ISSN:
1432-1327
Schlagwort(e):
Key words Ruthenium
;
DNA
;
N-glycolysis
;
Disproportionation
;
Cleavage
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
,
Chemie und Pharmazie
Notizen:
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 K G=1.1×104 to 2.8×104, 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 μ=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 k obs=5.6×10–4 s–1 at μ=0.1, T=25 °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=k 0[RuIII–GDNA]+k 1[RuIII–GDNA][OH–], where k 0=5.4×10–4 s–1 and k 1=8.8 M–1 s–1 at 25 °C, μ=0.1. The appearance of [(Gua)(py)(NH3)4RuIII] under argon, which occurs according to the rate law: d[RuIII–G]/dt=k 0[RuIII–GDNA]+k 1[OH–][RuIII–GDNA] (k 0=5.74×10–5 s–1, k 1=1.93×10–2 M–1 s–1 at T=25 °C, μ=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 °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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/s007750050319
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