Zinc(II), copper(II) and silver(I) salicylate-metronidazole complexes as novel antimicrobial agents

Combining zinc(II), copper(II) and silver(I) salicylates with metronidazole through via mechanochemistry and slurry, leads to the formation of the new metal complexes [Zn(Sal)₂(MET)₂] Form I (1a), [Zn(Sal)₂(MET)₂] Form II (1b), [Cu(Sal)₂(MET)₂(H₂O)] Form I (2a), [C(Sal)₂(MET)₂ (H₂O)] Form II (2b) and[Ag(Sal)(MET)] (3), that have been fully characterized via single crystal and powder X-ray diffraction and thermal techniques. Antimicrobial assays conducted on the thermodynamically stable forms of polymorphic zinc(II) and copper(II) complexes and the silver complex, have demonstrated that these complexes behave as effective agents against both Gram-positive and Gram-negative bacteria, including biofilm-forming strains, and evidence the potential application of crystal engineering strategies to modify and improve existing drugs in confronting the growing threat of antimicrobial resistance; our results are particularly promising if one considers the limited antimicrobial activity of pure metronidazole against aerobic pathogens.