A Thermodynamic analysis of the relationships between molecular size, hydrophobicity, aqueous solubility and octanol-water partitioning of organic chemicals

Abstract

This study presents a thermodynamic analysis of the relationship between molecular size, hydrophobicity, aqueous solubility and octanol-water partitioning for several classes of hydrophobic organic compounds including chlorinated dibenzo p-dioxins, PCBs, polynuclear aromatic hydrocarbons, alkylbenzenes, linear alcohols and alkanes. The purpose of the thermodynamic analysis is to explore the contribution of chemical-water and chemical-chemical interactions involved in the aqueous solution process. This is important for the development of relationships between the molecular structure and environmentally relevant properties of organic chemicals. The results show that the free energy of aqueous solvation is virtually independent on the molar volume of the solute for each of the congeneric series that was investigated. Within each congeneric series, congeners are therefore approximately equally “hydrophobic”, and the relationship between the aqueous solubility of (subcooled) liquid hydrophobic chemicals and molecular volume predominantly reflects the dependence of chemical-chemical interactions on the molecular volume in the (subcooled) liquid phase, rather than chemical-water interactions as is usually assumed. The results indicate that improvements of quantitative structure-aqueous solubility relationships may be achieved by modelling chemical-chemical interactions in the pure (subcooled) liquid phase, rather than merely chemical-water interaction, and that within congeneric series of non-polar organic substances, an increase in octanol-water and environmental partition coefficients with increasing congener size is due to an increase in the congener's lipophilicity, not hydrophobicity.