Solvent-free synthesis, x-ray studies and in vitro inhibitory activities of copper(II) complexes of non-steroidal anti-inflammatory drugs

摘要

Solid-state mechanochemical synthesis of [Cu(CAF)_2(H_2O)(OAc)]OAc complex 1a and [Cu(COD)_2(H_2O)(OAc)]OAc complex 2a were obtained by grinding stoichiometric amounts of Cu(CH_3COO)_2?H_2O and corresponding nonsteroidal anti-inflammatory drugs[(caffeine (CAF) and codeine(COD)], respectively, in a mortar with pestle. Solvent-based synthesis of 1b and 2b was also carried out by reaction of metal acetate salt and each drug by refluxing at 70 ℃ in CH3OH for 1 h for comparison purposes. The complexes 1a and 2a were characterized by comparison of elemental analysis, FT-IR, UV–Vis and 1H NMR spectra with those of the free ligand and solvent-based products (1b and 2b). The analytical and spectroscopic data of the complexes prepared via the two different methods are almost identical. X-ray diffraction patterns of the complexes prepared by mechanochemical method were different from that of the starting material suggesting formation of new metal complexes. In vitro inhibitory activities of both mechanochemical and solvent-based complexes were found to be higher than parent ligands, indicating that the antimicrobial effect of these drugs could be enhanced when they are chelated to the metal. The mechanochemical synthesis was carried out without the use of solvent or external heating. The method is faster and gives a higher yield than corresponding solvent-based reactions. The solid state reaction presented higher efficiency in terms of materials, energy and time compared to solvent-based synthesis.