Design, crystallography, characterization, Hirshfeld surface analysis, and antimalarial evaluation of a zinc(II) complex with 4-acylhydrazone-5-pyrazolone: a combined DFT and experimental approach

A new tridentate Schiff base ligand, designated as (E)-N’-((3,5-dimethylphenyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)benzohydrazide (Bz-L₁A), was synthesized along with its corresponding zinc(II) complex [Zn(Bz-L₁A)₂], and this complex elucidated through a variety of techniques, including single-crystal X-ray diffraction (SCXRD), elemental analysis, mass spectrometry,¹H-NMR, FT-IR, UV-Vis, and thermogravimetric analysis (TGA). The complex with Bz-L₁A as the ligand, along with spectroscopic evidence, confirms a distorted octahedral geometry around the zinc(II) center. Intermolecular interactions were analyzed in detail using 3D Hirshfeld surface mapping and the associated 2D fingerprint plots. Additionally, structural optimization was carried out through DFT calculations at the (DFT/B3LYP/6-31G/LanL2DZ) level and subsequently compared with the experimental results. In addition, density functional theory (DFT/B3LYP/6-31G/LanL2DZ) calculations were carried out to explore molecular electrostatic potential (MEP), optimized geometry, HOMO-LUMO energy gaps, vibrational frequencies, and bonding characteristics. The computational findings were contrasted with experimental results, demonstrating a strong correlation between theory and observation. The anti-malarial properties of the ligands and their corresponding zinc(II) complex were assessed against <i>Plasmodium falciparum</i>, with the zinc(II) complex demonstrating superior activity compared to the free ligand.