Spectrophotometric determination of the acid dissociation constants for cacodylic acid and p-Nitrophenol at elevated temperatures

Using 2.5-dinitrophenol as an optical indicator, the pK_a of cacodylic acid were spectrophotometrically determined at elevated temperatures under saturation vapor pressures. The result is pK_a = -26.41 + 1296/T + 4.973 InT whereT is in Kelvin. In a similar way, the pK_a ofp-nitrophenol were obtained up to 200‡C giving pK_a = -24.82 + 2135/T + 4.353 InT From these results, several thermodynamic functions of cacodylic acid andp- nitrophenol were calculated.     

The relationship among pKa, pH, and binding constants in the interactions between boronic acids and diols—it is not as simple as it appears

In our continuing efforts into designing boronic acid-based sensors that recognize cell-surface carbohydrates, it has been necessary to examine various factors that affect the binding affinity between a boronic acid moiety and a diol. The current prevailing view is that the strongest boronic acid/diol complexes are generated by a combination of high solution pH and a low boronic acid pK_a. However, there has never been a systematic examination of the relationship among the binding constants, boronic acid pK_a, and the pH of the solution. Herein we report our findings with a series of 25 arylboronic acids with various substituents and their binding affinities with diols. We have found that (1) the relationship between the pK_a of monosubstituted phenylboronic acid and its substituents can be described using a Hammet plot; (2) the optimal pH for binding is not always above the pK_a of the boronic acid, and is affected by the pK_a values of the boronic acid and the diol, and other unknown factors; and (3) the general belief that boronic acids with lower pK_a values show greater binding affinities for diols is not always true.     

Calculation of amino acid pKaS in a protein from a continuum electrostatic model: Method and sensitivity analysis

We used continuum electrostatic theory to calculate pK_as of amino acids in protein. A Green's function formalism, based on a finite-difference solution to the Poisson–Boltzmann equation for a unit point charge, yields electrostatic potentials that allow calculation of amino acid pK_as to an estimated accuracy of tenths of a pK_a unit. Improvements over previous methods include the ability to focus the finite difference grid to arbitrarily small grid spacing, an analytical representation of the molecular surface, and a novel procedure to calculate the reaction field potential. Using this method, we performed a sensitivity analysis of calculated pK_as in the photosynthetic reaction center. Calculated pK_as are most sensitive for residues that are not well-exposed to solvent. Variations in the parameters of the continuum electrostatic model cause pK_a shifts that are larger than the accuracy of the numerical method, but probably not large enough to account for some of the discrepancies between calculated and experimentally measured pK_as that have been reported for the reaction center. © 1996 by John Wiley & Sons, Inc.     

Spectrophotometric determination of dissociation constants for propionic acid and 2,5-dinitrophenol at elevated temperatures

Using the temperature dependence of pK_a for acetic acid, the pK_a for 2,5-dinitrophenol have been spectrophotometrically determined in acetate buffer at elevated temperatures under the saturation vapor pressures. For 2,5-dinitrophenol $$pK_a = - 33.206 + 2106.7/T + 5.495\ln T$$ where T is in Kelvin. Similarly, pK_a values of propionic acid were obtained at temperatures from 25°C to 175°C producing $$pK_a = - 43.703 + 2128.6/T + 7.2686\ln T$$ From this result, several thermodynamic functions of propionic acid were calculated and compared with those obtained from emf measurement.     

Multifunctional substances — Determination of pKa-values in overlapping ranges using an iteration procedure

Summary In multifunctional substances, pK_a-values from different functional groups may overlap. Therefore, systematically wrong results are obtained, if pK_a-values are used from titration charts without appropriate corrections. The iteration procedure presented in this article starts with the pK_a-values at the half-way neutralisation points. From these preliminary values, new positions in the charts are calculated, from which better approximations of the pK_a-values are obtained. These steps are repeated several times, until the results converge. Cefodizime (HR 221) with three acid/base functional groups was used as model substance. The disodium salt was titrated using three molar equivalents of 0.1 mol/l hydrochloric acid. Using the iteration procedure, three pK_a-values were obtained from the titration chart: 1. The amino-function: pK₁=2.85; 2. the first carboxyl-function: pK₂=3.37; 3. the second carboxyl-function: pK₃=4.18.     

Acid-base properties of bis(chloromethyl)phosphinic acid para-nitroanilide in aqueous micellar solutions of surface active agents

Micelles of the cation-active surface active agent (SAA), cetyltrimethylammonium bromide, decrease the pK_a of bis(chloromethyl)phosphinic acid pnitroanilide in aqueous solutions by two units, while micelles of the anionactive SAA, sodium dodecyl sulfate increase the pK_a of the same compound by 1.75 units. The presence of electrolytes in the solution lowers the influence of micelles on the acid-base properties of the anilide.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 991–994, May, 1990.     

