Free group contributions

Platts, J. A., Abraham, M. H., Butina, D., Hersey, A. Estimation of molecular linear free energy relationship descriptors by group contribution approach. 2. Prediction of partition coefficient. J. Chem. Inf. Comput. Sci. 2000, 40, 71-80. 

Much effort has been expended on models that can be used to predict the solubility behavior of solutes, with good success being attained using a semi-empirical, group contribution approach [75]. In this system, the contributions made by individual functional groups are summed to yield a composite for the molecule, which implies a summation of free energy contributions from constituents. This method has proven to be useful in the prediction of solubility in water and in water-cosolvent mixtures. In addition to the simplest methodology, a variety of more sophisticated approaches to the prediction of compound solubility have been advanced [68]. 

For intramolecular reactions the situation is different. Here the free-energy contribution from the non-reacting part of the molecule can be, and quite often is, most significant. Moreover, steric restrictions due to the intervening chain can significantly alter the way in which the end-groups interact in the... 

Xiang, T. X. and Anderson, B. D. (2002). A computer simulation of functional group contributions to free energy in water and a DPPC lipid bilayer, Biophys. J., 82, 2052-2066. 

Free energy changes and equilibrium constants calculated from the enthalpy and entropy values estimated by the group-contribution method generally are reliable only to the order of magnitude. For example, Andersen et al. [1] have found that their estimated enthalpies and entropies usually differ from experimental values [7]... 

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