Determination Of Protonation Constants Research Articles

Determination of Protonation Constants of Viral Inhibitor, Aurintricarboxylic Acid in SDS and CTAB Micellar Media: A Potentiometric Study

Protonation constants of a viral inhibitor, aurintricarboxylic acid were determined using potentiometric method of data acquisition followed by chemometric modelling methods of analysis in the presence of two different kinds of micellar media, CTAB, a cationic micelle and SDS, an anionic micelle. MINIQUAD75 program was used for the determination of the plausible species and their corresponding formation constants at 303 ± 0.1 K and 0.01 M ionic strength. Five formation constants were identified corresponding to five ionizable hydrogens. Species concentration distribution diagrams were generated using Origin software. Best-fit chemical models were selected on the basis of statistical parameters like standard deviation (SD), U (sum of the squares of the residuals in mass balance equations) and chi-square test. It was found that the formation constants are lower in CTAB micellar medium while there is no significant change in the presence of SDS compared to aqueous medium.

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants.

Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.

NMR-Based Determination of pH, Free of Electrodes and Reference Compounds.

A novel method was elaborated, and a set of 1H NMR-pH indicator molecules was selected to develop an NMR-based pH determination method, which does not need any glass or other electrodes or any separate reference compound, being thus devoid of the usual acid and base errors of the glass and combined electrodes. The method utilizes organic compounds of accurately known basicity and two or more carbon-bound protons, whose chemical shifts respond differently to pH changes. Accurate determination of protonation constants in pH extrema was achieved by the method of relative basicities using compounds of sequentially incremented protonation constants. The entire pH scale can be covered by six indicator molecules. The method was developed for two ionic strengths, 1.00 and 0.15 M.

Solution and solid-state studies of a new supramolecular proton transfer salt and its VO2 complex constructed with chelidamic acid and 3,4-diaminopyridine

The proton transfer compound (Hdap)(chelH)·2H2O (1) and its related anionic complex (Hdap) [VO2(chel)] (2), where chelH2 = 4-hydroxypyridine-2,6-dicarboxylic acid (chelidamic acid) and dap = 3,4-diaminopyridine, were synthesized and characterized by elemental analysis, spectroscopy (IR, UV–Vis), thermal (TG/DTG) analysis and single-crystal X-ray diffraction. Compound 1 resulted from proton transfer between chelH2 and dap in aqueous solution. In 1, two carboxylic acids of chelH2 were deprotonated and the protons transferred to the nitrogen atoms of one chelidamate anion and one dap moiety. Compound 2 resulted from complexation of 1 and vanadyl sulfate. In the crystal structure of 2, the metal ion is five coordinated by one tridentate ligand (chel)2− and two O2− anions, with (Hdap)+ as a counter cation. In both structures, a complicated hydrogen-bonding network accompanied with π–π, C–O···π and C–H···π stacking interactions leads to formation of a 3D supramolecular network. In the following, solution studies have been performed by means of pH potentiometric titrations method as a power technique. This method was used for determination of protonation constants of chelH2 and dap in their probable protonated forms and for calculation of equilibrium constants for the chelH2–dap proton transfer system and the stoichiometry and stability constants of binary and ternary complexes of this system with VO2+ ion in aqueous solution. The stoichiometries of the most complex species in solution were compared with the corresponding crystalline complexes in the solid state.

15]aneN4S: Synthesis, Thermodynamic Studies and Potential Applications in Chelation Therapy

The purpose of this work was to synthesize and characterize the thiatetraaza macrocycle 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S). Its acid-base behaviour was studied by potentiometry at 25 °C and ionic strength 0.10 M in KNO3. The protonation sequence of this ligand was investigated by 1H-NMR titration that also allowed the determination of protonation constants in D2O. Binding studies of [15]aneN4S with Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ metal ions were further performed under the same experimental conditions. The results demonstrated that this compound has a higher selectivity and thermodynamic stability for Hg2+ and Cu2+, followed by Ni2+. The UV-visible-near IR spectroscopies and magnetic moment data for the Co(II) and Ni(II) complexes indicated a tetragonal distorted coordination geometry for both metal centres. The value of magnetic moment and the X-band EPR spectra of the Cu(II) complex are consistent with a distorted square pyramidal geometry.

