Factors that influence the antiproliferative activity of half sandwich RuII-[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives.

Half sandwich Ru(II) – [9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely [Ru([9]aneS3)(en)Cl](PF6) (1), [Ru([9]aneS3)(bpy)Cl](PF 6 ) (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane, pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand. The model reactions of 1 – 3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5 ′ -monophosphate (5 ′ -GMP) were studied by NMR spectroscopy. All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF 6 ) 2 (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF 6 ) (10), were structurally characterized also by X-ray crystallography. The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1 – 3 with the biologically more relevant 5 ′ -GMP ligand were studied by UV-Vis spectroscopy. The rate of the reaction of 1 – 3 with 5 ′ -GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3 ≈ 2 > 1.