Spectrophotometric evaluation of overlapping ionization constants of bisbiacetylmonoxime-o-phenylenediimine

The acid-base properties of bisbiacetylmonoxime-o-phenylenediimine were studied spectrophotometrically. The ionization constants of the acid-base equilibria involved were calculated from the A = f(pH) dependence for the aqueous ethanolic solutions (2% ethanol, I = 0.1, room temperature). The pK_a values were evaluated by means of a variety of methods. Results obtained were compared with values reported in the literature for other dioximes derivatives.     

Development of a chemometric correlation technique to estimate acid-base descriptors for cationic acids in non-aqueous media

We propose a procedure for estimating acid-base constants in organic solvents or mixture of solvents from the corresponding pK_a values in aqueous medium and from certain properties of the organic solvents that characterize them. To accomplish this, we developed and validated a chemometric correlation for the calculation of the acid-base constants of different cationic acids in a broad variety of non-aqueous solvents. The parameters chosen for building the model were as follows: the acid-base constant of the compound in aqueous medium and those corresponding to the polarity-polarizability, basicity and acidity scales of the solvent. The results of the fitting were significant (p < 0.01), with a root mean error in cross-validation of 18%, with no overfitting. The prediction of the acid-base constants for an external set of compounds had a mean absolute prediction error value of less than 0.8 pK_a units.     

Determination of pKa values of some hydroxylated benzoic acids in methanol-water binary mixtures by LC methodology and potentiometry

An accurate estimation of pK_a values in methanol-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 pK_a values of 11 polyphenolic acids have been determined in methanol-water binary mixtures (10%, 20% and 30% (v/v)) by potentiometry, liquid chromatography (LC) and LC-DAD methodology.The results show a similar trend for the pK_a values of all the studied compounds, as they increase with increasing concentration of organic modifier, which allows a linear relationship between pK_a values and mole fraction of methanol to be obtained. The pK_a values obtained in aqueous medium have been compared with those given in the literature, and also with the values predicted by the SPARC on-line pK_a calculator. The data obtained have been used to test the feasibility of an estimation of dissociation constants in a methanol-water medium from the relationship between pK_a values and the organic cosolvent fraction in the mixtures.     

Keto-Enol tautomerization of quercetin in solutions of a cationic surfactant,miramistin

Tautomeric transformations of quercetin in solutions of a cationic surfactant, miramistin, have been spectrophotometrically studied. It has been established that, at pH ≥ 6, monoanions of enol-form quercetin are irreversibly transformed into keto-form monoanions, with the rate of this process depending on surfactant concentration and solution pH. It has been shown that the enol tautomer of quercetin is more stable in aqueous solutions, while the ketone form is stabilized in miramistin-containing media. The apparent dissociation constants have been determined for the enol (pK _a ^a= 6.60) and ketone = 5.64) tautomeric forms of quercetin in micellar solutions of miramistin.     

The Effect of a Cationic Gemini Surfactant,Ethonium, on the Physicochemical Properties of Quercetin in Solutions and on the Surface of Highly Dispersed Silica

The formation of supramolecular complexes with ethonium, a cationic gemini surfactant having a broad-spectrum antimicrobial activity, is shown to significantly alter the physicochemical properties (spectral, protolytic, and adsorption properties and solubility) of a natural f lavonol, quercetin. The constant of binding between quercetin and ethonium is calculated. Apparent dissociation constants pK _a1 ^a of quercetin in solutions of this cationic surfactant are for the first time determined within a broad concentration range. A shift in the pH dependence of quercetin adsorption by 0.5 units to the alkaline region upon the transition from a premicellar ethonium solution to a micellar one correlates with an increase in pK _a1 ^a under these conditions. The value of quercetin adsorption from aqueous ethonium solutions depends on the concentration of the cationic surfactant, pH of a solution, and the pK _a1 ^a value of the f lavonol bound into the supramolecular complex.     

