Oxidation of DNA by trans-dioxoruthenium(VI) complexes: self-inhibition of DNA cleavage by metal complexes'
| Autor: | James G. Goll, H. Holden Thorp |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Stereochemistry
Dimer Kinetics chemistry.chemical_element DNA oxidation Medicinal chemistry Ruthenium Inorganic Chemistry Metal chemistry.chemical_compound Reaction rate constant chemistry visual_art Materials Chemistry visual_art.visual_art_medium Physical and Theoretical Chemistry Isomerization DNA |
| Zdroj: | Inorganica Chimica Acta. 242:219-223 |
| ISSN: | 0020-1693 |
| DOI: | 10.1016/0020-1693(95)04870-7 |
| Popis: | The oxidation of DNA by complexes of transdioxoruthenium(VI) has been investigated. The complexes trans -Ru(bpy) 2 O 2 2+ , trans -Ru(tpy)(OH 2 )O 2 2+ , and trans -Ru(tmc)O 2 2+ all induce plasmid isomerization of ΦX174 DNA (bpy = 2,2′-bipyrdine, tpy = 2,2′,2′′-terpyridine, tmc= 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). Base release was not detected by HPLC from oxidations of calf thymus DNA, suggesting that sugar oxidation does not occur. The kinetics for trans -Ru(bpy) 2 O 2 2+ have been investigated in detail by optical spectroscopy. The spectra show that the initial reaction leads to the production of Ru(IV)O 2+ followed by slower formation of an oxo-bridged dimer. The raw kinetic traces exhibit a pre-steady-state phase indicative of initial DNA binding. Accordingly, the pseudo first-order rate constants for the steady-state phase are first-order in [DNA]. However, the kinetics show an inverse dependence on the concentration of ruthenium, suggesting that a product of the pre-steady-state phase inhibits the second phase of the reaction. These results are compared with those for Ru(tpy)(bpy)O 2+ and Os(tpy)(bpy)O 2+ to show that the reactivity of the metal complex can dramatically influence the kinetics and mechanism of DNA oxidation among cleavage agents of similar structure. |
| Databáze: | OpenAIRE |
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