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Oxidative reactions of the hydroxyl radical (·OH) with methimazole (MMI), an antithyroid drug, are crucial for understanding its fate in oxidizing environments. By synergistically integrating density functional theory and ultraperformance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF MS/MS) techniques, we elucidated the transients and transformation products (TPs) arising from the ·OH-MMI reactions. We probed two hydrogen-atom abstraction (HA) reactions, three radical adduct formation reactions, and single electron transfer (SET) at the M06-2 X /6-311++G(d,p)/SMD(water) level. All proposed reaction channels, except for HA from the methyl group and SET, were found to be barrier-free. SET is the dominant oxidation pathway, accounting for 44% of oxidations, as determined by branching ratio analysis. The selenium analogue, MSeI, exhibited minor reactivity differences compared to MMI, yet its overall patterns resembled those of ·OH-MMI reactions. TPs were generated experimentally by reacting MMI with ·OH produced by UV-photolysis of H 2 O 2 . Eight TPs were identified from an approximately 24% degradation of MMI using UPLC-Q-TOF MS/MS analysis, and an additional two TPs were identified from the approximately 52% degraded MMI sample. The exact identities of all of the TPs were established through their corresponding fragmentation patterns. This study elucidates the drug's susceptibility to free radical species under physiologically relevant conditions.

Togni reagents and their analogs, classified as hypervalent iodine(III) complexes, serve as potent trifluoromethylation agents. The interplay of cis and trans factors plays a pivotal role in shaping their performance, affecting aspects such as bond strength, interaction energies, stability, and subsequent nucleophilic reactions. In this context, we propose the utilization of the molecular electrostatic potential (MESP) at the carbon atom ( V C ) of the I-CF 3 moiety as a sensitive parameter to quantify the cis and trans influences in Togni-type reagents. Our study has shown that V C serves as a convenient probe for determining the heterolytic bond dissociation energy (BDE) and, consequently, assessing the reactivity of these reagents. Moreover, these parameters have been successfully applied to evaluate the strength of the σ-hole interactions with nucleophiles (Cl - and NMe 3 ). Additionally, we provide insights into interactions of Togni reagents with Brønsted acids such as HCl and HSO 3 F, elucidating them in terms of MESP topological parameters. These findings yield valuable information about the electronic properties of hypervalent iodine reagents, particularly Togni-type reagents, offering the potential for optimizing structurally modified reagents with enhanced activity and stability.

Understanding the characteristics of nitric oxide (NO) adsorption on metal-loaded zeolites is a prerequisite for developing efficient catalysts for NO abatement reactions. In this study, we probed the effect of the hydrogen bond that exists between adsorbed NO and Brønsted acid sites (BAS) in various metal-loaded ZSM-5 zeolites (M-ZSM-5, wherein M = Fe, Co, Ni, Cu, Zn, Pd, Ag, and Au) by using density functional theory calculations. The presence of a hydrogen bond has altered the NO adsorption energies significantly; appreciable stabilization via hydrogen bonding is noted for NO complexes of Zn, Fe, and Co, and reasonable stabilization is obtained for Ni and Cu complexes, whereas an anomalous effect of a hydrogen bond is identified in Ag, Pd, and Au species. Moderate weakening of the N-O bond in all NO-adsorbed complexes primarily due to a hydrogen bond has been realized in terms of Mayer bond order and quantum theory of atoms in molecules topological analyses; N-O bond activation follows the order Ag < Pd < Au < Ni < Cu < Co < Fe < Zn. We obtained a good correlation between hydrogen bond distance and molecular electrostatic potential at the O atom ( V O ) of NO adsorbed on BAS-free M-ZSM-5; which suggests that V O can be considered as a key descriptor to infer the strength of a hydrogen bond between the adsorbed NO and M-ZSM-5 with BAS. Finally, the energy decomposition analysis in combination with natural orbitals for chemical valence has provided the qualitative aspects of electron back-donation from the metal to the antibonding molecular orbital of NO; this back-donation is quite impressive in hydrogen-bond-assisted NO adsorption. We expect that the findings of this study will open up the possibility of the design of BAS-containing metal-loaded zeolites for the catalytic mitigation of NO.

Mechanistic details of hydroxyl radical ( • OH) mediated oxidations of 2-aminopurine (2AP) in the aqueous phase have been established in this study via a combination of DFT calculations (at the M05-2X/6-311+G(d,p) level with SMD solvation) and sonochemical end product analyses by the LC-Q-TOF-MS/MS method. Rate constants and branching ratios for single electron transfer (SET), two H-abstractions (HA), and seven radical adduct formation (RAF) reactions of • OH with 2AP were evaluated using transition state theory (TST). The RAF at the C8-position of 2AP is noted as the dominant process, which constitutes almost 46.1% of overall reaction routes. The SET mechanism accounts for the second major pathway (39.6%) followed by RAF at the C6-position (14.3%). Formations of 14 transformation products (TPs, i.e., the nonradical end products) in the sonochemical reactions of • OH with 2AP have been identified by means of the LC-Q-TOF-MS/MS technique. Among the 14 TPs (designated as TP1 to TP14), the lowest and highest mass to charge ratio ( m / z ) were respectively observed at 129 and 269 in ESI-MS positive ionization mode. The identities of all TPs have been proposed on the basis of elemental composition of [M + H] + ions and their respective MS-MS fragmentation pattern. Four TPs (including guanine) are considered as obtained directly from primary transients by radical elimination, radical-radical combination/disproportionation reactions. The remaining 10 TPs are postulated as a result of successive self- and/or cross-reactions of primary transients/four first generation TPs with reagents such as • OH, O 2 , and solvent H 2 O molecules.

