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

Bodor and Buchwald (8) have produced a two-parameter equation for calculati ng 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 W aals volume of the of the solute molecule, using an algorithm combining ana lytical and numerical techniques. This parameter can be obtained more simpl y by addition of increments for the various atoms making up the molecule. T he second parameter N, an integer, is obtained by summation of the integral N values associated with the different polar groups present in the molecul e, as long as these polar groups are not too close to each other. The N ter m 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 bondi ng sites of the various polar groups of the solute molecule. The detailed n ature of the hydrogen bonds between a polar group and water can be elucidat ed by calculations involving N and (V) over bar(0), the partial molal volum e in water of a solute molecule containing this group.