Chemical Repair of Radical Damage to the GC Base Pair by DNA-Bound Bisbenzimidazoles
Details
Publication Year 2024-05-09,Volume 128,Issue #18,Page 4367-4376
Journal Title
Journal of Physical Chemistry B
Publication Type
Research article
Abstract
The migration of an electron-loss center (hole) in calf thymus DNA to bisbenzimidazole ligands bound in the minor groove is followed by pulse radiolysis combined with time-resolved spectrophotometry. The initially observed absorption spectrum upon oxidation of DNA by the selenite radical is consistent with spin on cytosine (C), as the GC(•) pair neutral radical, followed by the spectra of oxidized ligands. The rate of oxidation of bound ligands increased with an increase in the ratio (r) ligands per base pair from 0.005 to 0.04. Both the rate of ligand oxidation and the estimated range of hole transfer (up to 30 DNA base pairs) decrease with the decrease in one-electron reduction potential between the GC(•) pair neutral radical of ca. 1.54 V and that of the ligand radicals (E(0)', 0.90-0.99 V). Linear plots of log of the rate of hole transfer versus r give a common intercept at r = 0 and a free energy change of 12.2 ± 0.3 kcal mol(-1), ascribed to the GC(•) pair neutral radical undergoing a structural change, which is in competition to the observed hole transfer along DNA. The rate of hole transfer to the ligands at distance, R, from the GC(•) pair radical, k(2), is described by the relationship k(2) = k(0) exp(constant/R), where k(0) includes the rate constant for surmounting a small barrier.
Publisher
ACS Publications
Keywords
*DNA/chemistry; *Base Pairing; Free Radicals/chemistry; Oxidation-Reduction; Benzimidazoles/chemistry; Animals; Cattle; Ligands; Bisbenzimidazole/chemistry; DNA Repair; DNA Damage; Cytosine/chemistry
Department(s)
Laboratory Research
Terms of Use/Rights Notice
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