The first palladium organometallic compounds bearing N‐trifluoromethyl N‐heterocyclic carbenes have been synthesized. These η3‐allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5‐triaza‐7‐phosphaadamantane (PTA) as co‐ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2‐methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3‐allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids.

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 reactivity of palladium(II) indenyl derivatives and their applications are topics relatively little studied, though in recent times these compounds have been used as pre-catalysts able to promote challenging cross-coupling...

Novel allyl palladium compounds stabilized by carbohydrate‐based N‐heterocyclic carbenes (NHCs) were prepared and characterized by nuclear magnetic resonance, high‐resolution mass spectrometry and elemental analysis. The antiproliferative activity of the compounds was tested on a panel of different tumor lines, especially ovarian cancer and MRC‐5 human lung fibroblasts (nontumor cells). These experiments showed that both mixed NHC/PPh3 and NHC/PTA (PTA = 1,3,5‐triaza‐7‐phosphaadamantane) allyl complexes have IC50 (half maximal inhibitory concentration) values comparable and sometimes even significantly lower than cisplatin. Moreover, the mixed NHC/PTA allyl complexes exhibit good activity toward the seven tumor lines tested with a substantial inactivity against normal cells, a necessary condition to avoid the general cytotoxicity of a metallo‐drug. Furthermore, this subclass of compounds proved particularly active on the A549 lung cancer tumor line (up to 100‐fold more cytotoxic than cisplatin) and exhibited satisfactory cytotoxicity against KURAMOCHI and OVCAR3 cell lines, which are currently considered the best in vitro models for serous ovarian cancer, the most lethal tumor for women worldwide.

A new dinuclear Pd(I) complex coordinating two bis(NHC) ligands revealed an unsuspected stability despite the unsaturation of the two metal centres. Even more surprisingly, the compound showed a high and...