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Comprehensive Summary: Layer‐by‐layer (LbL) solution processing is an efficient method to realize high performance organic solar cells (OSCs). One of the drawbacks of the LbL‐processed active layer is the large difference in the crystallinity of the donor and acceptor, which will lead to imbalance charge transfer and result in unfavorable charge recombination. Herein, we combined a novel volatile additive 3,5‐dichloro‐2,4,6‐ trifluorobenzotrifluoride (DTBF) with the LbL method to realize high‐efficiency OSCs. DTBF interacts with the non‐fullerene acceptor BTP‐4F by non‐covalent bonding, which enhances the crystallinity and compact stacking of BTP‐4F. DTBF doped OSC has balanced and efficient electron transport properties, longer carrier lifetime, higher exciton dissociation and charge collection efficiencies, lower energetic disorder than the control OSC without any additives. Benefiting from the optimization of charge dynamics and micro‐morphology by DTBF, the binary LbL‐processed OSC achieved synergistic improvements in open‐circuit voltage, short‐circuit current density and fill factor. As a result, a champion power conversion efficiency (PCE) of 19% is realized for DTBF‐optimized OSC, which is superior to the control OSC (17.55%). This work demonstrates a promising approach to modulate active layer morphology and fabricate high performance OSCs. [ABSTRACT FROM AUTHOR]

This study explores the use of nano SiO2 as a catalyst in the synthesis of imidazole derivatives, demonstrating its superior catalytic efficiency compared to conventional catalysts. The high surface area of nano SiO2 significantly enhances reactant interactions, resulting in higher yields of imidazole products. Detailed NMR spectral analysis provided precise characterizations of the imidazole derivatives, revealing well-defined chemical shifts. The influence of solvent polarity on absorption and fluorescence spectra was investigated, showing that polar solvents induce pronounced bathochromic shifts by stabilizing the excited states through hydrogen bonding and dipole interactions. Quantum yield and emission kinetics analyses highlighted the role of non-radiative decay pathways in reducing fluorescence efficiency. Furthermore, DFT calculations of HOMO–LUMO energies elucidated how substituents affect electronic transitions and solvatochromic shifts. These findings underscore the effectiveness of nano SiO2 as a catalyst, illustrate the impact of solvent interactions on molecular behavior, and provide comprehensive insights into the electronic properties of imidazole derivatives, offering valuable implications for both research and practical applications. [ABSTRACT FROM AUTHOR]

ABSTRACT New psychoactive substances (NPS)—designed to mimic various legal or illegal substances—are an emerging worldwide health problem. Their identification and quantification in either complex seized samples or powders are critical; moreover, their determination in biological fluids is an intriguing goal in the forensic toxicology field. Synthetic cathinones are one of the most important groups among NPS. The current paper was designed as a pilot study to investigate the application of NMR techniques to identify and quantify unknown NPS compounds in deuterated dimethyl sulfoxide (DMSO‐d6) and in urine using the synthetic cathinone benzylone (3,4‐methylenedioxy‐N‐benzylcathinone, BMDP) as a pilot compound. In the first part of our study, nuclear magnetic resonance (NMR) spectroscopic characterization was performed using 1D and 2D homonuclear and heteronuclear NMR spectroscopic methods as long as diffusion ordered spectroscopy (DOSY). Following the above, the assignment of benzylone in DMSO‐d6 was performed, and a distinct spectroscopic pattern was proposed. In the second part of our study, a NMR spectroscopic approach was applied for benzylone identification and quantification in a spiked with benzylone urine. Following the above, the assignment of benzylone in spiked urine was performed. A distinct pattern of the H11, H14, H15, and H8 signals on the 1H NMR spectra was observed and suggested as a “NMR spectroscopic pattern/signature” enabling the identification of benzylone moieties in urine. On the other hand, the applied NMR techniques showed low sensitivity in quantitating benzylone in spiked urine. Overall, our results are promising in using NMR for structure determination of unknown compounds in urine. [ABSTRACT FROM AUTHOR]

Polymeric carbon nitride has attracted significant interest in heterogeneous photocatalysis due to its activity under visible‐light irradiation. Herein, we report on using carbon nitride‐coated NMR tubes for in situ studies of photocatalytic reaction mechanisms. In a first step, we exploited carbon nitride‐coated crimp vials as batch photoreactors for visible photocatalytic fluorinations of unactivated C(sp3)−H bonds, with moderate to excellent yields and reusability over multiple cycles. Eventually, carbon nitride‐coated NMR tubes were used as a photoreactor by coupling them with optical fiber irradiation directly inside the spectrometer. This enabled us to follow the reaction with in situ NMR spectroscopy identifying reactive intermediates otherwise elusive in conventional analyses. The method provides advantages for the study of photocatalytic mechanisms of complex reactions and substantially reduces the need of comparative tests for depicting reaction intermediates and conversion pathways. [ABSTRACT FROM AUTHOR]

This study investigates the hydrogen‐bond geometry in six two‐component solid systems composed of quinoline and chloro‐nitrobenzoic acids. New X‐ray diffraction studies were conducted using both the conventional independent‐atom model and the more recent Hirshfeld atom‐refinement method, with the latter providing precise hydrogen‐atom positions. The systems can be divided into salts (the hydrogen atom transferred to the quinoline nitrogen), cocrystals (the hydrogen atom retained by the acid), and intermediate structures. Solid‐state NMR experiments corroborated the X‐ray diffraction‐derived H−N distances. DFT calculations, using five functionals including hybrid B3LYP and PBE0, showed varying energy profiles for the hydrogen bonds, with notable differences across functionals. These calculations revealed different preferences for salt or cocrystal structures, depending on the functional used. Path‐integral molecular dynamics simulations incorporating nuclear quantum effects demonstrated significant hydrogen‐atom delocalization, forming a hydrogen‐bond continuum, and provided average N−H distances in excellent agreement with experimental results. This comprehensive experimental and theoretical approach highlights the complexity of multicomponent solids. The study emphasizes that the classification into salts or cocrystals is frequently inadequate, as the hydrogen atom is often significantly delocalized in the hydrogen bond. This insight is crucial for understanding and predicting the behavior of such systems in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

The microtubule‐associated protein tau forms disease‐specific filamentous aggregates in several different neurodegenerative diseases. In order to understand how tau undergoes misfolding into a specific filament type and to control this process for drug development purposes, it is crucial to study in vitro tau aggregation methods and investigate the structures of the obtained filaments at the atomic level. Here, we used the tau fragment dGAE, which aggregates spontaneously, to seed the formation of full‐length tau filaments. The structures of dGAE and full‐length tau filaments were investigated by magic‐angle spinning (MAS) solid‐state NMR, showing that dGAE allows propagation of a chronic traumatic encephalopathy (CTE)‐like fold to the full‐length tau. The obtained filaments efficiently seeded tau aggregation in HEK293T cells. This work demonstrates that in vitro preparation of disease‐specific types of full‐length tau filaments is feasible. [ABSTRACT FROM AUTHOR]

