Deciphering Intermolecular Interactions in Molecular Crystals through Quantum Crystallography and Non-Covalent Interaction Analysis

Understanding intermolecular interactions in molecular crystals is fundamental for interpreting crystal packing, supramolecular organization, and the resulting physical or chemical properties of materials. Quantum crystallography provides a powerful tool for investigating these interactions directly from experimentally derived electron density distributions. In this presentation, I will discuss a series of studies on organic and metal–organic molecular crystals where experimental crystallography is integrated with electron-density-based analysis to obtain a deeper understanding of intermolecular interactions in the solid state.

Single-crystal X-ray diffraction experiments were used to determine accurate molecular geometries and crystal structures. To improve the description of hydrogen atoms and the underlying electron density distribution, Hirshfeld Atom Refinement (HAR) was employed, allowing the incorporation of quantum mechanical information into the crystallographic refinement process. The resulting electron density models were analyzed using the Quantum Theory of Atoms in Molecules (QTAIM), which provides a detailed topological framework for identifying bond critical points and characterizing the nature and strength of both covalent and non-covalent interactions.

To complement this analysis, non-covalent interaction (NCI) analysis and Hirshfeld surface approaches were used to visualize and quantify weak intermolecular contacts within the crystal lattice. These methods enable the identification of hydrogen bonding, π–π interactions, and dispersive contacts that collectively govern crystal packing and structural stability. By combining HAR refinement with QTAIM topology and NCI visualization, a consistent picture of intermolecular interactions emerges at both the electronic and structural levels.

Overall, this integrated crystallographic strategy demonstrates how modern electron-density analysis can provide detailed insight into supramolecular organization and structure–property relationships in molecular crystals, highlighting the growing role of quantum crystallography in contemporary structural chemistry.