Synthesis, Crystal Structure, and Biological Study of PtII Complexes with 4-Acyl-5-pyrazolones

The syntheses of new Pt-II complexes with 4-acyl-5-pyrazolones [HQ(Ph) = 1-phenyl-3-methyl-4-benzoylpyrazol-5-one, a; HQ(py,CF3) = 1-(2-pyridyl)-3-methyl-trifluoroacetylpyrazol-5-one, b] are reported: trans-[PtCl2(DMSO)(HQ(Ph))] (1a), cis-[PtCl2(DMSO)(HQ(Ph))] (2a), [PtCl(DMSO)(Q(py,CF3))] (1b), and [PtCl2(KQ(py,CF3))] (2b). All complexes were characterized by multinuclear (H-1, C-13, F-19, and Pt-195), multidimensional NMR spectroscopy and single-crystal X-ray diffraction analyses. The isomer trans-[PtCl2(DMSO)(HQ(Ph))] (1a) crystallizes in two polymorphic forms, which correspond to two different conformers. In the trans-syn conformer (1a(M)) (monoclinic, space group P2(1)/c), the H atom of the enol group [O(1)H(1)] establishes an intramolecular hydrogen bond with the ketone oxygen (O2), whereas in the trans-anti conformer (1a(O)) (orthorhombic, space group Pca2(1)), the same groups are involved in an analogous intermolecular H bond. Interestingly, the cis isomer (2a) showed in solution and at room temperature slow rotation around both the Pt-N1 and the Pt-S bonds, which restrained both the acylpyrazolone and DMSO ligand motion. Moreover, the water solubility of the complexes trans- and cis-[PtCl2(DMSO)(HQ(Ph))] (1a and 2a) and [PtCl2(KQ(py,CF3))] (2b) allowed to perform in vitro biological assays on platinum-sensitive human endometrium (HeLa) and platinum-resistant human breast (MCF-7) cancer cell lines. It was also possible to compare their cytotoxicity to cisplatin. Interestingly, trans isomer 1a showed higher cytotoxicity on HeLa cells compared to the cis isomer 2a.