Critical assessment of QTAIM descriptors of intermolecular interactions at the promolecular level

Structural Chemistry. 2025. Vol. 36. P. 1649–1666.

Romanenko A., Ivan V. Ananyev

Intermolecular interactions play a pivotal role in chemical processes such as catalysis, crystal formation, and drug-protein complexation. The Quantum Theory of Atoms in Molecules (QTAIM) provides a robust framework for analyzing these inter actions through topological descriptors of electron density. However, the computational cost of obtaining accurate electron density distributions for large systems remains a challenge. This study critically evaluates the promolecular approximation (Independent Atom Model, IAM) as a cost-effective alternative for QTAIM analysis, focusing on its ability to describe various non-covalent interactions, including hydrogen bonds, halogen bonds, π…π stacking, and dispersion interactions. By comparing promolecular and density functional theory (DFT) results across diverse molecular systems, we demonstrate that the IAM model reliably reproduces trends in QTAIM descriptors, particularly for weaker and medium-strength interac tions. However, in the case of some types of non-directional interactions, the molecular graph is often incorrectly predicted. Furthermore, we propose a semi-quantitative model to estimate intermolecular binding energies using promolecular-derived descriptors, showcasing the potential of IAM for large-scale applications in supramolecular chemistry and materials science

Keywords: electron density, non-covalent interactions, Promolecule, Independent atom model, Quantum Theory of Atoms in Molecules