Structural diversity of new mixed-ligand Ni(ii) complexes derived from ciprofloxacin and 2-methylbenzimidazole: synthesis, characterization, DFT insights, antimicrobial activity and DNA gyrase B (4DUH) docking

Abstract

A set of mixed ligand nickel(ii) complexes, namely, NiAC ([Ni(CIP)(MIM)(OAc)]), NiPE ([Ni(CIP)(MIM)(H2O)]ClO4), and NiCL([Ni(CIP)(MIM)(H2O)2Cl]), derived from the combination of ciprofloxacin (CIP) and 2-methylbenzimidazole (MIM), were synthesized in high yields (85–88%) and characterized by various physicochemical as well as computational techniques. The 1 : 1 : 1 stoichiometry was established by elemental analysis, whereas the non-electrolytic nature of the complexes was established by the molar conductance studies for NiAC (9.62 Ω−1 cm2 mol−1) and NiCL (10.85 Ω−1 cm2 mol−1), in comparison to the 1 : 1 electrolyte nature of the complex, NiPE (68.52 Ω−1 cm2 mol−1). The distorted tetrahedral geometry for the complexes, NiAC and NiPE, and octahedral geometry for the complex, NiCL, were established by the appearance of bands in the region 640, 610, 675 nm, respectively, in the electronic spectrum, as well as by the observed magnetic moments of 3.73, 3.68, 2.95 B.M., respectively. The bidentate coordination mode of CIP via the carboxylate and carbonyl groups, as well as the monodentate coordination mode of MIM via the nitrogen donor site were established by FT-IR analysis. Thermal analysis indicated good stability with decomposition above 225 °C, with NiO residues at the end of the reaction (∼11–13%). DFT results showed good reactivity for the complexes, especially NiAC, with the lowest HOMO–LUMO energy gap, i.e., ΔE = 1.54 eV, the highest electrophilicity, i.e., ω = 33.74 eV, and the highest softness, i.e., σ = 0.65 eV−1. The Ni(ii) complexes exhibited appreciable antibacterial and antifungal activities under the tested conditions. NiAC showed a MIC of 40 µM, while the other complexes displayed MIC values of 40–50 µM. The complexes achieved activity indices of 74.29–93.33% against bacteria and 80.00–95.00% against fungi. Molecular docking was done with the active site of DNA gyrase B, i.e., 4DUH, which showed good binding affinities with NiAC at −8.50 kcal mol−1 due to extensive hydrogen bonding and electrostatic interactions. The results revealed the synergistic effect of coordination that enhances biological activity and indicates that these complexes are promising antimicrobial agents.