A Simple Method for the Consecutive Determination of Protonation Constants through Evaluation of Formation Curves

A simple method is presented for the consecutive determination of protonation constants of polyprotic acids based on their formation curves. The procedure is based on generally known equations that describe dissociation equilibria. It has been demonstrated through simulation that the values obtained through the proposed method are sufficiently consistent with the actual values. In contrast with the universally known and applied Bjerrum's method, no differences in the accuracy of determination of subsequent protonation constant values are observed. The proposed method requires the value of one of the protonation constants (e.g., of the first one, K1) of the polyprotic acid. An iterative method is proposed for finding the value, starting from approximate values determined from the environment of point n = 0.5(n-average degree of protonation). Apart from high accuracy, the proposed method also has didactic advantages because it illustrates the problem of multiple acid equilibria in a visual (almost graphic) manner. The proposed method may also provide initial constant values for numerical methods of nonlinear approximation of the formation curve.

Microwave assisted synthesize of new some benzimidazole derivatives and determination of protonation constant of these compounds in non-aqueous media

A series of 2-substituted benzimidazole derivatives have been synthesized via microwave mediated process. Different benzimidazole derivatives were titrated with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, N , N -dimethylformamide,tert-butyl alcohol and acetonitrile), using potentiometric method. The half neutralization potential values and the corresponding pKa values were determined for all cases.

Diprotonation process of meso-tetraphenylporphyrin derivatives designed for Photodynamic Therapy of cancers: From Multivariate Curve Resolution to predictive QSPR modeling

Tetrapyrrole rings possess four nitrogen atoms, two of which act as Bröndsted bases in acidic media. The two protonation steps occur on a close pH range, particularly in the case of meso-tetraphenylporphyrin (TPP) derivatives. If the cause of this phenomenon is well known – a protonation-induced distortion of the porphyrin ring – data on stepwise protonation constants and on electronic absorption spectra of monoprotonated TPPs are sparse. A multivariate approach has been systematically applied to a series of glycoconjugated and hydroxylated TPPs, potential anticancer drugs usable in Photodynamic Therapy. The dual purpose was determination of protonation constants and linking substitution with basicity. Hard-modeling version of MCR-ALS (Multivariate Curve Resolution Alternating Least Squares) has given access to spectra and distribution profile of pure components. Spectra of monoprotonated species (H 3TPP +) in solution resemble those of diprotonated species (H 4TPP 2+), mainly differing by a slight blue-shift of bands. Overlap of H 3TPP + and H 4TPP 2+ spectra reinforces the difficulty to evidence an intermediate form only present in low relative abundance. Depending on macrocycle substitution, p K values ranged from 3.5 ± 0.1 to 5.1 ± 0.1 for the first protonation and from 3.2 ± 0.2 to 4.9 ± 0.1 for the second one. Inner nitrogens’ basicity is affected by position, number and nature of peripheral substituents depending on their electrodonating character. p K values have been used to establish a predictive Multiple Linear Regression (MLR) model, relying on atom-type electrotopological indices. This model accurately describes our results and should be applied to new TPP derivatives in a drug-design perspective.

Determination of protonation constants for 2-hydroxy-1-(2-hydroxy-4-sulpho-1-naphthylazo)-3-napthoic acid

Chemical speciation modelling in combination with potentiometric titration method was used to determine the protonation constants for 2-hydroxy-1-(2-hydroxy-4-sulpho-1-naphthylazo)-3-naphthoic acid, the Patton and Reeder's reagent, at 25° C in three ionic strengths of 0.1 mol dm-3, 0.01 mol dm-3 and 0.001 mol dm-3 NaNO3. Potentiometric titrations were performed and pH, titrant volume, temperature and free and total proton concentrations at each titration point were measured. Constants were determined for three of the four protonated sites and the forth one being a very low value as this site is always in the ionic form and is readily ionized in aqueous solutions.Keywords: Patton and Reeder; Protonation constants; Potentiometric titrations; Chemical speciation modelling DOI: 10.4038/josuk.v3i0.2737J. Sci. Univ. Kelaniya 3 (2007) : 47-52

Two macrocyclic pentaaza compounds containing pyridine evaluated as novel chelating agents in copper(II) and nickel(II) overload

