Prediction of the Hydrophobic Character of Aromatic Amines by Quantum Chemistry and QSPR Methods: The Case of Aniline and Its Derivatives

Abstract

This study established a relationship between the octanol/water partition coefficient (LogP) and molecular descriptors from quantum chemistry using a QSPR approach. To this end, a QSPR model based on three molecular descriptors, namely ionization energy (IE), total electronic energy (E_T), and dipole moment (μ), was developed. To evaluate the quality, robustness, and predictive power of the resulting model, several statistical and validation parameters were calculated ($R^2=0.9501$ ; $R_{adjusted}^2=0.9386$ ; s = 0.2000; F = 82.5446; $Q_{LOO}^2=0.9149$ ; $\overline{r_m^2\left(LOO\right)}=0.6651$ ; $\Delta r_m^2\left(LOO\right)=0.0000$ ; $Q_{ext}^2=0.9825$ ; $\overline{r_m^2\left(test\right)}=0.9013$ ; $\Delta r_m^2\left(test\right)=0.0787$ ). The values obtained for these different indicators reveal that the developed QSPR model is valid, robust, and efficient for predicting the octanol/water partition coefficient of the studied anilines. This model can therefore be applied to estimate the hydrophobic character of other compounds belonging to the same chemical family, provided they fall within its range of applicability. Consequently, the design of new anilines with specific octanol/water partition coefficients could be facilitated by modulating the three molecular descriptors included in the developed QSPR model.