Other Methods-based Solubility

The methods which have been outlined and illustrated above can be applied only to pure compounds. When a mixture is to be studied the problem becomes more complicated. It is often impossible to separate readily the constituents of a mixture by distillation or crystallization, and other methods based on the difference in chemical properties or solubilities of the constituents of the mixture, are often used. 

Thus, a list of 1 5 descriptors was calculated for these purposes, as described below. The partition coefficient log P (calculated by a method based on the Gho.sc/Crip-pen approach [11]) (see also Chapter X, Section 1.1 in the Handbook) was calculated because it affects the solubility dramatically [17, 18]. All the other descriptors were calculated with the program PETRA (Parameter Estimation for the Treatment of Reactivity Applications) [28. ... 

Gravimetric methods based on precipitation or volatilization reactions require that the analyte, or some other species in the sample, participate in a chemical reaction producing a change in physical state. For example, in direct precipitation gravimetry, a soluble analyte is converted to an insoluble form that precipitates from solution. In some situations, however, the analyte is already present in a form that may be readily separated from its liquid, gas, or solid matrix. When such a separation is possible, the analyte s mass can be directly determined with an appropriate balance. In this section the application of particulate gravimetry is briefly considered. 

Cristol et al. (17) have based a method for the determination of p,p -DDT in technical DDT on the fact that the p,pf isomer is almost insoluble in 70% aqueous ethyl alcohol and the o,p isomer is soluble. The method has not been tried with mixtures of the other chlorinated hydrocarbons. 

Other methods employ a microplate format followed by fast HPLC. Some researchers approach the determination from a different perspective. For example, an alternative method for ionizable substances is the pSol determination based on an acid-base titration.25 26 Kinetic solubility determinations involve determining the concentration of the compound in the buffer of interest when an induced precipitate first appears. 

The monazite sand is heated with sulfuric acid at about 120 to 170°C. An exothermic reaction ensues raising the temperature to above 200°C. Samarium and other rare earths are converted to their water-soluble sulfates. The residue is extracted with water and the solution is treated with sodium pyrophosphate to precipitate thorium. After removing thorium, the solution is treated with sodium sulfate to precipitate rare earths as their double sulfates, that is, rare earth sulfates-sodium sulfate. The double sulfates are heated with sodium hydroxide to convert them into rare earth hydroxides. The hydroxides are treated with hydrochloric or nitric acid to solubihze all rare earths except cerium. The insoluble cerium(IV) hydroxide is filtered. Lanthanum and other rare earths are then separated by fractional crystallization after converting them to double salts with ammonium or magnesium nitrate. The samarium—europium fraction is converted to acetates and reduced with sodium amalgam to low valence states. The reduced metals are extracted with dilute acid. As mentioned above, this fractional crystallization process is very tedious, time-consuming, and currently rare earths are separated by relatively easier methods based on ion exchange and solvent extraction. 

There are several properties of a chemical that are related to exposure potential or overall reactivity for which structure-based predictive models are available. The relevant properties discussed here are bioaccumulation, oral, dermal, and inhalation bioavailability and reactivity. These prediction methods are based on a combination of in vitro assays and quantitative structure-activity relationships (QSARs) [3]. QSARs are simple, usually linear, mathematical models that use chemical structure descriptors to predict first-order physicochemical properties, such as water solubility. Other, similar models can then be constructed that use the first-order physicochemical properties to predict more complex properties, including those of interest here. Chemical descriptors are properties that can be calculated directly from a chemical structure graph and can include abstract quantities, such as connectivity indices, or more intuitive properties, such as dipole moment or total surface area. QSAR models are parameterized using training data from sets of chemicals for which both structure and chemical properties are known, and are validated against other (independent) sets of chemicals. 

Differential Solubility Methods. Numerous methods have been developed to obtain one or more of the various caseins from whole casein or directly from skim milk based on their differential solubility (Thompson 1971 Mackinlay and Wake 1971 Whitney 1977). While some early procedures indicated the possibility of fractionating whole casein into different components, it was not until the 1950s that systematic procedures were proposed for the fractionation of casein into Warner s a-, 0-, and y-caseins. Hipp et al. (1952) developed two procedures which have been used extensively or partially incorporated into other methods. The first is based upon the differential solubilities of the caseins in 50% alcohol in the presence of ammonium acetate by varying the pH, temperature, and ionic strength. The second procedure involves the dispersion of whole casein in 6.6 M urea and the separa-... 

The method was tested on a validation set consisting of 205 compounds (41 nonpolar and 164 polar chemicals). In addition, the method was compared to regression methods using S and Kow as the input variables. Results show that this model outperforms and covers a wider range of chemical structures than models based on Kow aqueous solubility, or single MCIs. Meylan et al. (1992) concluded that the MCI-fragment contribution method was clearly superior in the prediction of K(k , although in many cases experimental values of S and Kow were not available and estimated values were used. They presented no direct comparison with other MCI-based estimation methods. 

The separation methods described in Section IV for pairs of optically active diastereoisomers have also been applied to mixtures of diaste-reoisomeric pairs of enantiomers. By one or other of the following methods, it was possible to separate diastereoisomeric pairs of enantiomers completely or, at least, to obtain enriched fractions. In chromatography under achiral conditions, enantiomers are eluted at identical rates. Therefore, the.pairs of enantiomers (RR )l(SS ) and (RS )I(SR ) can be separated chromatographically in the same way as a pair of optically active diastereoisomers (RS1) and (SS ). By application of the methods based on solubility differences for many examples, fractions containing the less soluble pair of enantiomers could be separated from fractions containing the more soluble pair of enantiomers. However, with respect to the separation.by solubility differences, the situation with two diastereoisomeric pairs of enantiomers is more complicated than that of a pair of... 

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