Determination of acid-base dissociation constants of very weak zwitterionic heterocyclic bases by capillary zone electrophoresis

Thermodynamic acid-base dissociation (ionization) constants (pK(a)) of seven zwitterionic heterocyclic bases, first representatives of new heterocyclic family (2,3,5,7,8,9-hexahydro-1H-diimidazo[1,2-c:2',1'-f][1,3,2]diazaphosphinin-4-ium-5-olate 5-oxides), originally designed as chiral Lewis base catalysts for enantioselective reactions, were determined by capillary zone electrophoresis (CZE). The pK(a) values of the above very weak zwitterionic bases were determined from the dependence of their effective electrophoretic mobility on pH in strongly acidic background electrolytes (pH 0.85-2.80). Prior to pK(a) calculation by non-linear regression analysis, the CZE measured effective mobilities were corrected to reference temperature, 25°C, and constant ionic strength, 25 mM. Thermodynamic pK(a) values of the analyzed zwitterionic heterocyclic bases were found to be particularly low, in the range 0.04-0.32. Moreover, from the pH dependence of effective mobility of the bases, some other relevant characteristics, such as actual and absolute ionic mobilities and hydrodynamic radii of the acidic cationic forms of the bases were determined.     

The sorption of divalent metal ions on AlPO4

The sorption of Cu(2+), Pb(2+), Ni(2+), and Cd(2+) ions on the aluminum(III) phosphate was observed to increase with increases in the concentration, temperature, and pH of the system. The apparent dissociation (pK(a)), binding (pK(b)) and exchange (pK(ex)) constants of aluminum(III) phosphate were evaluated and found to be dependent upon the temperature and nature of the metal cations. The values of the dissociation constants (pK(a)) followed the order Pb(2+)相似文献   

Determination of acid-base dissociation constants of azahelicenes by capillary zone electrophoresis

CZE was employed to determine acid-base dissociation constants (pK(a)) of ionogenic groups of azahelicenes in methanol (MeOH). Azahelicenes are unique 3-D aromatic systems, which consist of ortho-fused benzene/pyridine units and exhibit helical chirality. The pK(a) values of pyridinium groups of the studied azahelicenes were determined from the dependence of their effective electrophoretic mobility on pH by a nonlinear regression analysis. The effective mobilities of azahelicenes were determined by CZE at pH range between 2.1 and 10.5. Thermodynamic pK(a) values of monobasic 1-aza[6]helicene and 2-aza[6]helicene in MeOH were determined to be 4.94 +/- 0.05 and 5.68 +/- 0.05, respectively, and pK(a) values of dibasic 1,14-diaza[5]helicene were found to be equal to 7.56 +/- 0.38 and 8.85 +/- 0.26. From these values, the aqueous pK(a) of these compounds was estimated.     

Interactions of metal ions with water: ab initio molecular orbital studies of structure, vibrational frequencies, charge distributions, bonding enthalpies, and deprotonation enthalpies. 2. Monohydroxides

The formation and properties of a wide range of metal ion monohydroxides, M(n)(+)[OH(-)], where n = 1 and 2, have been studied by ab initio molecular orbital calculations at the MP2(FULL)/6-311++G**//MP2(FULL)/6-311++G** and CCSD(T)(FULL)/6-311++G**//MP2(FULL)/6-311++G** computational levels. The ions M(n)()(+) are from groups 1A, 2A, 3A, and 4A in the second, third, and fourth periods of the Periodic Table and from the first transition series. Geometrical parameters, vibrational frequencies, atomic charge distributions, orbital occupancies, and bonding enthalpies are reported. The M(n)(+)-O distances are shorter in the hydroxides than in the corresponding hydrates (published previously as Part 1, Inorg. Chem. 1998, 37, 4421-4431) due to a greater electrostatic interaction in the hydroxides. The natural bond orbitals for most of the first-row transition metal ion hydroxides do not contain a formal metal-oxygen bonding orbital; nevertheless the atomic charge distributions show that for both n = 1 and 2 a significant amount of electron density is consistently transferred from the hydroxide ion to the bound metal ion. Deprotonation enthalpies for the hydrates have been evaluated according to the simple dissociation process, M(n)(+)[OH(2)] --> M(n)(+)[OH(-)] + H(+), and also via proton transfer to another water molecule, M(n)(+)[OH(2)] + H(2)O --> M(n)(+)[OH(-)] + H(3)O(+). The drastic reduction in these deprotonation enthalpies as H(2)O molecules are sequentially bonded in the first coordination shell of the metal ion (amounting to 71, 64, 85, and 91 kcal/mol for the bonding of six water molecules to Mg(2+), Ca(2+), Mn(2+), and Zn(2+), respectively) is found to be due to the greater decrease in the bonding enthalpies for the hydroxides relative to the hydrates. Proton transfer to bases other than water, for example side chain groups of certain amino acids, could more than offset the decrease in deprotonation energy due to the filling of the first coordination shell. Linear relationships have been found between the pK(a) values for ionization of the Mg(2+), Ca(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+) aquo ions, and Delta for the bonding of the first water molecule, for the bonding of the hydroxide ion, and for proton dissociation from the monohydrate. Similar relationships have also been found between the pK(a) values and the reciprocal of the M-O bond lengths in both the monohydrates and hydroxides. Thus the ionization of metal hydrates in water echoes the properties of the monomeric species M(n)(+)[OH(2)].     

