2D Nuclear Magnetic Resonance Research Articles

Influence of alkali metals on water dynamics inside imidazolium-based ionic liquid nano-domains.

The global need to expand the design of energy-storage devices led to the investigation of alkali metal - Ionic Liquid (IL) mixtures as a possible class of electrolytes. In this study, 1D and 2D Nuclear Magnetic Resonance (NMR) and Electrochemical Impedance Spectroscopy (EIS) as well as Molecular Dynamics (MD) simulations were used to study the intermolecular interactions in imidazolium-based IL - water - alkali halide ternary mixtures. The 1H and 23Na 1D and 1H DOSY NMR spectra revealed that the presence of small quantities of NaCl does not influence the aggregation of water molecules in the IL nano-domains. The order of adding ionic compounds to water, as well as the certain water and NaCl molecular ratios, lead to the formation of isolated water clusters. Two ternary solutions representing different orders of compounds mixing (H2O+ IL + NaCl or H2O+ NaCl + IL) showed a strong dependence of the initial solvation shell of Na+ and the self-clustering of water. Furthermore, the behaviour of water was found to be independent from the conditions applied during the solution preparation, such as temperature and/or duration of stirring and aging. These findings could be confirmed by large differences in the amount of ionic species, observed in the ternary solutions and depending on the order of mixing/solute preparation.

Identification of fluid types and their implications for petroleum exploration in the shale oil reservoir: A case study of the Fengcheng Formation in the Mahu Sag, Junggar Basin, Northwest China

The Fengcheng Formation in the Junggar Basin is a typical shale oil reservoir. Fluid type identification and controlling factors on fluid combination types are significant challenges in shale oil exploration and development. By using two-dimensional (2D) nuclear magnetic resonance (NMR) technology, the accurate boundary values of each fluid type can be determined. Combined with thin sections, scanning electron microscopy (SEM), cathode-luminescence (CL), X-ray diffraction (XRD) and NMR, the effect of lithologies on fluid combination types has been evaluated. The results show that a total of six fluid types can be identified in the Fengcheng Formation, including free oil, adsorbed oil, kerogen, hydroxyls, adsorbed water and free water. Their boundary values on the NMR T1-T2 map can be determined by comparing fluid signals under the original state and water-saturated state after oil washing. In this study, different fluid types eliminated kerogen and hydroxyls can be combined into four fluid combination types defined as Type 1 (free oil, adsorbed oil and adsorbed water), 2 (free oil, adsorbed oil, free water and adsorbed water), 3 (adsorbed oil, free oil and free water) and 4 (movable fluids), existing in the dolomitic shale, mixed shale, felsic shale and sandstone, respectively. Meanwhile, the geometric means of T2 (T2gm) and T2 curves indicate that the pore size can effectively distinguish different lithologies and can be considered as an essential factor influencing the occurrence state of fluids. As the average pore size increases, free water emerges in the mixed shale, and adsorbed water disappears in the felsic shale. Furthermore, after the lithology transforms into sandstone, the fluid type is simple, and only movable fluids exist. Finally, the oil test results imply that the reservoirs with fluid combination Type 4 and Type 3 have relatively high oil production. Therefore, the subsequent orientation for petroleum exploration in shale oil reservoirs targets the sandstone and felsic shale interlayers in the Fengcheng Formation.

Solid-State NMR Spectra of Protons and Quadrupolar Nuclei at 28.2 T: Resolving Signatures of Surface Sites with Fast Magic Angle Spinning.

Advances in solid-state nuclear magnetic resonance (NMR) methods and hardware offer expanding opportunities for analysis of materials, interfaces, and surfaces. Here, we demonstrate the application of a very high magnetic field strength of 28.2 T and fast magic-angle-spinning rates (MAS, >40 kHz) to surface species relevant to catalysis. Specifically, we present as case studies the 1D and 2D solid-state NMR spectra of important catalyst and support materials, ranging from a well-defined silica-supported organometallic catalyst to dehydroxylated γ-alumina and zeolite solid acids. The high field and fast-MAS measurement conditions substantially improve spectral resolution and narrow NMR signals, which is particularly beneficial for solid-state 1D and 2D NMR analysis of 1H and quadrupolar nuclei such as 27Al at surfaces.

