DFT and molecular docking-guided investigation of mixed-ligand octahedral Fe(III) and Cu(II) Schiff-base and albendazole complexes with antimicrobial potential.

This work describes the synthesis of two novel octahedral mixed ligand transition metal complexes, FeHLAB and CuHLAB, which incorporate a combination of a Schiff-base (HL) ligand and albendazole (AB). Both of these complexes were synthesized in high yields of 88% and 85% for FeHLAB and CuHLAB, respectively, and both are thermally stable solids with a melting point of > 300 °C. Various characterization tools such as CHN & metal analysis, FT-IR, UV-Vis, magnetic susceptibility, mass spectra, molar conductance, and DFT analysis reveal an octahedral geometry involving N & O-donors along with chloride ions. The DFT results reveal that CuHLAB and FeHLAB have small HOMO-LUMO energy gaps (CuHLAB: 1.28 eV; FeHLAB: 2.96 eV) with enhanced softness and electrophilicity. All these make these complexes more chemically reactive. Antimicrobial activity was conducted, showing that metal complexes had high activity against four bacteria (E. coli, P. aeruginosa, B. cereus, S. aureus) and two fungi (A. flavus, C. albicans). CuHLAB was more active compared to FeHLAB and approached the activity of commercial medicines, which was in the range of 40-50 µM for the CuHLAB complex. A molecular docking study with E. coli DNA gyrase B (PDB code: 4DUH) showed that there was a binding affinity of - 8.80 kcal/mol for CuHLAB, which was mediated by hydrogen bonding, electrostatic, and hydrophobic interactions. This was consistent with its observed in vitro antimicrobial properties. In general, these mixed transition metal complexes, particularly CuHLAB, show strong antimicrobial activity, which provides an important approach to conserving water, soil, and public health as well as potentially thwarting economic loss.