Hybrid Thiohydantoins packing energetics and antimicrobial profiling: Synthesis, single crystal, PIXEL and QTAIM/NCI studies of two N-arylacetamide-thiophenytoins

Two novel thiohydantoin derivatives, 2-(2-(Methylthio)-5-oxo-4,4-diphenyl-4,5-dihydro-1H-imidazol-1-yl)-N-(p-tolyl) acetamide (1) and 2-(2-(Methylthio)-5-oxo-4,4-diphenyl-4,5-dihydro-1H-imidazol-1-yl)-N-(4-nitrophenyl) acetamide (2), were synthesized. Antimicrobial properties of the two newly synthesized compounds were studied against a panel of 12 microbial strains associated with urinary tract infections. This preliminary study reveals promising pharmacological activity against all tested microbial species. The spectroscopic characterization of the synthesized compounds has been performed by NMR (1H and 13C), FT-IR, high-resolution electrospray ionization mass spectrometry (ESI-HRMS) and structurally characterized by single crystal X-ray diffraction analysis. Single crystal X-ray diffraction shows that both compounds crystallized in monoclinic crystal system with P21/cand C2/c space group for compound (1) and compound (2) respectively. The crystal structures of both compounds are stabilized by various non-covalent interactions such as intermolecular hydrogen bonding interactions, C‒H···π interactions and π···π stacking interactions. These non-covalent interactions are characterized using Hirshfeld surface analysis, while the associated 2D fingerprint plots provide a quantitative assessment of the intermolecular interactions present in the crystal structures. The CLP-PIXEL method has been employed to calculate the interaction energies of the molecular pairs and the lattice energies of both compounds. High performance theoretical analysis namely Bader’s “Quantum Theory of Atoms in Molecules” (QTAIM), Non-covalent Interaction (NCI) plot index, and Reduced Density Gradient (RDG) analysis were carried out to characterise the non-covalent interactions of both compounds.