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Background: One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy. Methods: To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that these derivatives modulate hexokinase activity differently. Results: Fluorinated compounds show the most potent cytotoxic effects, indicated by the lowest IC50 values. These effects were more pronounced in hypoxic conditions. 19F NMR experiments and molecular docking confirmed that fluorinated derivatives bind hexokinase comparably to glucose. Enzymatic assays demonstrated that all halogenated derivatives are more effective HKII inhibitors than 2-DG, particularly through their 6-phosphates. By modifying the C-2 position with halogens, these compounds may overcome the poor pharmacokinetics of 2-DG. The modifications seem to enhance the stability and uptake of the compounds, making them effective at lower doses and over prolonged periods. Conclusions: This research has the potential to reshape the treatment landscape for GBM and possibly other cancers by offering a more targeted, effective, and metabolically focused therapeutic approach. The application of halogenated 2-DG analogs represents a promising advancement in cancer metabolism-targeted therapies, with the potential to overcome current treatment limitations.

The quinoline ring is found in many biologically active natural alkaloids and is still being highly exploited by researchers due to its numerous potential applications in fields ranging from pharmacology to material science. During our synthetic attempts for new quinoline-4-carboxylic acids, using an extended version of the Doebner reaction, a new puzzling compound emerged when para-iodine aniline was reacted with salicylaldehyde and pyruvic acid in acetic acid as a reaction medium. The chemical structure of this new compound was established based on the information obtained from 1D and 2D NMR experiments (1H-, 13C-, and 15N-NMR), corroborated with MS spectrometry and IR spectroscopy. The photophysical properties (UV–vis and fluorescence) were also investigated. The proposed structure contains as the main elements a 1,4-dioxane-2,5-dione core symmetrically substituted with a propylidene chain that has attached to it a salicylaldehyde fragment and a pyrrole-2-one ring containing two 4-iodophenyl fragments. The isolation of this compound, reported here for the first time, is direct evidence that unexpected compounds can emerge from “classical” synthetic pathways when the right components are combined.

In the context of our ongoing studies on chromane derivatives as inhibitors of the salicylate synthase from M. tuberculosis, we isolated a new, unexpected compound from the cyclization of 3-(propargyloxy)-5-benzyloxy-benzoic acid methyl ester. Its molecular structure was elucidated by means of 1D and 2D NMR analyses, FT-IR, ESI-MS, and HRMS.

In this study, we assessed the quantity, strength, and acidity of zeolite composites comprising Silicalite-1 grown on ZSM-5 crystals using a combination of infrared (IR) and solid-state nuclear magnetic resonance (NMR) spectroscopy. The composites were created through the direct growth of Silicalite-1 crystals on ZSM-5 (P_ZSM-5), either with or without the organic structure-directing agent (OSDA) introduced into the ZSM-5 channels (samples: H_ZSM-5_Sil1 and TPA_ZSM-5_Sil1). The results revealed that Silicalite-1 grew differently when the ZSM-5 core was in the H+ form (empty pores) compared to when the OSDA was still present in the sample. This distinction was evident in the textural properties, with a decrease in the micropore surface area and an increase in the external surface area in the H_ZSM-5_Sil1 compared to the parent sample. The TPA_ZSM-5_Sil1 composite exhibited characteristics similar to the parent zeolite. These findings were further supported by 29Si NMR, which revealed a comparable local order for the parent (P_ZSM-5) and TPA_ZSM-5_Sil1 samples, along with a broadening of the Q4 peak for the H_ZSM-5_Sil1 composite. Additionally, the acid sites were preserved in the TPA_ZSM-5_Sil1 composite, while in the H+-form core, the concentration of Brønsted acid sites significantly decreased. This reduction in isolated Brønsted acid sites was further corroborated by 1H NMR.

The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS. We observed negative correlations between adiponectin and VLDL, IDL, and small-dense LDL in healthy males, but neither in healthy females nor in females or males with MS. Additionally, adiponectin was positively correlated with some HDL subclasses in healthy males and females with MS, but not in healthy females or males with MS. Adjusting for age and either body mass index, waist circumference, C-reactive protein, or interleukin-6 weakened the associations between adiponectin and VLDL and IDL but not small-dense LDL. The adjustment weakened the associations between adiponectin and HDL in healthy males but not in females with MS. Based on our results, we conclude that sex and the presence of MS are strong determinants of the associations between adiponectin and serum lipoproteins and that the complex regulatory network comprising adiponectin and other molecular players involved in the regulation of lipoprotein metabolism is primarily operative in healthy males and females with MS.

Folic acid (FA) is an essential vitamin involved in crucial metabolic processes, while copper(II) ions play significant roles in various biological functions. This study aims to investigate the interaction between FA and Cu2+ using 1H and 13C NMR spectroscopy under different pH levels and concentrations. The research employed detailed NMR analysis to explore how Cu2+ binds to FA, focusing on changes in chemical shifts, diffusion coefficients, and copper-induced paramagnetic effects. The key findings reveal that Cu2+ predominantly coordinates with the pteridine ring (PTE) of FA, with minimal involvement from the glutamic acid (Glu) moiety. The interaction is strongly concentration-dependent: at lower FA concentrations, Cu2+ binds effectively to the PTE ring, while at higher concentrations, intermolecular interactions among FA molecules hinder copper binding. The study also observed pronounced paramagnetic effects on the PTE and p-aminobenzoic acid protons, with negligible effects on Glu signals. These results provide new insights into the structural characteristics of FA-Cu2+ complexes, contributing to a better understanding of their biochemical interactions and implications for folate metabolism.

