Water solubility prediction

Ktihne, R., Ebert, R-U., Schtitirmann, G. Model selection based on structural similarity - method description and application to water solubility prediction. f Chem. Inf Model. 2006, 46, 636-641. 

Problem 9.10 To be an active chemotherapeutic agent, a drug must be somewhat water soluble. Predict the solubility properties of epothilone B in water and organic solvents. 

In each of the following, both compounds are water-soluble. Predict whether a precipitate will form when solutions of the two are mixed, and, if so, identify the compound that precipitates, (a) Pb(N03)2, Nal (b) Ba(N03)2, KCl (c) (NH4)2S, AgNO,... 

Solvation increases solubility above predicted values. When the components of a solution possess an abnormally large attraction for each other, solvates are formed. Thus certain oxygen-containing compounds have a great tendency to form hydrates, thus contributing to increased water solubility hydrogen bondir also plays an important role. 

HEC is generally compatible with other ceUulosic water-soluble polymers to give clear, homogeneous solutions. When mixed with an anionic polymer such as CMC, however, interactions between the two polymers may result in synergistic behavior, ie, viscosities higher than predicted and calculated. HEC has excellent compatibiUty with natural gums. 

Polyphosphazenes can be considered as biomaterials in several different ways, depending on the type of utilization one can predict for these substrates. In this regard, we will consider three different topics concerning water-soluble POPs and their hydrogels, bioerodible POPs for drug delivery systems and for tissue engineering, and the surface implications of POP films. 

Here is a rule of thumb that can help us predict solubility in order to have a high water-solubility, there should be no more than 5 carbon atoms per OH group. A compound with two OH groups and 7 carbon atoms will be very soluble in water. A compound with one OH group and 7 carbon atoms will NOT be very soluble in water. There are, of course, many exceptions to this simplified rule of thumb, but the rule can be helpful whenever we need to make a quick prediction about the solubility of an alcohol. 

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. 

For aqueous solutions, ascorbate can be included in the hierarchy, while a-tocopherol has to be replaced by its water-soluble analogue trolox, which is often assumed to have the same standard reduction potential. The ordering of the antioxidants based on the two different determinations of E in water is rather similar, and it should be noted that ascorbate is the antioxidant which will regenerate the other antioxidants, with the ascorbate itself ending up being oxidised. In contrast to what was observed for DMF, the ordering in water predicts that quercetin could regenerate a-tocopherol from its oxidised form. 

Water solubility, dissociation constant(s) and n-octanol/water partition coefficients allow one to predict how an analyte may behave on normal-phase (NP), reversed-phase (RP), or ion-exchange solid-phase extraction (SPE) for sample enrichment and cleanup. 

A theoretical prediction of water-soluble polymer solutions is difficult to obtain due to their ability to build up aggregations and associations. A prediction of the viscosity yield is much easier to observe for solutions of synthetic polystyrene due to its simple solution structure. These solutions have been well characterized in other studies [19-23] concerning their chemical composition, molar mass and sample polydispersity. 

Anderson, B. D., Conradi, R. A., Predictive relationships in the water solubility of salts of a nonsteroidal anti-inflammatory drug, J. Pharm. Sci. 74, 815-820 (1985). 

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