Synthesis, characterization and antitumoral evaluation of transition metal complexes with bulky fluorinated and non-fluorinated β-diketonates

The coordination chemistry of β-diketones is central to inorganic research due to their versatile coordination and applications in catalysis and medicinal chemistry. In this study, we synthesized Cu(I), Ag(I) and first-row transition metal(II) complexes with the bulky β-diketone ligands HLMes, HLCF3, and HLPh. X-ray crystal structures show a planar CuO2C3 metallacycle in [Cu(LCF3)(PPh3)2], while a half-boat AgO2C3 core is displayed by [Ag(LPh)(PPh3)2]; both exhibit distorted tetrahedral geometry (Figure 1a and b). Whereas [Cu(LCF3)2] crystallizes as a square pyramidal complex with an apical THF molecule (Figure 1c), Cu(II) and Zn(II) complexes with HLMes ligand display square planar and distorted tetrahedral geometries (Figure 1d), respectively. Cu(I) complexes with HLCF3 and HLMes ligands exhibited superior antitumor activity against human tumor cell lines derived from solid tumors, compared to Ag(I) complexes and cisplatin. Notably, [Cu(LMes)(PPh3)2] was up to 16-fold more effective against 2D testicular carcinoma (NTERA-2), while [Cu(LCF3)(PPh3)2] had strong antiproliferative effects against 3D tumor spheroids (HCT-15). Among the first-row metal(II) complexes, [Mn(LMes)2(H2O)2] and [Cu(LMes)2] were the most active, with the Mn derivative being 15 times more potent than cisplatin against HCT-15 cells. Except for iron derivatives, the complexes displayed significant antitumor properties, even against cisplatin-resistant cancer cells. These results highlight the role of ligand design and coordination environment in enhancing the antitumor potential of transition metal complexes.