Thermodynamic Acid Dissociation Constants Research Articles

Effects of structural modification of the daunosamine moiety of anthracycline antibiotics on pKa values determined by capillary zone electrophoresis.

The thermodynamic acid dissociation constants (pKa1 and pKa2) of 16 anthracycline antibiotics, including doxorubicin (DOX) and daunorubicin (DAU), their epimers, epidoxorubicin (EDOX) and epidaunorubicin (EDAU), as well as novel anthracycline derivatives containing piperidine (FPIP), morpholine (FMOR) and hexamethylenoimine (FHEX) rings in the formamidine group of the daunosamine moiety were determined by analysis of the dependence between measured electrophoretic mobility and the pH of the buffer using the capillary zone electrophoresis method. The results obtained confirmed the ampholytic character of anthracyclines with at least two ionization states. The determined values were in the range of 8.36-9.28 and 9.38-11.48 for pKa1 and pKa2 arising from ionization of amino and phenolic groups, respectively. Structural modifications in the daunosamine moiety of the studied anthracyclines affected their pharmacological properties, such as antiproliferative activity.

Measurements of Thermodynamic Acid Dissociation Constants for Three HMG-CoA Reductase Inhibitors by using RPLC and Study of Validation in Pharmaceutical Tablets

Background: Present work was designed about the assignation of thermodynamic acid dissociation constants (pKa) of pravastatin, atorvastatin and rosuvastatin by using RPLC method. In the experiment, methanol-water binary mixture was chosen as hydroorganic solvent mixture. Method: Chromatographic study was performed with Nucleosil 300-5C4 column (5µm, 250x4.6 mm, I.D.) and the flow rate of the experiment was adjusted at 1 mL/min. The thermodynamic acid dissociation constant values and the intrinsic retention factors were estimated by use of a non-linear least squares fit of the data. The realibility of the RPLC methodology was investigated statistically using the difference between the experimental and theoretical results. Aqueous pKa values were also estimated with extrapolation by means of the Yasuda-Shedlovsky and mole fraction equations. Conclusion: Availability of present procedure in order to quantitatively determine the studied compounds was verified by the validation in suitability with the requirements laid down via ICH (International Conference on Harmonization) guidelines. Results of the analysis show that the method can be used for the estimation of studied drugs in pharmaceutical formulations, with great recovery, well precision and accuracy. Keywords: Statins, chromatographic retention, polarity parameter, thermodynamic dissociation constant, RPLC, method validation.

Determination of thermodynamic pKa values of pharmaceuticals from five different groups using capillary electrophoresis

A determination of the thermodynamic acid dissociation constants (pKa) of 22 frequently used pharmaceuticals using capillary electrophoresis in aqueous media is presented in this work. The investigated pharmaceuticals belong to different pharmacological groups: macrolides, fluoroquinolones, sulfonamides, β-lactams, tetracyclines, and other miscellaneous pharmaceuticals. The electrophoretic mobilities of the investigated analytes were monitored in a pH range from 2.00 to 10.82. The data were fitted with an appropriate mathematical model using a nonlinear regression analysis to obtain pKa values. Experimentally obtained data were well described by the mathematical model chosen for each analyte that was confirmed by r(2) values higher than 0.99 for most of the investigated analytes. Extrapolations to zero ionic strength were used to determine the thermodynamic pKa values. Experimentally obtained acid dissociation constants were interpreted using structural formulae of investigated analytes and the moieties corresponding to specific pKa were identified.

Studies of the pathways open to copper water oxidation catalysts containing proximal hydroxy groups during basic electrocatalysis.

