Site of OH Radical Attack on Dihydrouracil and Some of Its Methyl Derivatives

Abstract

The site of attack of OH radicals on dihydrouracil and five of its methylated derivatives was determined by pulse radiolysis using N,N,N',N'-tetramethylphenylenediamine (TMPD) to detect oxidizing radicals and tetranitromethane (TNM) as well as K3Fe(CN)6 to detect reducing radicals. In the case of dihydrouracil OH radicals abstract preferentially an H atom at C(6) to give the 6-yl radical (greater than or equal to 90 per cent) which at pH approximately 6.5 reduces TNM and K3Fe(CN)6 at almost diffusion-controlled rates. Only a small fraction of OH radicals abstract the H atom at C(5) (less than or equal to 10 per cent). The resulting 5-yl radical oxidizes TMPD to TMPD+ at pH 7-8. With the methylated derivatives of dihydrouracil, OH radicals react less selectively, especially in the case of N(1)-methyl derivatives. This methyl group is activated to a similar degree as the methylene group at C(6). In 1-Medihydrouracil the yield of N(1)-CH2 radicals is about 29 per cent, which has been deduced from the yield of formaldehyde formed after oxidation of this radical by TNM at pH approximately 6.5 and the subsequent hydrolysis. Radicals at the other methyl substituents are generated to a lesser extent (less than or equal to 10 per cent) and are relatively unreactive towards oxidizing agents such as TNM and K3Fe(CN)6 as well as towards the reducing agent TMPD. Although methyl substitution opens new routes for OH attack the preferred site of H abstraction remains C(6) (greater than 60 per cent).

Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

“…Moreover, the high electrophilicity of •OH 17 makes its addition to the electron rich C5-C6 double bond of thymine base favored over H-atom abstraction. 1, 2, 6–8,11,12 …”

“…1 Thus, the reactions of •OH with thymine and its derivatives are clearly kinetically controlled. 1, 2, 6–8, 11, 12 …”

Communication: Electronic UV-Vis transient spectra of the ·OH reaction products of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active space self-consistent field second-order perturbation (CASPT2//CASSCF) theory

“…Therefore, we can safely discard such species in the spectrum assignment. Discarding the N-H products contribution to the registered spectrum, which are not detected experimentally, 20 only C5 · remains as responsible for the observed band at ∼3.06 eV (∼405 nm). It can be readily seen that the 2 (π 1 →π 2 ) transition with a predicted energy of 3.24 eV (383 nm) has an oscillator strength value two orders of magnitude higher than the energetically closeby transitions.…”

Mechanistic insight into the role of Poly(ADP-ribosyl)ation in DNA topology modulation and response to DNA damage

“…PARP1-catalysed PARylation at 2′-OH of terminal cordycepin and ribonucleotide residues in DNA (31) points to a possible role of ADP-ribosylation in the repair of misincorporated ribonucleotides and other ribose-containing nucleoside analogues. Indeed, the presence of 2′-OH groups in DNA can be caused by ROS (48) and by misincoporation of ribonucleotides into DNA during DNA replication (49,50). Furthermore, using in vitro biochemical assays, Munnur et al demonstrated that human PARP family enzymes including PARP10, PARP11, PARP15 and a highly diverged PARP homologue, TRPT1, ADP-ribosylate phosphorylated ends of RNA, suggesting potential physiological relevance of this new nucleic acid modification (51).…”