Martí Rosés

Dissociation constants of neutral and charged acids in methyl alcohol. The acid strength resolution

Abstract A comprehensive and critical compendium of the pKa values in methanol of phenol derivatives, carboxylic acids, both aliphatic and aromatic acid derivatives, protonated amines and nitrogen-protonated heterocyclic bases is given in this paper. Values have been correlated with those obtained in aqueous solution and linear relationships for each series of compounds have been established. The proposed equations can be used to estimate accurately the dissociation constant value in water or in methanol of any compound of the mentioned chemical families, from the experimental value in methanol or in water, respectively. The acid strength resolution in the alcohol with reference to water is discussed according to the chemical structure of the compounds involved and to the solvating properties of methanol and water.

HYDROGEN BONDING. 42. CHARACTERIZATION OF REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC C18 STATIONARY PHASES

The linear free energy equation logk′ = c + rR2 + sπ2H + a∑α2H + b∑β2 + vVx was applied to the capacity factors for various sets of solutes on C18 stationary phases with aqueous methanol and acetonitrile eluents. Here, k′ are the capacity factors for a series of solutes with a given C18 phase and a given eluent, and R2, π2H, ∑α2H, ∑β2, Vx are parameters or descriptors of the solutes as follows: R2 is an excess molar refraction, π2H is the solute polarizability/dipolarity, ∑α2H and ∑β2 are the solute hydrogen–bond acidity and basicity and Vx is the solute volume. It is shown that although the regression coefficients r, s, a, b and v vary widely within the C18 column and mobile phase used, the ratios r/v, s/v, a/v and b/v are remarkably constant. Thus, for the retention of 25 series of solutes on six different C18 columns with 30-90% aqueous methanol as the eluent, all the 25 LFER equations can be combined into one general equation: logk′ = c + v(0.13 R2 − 0.32 π2H − 0.22 ∑α2H − 0.90 ∑β2O + 1.00 Vx) where only c and v vary from system to system. For 11 other phases for which data are available, the ratios v/A and (v + c)/A are constant, where A is the quantity of stationary phase per unit surface area. Similar results were found with C18 phases and aqueous acetonitrile as eluents. Although a first examination of equations based on the first equation above suggests that various C18 phases behave differently, for example the v coefficient, that is related to the observed hydrophobicity of a stationary phase relative to the mobile phase, varies considerably from phase to phase with the same eluent, a detailed analysis led to the conclusion that all the C18 phases examined have roughly the same hydrophobicity, when the v coefficients are corrected for the quantity of stationary phase per unit surface area. It is suggested that these corrected v coefficients, v/A and (v + c)/A, can be regarded as the ‘intrinsic’ phase hydrophobicity.

Comparison of the acidity of residual silanol groups in several liquid chromatography columns

The silanol acidity of Waters Resolve C18, Waters Resolve silica, Waters Symmetry C18, Waters Symmetry silica, Waters XTerra MS C18 and underivatized XTerra columns has been measured from the retention of LiNO3 with a methanol/water (60:40) mobile phase buffered to different pH values. The Li+ cation is retained by cationic exchange with the background cation of the mobile phase (Na+) through the ionized silanols. The number of active silanols increases in the order: XTerra MS C18 << Symmetry C18 < underivatized XTerra << Resolve C18 < Resolve silica approximately equal to Symmetry silica. XTerra MS C18 does not present any residual silanol acidity up to s(s)pH 10.0 (pH in 60% methanol) as measured by LiNO3. The underivatized XTerra packing and Symmetry C18 present active silanols only at s(s)pH values higher than 7.0. For the other three columns, two different types of silanols with different acidity (s(s)pKa values about 3.5-4.6 and 6.2-6.8, respectively) have been observed. Symmetry C18 shows evidence of the presence of active basic sites that retain NO3- by anionic exchange.

Solute–solvent and solvent–solvent interactions in binary solvent mixtures. Part 1. A comparison of several preferential solvation models for describing ET(30) polarity of bipolar hydrogen bond acceptor-cosolvent mixtures

The influence of solute–solvent and solvent–solvent interactions on the preferential solvation of solvatochromic indicators in binary solvent mixtures of Bipolar hydrogen bond acceptors has been studied. Several equations based on solvent exchange models that relate the transition energy of the Dimroth–Reichardt ET(30) indicator with the solvent composition are derived and compared. The models tested assume that the two solvents mixed interact to form a common structure with an ET(30) value not always intermediate between those of the solvents mixed. The solvatochromic indicator can be preferentially solvated by any of the solvents mixed or by the mixed solvent obtained. The parameters obtained explain the strong synergism observed for some of the mixtures with strong hydrogen bond donors (alcohols and chloroform).

Influence of mobile phase acid-base equilibria on the chromatographic behaviour of protolytic compounds.

