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]aneS(3) complexes ([9]aneS(3)=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]aneS(3))(dmso)(3)][CF(3)SO(3)](2) (7) with equivalent amounts of K(2)(dicarb) afforded the corresponding neutral complexes with the general formula [Ru([9]aneS(3))(dmso-S)(eta(2)-dicarb)] (where dicarb=ox (1), mal (2) and mmal (3)), while using half an equivalent of K(2)(ox), the symmetric dimer [{Ru([9]aneS(3))(dmso-S)}(2)(mu-eta(4)-ox)][CF(3)SO(3)](2) (4) was isolated. The reaction of with the oxalato complex fac-[Ru(dmso-S)(3)(dmso-O)(eta(2)-ox)] (9) yielded two asymmetric dimers, namely [{Ru([9]aneS(3))(dmso-S)}(mu-eta(4)-ox){fac-Ru(dmso-S)(3)(CF(3)SO(3))}][CF(3)SO(3)] (5) and [{Ru([9]aneS(3))(dmso-S)}(mu-eta(4)-ox){fac-Ru(dmso-S)(3)(dmso-O)}][CF(3)SO(3)](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]aneS(3))(eta(2)-dicarb)(H(2)O)], 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]aneS(3)) allows us to draw a number of general conclusions on the binding preferences of dicarb ligands on the octahedral Ru(II) center.

Half-sandwich RuII[9]aneS3 complexes structurally similar to antitumor-active organometallic piano-stool compounds: Preparation, structural characterization and in vitro cytotoxic activity

“…Finally, we are also planning to test the cytotoxic activity of the recently described dicarboxylate derivatives [Ru([9]-aneS 3 )(dmso-S)(g 2 -dicarb)] (dicarb = ox, mal, mmal) [11]. It will be interesting to assess whether, in further analogy with the piano-stool organometallic compounds, also in our case replacement of the neutral NAN chelating ligand by a dianionic chelating dicarboxylate leads again to a loss of activity.…”

“…The other chlorido (7,9,11,13,15) and dmso (8,10) derivatives (all yellow-to-orange solids) were prepared following procedures very similar to those for 5 and 6, respectively. For the sake of brevity, only the amounts of reactants, solvent, reaction time, yield and analytical and spectroscopic characterization for each product will be reported below, with the exception of compounds 12 and 14 that required slightly different synthetic procedures.…”

“…Thus, we developed a series of new half-sandwich Ru coordination compounds of general formulae [Ru( [9]aneS 3 3 SO 3 ] and [Ru( [9]aneS 3 )(dmso-S)(NAN)][CF 3 SO 3 ] 2 (NAN = nitrogen chelating ligand such as en or bpy), in which the aromatic fragment was replaced by the sulfur macrocycle 1,4,7-trithiacyclononane ( [9]aneS 3 ), while the rest of the coordination sphere remained unchanged [10]. More recently, we also prepared structurally similar RuA [9]aneS 3 complexes of general formula [Ru( [9]aneS 3 )(dmso-S)(g 2 -dicarb)], in which the neutral NAN chelating ligand was replaced by a dianionic chelating dicarboxylate (dicarb = ox, mal, mmal), and the oxalato-bridged dinuclear bis-half-sandwich species [{Ru( [9]aneS 3 )(dmso-S)} 2 (g 4 , l-ox)][CF 3 SO 3 ] 2 [11].…”

“…The oral carcinoma KB is a cell line more sensitive to the antiproliferative effects of the tested compounds: Chemical behavior in aqueous solution of the complexes bearing a 4,4 0 -substituted bpy ligand(5,6,8,(11)(12)(13)(14).…”

X-ray structure and cytotoxic activity of a picolinate ruthenium(II)-arene complex

“…In recent years, ruthenium complexes have gained much attention [19][20][21][22][23] in attempts to overcome the downsides of platinum complexes. Organometallic complexes and half-sandwich complexes of Ru(II) emerged as promising scaffolds for anticancer drug design.…”