Oxidative Hydroxylation Research Articles

CoOOH nanoflake as supporter of CRISPR-Cas12a system for facilitated imaging of miRNA-21 in cells

The aberrant expression of miRNA-21 in cells is frequently associated with the occurrence and metastasis of tumors. The CRISPR-cas12a system has been developed for in vitro detection of miRNA due to its distinctive signal amplification characteristics. But its intricate composition and challenges in cellular delivery have limited its application in cell imaging. In this study, we designed an electrostatic adsorption-based probe by combining positively charged cobalt hydroxyl oxide (CoOOH) nanoflakes with negatively charged CRISPR-cas12a system which allows for detection and intracellular imaging of miRNA-21. This method involves using ascorbic acid to reduce CoOOH nanoflakes into Co2+, which subsequently releases the active form of CRISPR-Cas12 for detecting miRNA-21. The probe has a linear detection range for miRNA-21 from 0.5 pM-50 pM and 100 pM-20 nM, with a detection limit of 0.32 pM. It also shows good selectivity, accuracy, good reproducibility and biocompatibility for miRNA-21 analysis. In subsequent cell experiments, the probe exhibits low cytotoxicity and remarkable cell imaging capabilities. Therefore, this probe offers an innovative approach for miRNA-21 analysis.

Finerenone: A Novel Drug Discovery for the Treatment of Chronic Kidney Disease.

The most common cause of chronic kidney disease (CKD) is diabetic nephropathy (DN). Primarilymineralocorticoid receptor antagonists (MRAs) (spironolactone and eplerenone), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were used for the treatment of CKD, but due to the high risk of hyperkalaemia, the combination was infrequently used. Currently after approval by FDA in 2021, finerenone was found to be effective in the treatment of CKD. Finerenone slowdowns the progression of diabetic nephropathy and lessens the cardiovascular morbidity in DN patients. The main objective of this review article is to provide a comprehensive and insightful overview of the role of finerenone by mainly focusing on its pharmacological properties, toxicity, uses, bioanalytical technique used for determination, and treatment options. Finerenone works by inhibiting the action of the mineralocorticoid receptor. Finerenone is quickly absorbed from the digestive tract after oral treatment and achieves peak plasma concentrations in 1-2 hours. Finerenone is actively metabolized through oxidation, epoxidation substitution, and direct hydroxylation. Elimination of finerenone is done through urine and feces. Determination of finerenone can be done through HPLC-MS and LSC. The present review covers the complete picture of ADME properties, bioanalytical techniques, clinical trials, toxicity, and possible avenues in this arena. Finerenone is effective compared to other mineralocorticoid receptor-like spironolactone and eplerenone, for the treatment of chronic kidney disease.

Regulating the Twisted Intramolecular Charge Transfer and Anti-heavy Atom Effect at Supramolecular Level for Favorable Photosensitizing Activity in Water.

Photosensitizing assemblies based on twisted intramolecular charge transfer (TICT) active donor-acceptor-donor (D-A-D) system BrTPA-Qx having bromine atoms at the periphery have been developed. Through strategic incorporation of bromine atoms at the para-position to the nitrogen-carbon bonds of phenyl rings at the periphery, halogen-halogen interactions are induced in BrTPA-Qx nanoassemblies in H2O:DMSO (99:1) solution. Hence, the anti-heavy atom effect is induced, and the limitations of TICT (dark excited state) and heavy atom effect (triplet deactivation via radiative decay) could be overcome. Because of TICT and anti-heavy atom effect, supramolecular BrTPA-Qx nanoassemblies demonstrate high efficiency in promoting activation of aerial oxygen via electron and energy transfer pathways in aqueous media. The significant influence of the stabilized TICT state and anti-heavy-atom effect in controlling the ROS generation was validated through in-depth solvent-dependent photophysical studies and investigations of the structure-activity relationship in several model compounds. The notable photosensitizing activity of BrTPA-Qx nanoassemblies is manifested in their ability to efficiently catalyze the oxidative coupling of benzylamine (via type I and type II mechanisms), Knoevenagel condensation of aromatic aldehydes (type II), and oxidative hydroxylation of arylboronic acids (type I) under mild conditions.

