Synthesis, biological evaluation, molecular electrostatic potential, DFT, and molecular docking of quinolines and their Cu(II) and Pd(II) complexes

Abstract In this study two derivatives of quinoline (D1) 2-(benzyloxy)-8-(piperidin-1-yl)quinoline, and (D2) 8-(pyrolidin-1-yl)quinolin-2-ol were synthesized, the D2 was further complexate with copper (II) (C-1) and palladium (II) (C-2). We subjected the two ligands, D1 and D2, to DFT calculations, molecular docking, and ADMET analysis. All four compounds (D1, D2, C-1, and C-2) underwent antibacterial, antifungal, antioxidant, and enzyme inhibition tests. These experimental tests were compared with DFT calculations, molecular docking, and ADMET analysis. The biological evaluation shows that the biological activities were enhanced after complexation. However, both the copper and palladium complexes are less effective than the standard. Molecular analysis of D1 and D2 involved examining FMO, NBO, MEP, and NLO using DFT with various functionals (CAM-B3LYP/ωB97XD/TPSSTPSS/PBEPBE) at a 6-311G(d,p) basis set. Synthesized derivatives were docked to specific proteins for antibacterial and antifungal assessment. In bacterial proteins, D1 showed the highest affinity for Escherichia coli (6RKU), D2 for Klebsiella pneumoniae (5YIG), and C-1 for Staphylococcus aureus (5CDP). Fungal proteins revealed D1’s highest affinity for Aspergillus flavus (6IV7), D2 for Aspergillus niger (7BLY), and C-1 for A. flavus (6IV7). ADMET assessment confirmed drug-likeness, indicating physiological activity, non-toxicity, and solubility in lipid and water.