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

Abstract

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=0.1M (Na+, ClO4−, Cl−, Tris), pH 7.4 (Tris–HCl), and T=310K. 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.