Combined DFT calculation, Hirshfeld surface analysis, and Energy framework study of non-covalent interactions in the crystal structure of (Z)-5-ethylidene-2-thiohydantoin determined by powder X-ray diffraction

The thiohydantoin core is used in the synthesis and development of new drugs. Furthermore, the study of these materials allows us to analyze the role that non-covalent interactions play in their supramolecular structure and how they can influence their pharmacological properties. Herein, a novel thiohydantoin compound, namely (Z)-5-ethylidene-2-thiohydantoin was synthesized and characterized by FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. Its crystal structure was determined and refined by powder X-ray diffraction techniques. This material crystallizes in the monoclinic system with space group P2₁/c, Z=4. The crystal packing is controlled by N–H···O, N–H···S and C–H···O hydrogen bond interactions, forming infinite two-dimensional sheets with graph-set motifs R²₂(8), R¹₂(7), and R⁶₆(26). NCI calculations, Hirshfeld surface analysis, and the Energy framework study reproduce in good agreement the crystal packing exhibited by the X-ray diffraction study.