Synthesis and Characterization of α-(acetylhydrazono)-benzylacetic Acid and Its Complexes with Trace Elements: Molecular Docking andAntimicrobial Activities

Abstract: A new ligand containing a hydrazone group based on acetylhydrazine and phenylglyoxylic acid – α-(acetylhydrazono)-benzylacetic acid (1) and its copper (2a), zinc (2b), and manganese (2c) complexes were synthesized. The structures of the obtained compounds were investigated by IR, UV, NMR, and EPR spectroscopy. The molar ratio of the ligand and metal in the complex 2:1 was confirmed by elemental and thermogravimetric analysis. An octahedral geometry is proposed for all investigated metal complexes. Despite extensive studies on hydrazone-based Schiff bases, few have integrated synthesis, spectroscopic characterization, antimicrobial evaluation, and molecular docking to develop new agents with enhanced biocidal activity. This study addresses this gap. Antimicrobial activity tests showed that compounds 1, 2a, and 2b exhibited inhibition zones ranging from 2.5 to 3.0 cm against tested bacteria and fungi, surpassing the activity of standard sodium pentachlorophenolate, which showed zones of 2.0–2.3 cm. The mechanisms of interaction between the ligand and its metal complexes with protein targets have been studied by molecular docking. Docking simulations revealed binding affinities in the range of –5.8 to –7.6 kcal/mol, with up to four hydrogen bonds observed in individual protein–ligand complexes. Copper complex (2a) showed the strongest interaction, involving both hydrogen bonding and hydrophobic Pi–Pi stacking interactions. Metal complexes were especially noted for offering a variety in binding mechanisms by facilitating different types of interactions. Additionally, molecular docking studies confirmed the binding stability of the ligand and metal complexes with the target proteins. These findings support the practical application of the synthesized compounds as promising candidates for drug design strategies, particularly in the development of novel antimicrobial therapeutics targeting resistant bacterial and fungal strains.