Synthesis, characterisation and biological studies of mixed-ligand nickel (II) complexes containing imidazole derivatives and thiosemicarbazide Schiff bases

Abstract

Four new mixed-ligand Ni(II) complexes (1–4) containing imidazole (im) or benzimidazole (bz) and tridentate Schiff bases derived from 2,4-dihydroxybenzaldehyde (24D) and 4-methyl-3-thiosemicarbazide (MT24D) or 4-phenyl-3-thiosemicarbazide (PT24D) were synthesised and characterised using elemental and spectral analysis including FTIR, UV–Vis, 1H NMR, 13C NMR and mass spectrometry for Schiff bases, while the complexes were additionally analysed using ICP-OES, molar conductivity, magnetic susceptibility measurements and single crystal X-Ray diffraction (SXRD) analysis. Magnetic susceptibility indicated a square planar geometry for all the metal complexes while molar conductance values showed that the complexes were non-electrolytes in DMSO. The molecular geometries of the neutral complex molecule in [Ni(MT24D)(bz)](bz). CH3OH (2′), that is 2 co-crystallised with a 1,3-benzimidazole molecule as a methanol solvate, and in the cation of [Ni(MT24D)(im)]O2CMe.2H2O (5), a reaction intermediate for 1, were established by X-ray crystallography. Each featured a trans-N2OS coordination geometry defined by phenoxide-O, imine-N and thiolate-S (2′) or thione-S (5) donors as well as the imine-N donors derived from 1,3-benzimidazole (2′) or imidazole (5) molecules. Systematic variations in geometric parameters were correlated with the form of the tridentate ligand, i.e. di-anionic (2′) or mono-anionic (5). In the crystal of 2′, supramolecular chains were sustained by hydrogen bonding and these were connected into a supramolecular layer by π … π stacking interactions occurring between coordinated benzimidazole rings. In the crystal of 5, hydrogen bonding led to a three-dimensional architecture. The Schiff bases and mixed-ligand Ni(II) complexes were tested for their cytotoxic activitY, but all compounds were inactive against the MDA-MB-231 and MCF-7 breast cancer cell lines. Interestingly, the antibacterial analysis of the compounds showed that the PT24D Schiff base, Ni(MT24D)im, Ni(MT24D)bz, and Ni(PT24D)bz complexes had specific and selective activity against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Propionibacterium acne (P. acne) and Enterobacteraerogenes (E. aerogenes). The DNA binding studies of mixed-ligand Ni(II) complexes against calf thymus DNA revealed that slight hypochromism was observed in the absorption spectra suggesting π-π interactions between the aromatic chromophores and the DNA base pairs where 2 had higher Kb values than 1 thus indicating stronger interactions.