Taurine is part of the cysteine cycle and is one of the few naturally occuring organosulfur‐based molecules in the human body. As implied by modern studies, protonated taurine is of biological impact. The first attempts to isolate its protonated species in the binary superacidic system HF/SbF5 were performed by Hopfinger, resulting in the isolation of monoprotonated taurine. Since the chosen conditions seemed rather harsh, investigations in less acidic systems were performed at room temperature to explore the involved protonated species. Herein, we present the structure of 2‐[dihydroxy(oxo)sulfanyliumyl]ethanaminium bis[hexafluoridoarsenate(V)], [H2O3SC2H4NH3][AsF6]2, the diprotonated form of 2‐aminoethanesulfonic acid (taurine). It was synthesized in the binary superacidic system HF/AsF5 and crystallizes as colourless needles. Diprotonated taurine was structurally characterized by single‐crystal X‐ray diffraction analysis, low‐temperature vibrational spectroscopy and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

A memorial tribute detailing the life and scientific accomplishments of Frank A. L. Anet, a pioneer of nuclear magnetic resonance (NMR) spectroscopy who discovered bedrock principles in organic chemistry and magnetic resonance. He was the first to show that nuclear Overhauser effects could provide structural information, significantly impacting future NMR applications. In the 1960s and 1970s, he built entire multinuclear NMR spectrometers operating as high as 396 MHz for protons, detecting nuclei inaccessible to commercial instruments, and operating at very low temperatures for studying molecular structure and dynamics. A titan of physical organic chemistry, Frank made important contributions in the areas of conformational analysis, stereochemistry, isotope effects, NMR relaxation theory, and chemical origins of life. [ABSTRACT FROM AUTHOR]

Homologous to the C‐terminus of E6AP (HECT) and RCC1‐like domain (RLD)‐containing protein 2 (HERC2) is a large, 528 kDa E3 ubiquitin ligase that is associated with cancer, oculocutaneous albanism type 2, Prader‐Willi syndrome, and other neurological diseases. HERC2 has been found to contribute to double‐stranded DNA break repairs, tumor suppression, maintaining centrosome architecture, and ubiquitylation. The C‐terminal portion of the HECT domain (C‐lobe) of HERC2 is responsible for transferring ubiquitin to a substrate but the precise function of the other eight domains in HERC2 are unknown. Interestingly, HERC2 contains a unique and negatively charged C‐terminal tail adjoined to the C‐lobe that is predicted to act as a linker to promote interactions between HERC2 and its binding partners. This study aims to better understand the function and relevance of HERC2 in disease by investigating the structural aspects of the HERC2 C‐lobe and HERC2 C‐terminal tail using AlphaFold followed by molecular dynamics (MD) simulations, multidimensional nuclear magnetic resonance (NMR), and circular dichroism (CD). Secondary structure content analysis from MD simulations and the fully resonance assigned 1H‐15N HSQC spectra of the HERC2 C‐lobe and the isolated C‐terminal tail confirm that the C‐lobe is well‐folded but the C‐terminal tail is disordered. CD melting curves indicate that the flexible C‐terminal tail provides improved stability to the C‐lobe. Additionally, MD simulations have identified that the interaction between residues D4829 and R4728 is prevalent among the non‐bonded contacts between the tail and the C‐lobe. Overall, our results demonstrate that the negatively charged C‐terminal tail is disordered, provides stability to the C‐lobe, and may act as a flexible scaffold for protein–protein interactions. [ABSTRACT FROM AUTHOR]

Adalimumab is a therapeutic monoclonal antibody developed to target human TNF an important mediator of immune-mediated inflammatory diseases such as rheumatoid arthritis, amongst others. The 48 kDa Fab fragment of adalimumab was produced in Escherichia coli using a single chain approach to allow complete isotopic incorporation of deuterium, carbon-13 and nitrogen-15 along with the protonated isoleucine-d, valine and leucine methyl groups. Here we report the near complete resonance assignment of the polypeptide backbone and the methyl groups of isoleucine, leucine and valine residues. [ABSTRACT FROM AUTHOR]

Trastuzumab is a therapeutic monoclonal antibody developed to target human epidermal growth factor receptor 2 (HER2) present at higher levels in early cancers. Here we report the near complete resonance assignment of trastuzumab-scFab fragment backbone and the methyl groups of isoleucine, leucine and valine residues, as well as their stereo-assignments. The antibody fragment was produced using a single chain approach in Escherichia coli. [ABSTRACT FROM AUTHOR]

para‐Nitrophenyl (PNP) ethers of glycosides are important building blocks en route to functional carbohydrates. They are stable in neutral media, however, under basic conditions such as during the Zemplén deacylation of sugars, aryl migration is frequently observed. We have employed a library of O‐PNP‐substituted methyl glycosides of the manno‐, galacto‐, gluco‐ and altro‐series to study the kinetics of aryl migration in MeOH/sodium methoxide using NMR spectroscopy revealing that migration between cis‐oriented OH groups is faster than between trans‐oriented ones. The rate constants of migration decrease in the order of Alt>Man>Gal>Glc and are related to the energy barriers of chair conformation inversion. The energy profile of the 3 to 4‐PNP migration in methyl mannoside was calculated using DFT methods suggesting the Meisenheimer complex is an intermediate of PNP migration and that coordination of the sodium cation has a major impact on the energy profile. [ABSTRACT FROM AUTHOR]

Due to its important role in the formation of humic acids (HA), improving lignin degradation during composting has usually been considered a challenge. One practice that could stimulate the biodegradation of this recalcitrant molecule is inoculation with exogenous lignolytic fungal strains. Two composts (C1) and (C2) from piles (H1) and (H2) were evaluated. H1 was the control pile and H2 was inoculated at maturity with Trametes trogii, resulting in a 35% increase in lignin degradation rate compared to H1. The aim of this study was to show the main effects of this increase on the humification process in the co-composting of green waste, coffee grounds and olive mill wastewater sludge (OMWWs). Microstructure of HA1 and HA2 extracted from C1 and C2, respectively, was also investigated by scanning electron microscopy (SEM) and SEM coupled with energy-dispersive X-ray spectroscopy (X-EDS). The results showed that there were several similarities between the compost samples tested. These included the mineral content, the degree of polymerization (PD)> 1 and the compact and rigid surface of the extracted HA. However, C2 was characterized by a higher humic content (HC), degree of polymerization (PD), humification index (HI) and percentage of humic acids (PHA) than C1. Carbon-13 nuclear magnetic resonance (13C-NMR) and Fourier transmission-infrared spectroscopy (FTIR) analysis showed that aliphatic groups such as hydroxyls, alcohols and carboxyls were predominant in both composts. SEM analysis in conjunction with X-EDS analysis of HA2 showed a higher proportion of carbon and potassium (18 and 7.93%) than in HA1 (14 and 0.95%). [ABSTRACT FROM AUTHOR]

