Search Results (234)

We report the synthesis of a modified benzothiazole sulfide. This compound contains a heterocyclic core, a Boc-protected hydroxylamine, and an appended alkyne. This benzothiazole was accessed through three total steps, including an amidation reaction and two nucleophilic aromatic substitutions. The identity of the title compound was confirmed through ¹H, ¹³C, ¹H–¹H COSY, HSQC, and HMBC NMR, in addition to IR, MALDI-MS, HRMS, and HPLC. Full article

Many genotoxic impurities (GTIs) remain “invisible” to conventional LC-MS due to poor ionization or chemical instability under electrospray ionization, yet their sub-ppm acceptable intake limits under ICH M7(R2) demand exceptional analytical sensitivity. Derivatization—the chemical introduction of ionizable moieties, stable tags, or MS/MS information carriers—offers a powerful strategy to overcome this limitation. This review provides a critical systematic overview of derivatization techniques for LC-MS analysis of GTIs over the past decade (2015–2025, based on a literature search across PubMed, Web of Science, and Scopus). We construct a functional-group-based strategic framework covering alkyl halides, nitroaromatics, sulfonyl chlorides, hydroxylamine, alcohols, aldehydes, carboxylic acids, and amines, while placing specific emphasis on typical impurities within these classes such as methyl iodide, methyl chloride, nitrobenzene, and benzenesulfonyl chloride, and discuss the evolution of reagents from simple “reaction tags” to “MS/MS information carriers” that provide characteristic neutral losses or product ions for enhanced selectivity. Quantitative analysis reveals that derivatization typically enhances ESI response by 2–3 orders of magnitude, consistently achieving LODs below 1 ppm—the ICH M7(R2) threshold. Key analytical trade-offs are critically evaluated, including the balance between derivatization efficiency and reaction time, by-product management, and the fundamental kinetic and chromatographic constraints that render post-column derivatization impractical for most GTIs. We conclude with perspectives on high-throughput automation, smart multifunctional reagents, online integration, and green chemistry, aiming to provide a practical roadmap for developing robust, sensitive, and regulatory-compliant LC-MS methods for GTI control. Full article

A major limitation hindering the practical application of heterogeneous Fenton-like systems is their inherently slow reaction kinetics, particularly near neutral pH. To address this issue, a hydroxylamine (HA)-enhanced NiFe₂O₄/H₂O₂ system was developed for phenol degradation. At an initial pH of 7, with 5 mmol/L HA and 10 mmol/L H₂O₂, the system achieved 97.8% phenol degradation within 60 min, compared with 17.4% in the HA-free system. XPS analysis showed that the Fe²⁺ proportion increased from 49.1% to 53.6% and the Ni²⁺ proportion increased from 52.1% to 63.4% after reaction. These changes are consistent with HA facilitating the formation or regeneration of reduced metal species, suggesting that HA may be related to accelerated Fe³⁺/Fe²⁺ or Ni³⁺/Ni²⁺ cycling. Radical scavenging experiments and electron paramagnetic resonance (EPR) results indicated that identified hydroxyl (•OH) and superoxide (O₂•⁻) radicals were the predominant reactive species. Metal-leaching and catalyst-removal experiments indicated that both heterogeneous and homogeneous processes contributed to phenol degradation. The results provide mechanistic insights into HA-enhanced H₂O₂ activation while also highlighting the need to consider metal leaching, HA-derived nitrogen products, and catalyst reusability. Full article

The target (1E,4E)-1,5-bis(2,4-dichlorophenyl)penta-1,4-dien-3-one oxime 4 was prepared in good yield, as a key aza-precursor for the Nazarov cyclization, through a two-step sequence in this study. Initially, the starting divinyl ketone 1a was obtained via a Claisen–Schmidt condensation reaction between 2,4-dichlorobenzaldehyde 3 and acetone in the presence of aqueous 20% NaOH. Subsequently, treating 1a with hydroxylamine hydrochloride under thermal conditions resulted in the expected oxime in excellent yield, and its structure was confirmed by analytic and spectroscopic techniques. 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

