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

Abstract

The crystal structures of [Ru^II(terpy)(bipy)Cl]Cl·2H₂O and [Ru^II(terpy)(en)Cl]Cl·3H₂O, 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)(H₂O)]²⁺ and [Ru^II(terpy)(en)(H₂O)]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)(H₂O)]²⁺ complex. Substitution reactions of the aqua complexes with chloride, cyanide and thiourea show that the [Ru^II(terpy)(en)(H₂O)]²⁺ complex is 30–60 times more labile than the [Ru^II(terpy)(bipy)(H₂O)]²⁺ complex at 25 °C. Water exchange reactions for both complexes were studied by ¹⁷O-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.