The Energy Aspect of Oil/Water Partition and Its Application to the Analysis of Quantitative Structure-Activity Relationships. Aliphatic Alcohols in the Liposome/Water Partition System

Abstract

Abstract The energy aspect of oil/water partition has been examined for several solutes in different partition systems by determining the thermodynamic parameters of the partition. The thermodynamic parameters changed systematically, depending on the polarity of the nonaqueous phase of the partition. To further investigate the partition system dependency of the QSAR (quantitative structure–activity relationships) treatments the thermodynamic properties have been determined for various aliphatic alcohols in a liposome/water system; the results are discussed with regard to the previous ones obtained in a 1-octanol/water system, while paying special attention to applicability in the QSAR analysis. The following trends were observed in common with the two partition systems of liposome/water and 1-octanol/water: 1. The enthalpy term (ΔHp°) can well reproduce the toxicity data for halogenated and nonhalogenated alcohols collectively, whereas the conventional logP (partition coefficient) term can be applied only for the two types of alcohols separately; 2. The entropy term (ΔSp°) adds a discernible contribution to the refinement of the regression analysis. A distinctive characteristic is also discussed from a statistical method of analysis for the thermodynamic properties obtained in the two partition systems.