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

Abstract 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.