Two pentaaza macrocycles containing pyridine in the backbone, namely 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene ([15]pyN 5), and 3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),15,17-triene ([16]pyN 5), were synthesized in good yields. The acid–base behaviour of these compounds was studied by potentiometry at 298.2 K in aqueous solution and ionic strength 0.10 M in KNO 3. The protonation sequence of [15]pyN 5 was investigated by 1H NMR titration that also allowed the determination of protonation constants in D 2O. Binding studies of the two ligands with Ca 2+, Ni 2+, Cu 2+, Zn 2+, Cd 2+, and Pb 2+ metal ions were performed under the same experimental conditions. The results showed that all the complexes formed with the 15-membered ligand, particularly those of Cu 2+ and especially Ni 2+, are thermodynamically more stable than with the larger macrocycle. Cyclic voltammetric data showed that the copper(II) complexes of the two macrocycles exhibited analogous behaviour, with a single quasi-reversible one-electron transfer reduction process assigned to the Cu(II)/Cu(I) couple. The UV–visible-near IR spectroscopic and magnetic moment data of the nickel(II) complexes in solution indicated a tetragonal distorted coordination geometry for the metal centre. X-band EPR spectra of the copper(II) complexes are consistent with distorted square pyramidal geometries. The crystal structure of [Cu([15]pyN 5)] 2+ determined by X-ray diffraction showed the copper(II) centre coordinated to all five macrocyclic nitrogen donors in a distorted square pyramidal environment.

Determination of Protonation Constants and Stability Constants of Lanthanides with Derivative of H4DOTA Complexes by the UV-VIS Spectrophotometry and Potentiometry

Methods of static potentiometry and UV-VIS spectrophotometry were applied for the determination of protonation constants of (10-[4-aminobenzyl(hydroxyl)phosphonylmethyl]-1,4,7,10-tetraazacyclo-1,4,7-triacetic acid) (DOTA(NH2)) and stability constants of holmium and yttrium complexes with DOTA(NH2). The DOTA(NH2) protonation constants of [HA] (log 1 = 12.7); [H2A] (log 2 = 21.4) and [H3A] (log 3 = 27.9) were experimentally determined by the static potentiometry. The stability constants of Ho-DOTA(NH2) (log KHo DOTA(NH2) = 18.0) and Y-DOTA(NH2) (log KY-DOTA(NH2) = 17.8) complexes were determined by UV-VIS spectrophotometry using the competitive reaction of the DOTA(NH2) – metal complexes with Arsenazo III.

Calcium−Phosphonate Interactions: Solution Behavior and Ca2+ Binding by 2-Hydroxyethylimino-bis(methylenephosphonate) Studied by Multinuclear NMR Spectroscopy

The tetra-acid 2-hydroxyethylimino-bis(methylenephosphonic acid) (HEIBPH, 1) and its ring condensation product, the triacid 2-hydroxy-2-oxo-4-phosphonemethyl-1,4,2-oxazaphosphorinane (2), were investigated for determination of protonation constants using (31)P, (1)H, and (13)C NMR spectroscopy in a wide pH range. As for other alpha-amino-phosphonic acids, the first protonation of 1 is straightforward and occurs at the nitrogen, while for 2 the first protonation occurs simultaneously at the exo phosphonate group, allowing estimation of the microscopic protonation constants. The complexation of Ca(2+) with 1 in a 1:1 molar ratio in aqueous solutions and in the presence of a 5-fold excess Na(+) is rationalized by the products LCaH(2), LCaH, LCaNaH, LCa, and LCa(2) (L = 1). Only the phosphonate groups are involved in Ca(2+) binding at pH > 3, while the phosphonate, hydroxyl, and amine functionalities coordinate to Ca(2+) at pH > 6-7, as soon as the proton at N is lost. Probable conformation states of ions of 1 and 2 are estimated by means of the dependence of vicinal coupling constants (3)J(HH) and (3)J(PC) from dihedral angles.

Determination of protonation constants of some tetracycline antibiotics by potentiometry and lc methods in water and acetonitrile-water binary mixtures

An accurate estimation of dissociation constants of tetracycline antibiotics in acetonitrile-water binary mixtures is very important for several separation techniques such as liquid chromatography and capillary electrophoresis that use these solvent mixtures. In this study, the pKa values of five tetracyclines (tetracycline, oxytetracycline, chlortetracycline, doxycycline and metacycline), have been determined in water and acetonitrile-water binary mixtures (10%, 20% and 30% (v/v)) by potentiometry and liquid chromatography (LC). The obtained results show a similar trend for the pKa1 values of five tetracycline antibiotics as they increase with increasing concentration of organic modifier, which allows a linear relationship between pKa1 values and mole fraction of acetonitrile to be obtained. The pKa values obtained in aqueous medium have been compared with the values predicted by the SPARC on-line pKa calculator.

