Based on Direct Computation

The computational method that appears a priori to be the most intellectually satisfying one for calculating partition coefficients is the direct simulation of a solute in water and organic solvent. Once the free energies of solvation in the aqueous and organic phases have been calculated, the calculation of log P is straightforward. 

The change in free energy for the transfer of a solute from an aqueous to an organic solvent can be computed using a continuum solvation model (the generalized Born/surface area, GB/SA) or a quantum mechanical model such as SMI, SM2, SMS,. . . , etc., where SM denotes solvation model. These methods are less CPU intensive than the molecular dynamics or Monte Carlo approaches described below. 

Using a continuum solvation model (GB/SA) based on molecular mechanics, log P values in the water/chloroform system were calculated using the free energy difference described by Eq. [36]  

Although promising for predicting the global log P of complex compounds, this approach is limited by the small number of continuum models currently available for organic solvents. 

Methods Based on Free Energy Perturbation Methods 

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