Major Oxidation Products Research Articles

Enantioselectively generating imidazolone dIz by the chiral DNA intercalating and “light-switching” Ru(II) polypyridyl complex via a novel flash-quench method

The 2-aminoimidazolone is a major and ubiquitous in vitro product of guanine oxidation. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to study guanine oxidation on double helical DNA. Herein we found that imidazolone dIz (2-amino-5-[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-4H-imidazole-4-one) and dZ (2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone) were the major oxidation products of double-strand DNA from the visible-light irradiation of the well-known DNA intercalating and light-switching Ru(OP)2dppz2+ (OP = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2′,3′-c]phenazine) in the presence of a typical quencher methyl viologen (MV2+). Using ESR spin-trapping method, the radical intermediate MV•+ with typical hyperfine pattern was detected which indicated the successful formation of the corresponding Ru3+ intercalated oxidant. The formation of dIz and dZ decreased markedly with the addition of nitrotetrazolium blue chloride (NBT), a typical O2•- reactant. With a more specific and highly sensitive O2•- probe CT02-H, its ESR signal decayed rapidly in the presence of Ru(OP)2dppz2+ and MV2+, suggesting that O2•- was indeed produced. More interestingly, enantio-selective generation of oxidation products from dsDNA was observed with the two chiral forms of Ru(OP)2dppz2+. This represents the first report that the flash-quench technique with MV2+ as the quencher can oxidize dsDNA effectively to form dIz and dZ via the Ru3+/O2•- mediated mechanism. Our new findings provide a novel method to generate two radicals simultaneously, G (-H)• and O2•-, in close proximity to one another in dsDNA.

Analysis of glycerol bound ω-oxo-fatty acids as ω-dioxane-FAME-derivatives

ω-oxo-fatty acids, also known as aldehydic fatty acids, are major products of fatty acid oxidation and pose potential health risks. When bound to glycerol, ω-oxo-fatty acids (core aldehydes) can be ingested with food. Challenges in GC–MS quantification include the absence of an appropriate internal standard. Additionally, substantial analyte losses during sample preparation, caused by the high volatility of short-chain compounds, alter their pattern based on molecular weight. In this study, among various tested derivatization methods, the formation of ω-dioxane derivatives demonstrated improved recovery rates after three evaporation cycles. For methyl 7-oxo-heptanoate, recovery increased from 43 % to 88 %, while recovery rates for different chain lengths and a novel synthesized internal standard improved from a range of 43 %–76 % to 87 %–92 %. Additionally, ω-dioxane derivatives displayed favorable GC–MS behavior, enabling clear identification and increased sensitivity. Finally, ω-oxo-fatty acids were quantified as their ω-dioxane-derivatives in thermally treated sunflower and rapeseed oil.

A sensitive GC-MS/MS method for the quantification of benzo[a]pyrene tetrol in urine.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants formed during the incomplete combustion of organic matter such as tobacco. Among these, benzo[a]pyrene (BaP) has been classified as a known carcinogen to humans. It unfolds its effect through metabolic activation to BaP-(7R,8S)-diol-(9S,10R)-epoxide (BPDE), the ultimate carcinogen of BaP. In this article, we describe a simple and highly sensitive GC-NICI-MS/MS method for the quantification of urinary BaP-(7R,8S,9R,10S)-tetrol (( +)-BPT I-1), the hydrolysis product of BPDE. The method was validated and showed excellent results in terms of accuracy, precision, and sensitivity (lower limit of quantification (LLOQ): 50pg/L). In urine samples derived from users of tobacco/nicotine products and non-users, only consumption of combustible cigarettes was associated with a significant increase in BPT I-1 concentrations (0.023 ± 0.016nmol/mol creatinine, p < 0.001). Levels of users of potentially reduced-risk products as well as non-users were all below the LLOQ. In addition, the urine levels of six occupationally exposed workers were analyzed and showed the highest overall concentrations of BPT I-1 (844.2 ± 336.7pg/L). Moreover, comparison with concentrations of 3-hydroxybenzo[a]pyrene (3-OH-BaP), the major detoxification product of BaP oxidation, revealed higher levels of 3-OH-BaP than BPT I-1 in almost all study subjects. Despite the lower levels, BPT I-1 can provide more relevant information on an individual's cancers susceptibility since BPDE is generated by the metabolic activation of BaP. In conclusion, BPT I-1 is a suitable biomarker to distinguish not only cigarette smokers from non-smokers but also from users of potentially reduced-risk products.