Ultrasmall silver nanoparticles (2 nm) were prepared by reduction with sodium borohydride (NaBH4) and stabilized by the ligand glutathione (a tripeptide: glycine–cysteine–glutamic acid). NMR spectroscopy and optical spectroscopy (UV and fluorescence) revealed that these particles initially consist of silver nanoparticles and fluorescing silver nanoclusters, both stabilized by glutathione. Over time, the silver nanoclusters disappear and only the silver nanoparticles remain. Furthermore, the capping ligand glutathione eliminates hydrogen sulfide (H2S) from the central cysteine and is released from the nanoparticle surface as tripeptide glycine–dehydroalanine–glutamic acid. Hydrogen sulfide reacts with the silver core to form silver sulfide. After four weeks in dispersion at 4 °C, this process is completed. These processes cannot be detected by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), or differential centrifugal sedimentation (DCS) as these methods cannot resolve the mixture of nanoparticles and nanoclusters or the nature of the nanoparticle core. X-ray photoelectron spectroscopy showed the mostly oxidized state of the silver nanoparticle core, Ag(+I), both in freshly prepared and in aged silver nanoparticles. These results demonstrate that ultrasmall nanoparticles can undergo unnoticed changes that considerably affect their chemical, physical, and biological properties. In particular, freshly prepared ultrasmall silver nanoparticles are much more toxic against cells and bacteria than aged particles because of the presence of the silver clusters.

Biliverdin IXβ reductase (BLVRB) has emerged as a promising therapeutic target for thrombocytopenia due to its involvement in reactive oxygen species (ROS) mechanisms. During the pursuit of inhibitors targeting BLVRB, olsalazine (OSA) became apparent as one of the most potent candidates. However, the direct application of OSA as a BLVRB inhibitor faces challenges, as it is prone to degradation into 5-aminosalicylic acid through cleavage of the diazenyl bond by abundant azoreductase (AzoR) enzymes in gut microbiota and eukaryotic cells. To overcome this obstacle, we devised olsalkene (OSK), an inhibitor where the diazenyl bond in OSA has been substituted with an alkene bond. OSK not only matches the efficacy of OSA but also demonstrates improved stability against degradation by AzoR, presenting a promising solution to this limitation. Furthermore, we have found that both OSK and OSA inhibit BLVRB, regardless of the presence of nicotinamide adenine dinucleotide phosphate, unlike other known inhibitors. This discovery opens new avenues for investigating the roles of BLVRB in blood disorders, including thrombocytopenia.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson’s coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

As obesity develops, metabolic changes increase the risk of non-communicable diseases such as type 2 diabetes (T2D). Weight loss is crucial for improving health in T2D and cardiometabolic conditions. However, weight loss rates vary between individuals, even with identical diets or energy restrictions, highlighting the need to identify markers or predictors of weight loss success to enhance intervention outcomes. Using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics, we investigated the change in serum polar metabolites in 28 women with overweight or obesity and prediabetes who completed an 8-week low-energy diet (LED) as part of the PREVIEW (PREVention of diabetes through lifestyle intervention and population studies in Europe and around the World) clinical trial. We aimed to characterize the metabolic shift in substrate oxidation under fixed energy intake (~4 MJ/day) and its relation to weight loss success. Nine of the thirty-four serum metabolites identified significantly changed during the LED phase: 3-hydroxybutyrate, O-acetylcarnitine, 2-hydroxybutyrate, mannose, dimethyl sulfone and isobutyrate increased, whilst choline, creatine and tyrosine decreased. These results confirmed a shift towards lipid oxidation, but no metabolites predicted the response to the LED-induced weight loss. Further studies in larger populations are required to validate these metabolites as biomarkers of diet exposure.

A novel tridentate ligand featuring an acridine core and pyrazole rings, namely 2,7- di-tert-butyl-4,5-di(pyrazol-1-yl)acridine, L, was designed and used to create two ruthenium(II) complexes: [RuL2](PF6)2 and [Ru(tpy)L](PF6)2. Surprisingly, the ligand adopted different coordination modes in the complexes: facial coordination for the homoleptic complex and meridional coordination for the heteroleptic complex. The electronic absorption and electrochemical properties were evaluated. Although both complexes exhibited favorable electronic properties for luminescence, neither emitted light at room temperature nor at 77 K. This study highlights the complex interplay between ligand design, coordination mode, and luminescence in ruthenium(II) complexes.

The data on the synthesis of N-aminomorpholine hydrazones are presented. It is shown that the interaction of N-aminomorpholine with functionally substituted benzaldehydes and 4-pyridinaldehyde in isopropyl alcohol leads to the formation of corresponding hydrazones. The structure of the synthesized compounds was studied by 1H and 13C NMR spectroscopy methods, including the COSY (1H-1H), HMQC (1H-13C) and HMBC (1H-13C) methodologies. The values of chemical shifts, multiplicity, and integral intensity of 1H and 13C signals in one-dimensional NMR spectra were determined. The COSY (1H-1H), HMQC (1H-13C), and HMBC (1H-13C) results revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The antiviral, cytotoxic, and antimicrobial activity of some synthesized hydrazones were investigated. It is shown that 2-((morpholinoimino)methyl)benzoic acid has a pronounced viral inhibitory property, comparable in its activity to commercial drugs Tamiflu and Remantadine. A docking study was performed using the influenza virus protein models (1930 Swine H1 Hemagglutinin and Neuraminidase of 1918 H1N1 strain). The potential binding sites that are complementary with 2-((morpholinoimino)methyl)benzoic acid were found.

Contrary to the 4′- and 5′-nitro- and aminofluoresceins, the corresponding 3′-derivatives are practically unexplored. In this paper, we describe the synthesis and spectral properties of 3′-nitrofluorescein and 3′-aminofluorescein, as well as their methyl esters. Among other methods, X-ray analysis, 13C NMR spectroscopy, and ESI mass spectrometry made it possible to establish the molecular structure of the target compounds as well as intermediates and by-products. Some unexpected products, though in small amounts, were revealed within the course of study. Whereas the fluorescence of the double-charged R2− ion of 3′-nitrofluorescein in both aqueous and organic solvents is weak, the R2− anion of 3′-aminofluorescein in a non-hydrogen bonding donor solvent, but not in water, exhibits intensive fluorescence, analogous to the case of 4′- and 5′-aminofluoresceins. Interestingly, the λmax values in water of the R2− ions bearing an NO2 group in the 3′- and 6′-positions are 7 to 10 nm higher than those of the 4′- and 5′-nitro derivatives. The difference was also observed in dimethyl sulfoxide. This correlates with the angles between the xanthene and phthalic planes of the dyes. The dye 3′-aminofluorescein could be used as a fluorescent indicator sensitive to hydrogen bonding ability of the solvent. It could also serve as a platform for synthesizing fluorescent molecular probes for biochemical research, analogous to the very popular application of 4′- and 5′-amino derivatives.