Carob leaves have gained attention for their bioactive properties and traditional medicinal uses, including as treatment for diabetes, digestive disorders, and microbial infections. The aim of this study was to explore the phytochemical composition of carob leaf acetone extracts using advanced spectroscopic techniques. The combined use of heteronuclear nuclear magnetic resonance (NMR) experiments with 1D selective nuclear Overhauser effect spectroscopy (NOESY) offers detailed structural insights and enables the direct identification and quantification of key bioactive constituents in carob leaf extract. In particular, the NMR and mass spectrometry techniques revealed the presence of myricitrin as a predominant flavonoid, as well as a variety of glycosylated derivatives of myricetin and quercetin, in acetone extract. Furthermore, siliquapyranone and related gallotannins are essential constituents of the extract. The potent inhibitory effects of the carob leaf extract on Staphylococcus aureus (MIC = 50 μg mL−1) and a-glucosidase enzyme (IC50 = 67.5 ± 2.4 μg mL−1) were also evaluated. Finally, the antibacterial potency of carob leaf constituents were calculated in silico; digalloyl-parasorboside and gallic acid 4-O-glucoside exert a stronger bactericidal activity than the well-known myricitrin and related flavonoids. In summary, our findings provide valuable insights into the bioactive composition and health-promoting properties of carob leaves and highlight their potential for pharmaceutical and nutraceutical applications. [ABSTRACT FROM AUTHOR]

Phytochromes perceive subtle changes in the light environment and convert them into biological signals by photoconversion between the red‐light absorbing (Pr) and the far‐red‐absorbing (Pfr) states. In the primitive bacteriophytochromes this includes refolding of a tongue‐like hairpin loop close to the chromophore, one strand of an antiparallel β‐sheet being replaced by an α‐helix. However, the strand sequence in the cyanobacterial phytochrome Cph1 is different from that of previously investigated bacteriophytochromes and has a higher β‐sheet propensity. We confirm here the transition experimentally and estimate minimum helix length using dynamic nuclear polarisation (DNP) magic angle spinning NMR. Sample conditions were optimized for protein DNP NMR studies at high field, yielding Boltzmann enhancements ϵB of 19 at an NMR field of 18.801 T. Selective labelling of Trp, Ile, Arg, and Val residues with 13C and 15N enabled filtering for pairs of labelled amino acids by the 3D CANCOCA technique to identify signals of the motif 483Ile‐Val‐Arg485 (IVR) present in both sheet and helix. Those signals were assigned for the Pfr state of the protein. Based on the chemical shift pattern, we confirm for Cph1 the formation of a helix covering the IVR motif. [ABSTRACT FROM AUTHOR]

Thermally stable trans‐bis(chelate)‐type Ru(II) complexes are challenging to prepare owing to steric hindrance between the two chelate ligands. Herein, we investigated the isomerization of a heteroleptic cis‐bis(chelate) complex to obtain its trans form. cis‐[Ru(acac)(bpy)(dmso‐S)2](OTf)⋅0.5H2O (1⋅(OTf)⋅0.5H2O; acac−=acetylacetonato; bpy=2,2'‐bipyridine; dmso=dimethyl sulfoxide; OTf−=CF3SO3−) was prepared by reacting trans(O,S)‐[Ru(bpy)(dmso‐S)2(dmso‐O)2](OTf)2 (P0) with Li(acac) in acetone at 298 K. In 1⋅(OTf)⋅0.5H2O, the two labile dmso‐O ligands of P0 were replaced by an acac− ligand. The dihedral angle between the chelate rings of bpy and acac− in 1+ was 76.7°, suggesting steric hindrance between ligands owing to the two bulky dmso‐S ligands at the cis position. 1⋅(OTf)⋅0.5H2O was thermally stable in DMSO and acetone; however, in methanol and water, a dmso‐S ligand was dissociated from 1+, and the complex isomerized to trans‐[Ru(acac)(bpy)(dmso‐S)(solvent)]+. Refluxing of 1⋅(OTf)⋅0.5H2O in methanol for 18 h, evaporation to dryness under vacuum, and treatment with water yielded trans‐[Ru(acac)(bpy)(dmso‐S)(OH2)](OTf) (2⋅(OTf)) with excellent purity. 2⋅(OTf) was characterized by X‐ray crystallography, elemental analysis, and 1H NMR spectroscopy. As expected, steric hindrance was not observed between the trans‐arranged bpy and acac−, and the two chelates laid flat on the equatorial plane in 2+. [ABSTRACT FROM AUTHOR]

Proteins with intrinsically disordered regions (IDRs) often undergo phase separation to control their functions spatiotemporally. Changing the pH alters the protonation levels of charged sidechains, which in turn affects the attractive or repulsive force for phase separation. In a cell, the rupture of membrane‐bound compartments, such as lysosomes, creates an abrupt change in pH. However, how proteins' phase separation reacts to different pH environments remains largely unexplored. Here, using extensive mutagenesis, NMR spectroscopy, and biophysical techniques, it is shown that the assembly of galectin‐3, a widely studied lysosomal damage marker, is driven by cation‐π interactions between positively charged residues in its folded domain with aromatic residues in the IDR in addition to π–π interaction between IDRs. It is also found that the sole two negatively charged residues in its IDR sense pH changes for tuning the condensation tendency. Also, these two residues may prevent this prion‐like IDR domain from forming rapid and extensive aggregates. These results demonstrate how cation‐π, π–π, and electrostatic interactions can regulate protein condensation between disordered and structured domains and highlight the importance of sparse negatively charged residues in prion‐like IDRs. [ABSTRACT FROM AUTHOR]

Metronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of 15N nuclei in these compounds using SABRE‐SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol‐d4 is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE‐SHEATH hyperpolarization of isotopically labeled [15N3]metronidazole and [15N3]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average 15N polarization of up to 7.2–7.4 % for both substrates. The highest 15N polarizations were observed in methanol‐d4 for [15N3]metronidazole and in ethanol for [15N3]nimorazole. At a clinically relevant magnetic field of 1.4 T the 15N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T1) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors. [ABSTRACT FROM AUTHOR]

In this study, we present a detailed analysis of the structural forms of asymmetric curcuminoids through single‐crystal X‐ray diffraction and nuclear magnetic resonance (NMR) spectroscopy. Curcuminoids substituted with electron‐withdrawing groups (Cl and Br) predominantly adopt the β‐keto‐enol form, whereas those with an OMe group exhibit both diketo and β‐keto‐enol forms. Variable‐temperature X‐ray diffraction studies confirm that the structural state of curcuminoids is influenced by temperature. Our findings also reveal that the β‐keto‐enol form is favored in acidic and neutral conditions, while the diketo form is more prevalent in basic environments. The theoretical Density Functional Theory (DFT) calculations further elucidate the energy differences between the diketo and β‐keto‐enol forms, emphasizing the significance of electronic effects and temperature on tautomeric distributions. These insights enhance our understanding of the structural dynamics of curcuminoids, with implications for their biological activity and pharmacological applications. [ABSTRACT FROM AUTHOR]

