Synthesis, Structural Characterization and Anti‐Proliferative Activity of (κ¹‐C)‐ and (κ²‐C,S)‐Pt^II Complexes Bearing Thioether‐Functionalized N‐Heterocyclic Carbenes

Abstract

A series of platinum(II) complexes bearing thioetherfunctionalized N-heterocyclic carbene ligands have been synthesized and characterized. The hemilabile and reversible character (i.e., coordination/decoordination) of the sulfur moiety in these platinum complexes has been established by ligand displacement (addition of pyridine) and ligand abstraction (on sil-[a] 161 1.64-1.58 (m, 1 H), 1.81-1.72 (m, 2 H), 2.15-2.05 (m, 2 H), 2.75-2.80 (m, 1 H), 3.29-3.20 (t, J = 7 Hz, 2 H, S-CH 2 ), 4.67 (t, J = 7 Hz, 2 H, N-CH 2 ), 5.72 (s, 2 H, N-CH 2 ), 6.60 (d, J = 2 Hz, 1 H, CH imid ), 6.96 (d, J = 2 Hz, 1 H, CH imid ), 7.43-7.29 (m, 5 H), 7.50 (d, J = 7 Hz, 2 H), 7.73 (t, J = 8 Hz, 1 H), 9.04 (d, J = 5 Hz, 2 H, CH pyr ) ppm. 13 C NMR (101 MHz, CDCl 3 ): δ = 25.8 (2 CH 2 ), 26.3 (2 CH 2 ), 29.5 (S-CH 2 ), 34.

Synthesis, Structural Characterization and Antiproliferative Activity of Gold(I) and Gold(III) Complexes Bearing Thioether‐Functionalized N‐Heterocyclic Carbenes

“…Notably, the IC 50 values do not vary significantly from gold(I) to gold(III) complexes; this is not surprising considering that it is possible that gold(III) complexes could be reduced in biological environment giving the gold(I) species [46–48] . For this reason, we have conducted in situ NMR investigations of the reactivity of the gold(III) complexes 10 (Figure S30 in Supporting Information) and 11 with reduced glutathione (GSH), a very abundant tripeptide in the cells, following a well established procedure [25,46] . We noticed that the gold(III) complexes react quickly with GSH in a DMSO‐ d 6 /D 2 O (1/1) mixture in few seconds affording the gold(I) complexes and the glutathione disulphide (GSSG).…”

“…The imidazolium salts used in this study are depicted in Figure 2 and their synthesis and characterization were recently reported by some of us [24,25] …”

“…Elemental analysis were carried out with a Thermo Scientific FLASH 2000 apparatus. The imidazolium salts were prepared following published procedures [24,25] …”

“…Thus, co‐administration of a “chemoprotective agent”, such as S‐containing oligopeptides, can significantly reduce the outbreak of side effects [23] . Recently, studies on chemoprotective action and cytotoxic properties of sulfur‐containing NHC ruthenium(II) and platinum(II) complexes have been reported by some of us [24,25] . We decided to expand the scope of the metal complexes with such type of ligands and in this paper, we report on the synthesis, characterization and the preliminary antiproliferative results of gold(I) and gold(III) complexes bearing thioether‐functionalized NHCs.…”

Anticancer platinum(II) complexes bearing N-heterocycle rings

“…The platinum drugs, including in their coordination sphere an S-donor ligand able to act as a chemoprotectant group, were investigated for their ability to reduce side-effects and to prevent the coordination of GSH to the platinum center. 44 Trans-platinum oxadiazoline complexes with such a hindered ligand as 7-nitro-1,3,5-triaza-adamantane (NO2-TTA) or hexamethylenetetramine (hmta) (Figure 3, XIII) were tested in vitro for their cytotoxic activity especially in cervical cancer HeLa and in the poorly responsible to cisplatin lung cancer cell lines A549. 45 All mononuclear complexes showed a high cytotoxic activity.…”