Half-sandwich RuII-[9]aneS3 complexes with dicarboxylate ligands: synthesis, characterization and chemical behavior

Abstract

With the aim of further developing the structure–activity relationship in biologically active half-sandwich Ru(II)-[9]aneS₃ complexes ([9]aneS₃ = 1,4,7-trithiacyclononane), a series of new mono- and dinuclear complexes bearing the chelating dicarboxylate ligands oxalate (ox), malonate (mal) and methylmalonate (mmal), have been synthesized and studied. Treatment of the precursor [Ru([9]aneS₃)(dmso)₃][CF₃SO₃]₂ (7) with equivalent amounts of K₂(dicarb) afforded the corresponding neutral complexes with the general formula [Ru([9]aneS₃)(dmso-S)(η²-dicarb)] (where dicarb = ox (1), mal (2) and mmal (3)), while using half an equivalent of K₂(ox), the symmetric dimer [{Ru([9]aneS₃)(dmso-S)}₂(µ-η⁴-ox)][CF₃SO₃]₂ (4) was isolated. The reaction of 7 with the oxalato complex fac-[Ru(dmso-S)₃(dmso-O)(η²-ox)] (9) yielded two asymmetric dimers, namely [{Ru([9]aneS₃)(dmso-S)}(µ-η⁴-ox){fac-Ru(dmso-S)₃(CF₃SO₃)}][CF₃SO₃] (5) and [{Ru([9]aneS₃)(dmso-S)}(µ-η⁴-ox){fac-Ru(dmso-S)₃(dmso-O)}][CF₃SO₃]₂ (6), depending on the reaction conditions. All new complexes were structurally characterized, both in solution (by NMR spectroscopy) and in the solid state (by X-ray crystallography). The chemical behavior of the complexes in aqueous solution was studied by UV-Vis and NMR spectroscopy in view of their potential antitumor activity: the monomers partially release a dmso ligand to yield the monofunctional aqua adduct [Ru([9]aneS₃)(η²-dicarb)(H₂O)], while the dimers rapidly open up the oxalato bridge to give two mononuclear fragments. Splitting of the asymmetric dimers 5 and 6 occurs selectively and the ox moiety remains bonded to the fac-Ru(dmso-S)₃ fragment. A detailed comparison of the structural and chemical features of 1–6 with those of similar dicarboxylate complexes possessing the fac-Ru(dmso-S)₃ fragment in place of Ru([9]aneS₃) allows us to draw a number of general conclusions on the binding preferences of dicarb ligands on the octahedral Ru(II) center.