Validation of critical points in the electron density as descriptors by building quantitative structure-property...

A crucial component of research in the field of quantitative structure-activity/property relationships is the identification of molecular descriptors relevant to the activity or property of interest. Descriptors based on the topology of the electron density as formulated in Bader's theory of atoms in molecules are investigated in detail in this work. In a model study, the authors investigate their ability to predict the atomic polar tensor (the gradient of the molecular dipole moment), which contains information on the vibrational intensities in infrared spectroscopy and constitutes a scheme for partitioning the total charge distribution into atomic charges. The atomic polar tensor may therefore be used to investigate whether the descriptors give adequate information on the local electronic structure in the molecule. Both the trace of the atomic polar tensor and for planar molecules its out-of-plane component may be interpreted as definitions of atomic charges suitable for prediction. Hydrogen and carbon atoms in a set of 60 aromatic compounds with various substituents have been studied. Excellent results for prediction of hydrogen and carbon charges have been achieved with cross-validated squared correlation coefficients between predicted and theoretical values varying from 0.92 and 0.977 for the most complex set of substituents when the value, Laplacian, and ellipticity of the electron density in the bond critical points are used as descriptors. The carbon charges defined from the trace of the atomic polar tensor are correlated with its out-of-plane component whereas such relationship is not observed for the hydrogen charges studied in this work.