Water oxidation can lead to a sustainable source of energy, but for water oxidation catalysts to be economical they must use earth abundant metals. We report here 2:1 6,6'-dihydroxybipyridine (6,6'-dhbp)/copper complexes that are capable of electrocatalytic water oxidation in aqueous base (pH = 10-14). Two crystal structures of the complex that contains 6,6'-dhbp and copper(II) in a ratio of 2:1 (complex 1) are presented at different protonation states. The thermodynamic acid dissociation constants were measured for complex 1, and these show that the complex is fully deprotonated above pH = 8.3 (i.e., under water oxidation conditions). CW-EPR, ENDOR, and HYSCORE spectroscopy confirmed that the 6,6'-dhbp ligand is bound to the copper ion over a wide pH range which shows how pH influences precatalyst structure. Additional copper(II) complexes were synthesized from the ligands 4,4'-dhbp (complex 2) and 6,6'-dimethoxybipyridine (complexes 3 and 4). A zinc complex of 6,6'-dhbp was also synthesized (complex 5). Crystal structures are reported for 1 (in two protonation states), 3, 4, and 5. Water oxidation studies using several of the above compounds (1, 2, 4, and 5) at pH = 12.6 have illustrated that both copper and proximal OH groups are necessary for water oxidation at a low overpotential. Our most active catalyst 1 was found to have an overpotential of 477 mV for water oxidation at a moderate rate of kcat = 0.356 s(-1) with a competing irreversible oxidation event at a rate of 1.082 s(-1). Furthermore, our combined work supports previous observations in which OH/O(-) groups on the bipyridine rings can hydrogen bond with metal bound substrate, support unusual binding modes, and potentially facilitate proton coupled electron transfer.

Acidic Dissociation of Chlorodifluoroacetic Acid: Determination of K°, ΔH°, and ΔS°

Using pH potentiometric measurements, concentration quotient and thermodynamic acid dissociation constants were determined for chlorodifluoroacetic acid. The determinations were carried out in aqueous media at seven temperatures ranging from 20 °C to 50 °C at an ionic strength of 0.25 mol dm-3. Standard enthalpies and entropies of the dissociation reaction were also obtained. At 25 °C, the thermodynamic values of these properties are K° = 0.495 ± 0.020, ΔH° = (−5.0 ± 1.1) kJ mol-1, and ΔS° = (−23.1 ± 3.6) J K-1 mol-1.

Protonation of Picolinic Acid: Determination of pK°, ΔH°, and ΔS°

Using pH potentiometric measurements, concentration quotient and thermodynamic acid dissociation constants were determined for the dissociation of 2-pyridinium carboxylic acid. The determinations were carried out in aqueous media at five temperatures ranging from 20 °C to 55 °C and at two ionic strengths (I = 0.10 mol dm-3 and I = 0.25 mol dm-3). Standard enthalpies and entropies of the dissociation reaction were also obtained. At 25 °C, the thermodynamic values of these properties are pK° = 0.840 ± 0.006, ΔH° = (−0.68 ± 0.23) kJ mol-1, and ΔS° = (−18.4 ± 0.8) J mol-1 K-1.

Consistency of pH standard values with the corresponding thermodynamic acid dissociation constants (Technical Report)

Abstract

Dissociation constants of chloroguaiacols in water: A comparison of measured and predicted values

AbstractChloroguaiacols are common components of bleached‐kraft pulp mill effluent known to bioaccumulate in aquatic organisms and to sorb on particulate material and sediments. Ionization properties of the chloroguaiacols must be known in order to explain their sorptive behavior in aquatic systems. To obtain this information, thermodynamic acid dissociation constants (pKa) of guaiacol (o‐methoxyphenol) and nine chloroguaiacols have been determined by spectrophotometric methods. These experimental pKa values have been compared with literature values, values predicted by the Hammett equation, and predictions by quantum chemical calculations using MOPAC 6.0 with AM1 and MNDO Hamiltonian operators. Experimental and predicted acidities were strongly correlated, and the correlation equations obtained have been used to calculate pKa values for those chloroguaiacols that were unavailable for experimental measurement.

