TY - JOUR
T1 - Chemical Repair of Radical Damage to the GC Base Pair by DNA-Bound Bisbenzimidazoles
AU - Anderson, Robert F.
AU - Shinde, Sujata S.
AU - Andrau, Laura
AU - Leung, Brenda
AU - Skene, Colin
AU - White, Jonathan M.
AU - Lobachevsky, Pavel N.
AU - Martin, Roger F.
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/5/9
Y1 - 2024/5/9
N2 - 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 (E0′, 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, k2, is described by the relationship k2 = k0 exp(constant/R), where k0 includes the rate constant for surmounting a small barrier.
AB - 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 (E0′, 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, k2, is described by the relationship k2 = k0 exp(constant/R), where k0 includes the rate constant for surmounting a small barrier.
UR - http://www.scopus.com/inward/record.url?scp=85192207230&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.4c01069
DO - 10.1021/acs.jpcb.4c01069
M3 - Article
C2 - 38686959
AN - SCOPUS:85192207230
SN - 1520-5207
VL - 128
SP - 4367
EP - 4376
JO - The Journal of Physical Chemistry B: Biophysical Chemistry, Biomaterials, Liquids, and Soft Matter
JF - The Journal of Physical Chemistry B: Biophysical Chemistry, Biomaterials, Liquids, and Soft Matter
IS - 18
ER -