The isoxazole-5-one ring system is a central structure in many synthetic bioactive molecules, showing a wide range of biological activities, including antibacterial, antitumor, anticorrosion, antifungal, antituberculosis, and antioxidant. They are also applied as agrochemicals with potential fungicidal effects. Given various applications, these pharmaceutically and biologically significant heterocyclic compounds have attracted the attention of chemistry researchers. This study aimed to investigate the application of glycerol as a reaction medium for the three-component synthesis of arylidenisoxazol-5(4H)-one derivatives. The results of the optimized investigations revealed that 3.0 mL of glycerol is the best reaction medium. Evaluation of the effect of reaction temperature showed that the best temperature for this strategy is 60 °C. In the present environmentally friendly study, the desired heterocyclic compounds were quickly synthesized via a one-pot three-component reaction of two keto-esters with hydroxylamine hydrochloride and a number of aryl/heteroaryl aldehydes. This synthetic approach has significant merits, such as cost-effectiveness of the reaction medium, rapid green synthesis, operational simplicity, easy workup, avoiding chromatographic purification, sustainability, acceptable yields, and relatively inexpensive as well as commercially available starting materials. Full article

Constructed wetlands (CWs) are widely used for wastewater treatment but can also serve as significant sources of nitrous oxide (N₂O), a potent greenhouse gas. Balancing efficient nitrogen removal with N₂O mitigation remains a critical challenge for sustainable wastewater management. This review systematically elucidates the key microbial mechanisms underlying N₂O emissions in CWs and summarizes corresponding mitigation strategies. Mechanistically, N₂O production is primarily driven by hydroxylamine oxidation and nitrifier denitrification mediated by ammonia-oxidizing microorganisms, as well as incomplete heterotrophic denitrification resulting from electron-donor limitation. These pathways are tightly regulated by spatiotemporal redox gradients, carbon-to-nitrogen ratios, and influent strength conditions. To address these emissions, this review synthesizes mitigation strategies from an engineering perspective. Optimization of operational parameters, such as intermittent aeration and water-level regulation, together with the application of novel functional substrates, such as biochar and iron-carbon micro-electrolysis, can effectively facilitate electron transfer and improve micro-redox conditions. Furthermore, optimized plant species selection and community design, along with emerging low-carbon biological nitrogen removal processes, such as autotrophic denitrification and partial denitrification coupled with anammox, offer promising approaches for substantial emission reduction. Overall, this review provides practical guidance for designing efficient, low-carbon CWs toward carbon neutrality. Full article

Nitrous oxide (N₂O) is a major greenhouse gas, and terrestrial ecosystems are among the primary sources of its emissions. Biochar is recognized as an effective soil amendment for mitigating N₂O emissions, but its long-term residual effects and microbial mechanisms in subtropical plantations remain unclear. Therefore, this study evaluated the residual effects of Eucalyptus-derived biochar on soil N₂O emissions six years after a single application and explored associations with nitrogen cycle functional genes. A field experiment was conducted in a Eucalyptus plantation in northern Guangxi with biochar applied at six rates (0–6% w/w). Soil N₂O fluxes were measured in the fifth and sixth years (2022–2023); soil chemical parameters, soil enzyme activities, and N₂O-related microbial functional genes (amoA, nirK, nirS and nosZ) abundance were analyzed. Biochar application significantly reduced ammonium nitrogen content but enhanced nitrate nitrogen content. Urease, protease, and sucrase activities increased, while nitrate reductase, nitrite reductase, and hydroxylamine reductase activities decreased. Furthermore, quantitative analysis revealed substantial variations in functional gene abundances. The abundance of ammonia-oxidizing archaea (AOA-amoA) exhibited a unimodal response, whereas ammonia-oxidizing bacteria (AOB-amoA) showed a robust dose-dependent accumulation. Notably, annual N₂O emissions were suppressed by up to 35.2%, driven by a 3.4-fold increase in nosZ gene abundance and a significant reduction in the (nirK + nirS)/nosZ ratio. This mitigation was attributed to enhanced N₂O consumption by nosZ-harboring denitrifiers and reduced heterotrophic ammonia oxidation. Overall, these findings highlight the pivotal role of long-term organic amendments in steering nitrogen transformation pathways, providing a theoretical basis for sustainable soil management in subtropical plantations. Full article

A new series of isoxazole-fused thiazole–oxazole derivatives (11a–n) was rationally designed and synthesised with the aim of developing potent carbonic anhydrase (CA) I and II inhibitors. The synthesis was achieved in five steps starting from 4-bromoacetophenone, involving key intermediates such as hydroxylamine hydrochloride, hydrazine hydrate, thioisocyanate, and various phenacyl bromide derivatives, using ethanol, triethylamine, tetrahydrofuran (THF), and dimethylformamide (DMF) as solvents. The synthetic route included the formation of a β-ketoester, isoxazole ester, hydrazine adduct, thiourea derivative, and, ultimately, a thiazole ring. The structures of the final compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR spectroscopy, and elemental analysis. All compounds were examined as inhibitors of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibited hCA I and hCA II in a non-competitive manner. To further explore the molecular basis of their inhibitory activity, in silico studies, including molecular docking and 300 ns molecular dynamics (MD) simulations, were carried out against both CA I and CA II isoforms. These simulations provided detailed insights into the dynamic behaviour, stability, and key binding interactions of the compounds within the enzyme active sites, supporting their potential as promising carbonic anhydrase inhibitors. Full article

