The molecular surface areas for 158 aliphatic hydrocarbons, olefins, alcohols, ethers, ketones, aldehydes, esters, and fatty acids have been computed and correlated with their aqueous solubilities. The hydrocarbon and functional group contributions to the free energy of solution are compared and discussed with particular regard to the chosen standard state. The results indicate that the functional group contributions to the free energy of solution in water are nearly equivalent from the pure liquid standard state while being significantly different when the gas phase (1 mmHg) standard state is chosen. The interpretation of the differing hydrocarbon surface area slopes is shown to be complicated by mutual miscibility considerations (water solubility in the pure liquid) and by the presence of curvature for the longer chain length (greater than Cio) compounds. The curvature in the alcohol and fatty acid data is shown to become very evident when correction is made to the pure (supercooled) liquid standard state for the solid compounds. Finally the surface area method is shown to hold considerable promise in its extension to the solubility estimation of complex organic molecules with limited aqueous solubilities.

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A group surface area approach is developed and applied to the estimation of the free energy changes for the following processes; (I) pure (supercooled) liquid to aqueous solution ( °), (II) pure (supercooled) liquid to gas ( ß]°), and (III) gas to aqueous solution ( ß3°).The corresponding estimates of eoiubWty (pure llquld/solutlon and gas/sdutlon) and vapor pressure at 298 K are easily made. The standard error of the estimate In the worst case (gas to solution) Is only 1.1 kJ mor1. Analysis of the surface area models shows that the single variable total surface area, TSA, can be used to estimate the pure (supercooled) liquid to aqueous solution free energy change, ÁG1°, with a standard error of 1.1 kJ/md. This apparent simplicity Is due to compensating changes In AG2°a nd G3°. For the latter two steps a partitioning of the TSA Into group areas Is required. Within the context of the surface area model, this Is attributed to significant differences In surface area coefficients for the aliphatic and aromatic hydrogens. The particular choice of group surface area terms In the final selected model shows good additivity as measured by application of the method to compounds not Included In the study.

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