Ligand-modulated redox, DNA-binding, and cytotoxic properties of novel Palladium(II) oxime complexes.

Three novel Pd(II) complexes, [Pd(L1)Cl₂], K[Pd(L2)Cl₂], and [Pd(L3)Cl₂] (L1 = 2-acetylpyridine oxime, L2 = 2-acetylpyrrole oxime, L3 = 2-acetylthiophene oxime), were synthesized and comprehensively investigated in terms of their DNA-binding and electrochemical and anticancer properties. DNA interaction studies, including UV-Vis absorption titration, thermal denaturation, fluorescence quenching, and viscosity measurements, indicated that the complexes interact with DNA predominantly through non-covalent modes, such as groove binding and electrostatic interactions, with partial intercalative contributions. Biological evaluation in HepG2 hepatocellular carcinoma, T98G glioblastoma, MCF-7 breast cancer, and L929 normal fibroblast cells demonstrated that [Pd(L1)Cl₂] exhibited the most pronounced dose- and time-dependent cytotoxic activity among the tested complexes. Further cellular assessments in T98G glioblastoma cells and L929 fibroblasts showed that the reduction in viability associated with [Pd(L1)Cl₂] exposure was accompanied by a progressive redistribution from morphologically viable cells toward AO/PI-defined apoptotic-like and necrotic-like categories, together with a cell type-dependent oxidative stress response that was more evident in T98G cells. Electrochemical investigations by cyclic voltammetry in DMF demonstrated that all complexes undergo ligand-centered, irreversible oxidation processes. Spectroelectrochemical and coulometric analyses confirmed a one-electron transfer from ligand-based orbitals, leading to the formation of reactive iminoxyl radical intermediates, which subsequently dimerize. Accordingly, the cytotoxic effect observed for the Pd(II) complexes suggest a possible relationship between their redox behavior and biological activity. Overall, the results highlight the crucial role of ligand structure in governing both the redox behavior and DNA-binding properties of Pd(II) complexes, providing valuable insights for the design of new metal-based therapeutic agents.