Search Results (123)

Background/Objectives: Vonoprazan is a potassium-competitive acid blocker with potential for the treatment of equine gastric ulcer syndrome. Vonoprazan metabolic pathways in horses have not been characterized. This study aimed to identify vonoprazan metabolites following oral administration and to determine the metabolic enzymes responsible for their metabolism using in vitro models. Methods: Six healthy adult Thoroughbred horses received vonoprazan (0.5 and 1 mg/kg PO) in a randomized crossover design. Plasma concentrations of vonoprazan-N-oxide (M-I) and vonoprazan-nitrone (M-III) were quantified using a validated liquid chromatography-tandem mass spectrometry method, and a non-compartmental pharmacokinetic analysis was performed. In vitro metabolism was evaluated using equine liver microsomes (ELMs) and equine recombinant CYP450 (eq-rCYP) enzymes. Enzyme kinetics were characterized using nonlinear regression modeling. Results: Both metabolites were detected in plasma after oral administration. Systemic exposure to M-I was markedly greater than M-III at both doses. At 1 mg/kg, mean ± SD C_max values were 39.2 ± 28.3 ng/mL for M-I and 1.67 ± 1.66 ng/mL for M-III. AUC_0–∞ increased dose-proportionally for both metabolites. In ELMs, M-I formation followed substrate inhibition kinetics, whereas M-III formation followed Michaelis–Menten kinetics. Among recombinant enzymes, CYP2D50 and CYP3A94 were the primary contributors to metabolite formation, exhibiting metabolite-specific kinetic profiles. Conclusions: These findings demonstrate that vonoprazan undergoes hepatic oxidative metabolism in horses, with M-I as the predominant circulating metabolite. Equine recombinants CYP2D50 and CYP3A94 appear to play central roles in equine vonoprazan metabolism, providing foundation for future evaluation of drug–drug interaction potential and clinical use in this species. Full article

The reaction of 2,5-dimethylfuran (DMF) with two equivalents of α-nitrosostyrene (NS) leading to a tricyclic 1,2-oxazine nitrone (TON) has been examined theoretically at the ωB97X-D/6-311G(d,p) computational level. In this case, the domino process should be considered: (i) a [4+2] cycloaddition (42CA) between DMF and NS yielding a bicyclic 1,2-oxazine (BO); and (ii) a second formal [3+2] cycloaddition (32CA) reaction between BO and NS yielding the final TON. Analysis of the reactivity indices shows that DMF and BO generated along the first 42CA reaction are strong nucleophiles, while NS is a strong electrophile. The first 42CA reaction takes place according to a one-step mechanism. In turn, the second 32CA proceeds according to a two-step mechanism through the zwitterionic intermediate ZW. It is worth noting that the activation enthalpy of the significant point (TS-1mn) of the 42CA is very low, 2.17 kcal·mol⁻¹, the reaction being strongly exothermic by −37.71 kcal·mol⁻¹. This cycloaddition reaction is completely meta regioselective and endo stereoselective. The first step of the formal 32CA reaction has an activation enthalpy of 8.48 kcal·mol⁻¹ (TS-21), the overall domino process being strongly exothermic by −40.34 kcal·mol⁻¹. Both TS-1mn and TS-21 are associated with highly asynchronous single bond processes. The high global electron density transfer (GEDT) found at both TSs, higher than 0.32e, points out the high polar character of these cycloaddition reactions, classified as reverse electron density flux (REDF). Electron Localization Function (ELF) analysis of TS-1mn and TS-21 shows that the C2-C3 and C3-N5 bonds are not formed at the same time, while in the intermediate ZW we observed the creation of one of them. Full article

