Synthesis, Crystal Structure and Antifungal Activity of (E)-1-(4-Methylbenzylidene)-4-(3-Isopropylphenyl) Thiosemicarbazone: Quantum Chemical and Experimental Studies

A novel (E)-1-(4-methylbenzylidene)-4-(3-isopropylphenyl) thiosemicarbazone was synthesized in a one-pot four-step synthetic route. Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonances (NMR), single-crystal X-ray diffraction, and UV-visible absorption spectroscopy were utilized to confirm the successful preparation of the title compound. Single-crystal data indicated that the intramolecular hydrogen bond N(3)-H(3)···N(1) and intermolecular hydrogen bond N(2)-H(2)···S(1) (1 − x, 1 − y, 1 − z) existed in the crystal structure and packing of the title compound. Besides the covalent interaction, the non-covalent weak intramolecular hydrogen bond N(3)-H(3)···N(1) discussed by atoms in molecules (AIM) theory also functioned in maintaining the title compound’s crystal structure. The strong intermolecular hydrogen bond N(2)-H(2)···S(1) (1 − x, 1 − y, 1 − z) discussed by Hirshfeld surface analysis played a major role in maintaining the title compound’s crystal packing. The local maximum and minimum electrostatic potential of the title compound was predicted by electrostatic potential (ESP) analysis. The UV-visible spectra and HOMO-LUMO analysis revealed that the title compound has a low ΔEHOMO–LUMO energy gap (3.86 eV), which implied its high chemical reactivity due to the easy occurrence of charge transfer interactions within the molecule. Molecular docking and in vitro antifungal assays evidenced that its antifungal activity is comparable to the reported pyrimethanil, indicating its usage as a potential candidate for future antifungal drugs.