Hydroxyl radical oxidation of chemical contaminants on indoor surfaces and dust

Humans are widely exposed to semivolatile organic contaminants in indoor environments. Many contaminants have long lifetimes following partitioning to the large surface reservoirs present indoors, which leads to long exposure times to gas-phase oxidants and multiphase chemistry. Studies have shown selective multiphase oxidation of organics on indoor surfaces, but the presence of hydroxyl radicals with nonselective reactivity and evidence of multiphase OH radical reactivity toward common indoor contaminants indicates that there may be additional unknown transformation chemistry indoors. We screened genuine indoor samples for 60 OH radical oxidation products of the common plasticizer and endocrine-disrupting contaminant bis(2-ethylhexyl) phthalate (DEHP) identified in laboratory experiments using nontargeted high-resolution mass spectrometry. At least 30 and 10 of these products are observed in indoor dust and DEHP films exposed to ambient indoor conditions, respectively, indicating that multiphase OH reactions occur indoors. Using the PROTEX model and a multimedia indoor chemical fate model, we demonstrate that these products have long indoor lifetimes and cause a higher potential for human exposure than DEHP. Some of these products are more active endocrine disruptors than DEHP itself, but most have unknown toxicities. Coexposure to all oxidation products will likely have an additive effect, leading to higher human health risks from indoor organic contaminants than previously thought. Due to the nonselective reactivity of OH radicals, it is likely that most indoor contaminants follow similar chemistry, and further study is needed to understand the prevalence and human health implications of such multiphase chemistry.

Homojunction-Incorporated Oxygen Vacancy Functionalized Spherical TiO2 Nanocrystals for the Electrochemical Detection of Chemical Oxygen Demand.

Chemical oxygen demand (COD) is a critical criterion for the analytical assessment of the degree of organic contaminants in an aqueous system. Typically, toxic and expensive reagents are employed in standardized COD analysis methods, leading to secondary pollution. In this work, we developed a rapid electrochemical method for COD detection based on the oxidation of hydroxyl radicals for organics in water by using oxygen vacancy doped anatase/rutile-TiO2 nanoparticles as electrooxidation catalysts. Homojunction interface generated increasing oxygen vacancies for enhancing electron-transfer rate and accelerating H2O oxidation to substantially improve ·OH yield. Oxygen vacancy further increased the oxygen evolution potential of the material. Initially, glucose was chosen as a standard analyte to evaluate electrochemical responses, and water from urban wastewater treatment plants was assessed as real samples subsequently. Excellent analytical characteristics were achieved with the A/R-TiO2 sensor under the optimal conditions, exhibiting a linear range from 1 to 300 mg L-1 and detection limit of 0.1 mg L-1 COD. The estimated COD values obtained from the samples were highly consistent with those determined using the conventional standard dichromate method. We have presented a fast, cost-effective, and ecologically sustainable method that outperforms the standard COD analysis method and holds great potential for the accurate determination of COD and boasts high detection sensitivity and a broad linear range.

Manipulating Pt-ZnO interface for fast selective oxidation of glycerol to glyceric acid in base-free medium

Fine constructing the desirable active sites of catalysts is critical for the efficient polyol oxidation. Herein, we conceptually manipulate the Pt-ZnO interfacial active site instead of traditional Pt-Pt active site to isolate oxidation reaction and carboxylic acid desorption for fast selective oxidation of glycerol to glyceric acid in base-free medium. Multiple characterizations (including in-situ spectroscopy, reaction kinetics and density functional theory calculation, etc.) revealed that the strong electronic delocalization of Pt d-partial and the synergistic effect of ZnO adsorption could collectively strengthen the adsorption of glycerol and then promote the C-H bond of RCH2O intermediate in the primary hydroxyl group oxidation, resulting in higher catalytic activity over the Pt-ZnO interface. Meanwhile, the abundant oxygen vacancy of well-dispersed nano-ZnO could preferentially adsorb the formed glyceric acid product, preventing the coverage of the efficient Pt-Pt and Pt-O-Zn active sites by carboxylic acid products. Such tailored interface strategy achieves 80.4 % glycerol conversion and 84.6 % glyceric acid selectivity in only 1 h, and the turnover frequency could also be as high as 1338.4 h−1 over the optimal Pt/ZnO-MCM-41 (200) catalyst. The methodology provided here constitutes a promising basis for highly efficient polyol oxidation catalysis under mild and green conditions.

