Metal Complexes Built From Salicylaldehyde Schiff Bases Show Antibacterial Power Rivaling Kanamycin

Chemists in Bangladesh and India have assembled a family of eleven transition metal complexes from salicylaldehyde-based Schiff base ligands and found that two of them, a copper(II) and a cadmium(II) compound, inhibit bacterial growth nearly as effectively as the clinical antibiotic kanamycin. The study, published in Discover Chemistry, combines classical laboratory synthesis with density functional theory calculations and molecular docking against the 16S ribosomal RNA subunit of bacteria, offering one of the more complete experimental-to-computational pipelines reported for this class of compounds. The work arrives at a moment when antimicrobial resistance is forcing researchers to look beyond conventional organic drug scaffolds toward metal-based alternatives that operate through entirely different mechanisms of attack.

Schiff bases, first reported by Hugo Schiff in 1864, form when a primary amine condenses with a carbonyl compound to create the characteristic azomethine, or HC=N, linkage. For more than a century and a half these molecules have served as workhorse ligands in coordination chemistry because their nitrogen, oxygen, and sometimes sulfur donor atoms grip metal ions with remarkable tenacity. The azomethine group is doubly important: it anchors the metal and it contributes directly to biological activity. Because the underlying aldehyde and amine building blocks can be swapped almost endlessly, chemists can tune the electronic and steric properties of the resulting ligands with fine precision, and decades of literature have documented antibacterial, antifungal, antioxidant, antiviral, antimalarial, anticancer, and anthelmintic behavior across this chemical family.

The research team, led by Md. Nur Amin Bitu and Md. Kudrat-E-Zahan at the University of Rajshahi with collaborators in Odisha and Riyadh, chose three amino acid precursors to build structural diversity into their ligand set. Salicylaldehyde was condensed with 6-aminohexanoic acid to give ligand L1, with L-arginine to give L2, and with DL-2-aminobutyric acid to give L3. Each condensation was carried out in a 3:1 ethanol-water mixture under reflux at roughly 80 degrees Celsius for four hours, yielding the lemon-yellow L1 at 92 percent, the yellowish-brown L2 at 93 percent, and the white L3 at 92 percent. The three ligands deliberately span an aliphatic chain, a guanidine-containing side group, and a short-chain architecture, allowing the team to probe how ligand structure governs both metal coordination and biological effect.

From these ligands the chemists generated eleven metal complexes. Ligand L1 yielded six: complexes of copper(II), manganese(II), cobalt(II), nickel(II), cadmium(II), and zirconyl(II), numbered 1 through 6. Ligand L2 produced nickel(II), cobalt(II), and manganese(II) complexes 7 through 9, while ligand L3 gave cadmium(II) and nickel(II) complexes 10 and 11. Synthesis relied on refluxing ethanolic solutions of the metal salts with the ligands, using a catalytic amount of potassium hydroxide as a deprotonating agent. The isolated solids were washed with diethyl ether and hexane and dried under vacuum, and elemental analysis confirmed purity, with carbon, hydrogen, and nitrogen deviations all within the accepted plus or minus 0.4 percent analytical tolerance.

Spectroscopy told the story of how the metals bind. In the free ligands, the azomethine stretching vibration appears at 1670 and 1634 inverse centimeters for L1 and L2 respectively; upon complexation this band shifts to between 1606 and 1641, a displacement of up to 64 inverse centimeters that signals coordination through the azomethine nitrogen. The phenolic O-H stretch likewise moved to lower frequency, and the asymmetric and symmetric carboxylate stretches shifted after complexation, demonstrating that the carboxylic oxygen also participates in binding. New medium-intensity bands between 597 and 673 and between 415 and 485 inverse centimeters were assigned to metal-oxygen and metal-nitrogen vibrations, the direct fingerprints of the coordination bonds. For ligand L3, the phenolic O-H position remained unchanged, indicating that in that ligand the phenolic oxygen stays out of the metal’s grip while the carboxylate and azomethine groups do the binding.

Electronic spectra and magnetic measurements then pinned down the geometries. Free L1 absorbs at 260 and 330 nanometers, corresponding to pi-to-pi-star transitions in the aromatic ring and n-to-pi-star transitions in the imine group; these bands red-shift and intensify upon metal binding as lone-pair electrons are donated to the metal center. New bands between 385 and 590 nanometers arise from metal-ligand charge transfer. Combining these data with effective magnetic moments, the team proposed octahedral geometries for complexes 1 through 3, tetrahedral geometries for complexes 4 through 9, and square-planar structures for complexes 10 and 11. The copper complex 1 shows a magnetic moment of 1.95 Bohr magnetons, consistent with a single unpaired electron in a Jahn-Teller distorted octahedral field, while the near-diamagnetic nickel complex 11 at 1.16 Bohr magnetons fits a square-planar d8 configuration. The authors are candid that single-crystal X-ray diffraction could not be obtained because the complexes are microcrystalline or amorphous, so these assignments rest on convergent but indirect spectroscopic and computational evidence.