Protolytic equilibria of 2-hydroxytropolone (4,5-d) thiophene in homogeneous and micellar solutions

The present study comprises an investigation of the optical absorption and fluorescence spectra of the title compound (HT) in homogeneous solutions of ethanol, cyclohexane, and sulphuric acid, and in aqueous micellar systems of anionic (NaLS), cationic (CTABr) and non-ionic (Triton X-100) surfactants.This compound behaves as monoprotic acid in buffer solutions of pH = 1–13 containing 3% v/v ethanol. It has pK = 8.2, but in the first excited singlet state the p_K* drops to 3.9. However, another protolytic equilibrium is established with pK₂ = 0.45 and pK*₂ = 2.15 in concentrated H₂SO₄ solutions.Contrary to all other media studied, the dissociated form of HT was observed in CTABr micellar solution with an apparent red shift indicating that the HT molecules are incorporated into the detergent layer of the micelles and at the interface of the aggregates.The influence of micellar solutions on the acid—base equilibrium of HT reveals that the effect of the charge distribution of the counter ions in the double layer is much larger than the effective dielectric constant at the site of solubilization.     

Interaction between primary aliphatic amines and carboxylic acid esters in aqueous micellar solutions of cationic surfactants

The effects of cetylpyridinium bromide (CPB) on the acid-base equilibria of primary aliphatic amines and on the kinetics of reactions of the amines withp-nitrophenyl acetate (PNPA) andp-nitrophenyl caprylate (PNPC) were studied by potentiometric titration and UV spectroscopy. The values of apparent pK _a of the amines in the micellar phase, binding constants of their neutral forms, and the surface potentials of micelles were determined. Cetylpyridinium bromide accelerates the aminolysis of PNPA by factors of 3 to 8 by forming mixed micellar aggregates with the amines. The shift of pK _a values of the amines in micellar solutions is not the only factor that enhances their reactivity. The substrate specificity was found: in contrast to the reaction with PNPA, CPB accelerates (by factors of 15 to 65) or retards (by factors of 4 to 6) the aminolysis of PNPA depending on the hydrophobicity of the nucleophilic reagent. The binding constants of substrates, the rate constants in the micellar phase, and the critical concentrations of micellization were determined from the data obtained. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1333–1338, July, 1998.     

Micellar effects on absorption spectra and protolytic equilibria of phenyl-pyridyl-ketones

The absorption spectra of the three isomeric phenyl-pyridyl-ketones were studied in anionic (SLS), cationic (CTAB) and non-ionic (Triton X-100) micellar solutions. The spectral changes of the n, π* transition in micelles compared to net water provided information on the location of the ketone molecules in the micelle and the partitioning of ketones between micelles and water. The apparent pK^a values of the three pyridyl ketones were determined in anionic, cationic and non-ionic micelles and compared to those in aqueous solution. The results indicate that the ketones reside within the interfacial head group region of the micelle. This location affects the protolytic equilibria: a decrease in nitrogen basicity in Triton X-100 (ΔK^a∼−0.6) and CTAB (ΔpK^a−0.5) and an increase in SLS (ΔpK^a+1.5) are attributed to a reduced polarity at the micelle surface and to an electrostatic surface potential.     

The influence of surfactants on the acid—base and redox properties of reagents of the diphenylamine series

The influence of aqueous solutions of surfactants on the redox and acid—base properties of diphenylamine redox reagents was studied by potentiometric titration and UV spectroscopy. The formal redox potentials, the pK _a values of the reagents in aqueous solutions and in the presence of surfactants, and the constants of binding of the reagents by micellar solutions of surfactants were estimated. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1386–1388, August. 2000.     

Development of negligible depletion hollow fiber membrane-protected liquid-phase microextraction for simultaneous determination of partitioning coefficients and acid dissociation constants

