Computational models for structure-hydrophobicity relationships of 4-carboxyl-2,6-dinitrophenyl azo hydroxynaphthalenes.

Some phenyl azo hydroxynaphthalene dyes (e.g., sunset yellow) are certified as approved colorants for food, cosmetics, and drug formulations. The hydrophobicity of 4 newly synthesized azo dyes of the phenyl azo hydroxynaphthalene class was investigated, as a training set, with the goal of developing models for quantitative structure-property relationships (QSPR). Retention behavior of the molecules reversed-phase thin-layer chromatography (RPTLC) was investigated using liquid paraffin-coated silica gel as the stationary phase. Mobile phases consisted of aqueous mixtures of methanol, acetone, and dimethylformamide (DMF). Basic hydrophobicity parameter (Rm w ), specific hydrophobic surface area (S), and isocratic chromatographic hydrophobicity index (φo) were computed from the chromatographic data. The hydrophobicity index (R m ) decreased linearly with increasing concentration of organic modifiers. Extrapolated Rm w values obtained by using DMF and acetone differ significantly from the value obtained by using methanol as organic modifier [P < 0.05, 1-way analysis of variance (ANOVA), Tukey's multiple comparison test]. Structure-property relationships showed that hydrophobicity was dependent on type and position of naphthalene ring substituents. R m decreased with the presence of a highly polar substituent (e.g., COOH). Owing to intramolecular interaction, R m increased when the common hydroxyl group (OH) is positioned ortho to the azo group, relative to para positioning, in 2 positional isomers. Pattern recognition data analysis underscores the utility of φ o as a more accurate hydrophobicity descriptor than Rm w . φ o is negatively correlated with theoretically calculated density, surface tension, and refractive index for the molecules. These models could be used to predict toxicity (absorption, distribution, metabolism, excretion, toxicity; ADMET) properties of the azo dyes and may also play useful roles in computer-assisted molecular discovery of nontoxic azo dyes.