OH Radical Oxidation of Organosulfates in the Atmospheric Aqueous Phase.

Organosulfates (OS, ROSO3-), ubiquitous constituents of atmospheric particulate matter (PM), influence both the physicochemical and climatic properties of PM. Although the formation pathways of OS have been extensively researched, only a few studies have investigated the atmospheric fate of this class of compounds. Here, to better understand the reactivity and transformation of OS under cloudwater- and aerosol-relevant conditions, we investigate the hydroxyl radical (OH) oxidation bimolecular rate constants (kOS+OHII) and products of five atmospherically relevant OS as a function of pH and ionic strength: methyl sulfate (MeS), ethyl sulfate (EtS), propyl sulfate (PrS), hydroxyacetone sulfate (HaS) and phenyl sulfate (PhS). Our results show that OS are oxidized by OH with kOS+OHII between 108 - 109 M-1 s-1, which corresponds to atmospheric lifetimes of minutes in aqueous aerosol to days in cloudwater. We find that kOS+OHII increases with carbon chain length (MeS < EtS < PrS) and aromaticity (PrS < PhS), but does not depend on solution pH (2, 9). In addition, we find that whereas the OH reactivity of the aliphatic OS studied here decreases by ∼2× with increasing ionic strength (0-15 M), the reactivity of PhS decreases by ∼10×. The oxidation of EtS and PrS produced organic peroxides (ROOH) as first-generation oxidation products, which subsequently photolyzed; the oxidation of PhS resulted in hydroxylated aromatic products. These results highlight the need for inclusion of OS loss pathways in atmospheric models, and suggest caution in using ambient OS concentration measurements alone to estimate their production rates.

Characterization of the Flavin-Dependent Monooxygenase Involved in the Biosynthesis of the Nocardiosis-Associated Polyketide†.

Some species of the Nocardia genus harbor a highly conserved biosynthetic gene cluster designated as the NOCardiosis-Associated Polyketide (NOCAP) synthase that produces a unique glycolipid natural product. The NOCAP glycolipid is composed of a fully substituted benzaldehyde headgroup linked to a polyfunctional alkyl tail and an O-linked disaccharide composed of 3-α-epimycarose and 2-O-methyl-α-rhamnose. Incorporation of the disaccharide unit is preceded by a critical step involving hydroxylation by NocapM, a flavin monooxygenase. In this study, we employed biochemical, spectroscopic, and kinetic analyses to explore the substrate scope of NocapM. Our findings indicate that NocapM catalyzes hydroxylation of diverse aromatic substrates, although the observed coupling between NADPH oxidation and substrate hydroxylation varies widely from substrate to substrate. Our in-depth biochemical characterization of NocapM provides a solid foundation for future mechanistic studies of this enzyme as well as its utilization as a practical biocatalyst.

Compatibility and stability of ademetionine 1,4-butanedisulfonate injection mixed with fructose and glucose diluents and pilot study of long-term storage impurities by LC-MS/MS

