Facile synthesis and characterization of two new Pd(II) cocrystal complexes based on multifunctional quinoxaline ligands: X-ray crystallography, quantum chemical studies, molecular docking and biological profile

Two new Pd(II) co-crystallized complexes, [Pd(L1)Cl2].C6H4O2 (Pd-1) and [Pd(L2)Cl2].C6H5Cl (Pd-2), were synthesized using quinoxaline derivatives L1 (6,7-dimethyl-2,3-di(2-pyridyl)quinoxaline) and L2 (6,7-dichloro-2,3-di(2-pyridyl)quinoxaline). X-ray analysis confirmed that the complexes contained p-benzoquinone (Pd-1) and chlorobenzene (Pd-2), with molecules arranged in supramolecular arrays through C-H center dot center dot center dot Cl and it it interactions. In Pd-1, the p-benzoquinone was formed by catalytic oxidation of the benzene solvent. Hirshfeld surface analysis clarified the crystal packing and interaction types. Density functional theory (DFT) estimated the stereochemistry and global reactivity descriptors for Pd-1 and Pd-2. DNA binding studies using calf thymus DNA (CT-DNA) revealed intrinsic binding constants of 2.65 x 104 M-1 (Pd-1) and 1.50 x 105 M-1 (Pd-2). Gel electrophoresis showed that Pd-2 had superior DNA cleavage efficiency compared to Pd-1. Antioxidant activity was measured via DPPH center dot and OH center dot scavenging, with Pd-2 (electron-withdrawing Cl groups in the parent ligand) showing higher activity than Pd-1 (electron-donating CH3 groups in the parent ligand). In vitro cytotoxicity tests on MCF7 (breast cancer) and HepG2 (liver cancer) cells showed Pd-2 to be more cytotoxic in MCF7 cells (IC50 = 18.75 f 0.98 mu M) than Pd-1 (IC50 = 23.93 f 1.23 mu M), and more potent than cisplatin (IC50 = 22.62 f 1.02 mu M). For HepG2 cells, both complexes had similar activity compared to cisplatin, with IC50 values of 24.50 f 1.64 mu M (Pd-1) and 26.85 f 1.35 mu M (Pd-2). Finally, the molecular docking studies revealed their binding modes with B-DNA (PDB: 1BNA) and human serum albumin (PDB ID: 1AO6).