OH Radical Reaction of 5-Substituted Uracils:  Pulse Radiolysis and Product Studies of a Common Redox-Ambivalent Radical Produced by Elimination of the 5-Substituents

Abstract

Using a redox titration method in the pulse radiolysis of N 2 O-saturated phosphate buffer solution, the redox properties of the intermediate radicals derived from OH radical reactions of 5-substituted uracils 1c-h (R ) F, Cl, Br, NO 2 , NH 2 , OH) have been characterized. While the primary intermediates were oxidizing C(5) radicals 2c-h and reducing C(6) radicals 3c-h of the respective OH adducts, a common allyl-type radical of "redox ambivalence" with limiting mesomeric forms of reducing carbon-centered 5-oxo-5,6-dihydrouracil-6-yl radical (4) and oxidizing oxygen-centered uracil-5-oxyl radical (5) was secondarily formed via elimination of 5-substituents from 3c-h. The rate of 5-substituent elimination decreased with varying structures of the 5-substituents in the order halo > amino, nitro > hydroxy groups. The common radical 4/5 showed weaker reducing/oxidizing abilities than the typical pyrimidine C(6) and C(5) radicals. The product study demonstrated that the one-electron reduction of 5-oxyl radical 5 by N,N,N′,N′-tetramethyl-p-phenylenediamine ((2.0 ( 0.1) × 10 8 dm 3 mol -1 s -1 ) increased the yield of isobarbituric acid (1h), while the one-electron oxidation of 5-oxo C(6) radical 4 by tetranitromethane increased the yield of isodialuric acid (6).

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

“…[1][2][3][4][5][6][7] It is well known that these reactions yield modified nucleobases which may cause mutations in DNA/RNA sequences and/or cell reproduction inability. 8 It has been demonstrated both experimentally 2,3,5,9 and theoretically [10][11][12][13] that addition to the C5-C6 double bond is the most favored mechanism in pyrimidine nucleobases. Using differential redox properties of the C5OH and C6OH radical adducts, 14 estimated values of the C5OH:C6OH ratios were determined during the 1980s decade.…”

“…16,17 In addition, transient absorption spectroscopy has been widely used for the direct observation of the carbon-centered radicals formed in the reactions. 1,5,9,15,18,19 Regarding the latter technique, the spectra related to the pyrimidine nucleobases 1, 9 and some of their derivatives as 5,6-dihydrouracil or 1,3-dimethyluracil 9 in aqueous solution were reported early in 1970s. For uracil, a broadband centered at around 3.26 eV (380 nm) was observed at pH 3.15.…”

Hydroxyl Radical Addition to Thymine and Cytosine and Photochemistry of the Adducts at the C6 Position

“…The accumulated evidence by different theoretical and experimental studies indicate that the main reactions that occur between the hydroxyl radical and the nucleobases consist on the addition to the double bonds and the abstraction of hydrogen atoms . In pyrimidines, the addition reaction takes place on the C5=C6 double bond as displayed in Scheme .…”

DFT study on addition reaction mechanism of guanine-cytosine base pair with OH radical

“…Candeias et al has been reported the addition reaction of OH radical with 2′‐deoxyguanosine, which yields two transient species, identified as the C4‐OH adduct and C8‐OH adduct . With regard to addition of OH radical with pyrimidines, C5C6 double bond is the most favorable 1,56,6872 . Therein, the hydroxylation is more likely to occur at C5 site than at C6 site in cytosine …”