Reactive oxygen species (ROS) regulate cellular signaling at physiological concentrations and drive tissue damage when their generation exceeds antioxidant defenses. The conceptual reframing of the field into oxidative eustress (low, controlled redox signaling) and oxidative distress (supraphysiological levels causing biomolecular damage), alongside parallel advances in detection chemistry and genetically encoded biosensors, has transformed how investigators measure ROS in living systems. This review provides a critical, methods-focused update covering the contemporary toolkit, with particular emphasis on advances from 2015 to 2026 while incorporating earlier foundational work where it remains indispensable to interpretation. Consistent with the title and reflecting both the maturity of the available chemistry and the weight of the recent literature, our emphasis falls on hydrogen peroxide and mammalian experimental systems; superoxide, the hydroxyl radical, and singlet oxygen are addressed primarily where their detection intersects with the platforms reviewed here, and non-mammalian models are considered only selectively. Readers seeking dedicated coverage of these other species or of plant, microbial, and invertebrate systems are directed to the specialized reviews cited throughout. Five complementary measurement platforms are evaluated: (i) electron paramagnetic resonance spectroscopy with classical nitrone spin traps and the newer cyclic hydroxylamine probes; (ii) small-molecule fluorescent probes, with particular emphasis on the boronate-based, activity-based sensing platform that has supplanted 2′,7′-dichlorofluorescin diacetate for hydrogen peroxide imaging; (iii) genetically encoded biosensors of the HyPer and roGFP families, which now permit ratiometric, organelle-resolved, and longitudinal measurements; (iv) mass-spectrometry-based quantification of oxidation products and radical adducts, including isoprostanes, 2-hydroxyethidium, and redox-modified cysteines via chemical proteomics; and (v) electrochemical and nanosensor approaches enabling real-time single-cell measurements. The selectivity, sensitivity, temporal resolution, spatial resolution, and quantitative capability of each platform are critically compared. Reliance on a single non-specific probe is no longer sufficient as the sole evidence base for quantitative or species-specific claims; contemporary investigators are expected to apply complementary approaches and to validate findings across modalities. Standardization of reporting, integration with single-cell omics, and clinical translation of validated mass-spectrometry biomarkers are identified as priorities for the coming decade. Full article

Sustainable agriculture, particularly efficient nitrogen management, is essential for maintaining soil fertility, improving crop quality, and reducing the environmental footprint of agricultural production. This study evaluated the effects of reduced soil-applied nitrogen and foliar application of the nitrogen–sulfur fertilizer Nitron-S on the quality of silage maize (Zea mays L.). A field experiment was conducted using a single-factor design with four fertilization treatments differing in nitrogen supply and foliar fertilization intensity. The silage maize cultivar Farmmortiz was grown under uniform manure application (30 t ha⁻¹) applied in autumn. The control treatment received the full soil-applied nitrogen rate, whereas experimental treatments received 50% of the conventional nitrogen dose supplemented with foliar Nitron-S at doses of 20, 40, and 60 dm³ ha^-1, applied twice during the growing season. After harvest, plant yield and selected quality parameters were determined, including dry matter, crude protein, sugars, starch, ash, neutral detergent fiber (NDF), acid detergent lignin (ADL), ammonia fraction, and organic matter digestibility (VOS). Fertilization treatments significantly affected most quality traits. The highest Nitron-S rate increased starch concentration (up to approximately 30% under N4) but also elevated ADL content (by about 25%) and slightly reduced VOS (only by about 1–3%. Partial replacement of soil-applied nitrogen with foliar nitrogen–sulfur fertilization improved the nutritional quality of maize silage and reduced nitrogen input. This approach may contribute to more sustainable maize production. Full article

The 1,3-dipolar cycloaddition of nitrones with hydrazones affords 5-iminoisoxazolidines as the major products, in contrast to the reaction with enals, which exclusively afford 4-acylisoxazolidines. This reversal of regioselectivity can be explained in terms of frontier orbital theory. The 5-iminoisoxazolidines are easily converted to 5-acylisoxazolidines. Full article

Drought stress is one of the major abiotic factors limiting crop growth and yield, particularly in wheat. Water deficit leads to reduced chlorophyll content, impaired photosynthetic performance, and decreased biomass accumulation. Nitrogen fertilization may influence plant physiological responses to drought; however, its capacity to alleviate drought-induced growth reduction remains uncertain. A pot experiment was conducted to evaluate the impact of different nitrogen-based fertilizers on wheat seedlings grown under irrigation level 60% PPW (control) and 30% PPW (drought stress) conditions, with balanced levels of phosphorus and potassium maintained in all treatments. Water deficit led to substantial reductions in chlorophyll content compared to optimally irrigated plants. Similarly, the performance index (PI) decreased by 139.3% at Term 1 (1 day after foliar nitrogen application) and 27.2% at Term 2 (7 days after application). The net photosynthetic rate (Pn) declined markedly under drought conditions and was not significantly improved by nitrogen fertilization, indicating a partial and mainly short-term physiological response to nitrogen under water deficit. The application of nitrogen fertilizers, particularly urea and Nitron S, modulated the relative chlorophyll content and selected chlorophyll fluorescence (Fv/Fm, Fv/Fo, PI) and gas-exchange (E, gs, Ci) parameters under drought conditions, mainly shortly after application. However, aboveground dry biomass under drought conditions was not significantly affected by any nitrogen fertilizer. Urea induced the most consistent short-term physiological responses under both irrigation regimes, with effects more pronounced shortly after application, whereas Nitron S showed fertilizer-specific effects under drought stress. Overall, the results demonstrate that foliar nitrogen fertilization can modulate short-term physiological responses of wheat seedlings to drought but does not translate into sustained improvements in Pn or biomass accumulation. In the context of climate change and increasing water scarcity, identifying nitrogen fertilizers that support physiological functioning without overestimating growth benefits has critical implications for sustainable wheat production. Optimizing nitrogen fertilization may, therefore, contribute to improved nutrient management strategies under water-limited conditions. Full article

