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Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the β-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by increasing flexibility. Further, the formation of a novel secondary Tsg101 adduct for several of the tested compounds and the commercial drug lansoprazole. The secondary adduct involved the loss of the 4-pyridyl substituent to form an irreversible species, with implications for increasing the half-life of the active species or its specificity toward Tsg101 UEV. It is also determined that sulfide derivatives display effective viral inhibition, presumably through cellular sulfoxidation, allowing for delayed conversion within the cellular environment, and identify SARS-COV-2 as a target of prazole inhibition. These results open multiple avenues for the design of prazole derivatives for antiviral applications.

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]

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]

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]

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]

Background: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases. Methods: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models. Results: CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R2 = 0.87, n = 173; lactic acid, R2 = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood–brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases. Conclusions: These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood–brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases. [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]

A series of chelating N N proligands, 3‐(2‐pyridyl)‐5‐alkyl‐1,2,4‐triazoles (HLAlk), where alkyl=methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl was used as building blocks for designing of coordination compounds. Their reaction with an equimolar amount of [PdCl2(CH3CN)2] led to formation of series of six novel palladium complexes [Pd(HLAlk)Cl2], in which ligands are coordinated in the acid form. New proligands and Pd(II) complexes were characterized by IR, 1H and 13C NMR spectroscopy and elemental analysis. The Pd(II) complexes showed an unusual downfield shift in 1H NMR of the aliphatic proton that is the closest to triazole ring, which suggests the C−H...Cl hydrogen bonding, supported by X‐ray data for Pd(HLc−Pr)Cl2 and Pd(HLc−Bu)Cl2. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The current work describes the synthesis, characterization and antimicrobial evaluation of a new series of pyrazolo‐triazaphosphorine derivatives. The synthesized compounds were confirmed by NMR (1H,13C,31P), IR spectroscopy, by elemental analysis and LCMS. The series of phosphorus products were screened for their antifungal activities and for their antibacterial activities. Finally, the antioxidant activity was tested for one of them (2a). The results were compared with biological activities of some drugs and demonstrate that the antibacterial and antifungal activities of 2 a–f, are influenced by the variation of the group R, R' and the donor or attractor effects of the group R′. Likewise, the donor effect of the group in compound 2 e has a positive influence on the antifungal activity and 2 e reacts against Alternaria alternata with the lowest IC50=0.795 μg mL−1 than drug. The phosphorus products can be used as some antibacterial and antifungal agents and one of the compounds(2a) have an excellent antioxidant power. [ABSTRACT FROM AUTHOR]

A novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites. Herein, we describe a fragment‐based competitive 19F Ligand Based NMR (LB‐NMR) screening platform that enables routine, quantitative ligand profiling focused at ligand‐binding hotspots. As a proof of concept, the method was applied to 4′‐phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). X‐ray crystallographic characterisation of the hits from a 960‐member fragment screen identified three ligand‐binding hotspots across the PPAT active site. From the fragment hits a collection of 19F reporter candidates were designed and synthesised. By rigorous prioritisation and use of optimisation workflows, a single 19F reporter molecule was generated for each hotspot. Profiling the binding of a set of structurally characterised ligands by competitive 19F LB‐NMR with this suite of 19F reporters recapitulated the binding affinity and site ID assignments made by ITC and X‐ray crystallography. This quantitative mapping of ligand binding events at hotspot level resolution establishes the utility of the fragment‐based competitive 19F LB‐NMR screening platform for hotspot‐directed ligand profiling [ABSTRACT FROM AUTHOR]

It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1‐13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio‐frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22‐fold (to 1,670) via parametric pumping. This active‐feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated. [ABSTRACT FROM AUTHOR]

Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1–7), incorporating either disulfide, or non‐reducible thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine‐tune the conformational properties of cyclic peptides, which may modulate their bioactivities. [ABSTRACT FROM AUTHOR]

α,β‐Dichlorocarbonyl compounds were synthesized by facile dichlorination of α,β‐unsaturated amides with TCIA‐PPh3 and the resultant amides were converted to ketones. Conformational analyses of the products were performed to confirm our previous hypothesis regarding vicinal dichlorinated carbonyl compounds. The compounds exhibited 1H NMR signals with large coupling constants (7–11 Hz) for the 1,2‐anti‐configuration and small coupling constants (3–4 Hz) for the 1,2‐syn‐configuration. The syn‐pentane interaction enabled rational conformational analysis of the α,β‐dichlorinated carbonyl compounds, although some interesting exceptions were observed. Consideration of these conformations is helpful in assigning relative configurations of α,β‐dihalogenated carbonyl compounds in general. [ABSTRACT FROM AUTHOR]

