Nuclear Magnetic Resonance Data Research Articles

Characterization of a Newly Available Coastal Marine Dissolved Organic Matter Reference Material (TRM-0522).

Recent methodological advances have greatly increased our ability to characterize aquatic dissolved organic matter (DOM) using high-resolution instrumentation, including nuclear magnetic resonance (NMR) and mass spectrometry (HRMS). Reliable DOM reference materials are required for further method development and data set alignment but do not currently exist for the marine environment. This presents a major limitation for marine biogeochemistry and related fields, including natural product discovery. To fill this resource gap, we have prepared a coastal marine DOM reference material (TRM-0522) from 45 m deep seawater obtained ∼1 km offshore of Sweden's west coast. Over 3000 molecular formulas were assigned by direct infusion HRMS, confirming sample diversity, and the distribution of formulas in van Krevelen space was typical for a marine sample, with the majority of formulas in the region H/C 1-1.5 and O/C 0.3-0.7. The extracted DOM pool was more nitrogen (N)- and sulfur (S)-rich than a typical terrestrial reference material (SRFA). MZmine3 processing of ultrahigh-performance liquid chromatography (UPLC)-HRMS/MS data revealed 494 resolvable features (233 in negative mode; 261 in positive mode) over a wide range of retention times and masses. NMR data indicated low contributions from aromatic protons and, generally speaking, low lignin, humic, and fulvic substances associated with terrestrial samples. Instead, carboxylic-rich aliphatic molecules were the most abundant components, followed by carbohydrates and aliphatic functionalities. This is consistent with a very low specific UV absorbance SUVA254 value of 1.52 L mg C-1 m-1. When combined with comparisons with existing terrestrial reference materials (Suwannee River fulvic acid and Pony Lake fulvic acid), these results suggest that TRM-0522 is a useful and otherwise unavailable reference material for use in marine DOM biogeochemistry.

Structure of amorphous materials in the NASICON system NaTi2Si x PO12

The structure of glasses in the sodium (Na) super-ionic conductor (NASICON) system NaTi2Si x PO12 with x = 0.8 and x = 1.0 was explored by combining neutron and high-energy x-ray diffraction with 29Si, 31P and 23Na solid-state nuclear magnetic resonance (NMR) spectroscopy. The 29Si magic angle spinning (MAS) NMR spectra reveal that the silica component remains fully polymerized in the form of Si4 units, i.e. the silicon atoms are bound to four bridging oxygen atoms. The 31P{23Na} rotational echo adiabatic passage double resonance (REAPDOR) NMR data suggest that the 31P MAS NMR line shape originates from four-coordinated P n units, where n = 1, 2 or 3 is the number of bridging oxygen atoms per phosphorus atom. These sites differ in their 31P-23Na dipolar coupling strengths. The results support an intermediate range order scenario of a phosphosilicate mixed network-former glass in which the phosphate groups selectively attract the Na+ modifier ions. Titanium takes a sub-octahedral coordination environment with a mean Ti–O coordination number of 5.17(4) for x = 0.8 and 4.86(4) for x = 1.0. A mismatch between the P–O and Si–O bond lengths of 8% is likely to inhibit the incorporation of silicon into the phosphorus sites of the NASICON crystal structure.

Novel Benzothiazole Derivatives Synthesis and its Analysis as Diuretic Agents

Benzothiazoles, an anticonvulsant, antiviral, antihypertensive, and cancer-fighting medication of the heterocyclic scaffold family, also acts as antibacterial and antiviral agents. There is much interest in this chemical’s production because of the strong and vital biological action it possesses. Substituted aromatic aldehydes were combined with 2-amino-benzothiazole-6-sulfonic acid amides, or Schiff base derivatives, to create Schiff base derivatives. Recrystallized, characterized, and tested for diuretic efficacy in vivo using online tools, m.p. (melting point), Rf, FTIR (Fourier transform infrared), 1H-NMR (proton nuclear magnetic resonance) data The molecular characteristics of all the substances created were estimated using Lipinski’s rule of 5, OSIRIS (software) molecular property explorer, Molsoft, and Autodock 4.0 docking software. Male Wistar rats were used to make all the compounds traditionally in order to test for diuretic activity. Neither the elemental nor the spectral information for the synthesized compounds disagreed. There were five different methods used to evaluate these compounds: Lipinski rule of five, Molsoft to determine molecular characteristics, PASS (prediction of activity spectra for substances) values to determine the diuretic effect, and OSIRIS software to determine toxicology. In order to investigate the diuretic effects of the selected drugs, docking analysis was used. Acetazolamide was shown to have a diuretic effect that was superior to that of compounds IIIb and IIIe, whereas 2-{(E)-[(3-hydroxyphenyl)methylidene]amino}-1,3-benzothiazole-6-sulfonamide (IIIb) was found to be the most promising potential.

