Bond Strength and Interaction Energies in Togni Reagents: Insights from Molecular Electrostatic Potential-Based Parameters.

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 (VC) of the I-CF3 moiety as a sensitive parameter to quantify the cis and trans influences in Togni-type reagents. Our study has shown that VC 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 NMe3). Additionally, we provide insights into interactions of Togni reagents with Brønsted acids such as HCl and HSO3F, 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.

Hydrogen-Bond-Assisted Adsorption of Nitric Oxide on Various Metal-Loaded ZSM-5 Zeolites.

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 (VO) of NO adsorbed on BAS-free M-ZSM-5; which suggests that VO 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.

Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil.

2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (eaq-), formate radical (CO2˙-) and 2-hydroxypropan-2-yl radical ((CH3)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 eaq- reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of eaq- and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO2˙- reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to eaq- 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 CO2˙- 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 eaq- and CO2˙- reactions with any pyrimidines or their thio analogues.

Identifying the Transients and Transformation Products in Hydroxyl Radical-Methimazole Reactions Using DFT and UPLC-Q-TOF MS/MS Approaches.

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 M06-2X/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 H2O2. 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.

Oxidation reactions of 1- and 2-naphthols: an experimental and theoretical study.

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.

Insights into the Mechanism of Hydroxyl Radical Mediated Oxidations of 2-Aminopurine: A Computational and Sonochemical Product Analysis Study.

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, O2, and solvent H2O molecules.