Ceftriaxone-based Schiff base transition metal(II) complexes. Synthesis, characterization, bacterial toxicity, and DFT calculations. Enhanced antibacterial activity of a novel Zn(II) complex against S. aureus and E. coli

Abstract

From the reaction of ceftriaxone 1 antibiotic with 2,6-diaminopyridine 2 a ceftriaxone-based Schiff base (H2L,3) was obtained and its transition metal complexes were synthesized. Spectroscopic and physicochemical techniques, namely, UV–visible, FT-IR, 1H NMR, EPR, mass spectrometry, molar conductance, magnetic susceptibility and density functional theory (DFT) calculations, together with elemental and thermal analyses, were used to find out the binding mode and composition of these complexes. The ceftriaxone-based Schiff base 3 behaves as a monoanionic tridentate N,N,O ligand. Spectral and magnetic data suggest an octahedral geometry for all complexes and the general formulae [M(HL)(OAc)(H2O)2] (M(II) = Mn2+4, Co2+5, Ni2+6, Cu2+7, Zn2+8), are proposed for them. All compounds were screened for antibacterial activity using both the agar disc diffusion method and the minimal inhibitory concentration (MIC). It was found that complex 8 exhibited the most promising bactericidal activity against S. aureus (MIC = 0.0048 μmol/ml) and E. coli (MIC = 0.0024 μmol/ml). It is more active than the free ligand 1 (MIC = 0.0560 μmol/ml for S. aureus and 0.0140 μmol/ml for E. coli). These MIC results were compared with those obtained using similar zinc(II) Schiff base complexes, and with the values obtained using ceftriaxone conjugated with silver and gold nanoparticles (NPs), using earlier published data. Synthesized metal complexes exhibited LC50 values >1000 ppm indicating their nontoxicity against brine shrimp nauplii (Artemia Salina).