CHEMICAL SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF COPPER(II), NICKEL(II) AND COBALT(II) COMPLEXES OF BENZYLACETONE-BENZOYLHYDRAZONE AND ITS PARA-NITRO- AND PARA-HYDROXYL- SUBSTITUTED ANALOGUES

Abstract

The incidence of multidrug resistant microbes has necessitated the continual search for synthetic chemical compounds that could inhibit the growth of these microorganisms. Hydrazone ligands and their metal(II) complexes have been promising as antimicrobial agents. Research had focused on the utilisation of transition metal to prepare metal(II) complexes of hydrazone such as acetophenone-benzoylhydrazone, 2-acetylpyridine-benzoylhydrazone and pyridoxal-isonicotinoylhydrazones. However, report on the synthesis, characterisation and antibacterial activity of metal(II) complexes of benzylacetone-benzoylhydrazone(babh), para-hydroxy-benzylacetone-benzoylhydrazone (p-OH-babh) and para-nitro-benzylacetone-benzoylhydrazone (p-NO2-babh), with copper(II), nickel(II) and cobalt(II) ions are scanty. The aim of this study was to synthesise and characterise metal(II) complexes of benzylacetone-benzoylhydrazone and evaluate their antibacterial properties.

The ligand precursors; benzoylhydrazide, para-hydroxy-benzoylhydrazide and para-nitro-benzoylhydrazide were subjected to separate condensation reactions with benzylacetone, under reflux, in methanol at 65oC. The ligands benzylacetone-benzoylhydrazone (babh), para-hydroxy-benzylacetone-benzoylhydrazone (p-OH-babh) and para-nitro-benzylacetone-benzoylhydrazone (p-NO2-babh) were then reacted with copper(II), nickel(II) and cobalt(II) (chloride, nitrate, acetate and sulphate salts) to form the complexes. The compounds were characterised using Nuclear Magnetic Resonance (1H NMR and 13C NMR), Infrared (IR), UV-Visible spectrometers, CHN elemental analyser, Magnetic susceptibility balance and Conductivity meter. Antibacterial activity was determined by agar diffusion method using different concentrations of the complexes (20, 10, 5, 2 and 1 mg/mL), against Gram-positive (Staphylococcus aureus NCTC 6571 and Bacillus cereus ATCC 11778) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumonia ATCC 13048) bacteria strains with innocula suspension of 106 CFU (colony forming units) mL-1.

High yields of synthesised ligands (89 – 96%) and complexes (31 – 81%) were obtained. The 1H NMR spectra showed (N-H) signal (ppm) in the range 9.90 to 11.20 (1H, s) and 13C NMR produced (C=N) signal in the range 160.10 to 163.30 ppm indicating the formation of the ligands. The ligands coordinated to metal ion in a neutral bidentate fashion through the carbonyl oxygen (C=O) and azomethine nitrogen (C=N). Two intraligand bands at 48,780-48,309 cm-1 and 38,460-37,195 cm-1 were obtained. These bands shifted to lower wavenumber in the spectra of the complexes, which indicated coordination of ligands to metal ions. The complexes showed d-d transitions typical of octahedral, tetrahedral and square planar geometries. A 1: 2 (metal: ligand) stoichiometry for each complex was established. Magnetic moments for copper(II) complexes ranged from 1.71 to 2.20 Bohr Magneton (B.M.) indicating octahedral geometry. Nickel(II) complexes had magnetic moments ranging from 2.80 to 3.20 B.M. which are typical for octahedral complexes except Ni(babh)2(OAc)2 that had 3.87 B.M. which indicated tetrahedral geometry. Cobalt(II) complexes had moment ranging from 4.74 to 5.39 B.M. showing high-spin octahedral complexes. Molar conductance values were less than 50 ohm-1 cm2 mol-1 revealing that the complexes were non-electrolytes. The metal(II) complexes displayed antibacterial activity against the tested organisms; Ni(p-NO2babh)Cl2.4H2O had the least inhibitory concentration of 5 mg/mL, while the ligands were not active. The complexes displayed moderate activity comparable to the Clinical and Laboratory Standards Institute (CLSI) guidelines.

The synthesised metal(II) complexes of benzylacetone-benzoylhydrazone exhibited four and six coordinate geometries. The chemical compounds had antibacterial activity and they could serve as precursors for new antibacterial agents.