The Crucial Role of Lattice Water in Directing Supramolecular Networks of Deferiprone Analogues: A Combined X-ray and DFT Study

Abstract

This work presents the synthesis, structural elucidation via X-ray diffraction, and Density Functional Theory (DFT) investigation of three novel ligands based on deferiprone: maltol-TAU (3), maltol-histidine (4), and maltol-histamine (5), derived from taurine, histidine, and histamine, respectively. Additionally, the copper(II) complex of the histamine derivative, [Cu(maltol-HISTA)₂(H₂O)₂]•2H₂O•2HCl (6), was synthesized and characterized. In the solid state, the supramolecular architectures of ligands 3-5 and complex 6 are primarily stabilized by hydrogen bonding and pi-stacking interactions.Theoretical modeling corroborated these observations, confirming that compounds 3, 4, and 5 possess protonated imidazole rings accompanied by sulfonate, carboxylate, and chloride counter-ions, respectively. A distinct conformational variation was observed regarding ring orientation: the hydroxypyridinone and imidazole rings are positioned nearly orthogonally in 4, whereas they adopt a parallel arrangement in 5. DFT calculations were further employed to analyze specific supramolecular assemblies, with a focus on the structural influence of co-crystallized water molecules. To rigorously characterize the H-bonding and non-covalent interactions, Quantum Theory of Atoms in Molecules (QTAIM) and Non-Covalent Interaction (NCI) plot analyses were utilized, providing detailed insight into the electronic and structural features of these potential coordination chemistry candidates.