Physicochemical characterization of phosphinic pseudopeptides by capillary zone electrophoresis in highly acidic background electrolytes

Phosphinic pseudopeptides (i.e., peptide isosteres with one peptide bond replaced by a phosphinic acid moiety) were analyzed and physicochemically characterized by capillary zone electrophoresis in the pH range of 1.1-3.2, employing phosphoric, phosphinic, oxalic and dichloroacetic acids as background electrolyte (BGE) constituents. The acid dissociation constant (pK(a)) of phosphinate group in phosphinic pseudopeptides and ionic mobilities of these analytes were determined from the pH dependence of their effective electrophoretic mobilities corrected to standard temperature and constant ionic strength of the BGEs. It was shown that these corrections are necessary whenever precise mobility data at very low pH are to be determined. Additionally, it was found that the ionic mobilities of the phosphinic pseudopeptides and pK(a) of their phosphinate group are affected by the BGE constituent used. The variability of migration behavior of the pseudopeptides can be attributed to their ion-pairing formation with the BGE components.     

Effect of temperature on the chromatographic retention of ionizable compounds. III. Modeling retention of pharmaceuticals as a function of eluent pH and column temperature in RPLC

We propose a general simple equation for accurately predicting the retention factors of ionizable compounds upon simultaneous changes in mobile phase pH and column temperature at a given hydroorganic solvent composition. Only four independent experiments provide the input data: retention factors measured in two pH buffered mobile phases at extreme acidic and basic pH values (e. g., at least +/- 2 pH units far from the analyte pK(a)) and at two column temperatures. The equations, derived from the basic thermodynamics of the acid-base equilibria, additionally require the knowledge of the solute pK(a )and enthalpies of acid-base dissociation of both the solute and the buffer components in the hydroorganic solvent mixture. The performance of the predictive model is corroborated with the comparison between theoretical and experimental retention factors of several weak acids and bases of important pharmacological activity, in mobile phases containing different buffer solutions prepared in 25% w/w ACN in water and at several temperatures.     

Influence of water content on the acidities in acetonitrile. Quantifying charge delocalization in anions

The effect of traces of water on the relative strengths of acids (ΔpK(a) values) in acetonitrile was quantitatively evaluated experimentally and computationally (COSMO-RS). Water affects first of all the anions by selective solvation. Expectedly, the more localized is the charge in acid anions the higher is the effect of water. The energetic effect of increasing water content from 0 to ca. 10,000 ppm on solvation enthalpies of anions ranged from 0.2-0.4 kcal mol?1 (anions with delocalized charges) to 15 kcal mol?1 in the case of the highly charge-localized acetate ion. In the case of ΔpK(a) values the change ranges from 0.01 to ca. 1.7 pK(a) units (acid pair involving acetic acid). The COSMO-RS method was found to satisfactorily describe the trends in ΔpK(a) values. To quantify the extent of charge localization/delocalization in anions a parameter, weighted average positive σ (WAPS), was introduced, which can be conveniently computed using the COSMO approach. WAPS characterizes the distribution of charge density across the molecular surface and was found to correlate well with the extent of water influence on the dissociation of the respective acid.     