SIMULATION OF THE KINETICS OF HETEROGENEOUS OXIDATION OF N-HEPTANE BY OXYGEN

The catalytic reaction of n-heptane (n-C7H16) oxidation with molecular oxygen has been studied. Various compositions of the polymer catalyst Mn-P4VP/MBAA (where Mn-P4VP is manganese-immobilised poly-4-vinylpyridine and MBAA is N,N′-methylene-bis-acrylamide) containing 2-5 wt% Mn were prepared and tested. The concentration of manganese in the catalyst based on immobilized metal-polymer complexes is within the range of 2-5 wt% Mn. The oxidation reaction was carried out at a ratio of components n-C7H16/O2/polymer catalyst with Mn = 1 : 3.38 : 0.003 and time 6 h within the temperature range 303-383 K. The data on the yield of the major products of n-heptane oxidation are presented, taking into account the initial components, catalyst composition, temperature and the time of oxygen contact with the reacting components. It has been established that during the oxidation of n-C7H16 (303-383 K), the yield of alcohols is higher than the yield of other oxidation products. The oxidative conversion of n-heptane increases from 45 to 75 mol% with an increase in temperature in the range of 303-383 K. For the multistage oxidation of n-heptane with oxygen, a kinetic model was selected and considered. On the basis of this model, the reaction rate constants were calculated in the range of 303-383 K considering the degree of heptane conversion. The activation energy of n-heptane oxidation was estimated, taking into account the method of choosing the most plausible parameter and experimental data on n-heptane convection.

Extending the freshness of tilapia surimi with pulsed electric field modified pea protein isolate-EGCG complex

The development of natural polyphenol-protein complexes for preserving surimi holds great promise. The effects of pea protein isolate (PPI) - (−)-Epigallocatechin-gallate (EGCG) non-covalent and covalent complexes modified by pulsed electric field (PEF) on the preservation of tilapia surimi were evaluated. Results showed that the PEF-treated PPI-EGCG non-covalent complex extended the shelf life of surimi by more than 6 days. This complex reduced the microbial activity and delayed the lipid and protein oxidation of surimi during chilled storage. Total viable count (TVC), thiobarbituric acid reactive substances (TBARS), and total volatile base nitrogen (TVB-N) of surimi with PEF-treated PPI-EGCG non-covalent complex on day 15 were 31.65 %, 68.67 %, and 54.46 % lower than untreated surimi, respectively. Moreover, the rate of colour deterioration and off-odour development were also delayed. The major products of lipid oxidation in surimi were reduced by 37.91 % for hexanal, 43.14 % for pentanal, 73.24 % for 1-octen-3-ol, and 39.32 % for 1-penten-3-ol on day 15. Structural analyses and computer simulations revealed that PEF was able to unfold the structure of PPI, thereby exposing more binding sites for EGCG. PEF-treated PPI-EGCG non-covalent complex allowed the slow dissociation of EGCG from PPI and maintained the antimicrobial and antioxidant activities of EGCG in a long storage time. Therefore, PEF-treated PPI-EGCG non-covalent complex was considered as a potential preservative in fish and fish products.

Effect of xanthan gum treatment on the shelf-life enhancement of retorted meatballs (Goshtaba): A traditional meat product of India

The quality of the meatballs (Goshtaba) deteriorates during storage owing to textural loss, lipid oxidation, and microbial activity. These deteriorations increase during storage, thereby lowering the quality and consumer acceptability of the product. Thus the present study evaluated the influence of xanthan gum and retorting process in preventing these deteriorations in meatballs. The elastic modulus of gum-treated meat paste was greater than the loss modulus values owing to higher cross-linking between peptide and polysaccharide chains. The cooking loss of goshtaba samples were 4.15 %, 3.50 %, 3.30 %, and 3.0 % for X (0.0), X (0.3), X (0.6), and X (0.9) samples respectively. The malonaldehyde content as a major lipid oxidation product was below the permissible limits of 2 mg/kg for both xanthan-treated and control goshtaba samples. The textural quality of the gum-treated product was well retained during storage compared to control samples. In microbiological analysis both treated and control goshtaba samples were free of a microbial count, indicating retorting as an efficient thermal method of processing and shelf stability of the developed product. The X (0.6) samples showed the best results as per the overall acceptability of products concerned during the storage period of 3 months.

