Structure elucidation and evaluation of the antimicrobial and antitumor activities of 5-methylthiazole-based Schiff base and its metal chelates

The current thiazole Schiff base ligand was obtained upon reacting 2-amino-5-methylthiazole with 2,4-dihydroxybenzaldehyde (H₂L). The transition metal chelates then were presented by reacting the ligand with Mn(II), Cu(II), and Zr(IV) salts in 1:1 molar ratio forming chelates, 1, 2 and 3, respectively. The reaction of the ligand with Cd(CH₃COO)₂ afforded Cd(II) complex, 4, in the molar ratio 2L:1 M. The type of contact that occurs between metal ions and the thiazole ligand was investigated by the assistance of magnetic susceptibility, FTIR, mass, UV-Visible and ¹H NMR spectral and micro-elemental analyses. The resulting data demonstrated that the ligand-metal interaction happened via the phenolic O-atom ortho-position and the imine group N- atom which is dehydrogenated to form the metal complexes. Solvent molecules attached to the metal ions in complexes, whether present or absent were suggested using TGA in addition to thermodynamic activation parameters for the thermal decomposition steps were computed by the Eyring equation. Magnetic moment and UV-Visible measurements indicated formation of square planar Cu(II) chelate and octahedral Zr(IV) chelate, while the Mn(II) and Cd(II) ions formed tetrahedral metal chelates. XRD and TEM used to reveal structural microcrystalline data of both the organic compound (H₂L) and inspected complexes. The patterns of X-ray diffraction introduced the crystalline nature of each of the free ligand, complexes 1, 3 and 4, whereas complex 3 was relatively amorphous without an even dispersion of the solid constituents throughout the precipitation procedure. The study rigorously analyzed molecular structures using Density Functional Theory (DFT) calculations, revealing significant variations in ligand bond lengths and angles upon complexation, and demonstrating the electron-donating and accepting properties of HOMO and LUMO orbitals. Biological activity for the prepared compounds was accomplished. They exhibited high activity, especially after chelation. The Antimicrobial activity afforded very auspicious data upon comparison with the applied reference antibiotic. The greatest anti-cancer activity has been achieved by Cu(II)-complex 2 which showed IC₅₀ value = 16.89 µg/ml against MCF-7 cell lines which is greater than the IC₅₀ value of scaled drug applied (IC₅₀ of 5-flurouracil = 28.0 µg/ml). Promising bioactive compounds' binding affinities with HepG-2 and MCF-7 DNA helices were estimated to apply molecular docking.