Calculating Virtual log Pin the Alkane/Water System (log PNalk) and Its Derived Parameters Δlog PNoct-alkand log DpHalk

Abstract

Growing interest in the use of both the logarithm of the partition coefficient of the neutral species in the alkane/water system (log P^N_alk) and the difference between log P^N_oct (the logarithm of the partition coefficient of the neutral species in the n-octanol/water system) and log P^N_alk (Δlog P^N_oct-alk) in the early stages of drug design has stimulated development of a computational tool based on the Volsurf software to predict virtual (=of each conformer) log P^N_alk and virtual log P^N_oct. From these two pieces of data, it is then possible to calculate Δlog P^N_oct-alk for a given compound as the difference between log P^N_oct and log P^N_alk. Once the pK_a is known and the legitimacy of neglecting the contribution made by the ionized species has been checked, it is also possible to calculate log D^pH_alk, which might be an important lipophilicity descriptor in absorption, distribution, metabolism, and excretion (ADME) prediction, from log P^N_alk.