Combined effect of solvent content, temperature and pH on the chromatographic behaviour of ionisable compounds

The organic solvent content and the pH in the mobile phase are the usual main factors in reversed-phase liquid chromatographic separations, owing to their strong effects on retention and/or selectivity. Temperature is often neglected. However, even in cases where the impact of this factor on selectivity is minor, the reduction in analysis time is still an interesting reason to consider it. In addition, ionisable compounds may exhibit selectivity changes, owing to the interaction of organic solvent and/or temperature with pH. The separation of ionisable compounds (nine diuretics: bendroflumethiazide, benzthiazide, bumetanide, chlorthalidone, furosemide, piretanide, probenecid, trichloromethiazide and xipamide, and two β-blockers: oxprenolol and propranolol) exhibiting different acid–base behaviour was studied. The compounds were tested in a Zorbax SB C18 column under a wide range of conditions: 25–45% (v/v) acetonitrile, pH 3–7 and 20–50 °C. Models considering two factors (organic solvent/pH and temperature/pH), and three factors (organic solvent/temperature/pH) were developed from a previously reported equation, which considers the polarity contributions of solute, stationary and mobile phases. This allowed a comprehensive method to predict the retention of the 11 compounds, the modification of their acid–base behaviour (i.e. determination of protonation constants and shifts of the retention versus pH curves), and the selectivity changes within the studied factor ranges.

Tutorial on a chemical model building by least-squares non-linear regression of multiwavelength spectrophotometric pH-titration data

Although the modern instrumentation enables for the increased amount of data to be delivered in shorter time, computer-assisted spectra analysis is limited by the intelligence and by the programmed logic tool applications. Proposed tutorial covers all the main steps of the data processing which involve the chemical model building, from calculating the concentration profiles and, using spectra regression, fitting the protonation constants of the chemical model to multiwavelength and multivariate data measured. Suggested diagnostics are examined to see whether the chemical model hypothesis can be accepted, as an incorrect model with false stoichiometric indices may lead to slow convergence, cyclization or divergence of the regression process minimization. Diagnostics concern the physical meaning of unknown parameters β qr and ɛ qr , physical sense of associated species concentrations, parametric correlation coefficients, goodness-of-fit tests, error analyses and spectra deconvolution, and the correct number of light-absorbing species determination. All of the benefits of spectrophotometric data analysis are demonstrated on the protonation constants of the ionizable anticancer drug 7-ethyl-10-hydroxycamptothecine, using data double checked with the SQUAD(84) and SPECFIT/32 regression programs and with factor analysis of the INDICES program. The experimental determination of protonation constants with their computational prediction based on a knowledge of chemical structures of the drug was through the combined MARVIN and PALLAS programs. If the proposed model adequately represents the data, the residuals should form a random pattern with a normal distribution N(0, s 2), with the residual mean equal to zero, and the standard deviation of residuals being near to experimental noise. Examination of residual plots may be assisted by a graphical analysis of residuals, and systematic departures from randomness indicate that the model and parameter estimates are not satisfactory.

The Determination of Protonation Constants of Some Amino Acids and Their Esters by Potentiometry in Different Media

In this study, stoichiometric protonation constants of L-tyrosine, L-cysteine, L-tryptophane, L-lysine, and L-histidine, and their methyl and ethyl esters in water and ethanol–water mixtures of 30, 50, and 70% ethanol (v/v), were determined potentiometrically using a combined pH electrode system calibrated as the concentration of hydrogen ion. Titrations were performed at 25∘C and the ionic strength of the medium was maintained at 0.10 mol⋅L−1 using sodium chloride. Protonation constants were calculated by using the BEST computer program. The effect of solvent composition on the protonation constants is discussed. The log10 K2 values of esters generally decreased with increasing ethanol content. However, the log10 K1 values of the esters of L-tyrosine, L-cysteine, and L-tryptophane were found to increase with increasing ethanol content in contrast those of L-lysine and L-histidine esters.

Determination of protonation constants of some fluorinated polyamines by means of 13C NMR data processed by the new computer program HypNMR2000. Protonation sequence in polyamines.

The p K(a) values of 6-fluoro-4,8-diazadodecane-1,12-diamine (6-fluorospermine) (1), 6,6-difluoro-4,8-diazadodecane-1,12-diamine (6,6-difluorospermine) (2), 6-fluoro-4-azaoctane-1,8-diamine (6-fluorospermidine) (3) and 6,6-difluoro-4-azaoctane-1,8-diamine (6,6-difluorospermidine) (4) in D(2)O solution have been determined at 40 degrees C from (13)C NMR chemical shifts data using the new computer program HypNMR2000. The enthalpies of protonation of compounds 1-4 and the parent amines spermine (5) and spermidine (6) have been determined from microcalorimetric titration data. The values of Delta H degrees were used to derive basicity constants relative to 25 degrees C. The NMR data have been analysed by two different methods to obtain information on the protonation sequence in the polyamines 1-5. The protonation sequence for spermine is related to its biological activity.