Elucidating the concentration-dependent effects of thiocyanate binding to carbonic anhydrase

Many proteins naturally carry metal centers, with a large share of them being in the active sites of several enzymes. Paramagnetic effects are a powerful source of structural information and, therefore, if the native metal is paramagnetic, or it can be functionally substituted with a paramagnetic one, paramagnetic effects can be used to study the metal sites, as well as the overall structure of the protein. One notable example is cobalt(II) substitution for zinc(II) in carbonic anhydrase. In this manuscript we investigate the effects of sodium thiocyanate on the chemical environment of the metal ion of the human carbonic anhydrase II. The electron paramagnetic resonance (EPR) titration of the cobalt(II) protein with thiocyanate shows that the EPR spectrum changes from A-type to C-type on passing from 1:1 to 1:1000-fold ligand excess. This indicates the occurrence of a change in the electronic structure, which may reflect a sizable change in the metal coordination environment in turn caused by a modification of the frozen solvent glass. However, paramagnetic nuclear magnetic resonance (NMR) data indicate that the metal coordination cage remains unperturbed even in 1:1000-fold ligand excess. This result proves that the C-type EPR spectrum observed at large ligand concentration should be ascribed to the low temperature at which EPR measurements are performed, which impacts on the structure of the protein when it is destabilized by a high concentration of a chaotropic agent.

Interrelationships between nematicity, antiferromagnetic spin fluctuations, and superconductivity: Role of hotspots in FeSe1−xSx revealed by high pressure Se77 NMR study

The sulfur-substituted FeSe, FeSe$_{1-x}$S$_{x} $, is one of the unique systems that provides an independent tunability of nematicity, antiferromagnetism and superconductivity under pressure ($p$). Recently Rana et al. [Phys. Rev. B 101, 180503(R) (2020)] reported, from $^{77}$Se nuclear magnetic resonance (NMR) measurements on FeSe$_{0.91}$S$_{0.09}$ under pressure, that there exists a clear role of nematicity on the relationship between antiferromagnetic (AFM) spin fluctuations and superconducting transition temperature ($T_{\rm c}$) where the AFM spin fluctuations are more effective in enhancing $T_{\rm c}$ in the absence of nematicity than with nematicity. Motivated by the work, we carried out $^{77}$Se NMR measurements on FeSe$_{1-x}$S$_{x}$ with $x$= 0.15 and 0.29 under pressure up to 2.10 GPa to investigate the relationship in a wide range of $x$ in the FeSe$_{1-x}$S$_x$ system. Based on the new results together with the previously reported data for $x$=0 [P. Wiecki et al., Phys. Rev. B 96, 180502(R) (2017)] and 0.09 [K. Rana et al. Phys. Rev. B 101, 180503(R) (2020)], we established a $p$ - $x$ - temperature ($T$) phase diagram exhibiting the evolution of AFM spin fluctuations. From the systematic analysis of the NMR data, we found that the superconducting (SC) state in nematic state arises from a non Fermi liquid state with strong stripe-type AFM spin fluctuations while the SC state without nematicity comes from a Fermi liquid state with mild stripe-type AFM spin fluctuations. Furthermore, we show that the previously reported impact of nematicity on the relationship between AFM fluctuations and superconductivity holds throughout the wide range of $x$ from $x$ = 0 to 0.29 in FeSe$_{1-x}$S$_{x}$ under pressure. We discuss the origin of the role of nematicity in terms of the different numbers of hotspots on Fermi surfaces with and without nematicity.

