Characterization of lipophilicity scales using vectors from solvation energy descriptors.
Lipophilicity scales were characterized by an approach using vectors provided from solvation energy descriptors (SED) of solutes such as an excess molar refraction, the dipolarity/polarizability, the hydrogen-bond acidity, the basicity, and the McGowan characteristic volume. The five components of the SED vector were obtained from the coefficients of the five SED terms of the linear solvation energy relationship (LSER) equation for the lipophilicity scales. The analogy between two lipophilicity scales was expressed as the angle between the two SED vectors, while the difference in the contribution of the five independent SEDs to these two lipophilicity scales was quantified by the difference of the unit vectors of the SED vectors. These approaches were applied to several lipophilicity scales measured using microemulsions, micelles, an immobilized artificial membrane column, and an octanol-water system. As a result, the quantitative classification of these scales was successfully carried out, and the difference in the scales was well characterized. In addition, this vector approach was extended to the estimation of the contribution of each constituent of the microemulsions to the lipophilicity scale. Furthermore, some biological parameters such as skin permeability and the distribution between blood and brain could be predicted by the summation of the SED vectors obtained from the chromatographic systems. These results suggest that complex biological systems can be expressed quantitatively by simple chemical models with their SED vectors.
Ishihama
Y
Y
Analytical Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. y-ishihama@hhc.eisai.co.jp
Asakawa
N
N
D000465:Algorithms; D001812:Blood-Brain Barrier; D002627:Chemistry, Physical / Q000592:standards*; D004655:Emulsions; D004735:Energy Transfer; D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D008954:Models, Biological; D012869:Skin Absorption; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D004655:Emulsions; D008055:Lipids; D008823:Micelles