Difunctionalised Chemosensors Containing Electroactive and Fluorescent Signalling Subunits

The new ligands 13-anthrylmethyl-7-ferrocenylmethyl-1,4,10-trioxa-7,13-diaza-cyclopentadecane (L1) and 1-anthrylmethyl-4,8,11-ferrocenylmethyl-1,4,8,11-tetraaza-cyclotetradecane (L2) have been synthesised, characterised, and their potential activity as chemosensors towards the metal cations Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ studied in 1,4-dioxane/water (70:30, v/v). Both ligands L1 and L2 are difunctionalised receptors containing redox-active (ferrocene) and fluorescent (anthracene) signalling subunits. The crystal structures of [H2L1][PF6]2 and [CuL2][PF6]2 were determined by single-crystal X-ray procedures. Potentiometric experiments in dioxane/water (70:30, v/v; 0.1 M KNO3; 25.0 ± 0.1 °C) for L1 and L2 allowed the determination of protonation constants and complex stability constants with the Cu2+ and Pb2+ metal ions. They form stable complexes with both ligands and show stability constants with values close to those reported for similar complexes. The electrochemical and fluorescence behaviour of L1 and L2 was studied as a function of the pH and in the presence of the Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, and Pb2+ metal cations. The fluorescence and electrochemical response of L1 and L2 is pH-dependent. Ligand L1 was able to electrochemically and selectively sense Pb2+ whereas L2 sensed Cu2+, Zn2+, and Cd2+ using electrochemical techniques. The maximum electrochemical shift (ca. 57 mV) was found for L2 in the presence of Cu2+ at pH = 8. Fluorescence studies showed that the emission intensities of L1 and L2 were selectively enhanced in the presence of Cu2+. Additionally, the [Cu(L2)]2+complex acted as anion-sensing receptor in acetonitrile. The oxidation potential of the ferrocenyl group of the [Cu(L2)]2+complex was cathodically shifted upon addition of anions. The largest electrochemical shift was observed in the presence of fluoride (210 mV). The fluorescence emission of the anthracene groups in [Cu(L2)]2+ was enhanced in the presence of fluoride, nitrate, and dihydrogenophosphate.

Determination of Diffuse Double Layer protonation constants for hydrous ferric oxide (HFO): supporting evidence for the Dzombak and Morel compilation

The acid-base properties of hydrous ferric oxide were studied by glass electrode potentiometry. From the Potentiometrie data, surface protonation constants were derived according to the Diffuse Double Layer convention. Chemical equilibrium modelling of the experimental system suggests that titration points below pH 4 should not be used for the determination of protonation constants because of potential HFO dissolution. Surface protonation constant, PZC and binding site estimates agree excellently with currently available best estimates.

Acid–base and copper(II) sorption properties of a natural lake sediment: Potentiometric and atomic absorption spectrometric characterisation

The interactions of the sediment surface with proton and copper(II) ions were investigated by means of alkalimetric titrations performed on suspensions containing different sediment–solution ratios at ionic strengths of 0.1 and 1.0 mol dm −3. As the equilibrium conditions are critical both in acid and in base media for the considered lake sediment, a batch-titration procedure was adopted, which permitted to fully overcome the data uncertainty related to signal drift. Potentiometric data were computed for the refinement of protonation and complexation constants by means of a program, which minimises the difference between calculated and experimental potential values during the refinement. In the elaboration of the potentiometric data some relevant aspects related to the batch-titration procedure were taken into account. As regards the influence of the ionic medium and ionic strength, the experimental data could be refined by assuming that the surface-active centers act independently of one another, without any appreciable effect due to the intervention of the surface charge. The computation showed that all the independent data were consistent and it was possible to refine three protonation constant values, one referring to groups titratable in the acid region and two to groups titratable in the base one. After the determination of protonation constants, copper(II)–sediment interaction was considered: the stability-constant values were calculated by elaborating pH-metric data recorded on the sediment–copper(II) system; copper(II) not adsorbed on the sediment was determined by atomic absorption spectrometry for each titration point; the good agreement between pCu calculated from potentiometric data and measured pCu, by supposing copper(II) mainly bonded to titratable groups, can be considered as a validation of the method.