Synthesis and characterization of the reactivity of new far-red fluorescent dyes and a boronate probe containing a tricyanopyrroline skeleton

Probes that exhibit turn-on fluorescence in the far-red region (600–750 nm) are in high demand because their use causes minimal autofluorescence and cellular damage. Here, we present a practical microwave-assisted synthesis of dyes containing a tricyanopyrroline (TCP) unit and a new boronate probe based on the TCP chemical scaffold. The proposed microwave-assisted method performs better in an eighteenth of the time than condensation in ethanol. We also present the simple methodology to detect peroxynitrite using the TCP-BOR redox probe in three different ways. First, the TCP-OH dye, which absorbs far-red light, is a major oxidation product that can be used for fluorescent detection. Second, peroxynitrite-specific products, nitrated TCP-NO2, and reduced TCP-H derivatives can easily be detected and quantified with HPLC due to a significant difference in the position of their absorption bands. Furthermore, the EPR signal recording of the spin adducts of the phenyl radical formed in the reaction of TCP-BOR with peroxynitrite and mass spectrometric analyses of these adducts can also be used to confirm the oxidation of the probe by peroxynitrite. TCP-OH was also detected in macrophages RAW 264.7 activated for the ONOO− production.

Oxidation characteristics and hazardous of α-pinene, β-pinene and turpentine

α-Pinene, β-pinene and turpentine are renewable resources that are widely used in fine chemicals, fuels and other applications, and the safety of their production, transport and use should be considered. In this work, the characteristics and hazardous of the oxidation process of α-pinene, β-pinene and turpentine were investigated by using a novel mini closed pressure vessel testing system (MCPVT). The oxidation products were resolved by gas chromatography-mass spectrometry (GC–MS). The results showed that α-pinene, β-pinene and turpentine were stable under nitrogen atmosphere and very active chemically under oxygen atmosphere. The activation energies (Ea) of α-pinene, β-pinene and turpentine were calculated to be 78.87, 109.69 and 98.82 kJ/mol, respectively, using pressure–time (P-t) curves. So, the reaction activity sequence was α-pinene > turpentine > β-pinene. The peroxide concentrations of α-pinene (363 K), β-pinene (358 K) and turpentine (363 K) could reach 81.94, 84.70 and 75.76 mmol/kg, respectively, at relatively low temperatures. 0.6 g of α-pinene exploded at a system temperature of 369 K and an oxygen pressure of 1.23 MPa. 0.6 g of β-pinene also exploded at a system temperature of 373 K and an oxygen pressure of 1.27 MPa. 0.4 g of turpentine experienced thermal runaway at a system temperature of 384 K and an oxygen pressure of 0.81 MPa. The major oxidation products of α-pinene are α-campholenaldehyde, laevo-pinocarveol, verbenol, verbenone, bicyclo (3.1.1)heptane-2, 3-diol, 2, 6, 6-trimethyl, 2-cyclohexen-1-ol, 2-methyl-5-(1-methylethenyl)-, (1R,5R)-rel-, cyclobutaneacetic acid, 3-acetyl-2, 2-dimethyl, myrtenol and myrtenal. The major thermal runaway products are water, ethanol, acetone, acetic acid, 2-pentanone, propyl acetate, toluene, cymene and methylacetophenone. The major oxidation products of β-pinene are nopinone, laevo-pinocarveol, pinocarvone, myrtenol, myrtenal and perillyl alcohol. The major thermal runaway products are water, ethanol, acetone, n-ethyl propanoate, toluene, butyl acetate, cymene, apocamphor, nopinone, bornyl formate, methylacetophenone and dihydronopol. The oxidation products and thermal runaway products of pinene were significantly different. Possible reaction pathways for α-pinene and β-pinene are proposed.

Chemical decontamination of methamphetamine and ephedrine using an activated peroxide-containing cleaning solution

Manufacture and recreational use of methamphetamine can result in widespread chemical contamination throughout a property. Hydrogen peroxide (H2O2)-based cleaning products have shown success against a number of chemical contaminants including agents of chemical warfare, and biological contaminants such as anthrax. They are considered to be environmentally friendly and economically viable and, as such, are used by many companies within the methamphetamine decontamination industry. The oxidative decontamination of methamphetamine and ephedrine hydrochloride was investigated in this current study, employing a commercially available H2O2-based decontamination product, Bio-Oxygen® Chem Decon. Methamphetamine and ephedrine were observed to degrade following pseudo-first order kinetics of (1.9 ± 0.4) × 10−2 min−1 and (2.2 ± 0.3) × 10−2 min−1, respectively. Major oxidation products identified through GC-MS analyses were phenylacetone oxime (from methamphetamine) and benzaldehyde (from ephedrine). LC-MS analysis revealed the presence of a number of N-oxygenated intermediates which allowed for the elucidation of an N-oxidation decomposition pathway reminiscent of flavin-containing monooxygenase enzymes. Using this information, further targeted research can be performed to understand the behaviour and persistence of these reaction products and accurate assessments can be achieved to estimate their impact on the exposure risks associated with chemical decontamination of amphetamine-type stimulants (ATS).