From Layered Antiferromagnet to 3D Ferromagnet: LiMnBi-to-MnBi Magneto-Structural Transformation

The intermetallic compound LiMnBi was synthesized by the two-step solid-state reaction from the elements. A synthesis temperature of 850 K was selected based on in situ high-temperature powder X-ray diffraction data. LiMnBi crystalizes in the layered-like PbClF structure type (a = 4.3131(7) Å, c = 7.096(1) Å at 100 K, P4/nmm space group, Z = 2). The LiMnBi structure is built of alternating [MnBi] and Li layers, as determined from single-crystal X-ray diffraction data. Magnetic property measurements and solid-state 7Li nuclear magnetic resonance data collected for polycrystalline LiMnBi samples indicate the long-range antiferromagnetic ordering of the Mn sublattice at ∼340 K, with no superconductivity detected down to 5 K. LiMnBi is air- and water-sensitive. Under aerobic conditions, Li can be extracted from the LiMnBi structure to form Li2O/LiOH and MnBi (NiAs structure type, P63/mmc). The obtained MnBi polymorph was previously reported to be one of the strongest rare-earth-free ferromagnets, yet its bulk synthesis in powder form is cumbersome. The proposed magneto-structural transformation from ternary LiMnBi to ferromagnetic MnBi involves condensation of the MnBi4 tetrahedra upon Li deintercalation and is exclusive to LiMnBi. In contrast, ferromagnetic MnBi cannot be obtained from either isostructural NaMnBi and KMnBi or from the structurally related CaMn2Bi2. Such a distinctive transformation in the case of LiMnBi is presumed to be due to its fitting reactivity to yield MnBi and a favorable interlayer distance between [MnBi] layers, while the interlayer distance in NaMnBi and KMnBi structural analogues is unfavorably long. The studies of delithiation from layered-like LiMnBi under different chemical environments indicate that the yield of MnBi depends on the type of solvent used and the kinetics of the reaction. A slow rate and mild reaction media lead to a high fraction of the MnBi product. The saturation magnetization of the “as-prepared” MnBi is ∼50% of the expected value of 81.3 emu/g. Overall, this study adds a missing member to the family of ternary pnictides and illustrates how soft-chemistry methods can be used to obtain “difficult-to-synthesize” compounds.

Nanostructure of hydrogenated amorphous silicon (a-Si:H) films studied by nuclear magnetic resonance

The aim of this work is to investigate the nanostructures of nanoporous materials by studying the anisotropy of the nuclear spin–spin and spin–lattice relaxations of the guest molecules trapped in the pores. The nuclear magnetic resonance (NMR) data are analyzed in the framework of the theory of the nuclear relaxation dominated by the dipole–dipole interactions in gas or liquid species contained in nanopores. A distinctive feature of this theory is the establishment of a relationship between the degree of orientation ordering of nanopores in the host matrix and their characteristic volume and the anisotropy of the NMR relaxation times.In this work the complex experimental and theoretical approach was applied to study the nanostructure of hydrogenated amorphous silicon (a-Si:H) films. A feature of this study is the simultaneous investigation of the three (T1, T1ρ, and T2) NMR relaxation times, for the same sample. This allows us to determine not only the degree of orientation ordering of nanopores but also to estimate their size (∼1 nm) and correlation times of the nanopore fluctuations. The obtained results demonstrate that the developed approach is effective in studying details of nanostructure of different nanoporous materials.

An empirical method to correct nuclear magnetic resonance porosity of tight sandstone using low-field nuclear magnetic resonance data

An empirical method to correct nuclear magnetic resonance porosity of tight sandstone using low-field nuclear magnetic resonance data

Deep Learning Methodology for Obtaining Ultraclean Pure Shift Proton Nuclear Magnetic Resonance Spectra

Nuclear magnetic resonance (NMR) is one of the most powerful analytical techniques. In order to obtain high-quality NMR spectra, a real-time Zangger-Sterk (ZS) pulse sequence is employed to collect low-quality pure shift NMR data with high efficiency. Then, a neural network named AC-ResNet and a loss function named SM-CDMANE are developed to train a network model. The model with excellent abilities of suppressing noise, reducing line widths, discerning peaks, and removing artifacts is utilized to process the acquired NMR data. The processed spectra with noise and artifact suppression and small line widths are ultraclean and high-resolution. Peaks overlapped heavily can be resolved. Weak peaks, even hidden in the noise, can be discerned from noise. Artifacts, even as high as spectral peaks, can be removed completely while not suppressing peaks. Eliminating perfectly noise and artifacts and smoothing baseline make spectra ultraclean. The proposed methodology would greatly promote various NMR applications.

