Correlation Analyses of Octanol/Water Partition Coeffcient of Substituted Benzoguanamines

Abstract

The effects of various substitutents in the phenyl moiety of ortho-, meta-, para-, and disubstituted benzoguanamines on the logarithmic 1-octanol/water partition coefficient, log P, were quantitatively examined by multiple regression analysis. The independent variables first used were empirical hydrophobic, electronic, and steric substituent parameters, π, σ, and E_s respectively. Then, semi-empirical molecular orbital calculation was performed with the use of the AM1 Hamiltonian, and the calculated net charges on hydrogen-bondable atoms were used in place of the σ parameters in the analysis. With empirical σ as well as theoretically calculated electronic parameters, not only statistically but also physicochemically highly significant correlation equations were formulated for benzoguanamine derivatives including the multifunctional 2, 6-diamino-1, 3, 5-triazine skeleton.