Investigation of the inherent characteristics of copper(II) Schiff base complexes as antimicrobial agents

We synthesised a sequence of structurally related copper(II) complexes of Schiff base ligands, 2-[(2-benzylamino-ethylimino)-methyl]-phenol [L1(H)], 2-[(2-benzylamino-ethylimino)-methyl]-4-methyl-phenol [L2(H)], and 2-[(2-benzylamino-ethylimino)-methyl]-4-bromo-phenol [L3(H)]. The complexes were characterized by ATR, UV-vis, EPR, ESI-MS, single crystal XRD, and elemental analyses. Based on the crystal structure, the ligand was coordinated to the copper(II) centre in a tridentate mode through phenolate(oxygen), imine nitrogen and amine nitrogen in an NNO fashion and the azide moiety served as an auxiliary ligand. Furthermore, we have investigated the antimicrobial activities of copper(II) complexes against clinically relevant fungal strains, including Candida albicans, Candida glabrata, and Candida tropicalis, as well as bacteria such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), representing Gram-negative and Gram-positive pathogenic strains. Comparing the activity of complex 2 (128-512 mu g mL(-1)) to complex 3 (64-128 mu g mL(-1)), the latter demonstrated more potent effectiveness against all of the tested fungal strains. The activity of the complexes against MRSA reveals the inhibitory concentrations of 1024 mu g mL(-1) for 1, 128 mu g mL(-1) for 2, and 256 mu g mL(-1) for 3. It is worth mentioning that, at their minimum inhibitory concentrations (MICs), the complexes are not toxic to Galleria mellonella. Furthermore, the spot and broth microdilution assay results were in good agreement with the actual metabolic viability of bacterial and fungal strains, in which the complexes were active while having no effect on the metabolite resazurin. Additionally, in silico studies have been employed to elucidate both non-bonding interactions and the mode of action across protein sequences of experimentally studied microbes. The performance of complexes closely mirrored the reactivity order determined in in vitro studies. The impeding properties of complexes can be due to the dysfunctioning of virulent genes and signalling proteins and also affect the activities of transferase and transcriptase proteins. Overall, the complexes are promising candidates for antimicrobial drug development. We anticipate utilising these molecules for clinical purposes.