A review about the influence of mobile phase acid-base equilibria on the liquid chromatography retention of protolytic analytes with acid-base properties is presented. The general equations that relate retention to mobile phase pH are derived and the different procedures to measure the pH of the mobile phase are explained. These procedures lead to different pH scales and the relationships between these scales are presented. IUPAC rules for nomenclature of the different pH are also presented. Proposed literature buffers for pH standardization in chromatographic mobile phases are reviewed too. Since relationships between analyte retention and mobile phase pH depends also on the pKa value of the analyte, the solute pKa data in water-organic solvent mixtures more commonly used as chromatographic mobile phase are also reviewed. The solvent properties that produce variation of the pKa values with solvent composition are discussed. Chromatographic examples of the results obtained with the different procedures for pH measurement are presented too. Application to the determination of aqueous pKa values from chromatographic retention data is also critically discussed.

Acidity in methanol–water

Abstract The different factors influencing acidity of solutes in methanol–water (acidity of the solute, basicity and dielectric constant of the solvent, and specific solute–solvent interactions) are discussed. General thermodynamic models and preferential solvation models are used to establish linear relationships between the acidity pK values of a family of compounds in any methanol–water mixture and the pK values of the compounds in water. The parameters (slope and intercept) of the relationships are related with solvent composition for the most common families of compounds (phenols, carboxylic acids, amines and pyridine derivatives). These equations allow accurate calculation of the pK values of any member of these families at any methanol–water mixture from the pK value of the compound in water, or conversely estimation of the pK value in water from pK values measured in methanol–water mixtures. Some examples of prediction, including chromatographic retention of acid–base compounds, are presented.

Retention of Ionizable Compounds on HPLC. 2. Effect of pH, Ionic Strength, and Mobile Phase Composition on the Retention of Weak Acids

A new model that relates the retention of a weak acid in HPLC columns with the pH and ionic strength of the mobile phase is derived and tested for different benzoic acids in methanol-water mobile phases. The proposed model uses the pH value in the mobile phase instead of the pH value in water, takes into account the effect of the activity coefficients, and considers different holdup times for the neutral and ionic species. The dependence of the holdup time of the ionic species on the mobile phase properties (pH, solvent composition, and ionic strength) is evaluated. It is demonstrated that the holdup time of the neutral species does not depend on the mobile phase properties, but the holdup time of the ionic species depends on the particular buffer used. The proposed equations can be combined with previously derived equations that relate the retention with the solvent composition of the mobile phase to establish a general model that relates the retention of the solute with the significant mobile phase properties:  composition, pH, and ionic strength.

Solute-solvent and solvent-solvent interactions in binary solvent mixtures. Part 7. Comparison of the enhancement of the water structure in alcohol-water mixtures measured by solvatochromic indicators

A preferential solvation model that takes into account the enhancement of the structure of water when small amounts of alcohol are added was applied to solvatochromic data for binary mixtures of water with 2-methylpropan-2-ol, propan-2-ol, ethanol and methanol. Application of the model allows the calculation of the effect of the enhancement of the water structure on solvatochromic solvent properties. It is demonstrated that the enhancement of water structure increases the solvent dipolarity/polarizability and hydrogen-bond donor acidity and decreases the solvent hydrogen-bond acceptor basicity. The effect decreases in the order 2-methylpropan-2-ol–water, propan-2-ol–water, ethanol–water and methanol–water.

Retention of ionizable compounds in high-performance liquid chromatography: 14. Acid–base pK values in acetonitrile–water mobile phases

Linear relationships between sspKa values in acetonitrile-water mixtures and wwpKa values in pure water have been established for five families of compounds: aliphatic carboxylic acids, aromatic carboxylic acids, phenols, amines, and pyridines. The parameters (slope and intercept) of the linear correlations have been related with acetonitrile-water composition. The proposed equations allow accurate estimation of the pKa values of any member of the studied families at any acetonitrile-water composition up to 60% of acetonitrile in volume (100% for pyridines). Conversely, the same equations can be used to estimate aqueous pKa values from chromatographic pKa values obtained from any acetonitrile-water mobile phase between the composition range studied. Estimation of pKa values have been tested with chromatographic literature data.

Retention of ionizable compounds on HPLC. 6. pH measurements with the glass electrode in methanol–water mixtures

The relationship, delta values, between the two rigorous pH scales, S(S)pH (pH measured in a methanol-water mixture and referred to the same mixture as standard state) and S(W)pH (pH measured in a methanol-water mixture but referred to water as standard state), in several methanol-water mixtures was determined (delta = S(W)pH-S(S)pH). Delta values were measured using a combined glass electrode and a wide set of buffer solutions. The results are consistent with those obtained with the hydrogen electrode. This confirms the aptness of the glass electrode to achieve rigorous pH measurements in methanol-water mixtures. An equation that relates delta and composition of methanol-water mixtures, and allows delta computation at any composition by interpolation, is proposed. Therefore, S(S)pH can be achieved from the experimental S(W)pH value and delta at any mobile phase composition. S(S)pH (or S(W)pH) values are related to the chromatographic retention of ionizable compounds through their thermodynamic acid-base constants in the methanol-water mixture used as mobile phase. These relationships were tested for the retention variation of several acids and bases with the pH of the mobile phase. Therefore, the optimization of the mobile phase acidity for any analyte can be easily reached avoiding the disturbances observed when W(W)pH is used.