Abstract
Considering the escalating global crisis concerning bacterial resistance to antibiotics, there is a critical need to develop innovative medications with distinct mechanisms of action, heightened efficacy, and enhanced selectivity to tackle the significant challenge posed by multi-drug resistance in bacterial infections. Schiff bases and their metal complexes have emerged as promising candidates, demonstrating potential for exceptional biological activities, making them compelling subjects for further exploration and evaluation. These compounds have exhibited diverse effects on various bacterial strains, albeit with limitations when interacting with specific types of bacteria. This underscores the necessity for a renewed focus on targeted structural modifications of these compounds to overcome these constraints, enhance their effectiveness, and achieve more robust activities against a wider spectrum of bacterial strains.
In this study, two bidentate Schiff base compounds, namely, 2-((2-bromo-4-chlorophenyl)imino)methyl)-5-chlorophenol (HL1) and 5-chloro-2-(((2,6-dimethylphenyl)imino)methyl)phenol (HL2), were synthesised through a condensation reaction between 5-chlorosalicylaldehyde with 2-bromo-4-chloroaniline and 2,6-dimethylaniline, respectively. These compounds were subsequently complexed with metal(II) salts of Co, Ni, Cu, and Zn to generate their corresponding homoleptic mononuclear complexes of the form (M(Ln)2; where M = Co, Ni, Cu, or Zn, and n = 1 or 2). The complexes Co(L1)2, Ni(L1)2, Cu(L1)2, Zn(L1)2, Co(L2)2, Ni(L2)2, Cu(L2)2 and Zn(L2)2, alongside their respective ligands were characterised using various characterisation techniques such as proton and carbon nuclear magnetic resonance spectroscopy (1H and 13C{H}-NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), CHN-elemental analysis (CHN-EA), and thermogravimetric
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analysis (TGA). Additionally, single crystal X-ray diffraction (SC-XRD) examination was used to determine the solid-state structures of HL1, HL2, Ni(L1)2, Cu(L1)2, Co(L2)2, Ni(L2)2, Cu(L2)2, and Zn(L2)2. The solid-state structures confirmed the composition of HL1 and HL2 unambiguously, whereas structures of the metal complexes revealed coordination of these via nitrogen and oxygen atoms of the azomethine and phenolic moieties, forming perfect to distorted square-planar coordination environments at the metal centres.
Prior to the antibacterial and antioxidant studies, the compounds were evaluated in acetonitrile (HL1 and related complexes) and methanol (HL2 and related complexes) solutions with time-dependent UV-Vis spectroscopy, revealing feasible stability for biological testing. In vitro assays on Gram-positive and Gram-negative bacterial strains of Staphylococcus aureus (Sa), Bacillus subtilis (Bs), Pseudomonas aeruginosa (Pa), Klebsiella pneumoniae (Kp), Escherichia coli (Ec), and DPPH radicals were conducted and benchmarked with positive controls, ciprofloxacin, and ascorbic acid. The findings show that the complexation of HL1 and HL2 enhance their activity, albeit lower than that of the control, except for Cu(L2)2. This study underscores that the Schiff base compounds, and their respective transition metal complexes show viability in the quest to discover therapeutic agents to combat AMR.