Studies of the molecular docking, antibacterial, antifungal, and DNA interaction of mixed-ligand Ni(II) complexes with gabapentin or pregabalin and diimine coligands

Abstract

A group of nickel(II) complexes with mixed ligands (1–9) belong to the form [Ni(L)2(H2O)2].2H2O; [Ni(L)(diimine)(NO3)].2H2O and [Ni(L)(diimine)(H2O)y].NO3·nH2O where L = gabapentin (Gpn) or pregabalin (Preg); y = 2, n = 4 and y = 4, n = 3½, the diimines are 1,10-phenanthroline (Phen), 2,2′-dipyridyl (2-Dipy) and 4,4′-dipyridyl (4-Dipy) have been effectively synthesized and described. XRD data using Expo2014 computer program treated the XRD data showing: monoclinic, tetragonal and triclinic crystal orders. IR spectra showed that Preg and Gpn used COOH– to ligate as monodentate ligand to the Ni2+. While 4-Dipy is bound as a monodentate ligand, Phen and 2-Dipy coordinate as bidentate chelating agents. The resulting magnetic moment values and UV–Vis spectra data confirmed deformed octahedral and tetrahedral to pseudo tetrahedral stereochemistry. The complexes' electronic absorption spectrum titration was used to compute the Kb values, which varied in the following order: 4-Dipy > 2-Dipy > Phen. The Ni2+ mixed-ligand complexes' in vitro biological activity was tested against Aspergillus fumigatus and Candida albicans fungus, as well as Gram + ve Staphylococcus aureus and Gram-ve Escherichia coli pathogenic bacteria. Molecular docking studies of the complexes was carried out using penicillin-binding proteins. Obtained data demonstrated the preferential binding of complex (9) within the catalytic Staph. aureus PBP4 pocket which came in good agreement with the in-vitro anti-bacterial activities.