To reduce unwanted fat bloom in the manufacturing and storage of chocolates, detailed knowledge of the chemical composition and molecular mobility of the oils and fats contained is required. Although the formation of fat bloom on chocolate products has been studied for many decades with regard to its prevention and reduction, questions on the molecular level still remain to be answered. Chocolate products with nut-based fillings are especially prone to undesirable fat bloom. The chemical composition of fat bloom is thought to be dominated by the triacylglycerides of the chocolate matrix, which migrate to the chocolate’s surface and recrystallize there. Migration of oils from the fillings into the chocolate as driving force for fat bloom formation is an additional factor in the discussion. In this work, the migration was studied and confirmed by MRI, while the chemical composition of the fat bloom was measured by NMR spectroscopy and HPLC–MS, revealing the most important triacylglycerides in the fat bloom. The combination of HPLC–MS with NMR spectroscopy at 800 MHz allows for detailed chemical structure determination. A rapid routine was developed combining the two modalities, which was then applied to investigate the aging, the impact of chocolate composition, and the influence of hazelnut fillings processing parameters, such as the degree of roasting and grinding of the nuts or the mixing time, on fat bloom formation.

Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital for bacterial cells and an emerging drug target for various bacterial infections. Understanding the enzymatic mechanisms and structural intricacies of bacterial Pth is pivotal in designing novel therapeutics to combat antibiotic resistance. This review provides a comprehensive analysis of the multifaceted roles of Pth in bacterial physiology, shedding light on its significance as a potential drug target. This article delves into the diverse functions of Pth, encompassing its involvement in ribosome rescue, the maintenance of a free tRNA pool in bacterial systems, the regulation of translation fidelity, and stress response pathways within bacterial systems. Moreover, it also explores the druggability of bacterial Pth, emphasizing its promise as a target for antibacterial agents and highlighting the challenges associated with developing specific inhibitors against this enzyme. Structural elucidation represents a cornerstone in unraveling the catalytic mechanisms and substrate recognition of Pth. This review encapsulates the current structural insights of Pth garnered through various biophysical techniques, such as X-ray crystallography and NMR spectroscopy, providing a detailed understanding of the enzyme’s architecture and conformational dynamics. Additionally, biophysical aspects, including its interaction with ligands, inhibitors, and substrates, are discussed, elucidating the molecular basis of bacterial Pth’s function and its potential use in drug design strategies. Through this review article, we aim to put together all the available information on bacterial Pth and emphasize its potential in advancing innovative therapeutic interventions and combating bacterial infections.

Neural networks (NNs) are emerging as a rapid and scalable method for quantifying metabolites directly from nuclear magnetic resonance (NMR) spectra, but the nonlinear nature of NNs precludes understanding of how a model makes predictions. This study implements an explainable artificial intelligence algorithm called integrated gradients (IG) to elucidate which regions of input spectra are the most important for the quantification of specific analytes. The approach is first validated in simulated mixture spectra of eight aqueous metabolites and then investigated in experimentally acquired lipid spectra of a reference standard mixture and a murine hepatic extract. The IG method revealed that, like a human spectroscopist, NNs recognize and quantify analytes based on an analyte’s respective resonance line-shapes, amplitudes, and frequencies. NNs can compensate for peak overlap and prioritize specific resonances most important for concentration determination. Further, we show how modifying a NN training dataset can affect how a model makes decisions, and we provide examples of how this approach can be used to de-bug issues with model performance. Overall, results show that the IG technique facilitates a visual and quantitative understanding of how model inputs relate to model outputs, potentially making NNs a more attractive option for targeted and automated NMR-based metabolomics.

Cytotoxins (CTs) are three-finger membrane-active toxins present mainly in cobra venom. Our analysis of the available CT amino acid sequences, literature data on their membrane activity, and conformational equilibria in aqueous solution and detergent micelles allowed us to identify specific amino acid residues which interfere with CT incorporation into membranes. They include Pro9, Ser28, and Asn/Asp45 within the N-terminal, central, and C-terminal loops, respectively. There is a hierarchy in the effect of these residues on membrane activity: Pro9 > Ser28 > Asn/Asp45. Taking into account all the possible combinations of special residues, we propose to divide CTs into eight groups. Group 1 includes toxins containing all of the above residues. Their representatives demonstrated the lowest membrane activity. Group 8 combines CTs that lack these residues. For the toxins from this group, the greatest membrane activity was observed. We predict that when solely membrane activity determines the cytotoxic effects, the activity of CTs from a group with a higher number should exceed that of CTs from a group with a lower number. This classification is supported by the available data on the cytotoxicity and membranotropic properties of CTs. We hypothesize that the special amino acid residues within the loops of the CT molecule may indicate their involvement in the interaction with non-lipid targets.

The origin of nuclear magnetic shielding in diamagnetic molecules is discussed, pointing out various contributions to the shielding from electrons and the effects of intra- and intermolecular interactions. In NMR practice, chemical shifts are determined first as the measure of shielding in observed samples. The descriptions of shielding and chemical shifts are not fully consistent. Gas phase studies permit the withdrawal of intermolecular contributions from shielding and obtaining the magnetic shielding data in isolated molecules. The shielding determination in molecules is possible using at least three methods delivering the reference shielding standards for selected nuclei. The known shielding of one magnetic nucleus can be transferred to other nuclei if the appropriate nuclear magnetic moments are available with satisfactory accuracy. It is possible to determine the nuclear magnetic dipole moments using the most advanced ab initio shielding calculations jointly with the NMR frequencies measurements for small-sized isolated molecules. Helium-3 gas is postulated as all the molecules’ primary and universal reference standard of shielding. It can be easily applied using common deuterium lock solvents as the secondary reference standards. The measurements of absolute shielding are available for everyone with the use of standard NMR spectrometers.