Capillary electrophoretic studies of acid-base properties of sanguinarine and chelerythrine alkaloids

Capillary zone electrophoresis with UV detection was used for determination of dissociation constants of alkaloids sanguinarine and chelerythrine. Despite the limited solubility of the uncharged forms of the alkaloids resulting in insufficient analytical signal at higher pH the reliable dissociation constants were obtained when acidified samples containing low amount of the alkaloid were injected into the capillary. The precipitation of the alkaloid in the capillary induced by injecting sample of low pH into the background electrolyte of higher pH does not affect the mobility of the alkaloid if its concentration injected exceeds the solubility only to a small extent. Dissociation constants (pK(R+)) of sanguinarine and chelerythrine calculated to 8.3 +/- 0.1 and 9.2 +/- 0.1, respectively, are relevant to Good buffers of ionic strength of 30 mM.     

New aspects of buffering with multivalent weak acids in capillary zone electrophoresis: pros and cons of the phosphate buffer

Phosphate buffer is frequently used as background electrolyte in capillary electrophoresis. It can cover a broad range of pH due to the three dissociation constants (pK1 = 2.0, pK2 = 7.2, and pK3 = 11.0) of phosphoric acid and because it is UV-light transparent. This contribution brings a theoretical study of the analytical separation performance (sample window, regions of peak symmetry, regions of fronting and tailing peaks) of phosphate buffer, serving as a model of buffering with multivalent weak acids. The study is based on the use of peak shape diagrams and covers the pH range 2.55-11.43. New important general knowledge has been revealed that single multivalent weak acids mimic the performance of background electrolytes with multiple coanionic species for anionic analyses. It is shown that simple phosphate buffers prepared by mixing phosphoric acid and potassium hydroxide may exhibit up to two regions of symmetry, of fronting as well as of tailing zones, on the mobility scale inside the sample window. Moreover they may exhibit a "schizophrenic" region of enormous electromigration dispersion.     

Determination of cationic mobilities and pKa values of 22 amino acids by capillary zone electrophoresis

The effective mobilities of the cationic forms of common amino acids--mostly proteinogenic--were determined by capillary zone electrophoresis in acidic background electrolytes at pH between 2.0 and 3.2. The underivatized amino acids were detected by the double contactless conductivity detector. Experimentally measured effective mobilities were fitted with the suitable regression functions in dependence on pH of the background electrolyte. The parameters of the given regression function corresponded to the values of the actual mobilities and the mixed dissociation constants (combining activities and concentrations) of the compound related to the actual ionic strength. McInnes approximation and Onsager theory were used to obtain thermodynamic dissociation constants (pK(a)) and limiting (absolute) ionic mobilities.     

Semi-empirical relationships between effective mobility,charge, and molecular weight of pharmaceuticals by pressure-assisted capillary electrophoresis: applications in drug discovery

Relationships between effective mobility (m(eff)), calculated charge (Z(c)), and molecular weight (MW) are semi-empirically derived for pharmaceuticals using pressure-assisted capillary electrophoresis (PACE). We determined the m(eff) at 12 different pH points (2.0-11.4) of 66 pharmaceutical-like compounds ranging in MW from 79 to 825 g/mol. Plots of the observed m(eff) values versus Z(c)/MW(x ) (where x is a fractional coefficient) gave linear relationships. For anions, it was found that the best correlation (R(2) = 0.9666) exists when the fractional coefficient is equal to 0.4920, resulting in the equation m(eff) = 0.1853 (Z(c)/MW (0.4920)). For cations, the best linear relationship (R(2) = 0.9861) gave the equation m(eff) = 0.3888 (Z(c)/MW (0.6330)). The m(eff), Z(c)/MW(x) relationships were then applied to: (i) developing a technique for selecting an appropriate pH to achieve optimal separation of pharmaceuticals and (ii) determining the maximum charge of a molecule in the pH range of determination of negative log of the dissociation constants (pK(a)) by PACE, thus enabling the correct choice of model equation to be automated without structure analysis.     

Prediction of acidity in acetonitrile solution with COSMO-RS

The COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of pK(a) values in acetonitrile. For a variety of 93 organic acids, the directly calculated values of the free energies of dissociation in acetonitrile showed a very good correlation with the pK(a) values (r(2) = 0.97) in acetonitrile, corresponding to a standard deviation of 1.38 pK(a) units. Thus, we have a prediction method for acetonitrile pK(a) with the intercept and the slope as the only adjusted parameters. Furthermore, the pK(a) values of CH acids yielding large anions with delocalized charge can be predicted with a rmse of 1.12 pK(a) units using the theoretical values of slope and intercept resulting in truly ab initio pK(a) prediction. In contrast to our previous findings on aqueous acidity predictions the slope of the experimental pK(a) versus theoretical DeltaG(diss) was found to match the theoretical value 1/RT ln (10) very well. The predictivity of the presented method is general and is not restricted to certain compound classes. However, a systematic correction of -7.5 kcal mol(-1) is required for compounds that do not allow electron-delocalization in the dissociated anion. The prediction model was tested on a diverse test set of 129 complex multifunctional compounds from various sources, reaching a root mean square deviation of 2.10 pK(a) units.     