Glycerol Electrooxidation at Industrially Relevant Current Densities Using Electrodeposited PdNi/Nifoam Catalysts in Aerated Alkaline Media

Through glycerol electrooxidation, we demonstrate the viability of using a PdNi catalyst electrodeposited on Ni foam to facilitate industrially relevant rates of hydrogen generation while concurrently providing valuable organic chemicals as glycerol oxidation products. This electrocatalyst, in a solution of 2 M NaOH and 1 M glycerol at 80 °C, enabled current densities above 2000 mA cm−2 (in a voltammetric sweep) to be obtained in atmospheres of both air and N2. Repeated potential cycling under an aerated atmosphere to these exceptional current densities indicated a high stability of the catalyst. Through steady state polarisation curves, 1000 mA cm−2 was reached below an anodic potential of 0.8 V vs RHE. Chronoamperometry showed glycerate and lactate being the major oxidation products, with increased selectivity for lactate at the expense of glycerate in aerated systems. Aerated atmospheres were demonstrated to consistently increase the apparent Faradaic efficiency to >100%, as determined by the concentration of oxidation products in solution. The excellent performance of PdNi/Ni in aerated solutions suggests that O2 removal from the electrolyte is not needed for an industrial glycerol electrooxidation process, and that combining electrochemical and chemical glycerol oxidation, in the presence of dissolved O2, presents an important process advantage.

Insights into the Oxidative Degradation Mechanism of Solid Amine Sorbents for CO2 Capture from Air: Roles of Atmospheric Water

AbstractDirect air capture (DAC) processes for extraction of CO2 from ambient air are unique among chemical processes in that they operate outdoors with minimal feed pretreatments. Here, the impact of humidity on the oxidative degradation of a prototypical solid supported amine sorbent, poly(ethylenimine) (PEI) supported on Al2O3, is explored in detail. By combining CO2 adsorption measurements, oxidative degradation rates, elemental analyses, solid‐state NMR and in situ IR spectroscopic analysis in conjunction with 18O labeling of water, a comprehensive picture of sorbent oxidation is achieved under accelerated conditions. We demonstrated that the presence of water vapor can play an important role in accelerating the degradation reactions. From the study we inferred the identity and kinetics of formation of the major oxidative products, and the role(s) of humidity. Our data are consistent with a radical mediated autooxidative degradation mechanism.

Insights into the Oxidative Degradation Mechanism of Solid Amine Sorbents for CO2 Capture from Air: Roles of Atmospheric Water.

Direct air capture (DAC) processes for extraction of CO2 from ambient air are unique among chemical processes in that they operate outdoors conditions with minimal feed pretreatments. Here, the impact of humidity on the oxidative degradation of a prototypical solid supported amine sorbent, poly(ethylenimine) (PEI) supported on Al2O3, is explored in detail. By combining CO2 adsorption measurements, oxidative degradation rates, elemental analyses, solid-state NMR and in situ IR spectroscopic analysis in conjunction with 18O labeling of water, a comprehensive picture of sorbent oxidation is achieved under accelerated conditions. We demonstrated that the presence of water vapor can play an important role in accelerating the degradation reactions. From the study we inferred the identity and kinetics of formation of the major oxidative products, and the role(s) of humidity. Our data are consistent with a radical mediated autooxidative degradation mechanism.

Mechanism of Fenton Oxidation of Levoglucosan in Water

Levoglucosan (Levo) is a major saccharide formed by the combustion of cellulosic materials. Levo was once considered an inert tracer of biomass-burning aerosols; however, recent studies have indicated that Levo in atmospheric condensed phases does indeed react with atmospheric reactants. Here, we report the results of a time-resolved mass spectrometric study of the oxidation of Levo in aqueous solutions with ferrous ion (Fe2+)/hydrogen peroxide (H2O2) (i.e., Fenton's reagent). The major products of the Fenton oxidation of Levo were oxygen-atom-incorporated species (Levo+nO, n = 1-3). Experiments using Levo-d7 (all C-H bonds replaced by C-D) and D2O or H218O as the solvent revealed that OH predominantly (∼85% of all C-H bonds) abstracts H atoms attached to the carbon atoms possessing a hydroxyl moiety (-OH), which is followed by the formation of a carbonyl moiety (-C═O). Subsequent hydration of these products results in the formation of geminal diols (detected as Levo+1O species). Our results also suggest the formation of α-hydroxy-hydroperoxides (detected as Levo+2O species) that exist in equilibrium, with the compounds possessing a -C═O moiety and with H2O2. H-abstractions from -O-H were found to be a minor reaction pathway (≤5% of all H-abstractions). The present proposed oxidation mechanisms improve our understanding of how the chemical components of atmospheric condensed phases change by metal-catalyzed aging processes without sunlight.