A new method based on negligible depletion hollow fiber-protected liquid-phase microextraction coupled with high-performance liquid chromatography (HPLC) was developed for the simultaneous determination of partitioning coefficients (K_OW) and acid dissociation constants (pK_a), by using phenol, 4-chlorophenol and 2,4-dichlorophenol as model compounds. A 37-mm length polypropylene hollow fiber membranes (600 μm inner diameter, 200 μm wall-thickness, 0.2 μm pore size, ∼70% porosity) with two-end sealed were filled with 1-octanol by ultrasonic agitation to prepare the extraction device. The extraction device was deployed in sample solutions, prepared by spiking target analytes in 1-octanol saturated aqueous solutions (500 mL), for negligible depletion extraction. After equilibrium was reached (∼5 h), the 1-octanol in the lumen of the hollow fiber membrane was collected for HPLC determination of the target analytes. As the depletion of the analytes in aqueous samples was negligible, the distribution coefficient (D_OW) could be calculated based on the measured equilibrium concentration in 1-octanol (C_O) and the initial concentration (C_W) in the aqueous sample of the target analyte (D_OW = C_O/C_W). The D_OW values measured at various pH values were nonlinearly regressed with pH to obtain the K_OW and pK_a values of a compound. Results showed that the measured values of the K_OW and pK_a of these model compounds agreed well with literature data.     

Acid-base properties and nucleophilicity of o-aminomethylphenols in aqueous micellar solutions and microemulsions

The pK _a values and constants of tautomeric equilibrium of several o-aminomethylphenols with different hydrophilic-lipophilic ability were measured in aqueous micellar solutions and in direct microemulsions based on cetyltrimethylammonium bromide. The kinetics of hydrolysis of p-nitrophenyl acetate at different pH and concentrations of aminomethylphenol and surfactant was studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1724–1729, October, 2006     

Calculations of pKa values of carboxylic acids in aqueous solution using density functional theory

With the specific aim of calculating the acidity equilibrium constant (K_a) of carboxylic acids in aqueous solution we investigated the solute-solvent interactions of these acids and their corresponding anions. The pK_a (−lg K_a) values have been calculated using density functional theory (DFT). The polarized continuum model (PCM) is used to describe the solvent. Using these methods, we successfully predicted the pK_as of 66 carboxylic acids in aqueous with the average error of 0.5 in pK_a units. Two different thermodynamic cycles have been studied. The theoretical values are in better agreement with the experimental results for those acids with moderate strength of acidity with the pK_a value higher than 3.     

Dissociation constants for the zinc(II)-8-hydroxyquinoline complexes in aqueous and sodium dodecyl sulfate micellar solutions

The constants of dissociation of 8-hydroxyquinoline (pK ₁ and pK ₂) and of its complexation with zinc ions (logβ₁, logβ₂) in sodium nitrate aqueous solutions at 293 K were calculated by modeling potentiometric titration data. The values of logβ were obtained under conditions such that the complexes occurred simultaneously in the solution and at optimum values of the ionic strength and the ratio between the metal and ligand concentrations. The apparent constants of dissociation of 8-hydroxyquinoline and of its complexation with zinc ions in a 0.01 M sodium dodecyl sulfate solution were calculated. An increase in pK and logβ was explained by the stabilization of the different forms of the ligand and its complexes in the surfactant micellar phase.     

The effect of electrolytes on the reaction rates and acid-base equilibria in ionic micelles

The influence of a number of electrolytes on the micellar effect of cetyltrimethylammoniurn bromide (CTAB) in the hydrolysis ofp-nitrophenyl acetate (1) and bis(p-nitrophenyl) methylphosphonate (2) and in the course of the acid-base dissociation of thep-nitroanilide of bis(chloromethyl)phosphinic acid (3) has been examined. The activity of the salts studied increases in the following order: MeCOOK2CO₃3<p-MeC₆H₄SO₃K. It has been found that in the presence of electrolytes the catalytic effect of CTAB micelles in the hydrolysis reactions of esters1 and2 decreases, and the pK _a value of anilide3 increases. The results obtained are interpreted in terms of the pseudophase model of micellar catalysis. The analysis of the experimental data carried out using logarithmic coordinates revealed a relationship between phase transitions in micellar catalysis and in micellization.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1396–1400, August, 1993.     

Protolytic properties of 2-acylthioacetamides

Concentration acidity of 2-acylthioacetamides dissolved in DMSO-H₂O was measured by the method of pH-metric titration. The data obtained were extrapolated for the determination of pK _a values of 2-acylthioacetamides in water and DMSO. We found that in aqueous solutions the acidity of thioacetarylamide (pK _a = 5.75?C6.01) was almost independent of the nature of substituents in their N-phenyl rings, whereas in DMSO solution the nature of substituents significantly affects their ionization constants (pK _a = 7.88?C11.70). The graphs were displayed and the acidity of N-aryl-3-oxobutanethioamides dependence on the Hammett constants of meta- and para-substituents in the phenyl rings derived. Water is shown to be a leveling, and DMSO a differentiating solvent for 2-acylthioacetamides.     

