Hard/soft selectivity in ligand substitution reactions of β-diketonate platinum(II) complexes

Abstract

The reactivity of platinum(II) complexes of the type [PtCl(O,O-acac)(L)] (1) and [Pt(O,O-acac)(gamma-acac)(L)] (2) (L = DMSO, a; DMS, b), with a range of hard and soft nucleophiles such as dimethylsulfide (DMS, b), triphenylphosphine, (PPh3, c), ethylene (eta2-C2H4, d), carbon monoxide (CO, e), pyridine (py, f), and guanosine (Guo, g) has been investigated. Interestingly, the complexes 1a and 1b undergo selective substitution of the chloro or sulfur ligand depending on the hard/soft character of the incoming nucleophile. The soft incoming ligand replaces the softer one and the hard ligand replaces the harder one, giving [PtCl(O,O'-acac)(L)] complexes (1b, 1c, 1d and 1e in the reaction of 1a with L = DMS, PPh3, eta2-C2H4, CO, respectively), and [Pt(O,O'-acac)(DMSO)(L')] (3f, 3g) and [Pt(O,O'-acac)(DMS)(L')] (4f, 4g) species in the reaction of 1a and 1b with L' = py and guo, respectively. In the cases of 2a and 2b complexes, where the pi-bonded acac (gamma-acac) replaces the chloro ligand, only in the presence of an incoming soft nucleophile substituting the soft sulfur ligand the reaction occurs. Equilibrium constants for the substitution reactions were measured by 1H NMR spectroscopy. Variable temperature 1H NMR spectroscopy studies, performed for the reaction of 1a and 2a complexes with DMS, revealed that the selective substitution of DMSO with DMS takes place in both cases, according to a second-order kinetic law. The calculated values of DeltaH++ and DeltaS++ are consistent with an associative mechanism. NMR spectroscopic characterization (1H, 13C, 195Pt, 31P) for the complexes and crystal structures of isolated complexes ([PtCl(O,O'-acac)(L)] (1) and [Pt(O,O'-acac)(gamma-acac)(L)] (2), L = DMSO, 1a and 2a; L = DMS, 1b and 2b; L = PPh3, 1c and 2c) are herein reported and discussed.

In Vitro and In Vivo Antitumor Activity of [Pt(O,O′-acac)(γ-acac)(DMS)] in Malignant Pleural Mesothelioma

“…Ptac2S was prepared according to previously reported procedures [4, 5]. CDDP was purchased from Sigma-Aldrich, Chemicals (Milan, Italy).…”

“…Thus, attention was paid to the design of new platinum compounds with stronger pharmacological properties, less toxicity and more favourable therapeutic indices equated to CDDP. In this context, [Pt(O,O′-acac)(γ-acac)(DMS)] (Ptac2S) [3, 4], a platinum drug for non genomic targets, has recently gained increasing attention as potential anticancer agent. This thanks to its high and selective cytotoxicity towards cancer, as observed in immortalized cell lines and confirmed in breast cancer cells in primary cultures [5–10] and in vivo [11, 12].…”

[Pt(O,O’-acac)(γ-acac)(DMS)] Alters SH-SY5Y Cell Migration and Invasion by the Inhibition of Na+/H+ Exchanger Isoform 1 Occurring through a PKC-ε/ERK/mTOR Pathway

“…[Pt(acac) 2 (DMS)] is very stable under physiological conditions [20] showing low reactivity with nucleobases and high specific reactivity with sulphur ligands [19], suggesting interaction with non-genomic targets, which could be proteins involved in key pathways of the cell metabolism [21]. The effectiveness of [Pt(acac) 2 (DMS)] on various cell cultures in vitro (from endometrium, breast, brain, mesothelium etc.)…”

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

“…[9] Therefore, the synthesis of other platinum anticancer drugs, which could produce different DNA adducts or target other proteins, enzymes, and pathways that are critical for cytotoxicity and apoptosis, became the focus of recent research. [10] In this context, new Pt II complexes containing coordinate O,OЈ-acetylacetonate chelate as a carrier ligand with an intriguing chemical reactivity [11][12][13][14] and interesting biological activities have been recently reported. [15][16][17][18][19][20] In the present work, we evaluate both the Pt II coordination ability of two 4-acyl-5-pyrazolones [HQ Ph = 4-benzoyl-3-methyl-1-phenylpyrazol-5-one, a; HQ py,CF3 = 3-methyl-1-(2-pyridyl)-trifluoroacetylpyrazol-5-one, b] and the cytotoxic activity of the corresponding platinum complexes.…”