Thermogravimetric analysis in nitrogen up to 800 degrees Celsius traced multi-stage decomposition pathways consistent with the proposed formulas. Complex 1 lost its carboxylate portions between 240 and 280 degrees Celsius with a 14.20 percent weight loss against a calculated 14.47 percent, and finally resolved to copper or copper oxide above 400 degrees. Complexes 2 and 3 decomposed in four stages beginning with lattice water loss around 50 to 180 degrees, and complexes 4 through 6 each released water, carboxylate, and organic fragments before collapsing to metal oxides between 450 and 630 degrees. The authors note that without complementary TG-MS or TG-FTIR techniques the decomposition assignments remain proposed rather than proven, an honest limitation they flag for future work.

Antibacterial testing by disc diffusion against Bacillus cereus, a Gram-positive strain, and Escherichia coli, a Gram-negative strain, revealed that complexation dramatically boosts activity compared with the free ligand. The cadmium complex 5 was the standout, producing a zone of inhibition of 32 plus or minus 0.26 millimeters against B. cereus, essentially matching kanamycin-30, and 24 plus or minus 0.26 millimeters against E. coli, below the antibiotic’s 29 plus or minus 0.10 millimeters. The copper complex 1 also performed well against both organisms. The team explains the enhancement through chelation theory: coordination reduces the polarity of the metal ion and delocalizes electron density over the chelate ring, raising lipophilicity so the complexes penetrate bacterial membranes more readily and reach intracellular targets such as DNA and enzymes. The authors stress that cadmium complexes require cytotoxicity evaluation against human cell lines before any therapeutic claim can be made, and that minimum inhibitory concentration testing was not performed, making these results preliminary and exploratory.

The computational arm of the study added mechanistic depth. Density functional theory calculations using the BP86 functional and def2-SV(P) basis sets in ORCA, with a conductor-like polarizable continuum model for water, showed that complex 5 has the most negative single-point energy of the series at minus 6299.1495 atomic units, marking it as the most thermodynamically stable, while complex 4 carries the largest dipole moment. The HOMO-LUMO gap of 2.571 electron volts and the highest chemical hardness of 1.2855 electron volts identified free ligand L1 as the most kinetically stable species, whereas complex 4, with the smallest gap and hardness, is the most reactive. Molecular docking against the 16S ribosomal RNA subunit of Thermus thermophilus, the same target through which kanamycin halts bacterial translation, showed that complex 1 achieved the strongest rRNA binding energy of the series, with the metal complexes generally matching or exceeding the affinities of kanamycin and pactamycin. The researchers caution that AutoDock Vina’s scoring function was developed for organic molecules and lacks validated metal parameters, so the docking results are qualitative indicators rather than mechanistic proof, and that complex 5 may act through additional targets such as membrane disruption. Together, the synthesis, spectroscopy, theory, and bioassays sketch a coherent picture of how simple amino acid-derived Schiff bases, when wrapped around the right metal, can become surprisingly potent antibacterial candidates.

Subject of Research: Transition metal complexes of salicylaldehyde-derived Schiff base ligands and their antibacterial activity

Article Title: Synthesis and antibacterial evaluation of transition metal complexes derived from salicylaldehyde based Schiff base ligands supported by DFT studies and molecular docking

Article References: Bitu, M. N. A., Uddin, S., Mohapatra, R. K., Azam, M., Mohapatra, P. K., Dash, G. C., Raval, M. K., & Kudrat-E-Zahan, M. (2026). Synthesis and antibacterial evaluation of transition metal complexes derived from salicylaldehyde based Schiff base ligands supported by DFT studies and molecular docking. Discover Chemistry, 3(1), Article 454. https://doi.org/10.1007/s44371-026-00900-5

Image Credits: AI Generated

DOI: 10.1007/s44371-026-00900-5

Keywords: Schiff base, salicylaldehyde, transition metal complexes, antibacterial activity, DFT, molecular docking, coordination chemistry, kanamycin, 16S rRNA, cadmium complex, chelation theory, antimicrobial resistance