Correlation of HPLC Retention Data of Triazines with the Inhibition of DHFR from L1210 Cells: Development of New Chromatographic Adsorption Parameter in QSAR

Abstract

The use of chromatographic retention measurements for quantitative structure—activity relationships (QSAR) was investigated by the development of an adjusted logarithmic retention factor. Retention data of 15 triazine derivatives, which inhibit dihydrofolate reductase were measured by HPLC on octyl-silica and silica gel columns. From these data two parameters were calculated. First, the intercept of the plot of the logarithmic retention factor versus acetonitrile concentration was calculated from the reversed-phase retention measurements (log k'o) and, second, the difference between the logarithmic retention factor at high ammonium salt concentration and low ammonium salt concentration in the mobile phase was calculated from retention measurements on the silica gel column. The first parameter represents hydrophobic properties and the second parameter characterizes adsorption properties of the triazine derivatives. The results show a correlation between the two above mentioned parameters and the inhibition of L1210/71 cell growth.     

Phase Equilibria in the System NH4Al(SO4)2–H2SO4–H2O

Equilibrium solubility curves of the ammonium aluminium sulphate in aqueous solutions of sulphuric acid have been calculated using checked literature data and our own measurements. The concentration of sulphuric acid ranged from 0 to 23 mass%, temperature range between 20 and 60°C has been extrapolated up to 75°C by means of a thermodynamically based correlation method. The solubility correlation as well as the hydration analysis implied a possible destructuralization of solutions at higher acid concentrations. This revised version was published online in August 2006 with corrections to the Cover Date.     

Fluorescence resonance energy transfer from tryptophan to folic acid in micellar media and deionised water

The fluorescence resonance energy transfer (FRET) from tryptophan (Trp) to folic acid (FA) in aqueous sodiumdodecyl sulphate, cetyltrimethyl ammonium bromide, and Brij-35 as well as deionised water was investigated using steady state and time resolved fluorescence techniques. The data obtained from steady state fluorescence spectral studies and time resolved measurement indicated that the FRET from Trp to FA occurred most effectively in aqueous sodium dodecyl sulphate micellar solutions. The distance between Trp and FA were evaluated. Binding constant, number of binding sites and thermodynamic parameters were determined for Trp-FA interactions in deionised water. The values of the thermodynamic parameters suggest that the hydrophobic forces and hydrogen bonding are the key interacting forces between Trp-FA interaction.     

Determination and correlation of the solubility of tricin in water and ethanol mixtures

The solubility of tricin in water and ethanol mixtures was measured over the temperature range of (288.15 to 328.15) K. The concentrations of tricin in the aqueous mixtures were assayed by the ultraviolet spectrophotometric method. The experimental solubility data indicated that the solubility of tricin increases with an increase in temperature and an enrichment in ethanol content. The two models, including the modified Apelblat equation and λh equation were used to correlate the experimental solubility data. The calculated solubility of tricin shows good agreement with the experimental results. Additionally, the estimation of thermodynamic properties including the activity coefficients, dissolution enthalpy, and entropy were obtained from the experimental data. Within the studied temperature range the dissolution process of tricin is endothermic, and the driving force is the entropy.     

Retention controlling and peak shape simulation in anion chromatography using multiple equilibrium model and stochastic theory

The stochastic theory of chromatography and an equilibrium based approach were used for the prediction of peak shape and retention data of anions. This attempt incorporating the potential advantages of two different chromatographic phenomena for analytical purposes. It is an integrated method to estimate kinetic and thermodynamic properties for the same chromatographic run of ions. The stochastic parameters of eluted anions, such as the residence time of the molecule on the surface of the stationary phase, and the average number of adsorption steps were determined on the basis of a retention database of organic and inorganic anions (formate, chloride, bromide, nitrate, sulphate, oxalate, phosphate) obtained by using carbonate/bicarbonate eluent system at different pHs (9-11) and concentrations (7-13 mM). In the investigated IC system the residence times are much higher and the average number of sorption steps is somewhat smaller than in RP-HPLC. The simultaneous application of the stochastic and the multispecies eluent/analyte model was utilized to peak shape simulation and the retention controlling of various anions under elution conditions of practical importance. The similarities between the measured and the calculated chromatograms indicates the predictive and simulation power of the combined application of the stochastic theory and the multiple species eluent/analyte retention model.     

