Intramolecular semiquinone disproportionation in DNA. Pulse radiolysis study of the one-electron reduction of daunorubicin intercalated in DNA

The one-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants. The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 x 10(8) mol-1.dm3.s-1) in a way entirely consiste...

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Bibliographic Details
Published in:Biochemistry (Easton) 1991-08, Vol.30 (33), p.8216-8222
Main Authors: Houee-Levin, Chantal, Gardes-Albert, Monique, Rouscilles, Annick, Ferradini, Christiane, Hickel, Bernard
Format: Article
Language:English
Subjects:
Antineoplastic agents
Benzoquinones - chemistry
Biological and medical sciences
Carbon Dioxide
Daunorubicin - chemistry
DNA - chemistry
Electron Transport
Free Radicals
General aspects
Intercalating Agents - chemistry
Kinetics
Macromolecular Substances
Medical sciences
Oxidation-Reduction
Pharmacology. Drug treatments
Pulse Radiolysis
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Summary:The one-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants. The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 x 10(8) mol-1.dm3.s-1) in a way entirely consistent with a simple competition between .COO- disproportionation and the drug reduction. The semiquinone drug disappears by a first-order reaction (k = 1340 s-1) producing the hydroquinone form. This reaction leads to an equilibrium similar to the one without DNA and the equilibrium constant is very close to its value free in water (Kc approximately 25). In addition, the stoichiometry of the first-order reaction is the one of a dismutation process. Therefore, it appears that the disproportionation occurs along an intramolecular path across DNA. This migration takes place under our experimental conditions, over a distance of ca. 100 base pairs, with a mobility of ca. 4.4 X 10(-11) m2.V-1.s-1, similar in magnitude to an excess electron mobility in doped organic polymers.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00247a018