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

Abstract

The reactions of tetrachloroauric(III) acid (HAuCl4) 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 {[AuCl4]- [bztH2]+} (1), and {[AuCl4]- [EtbzimH2]+ (H2O)} (2) (where bztH2+ and EtbzimH2+ are the desulfurated cations of the starting ligands). The reaction of HAuCl4 with 2-mercapto-nicotinic acid (mnaH2), however results in the formation of 2-sulfonate-nicotininc acid (C6H5NO5S) (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 (Ph3P)) 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 mnaH2 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 -SO3-, 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 HAuCl4 was inactive against sarcoma cells.

• Authors: K N Kouroulis, S K Hadjikakou, N Kourkoumelis, M Kubicki, L Male, M Hursthouse, S Skoulika, A K Metsios, V Y Tyurin, A V Dolganov, E R Milaeva, N Hadjiliadis
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Issue 47 Pg. 10446-56 (Dec 21 2009) ISSN: 1477-9234 [Electronic] England
• PMID: 20023866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coordination Complexes
• Thioamides
• Gold

Topics

• Animals
• Cell Line, Tumor
• Coordination Complexes (chemical synthesis, chemistry, toxicity)
• Crystallography, X-Ray
• Electrochemical Techniques
• Gold (chemistry)
• Molecular Conformation
• Rats
• Rats, Wistar
• Thioamides (chemistry)