Honey De-crystallization by radio frequency heating for process efficiency: Computational monitoring combined with time domain nuclear magnetic resonance

Industrial de-crystallization of honey is carried out by using hot water or air at 60 °C or higher temperatures with the cost of energy and longer process times. The objectives of this study were to apply RF processing for de-crystallization and monitor this process with time-domain nuclear magnetic resonance (TD-NMR) data and a computational model. For this purpose, crystallized honey samples were processed in a 10 kW - 27.12 MHz free-running oscillator RF system, and experimental temperature data were used to validate the developed computational model. TD-NMR experiments were performed to monitor the de-crystallization, and the obtained kinetics data were coupled with temperature increase to compute the crystal content changes through the process. The RF de-crystallization led to a significant decrease (>70% compared to the conventional processes) in process time for industrial scale processing demonstrating its sustainability.

Structures and Dynamics of DNA Mini-Dumbbells Are Force Field Dependent.

Flexible nucleic acid structures can be challenging to accurately resolve with currently available experimental structural determination techniques. As an alternative, molecular dynamics (MD) simulations can provide a window into understanding the unique dynamics and population distributions of these biomolecules. Previously, molecular dynamics simulations of noncanonical (non-duplex) nucleic acids have proven difficult to accurately model. With a new influx of improved nucleic acid force fields, achieving an in-depth understanding of the dynamics of flexible nucleic acid structures may be achievable. In this project, currently available nucleic acid force fields are evaluated using a flexible yet stable model system: the DNA mini-dumbbell. Prior to MD simulations, nuclear magnetic resonance (NMR) re-refinement was accomplished using improved refinement techniques in explicit solvent to yield DNA mini-dumbbell structures with better agreement between the newly determined PDB snapshots, with the NMR data itself, as well as the unrestrained simulation data. Starting from newly determined structures, a total aggregate of over 800 μs of production data between 2 DNA mini-dumbbell sequences and 8 force fields was collected to compare to these newly refined structures. The force fields tested spanned from traditional Amber force fields: bsc0, bsc1, OL15, and OL21 to Charmm force fields: Charmm36 and the Drude polarizable force field, as well as force fields from independent developers: Tumuc1 and CuFix/NBFix. The results indicated slight variations not only between the different force fields but also between the sequences as well. Given our previous experiences with high populations of potentially anomalous structures in RNA UUCG tetraloops and in various tetranucleotides, we expected the mini-dumbbell system to be challenging to accurately model. Surprisingly, many of the recently developed force fields generated structures in good agreement with experiments. Yet, each of the force fields provided a different distribution of potentially anomalous structures.

White analytical chemistry-driven stability-indicating concomitant chromatographic estimation of thiocolchicoside and aceclofenac using response surface analysis and red green blue model.

White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power and economical efficiency. White analytical chemistry-driven stability indicating chromatographic method has been developed for the concomitant analysis of thiocolchicoside and aceclofenac. The proposed chromatographic method has been developed using a safe and environmental-friendly organic solvent for the concomitant stability study of thiocolchicoside and aceclofenac. The analytical risk assessment was carried out for the identification of high-risk analytical risk factors and analytical method performance attributes. The mixture design was applied for the design of experiments-based response surface modelling of high-risk analytical risk factors and analytical method performance attributes. The degradation products were isolated and characterized using infra-red, nuclear magnetic resonance and mass spectral data. The proposed method was compared for its validation efficiency, greenness power and cost-efficiency with published chromatographic methods using the red, green and blue models. The white score of the proposed and reported method was calculated by averaging the red, blue and green scores of the methods. The proposed method was found to be robust, green and economical for the concomitant stability study of thiocolchicoside and aceclofenac. This article is protected by copyright. All rights reserved.

