Akademik Veri Yönetim Sistemi
Journal of Molecular Liquids, cilt.439, 2025 (SCI-Expanded, Scopus)
Two novel benzoin-derived Schiff base ligands, 4-chloro-2-((2-hydroxy-1,2-diphenylethylidene)amino)phenol ( CDAPH 2 ) and 2-((2-hydroxy-1,2-diphenylethylidene)amino)-4-methylphenol ( MDAPH 2 ), together with their Cu(II) and Mn(II) complexes, were synthesized to explore their structural features, electronic properties, and biological potential as inhibitors of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). The synthesized compounds were characterized through FT-IR, UV–vis, NMR, elemental analysis, ICP-OES, thermal analysis, magnetic susceptibility, and molar conductivity measurements. Density Functional Theory (DFT) calculations confirmed the experimental structures. They revealed that complexation reduced the HOMO–LUMO gap, with Mn(II) complexes showing the lowest SOMO–LUMO gaps, indicating higher chemical reactivity. Molecular electrostatic potential mapping identified imine nitrogen and phenolic/alcoholic oxygen atoms as primary coordination sites. At the same time, thermodynamic analysis suggested that Cu(II) complexes were more stable than Mn(II) analogs. ADMET predictions verified compliance with Lipinski's rules, acceptable aqueous solubility, good oral bioavailability, and low acute toxicity, with MDAPH 2 showing the highest predicted LD50 (2500 mg/kg). Molecular docking studies against VEGFR2 (PDB ID: 2XIR ) demonstrated strong binding affinities for all compounds, with MDAPH 2 achieving the most favorable score (−9.2 kcal/mol) through key hydrogen-bonding and hydrophobic interactions. A 100 ns molecular dynamics simulation of the MDAPH2–VEGFR2 complex confirmed its structural stability by maintaining consistent RMSD, RMSF, potential energy, and hydrogen bonding profiles. Collectively, these findings highlight the novelty of integrating experimental synthesis, comprehensive physicochemical characterization, advanced quantum chemical calculations, and in silico biological evaluation, and suggest that these benzoin-derived Schiff bases and their metal complexes hold significant promise as antiangiogenic and anticancer candidates.