Heavy metal contamination in soil and the resulting groundwater pollution are common at many brownfield sites. Soil washing, which dissolves contaminants into a washing solution to separate them from the soil matrix, has emerged as a promising remediation strategy. This study assessed the feasibility of applying soil washing to Pb-contaminated soil collected from an industrial area within the Trieste Port Authority (Italy) through a series of leaching tests. Batch tests were conducted using ethylenediaminetetraacetic acid (EDTA)-based extractants combined with various reducing agents to identify the most effective and environmentally sustainable washing solution. The results show that coupling EDTA with hydroxylamine hydrochloride or sodium dithionite significantly enhanced Pb solubilisation compared with EDTA alone, with dithionite emerging as the most suitable reducing agent due to its lower toxicity and reduced environmental impact. Sequential extraction tests revealed that up to 50% of total Pb could be removed after repeated washing cycles. Column leaching tests further confirmed the high efficiency of the EDTA–sodium dithionite system, achieving Pb removal rates of approximately 70% under continuous flow conditions. Overall, the results demonstrate that EDTA combined with low-dose sodium dithionite provides an effective and practical remediation strategy for heavily polluted industrial soils. Full article

The synthesis of hydroxamic acids from sterically hindered substrates, such as abietane-type resin acids, remains a synthetic challenge due to the congestion of the tricyclic skeleton. This study reports an efficient one-pot protocol for the direct conversion of abietic and dehydroabietic acids into their corresponding hydroxamic derivatives, achieving 65% and 74% isolated yields, respectively. Systematic screening of activating agents identified diethyl chlorophosphate (DCP) as the reagent for the hydroxyamidation. A critical finding of this work is that the optimization of the isolation process specifically minimizing the water amount during aqueous work-up was key to recovering these polar products and preventing important yield loss. The reaction proceeds through diethyl phosphate mixed anhydride intermediate, which was successfully isolated, providing direct experimental evidence of the activation pathway. The reaction mechanism was further elucidated using Density Functional Theory (DFT) calculations at the M062X/6-31G** level, identifying a concerted transition state for the simultaneous addition of hydroxylamine and expulsion of the phosphate group. Furthermore, the study rationalizes the observed chemoselectivity; although the ester is the more stable thermodynamic product, the formation of the N-hydroxy amide is kinetically favored through a substantially lower activation barrier. This combined experimental and theoretical approach establishes a practical and scalable methodology for the functionalization of abundant similar natural terpenoids. Full article

Alkyn-1,2-diones have gained great attention as useful building blocks in organic synthesis. Regioselective synthetic routes towards 3,5-disubstituted isoxazoles, containing the methylfuroyl or diterpenylfuroyl moiety at the C-3 or C-5 position from alkyne-1,2-diones 1, 2, 3, are reported. The reaction with hydroxylamine hydrochloride 6 in ethanol afforded the 1,2-addition products: 5-aryl-3-(methylfuran-2-carbonyl)isoxazoles (yield 61–94%) or 16-(5-arylisoxazole-3-carbonyl)labdatrienes (yield 48–97%). The reaction of alkynediones 1–3 with 6 in THF in the presence of triethylamine led to 5-hydroxy-4,5-dihydroisoxazoles and subsequent dehydration afforded regioisomeric 3-aryl-5-(methylfuran-2-carbonyl)isoxazoles or 16-(3-arylisoxazole-5-carbonyl)labda-trienes (yield 65–98%). New heterocyclic compounds exhibited significant analgesic action in acetic acid writhing and hot-plate tests, and the activity was comparable to reference drugs diclofenac sodium and celecoxib. Isoxazoles, which possessed the most analgesic activity, reduced the concanavalin A-induced inflammation by 34–51%; the effect was comparable to the drug indomethacin. The results of in vitro biological assays (MTT test) revealed that isoxazoles were non-toxic against the normal epithelial VERO cells, and 16-(3-aryl-5-hydroxyisoxazoline-5-carbonyl)labdatrienes 20–24 exhibited selective cytotoxicity against the breast adenocarcinoma MCF 7 (GI₅₀ = 4.7–8.3 μM) and cervical cancer cells C33 A (GI₅₀ = 3.4–4.7 μM). Molecular docking analysis to determine the binding potential of new molecules to the active site of human COX-1 and COX-2 enzymes was conducted. Full article