Simultaneous determination of equivalence volumes and thermodynamic acid dissociation constants from data for the acidic region of potentiometric titration curves

New iterative methods for the analysis of potentiometric titration data of weak monoprotic acids or of mixtures of two monoprotic acids are presented. These methods, using equations without approximations and data exclusively resulting from the acidic region of the titration curve, seem to be valid throughout the acidic strength range. In the titration of weak monoprotic acids, the proposed procedures are able to extract accurate values of the equivalence volume and also the thermodynamic dissociation constant. On the other hand, in the titration of mixtures of two monoprotic acids, the proposed approach is able to extract accurate values of the concentrations and the thermodynamic dissociation constants of the component acids even when their acidity strengths are similar. The test of the proposed procedures by means of ideal simulated data (free from any extraneous “noise”) and Monte Carlo simulated data revealed that these methods are fairly applicable even when the titration data are considerably obscured by “noise”. Further, for acids having p K ≥4 the proposed procedures lead to accurate results even when the pH data contain an important systematic error. The proposed procedures were also successfully applied to experimental titration data for weak acids. A procedure for the analysis of titration data carried out in binary water-dimethylformamide solvent systems is also presented.

Determination of limiting ionic mobilities and dissociation constants of some local anaesthtics

The limiting ionic mobilities and thermodynamic acid dissociation constants were calculated from isotachophoretic experiments for the local anaesthetics procaine, tetracaine, lidocaine, trimecaine, bupivacaine, cinchocaine, diperodone, diocaine, cocaine, psicaine-neu tropacocaine, amylocaine, β-eucaine and leucinocaine. The pH values at which the local anaesthetics with very similar limiting ionic mobilities can be isotachophoretically separated were determined from simulated mobility curves. The measuring apparatus employed a high-frequency contactless conductivity detector.

A spectrophotometric study of the acid-base equilibria of o-methyl red in aqueous solutions

The UV-visible spectra of o-methyl red were examined at 25°C in water at various acidities and the variations in the spectra were correlated with the structures of the several forms of the compound. The two acid-base equilibria that involve the monoprotonated form of o-methyl red were treated as overlapping equilibria. The thermodynamic acid dissociation constants (K a2 and K a3) of the diprotonated and the monoprotonated forms were found to be (4.16 ± 0.14) × 10 −3 and (1.40 ± 0.02 ) × 10 −5 mol dm −3, respectively. Complete extraction of o-methyl red from the aqueous phase into the CCl 4 phase was observed in the pH range 1.25–5.6. The significance of this result with respect to the structure of the monoprotonated form is discussed.

Thermodynamic acid dissociation constants for proton-ionizable crown compounds in aqueous dioxane

Thermodynamic acid dissociation constants ( T p K a ) have been determined in 70% di-oxane-water ( v v ) for eleven macrocyclic polyether (crown ether) compounds which have pendant proton-ionizable groups, and for three crown compounds in which the ionizable group is part of the ring structure itself. The influence of structural variation within the proton-ionizable macrocyclic compounds upon the thermodynamic acid dissociation constant is assessed.

Application of multilinear regression analysis to the evaluation of the standard EMF of the hydrogen—silver/silver chloride cell in methanol + water mixtures over wide ranges of temperature and composition

The one-stage multilinear regression method previously applied to the analysis of emf data for aqueous electrochemical cells as a function of temperature and solute concentration has been extended to the analysis of emf data for the cell: Pt|H 2|HCl ( m), CH 3OH( x), H 2O (1 − x) | AgCl|Ag as a function of methanol mole fraction ( x) as well as solute molality ( m) and temperature. In this way discrepancies between various sets of data are revealed and the consistent set of data for the standard potential of the cell so obtained can be used for the evaluation of thermodynamic acid dissociation constants and standard reference pH values in this important, much studied mixed aqueous solvent system.

Thermodynamics of proton-ligand dissociation equilibria in mixed solvents. acid dissociation of 2-isopropyltropolone in mixtures of water and dioxane

Thermodynamic acid dissociation constants, TpKa, of 2-isopropyltropolone (HIPT) have been determined by pH titration in aqueous and aqueous dioxane media at 25 and 35 ± 0.01°C applying an empirical pH correction for mixed aqueous media. HIPT is a very weak acid with TpKa between 7 and 9. The TpKa values do not vary linearly with the reciprocal of the dielectric constant of the medium, but a plot of TpKa vs. the mole fraction of dioxane is linear at a given temperature. The “true constant”, K′a, and solvation number, n, in the expression (H+)(A−)/(HA) = K′a(S)n = K*a for this reagent have been evaluated. Mean ionic radii, r ±, for the tropolonate ion, being in the region of 2.0–2.4 Å, slightly increases with dioxane percentages. Values of ΔG0, ΔH0 and ΔS0 have been evaluated. The effects of temperature as well as medium effects are briefly discussed.