Changes in the Quality of High-Oleic Sunflower Oil during the Frying of Shrimp (Litopenaeus vannamei).

Shrimp fried in vegetable oil is a very popular food, so it is important to study the changes in the quality of the oil during frying. In order to more precisely study the nature of frying oil during the cooking process, this study investigated the quality changes of high-oleic sunflower oil during the frying of South American white shrimp (Litopenaeus vannamei). The oxidation and hydrolysis products of frying oils were investigated by integrating the proton nuclear magnetic resonance technique with traditional oil evaluation indexes in an integrated manner. The results showed that the color difference as measured using the ΔE* value increased gradually during the process. Moreover, the acid value, carbonyl value, and total oxidation significantly increased with prolonged frying time. The major oxidation products formed during frying were (E,E)-2-alkenals, (E,E)-2,4-alkadienals, and E,E-conjugated hydroperoxides. This indicated that longer treatment times corresponded with an increased accumulation of aldehydes and ketones, and an increased degree of oxidative deterioration of the oil. However, the proportion of oleic acid in the frying oil increased with the frying of shrimp, reaching 80.05% after 24 h. These results contribute to our understanding of the oxidative deterioration of high-oleic oils during frying, and provide an important reference for the application properties of high-oleic oils.

Human intestinal Caco-2 cell model to evaluate the absorption of 7-ketophytosterols and their effects on cholesterol transport

7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16 %−1.68 % and 1.18 %−2.23 % respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral (BL)-to-apical (AP) direction were 0.42- and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols (P < 0.05), which means that their transport depends on niemann-pick c1-like 1 (NPC1L1) protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols (P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.

Autoxidation Mechanism and Kinetics of Methacrolein in the Atmosphere.

Elucidating the autoxidation of volatile organic compounds (VOCs) is crucial to understanding the formation mechanism of secondary organic aerosols, but it has been proven to be challenging due to the complexity of reactions under atmospheric conditions. Here, we report a comprehensive theoretical study of atmospheric autoxidation in VOCs exemplified by the atmospherically important methacrolein (MACR), a major oxidation product of isoprene. The results indicate that the Cl-adducts and H-abstraction products of MACR readily react with O2 and undergo subsequent isomerizations via H-shift and cyclization, forming a large variety of lowly and highly oxygenated organic molecules. In particular, the first- and third-generation oxidation products derived from the Cl-adducts and the methyl-H-abstraction complexes are dominated in the atmospheric autoxidation, for which the fractional yields are remarkably affected by the NO concentration. The present findings have important implications for a systematical understanding of the oxidation processes of isoprene-derived compounds in the atmospheric environments.

Discovery and properties of a monoclonal antibody targeting 8-oxoA, an oxidized adenine lesion in DNA and RNA

8-oxoA, a major oxidation product of adenosine, is a mispairing, mutagenic lesion that arises in DNA and RNA when •OH radicals or one-electron oxidants attack the C8 adenine atom or polymerases misincorporate 8-oxo(d)ATP. The danger of 8-oxoA is underscored by the existence of dedicated cellular repair machinery that explicitly excise it from DNA, the attenuation of translation induced by 8-oxoA-mRNA or damaged ribosomes, and its potency as a TLR7 agonist. Here we present the discovery, purification, and biochemical characterization of a new mouse IgGk1 monoclonal antibody (6E4) that specifically targets 8-oxoA. Utilizing an AchE-based competitive ELISA assay, we demonstrate the selectivity of 6E4 for 8-oxoA over a plethora of canonical and chemically modified nucleosides including 8-oxoG, A, m6A, 2-oxoA, and 5-hoU. We further show the ability of 6E4 to exclusively recognize 8-oxoA in nucleoside triphosphates (8-oxoATP) and DNA/RNA oligonucleotides containing a single 8-oxoA. 6E4 also binds 8-oxoA in duplex DNA/RNA antigens where the lesion is either paired correctly or base mismatched. Our findings define the 8-oxoAde nucleobase as the critical epitope and indicate mAb 6E4 is ideally suited for a broad range of immunological applications in nucleic acid detection and quality control.

