Beyond hydrogen bonds: unveiling the structure-directing role of side-on X⋯π interactions in adamantane–thiourea crystals

Abstract

This study presents a comprehensive experimental and computational investigation into the role of variable side-on X⋯π (X = O, S, Cl) interactions complementing conventional hydrogen-bonding in the molecular packing of four differently substituted 3-(adamantan-1-yl)-1-[(E)-(arylmethylidene)amino]thiourea derivatives (1–4). Single-crystal X-ray diffraction analyses reveal distinct molecular packing modes across the series: conventional hydrogen-bonding dominates in 1, while non-conventional non-covalent interactions involving the aryl rings are prominent in 2–4. Molecular electrostatic potential (MEP) surface analysis precisely maps electrophilic (amino N–H) and nucleophilic (thione-S, nitro-O, F, Cl atoms) regions, consistent with observed hydrogen-bonding patterns and revealing positive potentials over the aromatic rings (0.7 to 6.9 kcal mol⁻¹) that rationalize lone-pair (LP)⋯π interactions. Combined quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) plot analyses confirm the presence of LP⋯π contacts in 2 and 3 (S⋯π) and Cl⋯π interactions in 4, characterised by specific bond critical points and extended RDG isosurfaces. The Energy Decomposition Analysis (EDA) for LP⋯π-mediated dimers of 2–4 reveals that these interactions are predominantly stabilised by dispersion and correlation effects, with electrostatic contributions being minor. This joint crystallographic and computational approach elucidates how side-on X⋯π interactions contribute to crystal architecture, confirming their structure-directing role and offering insights for rational crystal engineering.