Mixed ligand 4-hydroxy acetanilide-febuxostat complexes of Co(II),- Ni(II), Cu(II) and Zr(IV): Synthesis, structural characterization, DFT calculations, antibacterial, antioxidant and molecular docking studies

The synthesized mixed ligand metal complexes were achieved by a combination of febuxostat (2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid) (FEB) and paracetamol (4-hydroxy acetanilide) (Para) together with crucial biologically relevant elements. These elements, including Co(II), Cu(II), Zr(IV), and Ni(II) chlorides, play important roles in various biological systems and mechanisms, such as antioxidant, antimicrobial systems, and contribute to diverse functions and structures. To identify chemical formulae and structures of synthesized complexes, physical-analytical, spectroscopic (XRD, FT-IR, ESR, 13C NMR, 1H NMR, and UV-visible), mass spectrometry (MS), TG-DTG studies were used and supported by computational approaches. FT-IR and 1H NMR data revealed that FEB chelated through sulfur of thiazole ring as a mono-negative bidentate type and deprotonated oxygen of carboxylate group, according to lack of characteristic band at 1677 cm−1 and signal at δ = 13.37 ppm (-OHCOOH), whereas Para chelated through nitrogen and oxygen of amide group as a neutral bidentate ligand. Magnetic moment and electronic spectra data revealed that complexes have an octahedral structure. The optical band gap (Eg) for our compounds was calculated and according to Eg values, all complexes were semi-conductors and fell into the class of solar materials compared with FEB and Para. XRD pattern showed the monoclinic polycrystalline structure for all compounds except the Zr(IV) complex was amorphous. Kinetic parameters of the thermal decomposition stages were calculated. DFT was utilized to confirm bonding mode for FEB and Para with metal ions and according to calculations of energy band gap (ΔE) of complexes, Cu(II) complex with smaller ΔE is more reactive but, Zr(IV) complex with higher ΔE is less reactive than FEB and Para. The antibacterial activity of FEB, Para, and their complexes were tested against two G-ve and three G+ve bacteria. Co(II) complex displayed remarkable effectiveness and high significance against all strains of bacteria, compared with other compounds tested. All compounds demonstrated antioxidant effects, Cu(II) and Zr(IV) show greater antioxidants than parent ligands with IC50 values 0.040 and 0.057 mg/mL. The binding pattern and active site of all compounds were put through molecular docking studies and compared with empirical biological data.