Synthesis and biological activity of platinum(II) and palladium(II) thiosalicylate complexes with mixed ancillary donor ligands

Abstract

A series of mixed-ligand thiosalicylate complexes of the type [M(SC₆H₄CO₂)(PPh₃)L] (M = Pt, L = pyridine (py), 4-methylpyridine, imidazole, 4-picolinic acid hydrazide {C₅H₄N[C(O)NHNH₂]-4}; M = Pd, L = pyridine) have been prepared by the one-pot reaction of [PtCl₂(cod)] or [PdCl₂(cod)] (cod = cycloocta-1,5-diene) with one equivalent of PPh₃ and thiosalicylic acid (HSC₆H₄CO₂H) in the presence of the nitrogen base. Single-crystal X-ray diffraction studies on [Pt(SC₆H₄CO₂)(PPh₃)(py)] and the previously reported complex [Pt(SC₆H₄CO₂)(PPh₃)(XyNC)] (Xy = 2,6-xylyl) indicates that the complexes have different geometries, though in each case the two ligands of highest trans-influence are mutually cis. The reaction of [PtCl₂(cod)] with PPh₃, thiosalicylic acid and ammonia led to the isolation of crystals of the dinuclear thiosalicylate-bridged complex [Pt(SC₆H₄CO₂)(PPh₃)(NH₃)Pt(SC₆H₄CO₂)(PPh₃)], which was characterised by X-ray crystallography and electrospray mass spectrometry. The conformation of the thiosalicylate ligand can vary widely with values for the dihedral angle between the ligand plane and the platinum(II) coordination plane varying from 12.4° to 70.9° in the seven complexes so far determined. The biological activities of selected platinum and palladium thiosalicylate and related complexes against P388 leukemia cells, bacteria and fungi are also reported. The complex [Pt(SCH₂CO₂)(PPh₃)₂] shows the highest activity against P388 cells (IC₅₀ 671 ng mL⁻¹).