The production of functionally active membrane proteins (MPs) in an adequate membrane environment is a key step in structural biology. Polymer–lipid particles based on styrene and maleic acid (SMA) represent a promising type of membrane mimic, as they can extract properly folded MPs directly from their native lipid environment. However, the original SMA polymer is sensitive to acidic pH levels, which has led to the development of several modifications: SMA-EA, SMA-QA, and others. Here, we introduce a novel SMA derivative with a negatively charged taurine moiety, SMA-tau, and investigate the formation and characteristics of lipid–SMA-EA and lipid–SMA-tau membrane-mimicking particles. Our findings demonstrate that both polymers can form nanodiscs with a patch of lipid bilayer that can undergo phase transitions at temperatures close to those of the lipid bilayer membranes. Finally, we discuss the potential applications of these SMAs for NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: The rapid growth of cancer cells is fuelled by excessive sugar uptake and utilisation. While laboratory experiments modelling cancer cell metabolism primarily focus on glucose, in this paper, we address the unexplored roles of other sugars (fructose, galactose, mannose and xylose) that are heavily abundant in the diet. In this study, we feed cancer cells with stable isotopes of those sugars and, using nuclear magnetic resonance spectroscopy, we assess how they are being metabolised by acute myeloid leukaemia cells. We provide a metabolic map detailing the unique metabolism of each of those sugars in cancer cells and we identify a novel role of galactose in supporting their building blocks' biosynthesis. We also demonstrate the ability of galactose to modulate cancer cells' responses to various drugs and chemotherapies. This study highlights the importance of mimicking human dietary compositions when studying cancer cell metabolism in the lab. Metabolism plays a central role in cancer progression. Rewiring glucose metabolism is essential for fulfilling the high energy and biosynthetic demands as well as for the development of drug resistance. Nevertheless, the role of other diet-abundant natural sugars is not fully understood. In this study, we performed a comprehensive 2D NMR spectroscopy tracer-based assay with a panel of 13C-labelled sugars (glucose, fructose, galactose, mannose and xylose). We assigned over 100 NMR signals from metabolites derived from each sugar and mapped them to metabolic pathways, uncovering two novel findings. First, we demonstrated that mannose has a semi-identical metabolic profile to that of glucose with similar label incorporation patterns. Second, next to the known role of fructose in driving one-carbon metabolism, we explained the equally important contribution of galactose to this pathway. Interestingly, we demonstrated that cells growing with either fructose or galactose became less sensitive to certain one-carbon metabolism inhibitors such as 5-Flurouracil and SHIN1. In summary, this study presents the differential metabolism of natural sugars, demonstrating that mannose has a comparable profile to that of glucose. Conversely, galactose and fructose contribute to a greater extent to one-carbon metabolism, which makes them important modulators for inhibitors targeting this pathway. To our knowledge, this is the first NMR study to comprehensively investigate the metabolism of key natural sugars in AML and cancer. [ABSTRACT FROM AUTHOR]

Endometriosis has a wide range of clinical manifestations, and the disease course is unpredictable, making the diagnosis a challenging task. Despite significant advances in the pathophysiology of endometriosis and various proposed theories, the exact etiology is not fully understood and is still unknown. The most commonly used biomarker of endometriosis is CA-125, however, it is nonspecific and is applied for cancers diagnosis. Therefore, the development of reliable noninvasive diagnostic tests for the early diagnosis of endometriosis remains one of the top priorities. Omics technologies are very promising approaches for constructing diagnostic models and biomarker discovery. Their use can greatly facilitate the study of such a complex disease as endometriosis. Nowadays, powerful analytical platforms commonly used in omics, such as gas and liquid chromatography with mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, have proven to be a promising tools for biomarker discovery. The aim of this review is to summarize the various features of the analytical approaches, practical challenges and features of gas and liquid chromatography with MS and NMR spectroscopy (including sample processing protocols, technological advancements, and methodology) used for profiling of metabolites, lipids, peptides and proteins in physiological fluids and tissues from patients with endometriosis. In addition, this report devotes special attention to the issue of how comprehensive analyses of these profiles can effectively contribute to the study of endometriosis. The search query included reports published between 2012 and 2022 years in PubMed, Web-of-Science, SCOPUS, Science Direct. [ABSTRACT FROM AUTHOR]

The α-dicarbonyl compounds are glycolysis metabolites with high reactivity that can cause damage to nucleic acids, proteins, and other macromolecules, leading to various chronic diseases. The rapid and accurate detection of α-dicarbonyl compounds in organisms is of great significance for understanding their roles in the initiation and progression of chronic diseases. Spectroscopic techniques, known for their effectiveness, sensitivity, and ease of use, are widely employed for this purpose. This review provides a concise overview of the analytical strategies and performance of spectroscopic techniques used in detecting α-dicarbonyl compounds, including nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, fluorescence spectroscopy, and ultraviolet-visible (UV-Vis) spectroscopy. Additionally, this review highlights the advancements and trends in the detection of α-dicarbonyl compounds. [ABSTRACT FROM AUTHOR]

In order to valorize the enzymatic hydrolysis residues (EHR) from the bioethanol industry, this work studies the effects on the structure, properties as well as shear resistance of EHR‐based phenol formaldehyde (EPF) adhesives prepared from EHR instead of commercial phenol. 2D heteronuclear signal quantum coherence NMR (2D HSQC NMR) and 31P NMR analysis reveal that lignin in EHR (EHL) possesses a high amount of G and H units which contain 1.9 mmol g−1 active sites (reaction site with formaldehyde). Fourier‐transform infrared (FT‐IR) characterization shows that the instead proportions of EHR with 5–30% in EPF adhesives do not show great influence on the chemical structure type and main functional groups of the prepared adhesives. The shear strength measurement results show that the strength of the 10%‐EPF adhesive is significantly improved by 29% compared to phenol‐formaldehyde (PF) adhesive, which is due to EHL in adhesives enhanced the cross‐linking of polymer chains. This work emphasizes the potential benefits of using industrial EHR to develop cost‐effective phenol formaldehyde adhesive preparation schemes, therefore giving an additional value to waste from biorefineries. [ABSTRACT FROM AUTHOR]

High‐resolution nuclear magnetic resonance (NMR) spectroscopy represents a key methodology for studying biomolecules and their interplay with other molecules. Recent developments in labeling strategies have made it possible to incorporate fluorine into proteins and peptides reliably, with manageable efforts and, importantly, in a highly site‐specific manner. Paired with its excellent NMR spectroscopic properties and absence in most biological systems, fluorine has enabled scientists to investigate a rather wide range of scientific objectives, including protein folding, protein dynamics and drug discovery. Furthermore, NMR spectroscopic experiments can be conducted in complex environments, such as cell lysate or directly inside living cells. This review presents selected studies demonstrating how 19F NMR spectroscopic approaches enable to contribute to the understanding of biomolecular processes. Thereby the focus has been set to labeling strategies available and specific NMR experiments performed to answer the underlying scientific objective. [ABSTRACT FROM AUTHOR]

In order to investigate the stability of an experimental anticancer platinum(IV) prodrug in cell culture media, (OC‐6‐33)‐dichloridobis((4‐ethoxy)‐4‐oxobutanoato)bis(ethylamine)‐platinum(IV) was synthesized with 15N labeled equatorial and fully 13C labeled axial ligands. The title compound as well as its stability in cell culture media was investigated in depth by 1H, 13C, 15N, and 195Pt one‐ and two‐dimensional NMR spectroscopy as well as HPLC‐MS. Different platinum(IV) compounds as a result of hydrolysis were detected in cell culture media as main species. Besides hydrolysis of one or both equatorial chlorido ligands, also hydrolysis of the ester moiety in the axial ligands and release of ethanol could be observed. The different mono and dihydroxidoplatinum(IV) species were proven by 195Pt and 13C NMR spectroscopy as well as HPLC coupled to MS and HRMS. Reduction of the title compound to the corresponding platinum(II) analog or reaction of the complex with ingredients of the cell culture media were not observed. In cell culture medium supplemented with fetal calf serum (FCS), the formation of hydrolysis species was slowed down by a factor of two. [ABSTRACT FROM AUTHOR]