Officinal plants are a source of metabolites whose chemical composition depends on pedoclimatic conditions. In this study, the NMR-based approach was applied to investigate the impacts of different altitudes and agronomical practices (Land, Mountain Spontaneous, and Organically Grown Ecotypes, namely LSE, MSE, and OE, respectively) on the metabolite profiles of Burdock root, Dandelion root and aerial part, and Lemon balm aerial part. Sugars, amino acids, organic acids, polyphenols, fatty acids, and other metabolites were identified and quantified in all samples. Some metabolites turned out to be tissue-specific markers. Arginine was found in roots, whereas myo-inositol, galactose, glyceroyldigalactose moiety, pheophytin, and chlorophyll were identified in aerial parts. Caftaric and chicoric acids, 3,5 di-caffeoylquinic acid, and chlorogenic and rosmarinic acids were detected in Dandelion, Burdock and Lemon balm, respectively. The metabolite amount changed significantly according to crop, tissue type, and ecotype. All ecotypes of Burdock had the highest contents of amino acids and the lowest contents of organic acids, whereas an opposite trend was observed in Lemon balm. Dandelion parts contained high levels of carbohydrates, except for the MSE aerial part, which showed the highest content of organic acids. The results provided insights into the chemistry of officinal plants, thus supporting nutraceutical–phytopharmaceutical research.

Coordination complexes of lanthanide metals with tris-1-naphthylphosphine oxide (Nap3PO, L) have not been previously reported in the literature. We describe here the formation of lanthanide(III) nitrate complexes Ln(NO3)3L4 (Ln = Eu to Lu) and the structures of [Ln(NO3)3L2]·2L (Ln = Eu, Dy, Ho, Er) and L. The core structure of the complexes is an eight-coordinate [Ln(NO3)3L2] with the third and fourth ligands H-bonded via their oxygen atoms to one of the naphthyl rings. The structures are compared with those of the analogous complexes of triphenylphosphine oxide and show that the Ln-O(P) bond in the Nap3PO complexes is slightly longer than expected on the basis of differences in coordination numbers. The reaction solutions, investigated by 31P and 13C NMR spectroscopy in CD3CN, show that coordination of L occurs across the lanthanide series, even though complexes can only be isolated from Eu onwards. Analysis of the 31P NMR paramagnetic shifts shows that there is a break in the solution structures with a difference between the lighter lanthanides (La–Eu) and heavier metals (Tb–Lu) which implies a minor difference in structures. The isolated complexes are very poorly soluble, but in CDCl3, NMR measurements show dissociation into [Ln(NO3)3L2] and 2L occurs.

Fermentation parameters, especially the duration, are important in imparting a peculiar taste and flavor to soy sauce. The main purpose of this research was to monitor metabolic changes occurring during the various time intervals of the fermentation process. NMR-based metabolomics was used to monitor the compositional changes in soy sauce during fermentation. The 1H-NMR spectra of the soy sauce samples taken from the fermentation tanks at 0 to 8 months were analyzed using 1H-NMR spectroscopy, and the obtained spectra were analyzed by multivariate statistical analysis. The Principal Component Analysis (PCA) and Partial Least Square Discriminate analysis (PLSDA) revealed the separation of samples fermented for various time durations under identical conditions. Key metabolites shown by corresponding loading plots exhibited variations in amino acids (lysine, threonine, isoleucine, etc.), acetate, glucose, fructose, sucrose, ethanol, glycerol, and others. The levels of ethanol in soy sauce increased with longer fermentation durations, which can be influenced by both natural fermentation and the intentional addition of ethanol as a preservative. The study shows that the variation in metabolite can be very efficiently monitored using 1H-NMR-based metabolomics, thus suggestion to optimize the time duration to get the soy sauce product with the desired taste and flavor.

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.

The use of modern spectroscopic methods of analysis, which provide extensive information on the chemical nature of substances, significantly expands our understanding of the molecular composition and properties of soil organic matter (SOM) and its transformation and stabilization processes in various ecosystems and geochemical conditions. The aim of this review is to identify and analyze studies related to the application of nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy techniques to study the molecular composition and transformation of organic matter in virgin and arable soils. This article is mainly based on three research questions: (1) Which NMR spectroscopy techniques are used to study SOM, and what are their disadvantages and advantages? (2) How is the NMR spectroscopy technique used to study the molecular structure of different pools of SOM? (3) How is ESR spectroscopy used in SOM chemistry, and what are its advantages and limitations? Relevant studies published between 1996 and 2024 were searched in four databases: eLIBRARY, MDPI, ScienceDirect and Springer. We excluded non-English-language articles, review articles, non-peer-reviewed articles and other non-article publications, as well as publications that were not available according to the search protocols. Exclusion criteria for articles were studies that used NMR and EPR techniques to study non-SOM and where these techniques were not the primary methods. Our scoping review found that both solid-state and solution-state NMR spectroscopy are commonly used to study the structure of soil organic matter (SOM). Solution-phase NMR is particularly useful for studying soluble SOM components of a low molecular weight, whereas solid-phase NMR offers advantages such as higher 13C atom concentration for stronger signals and faster analysis time. However, solution-phase NMR has limitations including sample insolubility, potential signal aggregation and reduced sensitivity and resolution. Solid-state NMR is better at detecting non-protonated carbon atoms and identifying heterogeneous regions within structures. EPR spectroscopy, on the other hand, offers significant advantages in experimental biochemistry due to its high sensitivity and ability to provide detailed information about substances containing free radicals (FRs), aiding in the assessment of their reactivity and transformations. Understanding the FR structure in biopolymers can help to study the formation and transformation of SOM. The integration of two- and three-dimensional NMR spectroscopy with other analytical methods, such as chromatography, mass spectrometry, etc., provides a more comprehensive approach to deciphering the complex composition of SOM than one-dimensional techniques alone.

