Solubility method comparisons

Glomme, A., Marz, J., Dressman, J. B. Comparison of a miniaturized shake-flask solubility method with automated potentiometric acid/base titrations and calculated solubilities. /. Pharm. Set. 2005, 94, 1-15. 

This observed behavior of soy proteins complicates the definition of soy protein solubility, the comparison of solubility data, and the interpretation of solubility experiments. Because the thermodynamic criteria are not met, protein solubility becomes an operationally defined quantity that depends upon the experimental methods of measurement. A number of different operational definitions have been used to measure protein solubility. Each has its own advantages and disadvantages, and limited utility. This plurality, though often desirable, makes it difficult to compare experimental results. 

Glomme A, Marz J, and Dressman JB. Comparison of a Miniaturized Shake-Flask Solubility Method with Automated Potentiometric Acid/Base Titrations and Calculated Solubilities. yPAarro Sci 2005 94 1-16. 

For soluble polymers, comparison with their solution spectra offers the simplest means to assign the resonances in their CPMAS/DD solid-state spectra. On the other hand, those polymers that cannot be dissolved, melted or sufficiently swollen to provide high-resolution liquid-state spectra for comparison, can be observed in the solid with methods comparable to those developed for editing solution-state spectra. It is easier to describe these methods with the aid of a qualitative understanding of how the dilute C and abundant spins interact in a typical solid, organic sample. 

To demonstrate the possibilities of the discussed variants of oxoacidity determination, let us consider the corresponding results obtained in Li -based chloride melts. The method for HCI/H2O acid-base pair yields for KCl-LiCl eutectic value of Q (pl ) ca. 8, whereas the solubility method gives value of and the use of Cr207/CrO acid-base pair permits to estimate plKci-Lici 3.6. It is interesting that the oxobasicity index of 2CsCl-LiCl melt is found in the mentioned above paper to be ca 3.8. The presented comparison shows that the use of HCI/H2O leads to overestimation of oxoacidic properties of the chloride melts whereas the results of other approaches are practically coincident. 

Characteristics of the system as nitrating reagents Wibaut, who introduced the competitive method for determining reactivities (his experiments with toluene, benzene and chlorobenzene were performed under heterogeneous conditions and were not successful), pointed out that solutions of nitric acid in acetic anhydride are useful in making comparisons of reactivities because aromatic compounds are soluble in them. ... 

These methods are now obsolete in comparison with spectroscopic methods. Werbel has shown that the structures of these isomers are easily determined by NMR (125) (see also Table VI-5). Furthermore. 2-imino-4-thiazoline derivatives are characterized by their stretching C=N vibration at 1580 cm , absent in their 2-aminothiazole isomers, and by the stretching NH vibration that appears in the range of 3250 to 3310 cm for the former and between 3250 to 3340 cm" for the latter (131). Ultraviolet spectroscopy also differentiates these isomers (200). They can be separated by boiling in ethanol the thiazoline isomer is usually far less soluble in this solvent (131),... 

Commercial Hquid sodium alumiaates are normally analyzed for total alumiaa and for sodium oxide by titration with ethylene diaminetetraacetic acid [60-00-4] (EDTA) or hydrochloric acid. Further analysis iacludes the determiaation of soluble alumiaa, soluble siHca, total iasoluble material, sodium oxide content, and carbon dioxide. Aluminum and sodium can also be determiaed by emission spectroscopy. The total iasoluble material is determiaed by weighing the ignited residue after extraction of the soluble material with sodium hydroxide. The sodium oxide content is determiaed ia a flame photometer by comparison to proper standards. Carbon dioxide is usually determiaed by the amount evolved, as ia the Underwood method. 

Eros D, Keri G, Kovesdi I, Szantai-Kis C, Meszaros G and Orfi L. Comparison of predictive ability of water solubility QSPR models generated by MLR, PLS and ANN methods. Mini Rev Med Chem 2004 4 167-77. 

Yang G, Ran Y and Yalkowsky SH. Prediction of the aqueous solubility comparison of the general solubility equation and the method using an amended solvation energy relationship. J Pharm Sci 2002 91 517-33. 

Furthermore, pH electrode calibration can be performed in situ by the new method [48], concurrently with the pKj determination. This is a substantial improvement in comparison to the traditional procedure of first doing a blank titration to determine the four Avdeef-Bucher parameters [24]. The traditional cosolvent methods used with sparingly soluble molecules can be considerably limited in the pH<4 region when DMSO-water solutions are used. This is no longer a serious problem, and routine blank titrations are now rarely needed in the new in situ procedure. 

As a result of Eq. (11) we are able to calculate the chemical potential of any molecule X in any liquid system S, relative to the chemical potential in a conductor, i.e. at the North Pole. Hence, COSMO-RS provides us with a vehicle that allows us to bring any molecule from its Uquid state island to the North Pole and from there to any other liquid state, e.g. to aqueous solution. Thus, given a liquid, or a reasonable estimate of AGjis of a soUd, COSMO-RS is able to predict the solubility of the compound in any solvent, not only in water. The accuracy of the predicted AG of transfer of molecules between different Uquid states is roughly 0.3 log units (RMSE) [19, 22] with the exception of amine systems, for which larger errors occur [16, 19]. Quantitative comparisons with other methods will be presented later in this article. 

Since most drug discovery projects deal with very sparingly soluble compounds, the usual CE sample concentration would lead to precipitation. The handling of real dmg candidate molecules is poorly developed in CE applications, in comparison to the most robust potentiometric method. 

Similarly, concepts of solvation must be employed in the measurement of equilibrium quantities to explain some anomalies, primarily the salting-out effect. Addition of an electrolyte to an aqueous solution of a non-electrolyte results in transfer of part of the water to the hydration sheath of the ion, decreasing the amount of free solvent, and the solubility of the nonelectrolyte decreases. This effect depends, however, on the electrolyte selected. In addition, the activity coefficient values (obtained, for example, by measuring the freezing point) can indicate the magnitude of hydration numbers. Exchange of the open structure of pure water for the more compact structure of the hydration sheath is the cause of lower compressibility of the electrolyte solution compared to pure water and of lower apparent volumes of the ions in solution in comparison with their effective volumes in the crystals. Again, this method yields the overall hydration number. 

To prevent the formation of wine crystals during the bottling process, winemakers use a method known as cold stabilization. By lowering the temperature of the wine to 19-23°F for several days or weeks, the solubility of tartrate crystals is lowered, forcing the crystals to sediment. The resulting wine is then filtered off the tartrate deposit. The temperature dependence of the solubility of potassium bitartrate is readily apparent in the following comparison while 162 ml of water at room temperature dissolves 1 g of the salt, only 16 ml of water at 100°C are needed to solubilize the same amount of saltJ l Recent developments employ a technique known as electrodialysis to remove tartrate, bitartrate, and potassium ions from newly fermented wine at the winery before potassium bitartrate crystals form. 

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