High-resolution Mass Spectrometry Analysis Research Articles

Vulnerability of wells in unconfined and confined aquifers to modern contamination from flood events

Groundwater is a primary potable water supply for coastal North Carolina (NC), but the increased intensity of extreme rainfall events and floods may exacerbate surface and subsurface processes that contribute anthropogenic chemicals to wells in the major confined aquifers of this region. We evaluated groundwater for organic chemicals of emerging concern (CEC) and the presence of tritium using flooded and not-flooded wells in the NC Department of Environmental Quality well monitoring network across the NC Coastal Plain. Flooded wells experienced standing water around the well casing at least once during the study period. Tritium concentrations, which indicate modern water presence (water recharged after 1953), were significantly greater in groundwater from flooded wells than not-flooded wells. In confined aquifers, modern water was detected at greater depths in flooded wells (206 m) than not-flooded wells (100 m). Suspect-screening high resolution mass spectrometry (HRMS) analysis of 150 groundwater samples yielded a total of 382 unique organic chemicals. Each groundwater sample contained, on average, 19 tentatively identified chemicals from the NIST 20 mass spectral database (M1) and 9 USEPA ToxCast chemicals. The number of tentatively-identified chemicals per sample was not significantly different among aquifers demonstrating the pervasive presence of the detected CECs in unconfined and confined aquifers. The presence of modern water in groundwater from flooded wells coincided with higher detection frequencies of certain organic contaminant classes, particularly pharmaceuticals, food additives, and regulated aromatic hydrocarbons. These results indicate that wells in both unconfined and confined aquifers are susceptible to modern water contamination during flood events; this finding has critical public health implications for coastal communities.

Untargeted metabolomics in the aqueous humor reveals the involvement of TAAR pathway in glaucoma

Understanding the metabolic dysfunctions and underlying complex pathological mechanisms of neurodegeneration in glaucoma could help discover disease pathways, identify novel biomarkers, and rationalize newer therapeutics. Therefore, we aimed to investigate the local metabolomic alterations in the aqueous humor and plasma of primary glaucomatous patients. This study cohort comprised primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and cataract control groups. Aqueous humor and plasma samples were collected from patients undergoing trabeculectomy or cataract surgery and subjected to high-resolution mass spectrometry (HRMS) analysis. Spectral information was processed, and the acquired data were subjected to uni-variate as well as multi-variate statistical analyses using MetaboAnalyst ver5.0. To further understand the localized metabolic abnormalities in glaucoma, metabolites affected in aqueous humor were distinguished from metabolites altered in plasma in this study. Nine and twelve metabolites were found to be significantly altered (p < 0.05, variable importance of projection >1 and log2 fold change ≥0.58/≤ −0.58) in the aqueous humor of PACG and POAG patients, respectively. The galactose and amino acid metabolic pathways were locally affected in the PACG and POAG groups, respectively. Based on the observation of the previous findings, gene expression profiles of trace amine-associated receptor-1 (TAAR-1) were studied in rat ocular tissues. The pharmacodynamics of TAAR-1 were explored in rabbits using topical administration of its agonist, β-phenyl-ethylamine (β-PEA). TAAR-1 was expressed in the rat's iris-ciliary body, optic nerve, lens, and cornea. β-PEA elicited a mydriatic response in rabbit eyes, without altering intraocular pressure. Targeted analysis of β-PEA levels in the aqueous humor of POAG patients showed an insignificant elevation. This study provides new insights regarding alterations in both localized and systemic metabolites in primary glaucomatous patients. This study also demonstrated the propensity of β-PEA to cause an adrenergic response through the TAAR-1 pathway.

