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/H 2 O 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 IC 50 values comparable or lower than cisplatin. The potent anticancer activity of two IPr Cl 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.
The Front Cover shows novel allyl and indenyl palladates with a promising biological activity. A wide range of these peculiar Pd(II) derivatives were prepared by a solvent‐free method consisting of grinding the corresponding Pd precursors with different azolium salts. These complexes are stable in chlorinated and polar solvents, and most of them showed excellent cytotoxicity towards ovarian cancer cell lines. Interestingly, the potent anticancer activity was also confirmed in a high‐grade serous ovarian cancer patient‐derived tumoroid, with a clear superiority of this class of compounds over classical platinum‐based agents. Finally, preliminary enzyme inhibition studies of the Pd(II) complexes against the model TrxR show that the compounds have high activity comparable to or even higher than those of auranofin and classical gold(I)‐NHC complexes. More information can be found in the Research Article by T. Scattolin, F. Visesntin, S. P. Nolan and co‐workers.
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