A MOLECULAR ORBITAL DESCRIPTION OF PARTITIONING OF AROMATIC COMPOUNDS BETWEEN POLAR AND NONPOLAR PHASES

The partitioning of aromatic molecules between immiscible nonpolar-polar phases (n-octanol-aqueous 50 mM sodium phosphate buffer (pH 7.4)) is considered experimentally and theoretically from a molecular orbital theory point of view. An equation is developed that satisfactorily describes the partitioning process: In P= a-a′ RT Σs|QsT | + b-b′ RT ΣsSsEwhere P is the chemical's partition coefficient, QsT is the charge density obtained from considerations of both π and σ electron frameworks for the aromatic compound, and SsE is induced polarization. Thirty aromatic molecules representing four chemical classes (hydrocarbons, heterocycles, substituted benzenes, and substituted indoles) have partition coefficients that are correlated by this model equation. These correlations provide new examples for the applicability of molecular orbital theory to studies of biological activity and chemical structure interrelationships. © 1969.