Fructose injection is occasionally used to dilute ademetionine 1,4-butanedisulfonate injection for patients who cannot receive glucose or sodium chloride injections in clinical settings. Since our PIVAS staff reported that discoloration occurred after ademetionine 1,4-butanedisulfonate dissolved with fructose injection, this study aims to investigate the stability of ademetionine 1,4-butanedisulfonate in fructose and glucose solutions. Ademetionine 1,4-butanedisulfonate was purchased and diluted with fructose or glucose injection for compatibility testing. The solutions were maintained under various conditions for different periods of time, after which the concentration of ademetionine 1,4-butanedisulfonate and other impurities was analyzed. The chemical structures of unknown impurities were further investigated by liquid chromatography-tandem mass spectrometry. The analytical method was validated and was deemed to be suitable for the analyses in this study. Compatibility tests indicated that ademetionine 1,4-butanedisulfonate is sensitive to temperature, illumination, and pH. When diluted with fructose or glucose, the concentration of ademetionine 1,4-butanedisulfonate decreased over time. The contents of impurities increased accordingly. Additionally, an unknown impurity was identified, speculated to be a hydroxyl oxidation product of ademetionine based on the LC-MS/MS results. Both fructose and glucose injections can be used as diluents for ademetionine 1,4-butanedisulfonate, and the resulting mixture remains stable for up to 8 h after preparation.

The Characteristics Analysis of Hyaluronic Acid Modified By Cold Atmospheric Plasma and Its Performance in Hydrogel Preparation

ABSTRACTHyaluronic acid (HA) is extensively utilized in biomedical applications, and its functionality can be enhanced by introducing aldehyde groups (─CHO) through oxidation. In this study, cold atmospheric plasma (CAP) was used to treat aqueous HA solutions, resulting in the formation of plasma‐modified HA (PMHA) containing ─CHO groups. The free radicals generated from interactions between water molecules and CAP particles reacted with HA, leading to the oxidation of hydroxyl groups into ─CHO and the cleavage of glycosidic bonds, causing molecular depolymerization. The PMHA was then used to synthesize hydrogels in combination with carboxymethyl chitosan and ɛ‐polylysine. This study presents an effective approach for generating HA with aldehyde functionalities and offers insights into the interaction between CAP and polysaccharides.

The surface electron transfer strategy promotes the hole of PDI release and enhances emerging organic pollutant degradation

In semiconductor photocatalysts, the easy recombination of photogenerated carriers seriously affects the application of photocatalytic materials in water treatment. To solve the serious problem of electron−hole pair recombination in perylene diimide (PDI) organic semiconductors, we loaded ferric hydroxyl oxide (FeOOH) on PDI materials, successfully prepared novel FeOOH@PDI photocatalytic materials, and constructed a photo-Fenton system. The system was able to achieve highly efficient degradation of BPA under visible light, with a degradation rate of 0.112 min−1 that was 20 times higher than the PDI system, and it also showed universal degradation performances for a variety of emerging organic pollutants and anti-interference ability. The mechanism research revealed that the FeOOH has the electron trapping property, which can capture the photogenerated electrons on the surface of PDI, effectively reducing the compounding rate of photogenerated carriers of PDI and accelerating the iron cycling and H2O2 activation on the surface of FeOOH at the same time. This work provides new insights and methods for solving the problem of easy recombination of carriers in semiconductor photocatalysts and degrading emerging organic pollutants.

Fibrous catalyst based on atomic Pd and N-doped holey graphene functionalized cotton fiber for continuous-flow reaction

Continuous-flow catalysis bridges the gap between bench-scale laboratories and production-scale factories and thus should be a green and promising technology for the manufacture of value-added chemicals. Here, we present the construction of a continuous-flow catalytic system by integrating a tubular reactor with novel catalytic fibers, which are comprised of single-atomic Pd (Pd1) and nitrogen-doped holey graphene (NHG) functionalized cotton fibers (CFs). Due to the loosely packed structure, highly exposed dual-active sites (i.e., single-atomic PdN4 sites and activated C sites in the NHG carbocatalyst) of the CF@(Pd1/NHG) catalytic fibers, the corresponding flowing system exhibites remarkably high catalytic performance (activity and durability) and processing rate in organic reactions, including oxidative hydroxylation of phenylboronic acid and reduction of nitroarenes. Typically, the processing rate of the catalytic system toward 4-nitrophenol (a representative nitroarene) reduction can reach up to 2.46 × 10−3 mmol·mg−1·min−1, significantly higher than that of those packing catalysts reported in recent years.

