Cytostatic metallo-drugs mostly bind to the nucleobases of DNA. A new family of dinuclear transition metal complexes was rationally designed to selectively target the phosphate diesters of the DNA backbone by covalent bonding. The synthesis and characterization of the first dinuclear NiII 2 complex of this family are presented, and its DNA binding and interference with DNA synthesis in polymerase chain reaction (PCR) are investigated and compared to those of the analogous CuII 2 complex. The NiII 2 complex also binds to DNA but forms fewer intermolecular DNA cross-links, while it interferes with DNA synthesis in PCR at lower concentrations than CuII 2. To simulate possible competing phosphate-based ligands in vivo, these effects have been studied for both complexes with 100–200-fold excesses of phosphate and ATP, which provided no disturbance. The cytotoxicity of both complexes has been studied for human cancer cells and human stem cells with similar rates of proliferation. CuII 2 shows the lowest IC50 values and a remarkable preference for killing the cancer cells. Three different assays show that the CuII 2 complex induces apoptosis in cancer cells. These results are discussed to gain insight into the mechanisms of action and demonstrate the potential of this family of dinuclear complexes as anticancer drugs acting by a new binding target.

Planar tridentate Lewis acids were synthesised by hydrosilylation reactions of triethynylbenzene with chlorosilanes. Hydrogenation of the rigid triethynylbenzene using hydrogen in the presence of Lindlar's catalyst resulted in the formation of trivinylbenzene. The hydrosilylation of this compound enabled the synthesis of flexible tridentate Lewis acids with SiClMe 2 and SiCl 2 Me, SiCl 3 groups. In order to increase the acidity, the [a] 2533 Scheme 2. Synthesis of 1,3,5-tris[(trimethylsilyl)ethynyl]benzene by Sonogashira cross-coupling reaction of 1,3,5-tribromobenzene and subsequent deprotection to 1,3,5-triethynylbenzene. Reagents and conditions: i) 1. TMSacetylene, I Pr 2 NH, CuI, PdCl 2 (PPh 3 ) 2 , reflux, 1 d; 2. aq. workup, 91 %; ii) THF, EtOH, 1 M NaOH, room temp., 1 d, 80 %.Scheme 3. Lindlar reduction of 1,3,5-trithynylbenzene and determination of conversion using GC-MS analysis after 18 h reaction time. Reagents and conditions: i) 1. EtOAc, Lindlar catalyst, quinoline, H 2 , room temp., 18 h; 2. aq. workup, 62 %.The gas chromatogram shows the presence of three other compounds resulting from further reduction of the double bonds in 3. Shorter reaction times, however, lead to incomplete Eur.