Composition and Structure of Aspen (Pópulus trémula) Hemicelluloses Obtained by Oxidative Delignification.

In this study, hemicelluloses of aspen wood (Pópulus trémula) were obtained by oxidative delignification in an acetic acid-water-hydrogen peroxide medium at temperatures of 70-100 °C and a process time of 1-4 h. The maximum polysaccharide yield of up to 9.68 wt% was reported. The composition and structure of the hemicelluloses were studied using a complex of physicochemical methods: gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, 2D nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. The xylose, mannose, galactose, and glucose monomer units were identified in the hemicelluloses by gas chromatography. The weight average molecular weight Mw of the products determined by gel permeation chromatography was found to range within 8932-33,142 g/mol. The reported Fourier-transform spectra of the hemicelluloses contain all the bands characteristic of heteropolysaccharides; a weak lignin absorption signal in the spectra at 1500-1510 cm-1 is attributed to a minor content of phenolic fragments in the structure of the obtained hemicelluloses. The use of thermogravimetric analysis established that the hemicelluloses isolated from aspen wood are resistant against heating to temperatures of up to 90-100 °C and, upon further heating up to 400 °C, start destructing at an increasing rate. The antioxidant activity of the hemicelluloses was examined using the compounds that mimic free radicals (1,1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals (salicylic acid). It was found that the activity of all polysaccharides in neutralizing DPPH and hydroxyl radicals is lower than the absorption capacity of vitamin C at all the tested concentrations (0.5, 2, and 5 mg/mL) and attains 81.7 and 82.9%, respectively.

High-field ex vivo and in vivo two-dimensional nuclear magnetic resonance spectroscopy in murine brain: Resolving and exploring the molecular environment.

The structural and chemical complexities within the brain pose a challenge that few noninvasive techniques can tackle with the dexterity of nuclear magnetic resonance (NMR) spectroscopy. Still, even with the advent of ultrahigh fields and of cryogenically cooled coils for in vivo research, the superposition of metabolic resonances arising from the brain remains a challenge. The present study explores the potential to tackle this milieu using a combination of two-dimensional (2D) NMR techniques, implemented on murine brains in vivo at 15.2T and ex vivo at 14.1T. While both experiments were affected by substantial inhomogeneous broadenings conveying distinct elongated lineshapes to the cross-peaks, the ability of increased fields to resolve off-diagonal resonances was clear. A comparison between the corresponding conventional and double quantum-filtered correlated spectroscopy traces enabled an improved assignment of in vivo resonances on the basis of more sensitive ex vivo 2D acquisitions, foremost on the basis of homonuclear cross-relaxation-driven correlations for peaks resonating downfield from water, and of heteronuclear correlations at natural abundance for the upfield protons. With the aid of such 2D correlations approximately 29 metabolites could be resolved and identified. This enhanced resolution was used to explore features related to the metabolites' diffusivities, their exposure to water, and their facility to undergo magnetization transfers to amide/amine/hydroxyl resonances. Cross-peaks from main murine brain biomolecules, including choline, creatine, γ-aminobutyric acid, N-acetyl aspartate, glutamine, and glutamate, showed enhancements in several of these various features, opening interesting vistas about metabolite compartmentalization as viewed by these 2D NMR experiments.

Isolation and Characterization of Rare Flavone Tetraglycosides from the Seeds of the Bioactive Plant: Peganum harmala L.

The phytochemical investigation of Peganum harmala L. seeds yielded two rare flavone tetraglycosides following isolation, purification, and analyses. The compound determined to be diosmetin-7-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (1) was first isolated from the species while the other compound characterized to be acacetin-7-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (2) was isolated from the genus Peganum for the first time. Their structures were primarily elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) (1H, 13C NMR, DEPT, COSY, HSQC and HMBC) and supported by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and MALDI-TOF-MS/MS analyses.

