Synthesis, structure, protolytic properties, alkylating and cytotoxic activity of novel platinum(II) and palladium(II) complexes with pyrazole-derived Ligands

Novel platinum(II) and palladium(II) complexes [PtCl2(HL1)] (3a), [NH2(CH3)(2)][PtCl2(L-1)] (3b), [PdCl2(HL1)] (4a), [NH2(CH3)(2)][PdCl2(L-1)] (4b) and [PdCl(CH3CN)(L-1)] (4c), where HL1 = 4-(2-hydroxybenzoyl)-2-(pyridin-2-yl)-1H-pyrazol-3-ol, have been synthesised as potential anticancer compounds. Protonation constants of the ligand were determined by pH-metric titration (log K-1 = 7.74 +/- 0.03; log K-2 = 2.85 +/- 0.05). The solid-state structures of complexes 3b and 4c have been determined by X-ray diffraction, showing square-planar coordination geometry of Pt-II and Pd-II ions. In addition, the compounds have been characterised by IR, H-1 NMR and FAB mass spectrometry. The results of preliminary studies on the cytotoxic activity in vitro against HL-60 and NALM-6 leukaemia cell lines are also reported and the IC50 values compared with those of the metal-free ligand and cisplatin. Cytotoxic evaluation revealed that Pt-II and Pd-II complexes were active in the micromolar concentration range. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).