Carbene-catalyzed chemoselective reaction of unsymmetric enedials for access to Furo[2,3-b]pyrroles

A carbene-catalyzed chemoselective reaction of unsymmetric enedials is disclosed. The reaction provides a concise access to bicyclic furo[2,3-b]pyrroles derivatives in excellent selectivity. A main challenge in this reaction is chemoselective reaction of the two aldehyde moieties in the enedial substrates. Mechanistic studies via experiments suggest that our chemoselectivity controls are mostly achieved on the reducing properties of different sited Breslow intermediates. Several side reactions processes and the corresponding side adducts are also studied by high resolution mass spectroscopy analysis. Our method allows for efficient assembly of the furo[2,3-b]pyrrole structural moieties and their analogues widely found in natural products and pharmaceuticals.

Pulsed versus direct current electrochemical co-catalytic peroxymonosulfate-based system: Elevated degradation and energy efficiency with enhanced oxidation mechanisms

In this work, the pulsed electrochemical (PE) system was investigated to activate peroxymonosulfate (PMS) with the addition of Fe(III) to achieve efficient degradation of sulfamethoxazole (SMX) with reduced energy consumption, in comparison with the direct current (DC) electrochemical system. The operational conditions of PE/PMS/Fe(III) system were optimized as 4 kHz pulse frequency, 50% duty cycle, and pH 3, at which 67.6% reduction of energy consumption and enhanced degradation performance were achieved compared to the DC/PMS/Fe(III) system. Results of electron paramagnetic resonance spectroscopy analysis and quenching and chemical probe experiment revealed the presence of •OH, SO4•−, and 1O2 in the system, with •OH being the dominant role. The concentrations of these active species were averagely 15 ± 1% higher in the PE/PMS/Fe(III) system than those of the DC/PMS/Fe(III) system. Identification of SMX byproducts was achieved based on high resolution mass spectrometry analysis to predict the degradation pathways. The SMX byproducts could eventually be eliminated by the PE/PMS/Fe(III) system with extended treatment time. Overall, the PE/PMS/Fe(III) system was demonstrated with high energy and degradation performance, and is appear to be an robust strategy for practical treatment of wastewater.

Thermal desorption direct analysis in real-time high-resolution mass spectrometry and machine learning allow the rapid authentication of ground black pepper and dried oregano: A proof-of-concept study.

Thermal desorption direct analysis in real-time high-resolution mass spectrometry (TD-DART-HRMS) approaches have gained popularity for fast screening of a variety of samples. With rapid volatilization of the sample at increasing temperatures outside the mass spectrometer, this technique can provide a direct readout of the sample content with no sample preparation. In this study, TD-DART-HRMS's utility for establishing spice authenticity was examined. To this aim, we directly analyzed authentic (typical) and adulterated (atypical) samples of ground black pepper and dried oregano in positive and negative ion modes. We analyzed a set of authentic ground black pepper samples (n = 14) originating from Brazil, Sri Lanka, Madagascar, Ecuador, Vietnam, Costa Rica, Indonesia, Cambodia, and adulterated samples (n = 25) consisting of mixtures of ground black pepper with this spice's nonfunctional by-products (pinheads or spent) or with different exogenous materials (olive kernel, green lentils, black mustard seeds, red beans, gypsum plaster, garlic, papaya seeds, chili, green aniseed, or coriander seeds). TD-DART-HRMS facilitated the capture of informative fingerprinting of authentic dried oregano (n = 12) originating from Albania, Turkey, and Italy and those spiked (n = 12) with increasing percentages of olive leaves, sumac, strawberry tree leaves, myrtle, and rock rose. A predictive LASSO classifier was built, after merging by low-level data fusion, the positive and negative datasets for ground black pepper. Fusing multimodal data allowed retrieval of more comprehensive information from both datasets. The resultant classifier achieved on the withheld test set accuracy, sensitivity, and specificity of 100%, 75%, and 90%, respectively. On the contrary, the sole TD-(+)DART-HRMS spectra of the oregano samples allowed construction of a LASSO classifier that predicted the adulteration of the oregano with excellent statistical indicators. This classifier achieved, on the withheld test set, 100% each for accuracy, sensitivity, and specificity.

