Novel Hydrazono-Oxime Ligand: Synthesis, Characterization of (2E,3Z)-3-(((E)-2,3-Dichlorobenzylidene)hydrazono)butan-2-one Oxime, Formation of Its Transition Metal Complexes, and Assessment of Their Antimicrobial Performance Against Selected Bacterial and Fungal Strains

Abstract

A novel tridentate hydrazone-oxime Schiff base ligand, namely (2E,3Z)-3-(((E)-2,3-dichlorobenzylidene)hydrazono)butan-2-one oxime, was synthesized and fully characterized, together with its coordination compounds formed with divalent first-row and post-transition metal ions, including Mn(II), Fe(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II), and Pd(II). The free ligand and its metal complexes were thoroughly characterized employing a suite of physicochemical and spectroscopic methods, such as Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy (1H and 13C), ultraviolet-visible (UV-Vis) spectrophotometry, and elemental (CHN) microanalysis, thereby confirming their proposed molecular structures, purity, and mode of coordination (predominantly through the azomethine N, oxime O, and hydrazone N/O donor atoms). In vitro antimicrobial susceptibility testing was conducted against representative Gram-positive (e.g., Staphylococcus aureus) and Gram-negative (e.g., Escherichia coli) bacterial strains, as well as clinically relevant fungal pathogens (e.g., Candida albicans, Aspergillus niger), utilizing standard agar diffusion and/or broth microdilution protocols. The results revealed that the metal complexes displayed markedly superior antimicrobial potency relative to the uncoordinated ligand, consistent with the well-documented chelation-enhanced bioactivity phenomenon in coordination chemistry. Notably, the Cu(II) and Ni(II) complexes exhibited the most pronounced inhibitory effects, as evidenced by larger zones of inhibition and/or lower minimum inhibitory concentration (MIC) values. Structure–activity relationship (SAR) considerations indicate that metal coordination significantly augments the lipophilicity of the resulting complexes, thereby facilitating enhanced permeation across microbial cell membranes and promoting stronger interactions with intracellular targets (e.g., enzyme active sites or nucleic acids), which collectively account for the observed amplification of antimicrobial efficacy. These observations underscore the promising potential of the reported hydrazone-oxime-derived metal complexes as lead candidates for the rational design and development of novel, metal-based antimicrobial therapeutics to address emerging resistance challenges in pathogenic microorganisms.