Design, antibacterial activity, computational analysis and molecular modeling study of a novel diimine-dioxime ligand and its Cu(II) complex
Journal of Molecular Liquids, cilt.433, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 433
- Basım Tarihi: 2025
- Doi Numarası: 10.1016/j.molliq.2025.127941
- Dergi Adı: Journal of Molecular Liquids
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
- Anahtar Kelimeler: Antibacterial activity, Density functional theory, Metal complex, Molecular docking, Molecular dynamics simulation, Schiff base
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
A novel diimine-dioxime ligand, 2-(biphenyl-4-yl)-2-(2-((1-(biphenyl-4-yl)-2-(hydroxyimino)ethylidene)amino)phenylimino)acetaldehyde oxime (H2BPOP), was successfully synthesized along with its homodinuclear Cu(II) complex with the general formula Cu2(BPOP)(H2O)(phen)2. The synthetic strategy involved a multi-step approach comprising a biphenyl-based ketoxime condensed with 1,2-phenylenediamine, followed by coordination with Cu(II) ions. The H2BPOP and its CuII2 complex were comprehensively characterized using 1H- and 13C-NMR, FT-IR, UV-vis spectroscopy, elemental analysis, ICP-OES, magnetic susceptibility, molar conductivity, and thermal analysis. Elemental analysis results confirmed a 2:1 metal-to-ligand stoichiometry in the dinuclear complex. Density functional theory calculations at the B3LYP/6-311G(d,p) level (LANL2DZ for Cu(II) ions) provided insights into the electronic structures and geometries, revealing distorted square pyramidal and square planar geometries around the Cu(II) centers. The molecular electrostatic diagram of the H2BPOP indicated electron-rich domains at the oxime and imine moieties, corroborating their involvement in metal coordination. A significant reduction in the HOMO/SOMO–LUMO energy gap was observed upon complexation, decreasing from 3.589 eV in the free ligand to 1.465 eV in the CuII2 complex. Thermodynamic parameters suggested greater stability for the complex than the free ligand, as evidenced by lower electronic energy, higher entropy, and increased chemical reactivity. Quantum chemical calculation results were consistent with experimental data, particularly in chemical shift values and vibrational modes. Antibacterial activity was evaluated against E. coli, S. typhimurium, S. aureus, and L. monocytogenes using the minimum inhibitory concentration method. The H2BPOP ligand exhibited the highest activity against E. coli (MIC = 16 μg/mL), while the CuII2 complex showed MIC values of 64 μg/mL against both E. coli and S. typhimurium and 32 μg/mL against L. monocytogenes. Molecular docking studies against β-ketoacyl-acyl carrier protein synthase III (PDB ID: 1HNJ) and lipoteichoic acid synthase (PDB ID: 2W5T) demonstrated stronger binding affinities for H2BPOP (−9.4 kcal/mol for 1HNJ and −9.1 kcal/mol for 2W5T) compared to its CuII2 complex (−8.1 kcal/mol and −8.3 kcal/mol, respectively). Furthermore, molecular dynamics simulations confirmed that the H2BPOP-1HNJ complex remained stable over 100 ns under physiological conditions. The overall findings from both in vitro and in silico evaluations highlight H2BPOP as a promising antibacterial candidate, while its homodinuclear Cu(II) complex exhibits moderate activity and distinct structural and electronic features.