Metabolic labeling of hyaluronan: Biosynthesis and quantitative analysis of 13C,15N-enriched hyaluronan by NMR and MS-based methods

Hyaluronan (HA), a member of the GAG family of glycans, has many diverse biological functions that vary a lot depending on the length of the HA chain and its concentration. A better understanding of the structure of different-sized HA at the atomic level is therefore crucial to decipher these biological functions. NMR is a method of choice for conformational studies of biomolecules, but there are limitations due to the low natural abundance of the NMR active nuclei 13C and 15N. We describe here the metabolic labeling of HA using the bacterium Streptococcus equi subsp. Zooepidemicus and the subsequent analysis by NMR and mass spectrometry. The level of 13C and 15N isotope enrichment at each position was determined quantitatively by NMR spectroscopy and was further confirmed by high-resolution mass spectrometry analysis. This study provides a valid methodological approach that can be applied to the quantitative assessment of isotopically labeled glycans and will help improve detection capabilities and facilitate future structure-function relationship analysis of complex glycans.

Cytotoxic screening of plants from the Brazilian Atlantic Forest has led to the identification of Casearia arborea and Sorocea hilarii as sources of antitumor compounds

In the present study, we have evaluated the cytotoxic activity of 282 extracts from 72 native plant species of the Brazilian Atlantic Forest biome. As a result, Casearia arborea and Sorocea hilarii leaves extracts showed cytotoxic activity against three tumour cell lines tested (B16F10, SW480 and Jurkat). After bioassay-guided fractionation, the bioactive fractions were submitted to the dereplication study via High-performance Liquid Chromatography, connected to High-resolution Mass Spectrometry (HPLC-ESI-QTOF/MS) analysis, combined with a Global Natural Products Social Molecular Networking (GNPS) tool. A combination of bioactivity-guided and dereplication approaches resulted in the putative annotation of 27 clerodane diterpenes and 9 flavonoids as main compounds present in the cytotoxic fractions of C. arborea. Regarding the active fraction of S. hilarii, 10 megastigmans, 17 spirostane steroids derivatives and 2 lignans were putatively identified. In conclusion, Casearia arborea and Sorocea hilarii are potential sources of antitumor compounds.

NO Generation from Nitrite at Zinc(II): Role of Thiol Persulfidation in the Presence of Sulfane Sulfur.

Nitrite-to-NO transformation is of prime importance due to its relevance in mammalian physiology. Although such a one-electron reductive transformation at various redox-active metal sites (e.g., Cu and Fe) has been illustrated previously, the reaction at the [ZnII] site in the presence of a sacrificial reductant like thiol has been reported to be sluggish and poorly understood. Reactivity of [(Bn3Tren)ZnII-ONO](ClO4) (1), a nitrite-bound model of the tripodal active site of carbonic anhydrase (CA), toward various organic probes, such as 4-tert-butylbenzylthiol (tBuBnSH), 2,4-di-tert-butylphenol (2,4-DTBP), and 1-fluoro-2,4-dinitrobenzene (F-DNB), reveals that the ONO-moiety in the [ZnII]-nitrite coordination motif of complex 1 acts as a mild electrophile. tBuBnSH reacts mildly with nitrite at a [ZnII] site to provide S-nitrosothiol tBuBnSNO prior to the release of NO in 10% yield, whereas the phenolic substrate 2,4-DTBP does not yield the analogous O-nitrite compound (ArONO). The presence of sulfane sulfur (S0) species such as elemental sulfur (S8) and organic polysulfides (tBuBnSnBntBu) during the reaction of tBuBnSH and [ZnII]-nitrite (1) assists the nitrite-to-NO conversion to provide NO yields of 65% (for S8) and 76% (for tBuBnSnBntBu). High-resolution mass spectrometry (HRMS) analyses on the reaction of [ZnII]-nitrite (1), tBuBnSH, and S8 depict the formation of zinc(II)-persulfide species [(Bn3Tren)ZnII-Sn-BntBu]+ (where n = 2, 3, 4, 5, and 6). Trapping of the persulfide species (tBuBnSS-) with 1-fluoro-2,4-dinitrobenzene (F-DNB) confirms its intermediacy. The significantly higher nucleophilicity of persulfide species (relative to thiol/thiolate) is proposed to facilitate the reaction with the mildly electrophilic [ZnII]-nitrite (1) complex. Complementary analyses, including multinuclear NMR, electrospray ionization-MS, UV-vis, and trapping of reactive S-species, provide mechanistic insights into the sulfane sulfur-assisted reactions between thiol and nitrite at the tripodal [ZnII]-site. These findings suggest the critical influential roles of various reactive sulfur species, such as sulfane sulfur and persulfides, in the nitrite-to-NO conversion.

