Charge and Delocalisation Effects on the Lipophilicity of Protonable Drugs

Abstract

The pH-lipophilicity profiles of ionisable drugs in water/1,2-dichloroethane have been determined in order to establish their ionic partition diagrams (diagram shown for N-methylephedrine). The results show how neutral species can alter the aqueous pH and how the ionic species can transfer into the organic phase. The difference between the partition coefficients of the ionic and neutral forms of a compound affords valuable information about the effect of the charge on lipophilicity and on the solvation properties of ions in different media. This study also shows that ion partitioning is determined by both the electrostatic field around the molecule and by the possibility of delocalising the charge over several atoms.