Catalytic performance of sewage sludge char and ash in the decomposition of NH3

The present study was conducted to study the catalytic performance of sewage sludge char and ash on NH3 decomposition by using a fixed bed reactor. The results indicated that sewage sludge char exhibited strong activity towards NH3 decomposition, which was highly influenced by temperature and atmosphere. The influence of atmosphere on NH3 decomposition was investigated at 973 K, it showed that the char activity was greatly promoted with the presence of O2, and the major product of NH3 oxidation catalyzed by relatively fresh char was N2 rather than NO. In contrast, the NH3 decomposition was suppressed with H2O introducing, and there was a significant amount of NO being produced. Compared to char, the in-situ combusted ash showed relatively poor catalytic performance with respect to NH3 conversion. At 973 K, the NH3 conversion catalyzed by ash was dominated by the inhabitation effect of H2O with the presence of both O2 and H2O. However, when the temperature increased to 1128 K, O2 tends to take a dominant role to promote NH3 conversion. By XRD analysis of the fresh and spent char, it was proposed that iron phosphide (Fe2P) may be responsible for the high activities towards NH3 decomposition, following a cycle mechanism.

Oxidative DNA damage in reconstituting T cells is associated with relapse and inferior survival after allo-SCT

AbstractAllogeneic hematopoietic stem cell transplantation (allo-SCT) is the only curative treatment option for a number of hematologic malignancies. Its therapeutic potential relies on the potency of donor T cells to eliminate residual malignant cells, the so-called graft-versus-leukemia (GVL) effect. Disease relapse remains the most frequent treatment failure and is associated with poor outcome. Therefore, it is inevitable to decipher mechanisms that weaken GVL. In recent years, studies of tumor biology have revealed that metabolic remodeling of the micromilieu can critically regulate immune responses. Accumulation of reactive oxygen species leads to a metabolic condition known as oxidative stress, which can severely hamper T cells. Currently, only a few studies, mainly using preclinical models, have demonstrated the occurrence of oxidative stress after allo-SCTs. Therefore, we sought to investigate oxidative stress in a well-characterized group of patients who underwent allo-SCT and its impact on reconstituting T cells. We identified high concentrations of serum 8-hydroxydeoxyguanosine (8-OHdG) as an established biomarker for oxidative stress. 8-OHdG is one of the major products of DNA oxidation, which is normally rapidly removed. After allo-SCT, T cells accumulated oxidative DNA damage. High cellular 8-OHdG content (8-OHdGhi) was associated not only with signs of enhanced T-cell activation but also premature exhaustion. The inability of 8-OHdGhi T cells to efficiently target malignant cells or produce cytotoxic granzyme B and interferon gamma was associated with a significantly increased relapse risk and a shorter overall survival. Taken together, our novel findings could give reason to focus on bolstering DNA repair in reconstituting T cells as a means to improve GVL efficacy.

Isolation and structural characterization of two novel oxidative degradation products of losartan potassium active pharmaceutical ingredient using advanced analytical techniques.

Losartan potassium (losartan) is the most frequently utilized antihypertensive medication in the world. However, partial oxidation of losartan produces toxic by-products that could be harmful to living organisms. Therefore, it is necessary to degrade the losartan and identify the potential toxic oxidative degradation products to minimize their formation during manufacturing, formulation, storage, and packing conditions. Oxidative degradation experiments of losartan were performed according to ICH guidelines. The degradation products were detected using ultra-high-performance liquid chromatography-mass spectrometry analysis, isolated by using preparative HPLC, and identified by using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopic techniques. The degradation products (DP-1, DP-2, and DP-3) were identified as (((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)amino)-2-oxoethylpentanoate, 5-(4'-((2 butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-yl)-1H tetrazol-1-ol, and 5-(4'-((2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1 yl)methyl)-[1,1'-biphenyl]-2-yl)-2H-tetrazol-2-ol, respectively. Forced degradation of losartan potassium API under oxidative condition indicates the formation of two major novel oxidative degradation products (DP-2 and DP-3) and one minor known degradation product (DP-1).Preparative HPLC used for the isolation of the resultant DPs and their structures were successfully established using UHPLC-MS, 1H NMR, 13C NMR, HSQC, HMBC, and HRMS spectroscopic techniques.