Solid–liquid phase equilibrium and mixing thermodynamic analysis of coumarin in binary solvent mixtures

The solubility of coumarin in three aqueous solvent mixtures (methanol + water, ethanol + water and acetone + water) was experimentally determined by a gravimetric method at atmospheric pressure. The experimental solubility data were fitted using the modified Apelblat equation, non-random two-liquid (NRTL) equation, the combined nearly ideal binary solvent/Redlich–Kister equation and the Jouyban?Acree equation, respectively. All the equations were proven to be able to correlate the experimental data, and the modified Apelblat equation could obtain better correlation results than the other three models. The solubility of coumarin increases with increase in temperature. At the same temperature, the solubility increases with increase in mole fraction of organic solvents except for the ethanol–water system which shows a unimodal curve. In addition, the apparent thermodynamic properties of the mixing process were calculated based on the NRTL model and the experimental solubility data.     

Thermodynamic Characteristics of Phenacetin in Solid State and Saturated Solutions in Several Neat and Binary Solvents

The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning calorimetry and spectroscopic solubility measurements. The temperature-related heat capacity values measured for both the solid and melt states were provided and used for precise determination of the values for ideal solubility, fusion thermodynamic functions, and activity coefficients in the studied solutions. Factors affecting the accuracy of these values were discussed in terms of various models of specific heat capacity difference for phenacetin in crystal and super-cooled liquid states. It was concluded that different properties have varying sensitivity in relation to the accuracy of heat capacity values. The values of temperature-related excess solubility in aqueous binary mixtures were interpreted using the Jouyban–Acree solubility equation for aqueous binary mixtures of methanol, DMSO, DMF, 1,4-dioxane, and acetonitrile. All binary solvent systems studied exhibited strong positive non-ideal deviations from an algebraic rule of mixing. Additionally, an interesting co-solvency phenomenon was observed with phenacetin solubility in aqueous mixtures with acetonitrile or 1,4-dioxane. The remaining three solvents acted as strong co-solvents.     

Retention and selectivity tests of silica-based and metal-oxide bonded stationary phases for RP-HPLC

Chromatographic properties of silica-, zirconia- and alumina-based columns with octadecyl-, polyethylene glycol- and pentafluorophenylpropyl-bonded stationary phases were tested. Selectivities of nine columns for LC were characterized using chromatographic methods including Walters, Engelhardt, Tanaka and Galushko hydrophobicity and silanol activity tests, measurements of methylene selectivity in various aqueous-methanol and aqueous-acetonitrile mobile phases and of gradient lipophilic capacity as a measure of the effect of the sample hydrophobicity on gradient-elution separations. A semi-empirical interaction indices model, assuming a predominant role of the solvophobic interactions of test compounds with different polarities, was compared with the linear free energy relationships approach taking into account selective polar interactions. The interaction indices model was applied to both non-polar stationary phases bonded on silica, alumina and zirconia supports, and to the non-modified adsorbents in the normal-phase LC. The retention data of isomeric naphthalene disulfonic acids were used to compare the attractive and repulsive ionic interactions of the columns in purely aqueous mobile phases. The results of the hydrophobicity and polarity tests were consistent, and allowed column characterization and classification. Silanol activity was important with octadecyl silica columns, but was relatively insignificant with bonded polyethylene glycol and pentafluorophenylpropyl phases on silica gel support. Polar interactions with the alumina and zirconia support materials significantly affect the retention.     