Nitrones are a significant class of compounds highly useful in organic synthesis; in particular, they are key intermediates for the synthesis of new biologically active nitrogen compounds. The first part of this review aims to provide a structured and concise overview of nitrones, summarizing their synthetic methodologies and highlighting the environmentally friendly approaches. Their fundamental transformations and a thorough explanation of their reactivities are addressed, either in rearrangements to similar compounds or as fragments/intermediates for more complex molecules. Lastly, physicochemical properties, therapeutic potential, and industrial applications are also addressed. This review gives an update on the scientific discoveries in the field of nitrones, focusing on organizing the existing information and highlighting subtle details to enhance chemical comprehension. Full article

In this work, the regio- and stereochemistry as well as the molecular mechanism of the cycloaddition reaction of nitrones with (E)-3-(methylsulfonyl)-propenoic acid derivatives were analyzed based on ωb97xD/6-311G(d,p) quantum chemical calculations. In light of these data, it is possible to propose selectivity of the analyzed processes, which was not clearly determined in light of previous experimental studies. Furthermore, the mechanism of the process was diagnosed. CDFT descriptors indicate that the reaction is triggered by a nucleophilic attack of the nitrone oxygen atom on the electrophilic carbon atom of (E)-3-(methylsulfonyl)-propenoic acid derivatives. In turn, PES analysis shows that, despite the nucleophilic-electrophilic character of the reactants, the corresponding transition states are only weakly polar and highly synchronous. IRC calculations rule out zwitterionic or biradical intermediates, confirming a single-step mechanism. The in silico ADME and PASS predictions indicate that the resulting isoxazolidines possess promising biological profiles, showing potential modulation of the serotonin system through 5-HT2A and 5-HT2C antagonism and stimulation of serotonin release, with structural features compatible with P450-mediated metabolism. Considering this attractive application potential, a detailed mechanistic investigation of their formation becomes essential for understanding and ultimately controlling the reaction pathways leading to these heterocycles. Full article

This study evaluates the feasibility of achieving chemoselective aldol reactions over competing Henry reactions and employs competition experiments to establish proof of concept. A typical reaction involved using in-water reaction conditions where a concentrated organic layer containing an aldol nucleophile (1.5 equiv), a Henry nucleophile (1.5 equiv), an aldehyde electrophile (1.0 equiv), and a proline-based amino acid catalyst (2.5 mol%) constituted one phase, while the second phase was water (15 equiv). Highly enantioenriched aldol products were formed in practical yields, and a variety of Henry nucleophiles (nitroalkanes, allylic nitro compounds, and ethyl nitroacetate) were tolerated. This systematic examination of nitro compounds (pK_a 5.5–10.0) established a pK_a of ≈7.0 as the critical threshold at which nitronate formation results in Henry product formation under catalysis with 1. Reactions alternatively performed in MeOH/H₂O (3:2 equiv) solvent combinations, at times, provided improved chemoselectivity or product dr over the use of water (15 equiv) alone but required longer reaction times to produce similar yields. Reactions constrained by solubility were investigated using mechanochemical methods, but these conditions failed to deliver practical yields of either competition product. In summary, defining this category of aldol chemoselectivity may provide new tactical opportunities for the synthesis of complex molecular targets. Full article

The course of the reactions of acetylenes with fluorinated nitrones in the presence of Zn(OTf)₂ and Et₂Zn was investigated. The formation of hydroxylamines and/or 1,2-oxazolines as products was observed. The desired hydroxylamines were formed as main products if reactions were carried out with the usage of Et₂Zn. In order to explain the obtained results, quantum mechanical calculations of the reaction paths leading to both products were carried out. Further research allowed us to develop the enantioselective variant of described reactions with the usage of enantiomerically pure AziPhenol ligand bearing chiral aziridine scaffold. Full article

