Hasil untuk "Organic chemistry"

Yonatan Uziel, Natan Orlov, Loay Atamneh et al.

Chemical monitoring of pollutants and hazardous materials in water supply systems traditionally depends on centralized laboratories, advanced instrumentation, and trained personnel, limiting accessibility and preventing real-time, on-site analysis. This work presents an alternative cost-effective, field-deployable approach that uses genetically engineered bioluminescent bioreporters, encapsulated in self-sufficient alginate capsules and integrated with an optoelectronic detection circuit, to detect and quantify target materials in water. We have developed a scalable single-channel prototype featuring four sensing tracks—two for sample measurement, one for clean water, and one for a standard reference solution. The latter employs the standard ratio (SR) method to ensure robust quantification, compensating for batch variability and environmental effects. System characterization showed high uniformity across tracks. Validation with nalidixic acid (NA) demonstrated reliable quantitative performance, with a blind test estimation of 5.6 mg/L for a true concentration of 5 mg/L, well within the calibration error range. Additional sensitivity testing confirmed detection of mitomycin C (MMC) at concentrations as low as 50 µg/L. Overall, the results highlight the potential of bacterial chemical sensing as a practical and scalable tool for real-time, in situ water quality monitoring networks.

Zdenek Krejcik, David Kundrat, Jiri Klema et al.

Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear. Methods In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients. Results Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity. Conclusions Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis. Graphical Abstract

Özlem Sefer, Emre Yörük, Fatma Berra Yücesan

Fusarium culmorum is a worldwide phytopathogenic fungus of small-grain cereals. Struggling strategies such as fungicide treatment and biocontrol agent usage are not long-term solutions due to the potential adverse effects on ecological environment and resistance development in fungal pathogens. In this study, potential suppressive effects of amino acid supplementation on F. culmorum were investigated. Potato dextrose agar (PDA) medium amended with 1 mg mL-1 and 2 mg mL-1 concentrations of L-arginine and L-methionine were used as experimental sets. PDA with no supplement and PDA amended with nicotinamide of 1 mg mL-1 and 2 mg mL-1 concentrations were used as negative and positive control sets, respectively. While L-arginine treatment led to significant increase in linear growth rate (LGR) with p<0.01, L-methionine decreased LGR values (p<0.001). Coupled Restriction Enzyme Digestion-Random Amplification (CRED-RA) essays yielded very similar alterations in terms of genomic template stability within the experiment groups of L-arginine and L-methionine treated sets. UPGMA-dendrogram (unweighted pair group method with arithmetic mean) revealed co-clustering of L-methionine and nicotinamide treated sets. Methylation-specific PCR (MSP) analysis showed that there was Type-II and Type-III methylation present in 2 mg mL-1 L-methionine treated sets. Gene expression analysis showed that L-methionine and L-arginine treatment led to contrast alteration in expressions of tri6 and FcStuA genes with significant differences (p<0.05-p<0.0001). Our results showed that L-methionine treatment could suppress potential aggressiveness of F. culmorum at phenotypic, epigenetics, and transcriptional levels

Hyebin Choi, Jisook Yim, Jiwon Yun et al.

Plasma-free metanephrines are the most sensitive and specific biochemical markers for diagnosing catecholamine-secreting tumors, such as pheochromocytoma and paraganglioma. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry method for quantifying metanephrine and normetanephrine in human plasma, using solid-phase extraction with a weak cation-exchange mechanism. Validation was performed according to the FDA Bioanalytical Method Validation Guidance and CLSI guideline C62-A. The method showed excellent linearity over concentration ranges of 0.11–13.92 nmol/L for metanephrine and 0.14–26.43 nmol/L for normetanephrine, with correlation coefficients exceeding 0.999. The accuracy, precision, and lower limit of quantification met the acceptance criteria of the study. Matrix effect evaluation revealed a process efficiency of 121% for metanephrine at the lowest concentration, slightly exceeding the acceptable range of 100 ± 15%. This was likely because of matrix-induced ion enhancement or variability in extraction efficiency. However, all other tested concentrations were within the acceptable limits. Overall, this method demonstrated high sensitivity, specificity, and reproducibility, making it suitable for routine clinical applications. Minor deviations at low concentrations do not compromise reliability; however, future optimizations, such as matrix-matched calibration, may further improve performance.

Nohaila Rharmili, Omar Abdellaoui, Fouad Ouazzani Chahdi et al.

The indoline portion of the title molecule, C16H13NO2, is planar. In the crystal, a layer structure is generated by C—H...O hydrogen bonds and C—H...π(ring), π-stacking and C=O...π(ring) interactions. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (43.0%), H...C/C...H (25.0%) and H...O/O...H (22.8%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. The volume of the crystal voids and the percentage of free space were calculated to be 120.52 Å3 and 9.64%, respectively, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated by the dispersion energy contributions in the title compound. Moreover, the DFT-optimized structure at the B3LYP/6-311G(d,p) level is compared with the experimentally determined molecular structure in the solid state.