Ion-Exchange Reaction of Silver(I) and Copper(II) in Optical Sensors Based on Thiaglutaric Diamide

Bulk optode membranes based on a recently reported thiaglutaric diamide ionophore were developed for measurements of silver(I) and copper(II) ions in aqueous solutions. The response properties of optical films containing ionophore and chromoionophores with different pK(a) values were investigated at different sample pH. At certain pH the measuring range of the optode can be shifted when choosing different chromoionophores. Optode with ionophore and chromoionophore V exhibited good responses to silver ions from 10(-6) - 10(-1) M at pH 5.5. The proposed sensor showed high selectivity, good reproducibility and stability. With a different chromoionophore ETH 5418 the optode could response to copper(II) ions from 10(-6) - 10(-2) M.     

Dependence of pKa on solute cavity for diprotic and triprotic acids

A systematic study of ΔG(aq)/pK(a) for monoprotic, diprotic, and triprotic acids has been carried out based on DFT/aug-cc-pVTZ combined with CPCM and SMD solvation modeling. All DFT/cavity set combinations considered showed similar accuracy for ΔG(aq)(1)/pK(a1) (70% within ±2.5 kcal mol(-1) of experiment) while only the M05-2X/Pauling cavity combination gave reasonable results for ΔG(aq)(2)/pK(a2) when both pK(a) values are separated by more than three units (70% within ±5.0 kcal mol(-1) of experiment). The choice of experimental data is critical to the interpretation of the calculated accuracy especially for several inorganic acids. For the calculation of ΔG(aq)(3)/pK(a3), the larger experimental uncertainty and an unrealistic orbital population of diffuse function for trianions in the gas phase hinders an evaluation of the predictive performance. We find the M05-2X functional with the Pauling cavity set is the best choice for ΔG(aq)(2)/pK(a2) prediction in aqueous media while all DFT/cavity sets considered were competitive for ΔG(aq)(1)/pK(a1).     

Influence of pH on electrophoretic behavior of phenothiazines and determination of pKa values by capillary zone electrophoresis

The influence of buffer pH on the electrophoretic behavior of 13 structurally related phenothiazines and determination of pK(a) values by capillary zone electrophoresis (CZE) were investigated. The results indicate that phenothiazines with a piperazine substituent behave quite differently from those with substituents having an aliphatic side chain or a piperidine moiety over the pH range studied. To separate these phenothiazines, it is preferable to select buffer pH in the range of 2.5-3.5. The pK(a) values of phenothiazines with three different types of substituents attached at the 10-position of the phenothiazine ring were determined. The determination of pK(a) values of phenothiazines allows us to rationalize the influence of buffer pH on the migration behavior of these compounds in CZE.     

A fast high throughput method for the determination of acidity constants by capillary electrophoresis. 3. Basic internal standards

A set of 25 monoprotic bases is proposed as internal standards for pK(a) determination by capillary electrophoresis. The pK(a) of the bases is determined and compared with available literature data. The capillary electrophoresis internal standard method offers numerous advantages over other typical methods for pK(a) determination, especially of analysis time and buffer preparation. However, it requires disposing of appropriate standards with reference pK(a) value. The set of bases established in this work together with the set of acids previously established provide a reference set of compounds with well-determined acidity constants that facilitate the process of selecting appropriate internal standards for fast pK(a) determination by capillary electrophoresis in high throughput screening of pharmaceutical drugs. In addition, the performance of the method when acidic internal standards are used for the determination of acidity constants of basic internal standards has also been tested. Although higher errors may be expected in this case, good agreement is observed between determined and literature values. These results indicate that in most cases structural similarity between the analyte and the internal standard might not be an essential requirement in the internal standard method.     

