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

Abstract

AbstractThe syntheses of new PtII complexes with 4‐acyl‐5‐pyrazolones [HQPh = 1‐phenyl‐3‐methyl‐4‐benzoylpyrazol‐5‐one, a; HQpy,CF3 = 1‐(2‐pyridyl)‐3‐methyl‐trifluoroacetylpyrazol‐5‐one, b] are reported: trans‐[PtCl2(DMSO)(HQPh)] (1a), cis‐[PtCl2(DMSO)(HQPh)] (2a), [PtCl(DMSO)(Qpy,CF3)] (1b), and [PtCl2(KQpy,CF3)] (2b). All complexes were characterized by multinuclear (1H, 13C, 19F, and 195Pt), multidimensional NMR spectroscopy and single‐crystal X‐ray diffraction analyses. The isomer trans‐[PtCl2(DMSO)(HQPh)] (1a) crystallizes in two polymorphic forms, which correspond to two different conformers. In the trans–syn conformer (1aM) (monoclinic, space group P21/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 (1aO) (orthorhombic, space group Pca21), 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)(HQPh)] (1a and 2a) and [PtCl2(KQpy,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.