Donghua Xu, Olivia Gordon, Muyang Ye et al.

Multicomponent metallic glasses (MGs) are a fascinating class of advanced alloys known for their exceptional properties such as limit-approaching strength, high hardness and corrosion resistance, and near-net-shape castability. One important question regarding these materials that remains unanswered is how the different elements and atomic bonds within them control their strength and deformability. Here, we present a detailed visual and statistical analysis of the behaviors of various elements and atomic bonds in the Zr₄₇Cu₄₆Al₇ (at%) MG during a uniaxial tensile test (in the z-direction) simulated using molecular dynamics. Specifically, we investigate the identities of atoms undergoing significant shear strain, and the averaged bond lengths, projected z-lengths, and z-angles (angles with respect to the z-direction) of all the atomic bonds as functions of increasing strain. We show that, prior to yielding, the Zr element and the intermediate (Zr-Zr, Cu-Al) and stronger (Zr-Al, Zr-Cu) bonds dominate the elastic deformation and strength, while the Cu and Al elements and the weaker Al-Al and Cu-Cu bonds contribute more to the highly localized shear transformation. The significant reconstruction, as signified by the cessation of bond-length increment and bond-angle decrement, of the intermediate and the stronger bonds triggers yielding of the material. After yielding, all the elements and bonds participate in the plastic deformation while the stronger bonds contribute more to the residual strength and the ultimate (fracture) strain. The results provide new insights into the atomic mechanisms underlying the mechanical behavior of multicomponent MGs, and may assist in the future design of MG compositions towards better combination of strength and deformability.

Aleksandra Trocha, Dorota G. Piotrowska, Iwona E. Głowacka

Simple and efficient strategies for the syntheses of enantiomerically enriched functionalized diethyl 2-amino-, 2,3-diamino- and 2-amino-3-hydroxypropylphosphonates have been developed starting from, respectively, <i>N</i>-protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl (<i>R</i>)- and (<i>S</i>)-2-(<i>N</i>-Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected (<i>R</i>)- and (<i>S</i>)-2,3-diaminopropylphosphonates were synthesized from (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of (<i>R</i>)- and (<i>S</i>)-2-(<i>N</i>-Boc-amino)-3-azidopropylphosphonates using triphenylphosphine. On the other hand, treatment of the corresponding (<i>R</i>)- and (<i>S</i>)-<i>N</i>-Bn-(aziridin-2-yl)methylphosphonates with glacial acetic acid led regiospecifically to the formation of (<i>R</i>)- and (S)-2-(<i>N</i>-Bn-amino)-3-acetoxypropylphosphonates.

Hong-Gyun Lee, Min-Ji Cho, Je-Min Choi

Mohamed W. Attwa, Ahmed H. Bakheit, Ali S. Abdelhameed et al.

Acalabrutinib, commercially known as Calquence^®, is a pharmacological molecule that has robust inhibitory activity against Bruton tyrosine kinase. The medicine in question was carefully developed by the esteemed pharmaceutical company AstraZeneca. The FDA granted authorization on 21 November 2019 for the utilization of acalabrutinib (ACB) in the treatment of small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) in adult patients. The aim of this study was to develop a UPLC–MS/MS method that is effective, accurate, environmentally sustainable, and has a high degree of sensitivity. The methodology was specifically developed with the intention of quantifying ACB in human liver microsomes (HLMs). The methodology described above was subsequently utilized to assess the metabolic stability of ACB in HLMs in an in vitro environment. The validation procedures for the UPLC–MS/MS method in the HLMs were conducted in accordance with the bioanalytical method validation criteria established by the U.S.- DA. The utilization of the StarDrop software (version 6.6), which integrates the P450 metabolic module and DEREK software (KB 2018 1.1), was employed for the purpose of evaluating the metabolic stability and identifying potential hazardous alarms associated with the chemical structure of ACB. The calibration curve, as established by the ACB, demonstrated a linear correlation across the concentration range of 1 to 3000 ng/mL in the matrix of HLMs. The present study conducted an assessment of the accuracy and precision of the UPLC–MS/MS method in quantifying inter-day and intra-day fluctuations. The inter-day accuracy demonstrated a spectrum of values ranging from −1.00% to 8.36%, whilst the intra-day accuracy presented a range of values spanning from −2.87% to 4.11%. The t_1/2 and intrinsic clearance (Cl_int) of ACB were determined through in vitro testing to be 20.45 min and 39.65 mL/min/kg, respectively. The analysis concluded that the extraction ratio of ACB demonstrated a moderate level, thus supporting the recommended dosage of ACB (100 mg) to be administered twice daily for the therapeutic treatment of persons suffering from B-cell malignancies. Several computational tools have suggested that introducing minor structural alterations to the butynoyl group, particularly the alpha, beta-unsaturated amide moiety, or substituting this group during the drug design procedure, could potentially enhance the metabolic stability and safety properties of novel derivatives in comparison to ACB.

