A robust synthesis, physicochemical characterization, stability determination and potential biomedical applications of novel Salen complexes supported by theoretical approaches

Abstract

A series of novel chelates incorporating Cu(II), Ni(II), VO(II), and Pd⁽II) ions with the ligand 2,2′-((1E,1′E)-((4-methyl-1,2-phenylene)bis(azanylylidene))bis(methanylylidene))bis(4-bromophenol) (MPZP) were synthesized and extensively characterized. Characterization techniques included thermogravimetric analysis (TGA), CHN elemental analysis, spectroscopic methods such as IR, NMR, and mass spectrometry, along with melting point determination, magnetic moment analysis, molar conductance, UV-vis spectroscopy, and computational studies. Conductivity measurements confirmed that all the chelates exhibited non-electrolytic behavior where MPZPCu (13.75 Ω⁻¹ cm² mol⁻¹), MPZPNi (12.15 Ω⁻¹ cm² mol⁻¹), MPZPPd (10.50 Ω⁻¹ cm2 mol⁻¹), and MPZPVO (8.90 Ω⁻¹ cm² mol⁻¹). FT-IR spectrum displays that the tested main ligand is coordinated with metal ions in a tetra-dentate behavior with ONNO donor sites. The ligand's coordination ability was assessed through magnetic and electronic spectra, which also revealed the geometry of the complexes: octahedral for Cu(II) and Ni(II), (μeff = 1.75 and 2.46 B.M, respectively), square pyramidal for the VO(II) complex with a magnetic moment 1.78 B.M, and diamagnetic square planar for Pd(II). Moreover, the obtained analytical data regarding complexation in solution, molar ratio and continuous variation methods suggest 1M: 1 L molar ratio. Also, the stability and formation constants of the investigated complexes was determined and follow the order: MPZPCu > MPZPNi > MPZPVO > MPZPPd complex. The pH profile revealed that the wide range of pH stability of the tested complexes (pH = 4–11). Computational analyses using density functional theory (DFT) with the B3LYP method provided insights into the molecular electrostatic potential (MEP) and the HOMO-LUMO energy levels. The results indicated a strong agreement between the DFT calculations and the experimental findings. Nonlinear optical properties were evaluated by calculating the molecular polarizability (α) and hyperpolarizability (β) parameters, leading to an enhancement of the unexpected optical characteristics of the synthesized materials. A molecular docking mechanism between the ligand and its Cu(II), Ni(II), VO(II), and Pd⁽II) chelates was investigated against microbial protein and breast cancer cell pocket receptors to establish how these substances attach to the protein's active sites. Moreover, the biological activity of the investigated compounds against selected strains of bacteria, fungi and cancer cell lines was determined. The findings demonstrated significant antimicrobial activity of the investigated metal chelates against various bacterial and fungal strains compared to its corresponding MPZP ligand. MPZPPd complex showed high antimicrobial activity (39.70 ± 0.10 and 37.45 ± 0.09) mm against M. luteus bacteria and G. candidum fungi, respectively. The chelates also showed promising anti-cancerr activity against MCF-7 (breast cancer), Hep-G2 (liver cancer), and HCT-116 (colon cancer) cell lines, highlighting their potential as therapeutic agents. The high cytotoxicity was clearly recorded for MPZPPd complex with IC₅₀ % (4.60, 4.75 and 6.25 µg/mL) respectively. Furthermore, antioxidant performance, tested using the DPPH assay for the investigated compounds, revealed satisfactory free radical scavenging activity. The MPZPPd exhibited significant free radical scavenging activity with an IC₅₀ value of 17.25 µg/mL.