Achieving stable partial nitritation (PN) in mainstream municipal wastewater treatment is critical for energy-efficient anammox-based nitrogen removal. However, selectively suppressing nitrite-oxidizing bacteria (NOB) while retaining ammonia-oxidizing bacteria (AOB) remains challenging. This study investigated the performance and microbial mechanisms of PN in a membrane-aerated biofilm reactor (MABR) under zero-pressure aeration. The results showed that zero-pressure aeration achieved a nitrite accumulation ratio (NAR) of 82.14%, significantly higher than that under constant aeration (13.2%) and intermittent aeration (53.5%). Zero-pressure aeration led to a significant increase in the fluorescence intensities of tyrosine/tryptophan protein in extracellular polymeric substances. 16S rRNA sequencing revealed that zero-pressure aeration achieved a modest reduction in the relative abundance of NOB Nitrospira from 3.39% to 2.74% while increasing the relative abundance of AOB Nitrosomonas from 0.04% to 1.09%. Enzyme activity assays further showed that zero-pressure aeration significantly decreased nitrite oxidoreductase (NXR) activity while maintaining ammonia monooxygenase (AMO) and hydroxylamine oxidoreductase (HAO) activities, providing direct functional evidence for NOB suppression. Zero-pressure operation required no external air supply, representing a passive aeration strategy for PN. These results suggest that zero-pressure aeration may reshape the competition between AOB and NOB by enriching AOB and suppressing NOB, providing a new energy-efficient pathway for mainstream nitrogen removal. Full article

Hydroxylamine-modified transition-metal oxides (HA-TMOs) represent a promising class of catalysts for activating peroxymonosulfate (PMS) to degrade antibiotics. However, identifying energy-efficient operational conditions remains challenging. This study established a comprehensive dataset encompassing 600 experimental records from both in-house experiments and literature and systematically compared 12 machine learning algorithms for predicting the antibiotic degradation efficiency (%) in hydroxylamine-modified transition metal oxide/peroxymonosulfate (HA-TMO/PMS) systems. Among these models, CatBoost delivered the best generalization (test-set R² = 0.8110, RMSE = 8.92, MAE = 6.15) across repeated 80/20 stratified splits with 5-fold cross-validation, outperforming other ensembles as confirmed by cumulative distribution plots and error-metric analyses. Moreover, the permutation importance analysis identified PMS dosage, HA level, pH, initial pollutant concentration, and catalyst loading as the dominant drivers governing the pollutant removal performance. The partial-dependence plots, incorporating two-variable interactions, elucidated the response surfaces and enabled the discovery of operating windows that jointly maximize degradation efficiency and minimize electrical energy per order (EE/O). ML-guided optimization yielded optimal conditions, which were experimentally verified with sulfamethoxazole (SMZ). The HA-Co₃O₄/PMS system achieved the highest degradation rate constant (k = 0.11 min⁻¹) and the lowest EE/O value (6.84 kWh·m⁻³·order⁻¹), markedly improving kinetics and reducing energy consumption compared with non-optimized runs. This work establishes an interpretable ML framework that connects catalyst properties and reaction conditions to degradation kinetics and mechanisms, providing a practical strategy for the screening and scale-up of energy-efficient HA-TMOs/PMS-based advanced oxidation processes (AOPs). Full article

The novel strain TD-94 with higher ammonia degradation efficiency was isolated from the activated sludge of SINOPEC and belongs to the family of Alcaligenes faecalis (A. faecalis) based on its 16sRNA sequence and physio-biochemical characteristics. It is a Gram-negative, highly heterotrophic aerobic ammoxidation bacterium that is capable of effectively treating ammonia-nitrogen wastewater. The genome size of strain TD-94 was 4,361,949 bp with a GC content of 56.47% and a total of 4101 genes, which accounted for 89.54% of the total genome length. Analysis of various databases showed that 649 genes were annotated in the GO database; a total of 2712, 4095 and 12 genes were annotated in the KEGG, COG, and ADRB databases, respectively; and there were 24 types of cytochrome P450, 477 signal peptides, and eight secondary metabolites. All these data provide a theoretical basis for the mechanism of action of the strain TD-94. Based on the whole-genome sequencing results, functional genes related to nitrogen metabolism in A. faecalis TD-94, including aerobic ammonia oxidation (AOB), hydroxylamine oxidoreductase (HAO), and pyruvic oxime dioxygenase (POD) were identified. Through growth curve analysis and the identification of functional genes, the nitrogen metabolism pathway of A. faecalis TD-94 was proposed, demonstrating that the strain TD-94 has good denitrification capabilities and a novel degradative pathway. Full article