Shuaijie He, Mingjie Wu, Song Li et al.

High-performance electrocatalysts are critical to support emerging electrochemical energy storage and conversion technologies. Graphite-derived materials, including fullerenes, carbon nanotubes, and graphene, have been recognized as promising electrocatalysts and electrocatalyst supports for the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and carbon dioxide reduction reaction (CO₂RR). Effective modification/functionalization of graphite-derived materials can promote higher electrocatalytic activity, stability, and durability. In this review, the mechanisms and evaluation parameters for the above-outlined electrochemical reactions are introduced first. Then, we emphasize the preparation methods for graphite-derived materials and modification strategies. We further highlight the importance of the structural changes of modified graphite-derived materials on electrocatalytic activity and stability. Finally, future directions and perspectives towards new and better graphite-derived materials are presented.

Thi Minh Nguyet Nguyen, So-Young Ban, Kyu-Been Park et al.

Chaga mushroom (<i>Inonotus obliquus</i>) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

Yu-Chieh Huang, Pierre Tremouilhac, An Nguyen et al.

Abstract ChemSpectra, a web-based software to visualize and analyze spectroscopic data, integrating solutions for infrared spectroscopy (IR), mass spectrometry (MS), and one-dimensional 1H and 13C NMR (proton and carbon nuclear magnetic resonance) spectroscopy, is described. ChemSpectra serves as web-based tool for the analysis of the most often used types of one-dimensional spectroscopic data in synthetic (organic) chemistry research. It was developed to support in particular processes for the use of open file formats which enable the work according to the FAIR data principles. The software can deal with the open file formats JCAMP-DX (IR, MS, NMR) and mzML (MS) proposing these data file types to gain interoperable data. ChemSpectra can be extended to read also other formats as exemplified by selected proprietary mass spectrometry data files of type RAW and NMR spectra files of type FID. The JavaScript-based editor can be integrated with other software, as demonstrated by integration into the Chemotion electronic lab notebook (ELN) and Chemotion repository, demonstrating the implementation into a digital work environment that offers additional functionality and sustainable research data management options. ChemSpectra supports different functions for working with spectroscopic data such as zoom functions, peak picking and automatic peak detection according to a default or manually defined threshold. NMR specific functions include the definition of a reference signal, the integration of signals, coupling constant calculation and multiplicity assignment. Embedded into a web application such as an ELN or a repository, the editor can also be used to generate an association of spectra to a sample and a file management. The file management supports the storage of the original spectra along with the last edited version and an automatically generated image of the spectra in png format. To maximize the benefit of the spectra editor for e.g. ELN users, an automated procedure for the transfer of the detected or manually chosen signals to the ELN was implemented. ChemSpectra is released under the AGPL license to encourage its re-use and further developments by the community.

Lidia Węglińska, Adrian Bekier, Katarzyna Dzitko et al.

Congenital and acquired toxoplasmosis caused by the food- and water-born parasite <i>Toxoplasma gondii</i> (<i>T. gondii</i>) is one of the most prevalent zoonotic infection of global importance. <i>T. gondii</i> is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (<b>1b</b>–<b>12b</b>) for their effects on <i>T. gondii</i> host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of <i>T. gondii</i> growth inhibition (IC₅₀) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with <i>meta</i>-fluoro <b>2b</b>, meta-chloro <b>5b</b>, meta-bromo <b>8b</b>, meta-iodo <b>11b</b> and para-iodo <b>12b</b> substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was <i>para</i>-iodo derivative <b>12b</b> that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles <b>1b</b>–<b>12b</b>, especially <b>12b</b> with IC₅₀ of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-<i>Toxoplasma</i> agents that effectively and selectively block the invasion and subsequent proliferation of <i>T. gondii</i> into host cells.

Ella Schoolaert, Luisa Cossu, Jana Becelaere et al.

