New dinuclear platinum complexes. Synthesis and kinetics of chloride substitution by thiourea and glutathione in water–DMF solution

• Two dinuclear platinum complexes have been synthesized.
• Chloride substitution by thiourea and glutathione in water–DMF medium has been studied.
• An unusual medium was applied due to extremely low solubility of the complexes in water.
• Trypan blue exclusion tests have been undertaken to estimate cytotoxicity of the complexes.

The first step of chloride substitution by thiourea and glutathione in two new dinuclear platinum(II) complexes, [Pt2(6NNpy)Cl4] (1) and [Pt2(8NNpy)Cl4] (2), where 6NNpy and 8NNpy are N1,N6-bis(2-pyridylmethyl)-1,6-hexanediamine and N1,N8-bis(2-pyridylmethyl)-1,8-octanediamine, respectively, has been studied using UV spectrophotometry. Because of a low solubility of the complexes in water, kinetic measurements have been studied in DMF–water medium (1:1 by volume) at ionic strength I = 0.1 M (Na+, ClO4−, Cl−, Tris), pH 7.4 (Tris–HCl), and T = 310 K. Addition of up to 50% DMF decreases reaction rate almost 20 times. The obtained rate constants have been recalculated to DMF-free conditions based on additional kinetic tests with PtCl42− in solutions with different DMF concentration. Chloride substitution by thiourea is almost 1 order of magnitude faster than by glutathione. Both dinuclear complexes react about 3 times faster with thiourea and glutathione than cisplatin. Trypan blue exclusion test of cell viability revealed that Pt2(8NNpy)Cl4 exhibit moderate cytotoxic activity against human melanoma cells, however due to its poor solubility in aqueous solutions and toxicity of DMF–water medium, conducted in vitro analysis have limited clinical value.

Reaction kinetics between two dinuclear platinum(II) complexes and thiourea and glutathione has been studied in water–DMF medium (1:1). The complexes were analyzed for their cytotoxicity.Figure optionsDownload as PowerPoint slide