Distinct Depth-Discrete Profiles of Microbial Communities and Geochemical Insights in the Subsurface Critical Zone.

Microbial assembly and metabolic potential in the subsurface critical zone (SCZ) are substantially impacted by subsurface geochemistry and hydrogeology, selecting for microbes distinct from those in surficial soils. In this study, we integrated metagenomics and geochemistry to elucidate how microbial composition and metabolic potential are shaped and impacted by vertical variations in geochemistry and hydrogeology in terrestrial subsurface sediment. A sediment core from an uncontaminated, pristine well at Oak Ridge Field Research Center in Oak Ridge, Tennessee, including the shallow subsurface, vadose zone, capillary fringe, and saturated zone, was used in this study. Our results showed that subsurface microbes were highly localized and that communities were rarely interconnected. Microbial community composition as well as metabolic potential in carbon and nitrogen cycling varied even over short vertical distances. Further analyses indicated a strong depth-related covariation of community composition with a subset of 12 environmental variables. An analysis of dissolved organic carbon (DOC) quality via ultrahigh resolution mass spectrometry suggested that the SCZ was generally a low-carbon environment, with the relative portion of labile DOC decreasing and that of recalcitrant DOC increasing along the depth, selecting microbes from copiotrophs to oligotrophs and also impacting the microbial metabolic potential in the carbon cycle. Our study demonstrates that sediment geochemistry and hydrogeology are vital in the selection of distinct microbial populations and metabolism in the SCZ. IMPORTANCE In this study, we explored the links between geochemical parameters, microbial community structure and metabolic potential across the depth of sediment, including the shallow subsurface, vadose zone, capillary fringe, and saturated zone. Our results revealed that microbes in the terrestrial subsurface can be highly localized, with communities rarely being interconnected along the depth. Overall, our research demonstrates that sediment geochemistry and hydrogeology are vital in the selection of distinct microbial populations and metabolic potential in different depths of subsurface terrestrial sediment. Such studies correlating microbial community analyses and geochemistry analyses, including high resolution mass spectrometry analyses of natural organic carbon, will further the fundamental understanding of microbial ecology and biogeochemistry in subsurface terrestrial ecosystems and will benefit the future development of predictive models on nutrient turnover in these environments.

ANTIMICROBIAL, PHYTOCHEMICAL AND TOXICOLOGICAL PROFILE OF ESSENTIAL OIL EXTRACTED FROM PANDANUS ODORIFER WITH AN AVAILABLE SIMULATION STUDY

