Aromaticity of Substituted Benzene Derivatives Employing a New Set of Aromaticity Descriptors Based on the Partition of Electron Density

Abstract

Aromatic compounds represent about two-thirds of known molecules. Despite that, aromaticity still lacks a precise definition, leading to the use of various descriptors to quantify it. In this work, we employ a new set of six descriptors (ACS Omega 2025, 10, 14157) built from components of the quadrupole moment formula presented tensor from the Stone's Distributed Multipole Analysis (DMA) to examine the aromaticity trends in monosubstituted benzene derivatives ( formula presented , formula presented , formula presented , formula presented , and formula presented ) and para-homodisubstituted analogs ( formula presented , formula presented , formula presented , and formula presented ). The formula presented tensor is the first term in the DMA electric multipole expansion to include out-of-plane electron density contributions. Using a machine learning clustering technique, we identified four groups of molecules: neutral with minimal formula presented variation, neutral with strong formula presented perturbation ( formula presented ), positively, and negatively charged species. Comparisons with the traditional aromaticity descriptors formula presented , formula presented , formula presented , and formula presented were carried out. Among the formula presented -based descriptors, formula presented , which is computed 1 Å above the ring plane, exhibited the highest correlation with those descriptors, though small ( formula presented ). All the formula presented -based descriptors reproduced the same trends of the traditional indices, except for the negative substituents, which were only correctly described by the former ones. We found that formula presented -based descriptors correlated with ionization potentials ( formula presented ), electron affinities ( formula presented ), electronegativities ( formula presented ), electrophilicity indexes ( formula presented ), and electron-donating/accepting power ( formula presented ), but not with the chemical hardness ( formula presented ). In contrast, formula presented , formula presented , and formula presented correlated only with formula presented , while formula presented showed no correlation. Therefore, our results show that the formula presented -based descriptors reflect the π-electron delocalization characteristic of aromaticity and also can describe frontier-orbital reactivity trends.