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The microwave-assisted synthesis of Pt(II) complexes containing several pyridines (i.e., pyridine L1 , 2-picoline L2 , 3-picoline L3 , 4-picoline L4 , 2,2′-bipyridine L5 ) is reported. For L1 – L5 , the reaction was successful in about 50% yield with all the ligands except L2 . The same method applied to 4,4′-bis(2-morpholinoethoxy)-2,2′-bipyridine ( L6 , a ligand showing interesting antiproliferative properties because of a high DNA affinity), was unsatisfactory. The corresponding complex cis -[PtCl 2 ( L6 )] was obtained only heating at reflux a mixture of [PtCl 2 (1,5-cyclooctadiene)] and L6 in acetonitrile for 24 h. Antiproliferative activity of [PtCl 2 ( L6 )] on four cancer cell lines (ovarian A2780 and its cisplatin-resistant variant A2780cisR, prostate PC3 and breast cancer MDA-MB-231) was compared with that of its ligand and the model complex [PtCl 2 ( L5 )]. These studies showed that [PtCl 2 ( L6 )] has just marginal activity towards the tested cells if compared with cisplatin.

Tridentate pyrazole-containing ligands of the Schiff base type, SalPz — HL 1 , Cl 2 SalPz — HL 2 and I 2 SalPz — HL 3 , were used to prepare a series of new Cu(II) complexes (CuSalPz — 1 , CuCl 2 SalPz — 2 and CuI 2 SalPz — 3 ). These new complexes have been studied by different analytical techniques (electrospray ionization mass spectrometry (ESI-MS), elemental analysis, FT-IR and EPR). The spectroscopic properties of 1 – 3 are consistent with the formation of Cu(II) complexes coordinated by monoanionic and tridentate (N,N,O)-chelators, behaving as monomeric species in aqueous solution, as shown by EPR studies. Crystals of 2 and 3 , obtained by slow concentration of methanolic solutions of the compounds, were also analyzed by X-ray diffraction analysis. The X-ray structural study has shown that 2 crystallized as a dinuclear compound, [Cu 2 (μ-Cl) 2 (Cl 2 SalPz) 2 ], while the solid state structure determined for 3 is best described by monomeric units of [CuCl(I 2 SalPz)] displaying short Cu···Cl intermolecular contacts. The in vitro evaluation of 1 – 3 comprised the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against several human cancer cell lines (PC-3 prostate, MCF-7 breast and A2780 and A2780cisR-ovary). The studies with plasmid DNA have shown that 2 and 3 induce extensive DNA cleavage in the presence of different additives. The cytotoxic activity of 2 and 3 is comparable to the one presented by cisplatin, with the exception of the A2780 cell line where cisplatin is more active. It has been found that the introduction of halogen substituents in the phenolate rings of the chelators enhanced the cytotoxicity of the respective Cu(II) complexes.

A new tetradentate ligand having two 3-hydroxy-4-pyridinonate moieties and one carboxylate group appended to a cyclohexane backbone is reported, together with the corresponding bidentate hydroxypyridinonate pendant arm. The synthesis and characterization of these ligands, as well as their complexation properties towards the first transition series of metal ions M(II) (M=Cu, Ni, Zn) in aqueous solution, are described and discussed herein. The tetradentate ligand forms quite stable complexes with this series of metal ions and in solution, it is proved to be a much more effective chelator than the corresponding bidentate derivative. The stability constants of the complexes formed with this set of bivalent ions follow the Irving–Williams order Ni Zn. The carboxylic group has no interaction with the metal centre, thus remaining free for potential interaction with biological ligands (e.g. proteins).