Biological impact of Pd(II) complexes: Synthesis, crystal structure, Hirshfeld surface analysis, NCI-RDG, molecular docking, molecular dynamic simulations

This work includes the synthesis of a new series of palladium-N-heterocyclic carbene complexes (3a-i). The new complexes were characterized using NMR (¹H and ¹³C), FTIR spectroscopic, and elemental analysis techniques. The crystal structure of complex 3a was obtained by utilizing the single-crystal X-ray diffraction method. X-ray studies show that the coordination environment of palladium atom is completed by the carbene atom of the NHC ligand, the nitrogen atom of the morpholine ring, and a pair of bromide ligand, resulting in the formation of slightly distorted square planar geometry. In order to gain more insight about structure the study also delved into the examination of various intermolecular interactions between neighboring molecules using Hirshfeld surfaces. A good agreement between experimental and theoretical data was observed. Furthermore, the antioxidant and the cytotoxicity activities of these compounds were assessed. Density Functional Theory (DFT) calculations showed that PEPPSI-type palladium (II)-NHC complexes (3a-i) are structurally stable with bond lengths like Pd1-C1 ranging from 1.980 to 1.983 Å and a HOMO-LUMO gap of about 3.55 eV, suggesting potential for biological applications. Molecular docking and ADMET analyses indicated strong binding to Keap1 (−190.22 to −211.96) but weaker affinity for CDK2 (−129.04 to −136.57), with high lipophilicity (log P: 4.869–5.069) and toxicity risks highlighting the need for optimization.