Despite the substantial global impact of ischemic stroke, current therapeutic options remain limited and only partially effective. To advance neuroprotective strategies that could improve the safety and efficacy of existing treatments while preserving brain tissue, we synthesized and evaluated seven new nitrones (MC3, MC5, MC7) and oximes (MC1, MC2, MC4, MC6) derived from different neuroactive steroids—ethisterone (MC1–3), mifepristone (MC4–5) and stanolone (MC6–7)—in an in vitro model of cerebral ischemia. Overall, these derivatives exhibited neuroprotective and antioxidant effects superior to those of the reference compounds cholesteronitrone ChN2, α-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC). Notably, nitrones showed greater neuroprotective, anti-necrotic, and antioxidant potency than their corresponding oximes, regardless of the degree of molecular conjugation. Among them, the stanolone-derived nitrone MC7, which lacks conjugated double bonds, displayed the most balanced and robust profile, consistently enhancing cell viability, reducing necrotic cell death, and suppressing superoxide anion production. Consequently, MC7 has been selected as a promising lead compound for further in vivo studies of cerebral ischemia. Full article

In this article, the 1,3-dipolar cycloaddition (1,3-DC) reactions between 4-acyl-1H-pyrrole-2,3-diones fused at the [e]-side with a heterocyclic moiety (FPDs) and diphenylnitrone are studied using Molecular Electron Density Theory (MEDT) at different computational levels. An analysis of the global reactivity descriptors has determined the role of the reagents. FPDs will act as electrophiles, while diphenylnitrone will be a nucleophile. It was found that the reactions proceed according to a one-step but asynchronous mechanism. Additionally, based on the Bonding Evolution Theory (BET) analysis of the model 1,3-DC reaction between FPDs 1b and diphenylnitrone 2, we can distinguish eight different phases. The formation of the first C1-O5 single bond takes place in phase VII through the disappearance of the V(C1) monosynaptic basin and the depopulation of the V″(O5) monosynaptic basin, while the formation of the second C2-C3 single bond begins at the last phase of the reaction through the connection of two V(C2) and V(C3) monosynaptic basins. Based on this, we can classify this reaction as a “one-step two-stage” process. Furthermore, molecular dynamics (MD) simulation analysis up to 100 ns demonstrated the stability of both the 2P3B–Ligand1 and 2P3B–Zidovudine complexes. An enhancer of shape compression was generated for ligand1, whereas Zidovudine generated a more packed and stable hydrogen bond network that would allow a better occupancy of the active site. Full article

The 1,3-dipolar cycloaddition reaction was applied to 9α-hydroxyparthenolide, an important sesquiterpene component of Anvillea radiata that was extracted directly from plant material collected in Morocco. Several new spiro-isoxazolidine derivatives were generated on the B-ring of 9α-hydroxyparthenolide (α-methylene-γ-butyrolactone (1)) by 1,3-dipolar cycloaddition of its exocyclic double bond with various nitrones. These compounds were fully characterized by spectroscopic methods. Full article

1,3-Dipolar cycloadditions on nitrone dipoles are key reactions to access five-membered heterocycles, which are useful intermediates in the synthesis of biologically relevant glycomimetics. The good atomic balance and high stereoselectivity characteristic of such reactions make them good candidates for the development of green protocols. In the present work, these features were maximized by avoiding the use of organic solvents and considering starting materials derived from biomass. Reactions involving (acyclic and cyclic) carbohydrate-derived nitrones as dipoles and levoglucosenone as dipolarophile were considered. Performing selected 1,3-dipolar cycloadditions in neat conditions showed reduced reaction times, maintaining similar selectivity and yields with respect to the classical protocols. The use of microwave irradiation and orbital shaking were also exploited to increase the sustainability of the synthetic protocols. The collected results highlight the potential of solvent-free 1,3-dipolar cycloadditions in the design of efficient synthetic routes according to green chemistry principles, such as prevention, atom economy, safer solvents and auxiliaries, and use of renewable feedstocks. Full article

A prototype of an industrial installation for the deposition of self-restoring nitride coatings on the surface of reed switch contacts using electro-spark erosion alloying was developed, manufactured, and tested under the laboratory conditions at LLC Nitron. It was shown that the coatings are formed inside a bulb of reed switches at the final stage of their production following the impact from the spark breakdown between the contacts, stimulated via alternating magnetic and electric fields. The nitrogen concentration in the surface layers of the nitride coatings, estimated by means of X-ray microanalysis, was ca. 19 at. % and their thickness, measured by time-of-flight secondary ion mass spectrometry via sputter depth profiling, ranged between 250 and 350 nm. The novelty of the presented work consists of the development of an innovative piece of equipment, the operating principle and design of which are protected by intellectual property rights (four Russian patents). The technological approach implemented in this installation differs from the industrial galvanic technology due to its high level of environmental safety and economic efficiency, since it does not require the use of gold, ruthenium, or other high-priced metals. Full article