Synthesis, Crystal Structure, and Biological Study of Pt^II Complexes with 4‐Acyl‐5‐pyrazolones

Abstract

The 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.

The crystal structure of a novel Pt(II) complex with 2¬-hydroxy-6-methylpyridine (Hmhp), trans-[PtCl2(dmso)(Hmhp)]·H2O

“…The four-fold coordination environment of platinum(II) consists of two trans positioned chlorides, a 2-hydroxy-6-methylpyridine ligand (Hmhp) and a dimethyl 0.0310 wR2 [b] [all data] 0.0809 (2-pic = 2-methylpyridine). [16][17][18] The platinum coordination environment in the latter complexes is highly reminiscent of that in the title compound: two trans positioned chlorides, a dmso ligand and an aromatic ligand bound via a nitrogen donor atom. The platinum-to-chloride bond lengths, 2.2884 9 17,19 The 2-hydroxy-6-methylpyridine ligand is bound to the metal ion via a nitrogen at 2.067(4) Å, a slightly longer distance than 2-picoline in trans-[PtCl 2 (dmso)(2-pic)] with the platinum-to-picoline bonds of 2.046(10) Å.…”

“…Similarly, an almost perpendicular orientation of the aromatic ligand is observed also for trans-[PtCl 2 (dmso) (HQ Ph )] and the title compound (see Figure 2). 16 The exact value of the dihedral angle between the plane of the Hmhp ligand and the platinum coordination plane is 88.8(1)°. The explanation lies in the nature of ortho substituents.…”

Pyrazolones as a potential anticancer scaffold: Recent trends and future perspectives

“…New Pt (II) metal complexes were synthesized using 4-acyl-5-pyrazolones and in vitro biological assays were performed on cancerous cell lines like HeLa and MCF-7 (platinum-resistant) using cisplatin as the reference standard. Trans-[PtCl 2 (DMSO) (HQPh)] (47) complex showed greater cytotoxic activity on HeLa cells than that of cis-[PtCl 2 (DMSO)(HQPh)] (48) complex (De Pascali et al, 2014). Ruthenium (II) metal complexes with aromatic nucleus were prepared from ligands (β-keto amine consisting of pyrazolone nucleus) to measure the effect of aromatic substituents with anticancer properties in respect to A2780 and A2780cisR oncogenic cell lines using MTT cytotoxicity bioassay.…”

On the Capability of Oxidovanadium(IV) Derivatives to Act as All-Around Catalytic Promoters Since the Prebiotic World

“…For example, dinuclear (η 6 -arene) ruthenium(II) acylpyrazolone complexes have been tested as anticarcinogens, showing cisplatin-like activity against epithelial carcinoma HeLa and MCF7 tumor cell lines, but a lower cytotoxicity toward normal cell lines [72]. A similar study has been also conducted on platinum complexes with acylpyrazolones as ligands, displaying good results in terms of cytotoxicity against the same tumor cell lines [73].…”