Betaines of squaric acid have gained research interest because of their structural and spectral properties. We elucidated the crystal and molecular structure of the triethylammonium betaine of squaric acid (1) by X-ray crystallography, IR, and NMR spectroscopy augmented by Hirshfeld surface analysis and DFT calculations. The crystal structure determination using Hirshfeld atom refinement reveals that the resonance hybrid structure with partial enolate character of the two lateral squaric acid C=O groups describes 1 best. The solid-state supramolecular structure features weak intermolecular C−H···O hydrogen bonds. The number of C=O bands in the IR spectrum in the solid-state is consistent with local C2v symmetry of the squaric acid residue in 1. The 13C NMR signals of this group in solution were assigned based on 2D NMR experiments and computational prediction using the Gauge-Independent Atom Orbital (GIAO) method. The present study provides the first structural characterization of a betaine of squaric acid containing a four-coordinate nitrogen atom directly attached to the four-membered ring.

The paper studies LiNbO3 (LN) crystals with a near-stoichiometric composition (NSLN). The study establishes the possibility of different physical methods to reveal NSLN crystals’ exact composition. The main goal was to establish how precisely these methods can reveal a NSLN composition, including a defective structure. This structure determines properties that are important for the application of the crystals. Two NSLN crystals with a different Li/Nb ratio have been studied by IR and NMR spectroscopy. NSLN crystals have been grown from a congruent melt with different K2O flux contents (5.0 and 5.5 wt%). The data on NSLN have been compared with the data on congruent (CLN) crystals. CLN are the most widely used LN crystals. The study has established that analysis of the IR spectra can determine the Li/Nb ratio within [Li2O] = 48.6 – 50.0 mol% range, while the 93Nb NMR spectra has a wider range of sensibility. LN crystals’ stoichiometry or the Li/Nb ratio determine the concentration of antisite defects NbLi. Niobium substitutes lithium in its octahedron. Such defects appear up to [Li2O] = 49.9 mol%. Thus, the study shows that IR and NMR spectroscopy are sensitive methods that can complement each other when determining the precise LN composition (Li/Nb ratio) and the presence of intrinsic defects in the crystals.

The aim of the work was the synthesis of a new 28-acetylbetulin derivative containing an ester group with a carbon–carbon triple bond in the C3 position. To obtain the title compound, a reaction of 28-acetylbetulin with but-2-ynoic acid was carried out according to the Steglich method. The synthetized compound was fully characterized by analyzing the nuclear magnetic resonance spectra (1H-NMR, 13C-NMR), as well as the heteronuclear single quantum coherence (HSQC), and by conducting a heteronuclear multiple bond coherence (HMBC) experiment. Infrared (IR) spectroscopy and high-resolution mass spectrometry (HRMS) were also performed. Additionally, pharmacokinetic parameters and drug similarity of the studied molecule were calculated using in silico methods.

The association between advanced oxidation protein products (AOPPs) and lipoprotein subclasses remains unexplored. Therefore, we performed comprehensive lipoprotein profiling of serum using NMR spectroscopy and examined the associations of lipoprotein subclasses with the serum levels of AOPPs in healthy volunteers (HVs) and patients with metabolic syndrome (MS). The serum levels of AOPPs were significantly positively correlated with the serum levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL); however, they were significantly negatively correlated with high-density lipoprotein (HDL). These lipoproteins (and their subclasses) differed markedly regarding the direction of correlations between their lipid contents and AOPPs. The strength of the correlations and the relative contributions of the subclasses to the correlations were different in the HVs and patients with MS. As revealed by orthogonal partial least squares discriminant analyses, the serum levels of IDL were strong determinants of AOPPs in the HVs, whereas the serum levels of VLDL and the lipid content of LDL were strong determinants in both groups. We conclude that IDL, VLDL, and LDL facilitate, whereas HDL diminishes the bioavailability of serum AOPPs. The presence of MS and the lipid contents of the subclasses affect the relationship between lipoproteins and AOPPs.

New arylamide- and arylthiourea-based chiral solvating agents (CSAs) were synthesized starting from commercially available isomannide and isosorbide. The two natural isohexides were transformed into the three amino derivatives, having isomannide, isosorbide, and isoidide stereochemistry, then the amino groups were derivatized with 3,5-dimethoxybenzoyl chloride or 3,5-bis(trifluoromethyl)phenyl isothiocyanate to obtain the CSAs. Bis-thiourea derivative containing the 3,5-bis(trifluoromethyl)phenyl moiety with exo–exo stereochemistry was remarkably efficient in the differentiation of NMR signals (NH and acetyl) of enantiomers of N-acetyl (N-Ac) amino acids in the presence of 1,4-diazabicyclo[2,2,2]octane (DABCO). Nonequivalences in the ranges of 0.104–0.343 ppm and 0.042–0.107 ppm for NH and acetyl groups, respectively, allowed for very accurate enantiomeric excess determination, and a reliable correlation was found between the relative positions of signals of enantiomers and their absolute configuration. Therefore, a complete stereochemical characterization could be performed. Dipolar interactions detected in the ternary mixture CSA/N-Ac-valine/DABCO led to the identification of a different interaction model for the two enantiomers, involving the formation of a one-to-one substrate/CSA complex for (S)-N-Ac-valine and a one-to-two complex for (R)-N-Ac-valine, as suggested by the complexation stoichiometry.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a pivotal immune checkpoint receptor, playing a crucial role in modulating T-cell activation. In this study, we delved into the underlying mechanism by which a common mutation, G199R, in the cytoplasmic domain of CTLA-4 impacts its inhibitory function. Utilizing nuclear magnetic resonance (NMR) spectroscopy and biochemical techniques, we mapped the conformational changes induced by this mutation and investigated its role in CTLA-4 activity. Our findings reveal that this mutation leads to a distinct conformational alteration, enhancing protein–membrane interactions. Moreover, functional assays demonstrated an improved capacity of the G199R mutant to downregulate T-cell activation, underscoring its potential role in immune-related disorders. These results not only enhance our understanding of CTLA-4 regulatory mechanisms but also provide insights for targeted therapeutic strategies addressing immune dysregulation linked to CTLA-4 mutations.