Mastering of analytical methods for accurate quantitative determinations of enantiomeric excess is a crucial aspect in asymmetric catalysis, chiral synthesis, and pharmaceutical applications. In this context, the phenomenon of Self‐Induced Diastereomeric Anisochronism (SIDA) can be exploited in NMR spectroscopy for accurate determinations of enantiomeric composition, without using a chiral auxiliary that could interfere with the spectroscopic investigation. This phenomenon can be particularly useful for improving the quantitative analysis of mixtures with low enantiomeric excesses, where direct integration of signals can be tricky. Here, we describe a novel analysis protocol to correctly determine the enantiomeric composition of scalemic mixtures and investigate the thermodynamic and stereochemical features at the basis of SIDA. Dipeptide derivatives were chosen as substrates for this study, given their central role in drug design. By integrating the experiments with a conformational stochastic search that includes entropic contributions, we provide valuable information on the dimerization thermodynamics, the nature of non‐covalent interactions leading to self‐association, and the differences in the chemical environment responsible for the anisochronism, highlighting the importance of different stereochemical arrangement and tight association for the distinction between homochiral and heterochiral adducts. An important role played by the counterion was pointed out by computational studies. [ABSTRACT FROM AUTHOR]

Organic‐inorganic hybrid perovskite materials, such as formamidinium lead iodide (FAPbI3), are among the most promising emerging photovoltaic materials. However, the spontaneous phase transition from the photoactive perovskite phase to an inactive non‐perovskite phase complicates the application of FAPbI3 in solar cells. To remedy this, alkali metal cations, most often Cs+, Rb+ or K+, are included during perovskite synthesis to stabilize the photoactive phase. The atomic‐level mechanisms of stabilization are complex. While Cs+ dopes directly into the perovskite lattice, Rb+ does not, but instead forms an additional non‐perovskite phase, and the mechanism by which Rb confers increased stability remains unclear. Here, we use 1H−87Rb double resonance NMR experiments to show that FA+ incorporates into the Rb‐based non‐perovskite phases (FAyRb1‐yPb2Br5 and δ‐FAyRb1‐yPbI3) for both bromide and iodide perovskite formulations. This is demonstrated by changes in the 1H and 87Rb chemical shifts, 1H−87Rb heteronuclear correlation spectra, and 87Rb{1H} REDOR spectra. Simulation of the REDOR dephasing curves suggests up to ~60 % FA+ incorporation into the inorganic Rb‐based phase for the bromide system. In light of these results, we hypothesize that the substitution of FA+ into the non‐perovskite phase may contribute to the greater stability conferred by Rb salts in the synthesis of FA‐based perovskites. [ABSTRACT FROM AUTHOR]

[Cp*Ir(R‐pica)Cl] (Cp*=pentamethylcyclopentadienyl anion, pica=2‐picolineamidate) complexes bearing carbohydrate substituents on the amide nitrogen atom (R=methyl‐β‐D‐gluco‐pyranosid‐2‐yl, 1; methyl‐3,4,6‐tri‐O‐acetyl‐β‐D‐glucopyranosid‐2‐yl, 2) were tested as catalysts for formic acid dehydrogenation in water. TOFMAX values over 12000 h−1 and 50000 h−1 were achieved at 333 K for 1 and 2, respectively, with TON values over 35000 for both catalysts. Comparison with the simpler cyclohexyl‐substituted analogue (3) indicated that glucosyl‐based complexes are much better performing under the same experimental conditions (TOFMAX=5144 h−1, TON=5000 at pH 2.5 for 3) owing to a lower tendency to isomerize to the less active k2‐N,O isomer upon protonation. The 5‐fold increase in TOFMAX observed for 2 with respect to 1 is reasonably due to an optimal steric protection by the acetyl substituent, which may prevent unproductive inner‐sphere reactivity. These results showcase a powerful strategy for the inhibition of the common deactivation pathways of [Cp*Ir(R‐pica)X] catalysts for FA dehydrogenation, paving the way for the development of better performing hydrogen storage systems. [ABSTRACT FROM AUTHOR]

SSR128129E (SSR) is a unique small‐molecule inhibitor of fibroblast growth factor receptors (FGFRs). SSR is a high‐affinity allosteric binder that selectively blocks one of the two major FGFR‐mediated pathways. The mechanisms of SSR activity were studied previously in much detail, allowing the identification of its binding site, located in the hydrophobic groove of the receptor D3 domain. The binding site overlaps with the position of an N‐terminal helix, an element exclusive for the FGF8b growth factor, which could potentially convert SSR from an allosteric inhibitor into an orthosteric blocker for the particular FGFR/FGF8b system. In this regard, we report here on the structural and functional investigation of FGF8b/FGFR3c system and the effects imposed on it by SSR. We show that SSR is equally or more potent in inhibiting FGF8b‐induced FGFR signaling compared to FGF2‐induced activation. On the other hand, when studied in the context of separate extracellular domains of FGFR3c in solution with NMR spectroscopy, SSR is unable to displace the N‐terminal helix of FGF8b from its binding site on FGFR3c and behaves as a weak orthosteric inhibitor. The substantial inconsistency between the results obtained with cell culture and for the individual water‐soluble subdomains of the FGFR proteins points to the important role played by the cell membrane. [ABSTRACT FROM AUTHOR]

The hydrostannylation of white phosphorus (P4) allows this crucial industrial precursor to be easily transformed into useful P1 products via direct, 'one pot' (or even catalytic) procedures. However, a thorough mechanistic understanding of this transformation has remained elusive, hindering attempts to use this rare example of successful, direct P4 functionalization as a model for further reaction development. Here, we provide a deep and generalizable mechanistic picture for P4 hydrostannylation by combining DFT calculations with in situ 31P NMR reaction monitoring and kinetic trapping of previously unobservable reaction intermediates using bulky tin hydrides. The results offer important insights into both how this reaction proceeds and why it is successful and provide implicit guidelines for future research in the field of P4 activation. [ABSTRACT FROM AUTHOR]

Lipid analysis is an integral part of food authentication and quality control which provides consumers with the necessary information to make an informed decision about their lipid intake. Recent advancement in lipid analysis and lipidome scope represents great opportunities for food science. In this review we provide a comprehensive overview of available tools for extraction, analysis and interpretation of data related to dietary fats analyses. Different analytical platforms are discussed including GC, MS, NMR, IR and UV with emphasis on their merits and limitations alongside complementary tools such as chemometric models and lipid-targeted online databases. Applications presented here include quality control, authentication of organic and delicacy food, tracing dietary fat source and investigating the effect of heat/storage on lipids. A multitude of analytical methods with different sensitivity, affordability, reproducibility and ease of operation are now available to comprehensively analyze dietary fats. Application of these methods range from studies which favor the use of large data generating platforms such as MS-based methods, to routine quality control which demands easy to use affordable equipment as TLC and IR. Hence, this review provides a navigation tool for food scientists to help develop an optimal protocol for their future lipid analysis quest. [ABSTRACT FROM AUTHOR]

