Preparation, Identification, and Antimicrobial Analysis, Molecular Docking, Molecular Dynamics Simulation, ADMET, DFT, of Dual-Ligand Complexes of Schiff Bases with M (III) Ions (M = Fe, La, and Cr)

Novel mixed-ligand Schiff base complexes were synthesized by coordinating 2-[(1E)-N-(2-hydroxyphenyl)ethanimidoyl]phenol (L1) and o-phenylenediamine (L2) with Cr(III), Fe(III) and La(III) ions. Elemental analyses, molar conductance and spectroscopic data confirmed the formation of stable 1:1:1 [M:L1:L2] nonelectrolytic complexes. In vitro antimicrobial evaluation revealed that Cr(III) and Fe(III) complexes exhibited superior antibacterial activity, notably against E. coli (34 mm) and S. aureus (27–34 mm), surpassing the free ligand and Ampicillin. Cr(III) also showed the strongest antifungal activity against A. flavus and C. albicans, whereas La(III) exhibited limited effects. Molecular docking against bacterial and fungal targets (PDB IDs: 1NNI, 1T2P, 5OE3, 5V5Z, 6G9S, 7SV2) demonstrated enhanced binding affinities of the metal complexes, with Cr(III) showing the highest stability, further supported by MD simulations, MM/GBSA, PCA and DCCM analyses. In silico ADMET studies indicated high gastrointestinal absorption, blood–brain barrier permeability and overall compliance with drug-likeness rules. Cr(III) and Fe(III) complexes combined favorable solubility, bioavailability and metabolic stability, while La(III) showed reduced solubility and higher molecular weight. However, metal coordination significantly improves the biological activity of Schiff base ligands, highlighting Cr(III) and Fe(III) complexes as promising antimicrobial agents.