Solid-solute phase equilibria in aqueous solution. IV. Calculation of Phase Diagrams

The thermodynamic principles of conventional (T-x, P-T) phase diagrams and solubility (log ΣK-x) diagrams depicting solid-solute phase equilibria in aqueous solution are derived from a unifying point of view. It is shown that thermodynamic quantities necessary for the construction of conventional phase diagrams can be obtained from solubility measurements. The unary system calcite-aragonite and the binary system aragonite-strontianite, where solubility data are available over the whole compositional range, have been selected as examples. In the latter case, the constraint of constant composition of the solid phase leading to a metastable equilibrium with the respective solute species is an essential point in the thermodynamic derivation and was observed experimentally as well.     

A new approach in modelling phase equilibria and gas solubility in electrolyte solutions and its applications to gas hydrates

This paper presents a new predictive model for phase equilibria and gas solubility calculations in the presence of electrolyte solutions. It treats salts as pseudo-components in an equation of state (EoS) by defining the critical properties and acentric factor for each salt. The water–salt, gas–salt and salt–salt binary interaction parameters (BIP) have been determined by using available experimental data on freezing point depression and boiling point elevation as well as gas solubility and salt solubility data in saline solutions.The methodology has been applied in modelling sodium chloride, potassium chloride and their mixtures, as well as solubility of methane and carbon dioxide in aqueous single and mixed electrolyte solutions.The developed model is capable of accurately predicting the phase behaviour, gas hydrate stability zone and potential salt precipitation in single and mixed electrolyte solutions. The model predictions are compared with available independent experimental data, including hydrate inhibition characteristics of single and mixed electrolyte solutions, and good agreement is demonstrated.     

Solubility parameter determination of cationic surfactants by inverse GC

Summary The solubility parameters of cationic surfactants were obtained using the inverse gas chromatographic technique. The surfactants didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and dodecyl pyridinium chloride were used as stationary phase and retention data of different probe solutes were measured at different temperatures. The results were analysed by the combination of Flory-Huggins and Hildebrand theories, and the solubility parameters of the surfactants were obtained in a range of temperatures between 80–120°C.     

Modeling of size-exclusion chromatography of electrolytes on non-ionic nanoporous adsorbents

A dynamic model has been developed for chromatographic separation of mixed electrolyte solutions with non-ionic nanoporous adsorbents. The thermodynamic equilibrium condition at the pore entrance is written in terms of mixing, electrostatic and size-exclusion effects. The model is tested against experimental data measured with three binary mixtures on hypercrosslinked polystyrene and nanoporous carbon. The selectivity of the nanoporous adsorbents can be explained by the size-exclusion of the electrolytes and enrichment of both electrolytes in frontal chromatographic runs can be correlated satisfactorily with the proposed model. The model is also used to demonstrate continuous separation in a simulated moving-bed (SMB) system.     

固定化冠醚树脂的特性及离子色谱应用研究 Ⅱ.间接光度检测中苦味酸淋洗剂的一些性质

本文报道用固定化冠醚作色谱填料的无抑制柱间接光度离子色谱法中高灵敏度淋洗剂的性能。苦味酸具有稳定的生色基团和较高的摩尔吸光系数,光学性质良好,是间接光度离子色谱法中优良的淋洗剂。苦味酸浓度以4×10~(-6)mol/L 为最佳。在苦味酸中引入少量甲醇、乙醇、丙酮或氯仿,对提高淋洗剂的灵敏度有利。在苦味酸浓度相同的条件下比较几种填料,其色谱峰高按如下次序递增,固定化二苯并-18-冠-6<固定化二苯并-30-冠-10<固定化苯并-15-冠-5。     

Influence of surface modification on protein retention in ion-exchange chromatography: Evaluation using different retention models

A large number of different stationary phases for ion-exchange chromatography (IEC) from different manufacturers are available, which vary significantly in a number of chemical and physical properties. As a consequence, binding mechanisms may be different as well. In the work reported here, the retention data of model proteins (α-lactalbumin, β-lactoglobulin A, bovine serum albumin and alcohol dehydrogenase) were determined for three anion-exchange adsorbents based on synthetic copolymer beads with differences in the functional group chemistry. Fractogel EMD DEAE and Fractoprep DEAE consist of functional groups bound to the surface via “tentacles”, ToyopearlDEAE by a short linker. Three models which describe chromatographic retention were used to analyse the characteristic parameters of the protein/stationary-phase interactions. The number of electrostatic interaction between the stationary phase and the model proteins, the protein specific surface charge densities and the interacting surface of the proteins with the adsorptive layer of the chromatographic media depend on the surface modification as well as on the molecular mass of the model proteins. In general, protein retention of the model proteins on the weak anion exchangers was found to be greater if the stationary phase carries tentacles and protein mass is above 60 kDa.     