Acid-Base Properties of the Ground and Excited States of Ruthenium(II) Tris(4′-methyl-2,2′-bipyridine-4-carboxylic Acid)

The acid dissociation constant, pK_a, for the ground and excited states of ruthenium tris(4′-methyl-2,2′-bipyridine-4-carboxylic acid) complex have been measured. The ground state pK_a obtained from the pH titration curve of the complex absorption at 454 nm was 2.5. The lifetimes of the excited-state for deprotonated and protonated ruthenium complexes are 595 and 150 ns, respectively. The excited-state pK_a* is obtained from the emission titration curve at 630 nm and corrected for the excited-state lifetime to be 4.2. The increase of 1.7 pH units in the acid dissociation constant in the excited-state indicates that the ligand is much more basic in the excited-state. This result confirms the MLCT assignment for the lowest electronic transition of [Ru(mbpyCOOH)₃]²⁺.     

Multiwavelength Spectrophotometric Determination of Acid Dissociation Constants. Deconvolution of Binary Mixtures of Ionizable Compounds

ABSTRACT

A spectral deconvolution method based on target factor analysis has been developed to determine pK_a values of binary mixtures of monoprotic and/or diprotic ionizable compounds. The technique makes use of the approach of Frans and Harris, which has been implemented previously for mixtures of monoprotic compounds (Anal. Chem. 1985, 57, 1718-1721), to extract the unknown pK_a values. The method has been illustrated by using the multiwavelength spectrophotometrictitation data of binary mixtures of: I. benzoic acid and phenol, 2. benzoic acid and nicotinic acid, 3. p-aminosalicylic acid and phthalic acid. It was demonstrated that the pK_a values as determined in this study are in good agreement with the literature.     

Hydrolysis of bis(chloromethyl)phosphonic acid p-nitroanilide in aqueous micellar surfactant solutions

The hydrolysis of bis(chloromethyl)phosphonic acid p-nitroanilide has been studied in the pH range 6.86–13.0 and the effects of ionic surfactant micelles on this process have also been examined. The nature of the micellar effects of cetyltrimethylammonium bromide (CTAB) and sodium dodecylsulfate (SDS) on this reaction lead us to conclude that both the neutral and anionic forms of the substrate are reactive, and that in the range of pH > pK_a hydrolysis of the ionic form of the anilide predominates, while at pH < pK_a the reaction of the neutral form is predominant. The binding constants for both the neutral and anionic forms of bis(chloromethyl)phosphonic acid p-nitroanilide in micellar CTAB and SDS solutions have been determined using a kinetic method, as well as by measuring the changes in the acid-base properties of the substrate resulting from the influence of micelles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1718–1722, August, 1990.     

Calculations of pKa values of carboxylic acids in aqueous solution using Möller-Plesset perturbation theory

The acidity constants of some carboxylic acids in aqueous solution have been calculated. The calculations were carried out using Möller-Plesset (MP) perturbation theory. The Polarizable Continuum Model (PCM) is used to describe the solvent. This model furnishes pK_a values that agree more closely with experimental data than those obtained at the level of Hartree-Fock (HF) and Density Functional Theory (DFT-B3LYP). The root-mean-square of errors of the calculated pK_a values are less than 1.0 for the studied acids. The molecules analyzed consist of acids with pK_a values in the range of 1.30 to 5.05, and have been partitioned into three classes. Class I includes acids with pK_a values higher than 4.00. Class II includes strong acids with pK_a values between 3.00 to 4.00. Class III includes very strong acids with pK_a values less than 3.00. The calculated pK_a values for the acids in Class I and Class II agree more closely with experimental values. The root-mean-square of errors for the Class I and Class II compounds are 0.70 and 0.78 pK_a units, respectively.     

Thermodynamic dissociation constants of silychristin, silybin, silydianin and mycophenolate by the regression analysis of spectrophotometric data

