Synthesis, crystal structure and biological characterization of a novel palladium(II) complex with a coumarin-derived ligand

Methyl 2-methyl-4-oxo-4H-chromene-3-carboxylate (1) was treated with 25% aqueous ammonia to give 3-(1-aminoethylidene)-2H-chromene-2,4(3H)-dione (2). Compound 2 was used as a ligand for the formation of a palladium(ii) complex. The structures of the ligand and its palladium complex 3 were determined by IR and H-1 NMR spectroscopy, FAB mass spectrometry and elemental analysis. The single-crystal Xray structure of 3 was also solved. Ligand 2 in 20% dioxane solution shows two protonation constants -log beta(12) = 4.28 +/- 0.01 and log beta(12) = 7.66 +/- 0.03. In complex 3 two ligand molecules chelate to the Pd ion through their N and O donors, giving a four-coordinate Pd-II center with a cis-N2O2 donor set. The coordination geometry at Pd-II is square-planar with typical values for the distances from the Pd atom to the coordinated atoms. The cytotoxicity of compound 3 was determined on three cancer cell lines. IC50 values of 9.7, 7.8 and 7.8 nm were found for A546, HeLa and K562 cells, respectively, which is notably lower than carboplatin, which shows corresponding IC50 values of 105.98, 73.49 and 60.92 mum. Double-stranded DNA treated with 3 shows a significant increase in the Deltaepsilon value in the CD spectra, as well as a lower electrophoretic mobility than parent DNA. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).