Synthesis, characterization, antibacterial properties, mode of action and molecular docking studies of copper pyridyl complexes against drug-resistant bacteria

A series of four new copper complexes containing pyridyl-based ligands of the type [Cu(Cl)2(L)2] were prepared by solid-state methods and evaluated for antibacterial activity. Their elemental analysis showed that the grinding method produced pure complexes. FTIR spectroscopy confirmed the coordination of ligands to copper ions by identifying shifts in vibrational frequencies. Furthermore, their successful synthesis was confirmed by the coordinating bonds being shifted to lower frequencies. Electronic spectra and magnetic susceptibility data proved the complexes to be d9 tetrahedral complexes. Thermal studies of the copper complexes indicated that they had good thermal stability. In the thermal analysis, a recurring pattern emerges as each copper complex experiences multiple mass losses and exhibits characteristic transitions in DSC profiles, shedding light on their distinct thermal behaviors. The mass spectra of the copper complexes showed that the data agreed with the elemental analysis and other elucidation techniques. The complexes displayed characteristic molecular ion peaks and ad-ducts consistent with their calculated masses, substantiating the successful synthesis of these complexes and enhancing understanding of their composition and stability. The copper complexes also displayed solubility in highly polar and heavy solvents thus reduced the chances of forming good-quality crystals. The copper com-plexes were more effective against Gram-positive bacteria, with CuL4 performing best, notably against MRSA and S. aureus. All of the active complexes were bacteriostatic against MRSA and S. aureus based on the time kill kinetics. Additionally, it was shown that the CuL4 and Cu4PY-H disrupted the S. aureus cell membrane more effectively than the AgSD control. Finally, the CuL4 membrane disruption studies were not significantly different to the AgSD control on MRSA. The results of cell membrane disruption were supported by molecular docking scores, where CuL4 outperformed the other active compounds, and the trends corroborated the experimental results.