Electrochemical oxidation of bisphenol A with a Fe-N-C/persulfate three-dimensional electrochemical system

In this study, an effective three-dimensional (3D) electrochemical system based on persulfate was developed, utilizing Fe-N-C compostie as the particle electrodes, and its electrocatalytic performance for the oxidation of bisphenol A was evaluated. With the synergetic effect of Fe-N-C catalyst and electric current, peroxydisulfate is activated to generate highly oxidative sulfate radicals (SO4•−) and hydroxyl radicals (•OH), and the •OH playing a leading role in the oxidation of BPA. In this process, the redox cycle of Fe2+/Fe3+ acts as the main catalytic active center to produce SO4•−, •OH and O2•−, while pyridine N and graphite carbon cooperate to catalyze the formation of 1O2 and promote direct electron transfer, with their reduction by 37.19 % and 3.34 %, respectively, highlighting their crucial role in these processes. During the degradation of bisphenol A, coupling polymerization occurred at the same time, which may be due to the stabilization and instantaneous resonance of the intermediate on the surface of the catalyst caused by direct electron transfer, which induced the polymerization of oxide intermediate. 1O2 not only oxidizes BPA into low molecular weight products, but also extracts hydrogen atoms to form phenoxy free radicals. The coupling of these free radicals promotes the formation of macromolecular polymers and separation from water. This parallel treatment mechanism of degradation and polymerization effectively reduces the emission of CO2 and the mineralization of organic matter. Based on the above findings, the E/PDS/Fe-N-C system has broad potential in the treatment of environmental pollutants.

Fluoropyridine modulated local charge distribution of carbon nitride to facilitate photocatalytic oxidative γ-valerolactone production

Synthesis of γ-valerolactone (GVL) from renewable biomass resources under mild reaction condition with metal-free catalysis is attractive but challenging. Herein, a novel porous fluoropyridine-incorporated carbon nitride (FPCN) was constructed and applied for photocatalytic oxidation of biomass-based 5-methyltetrahydrofurfural alcohol (5-MTHFA) to GVL. The catalyst exhibits excellent photocatalytic activity (93% 5-MTHFA conversion), with an 81% GVL yield, which is significantly higher than that of pyridine-incorporated carbon nitride and pure g-C3N4. Catalyst characterization and density functional theory (DFT) calculations showed that the porous structure of FPCN provides more exposed active sites for catalytic reaction, and the incorporated fluoropyridine rings effectively modulate the localization of electron cloud density, resulting in an enhanced photogenarated carrier separation efficiency and adsorption capacity for 5-MTHFA. Mechanistic studies reveal that photocatalytic oxidation process of 5-MTHFA mainly involves hydroxyl group oxidation and decarboxylation. This work provides new insight into designing carbon nitride-based photocatalysts for the efficient selective oxidation of renewable biomass to produce fine chemicals.

Heterogenization of Homogeneous Donor-Acceptor Conjugated Polymers for Efficient Photooxidation: An Approach Toward Sustainable and Recyclable Photocatalysis.

Recovery of homogeneous photocatalysts from reaction mixture is challenging, affecting the cost-effectiveness, and masks their advantages, including 4-8 fold higher catalytic activity than corresponding heterogeneous counterparts. Incorporation of long alkyl chains within the rigid π-conjugated backbone of conjugated polymers can augment their solubility in particular organic solvents; accordingly, they can function as homogeneous photocatalysts. Consequently, these polymers facilitate the recovery of catalysts through the reverse dissolution process, thus creating a well-suited platform to meet certain advantages of both homo- and heterogeneous photocatalysts. This work exemplifies the unprecedented perks of donor-acceptor conjugated polymers from benzodithiophene and substituted dibenzothiophene sulfone moieties for their homogeneous phase photoredox activities along with their heterogeneous recovery and reuse up to five runs. The potential intermediate singlet oxygen (1O2) and superoxide (O2•-) as reactive oxygen species generated by these photostable conjugated polymers efficiently catalyze the visible-light-driven oxidation of aryl sulfides (up to 92% yield) and oxidative hydroxylation of phenylboronic acids (up to 93% yield), respectively. Therefore, to actualize the heightened catalytic performance and formulate a design strategy for polymeric photoredox catalyst, our work introduces an alternative approach to the advancement of photocatalysis with diverse catalytic activities.