Plant-derived essential oils are natural sources of antimicrobial and pharmaceutical agents besides their broad spectrum of use in the cosmetic, food, and perfume industries. The essential oil from the flowers of P. odorifer was extracted using the hydro distillation method. The major compound from the essential oil was identified by high-resolution mass spectroscopy (HRMS) analysis the identified phytochemicals include p-benzoquinone, 2-phenethyl alcohol, p-cymene, 2-phenethyl methyl either alpha-Terpineol, Psoralen, Isoplumbagin, Genipin, Artemidiol, Pinocembrin, (-)-Glycinol and, Iprobenfos. Two of its major phytochemicals,2-phenethyl methyl ether (PEME) and alpha-terpineol identified through HRMS were procured from Sigma-Aldrich. The antimicrobial properties of the PEME, essential oil, and terpineol was determined using agar well diffusion and micro broth dilution method against four clinically isolated multidrug-resistant (MDR) pathogenic bacteria viz. Staphylococcus aureus, Streptococcus pyogenes, Acinetobacter baumanni, and Pseudomonas aeruginosa. PEME and alpha-terpineol exhibited significant antibacterial activity against all the isolated pathogenic MDR bacteria. No pathological abnormalities were noticed even if it was provided at the highest treatment dose of 800 mg/kg body weight. Further In silico study of molecular interaction analyses have been performed for the proteins Extracellular Adhesion Protein (EAP), Protein A, and Toxic Shock Syndrome Toxin (TSST) of Staphylococcus aureus with the ligand 2-methoxyethyl benzene which shows better interaction with the target. This study validated the robust antibacterial activity of the essential oil of P. odorifer against both gram-positive and negative bacteria. Further, it is validated that the antibacterial activity was mainly because of the presence of two major phytochemicals, PEME and terpineol identified by HRMS analysis.

Synthesis by microwave irradiation of new pyrazole-imidazoline-pyrimidine analogs: Physicochemical and photophysical properties and their biological activity against Trypanosoma cruzi

Pyrazole derivatives are pharmacologically important agents that possess a wide spectrum of biological activities. Thus, the optimization of their synthetic approaches is of great interest for medicinal and pharmaceutical chemistry. In this work, eleven new 7-aryl-2,3-dihydro-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidines 1(a-k) were synthesized employing microwave irradiation conditions (150 W, 15–45 min). All compounds were completely characterized through Fourier Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and High-resolution Mass Spectrometry (HRMS) analyses. The in silico prediction of physicochemical properties showed that all analogs do not violate Lipinki's rule with prediction of good oral bioavailability. Analogs showed low activity against T. cruzi. Correlated experimental methods have been applied to investigate the photophysical properties of 1(a-k), describing their absorption properties in function of substituents. The molecular set exhibits a cyan emission, enabling it to investigate the basic fluorescence spectroscopy in solution.

Lipid Metabolism Reprogramming and Trastuzumab Resistance in Breast Cancer Cell Lines Overexpressing the ERBB2 Membrane Receptor.

Trastuzumab (Tz), an antibody targeting ERBB2, has significantly improved the prognosis for breast cancer (BCa) patients with overexpression of the ERBB2 receptor. However, Tz resistance poses a challenge to patient outcomes. Numerous mechanisms have been suggested to contribute to Tz resistance, and this study aimed to uncover shared mechanisms in in vitro models of acquired BCa Tz resistance. Three widely used ERBB2+ BCa cell lines, adapted to grow in Tz, were examined. Despite investigating potential changes in phenotype, proliferation, and ERBB2 membrane expression in these Tz-resistant (Tz-R) cell lines compared to wild-type (wt) cells, no common alterations were discovered. Instead, high-resolution mass spectrometry analysis revealed a shared set of differentially expressed proteins (DEPs) in Tz-R versus wt cells. Bioinformatic analysis demonstrated that all three Tz-R cell models exhibited modulation of proteins associated with lipid metabolism, organophosphate biosynthesis, and macromolecule methylation. Ultrastructural examination corroborated the presence of altered lipid droplets in resistant cells. These findings strongly support the notion that intricate metabolic adaptations, including lipid metabolism, protein phosphorylation, and potentially chromatin remodeling, may contribute to Tz resistance. The detection of 10 common DEPs across all three Tz-resistant cell lines offers promising avenues for future therapeutic interventions, providing potential targets to overcome Tz resistance and potentially improve patient outcomes in ERBB2+ breast cancer.

Xanthophyll esterases in association with fibrillins control the stable storage of carotenoids in yellow flowers of rapeseed (Brassica juncea).