Two New C21 Steroids from Gymnema tingens

AbstractTwo new C21 steroids, named 12‐O‐acetyl‐(20S)‐O‐(N‐methyl)anthraniloyl sarcostin‐5α,6β‐hexahydroxypregnane (1) and 12‐O‐acetyl‐(20S)‐O‐(N‐methyl)anthraniloyl sarcostin 3‐O‐β‐D‐cymaropyranoside (2), together with eight known compounds (3–10) were isolated from the dried whole plants of Gymnema tingens. The structures of the new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. Compounds 1–9 were tested for glucose uptake in L6 cells, and compounds 3 and 4 showed the most potent glucose uptake activity with the enhancement by 2.98‐ and 3.36‐fold.

Structural Fingerprinting of Antisense Oligonucleotide Therapeutics by Solution NMR Spectroscopy.

Antisense oligonucleotide (ASO) therapeutics are an emerging class of biopharmaceuticals to treat and prevent diseases, particularly those involving "undruggable" protein targets. Impurities generated throughout the ASO drug manufacturing and formulation pipeline can be detrimental to drug safety and efficacy. Therefore, analytical techniques are needed to rigorously characterize these molecules for quality assurance purposes. We demonstrate 1D and 2D nuclear magnetic resonance (NMR) spectroscopy methods that can generate high-resolution structural "fingerprints" of ASOs. 1D1H and 31Pmeasurements are shown to provide rapid initial assessment of the ASO integrity. Inparticular, a well-resolved pair of 31P signals arising from the 5´-end of the phosphorodiamidatemorpholino oligomer (PMO) are sensitive to complex formation and oligomerization state. 2D 1H-1H, 1H-13C, and 1H-15 N experiments, although less sensitive, are further shown to enable resonance assignment,which will allow the tracking of structural changes at high-resolution during the drug development andmanufacturing processes. We further anticipate that the described NMR approaches will be broadlyapplicable to fully formulated ASO therapeutics, including modalities other than PMOs.

Multi-spectroscopic characterization of bitumen and its polarity-based fractions

• Insights on H/C-ratio, aromatic systems and average molecular sizes are obtained. • NMR reveals varying chain lengths of aliphatic substituents throughout the fractions. • Characteristic NMR shifts in the resins suggest presence of some esters or amides. • 31 P NMR after derivatization, shows minor amounts of alcohols and carboxylic acids. Bitumen contains a complex mixture of molecules, ranging from simple linear alkanes to complex polyaromatic systems. Used in road construction, those structures are permanently influenced by atmospheric processes, which result in oxidation, degradation, loss of volatiles and structural rearrangements. In order to understand those molecular changes, a profound description of the unaltered system is needed. In this study, structural and chemical peculiarities of bitumen and its polarity-based fractions were analysed using nuclear magnetic resonance (NMR) techniques in combination with infrared/fluorescence spectroscopy and elemental analysis. The bitumen sample was separated into saturates, aromatics, resins and asphaltenes. Elemental analysis provided insights into variations of heteroatom content and hydrogen-carbon ratio among the fractions. Fluorescence spectroscopy showed an increase in the aromatic condensation degree with rising polarity. The combination of heteronuclear single quantum coherence (HSQC) and elemental analysis facilitated the assessment of length and branching extent of aliphatic side chains, throughout the fractions. Another 2D NMR technique, heteronuclear multiple bond coherence (HMBC) found evidence for minor contributions of carboxylic esters or amides within the resins. Hydroxyl and amino groups were analysed by 31 P NMR after derivatization, revealing minor amounts of alcohols, amides and carboxylic acids in the most polar fractions. Additionally, diffusion ordered spectroscopy was carried out to obtain estimations on average molecular sizes and weights. Applying in-depth NMR analysis to bitumen and combining it with complementary analytical techniques, this study provides a unique basis for future ageing studies and demonstrates how multi-spectroscopy can give new insights into bitumen structure and chemistry.

Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B.

Natural nitrogen heterocycles biotransformation has been extensively used to prepare synthetic drugs and explore the fate of therapeutic agents inside the body. Herein, the ability of filamentous fungi to biotransform boldine and berberine was investigated. Docking simulation studies of boldine, berberine and their metabolites on the target enzymes: telomerase (TERT) and human protein tyrosine phosphatase 1B (PTP-1B) were also performed to investigate the anticancer and antidiabetic potentials of compounds in silico. The biotransformation of boldine and berberine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002, Cunninghamella blackesleeana MR198 and Cunninghamella blackesleeana NRRL 1369 via demethylation, N- oxidation, glucosidation, oxidation and hydroxylation reactions produced seven metabolites, namely: 1,10-didesmethyl-boldine (1), laurolitsine (2), 1,10-didesmethyl-norboldine (3), boldine-9-O-β-D-glucoside (4), tridesmethyl berberine (5), demethylene berberine (6), and lambertine (7). Primarily, the structures of the metabolites were established by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses and mass spectrometry. In silico molecular docking simulation of the metabolites of boldine and berberine to the proteins TERT and PTP-1B, respectively, revealed good binding MolDock scores comparable to boldine and berberine and favorable interactions with the catalytic sites of the proteins. In conclusion, this study presented promising biologically prepared nitrogen scaffolds (isoquinolines) of boldine and berberine.

Acyltransferase Domain Swapping for the Production of Tenvermectin B Metabolites in Genetically Engineered Strain Streptomyces avermitilis HU02.

Tenvermectins A and B (TVMs A and B) are hybrid natural compounds of avermectins and milbemycins with enhanced insecticidal activity. Aiming at obtaining a strain for the production of the higher activity metabolite-TVM-B as a major constituent, a recombinant strain Streptomyces avermitilis HU02 was constructed by a domain swapping strategy in which milA1-AT0 gene in S. avermitilis MHJ1011 was replaced by eryA1-AT0 gene from Saccharopolyspora erythraea ATCC 40137. Chemical investigation on the culture of S. avermitilis HU02 led to the isolation of a large amount of TVM-B and trace amounts of five new TVM-B analogues. The structures of new metabolites were elucidated by extensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The bioassay test indicated that five new TVM-B analogues exhibited potent insecticidal activity against Tetranychus cinnabarinus and Bursaphelenchus xylophilus. This study provided a feasible route to the low-cost production of TVM-B and enriched the structural diversity of TVM-B metabolites.

Inositol Derivatives with Anti-Inflammatory Activity from Leaves of Solanum capsicoides Allioni

Eight new inositol derivatives, solsurinositols A–H (1–8), were isolated from the 70% EtOH extract of the leaves of Solanum capsicoides Allioni. Careful isolation by silica gel column chromatography followed by preparative high-performance liquid chromatography (HPLC) allowed us to obtain analytically pure compounds 1–8. They shared the same relative stereochemistry on the ring but have different acyl groups attached to various hydroxyl groups. This was the first time that inositol derivatives have been isolated from this plant. The chemical structures of compounds 1–8 were characterized by extensive 1D nuclear magnetic resonance (NMR) and 2D NMR and mass analyses. Meanwhile, the in vitro anti-inflammatory activity of all compounds was determined using lipopolysaccharide (LPS)-induced BV2 microglia, and among the isolates, compounds 5 (IC50 = 11.21 ± 0.14 µM) and 7 (IC50 = 14.5 ± 1.22 µM) were shown to have potential anti-inflammatory activity.

Drimane-Type Sesquiterpenoids Derived from the Tropical Basidiomycetes Perenniporia centrali-africana and Cerrena sp. nov.