Investigation of the Influence of Copovidone Properties and Hot-Melt Extrusion Process on Level of Impurities, In Vitro Release, and Stability of an Amorphous Solid Dispersion Product.

Hot-melt extrusion (HME) is a widely used method for creating amorphous solid dispersions (ASDs) of poorly soluble drug substances, where the drug is molecularly dispersed in a solid polymer matrix. This study examines the impact of three different copovidone excipients, their reactive impurity levels, HME barrel temperature, and the distribution of colloidal silicon dioxide (SiO2) on impurity levels, stability, and drug release of ASDs and their tablets. Initial peroxide levels were higher in Kollidon VA 64 (KVA64) and Plasdone S630 (PS630) compared to Plasdone S630 Ultra (PS630U), leading to greater oxidative degradation of the drug in fresh ASD tablets. However, stability testing (50 °C, closed container, 50 °C/30% RH, open conditions) showed lower oxidative degradation impurities in ASD tablets prepared at higher barrel temperatures, likely due to greater peroxide degradation. Plasdone S630 is suitable for ASDs with drugs prone to oxidative degradation, while standard purity grades may benefit drugs susceptible to free radical degradation, as they generate fewer free radicals post-HME. ASD tablets exhibited greater physical stability than milled extrudate samples, likely due to reduced exposure to stability conditions within the tablet matrix. Including SiO2 in the extrudate composition resulted in greater physical stability of the ASD system in the tablet; however, it negatively affected chemical stability, promoting greater oxidative degradation and hydroxylation of the drug substance. No impact of the distribution of SiO2 on drug release was observed. The study also confirmed the congruent release of copovidone, the drug substance, and Tween 80 using flow NMR coupled with in-line UV/vis. This research highlights the critical roles of peroxide levels and SiO2 in influencing the dissolution and physical and chemical stability of ASDs. The findings provide valuable insights for developing stable and effective pharmaceutical formulations, emphasizing the importance of controlling reactive impurities and excipient characteristics in ASD products prepared by using HME.

In-situ atomic hydrogen generation: A key to elevating membrane cleaning via citric acid-modified Fenton-like system

Oxidation process has been widely used to clean irreversible membrane fouling, and the development of novel oxidative cleaning process has attracted worldwide attention. In this study, a novel cleaning process with the combination of sodium percarbonate (SPC), citric acid (CA), and ferrous ion (Fe(II)) was introduced to remove organic fouling derived from the complexation of humic acid (HA) and calcium ions (Ca2+) for the first time. Remarkably, both flux recovery and resistance removal could reach 99 % within one hour. The efficiency and durability of this novel cleaning system were confirmed through comprehensive characterization and cyclic cleaning test of the ultrafiltration membranes. Furthermore, it effectively removed various natural organic matter-induced fouling and performed well in long-term experiments. This outstanding performance is due to the synergy between oxidative hydroxyl radicals (HO) and reductive atomic hydrogen (H*) in SPC/CA/Fe(II). Analysis of intermediate/final products confirmed that H* is generated through the reaction of CA and HO and absorbed by HA. Confocal laser scanning microscopy (CLSM) revealed that this absorption makes HA more susceptible to HO attack, resulting in enhanced cleaning performance. This mechanism demonstrates the potential of advanced reduction–oxidation systems for membrane cleaning, offering new insights for the development of novel cleaning methods.

