Structure and reactivity of [Ru II (terpy)(N^N)Cl]Cl complexes: consequences for biological applications.

The crystal structures of [Ru ^II (terpy)(bipy)Cl]Cl·2H ₂ O and [Ru ^II (terpy)(en)Cl]Cl·3H ₂ O, where terpy = 2,2':6',2''-terpyridine, bipy = 2,2'-bipyridine and en = ethylenediamine, were determined and compared to the structure of the complexes in solution obtained by multi-nuclear NMR spectroscopy in DMSO _d-6 as a solvent. In aqueous solution, both chlorido complexes aquate fully to the corresponding aqua complexes, viz. [Ru ^II (terpy)(bipy)(H ₂ O)] ²⁺ and [Ru ^II (terpy)(en)(H ₂ O)] ²⁺ , within ca. 2 h and ca. 2 min at 37 °C, respectively. The spontaneous aquation reactions can only be suppressed by chloride concentrations as high as 2 to 4 M, i.e. concentrations much higher than that found in human blood. The corresponding aqua complexes are characterized by pK _a values of ca. 10 and 11, respectively, which suggest a more labile coordinated water molecule in the case of the [Ru ^II (terpy)(en)(H ₂ O)] ²⁺ complex. Substitution reactions of the aqua complexes with chloride, cyanide and thiourea show that the [Ru ^II (terpy)(en)(H ₂ O)] ²⁺ complex is 30-60 times more labile than the [Ru ^II (terpy)(bipy)(H ₂ O)] ²⁺ complex at 25 °C. Water exchange reactions for both complexes were studied by ¹⁷ O-NMR and DFT calculations (B3LYP(CPCM)/def2tzvp//B3LYP/def2svp and ωB97XD(CPCM)/def2tzvp//B3LYP/def2svp). Thermal and pressure activation parameters for the water exchange and ligand substitution reactions support the operation of an associative interchange (I _a ) process. The difference in reactivity between these complexes can be accounted for in terms of π-back bonding effects of the terpy and bipy ligands and steric hindrance on the bipy complex. Consequences for eventual biological application of the chlorido complexes are discussed.