Biosynthesis, stabilization, and storage of carotenoids are vital processes in plants that collectively contribute to the vibrant colors observed in flowers and fruits. Despite its importance, the carotenoid storage pathway remains poorly understood and lacks thorough characterization. We identified two homologous genes, BjA02.PC1 and BjB04.PC2, belonging to the esterase/lipase/thioesterase (ELT) family of acyltransferases. We showed that BjPCs in association with fibrillin gene BjFBN1b control the stable storage of carotenoids in yellow flowers of Brassica juncea. Through genetic, high-resolution mass spectrometry and transmission electron microscopy analyses, we demonstrated that both BjA02.PC1 and BjB04.PC2 can promote the accumulation of esterified xanthophylls, facilitating the formation of carotenoid-enriched plastoglobules (PGs) and ultimately producing yellow pigments in flowers. The elimination of BjPCs led to the redirection of metabolic flux from xanthophyll ester biosynthesis to lipid biosynthesis, resulting in white flowers for B. juncea. Moreover, we genetically verified the function of two fibrillin genes, BjA01.FBN1b and BjB05.FBN1b, in mediating PG formation and demonstrated that xanthophyll esters must be deposited in PGs for stable storage. These findings identified a previously unknown carotenoid storage pathway that is regulated by BjPCs and BjFBN1b, while offering unique opportunities for improving the stability, deposition, and bioavailability of carotenoids.

New insights into the bioaccessibility and metabolic fates of short-chain bioactive peptides in goat milk using the INFOGEST static digestion model and an improved data acquisition strategy

The metabolic fates of potentially bioactive short-chain peptides (SCPs; amino acid numbers between 2 and 4) in gastrointestinal digestion have received little attention due to their low concentration and broad suppression during high resolution mass spectrometry (HRMS) analysis. A tailored workflow integrating mesoporous magnetic solid phase extraction and a novel ion transmission strategy (data-dependent acquisition combined with both an inclusion list and an exclusion list followed by a data-independent acquisition) was used to profile the composition of SCPs during in vitro simulated digestion (LOQ 0.02 to 0.1 μg L-1). A total of 47 dipeptides, 59 tripeptides, and 21 tetrapeptides were identified and quantified from 0.01 to 27.84 mg L-1 (RSD ≤ 9.1%) based on parallel reaction monitoring and an internal standard method. The structural properties of stable SCPs resistant to intestinal digestion were determined by analysis of variance (p < 0.05), with a Pro residue at the C-terminal or penultimate position, a slightly greater negative charge at pH 7.0, and fewer C-terminal aliphatic and polar amino acids. SCPs' metabolic fates varied during digestion, but the overall trend of content change for either total or individual SCP increased as the digestion proceeded, and they were further assessed by a database-driven bioactivity search, which matched a wide variety of bioactivities with the predominance of dipeptidyl peptidase (DPP) IV and angiotensin-converting enzyme (ACE) inhibitors. This study facilitated the understanding of bioaccessibility of the food-derived SCPs and provided essential guidelines for the properties of conserved structure in vivo.

Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches.