[Display omitted] Understanding polyelectrolyte complexation remains limited due to the absence of a systematic methodology for analyzing the distribution of components between the polyelectrolyte complex (PEC) and the dilute phases. We developed a methodology based on NMR to quantify all components of solid-like PECs and their supernatant phases formed by mixing different ratios of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid)-sodium salt (PAA). This approach allowed for determining relative and absolute concentrations of polyelectrolytes in both phases by 1H NMR studies. Using 23Na and 35Cl NMR spectroscopy we measured the concentration of counterions in both phases. Regardless of the mixing ratio of the polyelectrolytes the PEC is charge-stoichiometric, and any excess polyelectrolytes to achieve charge stoichiometry remains in the supernatant phase. The majority of counterions were found in the supernatant phase, confirming counterion release being a major thermodynamic driving force for PEC formation. The counterion concentrations in the PEC phase were approximately twice as high as in the supernatant phase. The complete mass balance of PEC formation could be determined and translated into a molecular picture. It appears that PAH is fully charged, while PAA is more protonated, so less charged, and some 10% extrinsic PAH-Cl- pairs are present in the complex. [ABSTRACT FROM AUTHOR]

Gas‐phase enzymatic catalysis offers great potential for both green synthesis and the efficient degradation of volatile chemicals. However, solid enzymes often exhibit extremely low activity compared to their counterparts in native aqueous phase. Although a few immobilization methods have succeeded in increasing activity by preserving enzyme structure, approaches for boosting enzyme activity remain underdeveloped. In this study, we propose a general and facile method to boost enzyme activity in the gas phase, which utilizes amphiphilic polymers to energize enzyme conformational dynamics and thus enhance enzyme catalysis kinetics. The triblock copolymer Pluronics with low melting points were co‐lyophilized with Candida antarctica lipase B (CalB), yielding Pluronic/CalB powders that appeared a 70‐fold increase in activity compared to free CalB powder. Low‐field nuclear magnetic resonance (LF‐NMR), solid‐state nuclear magnetic resonance (ssNMR) and dielectric relaxation spectroscopy identified the enhancement of enzyme dynamics on the µs–ms timescale, whereas Fourier transform infrared spectroscopy (FTIR) detected structural perturbations of the native enzyme in Pluronic/CalB. The apparent activity of the enzyme/polymer powders correlated positively with both enzyme dynamics and polymer flexibility. These findings provide new molecular physical insights into gas‐phase enzyme catalysis, which are essential for advancing enzyme applications in nonnatural scenario. [ABSTRACT FROM AUTHOR]

The reactions of suspensions of the freshly prepared complexes [Ph2P(CH2)nPPh2] CoCl2 (n = 2 (dppeCoCl2), n = 3 (dpppCoCl2), n = 4 (dppbCoCl2); dppe is bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, dppb is 1,4-bis-(diphenylphosphino)butane) with the salts [Na][R2C2B8H9] (R = H, Ph), which were obtained in situ by the treatment of carboranes 5,6-nido-R2C2B8H10 (R = H (1a), Ph (1b)) with NaH in THF at room temperature, afforded 18-electron cobaltahydridocarboranes with isonido structures, [1,1-{κ2-Ph2P(CH2)nPPh2}-1-H-isonido-1,2,4-CoR2C2B8H8] (R = H, n = 2 (2a), 3 (2b), 4 (2c); R = Ph, n = 2 (2d)). The treatment of nido-carborane 1a with potassium hydroxide followed by the addition of [Ph2P(CH2)nPPh2]CoCl2 (n = 2–4) in ethanol at 20 °C resulted in the formation of ethoxy-substituted complexes [1,1-{κ2-Ph2P(CH2)nPPh2}-1-H-3-(EtO)-isonido-1,2,4-CoC2B8H9] (3a–c, n = 2–4) apart from compounds 2a–c. All the newly prepared compounds were characterized by a combination of elemental analysis, multinuclear NMR spectroscopy, and IR spectroscopy. The structure of complex 2a was studied by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Herein, the successful syntheses of D3‐ and 13C‐N‐methyl and D9‐tert‐butyl Hoechst dyes are presented. This includes the preparation of the labelled D3‐ and 13C‐N‐methyl piperazines and D9‐tert‐butylated hydroxytoluene precursors. The tert‐butyl Hoechst dye is known to bind a specific RNA aptamer. Spectroscopic NMR studies of the labelled Hoechst dye‐aptamer complexes allowed for the unambiguous assignment of chemical shifts, as well as the dynamics of the bound dye. [ABSTRACT FROM AUTHOR]

The structural variability of a compound class is an important criterion for the research into phosphor host lattices for phosphor‐converted light‐emitting diodes (pc‐LEDs). Especially, nitridophosphates and the related class of imidonitridophosphates are promising candidates. Recently, the ammonothermal approach has opened a systematic access to this substance class with larger sample quantities. We present the successful ammonothermal synthesis of the imidonitridophosphate Ba4P4N8(NH)2:Eu2+. Its crystal structure is solved by X‐ray diffraction and it crystallizes in space group Cc (no. 9) with lattice parameters a=12.5250(3), b=12.5566(4), c=7.3882(2) Å and β=102.9793(10)°. For the first time, adamantane‐type (imido)nitridophosphate anions [P4N8(NH)2]8− are observed next to metal ions other than alkali metals in a compound. The presence of imide groups in the structure and the identification of preferred positions for the hydrogen atoms are performed using a combination of quantum chemical calculations, Fourier‐transform infrared, and solid‐state NMR spectroscopy. Eu2+ doped samples exhibit cyan emission (λmax=498 nm, fwhm=50 nm/1981 cm−1) when excited with ultraviolet light with an impressive internal quantum efficiency (IQE) of 41 %, which represents the first benchmark for imidonitridophosphates and is promising for potential industrial application of this compound class. [ABSTRACT FROM AUTHOR]