Five new drimane-type sesquiterpenoids were isolated from cultures of the tropical basidiomycetes, Perenniporia centrali-africana (originating from Kenya) and Cerrena sp. nov. (originating from Thailand). A new pereniporin A derivative (1), a new drimane-type sesquiterpene lactam (2), and the new 6,7-Dehydro-isodrimenediol (3) were isolated from P. centrali-africana. In parallel, the two new drimane-type sesquiterpene lactams 5 and 6 were isolated together with known isodrimenediol (4) from Cerrena sp. This is the first report of drimane-type sesquiterpene lactams from basidiomycetes. The structures were elucidated based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. The compounds were devoid of significant antimicrobial and cytotoxic activities.

Formation of Previously Undescribed Δ7-Phytosterol Oxidation Products and Tocopherylquinone Adducts in Pumpkin Seed Oil during Roasting, Screw-Pressing, and Simulated Culinary Processing at Elevated Temperatures.

The influence of pumpkin seed roasting conditions (110-140 °C) and screw-pressing on the formation of previously undescribed Δ7-phytosterol oxidation products and tocopherylquinone adducts with nucleophilic phosphatidylethanolamine species was investigated. The roasting process of pumpkin seed paste at a temperature above 120 °C for 30 min considerably enhanced the formation of Δ7-oxysterols. Targeted analysis [electron impact mass spectrometry (MS), 1D-nuclear magnetic resonance] led to the identification of five novel markers of pumpkin paste roasting, among which (3β,5α,22E,24S)-stigmasta-7,22-dien-6-one-3-ol (6-oxo-α-spinasterol), stereoisomers of (3β,5α,22E)-7,8-epoxystigmast-22-en-3-ol (7,8-epoxy-α-spinasterol), and (3β,5α)-22,23-epoxystigmast-7-en-3-ol (7,8-epoxy-α-spinasterol) were reported in edible oils for the first time. Simulated culinary processing provided novel stereoisomers of (3β,5α,22E)-stigmasta-7,22-dien-3,6-diol, unusual (3β,5α,22E)-stigmasta-7,22-dien-6,15-dione-3-ol, and (5α,22E)-stigmasta-7,22-dien-3-one accompanied by minor stereoisomers of (3β,5α)-7,8;22,23-diepoxystigmastan-3-ol. Moreover, a clear relationship between the pumpkin seed oil stability index and synergistic effect of glycerophospholipids with present tocochromanols was found. High-resolution atmospheric pressure chemical ionization-MS experiments clearly demonstrated the formation of various γ-tocopherylquinone adducts with primary amines, namely, octylamine. The mitigation strategy of potentially detrimental oxysterols from pumpkin seed oil included optimization of processing parameters while maintaining the formation of desirable sensory-active compounds.

A Strategy for Pinpointing Natural Bioactive Components Using Two-Dimensional Bioassay Profilings Combined with Comprehensive Two-Dimensional Countercurrent Chromatography × High-Performance Liquid Chromatography.

Inspired by the interpretation of two-dimensional (2D) nuclear magnetic resonance spectra, an efficient strategy was proposed for pinpointing bioactive components from complex natural products. An off-line comprehensive countercurrent chromatography (CCC) × high-performance liquid chromatography (HPLC) was employed to achieve a 2D chemical chromatogram, and 2D bioassay profilings were obtained from bioassays of the eluent of the first dimension (1D) CCC and the eluent of the second dimension (2D) HPLC. Then 2D chemical chromatograms and 2D bioassay profilings were matched for pinpointing bioactive natural components from complex matrices. Thus, bioactive components in a complex matrix could be efficiently analyzed, separated, and bioactivity-determined. This experimental scheme was successfully demonstrated with a traditional medicinal herb Polygonum cuspidatum Sieb. et Zucc. The feasibility of this 2D strategy was verified with tyrosinase inhibition assay, α-glucosidase inhibition assay, DPPH radical scavenging assay, and ABTS•+ decolorization assay. Eight natural inhibitors were successfully pinpointed and identified from P. cuspidatum. Both pieceid-2″-O-gallate (10) and vanicoside B (20) were screened and identified as natural tyrosinase inhibitors for the first time. Meanwhile, vanicoside B (20) was also found as the strongest α-glucosidase inhibitor among all the isolated components. Most of the compounds exhibited much higher radical scavenging activities. Compared with traditional methodology based on one-dimensional chromatographic separation, the present 2D strategy would be more precise, efficient, and convenient to screen and separate bioactive compounds from complex matrices.