Bifunctional 0D carbon quantum dot cathode electrocatalyst coupled with atomic hydrogen and hydroxyl radicals for efficient removal of oxytetracycline hydrochloride

Efficient removal of antibiotics is difficult to achieve by conventional single-oxidation or reduction processes. Herein, a bifunctional cathodic electrocatalyst coupling atomic hydrogen (H*) reduction with hydroxyl radical (·OH) oxidation in an efficient electrocatalytic process was developed for the effective degradation of oxytetracycline hydrochloride (OTC). Pd particles were dispersed on B-doped carbon quantum dots to prepare a Pd-B-doped carbon quantum dots/titanium (Pd-BCQD/Ti) electrode as a bifunctional cathode catalyst. The electrode can simultaneously generate H* through the H2O/H+ reduction process, H2O2 through the oxygen reduction process, and then generate ·OH. H* performs nucleophilic hydrogenation reduction of OTC molecules, and ·OH performs electrophilic oxidation of the carbon skeleton, and both act synergistically with the active chlorine species (HClO) generated at the anode. The experimental results showed that the electrode achieved 90.50 % removal of OTC within 60 min. In addition, the Pd-BCQD/Ti electrode reduces energy consumption while increasing current efficiency. The degradation effect was more than 85.80 % in the pH range of 3∼9, indicating fairly stable catalytic activity over a wide pH range. The degradation efficiency was basically unchanged after ten cycles, and the reactivity was still high in the actual water. Intermediates were analyzed based on LC-MS to explore the degradation pathways of OTC. The toxicity of the intermediates generated during OTC degradation was predicted based on quantitative conformational relationships. This study provides a feasible strategy for the preparation of bifunctional catalysts based on zero-dimensional BCQD for efficient green antibiotic wastewater treatment.

Molecular weight fraction-specific transformation of natural organic matter during hydroxyl radical and sulfate radical oxidation

Aquatic natural organic matter (NOM) is one of the main scavengers of reactive species (e.g., •OH and SO4•−) during oxidation processes and undergoes complex transformations. Here, the organic content, optical properties, and redox state in various MW fractions and bulk Suwannee River NOM (SRNOM) were simultaneously evaluated during •OH and SO4•− oxidation processes for the first time. The SRNOM transformation pathways were specific to radical species and MW fractions, which was evidenced by a proportional decrease in electron-donating moieties and chromophores during •OH oxidation but a higher decrease in electron-donating moieties than chromophores during SO4•− oxidation, particularly in lower MW fractions (<3 kDa). The •OH decomposed reactive moieties mainly via aromatic ring opening or depolymerization in all MW fractions. SO4•− oxidation followed a similar pathway in higher MW fractions (>3 kDa) but mainly formed compounds with UV-absorbing properties (e.g., quinones) in lower MW fractions (<3 kDa). With competitive kinetics and depolymerization model, •OH was quantified as approximately 10 times more reactive towards MW fractions than SO4•−. However, the SO4•− concentrations were approximately 10 times those of •OH, resulting in comparable performance to •OH oxidation. SRNOM depolymerization by •OH and SO4•− resulted in formation of more precursors of disinfection byproducts than the parent constituents, especially for •OH. This work improves our understanding of the transformation of specific SRNOM fractions during radical oxidation processes.

CYP4CE1 Metabolized Nitenpyram through Two Types of Oxidation Reaction, Hydroxylation, and N-Demethylation.

Nitenpyram, taking the place of imidacloprid, is a widely used neonicotinoid insecticide to control Nilaparvata lugens in Asia. Two P450s, CYP4CE1 and CYP6ER1, are key factors in the metabolic resistance against nitenpyram and imidacloprid. In this study, we found that CYP4CE1 expression was strongly associated with nitenpyram resistance in 8 field-collected populations, whereas CYP6ER1 expression correlated with imidacloprid resistance. Hence, we focused on nitenpyram metabolism by CYP4CE1, due to that imidacloprid metabolism by CYP6ER1 has intensively investigated. Mass spectrometry analysis revealed that recombinant CYP4CE1 metabolized nitenpyram into three products, N-desmethyl nitenpyram, hydroxy-nitenpyram, and N-desmethyl hydroxy-nitenpyram, with a preference for hydroxylation. In contrast, CYP6ER1 metabolized nitenpyram into a single product, N-desmethyl nitenpyram. These results provide new insights into the specific catalytic mechanisms of P450 enzymes in neonicotinoid metabolism and underscore the importance of different catalytic reactions in neonicotinoid insecticide resistance.