title: Effects of trans-pyridine ligands on the interactions of RuII and RuIII ammine complexes N7-coordinated to purine nucleosides and DNA.
abstract: DNA binding by trans-[(H2O)(Pyr)(NH3)4RuII]2+ (Pyr = py, 3-phpy, 4-phpy, 3-bnpy, 4-bnpy) is highly selective for G7 with KG = 1.1 x 10(4) to 2.8 x 10(4), with the more hydrophobic Pyr ligands exhibiting slightly higher binding. A strong dependence on ionic strength indicates that ion-pairing with DNA occurs prior to binding. At mu = 0.05, d[RuII-DNA]/dt = k[RuII][DNA], where k = 0.17-0.21 M-1 s-1 with the various Pyr ligands. The air oxidation of [(py)(NH3)4RuII]n-DNA to [(py)(NH3)4RuIII]n-DNA at pH 6 occurs with a pseudo-first-order rate constant of kobs = 5.6 x 10(-4) s-1 at mu = 0.1, T = 25 degrees C. Strand cleavage of plasmid DNA appears to occur by both Fenton/Haber-Weiss chemistry and by base-catalyzed routes, some of which are independent of oxygen. Base-catalyzed cleavage is more efficient than O2 activation at neutral pH and involves the disproportionation of covalently bound RuIII and, in the presence of O2, Ru-facilitated autoxidation to 8-oxoguanine. Disproportionation of [py(NH3)4RuIII]n,-DNA occurs according to the rate law: d[RuII-GDNA]/dt = k0[RuIII-GDNA] + k1[RuIII-GDNA][OH-], where k0 = 5.4 x 10(-4) s-1 and k1 = 8.8 M-1 s-1 at 25 degrees C, mu = 0.1. The appearance of [(Gua)(py)(NH3)4RuIII] under argon, which occurs according to the rate law: d[RuIII-G]/dt = k0[RuIII-GDNA] + k1[OH-][RuIII-GDNA] (k0 = 5.74 x 10(-5) s-1, k1 = 1.93 x 10(-2) M-1 s-1 at T = 25 degrees C, mu = 0.1), is consistent with lysis of the N-glycosidic bond by RuIV-induced general acid hydrolysis. In air, the ratio of [Ru-8-OG]/[Ru-G] and their net rates of appearance are 1.7 at pH 11, 25 degrees C. Small amounts of phosphate glycolate indicate a minor oxidative pathway involving C4' of the sugar. In air, a dynamic steady-state system arises in which reduction of RuIV produces additional RuII.
authors.affiliation: Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: M J
authors.initials: MJ
authors.lastname: Clarke
mesh_terms: D000588:Amines / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004563:Electrochemistry; D004586:Electrophoresis; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics; D011684:Purine Nucleosides / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D011684:Purine Nucleosides; D011725:Pyridines; D017975:Ruthenium Compounds; D004247:DNA; D006861:Hydrogen Peroxide