Mixed dissociation constants of four drug acids, i.e. silychristin, silybinin, silydianin and mycophenolate at various ionic strengths I of range 0.01 and 0.30 and at temperatures of 25 and 37 °C were determined using the SQUAD(84) regression analysis program applied to pH-spectrophotometric titration data. The proposed strategy of an efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of silychristin. The thermodynamic dissociation constant pK_a^T was estimated by non-linear regression of {pK_a, I} data at 25 and 37 °C: for silychristin pK_a,1^T=6.52(16) and 6.62(1), pK_a,2^T=7.22(13) and 7.41(5), pK_a,3^T=8.96(9) and 8.94(9), pK_a,4^T=10.17(7) and 10.03(8), pK_a,5^T=11.89(4) and 11.63(7); for silybin pK_a,1^T=7.00(4) and 6.86(5), pK_a,2^T=8.77(11) and 8.77(3), pK_a,3^T=9.57(8) and 9.62(1), pK_a,4^T=11.66(3) and 11.38(1); for silydianin pK_a,1^T=6.64(7) and 7.10(6), pK_a,2^T=7.78(5) and 8.93(1), pK_a,3^T=9.66(9) and 10.06(11), pK_a,4^T=10.71(7) and 10.77(7), pK_a,5^T=12.26(5) and 12.14(5); for mycophenolate pK_a^T=8.32(1) and 8.14(1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of parameter estimates to be found.     

Acidity Constants of Supported Salts of Heteropoly Acids Using a Methodology Related to the Potentiometric Mass Titration Technique

Using a potentiometric mass titrationmethod, the pK_a values of 12-molybdophosphoric acid (MPA) and 12-tungstophosphoric acid (TPA) were determined in aqueous solution and as a solid suspension in acetonitrile. The results were compared with the earlier reported values obtained using other methods like calorimetry and adsorption (Cal-ad). The acidity values in terms of pK_a and the number of acid sites were determined for the ammonium salts of MPA and TPA, and ammonium salts incorporated with vanadium and ammonium salts impregnated on a ZrO₂ support. The effect of the amount of the salt or acid in the suspension of acetonitrile on the potentiometric titration behavior was also studied and it was found that 0.1 g of the substance gives a good neutralization jump in the titration curve.     

Evaluation of the acidic properties of hydroxycoumarins and choice of solvents for performing potentiometric analysis

The relative acidity constants (pK_a) for 17 hydroxycoumarins in water, methanol, acetone (Ac), dimethylformide (DMFA), and dimethyl sulfoxide (DMSO) have been determined by Henderson's method. The existence of a linear relationship between pK_a in water and pK_a in acetone, dimethylformamide, and dimethyl sulfoxide has been established. From the pK_a values the sequence of neutralization of the hydroxy groups has been determined: their acidic properties decrease in the sequence 4-OH > 7-OH > 6-OH > 8-OH. A quantitative evaluation of the conditions of titration in five solvents on the basis of the titration constants (pK_t) and of the values of the potential jumps and the shape of the potentiometric titration curves has permitted acetone to be proposed as the optimum solvent for the performance of potentiometric analysis.All-Union Scientific-Research Institute of Drug Chemistry and Technology, Khar'kov. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 770–773, November–December, 1985.     

The deprotonation and protonation equilibria of a hypericin derivative in aqueous solution

Summary A hypericin derivative ,'-appended at the methyl groups with two polyethylene glycol moieties (about 23 units long) and capped with acetyl groups was synthesized starting from emodin. This derivative proved to be soluble in water and was investigated by means of spectrophotometric titrations and electrophoresis experiments. Deprotonation at thebay-region hydroxyl group was observed atpK _a=1.6. This was followed by a second deprotonation step of aperi-hydroxyl group at apK _a value of 9.4. This derivative could be protonated at the carbonyl group characterized by apK _a value of –5.7. FrompK _a determinations in water-ethanol mixtures the correspondingpK _a values of hypericin itself determined in such mixtures were extrapolated to the aqueous phase. This resulted in estimatedpK _a values of 1.8, 9.2, and –6.

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Deprotonierungs- und Protonierungsgleichgewichte eines Hypericinderivates in wäßriger Lösung

Zusammenfassung Ein an den Methylgruppen von Hypericin mit endständig acetylierten Polyethylenglykolketten (ungefähr 23 Einheiten lang) ,'-disubstituiertes Derivat wurde ausgehend von Emodin synthetisiert. Dieses Derivat ist wasserlöslich, und es wurde mit Hilfe von spektrophotometrischen Titrationen und Elektrophorese untersucht. Die Deprotonierung derbay-Hydroxylgruppe erfolgt beipK _a=1.6. Diese wird von einem zweiten Deprotonierungsschritt an einerperi-Hydroxylgruppe bei einempK _a-Wert von 9.4 gefolgt. Dieses Derivat konnte an der Carbonylgruppe protoniert werden, was durch einenpK _a-Wert von –5.7 charakterisiert ist. Ausgehend vonpK _a-Messungen in Wasser-Ethanol-Mischungen wurden die entsprechendenpK _a-Werte auch für das Hypericin selbst in wäßriger Phase extrapoliert. Dies führte zu geschätztenpK _a-Werten von 1.8, 9.2 und –6.