There is a growing interest in developing paramagnetic nanoparticles as responsive magnetic resonance imaging (MRI) contrast agents, which feature switchable T1 image contrast of water protons upon biochemical cues for better discerning diseases. However, performing an MRI is pragmatically limited by its cost and availability. Hence, a facile, routine method for measuring the T1 contrast is highly desired in early‐stage development. This work presents a single‐point inversion recovery (IR) nuclear magnetic resonance (NMR) method that can rapidly evaluate T1 contrast change by employing a single, optimized IR pulse sequence that minimizes water signal for "off‐state" nanoparticles and allows for sensitively measuring the signal change with "switch‐on" T1 contrast. Using peptide‐induced liposomal gadopentetic acid (Gd3+‐DTPA) release and redox‐sensitive manganese oxide (MnO2) nanoparticles as a demonstration of generality, this method successfully evaluates the T1 shortening of water protons caused by liposomal Gd3+‐DTPA release and Mn2+ formation from MnO2 reduction. Furthermore, the NMR measurement is highly correlated to T1‐weighted MRI scans, suggesting its feasibility to predict the MRI results at the same field strength. This NMR method can be a low‐cost, time‐saving alternative for pre‐MRI evaluation for a diversity of responsive T1 contrast systems. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to produce novel of the new functionally substituted nicotinohydrazones, analyze their anti-inflammatory activity, and assess their toxicity. A promising avenue for the advancement of novel bioactive compounds is the pursuit of "hybrid molecules" that contain pharmacophore fragments within their structural composition, with a particular focus on the examination of these molecules for the discovery of novel biological activities. Methods: The synthesis of nicotinic acid hydrazones (II–VI) was performed by condensation of nicotinic acid hydrazide with various aldehydes in ethanol when refluxing the reaction mixture at 60–70°C. The anti-inflammatory activity was studied using the formalin paw edema method in non-linear white rats. The acute inflammatory reaction was reproduced by subplantar (i.e., underplantar or plantar aponeurosis) injection of 0.1 mL of a 2% formalin solution into the right paw using a conventional insulin syringe. Results and Discussion: The structure of the new functionally substituted nicotinohydrazones has been confirmed by a combination of the 1H and 13C NMR methods, and COSY (1H-1H), HMQC (1H–13C), and HMBC (1H–13C) two-dimensional NMR spectroscopy methods.1H, and 13C NMR spectroscopy were used to investigate all the prepared derivatives. The acute toxicity of the aforementioned compounds was preliminarily evaluated using a specially developed Toxicity Assessment Software Tool within the United States Environmental Protection Agency. The LD50 values for rats following oral administration of the compounds tested by the QSAR method. According to the projected toxicological effects, compounds (II), (III) can be classified into Class 4 in terms of toxicity. Compounds (IV), (V) and (VI) have low toxicity and very low toxicity, respectively. Conclusions: The anti-inflammatory activity of the synthesized hydrazones has been evaluated and it has been demonstrated that these compounds were ineffective in comparison with ibuprofen at a dosage of 100 mg/kg (p2 < 0.05). The low toxicity level of all the tested compounds was predicted by the computer modeling. The LD50 values of the compounds range from 445.461 to 1491.991 mg/kg. The studies on the model of formalin paw edema in nonlinear white rats indicate the absence of an anti-inflammatory effect of the tested compounds. [ABSTRACT FROM AUTHOR]

Objective: To synthesize bis-Schiff bases bearing thiobarbituric acid and to screen their anti-urease inhibitory potential. Methods: In this study, 1,3-dimethylbarbituric acid derivatives were synthesized by a four-step process. Using K2CO3, 2,4-dihydroxy benzaldehyde and chloro ethyl acetate were esterified in DMF in the first step under reflux condition. The reaction was then carried out by combining the esterified aldehyde with 1,3-dimethylbarbituric acid at room temperature for about an 1 h. Hydrazine hydrate was then mixed with compound (II) in ethanol solvent with acetic acid acting as catalyst. Finally, substituted aromatic aldehydes were treated with bis-hydrazide (III) using ethanol and acetic acid as a catalyst. Results: The newly synthesized compounds were screened for their urease inhibition (in vitro). Four analogs, including (IIIj) (IC50 = 15.22 ± 0.49 μM), (IIIg) (IC50 = 16.05 ± 0.16 μM), (IIIa) (IC50 = 16.29 ± 0.73 μM), and (IIIb) (IC50 = 21.17 ± 0.21 μM) were found most powerful inhibitors than standard thiourea (IC50 = 22.80 ± 2.20 μM). The urease inhibition was also seen in compound (IIIi), (IIIc), (IIIh), (IIIe), (IIId), and (IIIf) however it was less from standard. The structure stability and chemical reactivity of the compounds were checked by density functional theory (DFT) method. Furthermore, the molecular docking simulation was performed to check the protein (urease) and ligand interactions and binding affinities by using AutoDock Vina. Conclusions: The synthesized derivatives attributed temendous potential against urease enzyme. Compound (IIIj) was found as the most potent anti-urease agent. Additional research including taxicological and in vivo is necessary to know the safety, effectivness and mechanism of action of these potent molecules. [ABSTRACT FROM AUTHOR]

Bacillus circulans xylanase (BcX) from the glycoside hydrolase family 11 degrades xylan through a retaining, double‐displacement mechanism. The enzyme is thought to hydrolyze glycosidic bonds in a processive manner and has a large, active site cleft, with six subsites allowing the binding of six xylose units. Such an active site architecture suggests that oligomeric xylose substrates can bind in multiple ways. In the crystal structure of the catalytically inactive variant BcX E78Q, the substrate xylotriose is observed in the active site, as well as bound to the known secondary binding site and a third site on the protein surface. Nuclear magnetic resonance (NMR) titrations with xylose oligomers of different lengths yield nonlinear chemical shift trajectories for active site nuclei resonances, indicative of multiple binding orientations for these substrates for which binding and dissociation are in fast exchange on the NMR timescale, exchanging on the micro‐ to millisecond timescale. Active site binding can be modeled with a 2 : 1 model with dissociation constants in the low and high millimolar range. Extensive mutagenesis of active site residues indicates that tight binding occurs in the glycon binding site and is stabilized by Trp9 and the thumb region. Mutations F125A and W71A lead to large structural rearrangements. Binding at the glycon site is sensed throughout the active site, whereas the weak binding mostly affects the aglycon site. The interactions with the two active site locations are largely independent of each other and of binding at the secondary binding site. [ABSTRACT FROM AUTHOR]

The reactions of suspensions of the freshly prepared complexes [Ph2P(CH2)nPPh2] CoCl2 (n = 2 (dppeCoCl2), n = 3 (dpppCoCl2), n = 4 (dppbCoCl2); dppe is bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, dppb is 1,4-bis-(diphenylphosphino)butane) with the salts [Na][R2C2B8H9] (R = H, Ph), which were obtained in situ by the treatment of carboranes 5,6-nido-R2C2B8H10 (R = H (1a), Ph (1b)) with NaH in THF at room temperature, afforded 18-electron cobaltahydridocarboranes with isonido structures, [1,1-{κ2-Ph2P(CH2)nPPh2}-1-H-isonido-1,2,4-CoR2C2B8H8] (R = H, n = 2 (2a), 3 (2b), 4 (2c); R = Ph, n = 2 (2d)). The treatment of nido-carborane 1a with potassium hydroxide followed by the addition of [Ph2P(CH2)nPPh2]CoCl2 (n = 2–4) in ethanol at 20 °C resulted in the formation of ethoxy-substituted complexes [1,1-{κ2-Ph2P(CH2)nPPh2}-1-H-3-(EtO)-isonido-1,2,4-CoC2B8H9] (3a–c, n = 2–4) apart from compounds 2a–c. All the newly prepared compounds were characterized by a combination of elemental analysis, multinuclear NMR spectroscopy, and IR spectroscopy. The structure of complex 2a was studied by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK oncoproteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but their influence on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, a nuclear magnetic resonance (NMR)-based approach was utilized. The observed differences identified a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis-free survival (DMFS), post-progression survival (PPS), and recurrence-free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, whereas DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts poor outcomes for patients with breast cancer patients. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence. [ABSTRACT FROM AUTHOR]

