Is the aromatic fragment of piano-stool ruthenium compounds an essential feature for anticancer activity? The development of new Ru(II)-[9]aneS3 analogues.

New half-sandwich RuII-[9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) were prepared from Ru-[9]aneS3–dmso precursors and structurally characterized, both in solution and in the solid state. Some of them are analogs of known cytotoxic organometallic RuII-(η6-arene) and RuII-(η5-cyclopentadienyl) compounds, in which the aromatic fragment is replaced by the sulfur macrocycle 1,4,7-trithiacyclononane. Similarly to the aromatic analogs in aqueous solution the Ru-[9]aneS3 complexes hydrolyze a chloride or a dmso to give the corresponding aquo species. Preliminary in vitro tests performed on selected complexes against the mouse adenocarcinoma cancer cell line (TS/A) and the human mammary normal cell line (HBL-100) showed that the Ru-[9]aneS3 compounds have a cytotoxicity comparable to that of the corresponding organometallic analogs. These results suggest that the aromatic fragment of the piano-stool RuII compounds might be effectively replaced by another face-capping ligand.