NMR-based petrophysical parameter calculation with sparse inversion in tight reservoirs

Porosity, permeability, and saturation are important parameters reflecting the petrophysical properties of cores. The petrophysical parameters can be calculated from the inverted nuclear magnetic resonance (NMR) spectra. However, the continuous relaxation time distribution in the traditional NMR spectra is inconsistent with the sparse NMR relaxation signatures of the pore fluid. In this paper, a sparse inversion method was proposed to process NMR data in tight reservoirs, and the petrophysical parameters were calculated from the sparse NMR spectra. In the sparse inversion process, the relaxation time range of the core was first determined, only one new relaxation time was added to the sparse inversion in each iteration, and then the insignificant signal was eliminated. The signal amplitudes of sparse NMR spectra are constrained by the amplitude of the first echo to avoid the influence of noise. Compared with the traditional NMR spectra, the relaxation time is sparse and unfixed in the sparse NMR spectra. The T2 data of tight sandstone and T1-T2 data of shale were processed, and petrophysical parameters were evaluated to verify the effectiveness of the proposed method. The results indicate that the sparse NMR spectra can be better used to accurately calculate the petrophysical parameters in tight reservoirs, including porosity, permeability, and saturation.

NMR derived changes of lipoprotein particle concentrations related to impaired fasting glucose, impaired glucose tolerance, or manifest type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (T2D) and corresponding borderline states, impaired fasting glucose (IFG) and/or glucose tolerance (IGT), are associated with dyslipoproteinemia. It is important to distinguish between factors that cause T2D and that are the direct result of T2D.MethodsThe lipoprotein subclass patterns of blood donors with IFG, IGT, with IFG combined with IGT, and T2D are analyzed by nuclear magnetic resonance (NMR) spectroscopy. The development of lipoprotein patterns with time is investigated by using samples retained for an average period of 6 years. In total 595 blood donors are classified by oral glucose tolerance test (oGTT) and their glycosylated hemoglobin (HbA1c) concentrations. Concentrations of lipoprotein particles of 15 different subclasses are analyzed in the 10,921 NMR spectra recorded under fasting and non-fasting conditions. The subjects are assumed healthy according to the strict regulations for blood donors before performing the oGTT.ResultsUnder fasting conditions manifest T2D exhibits a significant concentration increase of the smallest HDL particles (HDL A) combined with a decrease in all other HDL subclasses. In contrast to other studies reviewed in this paper, a general concentration decrease of all LDL particles is observed that is most prominent for the smallest LDL particles (LDL A). Under normal nutritional conditions a large, significant increase of the concentrations of VLDL and chylomicrons is observed for all groups with IFG and/or IGT and most prominently for manifest T2D. As we show it is possible to obtain an estimate of the concentrations of the apolipoproteins Apo-A1, Apo-B100, and Apo-B48 from the NMR data. In the actual study cohort, under fasting conditions the concentrations of the lipoproteins are not increased significantly in T2D, under non-fasting conditions only Apo-B48 increases significantly.ConclusionIn contrast to other studies, in our cohort of “healthy” blood donors the T2D associated dyslipoproteinemia does not change the total concentrations of the lipoprotein particles produced in the liver under fasting and non-fasting conditions significantly but only their subclass distributions. Compared to the control group, under non-fasting conditions participants with IGT and IFG or T2D show a substantial increase of plasma concentrations of those lipoproteins that are produced in the intestinal tract. The intestinal insulin resistance becomes strongly observable.

Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine.

In this study, we used solid-phase extraction with liquid chromatography-ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK nuclear magnetic resonance (NMR) data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via NMR spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation and identification of the latest ketamine-type new psychoactive substance metabolites.

Conditional Molecular Generation Net Enables Automated Structure Elucidation Based on 13C NMR Spectra and Prior Knowledge.

Structure elucidation of unknown compounds based on nuclear magnetic resonance (NMR) remains a challenging problem in both synthetic organic and natural product chemistry. Library matching has been an efficient method to assist structure elucidation. However, it is limited by the coverage of libraries. In addition, prior knowledge such as molecular fragments is neglected. To solve the problem, we propose a conditional molecular generation net (CMGNet) to allow input of multiple sources of information. CMGNet not only uses 13C NMR spectrum data as input but molecular formulas and fragments of molecules are also employed as input conditions. Our model applies large-scale pretraining for molecular understanding and fine-tuning on two NMR spectral data sets of different granularity levels to accommodate structure elucidation tasks. CMGNet generates structures based on 13C NMR data, molecular formula, and fragment information, with a recovery rate of 94.17% in the top 10 recommendations. In addition, the generative model performed well in the generation of various classes of compounds and in the structural revision task. CMGNet has a deep understanding of molecular connectivities from 13C NMR, molecular formula, and fragments, paving the way for a new paradigm of deep learning-assisted inverse problem-solving.