2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (e aq - ), formate radical (CO 2 ˙ - ) and 2-hydroxypropan-2-yl radical ((CH 3 ) 2 ˙COH) reactions in aqueous medium. Transients were characterized by absorption spectroscopy and the experimental findings were rationalized by DFT calculations at LC-ωPBE and M06-2X levels using a 6-311+G(d,p) basis set and SMD solvation. In e aq - reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of e aq - and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO 2 ˙ - reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to e aq - reactions); the second mechanism led to 2 center-3 electron, sulfur-sulfur bonded neutral dimer radicals, TCdim˙ and TUdim˙. DFT calculations demonstrated that H-abstraction by CO 2 ˙ - from TC(TU) results in S-centered radical which upon combination with TC(TU) provide the dimer radical. In some cases, DFT energy profiles were further validated by CBS-QB3//M06-2X calculations. This is the first time report for a contradictory behavior in the mechanisms of e aq - and CO 2 ˙ - reactions with any pyrimidines or their thio analogues.

The transients formed during the reactions of oxidizing radicals with 1-naphthol (1) and 2-naphthol (2) 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 1 and 2 exhibited λ(max) at 340 and 350 nm at neutral pH. The rate constants of the (•)OH reactions of 1 (2) were determined from build-up kinetics at λ(max) of the transients as (9.63 ± 0.04) × 10(9) M(-1) s(-1) ((7.31 ± 0.11) × 10(9) M(-1) s(-1)). DFT calculations using the B3LYP/6-31+G(d,p) method have been performed to locate favorable reaction sites in both 1 and 2 and identification of the pertinent transients responsible for experimental results. Calculations demonstrated that (•)OH additions can occur mostly at C1 and C4 positions of 1, and at C1 and C8 positions of 2. Among several isomeric (•)OH adducts possible, the C1 adduct was found to be energetically most stable both in 1 and 2. Time-dependent density functional theory (TDDFT) calculations in the solution phase has shown that the experimental spectrum of 1 was mainly attributed by 1a4 (kinetically driven (•)OH-adduct) formed via the addition of (•)OH at the C4 position which was 0.73 kcal/mol endergonic compared to 1a1 (thermodynamic (•)OH adduct), whereas 2a1 (thermodynamic/kinetic (•)OH-adduct) was mainly responsible for the experimental spectrum of 2. Naphthoxyl radicals of 1 and 2 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 1 and 2. Further, UV photolysis of aqueous solutions of 1 and 2 containing H2O2 (UV/H2O2) were used for the (•)OH induced oxidation product formations up on 60% degradations of 1 and 2; 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 1 and 2 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 1 and 2 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.

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 λ(max) at 430 nm. A bimolecular rate constant, k(2) of 9.6 × 10(9) 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 × 10(3) M(-1) was determined. The transient formed in the reaction of 1 with pulse radiolytically produced Br(2)(•-) at pH 6.5 as well as Cl(2)(•-) at pH 1 has also produced λ(max) 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(•+) (λ(max) = 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, -NH(2), -N(CH(3))(2), -OCH(3), -CF(3), -CH(3), -CH(2)CH(3), 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.

Pulse radiolysis and density functional theory (DFT) calculations at B3LYP/6-31+G(d,p) level have been carried out to probe the reaction of the water-derived hydroxyl radicals (*OH) with 5-azacytosine (5Ac) and 5-azacytidine (5Acyd) at near neutral and basic pH. A low percentage of nitrogen-centered oxidizing radicals, and a high percentage of non-oxidizing carbon-centered radicals were identified based on the reaction of transient intermediates with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate), ABTS2-. Theoretical calculations suggests that the N3 atom in 5Ac is the most reactive center as it is the main contributor of HOMO, whereas C5 atom is the prime donor for the HOMO of cytosine (Cyt) where the major addition site is C5. The order of stability of the adduct species were found to be C6-OH&#95;5Ac*>C4-OH&#95;5Ac*>N3-OH&#95;5Ac*>N5-OH&#95;5Ac* both in the gaseous and solution phase (using the PCM model) respectively due to the additions of *OH at C6, C4, N3, and N5 atoms. These additions occur in direct manner, without the intervention of any precursor complex formation. The possibility of a 1,2-hydrogen shift from the C6 to N5 in the nitrogen-centered C6-OH&#95;5Ac* radical is considered in order to account for the experimental observation of the high yield of non-oxidizing radicals, and found that such a conversion requires activation energy of about 32 kcal/mol, and hence this possibility is ruled out. The hydrogen abstraction reactions were assumed to occur from precursor complexes (hydrogen bonded complexes represented as S1, S2, S3, and S4) resulted from the electrostatic interactions of the lone pairs on the N3, N5, and O8 atoms with the incoming *OH radical. It was found that the conversion of these precursor complexes to their respective transition states has ample barrier heights, and it persists even when the effect of solvent is considered. It was also found that the formation of precursor complexes itself is highly endergonic in solution phase. Hence, the abstraction reactions will not occur in the present case. Finally, the time dependent density functional theory (TDDFT) calculations predicted an absorption maximum of 292 nm for the N3-OH&#95;5Ac* adduct, which is close to the experimentally observed spectral maxima at 290 nm. Hence, it is assumed that the addition to the most reactive center N3, which results the N3-OH&#95;5Ac* radical, occurs via a kinetically driven process.