Use of substituent constants in structure-activity relations and the importance of the choice of standard state

The value of the hydrophobic group substituent constant (π), calculated from logarithms of partition coefficients, is normally independent of the choice of the standard state used for the partition studies. However, in some cases e.g. when a partition coefficient for the intact molecule is taken as being equivalent to a π value, the choice of standard state is of utmost importance. It is suggested that π values may be additive on the mole fraction (thermodynamic partition coefficient) scale and not the molar scale as has been previously assumed. Consequently, some published π values may be in error.