Synthesis, structural, equilibrium, anticancer, DNA binding, and computational investigation of binary and ternary palladium(II) complexes based on N-(2-hydroxyethyl)ethylenediamine

Novel palladium complexes, [Pd(hydten)Cl₂] (1) and [Pd(hydten)ox] (2), where hydten = N-(2-hydroxyethyl)ethylenediamine and ox = oxalate, were synthesized. The structure is confirmed using X-ray crystallography for (1) and different physicochemical techniques. A comprehensive analysis was conducted to investigate the composition, stability constants, and speciation curves of [Pd(hydten)(H₂O)₂]²⁺ complexes with some bio-ligands such as amino acids, peptides, and DNA constituents. This analysis aims to gain a deeper understanding of the distribution of different species in physiological environments. The interaction with DNA, one of the primary targets for chemotherapeutic drugs, was validated using the UV-Vis spectroscopic technique combined with molecular docking analysis. The geometrical optimization of each compound was performed by density functional theory (DFT), with the complete allocation of HOMO/LUMO electron clouds. <i>In vitro</i>, bio-evaluating the anticancer potency of each compound was accomplished on colon cancer (HCT116), bladder cancer (T24), liver cancer (HepG2), lung cancer (A549) cancer cell lines as well as non-malignant lung cell (WI-38). The [Pd(hydten)Cl₂] exhibits enhanced selective cytotoxicity contra the HCT116 malignant cell line (IC₅₀ = 13.87 ± 3.72 μM), lower than that of 5-fluorouracil (5-FU, IC₅₀=23.4 ± 2.4 μM), with minimal effects on healthy WI-38 cells.