The acid-base equilibrium constants of 1,2,3,4-tetrahydro-8-oxyquinoline in aqueous solution

The dissociation constants of 1,2,3,4-tetrahydro-8-oxyquinoline in aqueous solution, pK ₁ = 5.51 ± 0.07 and pK ₂ = 9.7 (298 K), were determined by pH-metric titration and computer simulation. The influence of heteroring hydrogenation on the acid-base properties of 8-oxyquinoline is discussed.     

Infrared spectroscopic study of hydrogen-bonded complexes of triphenylcarbinol and triphenylsilanol with ethers

Hydrogen bonding between triphenylcarbinol and triphenylsilanol with eight ethers of different types was investigated. Shifts of OH frequencies of the formed complexes were recorded in dilute CCl₄ solutions of the components. The observed shifts were correlated with the nucleophilicity parameters of the ethers, with their polarity and polarizability factors, their pK_a values and association constants of the ether-‘ol’ complexes. The silanol-ether interaction is perceptibly stronger than the ether-carbinol one. The acid-base mechanism in the interactions dominates, but polar and steric factors play a significant role in some cases.     

The effects of cationic and zwitterionic micelles on the keto-enol interconversion of 2-phenylacetylfuran and 2-phenylacetylthiophene

The presence of micelles from cationic and zwitterionic surfactants increases the apparent acidity of either the keto and the enol forms of 2-phenylacetylfuran (2PAF) and 2-phenylacetylthiophene (2PAT). This effect can be attributed to the affinity of the surfactant micelles for the enolate of the two substrates. Although the equilibrium constants for keto-enol tautomerism of 2PAF and 2PAT, K_T=[enol]/[ketone]=pK_a^KH−pK_a^EH, do not change much, the presence of micelles provides an efficient method for producing appreciable quantities of the enolates under mild experimental conditions and in aqueous solutions. The obtained rate-profiles for the ketonisation reactions and the consistency of the kinetic rate constants over a wide range of ‘pH’ in several overlapping buffers indicate that the pH of the aqueous pseudophase (but not that at the micellar surface) can be controlled by buffers. Moreover, the increase of the acidity and the decrease of the ‘water’ rate of ketonisation of the enols of 2PAF and 2PAT upon addition of surfactants allow the uncovery of a metal ion catalysed pathway that cannot be observed in absence of surfactants.     

Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: validation study in a new cosolvent system

In this paper the validation of pK_a determination in MDM-water mixtures is presented. The MDM-water mixture is a new multicomponent cosolvent mixture (consisting of equal volumes of methanol, dioxane and acetonitrile, as organic solvents) that dissolves a wide range of poorly water-soluble compounds. The cosolvent dissociation constants (p_sK_a) of 50 chemically diverse compounds (acids, bases and ampholytes) were measured in 15-56 wt% MDM-water mixtures by potentiometric or spectrophotometric titration and the aqueous pK_a values obtained by extrapolation. Three different extrapolation procedures were compared in order to choose the best extrapolation in MDM-water mixture using a sub-set of 30 water-soluble compounds. The extrapolated results are in good agreement with pK_a values measured in aqueous medium. No significant difference was found among these extrapolation procedures thus the widely used Yasuda-Shedlovsky plot was proposed for MDM cosolvent also. Further we also present that the single point estimation based on measurement in 20%/v MDM-mixture using a general calibration equation may be suitable for rapid pK_a determination in the early phase of drug research.     

Spectrofluorimetric determination of 1,4-thienodiazepines

The fluorescence characteristics of four 1,4-thienodiazepines in aqueous and methanolic solutions and the effect of pH on fluorescence intensity are described. The pK_a values are calculated. Fluorimetric methods with limits of detection between 3 and 38 ng ml^?1 were developed, and applied for determinations of one drug in tablets, and the others in serum after extraction with a Sep-Pak C₁₈ cartridge.