ortho‐Phosphinophenol (oPP) is an unusual example of an air‐stable primary phosphine and a valuable precursor to a variety of useful organophosphorus compounds. The presence of PH2 and OH functionalities offers the possibility of intermolecular and intramolecular P⋅⋅⋅HO hydrogen bonding (HB). The close proximity of these two groups also offers the opportunity for intramolecular PH2⋅⋅⋅HO dihydrogen bonding (DHB). This work provides experimental and computational evidence for these various types of interactions. In the solid state, oPP is associated by significant intermolecular P⋅⋅⋅HO hydrogen bonds as revealed by a single crystal X‐ray structural determination. Multinuclear NMR and IR spectroscopic studies, coupled with DFT computational studies, suggest that oPP adopts multiple conformations in solution whose nature varies with the identity of the solvent. In the gas phase or non‐polar solvents (such as cyclohexane) an equilibrium between four conformations of oPP is proposed. Interestingly, in silico, a conformational isomer having bifurcated intramolecular PH2⋅⋅⋅HO DHB (PP4) is found to be more stable than a conformational isomer having intramolecular P⋅⋅⋅HO HB (PP1). In polar solvents (S), NMR studies indicate intermolecular OH⋅⋅⋅S HB plays a dominant role in modulating 31P NMR chemical shifts over a 17 ppm range. [ABSTRACT FROM AUTHOR]

We previously described NMR based fingerprint matching with peptide backbone resonances as a fast and reliable structural dereplication approach for Pseudomonas cyclic lipodepsipeptides (CLiPs). In combination with total synthesis of a small library of configurational CLiP congeners this also allows unambiguous determination of stereochemistry, facilitating structure‐activity relationship studies and enabling three‐dimensional structure determination. However, the on‐resin macrocycle formation in the synthetic workflow brings considerable burden and limits universal applicability. This drawback is here removed altogether by also transforming the native CLiP into a linearized analogue by controlled saponification of the ester bond. This eliminates the need for macrocycle formation, limiting the synthesis effort to linear peptide analogues. NMR fingerprints of such linear peptide analogues display a sufficiently distinctive chemical shift fingerprint to act as effective discriminators. The approach is developed using viscosin group CLiPs and subsequently demonstrated on putisolvin, leading to a structural revision, and tanniamide from Pseudomonas ekonensis COR58, a newly isolated lipododecapeptide that defines a new group characterized by a ten‐residue large macrocycle, the largest to date in the Pseudomonas CLiP portfolio. These examples demonstrate the effectiveness of the saponification‐ enhanced approach that broadens applicability of NMR fingerprint matching for the determination of the stereochemistry of CLiPs. [ABSTRACT FROM AUTHOR]

A new bismuth complex with the N-(5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide ligand (L = C11H13N2OS) was synthesized for further medical use. The complex and the ligand exhibit anticancer activity. The structure of the complex was characterized by NMR spectroscopy, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and laser-induced electron transfer desorption/ionization (LETDI) mass spectrometry. The Bi: L ratio is 1: 1; the components are connected by an ionic (ion-dipole) interaction. The reaction of bismuth(iii) chloride with ligand hydrobromide (L•HBr) affords the complex {(C11H13N2OS)3[Bi2Cl9]}. The composition of this complex was confirmed by X-ray diffraction, ICP-AES, and LETDI methods. [ABSTRACT FROM AUTHOR]

The aggregation of amyloid peptides and proteins into toxic oligomers is a hallmark of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Machado‐Joseph's disease, and transmissible spongiform encephalopathies. Inhibition of amyloid oligomers formation and interactions with biological counterparts, as well as the triggering of non‐toxic amorphous aggregates, are strategies towards preventive interventions against these pathologies. NMR spectroscopy addresses the need for structural characterization of amyloid proteins and their aggregates, their binding to inhibitors, and rapid screening of compound libraries for ligand identification. Here we briefly discuss the solution experiments constituting the NMR spectroscopist's toolkit and provide examples of their application. [ABSTRACT FROM AUTHOR]

Solution state 1H NMR spectroscopy provides valuable insights into molecular structure and conformation. However, when the spectrum exhibits severe signal overlap, it hampers the extraction of key structural information. Here, an ultraselective, ultrahigh resolution TOCSY method is introduced that greatly reduces spectral complexity, allowing the extraction of previously inaccessible spectral information. It combines the recently developed GEMSTONE excitation with homonuclear decoupling to provide highly simplified through‐bond correlation 1D 1H NMR spectra, showing all signals within the selected spin system as singlets. The new method can greatly facilitate the analysis of mixtures, as shown here for a mixture of Cinchona alkaloids (popular catalysts in asymmetric synthesis) and a mixture of glucocorticoids (used for treating conditions such as asthma). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]