A sulfide solid electrolyte was synthesized using a solution‐phase approach via the dissolution of Li3PS4 in ethanol followed by heat treatment (90–300 °C). This method yielded an electrolyte with a maximum lithium‐ion conductivity of 1.7×10−5 S cm−1 at 200 °C (down to 25 % of the pristine Li3PS4); however, increasing the heating temperature resulted in a significant decrease in conductivity. Nuclear magnetic resonance spectroscopy revealed the decomposition of the PS43− unit into P2Sx dimers (P2S74− and P2S64−) at high temperatures. X‐ray absorption spectroscopy further confirmed a core‐shell structure in the solution‐phase‐synthesized electrolyte, with an enriched shell of oxygen‐substituted P(S/O)x phases. Both the P2Sx dimers in the core and the oxygen‐rich shell may have contributed to the reduction in lithium‐ion conductivity. Moreover, the oxygen‐rich shell unexpectedly suppressed undesirable side reactions at the solid electrolyte/cathode interface. This study demonstrates the functionalization of solution‐phase synthesis for sulfide solid electrolytes from ethanol, with a trade‐off between conductivity and interface stability. Further optimizing the heat treatment process and shell engineering are promising avenues for enhancing the performance of all‐solid‐state batteries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plastic pollution and microplastic (MP) debris are some of the most significant solid waste pollutants, threatening the marine environment and causing sediment accumulation. Coastal seagrass areas are usually important habitats that support multiple living species and provide several ecosystem services. This study aimed to determine the abundance, characteristics, and composition of microplastics on the southern side of the Tunisian Mediterranean Sea by using Posidonia oceanica (P. oceanica) as a crucial trap for microplastics. Samples of Posidonia leaves were collected from the Tunisian coastal area of Gabes-City. The characterization of microplastic detritus was carried out by stereomicroscopy, and acid digestion of Posidonia tissue leaves was performed for qualitative and quantitative analysis of MPs using NMR spectroscopy. The study revealed pellets, threads, and fragments of polymers as the frequent forms found in MPs. Polyethylene, polystyrene, and bis(2-ethyl-hexyl) phthalates were the most abundant materials detected. P. oceanica leaves contributed notably to microplastic subsidence, seafloor horizontal migration, and sediment burial. Thus, marine flora appeared to be a good tool to detect and monitor plasticizers, and further studies of the P. oceanica seagrass areas will help in developing a more comprehensive knowledge of chemicals spreading over a geographical zone. The results obtained will be used for developing baseline data on plasticizer contamination on the wide-ranging marine coast. [ABSTRACT FROM AUTHOR]

SHP2 is a tyrosine phosphatase that plays a regulatory role in multiple intracellular signaling cascades and is known to be oncogenic in certain contexts. In the absence of effectors, SHP2 adopts an autoinhibited conformation with its N-SH2 domain blocking the active site. Given the key role of N-SH2 in regulating SHP2, this domain has been extensively studied, often by X-ray crystallography. Using a combination of structural analyses and molecular dynamics (MD) simulations we show that the crystallographic environment can significantly influence the structure of the isolated N-SH2 domain, resulting in misleading interpretations. As an orthogonal method to X-ray crystallography, we use a combination of NMR spectroscopy and MD simulations to accurately determine the conformation of apo N-SH2 in solution. In contrast to earlier reports based on crystallographic data, our results indicate that apo N-SH2 in solution primarily adopts a conformation with a fully zipped central β-sheet, and that partial unzipping of this β-sheet is promoted by binding of either phosphopeptides or even phosphate/sulfate ions.

L-Proline (l-Pro) is a non-essential amino acid which, in high concentrations, can cause neurological problems including seizures, although the causative mechanism for this is unclear. Here, we studied the impact of physiological levels of proline on brain energy metabolism and investigated the metabolism of l-Pro itself, using the cortical brain tissue slice and stable isotope labelling from [1-13 C]glucose and [1,2-13 C]acetate detected by NMR spectroscopy and LCMS. l-Pro was actively taken up by the slices and significantly reduced the total metabolic pools of all measured metabolites with glutamine the least affected, while reducing net flux of 13C into glycolytic byproducts (lactate and alanine). Conversely, net flux into Krebs cycle intermediates was increased, suggesting that L-Pro at lower concentrations was driving increased mitochondrial activity in both neurons and glia at the expense of glycolysis and metabolic pool sizes. As there was no evidence of metabolism of [1-13 C] l-Pro in slices under normo-glycemic conditions, the effect of proline on metabolism was not due to displacement of metabolites by added l-Pro. Comparison of the metabolic fingerprint generated by l-Pro in slices metabolizing [3-13 C]pyruvate with that generated by ligands active in the GABAergic system suggested that l-Pro may engender effects similar to that of the inhibitory neurotransmitter and metabolite γ-aminobutyric acid (GABA), in line with previous suggestions that l-Pro may be a GABA mimetic in addition to its role as a modulator of mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

The present study endeavors to decode the details of the transcriptional autoregulation effected by the MazE9 antitoxin of the Mycobacterium tuberculosis MazEF9 toxin–antitoxin system. Regulation of this bicistronic operon at the level of transcription is a critical biochemical process that is key for the organism's stress adaptation and virulence. Here, we have reported the solution structure of the DNA binding domain of MazE9 and scrutinized the thermodynamic and kinetic parameters operational in its interaction with the promoter/operator region, specific to the mazEF9 operon. A HADDOCK model of MazE9 bound to its operator DNA has been calculated based on the information on interacting residues obtained from these studies. The thermodynamics and kinetics of the interaction of MazE9 with the functionally related mazEF6 operon indicate that the potential for intracellular cross‐regulation is unlikely. An interesting feature of MazE9 is the cis ⇌ trans conformational isomerization of proline residues in the intrinsically disordered C‐terminal domain of this antitoxin. [ABSTRACT FROM AUTHOR]

Abstract Precise, fast, and reliable identification and quantification of microplastic contamination are essential for determining their environmental concentrations for risk assessments. This study investigates the use of nuclear magnetic resonance (NMR) spectroscopy to quantify microplastics by analysing dilution series of polystyrene (PS), polyisoprene-cis (PI), polybutadiene-cis (PB), polylactic acid (PLA), polyvinyl chloride (PVC) and polyurethane (PU). Each polymer type was dissolved in a suitable solvent and an internal standard was utilized for quantification. Detection and quantification limits for each polymer type were established in two ways: (1) by using an equation based on proton signals and an internal standard with known concentration and (2) by using the LOQ based on the signal-to-noise ratio. Both data sets were compared and showed that using the internal standard (method 1) results in more accurate and lower concentration limits in the range of 0.2–8 µg mL−1 for all six polymer types, while the LOQ based on the SNR (method 2) gives consistently higher concentration limits (1–10 µg mL−1). The research shows the accuracy, efficacy, and reliability of quantitative NMR spectroscopy for polymer analysis in these concentration ranges compared to established quantifying methods, such as, PyGC/MS, FTIR, or Raman spectroscopy.