Calculation of octanol-water partition coefficients of organic solutes from their molecular volumes

Bodor and Buchwald (8) have produced a two-parameter equation for calculating the logarithm of the partition coefficient (log P) of an organic solute between n-octanol and water. They computed the first parameter, a van der Waals volume of the solute molecule, using an algorithm combining analytical and numerical techniques. This parameter can be obtained more simply by addition of increments for the various atoms making up the molecule. The second parameter N, an integer, is obtained by summation of the integral N values associated with the different polar groups present in the molecule, as long as these polar groups are not too close to each other. The N term results in a decrease in log P. The N parameter is thought to measure the total number of H-bonds between the hydrogen of water and H-acceptor bonding sites of the various polar groups of the solute molecule. The detailed nature of the hydrogen bonds between a polar group and water can be elucidated by calculations involving N and V over-bar 0, the partial molal volume in water of a solute molecule containing this group.