Antitumor Potential of Withanolide Glycosides from Ashwagandha (Withania somnifera) on Apoptosis of Human Hepatocellular Carcinoma Cells and Tube Formation in Human Umbilical Vein Endothelial Cells.

Hepatocellular carcinoma (HCC) is the fastest-growing tumor capable of spreading to other organs via blood vessels formed by endothelial cells. Apoptosis and angiogenesis-targeting therapies are attractive for cancer treatment. In this study, we aimed to study the in vitro cytotoxicity of Withania somnifera against human HCC (HepG2) cells, identify potential antitumoral withanolide glycosides from the active fraction, and elucidate cytotoxic molecular mechanisms of identified bioactive compounds. W. somnifera (Solanaceae), well-known as ‘ashwagandha’, is an Ayurvedic medicinal plant used to promote health and longevity, and the MeOH extract of W. somnifera root exhibited cytotoxicity against HepG2 cells during initial screening. Bioactivity-guided fractionation of the MeOH extract and subsequent phytochemical investigation of the active n-BuOH-soluble fraction resulted in the isolation of five withanolide glycosides (1–5), including one new metabolite, withanoside XIII (1), aided by liquid chromatography–mass spectrometry-based analysis. The new compound structure was determined by 1D and 2D nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, electronic circular dichroism, and enzymatic hydrolysis. In addition, withanoside XIIIa (1a) was identified as the new aglycone (1a) of 1. Isolated withanolide glycosides 1–5 and 1a were cytotoxic toward HepG2 cells; withagenin A diglucoside (WAD) (3) exhibited the most potent cytotoxicity against HepG2 cells, with cell viability less than 50% at 100 μM. WAD cytotoxicity was mediated by both extrinsic and intrinsic apoptosis pathways. Treatment with WAD increased protein expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Bcl-2-associated X protein (Bax), and cleaved poly(ADP-ribose) polymerase (cleaved PARP) but decreased expression levels of B-cell lymphoma 2 (Bcl-2). Moreover, WAD inhibited tubular structure formation in human umbilical vein endothelial cells (HUVECs) by inhibiting the protein expression of vascular endothelial growth factor receptor 2 and its downstream pathways, including extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). These effects were also enhanced by co-treatment with ERK and PI3K inhibitors. Overall, these results indicate that WAD (3) induced HepG2 apoptosis and inhibited HUVEC tube formation, suggesting its potential application in treating liver cancers.

Identification of Cyclic Dipeptides and a New Compound (6-(5-Hydroxy-6-methylheptyl)-5,6-dihydro-2H-pyran-2-one) Produced by Streptomyces fungicidicus against Alternaria solani.

As an important microbial resource, Actinomycetes, especially Streptomyces, have important application values in medicine and biotechnology. Streptomyces fungicidicus SYH3 was isolated from soil samples in tomato-growing areas and showed good inhibitory effects on Alternaria solani in tomato. To obtain pure active compounds, SYH3 fermentation broth was subjected to XAD-16 macroporous resin and silica gel column chromatography. Combined with the repeated preparation and separation of preparative high-performance liquid chromatography (HPLC), a total of four monomer compounds were obtained after activity tracking. Compound 4 was identified as a new six-membered lactone ring compound named 6-(5-hydroxy-6-methylheptyl)-5,6-dihydro-2H-pyran-2-one by 1D and 2D nuclear magnetic resonance (NMR) data and mass spectrometry (MS). The other three active compounds belong to the cyclodipeptide, and their half maximal inhibitory concentration (IC50) values against A. solani were 43.4, 42.9, and 30.6 μg/mL, respectively. Compound 4 significantly inhibited the spore germination and induced swollen and deformed local hyphae of A. solani with an IC50 value of 24.9 μg/mL. Compound 4 also had broad-spectrum antifungal activity and had a good antifungal effect on the tested plant-pathogenic fungi. The modes of action of new compound (4) still require further investigation, representing a novel and effective anti-fungal agent for future application.

