MIA molecular descriptors generated from gauche and anti conformations of 1,2-disubstituted ethanes to predict dipole moments

Abstract 1,2-Disubstituted ethanes adopt gauche and anti conformations whose stability is governed by steric, electrostatic, and hyperconjugative effects. These conformations differ in energy and molecular properties such as dipole moments, which influence lipophilicity, solubility, and other physicochemical characteristics. Accurate prediction of dipole moments is therefore important for understanding these properties. Here, a quantitative structure–property relationship (QSPR) approach based on multivariate image analysis (MIA) descriptors was employed to predict dipole moments from quantum-chemically optimized geometries. The conformational behavior of 1,2-disubstituted ethanes bearing F, Cl, Br, CN, and NO₂ substituents was revisited using density functional theory, and MIA-QSPR models were developed for their gauche and anti conformers. Predictions of conformer populations and absolute and relative energies showed limited performance, whereas dipole moments were predicted robustly, with r ² = 0.74, q ² = 0.64, and r ²pred = 0.83. These results demonstrate the potential of MIA-QSPR for rapid dipole-moment prediction.