Theoretical Study On The Transition States Of Tumor Active Pd Complexes Interaction With Target Molecule

We present a theoretical study of palladium complexes with large steric ammine ligand and ethylenediamine bidentate ligand interacting with DNA bases by density functional theory in this thesis.Palladium(II) complexes coordinated to large planar amine ligands represent a lead structure of considerable interest in current antitumor drug design. but the question was whether these complexes can bind to DNA bases affording bifunctional adducts for great steric hindrance provided by the bulky ligands. We studied the interaction of the palladium(II) complex, PdCl2L2, where L was 2-hydroxypydridine, with DNA bases using density functional theory and combining with isoelectric focusing polarized continuum (IEF-PCM) solvation model. Activation free energies for the complex monofunctional and bifunctional binding to DNA bases were lower than those for platinum-based antitumor agents. All reactions under study were exothermic in aqueous solution. We conclude that the large planar amine ligands in the palladium complexes will not hinder formation of bifunctional adducts with DNA bases. We also expect the rates for monofunctional and bifunctional binding to DNA bases to be faster than those of platinum-based agents.Palladium complexes with ethylenediamine bidentate ligand does not only represent a lead structure in current antitumor drug design, but also extensively used as the metal corner in the design and synthesis of molecular architectures. There have been controversial discussions about the structures of [Pd(en)(guanine)4]. We present a computational study and suggest that the tetramer adopts a structure of—N1—Pd—N7—corners. The—NH2…O=C hydrogen bonds are cooperatively formed among four guanines, which play a pivotal role in stabilizing the tetramer.