Pancreatic cancer is the seventh most prevalent cause of mortality globally. Since time immemorial, plant-derived products have been in use as therapeutic agents due to the existence of biologically active molecules called secondary metabolites. Flavonoids obtained from plants participate in cell cycle arrest, induce autophagy and apoptosis, and decrease oxidative stress in pancreatic cancer. The present study involves network pharmacology-based study of the methanolic leaf extract of Trema orientalis (MLETO)Linn. From the high-resolution mass spectrometry (HRMS) analysis, 21 nucleated flavonoids were screened out, of which only apigeniflavan was selected for further studies because it followed Lipinski's rule and showed no toxicity. The pharmacokinetics and physiochemical characteristics of apigeniflavan were performed using the online web servers pkCSM, Swiss ADME, and ProTox-II. This is the first in silico study to report the efficiency of apigeniflavan in pancreatic cancer treatment. The targets of apigeniflavan were fetched from SwissTargetPrediction database. The targets of pancreatic cancer were retrieved from DisGeNET and GeneCards. The protein-protein interaction of the common genes using Cytoscape yielded the top five hub genes: KDR, VEGFA, AKT1, SRC, and ESR1. Upon molecular docking, the lowest binding energies corresponded to best docking score which indicated the highest protein-ligand affinity. Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was employed to see the involvement of hub genes in pathways related to pancreatic cancer. The following, pancreatic cancer pathway, MAPK, VEGF, PI3K-Akt, and ErbB signaling pathways, were found to be significant. Our results indicate the involvement of the hub genes in tumor growth, invasion and proliferation in the above-mentioned pathways, and therefore necessitating their downregulation. Moreover, apigeniflavan can flourish as a promising drug for the treatment of pancreatic cancer in future.

Elimination of the Ion–Molecule Association in Electrospray High-Resolution Mass Spectrometry Analyses for Petroleum Fractions

Electrospray ionization (ESI) coupled with high-resolution mass spectrometry (HRMS) is rapidly developing into a powerful tool for the molecular characterization of petroleum fractions. However, the occurrence of ion–molecule aggregates seriously affects the interpretation of the mass spectrometry results. Ion–molecule aggregates are not inherent compounds in petroleum but they are produced during the analysis of petroleum samples by high-resolution mass spectrometry. Also, the classes of aggregates are the same as many compounds in petroleum. Therefore, the removal of these species is crucial, and their analysis from methods of dissociation and mechanism points of view is essential for this purpose. In this study, aggregates of a vacuum gas oil fraction were analyzed and the types were defined. The compositions of the aggregates were characterized by changing operating conditions. Several factors affecting the aggregates were evaluated by a parameter of dissociation efficiency. By establishing the operating methods, the residual content of the aggregates can be controlled by less than 1% of the total ions. The results are instructive for the molecular characterization of petroleum fractions by using mass spectrometry with ESI ionization.

Analytical characterization and differentiation between threo- and erythro-4-fluoroethylphenidate.

Methylphenidate analogs appeared on the drug market during the last years. Its analogs contain two chiral centers and, thus, have potential varying configurations (i.e., threo and erythro forms). This study presents the analytical characterization of 4-fluoroethylphenidate (4-FEP) and its differentiation between threo- and erythro-4-FEP. Analysis of the samples included high-performance liquid chromatography (HPLC), gas chromatography-electron ionization-mass spectrometry (GC-EI-MS), high-resolution mass spectrometry (HRMS) analyses, nuclear magnetic resonance (NMR) spectroscopy and X-ray crystal structure analysis. NMR spectroscopic investigations confirmed the differences between threo- and erythro-4-FEP, and demonstrated that both isomers could be separated using HPLC and GC methods. Two samples obtained from one vendor in 2019 consisted of threo-4-FEP, whereas the other two samples obtained from a different vendor in 2020 consisted of a mixture of threo- and erythro-4-FEP. Several analytical approaches including HPLC, GC-EI-MS, HRMS analyses, NMR spectroscopy and X-ray crystal structure analysis enabled the unambiguous identification of threo- and erythro-4-FEP. The analytical data presented in this article will be useful for identifying threo- and erythro-4-FEP included in illicit products.