Zinc alumotitanate sorbents with various compositions were prepared through sol-gel synthesis with the use of ethyl acetoacetate as a chelating agent. The formation and decomposition of chelates, providing insight into sol-gel process advancement, have been successfully monitored via 1H NMR, 13C NMR, and FTIR spectroscopy. It has been established that Al(OBus)3 and Ti(OBun)4 react completely with Eaa, forming chelates after 1 h, while after 24 h hydrolysis is already advanced. Hydrolysis is accelerated in the presence of Zn(NO2)3·6H2O, supplying the water needed for hydrolysis. In dried gels, the amount of ethyl acetoacetate is greatly reduced, and it is mainly present unbound. According to XRD analysis, samples with none or less titania are composed of layered double hydroxide, while in samples with greater amounts of titania, crystal nitrates are present. In all samples except those without Al, the spinel phase with variable composition crystallizes.

In order to characterize red wine polymers with regard to their binding properties to aroma compounds (odorants), a qualitative and quantitative analysis of chemical degradation products after different chemical treatments (thiolytic, acidic, and alkaline depolymerization) of high -molecular-weight (HMW) fractions of red wine was performed. Using 1H NMR, LC-ToF-MS, LC-MS/MS, and HPIC revealed key structural features such as carbohydrates, organic acids, phenolic compounds, anthocyanins, anthocyanidins, amino acids, and flavan-3-ols responsible for odorant-polymer interactions. Further, NMR-based interaction studies of the selected aroma compounds 3-methylbutanol, cis-whisky lactone, 3-methylbutanoic acid, and 3-isobutyl-2-methoxypyrazine with HMW polymers after chemical treatment demonstrated a reduced interaction affinity of the polymer compared to the native HMW fractions, and further, the importance of aromatic compounds such as flavan-3-ols for the formation of odorant polymer interactions. In addition, these observations could be verified by human sensory experiments. For the first time, the combination of a compositional analysis of red wine polymers and NMR-based interaction studies with chemically treated HMW fractions enabled the direct analysis of the correlation of the polymer’s structure and its interaction affinity with key odorants in red wine.

A series of molybdenum(VI) complexes with aryl-functionalized alkyl dihydrazones was prepared by the reaction of [MoO2(acac)2] and the appropriate dihydrazone in methanol. Their solid-state structures were elucidated via single-crystal X-ray diffraction (SC-XRD) and Fourier-transform infra-red (FTIR) spectroscopy, while the thermal stability of compounds was inspected by combined thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) experiments. The behaviour of complexes in DMSO-d6 solution was explored by nuclear magnetic resonance (NMR). The relevant data show that all complexes are dinuclear, with dihydrazones acting as ditopic hexadentate ligands. The in vitro cytotoxic activity of the prepared molybdenum(VI) complexes was evaluated on THP-1 and HepG2 cell lines, while their antibacterial activity was tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Moraxella catarrhalis bacteria. The majority of compounds proved to be non-cytotoxic, while some exhibited superior antibacterial activity in comparison to dihydrazone ligands.

Protected Designation of Origin cheeses are products with high-quality standards that can claim higher prices on the market. For this reason, non-PDO cheeses with lower quality can be mislabeled as PDO or mixed with it for economic gain especially when the product is in a shredded form. Luckily, the production of PDO cheese is subjected to strict procedural specification rules that result in a product with a defined profile of its metabolites, which can be used for authentication purposes. In this study, an NMR metabolomic approach combined with multivariate analysis was implemented to build a classification model able to discriminate PDO Grana Padano cheese from a large dataset of competitors. The great advantage of the proposed approach is a simple sample preparation, obtaining a holistic overview of the analyzed samples. The untargeted approach highlighted a “typical profile” of Grana Padano samples, which could be used for protection purposes. In parallel, the targeted results allowed us to identify potential chemicals, such as lactate, some amino acids and lipids. These initial results could open the road to a potential new additional tool to check the authenticity of PDO cheeses in the future.

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pKa) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pKa value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pKa > 11.5 (N1 of G12) and pKa 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses.

A binuclear tungsten(0) complex with an asymmetric bridging 1,2-diphosphole ligand was prepared by the photolysis of tungsten hexacarbonyl in the presence of 1-isopropyl-2-phenyl-1,2,5,6-tetrahydroacenaphtho [5,6-cd][1,2]diphosphole. The tungsten complex 1 was characterized by high resolution mass spectrometry, multinuclear NMR spectroscopy (1H, 13C, 31P), and elemental microanalysis. The structure of the trans isomer was resolved by single crystal X-ray diffraction, showing a slight elongation of the P−P bond upon coordination to the W(CO)5 groups.

Two novel Sb(III) and Sb(V) peri-substituted acenaphthene phosphorus−antimony compounds were prepared. The Sb(III) compound, 1, was prepared via reacting the organolithium precursor with dichloro(p-tolyl)Stibine, and 2 was prepared by the chlorination of 1. Both 1 and 2 were characterized by multinuclear (1H, 13C and 31P) NMR spectroscopy, and their molecular structures resolved by single-crystal X-ray diffraction. Both compounds show a dative P−Sb interaction with the antimony being the acceptor group in both cases owing to its Lewis acidity.

Isoetin derivatives are a rare class of flavonoids with a rather erratic occurrence across the plant kingdom. The Cichorieae tribe of the Asteraceae family has proven to be a rich source and a centre of chemical diversity of this class of compounds. Here, we describe the chromatographic isolation and mainly NMR-based structure elucidation of a previously undescribed isoetin derivative from Leontodon hispidus L. (Asteraceae, Cichorieae). The chemophenetic relevance is discussed briefly.