Capillary electrophoresis in N,N-dimethylformamide

N,N-Dimethylformamide (DMF) is a dipolar protophilic solvent with physicochemical properties that makes it suitable as solvent for capillary electrophoresis (CE). It is prerequisite for the proper application of CE to adjust and to change the pH of the background electrolyte (BGE) in a defined manner. This was done in the present work using benzoic acid-benzoate by selecting different concentration ratios of acid and salt, and calculating the theoretical pH from the activity-corrected Henderson-Hasselbalch equation. The mobilities of the analytes (chloro- and nitro-substituted phenolates) were found to follow reasonably well the typical sigmoid mobility versus pH curve as predicted by theory. The actual mobilities and pK(a) values (at 25 degrees C) of the analytes were derived from these curves. pK(a) values were in the range of 11.1-11.7, being thus 3-4.4 units higher than in water. This pK(a) shift is caused by the destabilization of the analyte anion and the better stability (solubility) of the molecular analyte acid in DMF, which overcome the higher basicity of DMF compared to water. Absolute mobilities were calculated from the actual mobilities; they were between 32x10(-9) and 42x10(-9) m(2)/Vxs. Slight deviations of the measured mobilities from the theoretical mobility versus pH curve were discussed on the bases of ion pairing and heteroconjugation and homoconjugation of either buffer components or buffer components and analytes. Heteroconjugation was used as a mechanism for the electrically driven separation of neutral analyte molecules in a BGE where salicylate acted as complex forming ion. Rough estimation of the complexation constants for the phenolic analytes gave values in the range of 100-200 L/mol. Addition of water to the solvent decreased the effect of heteroconjugation, but it was still present up to the surprisingly high concentration of 20% water. Electrophoretically relevant parameters like ionic mobilities and pK(a) values, and conjugation and ion pairing are dependent on the water content of the solvent. The water uptake of DMF was measured when exposed to humidity of ambient air. The resulted behavior of the water uptake was found rather similar to that for acetonitrile and methanol.     

Accurate determination of low pK values by (1)H NMR titration

The NMR titration methodology to determine acid dissociation constants in aqueous solutions is extended for pK(a) values between 0 and 2, where potentiometric titrations are no longer applicable. (1)H NMR spectra are acquired for single samples of constant acid concentration (e.g. 0.02M), controlled ionic strength (I=1M with HNO(3)/NaNO(3)) and varying pH. To avoid biased pH readings due to the acid error of the glass electrode, true, concentration-based pH values are deduced by combination of the charge balance equation with information from (1)H NMR chemical shifts of the investigated acid. The method has been tested on histidine (pK(1)=1.83+/-0.02) and yielded the dissociation constant of dichloroacetic acid (pK=1.06+/-0.01) for the first time with good accuracy and precision. Dichloroacetic acid is recommended as an NMR spectroscopical "indicator molecule" for in situ monitoring the pH in strong acidic solutions of other equilibrium systems.     

葡萄糖水溶液中碳酸盐热力学研究 1.二氧化碳-碳酸氢钠-氯化钠-葡萄糖-水体系

在278.15～318.15K和一定离子强度范围内,测定了无液接电池Pt,(1-x)H~2+xCO~2│NaHCO~3(m~1),NaCl(M~2),.CO~2(m~3),葡萄糖(m~4)│AgCl-Ag的电动势,利用改进的Harned外推法和我们提出的多项式拟合法确定了二氧化碳在15%葡萄糖水溶液中的一级酸常数K 两种方法所得PK 值在实验误差范围内一致.PK 随温度变化符合经验方程PK =A~1+A~2/T+A~3T,并计算了二氧化碳在葡萄糖水溶液中解离过程的各热力学量.     

Simultaneous analysis of polyhydroxylated alkaloids by capillary electrophoresis using borate complexation and evaluation of sweeping technique for sensitivity improvement

Summary Capillary zone electrophoresis coupled to UV detection was used for the simultaneous analysis of naturally occurring polyhydroxylated alkaloids. This separation was based on anin-situ complexation with borate ions. The effect of parameters such as borate concentration, capillary temperature and analyte molecular structure on migration times and selectivity were discussed. The best separation was obtained with a fused silica capillary (48.5 cm total length ×50 μm I.D., with a bubble factor of 3), 80 mM sodium tetraborate aqueous solution at pH 9.2 and temperature of 20°C. The method was validated and showed good data in terms of migration time and peak area reproducibility, selectivity, linearity and accuracy. The validated method was applied to determine miglitol in commercially available pharmaceutical tablets. To further improve method sensitivity, a sweeping technique involving borate ions was evaluated. This technique was found very sensitive to the analyte complexation with borate, borate concentration, and temperature as well as sample matrix. In the case of miglitol, a 35-fold improvement in peak height was achieved.