Equilibrium, DNA binding, docking, and antimicrobial studies of Ni(II) and Cu(II) chelates with 1‐(4′‐nitrobenzoyl)‐3‐thiosemicarbazide

Abstract

Ni(II) and Cu(II) chelates of 1‐(4′‐nitrobenzoyl)‐3‐thiosemicarbazide (PNBTSC, HL) were synthesized and characterized by liquid chromatography‐mass spectrometry (LC–MS), thermogravimetric analysis (TGA), infra‐red (IR), UV–visible, and electron spin resonance (ESR) spectral techniques, which revealed the tetragonally distorted octahedral geometry around the central metal ion in both the chelates. The kinetic and thermodynamic properties were calculated using the Coats–Redfern relation. Thermal decomposition processes of chelates indicate the thermally stability of the chelates. The optimized molecular geometry, atomic charges, energies of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), and energy gap 0.11203 eV of HL have been studied by density functional theory (DFT) calculations, which revealed the soft nature and high reactivity of the compound. Equilibrium studies of the 1‐(4‐nitrobenzoyl)‐3‐thiosemicarbazide with Ni(II) ion in 70% v/v DMF‐water medium have been evaluated. The pKa value of HL was found to be 7.1, and the truen¯ values indicated the formation of 1:1 and 1:2 chelates in solution. DNA binding affinities of synthesized metal chelates with calf thymus DNA using UV absorption spectroscopy, spectro‐fluorimetry, and viscosity measurements revealed hypochromism and intercalative mode of binding. The Kb values from the absorption studies are 5.00 × 106 and 3.33 × 106 M−1, and Ksv values from fluorescence studies are 0.108 and 0.395 M−1 for chelates 1 and 2, respectively. The cleavage of supercoiled pBR33 DNA without any additives was studied using gel electrophoresis method which exhibited hydrolytic cleavage of plasmid DNA. Molecular docking studies carried out for the complexes also inferred intercalative mode of binding with DNA. The inhibition constants for HL, 1, and 2 are 107.09, 21.66, and 184.45 μM, respectively. Ligand and its metal chelates screened for antimicrobial activity against Gram positive and Gram negative bacteria revealed higher activity in chelates.