Lithium oligo-α-pyridylamides are useful intermediates in coordination chemistry. Upon trans-metalation they have afforded a variety of extended metal atom chains (EMACs), which are currently investigated as molecular wires and single-molecule magnets. However, structural information on this class of compounds is scarce. Two trilithium salts of a new, sterically encumbered oligo-α-pyridylamido ligand were isolated in crystalline form and structurally characterized in the solid state and in solution. Lithiation of N2-(trimethylsilyl)-N6-{6-[(trimethylsilyl)amino]pyridin-2-yl}pyridine-2,6-diamine (H3L) with n-BuLi in thf yielded dimeric adduct [Li6L2(thf)6] (1), which was crystallized from n-hexane/thf as 1·C6H14. Crystals of a tetra-thf solvate with formula [Li6L2(thf)4] (2) were also obtained. The compounds feature two twisted L3− ligands exhibiting a cis-cis conformation and whose five nitrogen donors are all engaged in metal coordination. The six Li+ ions per molecule display coordination numbers ranging from 3 to 5. Compound 1·C6H14 was investigated by multinuclear 1D and 2D NMR spectroscopy, including 1H DOSY experiments, which indicated retention of the dimeric structure in benzene-d6 solution. To the best of our knowledge, 1 and 2 are the longest-chain lithium oligo-α-pyridylamides structurally authenticated so far, thereby qualifying as appealing intermediates to access high-nuclearity EMACs by trans-metalation.

The scopes and limitations of theoretical methods for estimating various NMR metrics of NHCs are considered on a wide range of model NHCs and their derivatives, using a number of computational approximations. On the whole, the most reliable, from the point of view of predictability and insusceptibility to additional effects, are 31P/13C NMR shifts of NHC–phosphinidene adducts and 13C CSs of carbenes themselves. The method based on the analysis of 77Se CS NHC–selenoureas has some limitations since the observed NMR parameters can also be modulated by exchange effects due to their formation with non-classical hydrogen bonds. As for HEP, since the delicate balance of electron distribution between Pd and two carbon centers can nonlinearly affect relativistic spin–orbit effects, the accuracy of the estimation of this metric may still be limited. 13C CSs of NHC–azolium salts do not seem to be reliable, since the observed values are strongly influenced by the effects of the exchange between different forms with counterions, which are difficult to estimate correctly.

[PtCl2{Te(CH2)6}2] (1) was synthesized from the cyclic telluroether Te(CH2)6 and cis-[PtCl2(NCPh)2] in dichloromethane at room temperature under the exclusion of light. The crystal structure determination showed that in the solid state, 1 crystallizes as yellow plate-like crystals of the cis-isomer 1cis and the orange-red interwoven needles of 1trans. The crystals could be separated under the microscope. NMR experiments showed that upon dissolution of the crystals of 1cis in CDCl3, it isomerizes and forms a dynamic equilibrium with the trans-isomer 1trans that becomes the predominant species. Small amounts of cis-trans-[Pt3Cl6{Te(CH2)6}4] (2) and cis-trans-[Pt4Cl8{Te(CH2)6}4] (3) were also formed and structurally characterized. Both compounds show rare bridging telluroether ligands and two different platinum coordination environments, one exhibiting a cis-Cl/cis-Te(CH2)6 arrangement and the other a trans-Cl/trans-Te(CH2)6 arrangement. Complex 2 has an open structure with two terminal and two bridging telluroether ligands, whereas complex 3 has a cyclic structure with four Te(CH2)6 bridging ligands. The bonding and formation of the complexes have been discussed through the use of DFT calculations combined with QTAIM analysis. The recrystallization of the mixture of the 1:1 reaction from d6-DMSO afforded [PtCl2{S(O)(CD3)2}{Te(CH2)6}] (4) that could also be characterized both structurally and spectroscopically.

The Animal Metabolite Database (AMDB, https://amdb.online) is a freely accessible database with built-in statistical analysis tools, allowing one to browse and compare quantitative metabolomics data and raw NMR and MS data, as well as sample metadata, with a focus on the metabolite concentrations rather than on the raw data itself. AMDB also functions as a platform for the metabolomics community, providing convenient deposition and exchange of quantitative metabolomic data. To date, the majority of the data in AMDB relate to the metabolite content of the eye lens and blood of vertebrates, primarily wild species from Siberia, Russia and laboratory rodents. However, data on other tissues (muscle, heart, liver, brain, and more) are also present, and the list of species and tissues is constantly growing. Typically, every sample in AMDB contains concentrations of 60–90 of the most abundant metabolites, provided in nanomoles per gram of wet tissue weight (nmol/g). We believe that AMDB will become a widely used tool in the community, as typical metabolite baseline concentrations in tissues of animal models will aid in a wide variety of fundamental and applied scientific fields, including, but not limited to, animal modeling of human diseases, assessment of medical formulations, and evolutionary and environmental studies.

Cupriavidus metallidurans is a Gram-negative bacterium that has attracted the attention of the scientific community since its discovery back in 1976. It was initially studied as a model organism for bioremediation processes due to its ability to survive in heavy metal-rich environments. However, in recent years, there is evidence that this bacterium can be a potential pathogen for humans. How C. metallidurans can survive in such different environments is unknown and prompted the following work. Its great adaptability could be explained by the structural and conformational studies of the O-antigen portion of the lipopolysaccharide, the main constituent of the outer membrane of Gram-negative bacteria, which is the one in direct contact with the external environment. Therefore, a combination of chemical and spectroscopic analyses was used to define the O-antigen structure, disclosing that it is a polysaccharide constituted of a linear tetrasaccharide repeating unit that does not resemble other structures already reported for bacteria: [4)-α-d-GalNAc-(1→3)-α-d-Qui2NAc4NHBA-(1→3)-α-l-Rha-(1→3)-α-l-Rha-(1→]. Interestingly, the molecular dynamics studies revealed that the three-dimensional structure of the O-antigen is highly flexible: it might adopt three different right-handed helix conformations described by a two, three, or four-fold symmetry. This conformational behavior could represent the reason behind the survival of C. metallidurans in different environments.

