium and the number of solvate water molecules in the internal coordination sphere. The stability constants of complexes with La(NO3)3, Nd(NO3)3, Eu(NO3)3, and Lu(NO3)3 were measured to demonstrate higher efficiency of fluorinated ligands. NMR titration was performed for this ligand, and it was found that complexation with lutetium leads to an approximately 13 ppm shift of the corresponding signal in the 19F NMR spectrum. The possibility of formation of a polymeric oxo-complex of this ligand with lutetium nitrate was demonstrated. Experiments on the liquid-liquid extraction of Am(III) and Ln(III) nitrates were carried out to demonstrate advantageous features of chlorinated and fluorinated pyrrolidine diamides.

Computational Lower Bounds of the Maxwell Eigenvalues

A method to compute guaranteed lower bounds to the eigenvalues of the Maxwell system in two or three space dimensions is proposed as a generalization of the method of Liu and Oishi [SIAM J. Numer. Anal., 51 (2013), pp. 1634–1654] for the Laplace operator. The main tool is the computation of an explicit upper bound to the error of the Galerkin projection. The error is split into two parts. One part is controlled by a hypercircle principle and an auxiliary eigenvalue problem. The second part requires a perturbation argument for the right-hand side replaced by a suitable piecewise polynomial. The latter error is controlled through the use of the commuting quasi-interpolation by Falk and Winther and computational bounds on its stability constant. This situation is different from the Laplace operator where such a perturbation is easily controlled through local Poincaré inequalities. The practical viability of the approach is demonstrated in test cases for two and three space dimensions.

Water-Soluble Dicationic Deuteroporphyrin Derivative for Antimicrobial PDT: Singlet Oxygen Generation, Passive Carrier Interaction and Nosocomial Bacterial Strains Photoinactivation

Multidrug resistance of pathogenic microflora is a serious threat to the modern community looking for new approaches to treating superinfections. In this sense, antimicrobial photodynamic therapy (aPDT) is an effective and safe technique considered to be a promising alternative or an important supplement to the traditional clinically applied methods for inactivating antibiotic resistant pathogens. Macroheterocyclic photosensitizers (PS) of three generations are proposed for clinical practice. They are known as the key compounds for PDT able to be localized selectively in microbial cells and to be activated with the red light producing toxic reactive oxygen species (ROS). However, these neutral and anionic PSs possess low affinity towards the outer lipopolysaccharide membrane of Gram-negative bacteria and, consequently, poor ability to kill these pathogens under irradiation. In contrast, cationic PSs containing one or more charged groups, especially those bound to an appropriate carrier, provide efficient inactivation of microorganisms. In this paper, we focus on the study of photophysics, aggregation and photoinduced antimicrobial activity of the water-soluble derivative of deuteroporphyrin-IX, a blood group porphyrin, bearing two cationic trialkylammonium fragments. This potential photosensitizing agent is found to generate singlet oxygen in a non-polar environment and forms stable nano-sized molecular complexes with passive non-ionic carrier Tween 80, localizing in an aqueous surfactant solution as a non-aggregated form in the surface micellar layer. Two different modes of PS/Tween 80 binding characterized by their own stability constants and interaction stoichiometry are observed. Microbiological experiments clearly demonstrate that the increased permeability of the outer bacterial membrane caused by the application of the intramicellar form of the photosensitizer or addition of some potentiation agents leads to pronounced light phototoxicity of the pigment against antibiotic-resistant nosocomial strains of Gram-negative bacterial pathogens.

Solubilities of heavy rare earth sulfates in water (gadolinium to lutetium) and H2SO4 solutions (dysprosium)

Solubilities of rare earth element (REE) sulfates are critical in hydrometallurgical process development for REE extraction, but measurements are notably lacking for heavy REE sulfates. Therefore, solubilities of heavy REE sulfates are measured for binary REE2(SO4)3–H2O systems from 25 to 95 °C for gadolinium through lutetium. Solubility isotherms are also determined for the ternary Dy2(SO4)3–H2SO4–H2O system at 25–95 °C and 0.05–0.5 M H2SO4. Saturating solid phases are identified by X-ray diffraction and thermogravimetric analyses. For all REEs, the octahydrates, REE2(SO4)3•8H2O, are the equilibrium saturating solid phases at 25–95 °C. Solubilities decrease strongly with increasing temperature, indicative of exothermic heats of solution for REE sulfate octahydrates. Within the REE series, solubilities increase markedly (an order of magnitude) from gadolinium through lutetium sulfate. Changes in solubilities are juxtaposed with stability constants for REE sulfate complexes, REESO4+ and REE(SO4)2−. As these species are inner-sphere complexes, water of hydration is released from REE3+ during complex formation which increases water activity. Hence, heavy REEs with larger complex stability constants also display lower solubilities, and vice versa. In sulfuric acid solutions, dysprosium sulfate solubility increases and passes through a maximum with increasing sulfuric acid concentration, as with other REE sulfates. The maximum solubility is postulated to relate to the dissociation constant of bisulfate (HSO4−), which passes through a minimum with increasing sulfuric acid concentration. The formation of bisulfate consumes some free sulfate thereby increasing REE sulfate solubility.

Aquatic Chemistry of Pentavalent Plutonium: Determination of the First Hydrolysis Constant

Up to now, no recommendations have been made by the Organisation for Economic Co-operation and Development Nuclear Energy Agency (OECD-NEA) for the first two hydrolysis constants of pentavalent plutonium. We have determined them, as well as those of Np(V), by means of capillary electrophoresis coupled with inductively coupled plasma mass spectrometry (CE-ICP-MS) in 0.1 M NaCl at 25 °C. The hydrolysis constants of Pu(V) were compared to those of Np(V), for which consensual values have been proposed by the OECD-NEA. The first hydrolysis stability constant for Pu(V) extrapolated at zero ionic strength is, as expected, close to that of Np(V) . We have obtained an excellent agreement with the OECD-NEA value for Np(V) []. Based on eight independent values including our own, we propose a new, robust value for the first hydrolysis of Np(V): . The determination of the second hydrolysis constant for Np(V) by CE-ICP-MS deviates from the value adopted by the OECD-NEA . This discrepancy might be explained by the association of a sodium counter cation with the species . A stability constant is proposed at zero ionic strength and 25 °C for this association: . As a result, it is considered that the second hydrolysis constant for Pu(V), , is also a mixed constant, taking into account both the hydrolysis and the association with a sodium cation.