Reactivity of Palladium(II)-η3-Allyl Complexes with Chalcogenolates: A Density Functional Study of Their Antitumor Implications

Palladium complexes are emerging as potential antitumor compounds. Recent experimental evidence suggests that the mechanism of action of some organopalladium derivatives might involve the target of proteins such as Thioredoxin Reductase (TrxR). In this work, we investigate different possible chemical mechanisms of interaction between selected palladium(II)-η³-allyl complexes and thiolates or selenolates, which are key functional groups present in the catalytic pocket of TrxR. Our investigation, focusing on both anionic and cationic complexes, suggests that in all cases, the interaction between the organopalladium species and chalcogenolates occurs via a ligand exchange reaction, which leads to the formation of a new Pd–S or Pd–Se bond. Allyl substitution, which takes place with the formation of a new C–S or C–Se bond, always appears to be the least favored reaction, from both the kinetic and thermodynamic points of view.