Synthesis, Structure, Protolytic Properties, Alkylating and Cytotoxic Activity of Novel Platinum(II) and Palladium(II) Complexes with Pyrazole‐Derived Ligands

Abstract

Abstract Novel platinum(II) and palladium(II) complexes [PtCl 2 (HL 1 )] ( 3a ), [NH 2 (CH 3 ) 2 ][PtCl 2 (L 1 )] ( 3b ), [PdCl 2 (HL 1 )] ( 4a ), [NH 2 (CH 3 ) 2 ][PdCl 2 (L 1 )] ( 4b ) and [PdCl(CH 3 CN)(L 1 )] ( 4c ), where HL 1 = 4‐(2‐hydroxybenzoyl)‐2‐(pyridin‐2‐yl)‐1 H ‐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, 1 H 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 IC 50 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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)