Voriconazole (VN) is an antifungal drug indicated for the treatment of several fungal infections. Due to its side effects, some works involving late-stage functionalization of VN have been reported in the literature. Here, we disclose a new VN derivative, the 6-[(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5-fluoropyrimidine-4-carbaldehyde (VN-CHO). This compound results from the photoredox-catalyzed hydroxymethylation of VN, affording a hydroxymethylated derivative (VN-CH2OH), followed by oxidation of the former CH2OH group. VN-CHO was obtained in good yield (70% yield) and its structure was unveiled by 1D (1H and 13C) and 2D (HSQC and HMBC) NMR techniques. The introduction of a formyl group in VN structure creates a very promising site for further functionalization in a molecule which originally does not have many active sites.

3-(5-Phenyl-2H-tetrazol-2-yl)pyridine was synthesized by treating 5-phenyl-1H-tetrazole with pyridin-3-ylboronic acid under Chan–Evans–Lam coupling conditions. The structure and identity were confirmed by 1H, 13C-NMR spectroscopy, IR spectroscopy, UV–Vis spectroscopy, high-resolution mass spectrometry, and TLC. The molecular structure was studied experimentally by sequential X-ray diffraction analysis and theoretically by DFT B3LYP quantum chemistry calculation.

Background: One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy., Methods: To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that these derivatives modulate hexokinase activity differently., Results: Fluorinated compounds show the most potent cytotoxic effects, indicated by the lowest IC 50 values. These effects were more pronounced in hypoxic conditions. 19 F NMR experiments and molecular docking confirmed that fluorinated derivatives bind hexokinase comparably to glucose. Enzymatic assays demonstrated that all halogenated derivatives are more effective HKII inhibitors than 2-DG, particularly through their 6-phosphates. By modifying the C-2 position with halogens, these compounds may overcome the poor pharmacokinetics of 2-DG. The modifications seem to enhance the stability and uptake of the compounds, making them effective at lower doses and over prolonged periods., Conclusions: This research has the potential to reshape the treatment landscape for GBM and possibly other cancers by offering a more targeted, effective, and metabolically focused therapeutic approach. The application of halogenated 2-DG analogs represents a promising advancement in cancer metabolism-targeted therapies, with the potential to overcome current treatment limitations.

Here, we describe a magnetic resonance spectroscopy characterization of selenium cyanide compounds, Se(CN)2, Se2(CN)2 and Se3(CN)2. Selenim-77 and carbon-13 nuclides were used to provide data of these species at room temperature. This is the first structural characterization performed using NMR for Se3(CN)2, while only low-temperature analyses have been conducted so far for Se(CN)2 and Se2(CN)2. Based on these limitations, a characterization study was deemed mandatory, especially from a synthetic chemistry point of view. In addition to these analyses, we carried out a purity assessment for Se3(CN)2 according to the melting point parameter along with a solubility evaluation.

This paper highlights the molecular composition of native peat and preparations of humic substances (HSs) isolated from permafrost hummock peatlands (Histosols) of the forest tundra zone of the European north-east of Russia. The structural and functional parameters of humic—(HAs) and fulvic acids (FAs) of the peatlands studied are determined by the combined action of cryogenic processes, species composition and the degree of peat decomposition, which reflects the climatic conditions during peat formation in the Holocene. The predominance of the proportion of HAs over FAs in the composition of peat, as well as the low acidity of FAs, makes HS-based preparations highly promising for use as organic fertilizers. The high contents of alkyl and carbohydrate fragments in the structure of the studied HSs allow us to recommend them for use in mineral loamy-textured soils.

Mulberry leaves contain α-glucosidase inhibitors, which have hypoglycemic effects and are considered functional foods. However, few reports have covered the effects of mulberry leaf components on normal gut microbiota and gut metabolites. Herein, gut microbiota analysis and NMR-based metabolomics were performed on the feces of mulberry leaf powder (MLP)-treated mice to determine the effects of long-term MLP consumption. Gut microbiota in the mouse were analyzed using 16S-rRNA gene sequencing, and no significant differences were revealed in the diversity and community structure of the gut microbiota in the C57BL/6 mice with or without MLP supplementation. Thirty-nine metabolites were identified via 1H-NMR analysis, and carbohydrates and amino acids were significantly (p < 0.01–0.05) altered upon MLP treatment. In the MLP-treated group, there was a marked increase and decrease in maltose and glucose concentrations, respectively, possibly due to the degradation inhibitory activity of oligosaccharides. After 5 weeks, all amino acid concentrations decreased. Furthermore, despite clear fluctuations in fecal saccharide concentrations, short-chain fatty acid production via intestinal bacterial metabolism was not strongly affected. This study provides the knowledge that MLP administration can alter the gut metabolites without affecting the normal gut microbiota, which is useful for considering MLP as a healthy food source.

Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC50 values below 10 μM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines.

Considering the relationship between disease severity and the extent of metabolic derangement in heart failure, we hypothesized that the serum levels of metabolites may have prognostic value for 1-year mortality in acute heart failure (AHF). The AHF study was a prospective, observational study enrolling consecutive patients hospitalized due to AHF. Metabolites were measured in serum collected at admission using NMR spectroscopy. Out of 315 AHF patients, 118 (37.5%) died within 1 year after hospitalization for AHF. The serum levels of 8 out of 49 identified metabolites were significantly different between patients who were alive and those who died within 1 year after hospitalization for AHF. Of these, only valine was significantly associated with 1-year mortality (hazard ratio 0.73 per 1 standard deviation increase, 95% confidence interval: 0.59–0.90, p = 0.003) in the multivariable Cox regression analyses. Kaplan–Maier analysis showed significantly higher survival rates in AHF patients with valine levels above the median (>279.2 µmol/L) compared to those with valine levels ≤ 279.2 µmol/L. In a receiver operating characteristics curve analysis, valine was able to discriminate between the two groups with an area under the curve of 0.65 (95% CI 0.59–0.72). We conclude that valine serum levels might be of prognostic value in AHF.