Synthesis, structural insights, antimicrobial potency, and theoretical studies of Cu(II), Ni(II), and Cd(II) complexes derived from Coumarin-based 1,2,4-Triazine

Abstract

A novel hydrazone ligand, 4-{[−1-(4-hydroxycoumarin-3-yl)ethylidene]amino}-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one (CEAT), was synthesized via condensation of 3-acetyl-4-hydroxycoumarin with 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one. Coordination of CEAT with Ni²⁺, Cu²⁺, and Cd²⁺ ions afforded M(CEAT) complexes in a 1:1 stoichiometric ratio. The current compounds were characterized by elemental analysis, TGA, magnetic susceptibility, molar conductivity, IR, ¹H and ¹³C NMR, mass spectrometry, UV–Vis, ESR, and XRD. Spectral data confirmed CEAT as a monobasic ONS tridentate ligand, coordinating via azomethine nitrogen, phenolic oxygen, and thione sulfur atoms, forming a tetrahedral geometry for Cu(CEAT) and octahedral geometries for Ni(CEAT) and Cd(CEAT) complexes. Also, the overall shape and nature of the ESR signal are consistent with a distorted tetrahedral geometry around the copper center. The molar conductivity data indicate that Cu(CEAT) and Ni(CEAT) complexes are neutral, whereas Cd(CEAT) falls within the characteristic range for a 1:1 electrolyte. The XRD analysis confirmed the crystalline nature of the present complexes with crystallite sizes of 12–21 nm. Antimicrobial evaluation showed that complexation markedly enhanced bioactivity compared to the free ligand, where Ni(CEAT) exhibiting the strongest antibacterial effect against Escherichia coli (MIC = 19.2 μg/mL) and notable antifungal potency against Candida albicans (MIC = 15.4 μg/mL). Density Functional Theory (DFT) calculations were performed to optimize the molecular geometries of the CEAT ligand and its metal complexes, alongside the evaluation of key quantum chemical descriptors. Moreover, the computed first hyperpolarizability values of the synthesized compounds are better than those of urea, suggesting their promising potential for nonlinear optical (NLO) applications. Comparative analysis between theoretical predictions and experimental antimicrobial results provided mechanistic insight into enhanced bioactivity. In silico ADMET and toxicity profiling further indicated that the CEAT ligand and its complexes possess favorable pharmacokinetic attributes, including suitable oral bioavailability, low predicted systemic toxicity, and high metabolic compatibility. Molecular docking against E. coli 1HNJ protein demonstrated strong and stable binding, where Ni(CEAT) showing the highest affinity (−10.30 kcal/mol), correlating with its superior in vitro antimicrobial performance.