Oxidation reactions of 2‑Thiouracil: A theoretical and pulse radiolysis study

Abstract

The reaction of hydroxyl radical (•OH) with the nucleic acid base analogue 2-thiouracil (1) has been studied by pulse radiolysis experiments and DFT. The generic intermediate radicals feasible for the •OH reactions with 1, namely,one electron oxidation product (1•+), •OH-adducts (3•, 4•, and 5•), and H-abstracted radicals (6• and 7•), were characterized by interpreting their electronic and structural properties along with calculated energetics and UV−vis spectra. Pulse radiolysis experiments showed that the transient formed in the reaction of •OH with 1 in water at pH 6.5 has λmax at 430 nm. A bimolecular rate constant, k2 of 9.6 × 109 M−1 s−1, is determined for this reaction via competition kinetics with 2-propanol. The experiments suggested that the transient species could be a dimer radical cation 2•+, formed by the reaction of 1 with the radical cation 1•+. For this reaction, an equilibrium constant of 4.7 × 103 M−1 was determined. The transient formed in the reaction of 1 with pulse radiolytically produced Br2 •− at pH 6.5 as well as Cl2 •− at pH 1 has also produced λmax at 430 nm and suggested the formation of 2•+. The calculated UV−vis spectra of the transient species (1•+, 3•, 4•, 5•, 6•, and 7•) showed no resemblance to the experimental spectra, while that of 2•+ (λmax = 420 nm) agreed well with the experimental value and thus confirmed the formation of 2•+. The 420 nm peak was due to σ → σ* electronic excitation centered on a 2-center−3-electron (2c−3e) sulfur−sulfur bond [−S∴S−]. 2•+ is the first reported example of a dimer radical cation in a pyrimidine heterocyclic system. Further, 5-C and 6-C substituted (substituents are −F, −Cl, −NH2, −N(CH3)2, −OCH3, −CF3, −CH3, −CH2CH3, n-propyl, phenyl, and benzyl) and 5,6-disubstituted 2-thiouracil systems have been characterized by DFT and found that the reaction (1 + 1•+ → 2•+) is exergonic (1.12−13.63 kcal/mol) for many of them