     

Synthesis and properties of 1-dinitromethyl-3-R-1,2,4-triazoles

Reductive denitration of 1-trinitromethyl-3-R-1,2,4-triazoles by KI or NH₂OH followed by the treatment of the formed 1-dinitromethyl-3-R-1,2,4-triazoles salts with sulfuric acid yielded dinitromethyl compounds (R = H, N₃, Cl, NO₂), sufficiently strong CH-acids (pK_a 1.37–0.12) whose typical reactions are similar to those of gem-dinitrocompounds from the aliphatic series. The spectral data and the analysis of correlation relations between pK_a of 1-dinitromethyl-3-R-1,2,4-triazoles and the substituent constants confirm that their structure is analogous to that of the majority of compounds belonging to the mentioned series.     

X=Y-ZH systems as potential 1.3-dipoles : Part 14. bronsted and Lewis acid catalysis of cycloadditions of arylidene imines of α-amino acid esters

Cycloadditions of arylidene imines of α-amino acid esters to a range of dipolarophiles show substantial rate enhancements in the presence of Bronsted and Lewis acids. For Bronsted acids the rate is related to the pK_a of the acid and cycloadditions to reactive dipolarophiles occur at room temperature. For the Lewis acids studied the rate acceleration decreases in the order Zn(OAc)₂ > AgOAc> LiOAc> MgOAc₂ but is also anion dependent with LiBr> LiOAc and AgOAc> AgOTs. The Lewis acid catalysed processes are believed to be examples of cycloadditions of metallo-1,3-dipoles. In both Bronsted and Lewis acid catalysed processes the cycloadditions are regio- and stereo-specific.     

Protonation equilibria of rauwolfia alkaloids in sulfuric acid solutions

The pK_a values for the indole ring protonation equilibria of the Rauwolfia alkaloids, yohimbine, ajmalicine, reserpine and reserpiline have been measured in strongly sulfuric acid solutions. The alkaloids obey the H_I acidity function stablished by Hinman and Lang for indole ring protonation, but they are considerably weaker bases than alkylindoles. Evidences indicating that these compounds behave as carbon bases are reported.     

Reversed Phase High Performance Liquid Chromatography Using Carboxylic Acids in the Mobile Phase

Abstract

This report describes the use of different carboxylic acids as mobile phase modifiers. The effect on retention of acid chain length, pH, and eluent composition for a series of phenylalkanols, phenol, and the amines aniline, N-methylaniline, and benzylamine is discussed. The retention of both neutral and positively charged compounds is influenced by the dissociation equilibrium of the carboxylic acid in the mobile phase. By using l-pentanol to coat excess exposed silanol groups on the reversed phase column used, the inflection in the retention of both neutral and charged solutes as pH is changed occurs at the pK_a of the acid in the mobile phase. In addition, by using an acid and amine with the same or similar pK_a values, selective ion-pairing of this pair over others with dissimilar pK_a values can be promoted. Application of this technique to the selective retention of amino acids and peptides was unsuccessful.     

Simple methods for the estimation of ionization constants of substituted pyridine N-oxides in polar aprotic solvents and water

A direct method for the determination of the pK _a values of acids conjugated to substituted pyridine N-oxides has been proposed which is based on the pH measurement of the solution of the basic salt. It has been experimentally shown that the method is reliable when applied to N-oxides of not too low basicity (pK _a >5). Correlation has been performed between the pK _a values in aqueous and aprotic media solutions which shows the great influence of the solvation effect on the acid-base equilibria. The good correlation between the pK _a values in aqueous and non-aqueous solutions enables the pK _a values in water to be estimated with sufficient accuracy, even in the cases when the experimental limitations make the determination impossible which is shown on the basis of selected examples.     

Evaluation of the acidic properties of hydroxycoumarins and choice of solvents for performing potentiometric analysis

The relative acidity constants (pK_a) for 17 hydroxycoumarins in water, methanol, acetone (Ac), dimethylformide (DMFA), and dimethyl sulfoxide (DMSO) have been determined by Henderson's method. The existence of a linear relationship between pK_a in water and pK_a in acetone, dimethylformamide, and dimethyl sulfoxide has been established. From the pK_a values the sequence of neutralization of the hydroxy groups has been determined: their acidic properties decrease in the sequence 4-OH > 7-OH > 6-OH > 8-OH. A quantitative evaluation of the conditions of titration in five solvents on the basis of the titration constants (pK_t) and of the values of the potential jumps and the shape of the potentiometric titration curves has permitted acetone to be proposed as the optimum solvent for the performance of potentiometric analysis.