This work shows the design of highly porous membranes with tunable wettability based on poly(2-n-propyl-2-oxazoline) (PnPrOx) nanofibers. Wicking and advanced contact angle experiments demonstrate the high potential for applications requiring specific interactions with aqueous media. PnPrOx is a popular member among the biocompatible poly(2-oxazoline)s due to its thermoresponsiveness in aqueous solutions, enabling the production of ‘smart materials’. On material level, however, many interesting properties of this polymer remain undiscovered. Electrospinning is an ideal technique to transfer the properties observed in solutions to end-material properties, as the polymer is processed into highly porous, nanofibrous membranes. PnPrOx' electrospinnability is here investigated in environmentally friendly ethanol/water solvent systems, ensuring industrial scalability. The nanofibrous membranes show increased hydrophobicity exhibiting the rose-petal effect. Upon functionalization with tannic acid, the hydrophobic membranes are transformed into hydrophilic nanofibers showing water-stability in both fresh and salty water, even below the polymer cloud point temperature. By varying the tannic acid amount, the hydrophilicity can be fine-tuned as the contact area between water droplets and surface, the rate and manner of water uptake and the extent of the rose-petal effect can be manipulated easily. Hence an interesting material is designed for applications in which water caption and transport are important.

Belal J. Muhialdin, Nazamid Saari, Anis Shobirin Meor Hussin

The challenges to fulfill the demand for a safe food supply are dramatically increasing. Mycotoxins produced by certain fungi cause great economic loss and negative impact on the sustainability of food supplies. Moreover, the occurrence of mycotoxins at high levels in foods poses a high health threat for the consumers. Biological detoxification has exhibited a high potential to detoxify foodstuffs on a cost-effective and large scale. Lactic acid bacteria showed a good potential as an alternative strategy for the elimination of mycotoxins. The current review describes the health and economic impacts associated with mycotoxin contamination in foodstuffs. Moreover, this review highlights the biological detoxification of common food mycotoxins by lactic acid bacteria.

Xiaobei Jin, Jingpeng Li, Rong Zhang et al.

Bamboo-plastic composites (BPCs) as new biomass-plastic composites have recently attracted much attention. However, weak mechanical performance and high moisture absorption as well as low thermal stability greatly limit their industrial applications. In this context, different amounts of halloysite nanotubes (HNTs) were used as a natural reinforcing filler for BPCs. It was found that the thermal stability of BPCs increased with increasing HNT contents. The mechanical strength of BPCs was improved with the increase in HNT loading up to 4 wt% and then worsened, while the impact strengths were slightly reduced. Low HNT content (below 4 wt%) also improved the dynamic thermomechanical properties and reduced the water absorption of the BPCs. Morphological studies confirmed the improved interfacial compatibility of the BPC matrix with 4 wt% HNT loading, and high-concentration HNT loading (above 6 wt%) resulted in easy agglomeration. The results highlight that HNTs could be a feasible candidate as nanoreinforcements for the development of high-performance BPCs.

Deepak Subedi, Surya Prasad Devkota, Dharm Raj Bhatta et al.

Keli Cui, Meng Gao, Hongyi Zhao et al.

An efficient arylation of SEM-protected pyrroles by the Suzuki&#8211;Miyaura coupling reaction has been developed. The reaction can be carried out under mild conditions to provide aryl-substituted pyrroles in moderate to excellent yields. The scope and limitations of the methodology were evaluated, and the reaction was tolerant of a wide range of functionalities. Compared to the reported methods, the protocol has some advantages, such as commercially available materials, no debrominated by-products being formed, and the amine-protecting group being stable under the reaction conditions. The synthetic utility of the product has also been demonstrated, with several common transformations of the aryl-substituted pyrrole product being conducted. This protocol will offer the opportunity to explore other metal-catalyzed cross-coupling reactions employing SEM-protected pyrroles.

C. D. Christopoulos, S. Garimella, S. Garimella et al.

<p>Compositional analysis of atmospheric and laboratory aerosols is often conducted via single-particle mass spectrometry (SPMS), an in situ and real-time analytical technique that produces mass spectra on a single-particle basis. In this study, classifiers are created using a data set of SPMS spectra to automatically differentiate particles on the basis of chemistry and size. Machine learning algorithms build a predictive model from a training set for which the aerosol type associated with each mass spectrum is known a priori. Our primary focus surrounds the growing of random forests using feature selection to reduce dimensionality and the evaluation of trained models with confusion matrices. In addition to classifying  ∼ 20 unique, but chemically similar, aerosol types, models were also created to differentiate aerosol within four broader categories: fertile soils, mineral/metallic particles, biological particles, and all other aerosols. Differentiation was accomplished using  ∼ 40 positive and negative spectral features. For the broad categorization, machine learning resulted in a classification accuracy of  ∼ 93&thinsp;%. Classification of aerosols by specific type resulted in a classification accuracy of  ∼ 87&thinsp;%. The <q>trained</q> model was then applied to a <q>blind</q> mixture of aerosols which was known to be a subset of the training set. Model agreement was found on the presence of secondary organic aerosol, coated and uncoated mineral dust, and fertile soil.</p>

T. McMeekin