ChemInform Abstract: THERMODYNAMIC ACID DISSOCIATION CONSTANTS OF PYRAZOLONES IN DIOXANE‐WATER MIXTURES

Chemischer InformationsdienstVolume 13, Issue 6 Article ChemInform Abstract: THERMODYNAMIC ACID DISSOCIATION CONSTANTS OF PYRAZOLONES IN DIOXANE-WATER MIXTURES J. P. SHUKLA, J. P. SHUKLASearch for more papers by this authorA. K. SABNIS, A. K. SABNISSearch for more papers by this authorM. S. SUBRAMANIAN, M. S. SUBRAMANIANSearch for more papers by this author J. P. SHUKLA, J. P. SHUKLASearch for more papers by this authorA. K. SABNIS, A. K. SABNISSearch for more papers by this authorM. S. SUBRAMANIAN, M. S. SUBRAMANIANSearch for more papers by this author First published: February 9, 1982 https://doi.org/10.1002/chin.198206076Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume13, Issue6February 9, 1982 RelatedInformation

Isotachophoretic determination of mobility and p Ka by means of computer simulation : I. Estimation of accuracy of the evaluated constants

The accuracy has been estimated for the absolute mobility, m o, and thermodynamic acid dissociation constants, p K a, evaluated by analysing a qualitative index, R E, obtained by means of isotachophoresis. For several model mono- and divalent anions, m o could be determined within ca. ±0.2ṡ10 -5 to ±1.2ṡ10 -5 cm 2 V -1 sec -1 and p K a to ca. ±0.01 or less, when the reproducibility of a R E value was ±0.02. The accuracy, especially that of p K a, was closely influenced by the pH of the leading electrolyte, the p K a of the buffer used and the m o and p K a of the sample itself. Statistically, the accuracy may be improved by the use of a set of different R E values obtained under different electrolyte conditions.

Thermodynamic acid dissociation constants of pyrazolones in dioxane—water mixtures

Thermodynamic acid dissociation constants of pyrazolones in dioxane—water mixtures

Acid properties of some phosphonocarboxylic acids

Thermodynamic acid dissociation constants were determined for phosphonoacetic acid (PAA) in aqueous solution at 25°C by coulometric titrations at different ionic strengths and extrapolation of the results to I=0. The respective values are pK1∼2.0, pK2=5.11±0.04, and pK3=8.69±0.05. The enthalpy and entropy of dissociation for the second and the third dissociation steps, determined from the temperature dependence of pK's, are ΔH 2 o =0.2±0.3 kcal-mole−1, ΔS 2 o =22.6±0.9 e.u., ΔH 3 o =1.3±0.4 kcal-mole−1, and ΔS 3 o =11.7±0.4 e.u. Phosphorus-31 and carbon-13 NMR studies of PAA solutions as a function of pH gave the deprotonation sequence of the triacid. Acidity constants were also determined for phosphonoformic acid, 2-phosphonopropionic acid, and 3-phosphonopropionic acid at an ionic strenght of 0.05.

Thermodynamic acid dissociation constants of aromatic thiols

The thermodynamic acid dissociation constants of thiophenol and a series of meta- and para-substituted thiophenols have been measured in water at 25°C by the e.m.f.–spectrophotometric method. The results and the significance of the linear free energy relationship for thiophenols are discussed and compared with the limited data available in the literature.

Acid dissociation of some β-diketones in mixtures of water and dioxane—a thermodynamic study

Thermodynamic acid dissociation constants, T p K a , of seven β-diketones have been determined potentiometrically in aqueous and aqueous dioxane media at 25±0.1°C. The T p K a order of these reagents is: DBM>AcAc>BA>TFAA>TTA>BTFA>HFAA. T p K a values are found to vary linearly as a function of mole fraction of dioxane in all cases. The effect of different substituents on these constants is also discussed briefly.