Cobalt(II) Oxide Solubility and Phase Stability in Alkaline Media at Elevated Temperatures

A platinum-lined, flowing autoclave facility was used to investigate the solubility behavior of cobalt(II) oxide (CoO) in deoxygenated ammonium and sodium hydroxide solutions between 22 and 288°C. Co(II) ion activity in aqueous solution was controlled by a hydrous Co(II) oxide when nitrogen was used for deoxygenation and by metallic cobalt when hydrogen was used. Measured cobalt solubilities are interpreted using a Co(II) ion hydroxo- and amminocomplexing model and thermodynamic functions for these equilibria were obtained from a least-squares analysis of the data. A common set of thermodynamic properties for the species Co(OH)⁺, Co(OH)₂(aq) and Co(OH)(NH₃)⁺ is provided to permit accurate cobalt oxide solubility calculations over broad ranges of temperature and alkalinity.     

Measurement and correlation of the solubility of MnSO4·H2O in ethanol + water + MgSO4·7H2O solutions

Data on the solubility of manganese sulphate monohydrate in water, and in aqueous alcohols is essential for salting-out crystallisation studies. The solubilities of the quaternary system MnSO₄·H₂O + MgSO₄·7H₂O + H₂O + EtOH were determined in the temperature range 293.2–323.2 K over the ethanol mole fraction range of 0.00–0.12. The solubility data were used for modelling with the modified extended electrolyte non-random two-liquid (NRTL) equation. The present extension uses ion-specific parameters instead of the electrolyte-specific NRTL binary interaction parameters. This approach has feasibility for many electrolytes and mixed aqueous solution systems in principle. The model was found to correlate the solubility data satisfactorily.     

A Chromatographic Study of the Lewis Acid-Base Chemistry of Zirconia Surfaces

Abstract

The chromatographic properties of porous microparticulate zirconium oxide surfaces in aqueous media are highly dependent upon the chemical composition of the eluent. In particular, retention is controlled by the type and concentration of “hard” Lewis bases when these species are present in the eluent. Ligand exchange is the dominant mechanism for the retention of solutes which are Lewis bases. Consequently, the capacity factor and plate height depend on both the thermodynamic and kinetic properties of whatever competing Lewis bases may be present in the eluent. These Lewis base eluent components act to control retention in two ways. They modify the net ligand exchange contribution to retention, and they serve as sites for secondary interactions, such as hydrogen bonding and hydrophobic interactions between solutes and the dynamic stationary phase.     

Abraham Model Correlations for Triethylene Glycol Solvent Derived from Infinite Dilution Activity Coefficient,Partition Coefficient and Solubility Data Measured at 298.15 K

A gas chromatographic headspace analysis method was used to experimentally determine gas-to-liquid partition coefficients and infinite dilution activity coefficients for 29 liquid organic solutes dissolved in triethylene glycol at 298.15 K. Solubilities were also determined at 298.15 K for 23 crystalline nonelectrolyte organic compounds in triethylene glycol based on spectroscopic absorbance measurements. The experimental results of the headspace chromatographic and spectroscopic solubility measurements were converted to gas-to-triethylene glycol and water-to-triethylene glycol partition coefficients, and molar solubility ratios using standard thermodynamic relationships. Expressions were derived for solute transfer into triethylene glycol by combining our measured experimental values with published literature data. Mathematical correlations based on the Abraham model describe the observed partition coefficient and solubility data to within 0.16 log₁₀ units (or less).