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.