New half-sandwich R-II-[9]aneS(3) complexes ([9]aneS(3) = 1,4,7-trithiacyclononane), namely [RuCl2(PTA)([9]aneS(3))] (4), [RuCl(PTA)(2)([9]aneS(3))][OTf] (5), [RuCl(en)([9]aneS(3))][OTf] (6), [RuCl(enac)([9]aneS(3))][OTf] (7), [RuCl(bipy)([9]ane-S-3)][OTf] (8), and [Ru(dmso-S)(bipy)([9]aneS(3))][OTf](2) (9) [PTA = 1,3,5-triaza-7-phosphaadamantane; enac = 1,2-bis-(isopropyleneimino)ethane; OTf = CF3SO3-] were prepared from Ru-[9]aneS(3)-dmso precursors and structurally characterized, both in solution and in the solid state by X-ray crystallography. Some of them are analogs of known cytotoxic organometallic Ru-II-(eta(6)-arene) and Ru-II-(eta(5)-cyclopentadienyl) compounds, in which the aromatic fragment is replaced by the sulfur macrocycle 1,4,7-trithiacyclononane, while the rest of the coordination sphere is left unchanged. Similarly to the aromatic analogs for which data are available, in aqueous solution the Ru-[9]aneS(3) complexes (with the exception of 5) hydrolyze a chloride (or a dmso in the case of 9) to give the corresponding aquo species. This process is rapidly reversed in the presence of free chloride, and coordination of phosphate is likely to occur to the aquo species in phosphate buffered solutions at physiological pH. Preliminary in vitro tests performed on complexes 4-6 against the mouse adenocarcinoma cancer cell line (TS/A) and the human mammary normal cell line (HBL-100) showed that, in general, the Ru-[9]aneS(3) compounds have a cytotoxicity comparable to that of the corresponding organometallic analogs. These results suggest that the aromatic fragment of the piano-stool Ru-II compounds is not an essential feature for the in vitro anticancer activity, and it might be effectively replaced by another face-capping ligand with a low steric demand, such as [9]aneS(3). ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)