Biological activity evaluation and molecular docking studies of newly synthesized β-ketoiminato-based palladium complexes

A series of palladium(II) β-ketoiminato complexes, [Pd(CH 3 C( NAr )CHC(O)Ph) 2 ] ( 4a – j ), were synthesized via the reaction of N-aryl-substituted β-ketoiminate precursors with [PdCl 2 (CH 3 CN) 2 ] in the presence of t BuOK. Single-crystal X-ray diffraction of 4a – h and 4j confirmed a square-planar Pd(II) coordination. Notably, 4b exhibited C–H···Pd anagostic interactions, contributing to lattice stability, which was further analyzed using Hirshfeld surface 2D fingerprint plots. Computational studies, including non-covalent interaction (NCI) plots and quantum theory of atoms in molecules (QTAIM), provided insights into these interactions. Complexes 4a – j show characteristic ILCT (π → π *) bands in their UV–Vis spectra, which were additionally confirmed by TD-DFT calculations. DFT analysis reveals that the HOMO is composed of contributions from both the Pd(II) center and β-ketoiminato ligand orbitals, while the LUMO is primarily derived from β-ketoiminate ligand orbitals. The anticancer potential of 4 a– j was evaluated against MCF-7 and HT-29 cell lines. Complexes 4a – d and 4f exhibited significant cytotoxicity, effectively inhibiting HT-29 cell migration. Among them, 4c demonstrated the highest potency, with an IC50 of 1.73 μM, significantly reducing HT-29 cell viability . The ability of Pd(II) complexes to interact with three targeted proteins, namely, PIK3CA-E545K, ERBB4-Y1242C, and BRAF-V600E was evaluated through molecular docking studies, revealing moderate to high binding affinities . Notably, complex 4c demonstrated the strongest interactions across all targets. • Synthesis, characterization, computational, and biological assessment β-Ketoiminato-Based Palladium Complexes were performed. • Single crystal confirmed the square-planar tetrahedral geometry possessing C6-ring motifs on either side of the Palladium atom. • Hirshfeld surface analysis was conducted to examine and comprehend short contacts and non-covalent interactions. • Computational chemistry study was performed to compare experimental data with theory and predict structures. • Cytotoxic activities were obtained against breast (MCF-7) and colon (HT-29) cell lines. • -.