Calculation of octanol/water partition coefficients using a quantum mechanical-continuum solvent model for solvation

The partition of a chemical compound between lipophilic membranes or tissues and aqueous phase of living organisms is often modeled by the 1-octanol/water partition coefficient (log K-ow). However, due to experimental difficulties, some theoretical methods for estimation of log K-ow on the basis of molecular structure have been developed. In this paper we present a new method for prediction of octanol/water partition coefficients from calculated solvation free energy in octanol and water, taking into account the fine details of molecular structure. A program that combines the semiempirical quantum method AM1 with the Poisson - Boltzmann equation, performs the calculation. This methodology was applied to the calculation of log K-ow for a set of twelve chlorinated benzene derivatives. The obtained results are in good agreement with the experimental values. Hence, the method can be used to evaluate the log K-ow values with higher accuracy for both known and novel compounds.