Metabolomics meets systems immunology.

Metabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. Here, we provide an overview on recent technological developments of metabolomic applications in immunological research. To begin, two widely used metabolomics approaches are compared: targeted and untargeted metabolomics. Then, we provide a comprehensive overview of the analysis workflow and the computational tools available, including sample preparation, raw spectra data preprocessing, data processing, statistical analysis, and interpretation. Third, we describe how to integrate metabolomics with other omics approaches in immunological studies using available tools. Finally, we discuss new developments in metabolomics and its prospects for immunology research. This review provides guidance to researchers using metabolomics and multiomics in immunity research, thus facilitating the application of systems immunology to disease research.

Bioactive Compounds from Mimosa pudica Leaves Extract with Their α- glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activities in vitro and in silico Approaches

<p>Background: Mimosa pudica Linn has been used in traditional medicine to support the treatment of type 2 diabetes. In the present study, we aimed to isolate and evaluate α-glucosidase and Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activities of bioactive compounds from Mimosa pudica’s leaf extract. <p> Methods: Mimosa pudica leaves were extracted with 80% of ethanol. Bioactive compounds were isolated using a column chromatographic technique and elucidated the structure based on the nuclear magnetic resonance and electrospray ionization mass spectrometry spectral data. The α- glucosidase and PTP1B inhibitory activities of the isolated compounds were evaluated using pnitrophenyl phosphate and p-nitrophenyl-α-D-glucopyranoside as a substrate, respectively. Molecular docking and molecular dynamics are used to study the interaction between isolated compounds and proteins. Lipinski’s rule of five was used to evaluate the drug-like properties of isolated compounds. Predict pharmacokinetic parameters were evaluated using the pkCSM tool. <p> Results: Protocatechuic acid and syringic acid were isolated and identified using spectroscopic methods. Protocatechuic acid and syringic acid considerably inhibited α-glucosidase enzyme at IC<sub>50</sub> values of 416.17 ± 9.41 μM and 490.78 ± 9.28 μM, respectively. Furthermore, protocatechuic acid and syringic acid expressed strong PTP1B inhibitory activity at IC<sub>50</sub> values of 248.83 ± 7.66 μM and 450.31 ± 7.77 μM, respectively. Molecular docking and molecular dynamics results showed the interactions of protocatechuic acid and syringic acid with amino acids of PTP1B and α-glucosidase enzyme. Lipinski’s rule of five and absorption, distribution, metabolism, excretion, and toxicity studies predicted that protocatechuic acid and syringic acid have drug-likeness properties. In molecular docking simulation, protocatechuic acid and syringic acid gave relatively negative free binding energies and interacted with many amino acids in the active sites of PTP1B and α-glucosidase. The molecular dynamics simulation results of the complexes were also relatively stable. <p> Conclusion: Our results showed that protocatechuic and syringic acids could be promising compounds for type 2 diabetes treatment.</p>

Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

Characterization of the recently detected cathinone N-cyclohexyl butylone: From structure elucidation to in silico supported pharmacological/toxicological considerations

One of the most widely consumed new psychoactive substances (NPS) families in Europe are synthetic cathinones. Cathinone structure can be easily modified resulting in new derivatives that rapidly reach drug markets. In this work, the recently detected synthetic cathinone N-cyclohexyl butylone has been characterized by gas chromatography coupled to mass spectrometry (GC–MS), liquid chromatography coupled to high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) and Fourier-transformed infrared (FTIR) spectroscopy, using research chemicals samples collected by the drug analysis service Energy Control from anonymous users. Compound identification was performed by the combination of HRMS and NMR data. The elemental composition and putative moieties of the compound were determined based on the accurate-mass ions observed by HRMS. Then, different NMR experiments, including bidimensional, allowed the establishment of the chemical structure and confirmation of compound identity. Furthermore, FTIR spectrum was also acquired in order to provide a complete analytical characterization of the novel cathinone. Finally, pharmacological/toxicological characterization was attempted using in silico methods. Based on these predictions, N-cyclohexyl butylone probably has similar effects to stimulants like MDMA.