A tetranuclear palladium(II) complex featuring a distinctive Pd$_4$N$_4$ “cuneane”-type core: crystal structure, in vitro cytotoxicity, DFT and docking simulations

A mono-Schiff base ligand, N-(3-methoxysalicylidene)-phenylenediamine (H$_2$L), featuring an unprotected vicinal aromatic amine, was synthesized to investigate its coordinating behavior with palladium(II) ions. The resulting complex was characterized by elemental analysis, $^1$HNMR and FT-IR spectroscopy, ESI-MS, TGA, and SC-XRD. Crystal structure analysis of the complex revealed that each twofold deprotonated mono-Schiff base ligand acts simultaneously as a tridentate NNO chelating and bridging ligand, giving rise to a self-assembled tetranuclear palladium(II) complex, [PdL]$_4$, featuring a “cuneane”-type Pd$_4$N$_4$ core. The in vitro cytotoxic activities of H$_2$L, [PdL]$_4$, and cisplatin were evaluated against human breast carcinoma (MCF-7), colorectal cancer (HCT-116), and nontumorigenic human breast (MCF-10A) cell lines using the MTT assay. Based on CC$_{50}$ values, [PdL]$_4$ exhibited greater cytotoxic potency against both cancer cell lines compared to the free ligand. Notably, [PdL]$_4$ was less cytotoxic to MCF-10A cells, with selectivity indices (SIs) of 4.4 for MCF-7 and 3.2 for HCT-116 cells. The complex remained stable over pH 4–10, and its spectroscopic profile showed no significant changes after 48 h in Tris buffer. ... mehrDNA-binding studies indicated interactions of H$_2$L and [PdL]$_4$ with CT-DNA, while viscosity measurements suggested a mixed binding mode, with a partial intercalative contribution for both compounds. DFT, MEP, and FMO analyses were performed to examine the optimized structures, electronic properties, and potential reactive sites of H$_2$L and [PdL]$_4$. Furthermore, molecular docking simulations suggested that both compounds interact with DNA through a groove-associated mode. The predicted binding affinity for [PdL]$_4$ was higher than that of H$_2$L.