Indenyl and Allyl Palladate Complexes Bearing N-Heterocyclic Carbene Ligands: an Easily Accessible Class of New Anticancer Drug Candidates

The mechanochemical syntheses of allyl and indenyl palladate complexes are reported. All compounds were obtained in quantitative yields and microanalytically pure without the need of any workup. These complexes are stable in chlorinated and polar (DMSO or DMSO/H2O solutions) solvents. In chlorinated solvents, they appear as ionic pairs of which crystals suitable for single X-ray diffraction studies have been obtained. Bonding and solvation properties are rationalized through scalar relativistic DFT calculations. Moreover, most complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with IC50 values comparable or lower than cisplatin. The potent anticancer activity of two IPrCl and IPr*-based palladate complexes was examined in a high-grade serous ovarian cancer (HGSOC) patient-derived tumoroid. Moreover, the inhibition of the antioxidant enzyme thioredoxin reductase (TrxR) was noticed, and structure-activity relationships could be derived, suggesting the ROS detoxifying system is involved in the mode of action.