Investigating migration potential of a new rechargeable antimicrobial coating for food processing equipment

Antimicrobial coatings are designed to inhibit the growth of pathogens and have been used to reduce foodborne illness bacteria on food processing equipment. Novel N-halamine based antimicrobial coatings are highly advantageous due to their unique properties and low cost, and are being investigated for applications in food safety, health care, water and air disinfection, etc. In this study, we evaluated the chemical safety of a novel N-halamine antimicrobial polymer coating (Halofilm) for use on food processing equipment. Migration tests were performed on stainless steel tiles prepared with four different treatment groups: negative control, positive control, Halofilm coating without chlorination, and Halofilm coating with chlorination. An LC-MS/MS method was developed and validated for four formulation components: polyethylenimine (PEI), Trizma® base, hydantoin acrylamide (HA) and dopamine methacrylamide (DMA), followed by stability and recovery tests. Migration tests were conducted at 40 °C with three food simulants (10, 50 and 95% ethanol/water) to mimic various food properties, and aliquots of migration extracts were analyzed at 2, 8, 72, 240 and 720 h. In general, measured concentration levels were consistent among simulant types for the four tested chemicals. Chlorinated tiles had non-detects for three analytes (PEI, HA and DMA), and less than 0.05 mg/kg of HA migration over 30 days. A chlorination step could possibly change the measured mass (m/z) hence leading to non-detects in targeted LC-MS/MS. In non-chlorinated tiles, all four compounds were detected during the migration test. This suggests that addition of the chlorination step may have a stabilizing effect on the polymer. Additionally, full scan high resolution mass spectrometry (HRMS) analysis was employed to screen for migration of other extractable and leachable (E&L) chemicals, which led to the identification of eight common E&L chemicals. To our knowledge, this is the first report evaluating chemical migration from an N-halamine antimicrobial polymer coating product.

Metabolomic differentiation of benign vs malignant pulmonary nodules with high specificity via high-resolution mass spectrometry analysis of patient sera

Differential diagnosis of pulmonary nodules detected by computed tomography (CT) remains a challenge in clinical practice. Here, we characterize the global metabolomes of 480 serum samples including healthy controls, benign pulmonary nodules, and stage I lung adenocarcinoma. The adenocarcinoma demonstrates a distinct metabolomic signature, whereas benign nodules and healthy controls share major similarities in metabolomic profiles. A panel of 27 metabolites is identified in the discovery cohort (n = 306) to distinguish between benign and malignant nodules. The discriminant model achieves an AUC of 0.915 and 0.945 in the internal validation (n = 104) and external validation cohort (n = 111), respectively. Pathway analysis reveals elevation in glycolytic metabolites associated with decreased tryptophan in serum of lung adenocarcinoma vs benign nodules and healthy controls, and demonstrates that uptake of tryptophan promotes glycolysis in lung cancer cells. Our study highlights the value of the serum metabolite biomarkers in risk assessment of pulmonary nodules detected by CT screening.

Molecular hybrid of 1,2,3-triazole and schiff base as potential antibacterial agents: DFT, molecular docking and ADME studies

Hybrid drugs help combat antibacterial drug resistance, which is an increasing problem globally. In addition to saving time and money, hybrid drugs offer multiple benefits. Using the triazole precursor compound 5 in conjunction with primary amines, a series of novel 1,2,3-triazole and Schiff base compounds were synthesized (6–16). Their chemical structures were characterized using 1H NMR, 13C NMR, FTIR, CHN-elemental, high-resolution mass spectrometry and SC-XRD analyses. All the compounds showed good antibacterial activities against twelve bacterial strains at different concentrations. From the minimum inhibitory concentration and cytotoxicity studies, compounds 7, 9, 10, 11, 12 and 15 were selected as the most potent potential drug candidates against Mycobacterium smegmatis, Proteus mirabilis, Escherichia coli and Klebsiella pneumonia. Molecular docking studies of the most active compounds were done against their specific bacteria targets. Experimentally observed structure-activity relationships (SARs) for the most active compounds are consistent with molecular docking studies, indicating that benzylic (7 and 9), heterocyclic (10, 11, and 12) and electron-withdrawing (15) subunits enhance antibacterial activity. The absorption, distribution, metabolism, and excretion (ADME) parameter, Molinspiration bioactivity score, and the PreADMET properties revealed that most of the synthesized compounds possess desirable physicochemical properties for druglikeness and may be considered as orally active potential drugs.