Transition Metal Complex Based On Phenoliccarboxylic Ligand: Spectroscopic Inspection, DFT/TDDFT Computations, Cytotoxicity and Molecular Docking Investigation

The study was designed to explore the synthesis, characterization, and biological evaluation of a novel Mn-(II)-3-[(3-carboxy-2-hydroxyphenyl)-methyl]-2-hydroxybenzoic complex, [Mn-(CHB-2H)·4H₂O)]·2H₂O, in comparison to its corresponding ligand (CHB). The manganese-(II) complex (Mn-(II)-CHB) was synthesized from CHB and manganese-(II) acetate in ethanol solution using the conventional method. Because most of the chemo drugs are nonselective and may cause damage to normal tissues, finding new anticancer medications or developing anticancer agents is becoming more crucial. The work's objective was to minimize the toxic side effects of most chemo drugs and improve available chemotherapy against human liver cancer. PXRD, TEM, thermal (TGA, DSC), magnetic investigations, UV-vis, FT-IR, MS, ¹H/¹³C NMR, and elemental analysis helped to describe the structure of the ligand and the complex. The octahedral complex has been postulated through experimental and theoretical data. Different thermal (kinetic and thermodynamic) parameters were calculated using the Coats-Redfern model. The kinetic parameters revealed that the decomposition reactions of the synthesized complex followed the first-order model with the rate constant values ranging from 0.022 to 0.193 min^-1 and the activation energies were 42.18, 19.79, 55.72, and 13.20 kJmol^-1. Spherical granules were identified using the morphological analysis (TEM). The average particle sizes of CHB and Mn-(II)-CHB are 118 and 28 nm, respectively. The notable reduction in particle size indicates that the modification with Mn-(II) has changed the physical characteristics, confirming the formation of the nanocompound. XRD data reflect that the Mn-(II)-CHB complex is amorphous, while the CHB ligand is crystalline. Electronic spectra quantified the optical properties like energy gap, refractive index, optical conductivity, and penetration depth. The compounds' band gap values (CHB = 3.20 eV and Mn-(II)-CHB = 2.12 eV) are within the semiconductor range. The structural and electronic properties of the Mn-(II)-CHB were elucidated through density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations. The optimized high-spin sextet geometry, detailed frontier orbital analysis, and computed UV-vis spectrum reveal strong metal-ligand orbital mixing and a large HOMO-LUMO gap consistent with high kinetic stability and selective charge-transfer excitations. The examination of cytotoxicity against hepatocellular (HepG-2) cells, which are a type of human liver cancer cell, demonstrated significant growth inhibition. Based on experiment results, the CHB gave a respectable effect to prevent 50% of cell multiplication (IC₅₀ = 66.78 ± 4.76 μM). A molecular docking simulation was conducted to assess the binding mode and affinity of the target compounds toward peroxisome proliferator-activated receptors [PDB ID: 1i7i], which are associated with hepatocellular malignancies. The enhanced binding affinity of the Mn-(II) complex (-7.9 kcalmol^-1) compared to the parent ligand (-7.4 kcalmol^-1) correlates with its improved anticancer activity. The investigated assays suggest that the synthesized compounds are potent antiliver cancer agents.