Synthesis, crystal structure, DFT calculations, and molecular docking of N-(4-bromophenyl)pyridine-2-carboxamide palladium(II) complexes

A novel palladium(II) complex, ([N-(4-bromophenyl)pyridine-2-carboxamidato]-(chloro)-(pyridine)‑palladium, C2 ) was synthesized from an aqueous solution of potassium tetrachloropalladate, pyridine and the N - (4- bromophenyl) pyridine-2-carboxamide ligand. Single crystal X-ray crystallography analysis reveals that the asymmetric units of C 17 H 15 BrClN 3 O 2 Pd belong to the orthorhombic crystal system with the Pbca space group. The experimentally determined structure of C2 was examined and compared to a previously synthesized analogous bis[N-(4-bromophenyl)pyridine-2-carboxamidato]palladium complex ( C1 ) by density functional theory (DFT) and molecular docking studies. DFT b3lyp/3-21g method gave reasonably low optimization energies and band energy value of ∼3.2 eV for both complexes, suggesting they are chemically reactive. Molecular docking simulations through the docking scores show that C2 (−121.2 and −119.2 kcal/mol) is more potent than C1 (−73.1 and −106.6 kcal/mol) against prostate and cervical cancers, while C1 (−78.5 and −108.3 kcal/mol) is more potent than C2 (−88.5 and −116.5 kcal/mol) against skin and breast cancer. Some key interacting residues in the binding site of prostate cancer protein include Trp227, Phe306, Phe311, and Tyr317. The cervical cancer protein includes Tyr15, Asp127, Val18 and Glu12. For skin cancer protein, they are Arg223, Glu226, Leu227 and Ile224; and for breast cancer protein are Cys2085, Glu2052, Phe2048, and Gln2082. Generally, the Pd(II) complexes show promising anticancer potential and could potentially be a more effective chemotherapeutic than the standard carboplatin drug.