Hydrogen Bonding. 32. An Analysis of Water-Octanol and Water-Alkane Partitioning and the Δlog P Parameter of Seiler

• Published in: Journal of pharmaceutical sciences 1994-08, Vol.83 (8), p.1085-1100
• Main Authors: Abraham, Michael H., Chadha, Harpreet S., Whiting, Gary S., Mitchell, Robert C.
• Format: Article
• Language: English
• Subjects: Alkanes - chemistry; Chemical Phenomena; Chemistry, Physical; Hydrogen Bonding; Octanols - chemistry; Solubility; Water - chemistry
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600830806

A general linear solvation energy equation has been used to analyze published partition coefficients in the systems water-octanol (613 solutes), water-hexadecane (370 solutes), water-alkane (200 solutes), and water-cyclohexane (170 solutes). The descriptors used in the equation areR2, an excess molar refraction; π2H, the solute dipolarity/polarizability; ∑α2Hand ∑β2H, the effective solute hydrogen-bond acidity and basicity; and VX, the characteristic volume of McGowan. It is shown that the water-octanol partition coefficient is dominated by solute hydrogen-bond basicity, which favors water, and by solute size, which favors octanol, but solute excess molar refraction and dipolarity/polarizability are also significant. For the water-alkane partition coefficients, the same factors are at work, together with solute hydrogen-bond acidity as a major influence that favors water. An analysis of 288 ΔlogPvalues shows that solute hydrogen-bond acidity is the major factor but that solute hydrogen-bond basicity and, to a lesser extent, solute dipolarity/polarizability and size are also significant factors that influence the ΔlogPparameter.