Solubility group contribution methods

An extensive series of studies for the prediction of aqueous solubility has been reported in the literature, as summarized by Lipinski et al. [15] and jorgensen and Duffy [16]. These methods can be categorized into three types 1 correlation of solubility with experimentally determined physicochemical properties such as melting point and molecular volume 2) estimation of solubility by group contribution methods and 3) correlation of solubility with descriptors derived from the molecular structure by computational methods. The third approach has been proven to be particularly successful for the prediction of solubility because it does not need experimental descriptors and can therefore be applied to collections of virtual compounds also. 

The group contribution method allows the approximate calculation of solubility by summing up fragmental values associated with substmctural units of the compounds (see Section 7.1). In a group contribution model, the aqueous solubility values are computed by Eq. (12), where log S is the logarithm of solubility, C is the number of occurrences of a substmctural group, i, in a molecule, and is the relative contribution of the fragment i. 

The disadvantages of the group contribution method are that 1) the groups included must be defined in advance and therefore the solubility of a new compound... 

QSAJi Methods for Fluid Solubility Prediction. Several group contribution methods for predicting Hquid solubiHties have been developed. These methods as weU as other similar methods are often called quantitative stmcture-activity relationships (QSARs). This field is experiencing rapid development. 

Ktihne, R., Ebert, R.-U., Kleint, F., Schmidt, G., Schuurmann, G. (1995) Group contribution methods to estimate water solubility of organic chemicals. Chemosphere 30, 2061-2077. 

It is possible to calculate the solubility parameter and the solubility parameter components of almost all molecules and polymers by a group contribution method (Van Krevelen, 1990 Bicerano, 1996). For this purpose, as explained by Van Krevelen (1990) it is useful to introduce the molar attraction constant simply defined as ... 

A newer approach uses group-contribution methods to predict solubility. It has been remarkably successful when applied to nonpolymer solutions and there are indications that it will be equally successful for treating polymer solutions (17). 

In group contribution methods, solubility is assumed to be an additive-constitutive property. That is, each fragment of a molecule possesses some intrinsic solubility. Thus, solubility of a molecule can be expressed as a summation of the solubility of all the groups as... 

The group contribution method has also been pursued by other researchers. Klopman et al. (1992) deLned contribution values to aqueous solubility for a large set of groups and determined solubility using Equation 3.50 ... 

Example 2. Estimate the solubility of naphthalene and methylparaben in water, using the group contribution method. 

The Hildebrand solubility parameters may be calculated using group contribution methods, wherein the overall solubility parameter is the sum of contributions from Van derV feals dispersion forces, Sd dipole-dipole interaction and hydrogen bonding. 

Yalkowsky, Myrdal, and co-workers have developed the AQUAFAC group contribution method which predicts the molar activity coefficient ym from which the molar solubility S can be deduced, using supplemental information on the fugacity ratio F (Myrdal et al., 1992,1993,1995). The method exploits the AQUASOL database described by Dannenfelser and Yalkowsky (1991) and Yalkowsky and Dannenfelser (1991). The fugacity ratio (which is termed the "ideal solubility" in their publication) is expressed as... 

Two methods are recommended for routine use for estimating solubility the correlation with octanol water partition coefficient method and the AQUAFAC group contribution method. When possible, use both approaches and compare the results. Insights can also be obtained if solubility data are available for structurally similar compounds. Both methods are illustrated below. 

This approach to estimating solubilities and diffusion rates has not been applied to other classes of solutes, even though the solubility parameters can be easily estimated by group contribution methods and AHf and T can be determined by differential scanning calorimetry. 

The other approach recommended by Mackay (2000) is a group contribution method to derive the molar activity coefficient, calculating the solubility (the AQUAFAC method, Myrdal et al. [1992 1993 1995]). 

Baner, A. L. The estimation of partition coefficients, solubility coefficients and permeability coefficients for organic molecules in polymers using group contribution methods. New Developments in the Chemistry of Packaging Materials. ACS Symposium Dallas 1998. ACS Symposium Series, ACS Washington D.C. 1999. 

Goydan. R Reid, R.C., Tseng, H. Estimation of the solubilities of organic compounds in polymers by group-contribution methods. Ind. Eng. Chem. Res., 1989.28 445-454. 

Although rigorous additivity rules are not applicable in this case, a fair estimation of the cohesive energy and the solubility parameter of polymers can be made by group contribution methods. 

---