Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides

摘要

The reactions of tetrachloroauric(III) acid (HAuCl_ 4) with the thioamides; 2-mercapto-benzothiazole (mbztH) and 5-ethoxy-2-mercapto- benzimidazole (EtmbzimH) lead to the desulfuration of the ligands and the formation of the ionic complexes {[AuCl_ 4]~ -[bztH_ 2]~ +} (1), and {[AuCl_ 4]~ -[EtbzimH_ 2]~ +(H_ 2O)} (2) (where bztH_ 2~ + and EtbzimH_ 2~ + are the desulfurated cations of the starting ligands). The reaction of HAuCl_ 4 with 2-mercapto-nicotinic acid (mnaH_ 2), however results in the formation of 2-sulfonate-nicotininc acid (C_ 6H_ 5NO_ 5S) (3) with the simultaneous oxidation of the sulfur atom. On the other hand, the reactions of the gold(I) complex [Au(tpp)Cl] (4) (tpp = triphenylphosphine (Ph_ 3P)) with the thioamides; 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence of potassium hydroxide resulted in the formation of the gold(I) complexes of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7) without ligand desulfuration. All complexes have been characterized by elemental analysis, FT-IR, far-FT-IR, ~1H-NMR, spectroscopic techniques and X-Ray crystallography. The electrochemical behavior of 1, 2 and 4-7 complexes and the ligands EtmbzimH, mbztH and mnaH_ 2 was also studied in acetonitrile and DMF using cyclic voltammetry. The results are in support of a mechanism of desulfuration of the ligands by Au(III), involving a first oxidation of S to -SO_ 3~ -, followed by a C-S bond cleavage. This is also supported by PM6 calculations of bond dissociation energies of the various compounds involved. Complexes 1, 2 and 4-7 were tested for in vitro cytotoxicity against leiomyosarcoma cells and the results are discussed in relation with the geometry of the complexes and compared with those of cisplatin and other metals. Complexes 1 and 5 showed higher activity than that of cisplatin, while HAuCl_ 4 was inactive against sarcoma cells.