Oxidation Reactions of 2‑Thiouracil: A Theoretical and Pulse Radiolysis Study

The reaction of hydroxyl radical (^•OH) with the nucleic acid base analogue 2-thiouracil (<b>1</b>) has been studied by pulse radiolysis experiments and DFT. The generic intermediate radicals feasible for the ^•OH reactions with <b>1</b>, namely, one electron oxidation product (<b>1</b>^•+), ^•OH-adducts (<b>3</b>^•, <b>4</b>^•, and <b>5</b>^•), and H-abstracted radicals (<b>6</b>^• and <b>7</b>^•), 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 <b>1</b> in water at pH 6.5 has λ_max at 430 nm. A bimolecular rate constant, <i>k</i>₂ 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 <b>2</b>^•+, formed by the reaction of <b>1</b> with the radical cation <b>1</b>^•+. For this reaction, an equilibrium constant of 4.7 × 10³ M^–1 was determined. The transient formed in the reaction of <b>1</b> with pulse radiolytically produced Br₂^•– at pH 6.5 as well as Cl₂^•– at pH 1 has also produced λ_max at 430 nm and suggested the formation of <b>2</b>^•+. The calculated UV–vis spectra of the transient species (<b>1</b>^•+, <b>3</b>^•, <b>4</b>^•, <b>5</b>^•, <b>6</b>^•, and <b>7</b>^•) showed no resemblance to the experimental spectra, while that of <b>2</b>^•+ (λ_max = 420 nm) agreed well with the experimental value and thus confirmed the formation of <b>2</b>^•+. 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−]. <b>2</b>^•+ 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, <i>n</i>-propyl, phenyl, and benzyl) and 5,6-disubstituted 2-thiouracil systems have been characterized by DFT and found that the reaction (<b>1</b> + <b>1</b>^•+ → <b>2</b>^•+) is exergonic (1.12–13.63 kcal/mol) for many of them

Oxidation Reactions of 1- and 2‑Naphthols: An Experimental and Theoretical Study

The transients formed during the reactions of oxidizing radicals with 1-naphthol (<b>1</b>) and 2-naphthol (<b>2</b>) in aqueous medium have been investigated by pulse radiolysis with detection by absorption spectroscopy and density functional theory (DFT) calculations. The transient spectra formed on hydroxyl radical (^•OH) reactions of <b>1</b> and <b>2</b> exhibited λ_max at 340 and 350 nm at neutral pH. The rate constants of the ^•OH reactions of <b>1</b> (<b>2</b>) were determined from build-up kinetics at λ_max of the transients as (9.63 ± 0.04) × 10⁹ M^–1s^–1 ((7.31 ± 0.11) × 10⁹ M^–1s^–1). DFT calculations using the B3LYP/6-31+G­(d,p) method have been performed to locate favorable reaction sites in both <b>1</b> and <b>2</b> and identification of the pertinent transients responsible for experimental results. Calculations demonstrated that ^•OH additions can occur mostly at C1 and C4 positions of <b>1</b>, and at C1 and C8 positions of <b>2</b>. Among several isomeric ^•OH adducts possible, the C1 adduct was found to be energetically most stable both in <b>1</b> and <b>2</b>. Time-dependent density functional theory (TDDFT) calculations in the solution phase has shown that the experimental spectrum of <b>1</b> was mainly attributed by <b>1a</b>_<b>4</b> (kinetically driven ^•OH-adduct) formed via the addition of ^•OH at the C4 position which was 0.73 kcal/mol endergonic compared to <b>1a</b>_<b>1</b> (thermodynamic ^•OH adduct), whereas <b>2a</b>_<b>1</b> (thermodynamic/kinetic ^•OH-adduct) was mainly responsible for the experimental spectrum of <b>2</b>. Naphthoxyl radicals of <b>1</b> and <b>2</b> have been predicted as the transient formed in the reaction of ^•OH at basic pH. In addition, the same transient species resulted from the reactions of oxide radical ion (O^•–) at pH ≈ 13 and azide radical (N₃^•) at pH 7 with <b>1</b> and <b>2</b>. Further, UV photolysis of aqueous solutions of <b>1</b> and <b>2</b> containing H₂O₂ (UV/H₂O₂) were used for the ^•OH induced oxidation product formations up on 60% degradations of <b>1</b> and <b>2</b>; profiling of the oxidation products were performed by using an ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF-MS) method. According to the UPLC–Q-TOF-MS analyses, the preliminary oxidation products are limited to dihydroxy naphthalenes and naphthoquinones with N₂-saturation, while some additional products (mainly isomeric monohydroxy-naphthoquinones) have been observed in the degradations of <b>1</b> and <b>2</b> in the presence of O₂. We postulate that dihydroxy naphthalenes are derived explicitly from the most favorable ^•OH-adducts speculated (preference is in terms of the kinetic/thermodynamic dominancy of transients) by using theoretical calculations which in turn substantiate the proposed reaction mechanisms. The observations of ^•OH-adducts for an aromatic phenol (herein for both <b>1</b> and <b>2</b> at pH 7) rather than phenoxyl type radical in the pulse radiolysis experiments is a distinct and unique illustration. The present study provides a meaningful basis for the early stages associated with the ^•OH initiated advanced oxidation processes of 1- and 2-naphthols