Antitobacco Mosaic Virus Activity of a New Eremophilane Glucoside From the Leaves of Nicotiana tabacum L

A new eremophilane-type sesquiterpene glucoside, 13-hydroxycapsidiol 3- O- β-D-glucoside (1), was isolated from the leaves of Nicotiana tabacum L. The structure of this new metabolite was determined by one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and comparison with values reported in the literature. Compound 1 was the second glycosylated eremophilane sesquiterpenoid isolated from plants of the Solanaceae family and exhibited a more potent anti-tobacco mosaic virus (anti-TMV) activity, with an inhibition rate of 39.4% at 20 μM, than the positive control ningnanmycin (34.8%).

Boronate derivatives of damnacanthal: Synthesis, characterization, optical properties and theoretical calculations

The natural anthraquinone Damnacanthal (1) was isolated from the roots of Morinda panamensis and used as a building block in the construction of five fluorescent boronate derivatives (4a–4e). The novel compounds were obtained in moderate yields by the condensation of 1, anthranilic acid (2) and diverse phenylboronic acids (3a–3e) in acetonitrile. Boronate derivatives were fully characterized by 1H, 13C, 11B and 2D nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–vis), and high-resolution mass spectrometry (HR-MS). The photophysical properties were evaluated in tetrahydrofuran revealing that the optical band gap (Egopt) values increase from 2.54 eV for 4a to 2.65 eV for 4d. The maximum emission wavelength and fluorescence quantum yield (ΦF) of the boron complexes were found to be sensitive to the substituents on the phenyl group attached to the boron atom. The resulting derivatives 4a–4c presented emission bands at approximately 522 nm (ΦF = 0.41, 0.13 and 0.37%, respectively); while derivatives 4d and 4e presented broad emission bands with maxima at 676 nm (ΦF = 6.27%) and 614 nm (ΦF = 0.78%), respectively. The molecular geometry, electronic properties and intramolecular non-covalent interactions of the new molecules were evaluated using density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) methods. The value of the energy gap between the HOMO and LUMO increases from 2.89 eV for 4b, 2.96 eV for 4c, 3.04 eV for 4e, 3.08 eV for 4a to 3.32 eV for 4d. Furthermore, compound 4d showed a higher rotational energy barrier (3.33 kcal/mol) at the dihedral angle N1/B1/C24/C25 than its analogs, due to the F∙∙∙π and F∙∙∙O interactions.

Bucket Fuser: Statistical Signal Extraction for 1D 1H NMR Metabolomic Data.

Untargeted metabolomics is a promising tool for identifying novel disease biomarkers and unraveling underlying pathomechanisms. Nuclear magnetic resonance (NMR) spectroscopy is particularly suited for large-scale untargeted metabolomics studies due to its high reproducibility and cost effectiveness. Here, one-dimensional (1D) 1H NMR experiments offer good sensitivity at reasonable measurement times. Their subsequent data analysis requires sophisticated data preprocessing steps, including the extraction of NMR features corresponding to specific metabolites. We developed a novel 1D NMR feature extraction procedure, called Bucket Fuser (BF), which is based on a regularized regression framework with fused group LASSO terms. The performance of the BF procedure was demonstrated using three independent NMR datasets and was benchmarked against existing state-of-the-art NMR feature extraction methods. BF dynamically constructs NMR metabolite features, the widths of which can be adjusted via a regularization parameter. BF consistently improved metabolite signal extraction, as demonstrated by our correlation analyses with absolutely quantified metabolites. It also yielded a higher proportion of statistically significant metabolite features in our differential metabolite analyses. The BF algorithm is computationally efficient and it can deal with small sample sizes. In summary, the Bucket Fuser algorithm, which is available as a supplementary python code, facilitates the fast and dynamic extraction of 1D NMR signals for the improved detection of metabolic biomarkers.