NMR-based automated protein structure determination.

PubMed

Würz, Julia M; Kazemi, Sina; Schmidt, Elena; Bagaria, Anurag; Güntert, Peter

2017-08-15

NMR spectra analysis for protein structure determination can now in many cases be performed by automated computational methods. This overview of the computational methods for NMR protein structure analysis presents recent automated methods for signal identification in multidimensional NMR spectra, sequence-specific resonance assignment, collection of conformational restraints, and structure calculation, as implemented in the CYANA software package. These algorithms are sufficiently reliable and integrated into one software package to enable the fully automated structure determination of proteins starting from NMR spectra without manual interventions or corrections at intermediate steps, with an accuracy of 1-2 Å backbone RMSD in comparison with manually solved reference structures. Copyright © 2017 Elsevier Inc. All rights reserved.

Vivaldi: visualization and validation of biomacromolecular NMR structures from the PDB.

PubMed

Hendrickx, Pieter M S; Gutmanas, Aleksandras; Kleywegt, Gerard J

2013-04-01

We describe Vivaldi (VIsualization and VALidation DIsplay; http://pdbe.org/vivaldi), a web-based service for the analysis, visualization, and validation of NMR structures in the Protein Data Bank (PDB). Vivaldi provides access to model coordinates and several types of experimental NMR data using interactive visualization tools, augmented with structural annotations and model-validation information. The service presents information about the modeled NMR ensemble, validation of experimental chemical shifts, residual dipolar couplings, distance and dihedral angle constraints, as well as validation scores based on empirical knowledge and databases. Vivaldi was designed for both expert NMR spectroscopists and casual non-expert users who wish to obtain a better grasp of the information content and quality of NMR structures in the public archive. Copyright © 2013 Wiley Periodicals, Inc.

Authentication of animal origin of heparin and low molecular weight heparin including ovine, porcine and bovine species using 1D NMR spectroscopy and chemometric tools.

PubMed

Monakhova, Yulia B; Diehl, Bernd W K; Fareed, Jawed

2018-02-05

High resolution (600MHz) nuclear magnetic resonance (NMR) spectroscopy is used to distinguish heparin and low-molecular weight heparins (LMWHs) produced from porcine, bovine and ovine mucosal tissues as well as their blends. For multivariate analysis several statistical methods such as principal component analysis (PCA), factor discriminant analysis (FDA), partial least squares - discriminant analysis (PLS-DA), linear discriminant analysis (LDA) were utilized for the modeling of NMR data of more than 100 authentic samples. Heparin and LMWH samples from the independent test set (n=15) were 100% correctly classified according to its animal origin. Moreover, by using 1 H NMR coupled with chemometrics and several batches of bovine heparins from two producers were differentiated. Thus, NMR spectroscopy combined with chemometrics is an efficient tool for simultaneous identification of animal origin and process based manufacturing difference in heparin products. Copyright © 2017 Elsevier B.V. All rights reserved.

Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis.

PubMed

Emwas, Abdul-Hamid; Roy, Raja; McKay, Ryan T; Ryan, Danielle; Brennan, Lorraine; Tenori, Leonardo; Luchinat, Claudio; Gao, Xin; Zeri, Ana Carolina; Gowda, G A Nagana; Raftery, Daniel; Steinbeck, Christoph; Salek, Reza M; Wishart, David S

2016-02-05

NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many "unwanted" or "undesirable" compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

Automated Microflow NMR: Routine Analysis of Five-Microliter Samples

PubMed Central

Jansma, Ariane; Chuan, Tiffany; Geierstanger, Bernhard H.; Albrecht, Robert W.; Olson, Dean L.; Peck, Timothy L.

2006-01-01

A microflow CapNMR probe double-tuned for 1H and 13C was installed on a 400-MHz NMR spectrometer and interfaced to an automated liquid handler. Individual samples dissolved in DMSO-d6 are submitted for NMR analysis in vials containing as little as 10 μL of sample. Sets of samples are submitted in a low-volume 384-well plate. Of the 10 μL of sample per well, as with vials, 5 μL is injected into the microflow NMR probe for analysis. For quality control of chemical libraries, 1D NMR spectra are acquired under full automation from 384-well plates on as many as 130 compounds within 24 h using 128 scans per spectrum and a sample-to-sample cycle time of ∼11 min. Because of the low volume requirements and high mass sensitivity of the microflow NMR system, 30 nmol of a typical small molecule is sufficient to obtain high-quality, well-resolved, 1D proton or 2D COSY NMR spectra in ∼6 or 20 min of data acquisition time per experiment, respectively. Implementation of pulse programs with automated solvent peak identification and suppression allow for reliable data collection, even for samples submitted in fully protonated DMSO. The automated microflow NMR system is controlled and monitored using web-based software. PMID:16194121

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

PubMed

Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

2008-01-01

The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

Compositional differences among Chinese soy sauce types studied by (13)C NMR spectroscopy coupled with multivariate statistical analysis.

PubMed

Kamal, Ghulam Mustafa; Wang, Xiaohua; Bin Yuan; Wang, Jie; Sun, Peng; Zhang, Xu; Liu, Maili

2016-09-01

Soy sauce a well known seasoning all over the world, especially in Asia, is available in global market in a wide range of types based on its purpose and the processing methods. Its composition varies with respect to the fermentation processes and addition of additives, preservatives and flavor enhancers. A comprehensive (1)H NMR based study regarding the metabonomic variations of soy sauce to differentiate among different types of soy sauce available on the global market has been limited due to the complexity of the mixture. In present study, (13)C NMR spectroscopy coupled with multivariate statistical data analysis like principle component analysis (PCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) was applied to investigate metabonomic variations among different types of soy sauce, namely super light, super dark, red cooking and mushroom soy sauce. The main additives in soy sauce like glutamate, sucrose and glucose were easily distinguished and quantified using (13)C NMR spectroscopy which were otherwise difficult to be assigned and quantified due to serious signal overlaps in (1)H NMR spectra. The significantly higher concentration of sucrose in dark, red cooking and mushroom flavored soy sauce can directly be linked to the addition of caramel in soy sauce. Similarly, significantly higher level of glutamate in super light as compared to super dark and mushroom flavored soy sauce may come from the addition of monosodium glutamate. The study highlights the potentiality of (13)C NMR based metabonomics coupled with multivariate statistical data analysis in differentiating between the types of soy sauce on the basis of level of additives, raw materials and fermentation procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data.

PubMed

Vu, Trung N; Valkenborg, Dirk; Smets, Koen; Verwaest, Kim A; Dommisse, Roger; Lemière, Filip; Verschoren, Alain; Goethals, Bart; Laukens, Kris

2011-10-20

Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline. We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data. The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from http://code.google.com/p/speaq/.

NMR structural study of the prototropic equilibrium in solution of Schiff bases as model compounds.

PubMed

Ortegón-Reyna, David; Garcías-Morales, Cesar; Padilla-Martínez, Itzia; García-Báez, Efren; Aríza-Castolo, Armando; Peraza-Campos, Ana; Martínez-Martínez, Francisco

2013-12-31

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

Holistic Analysis Enhances the Description of Metabolic Complexity in Dietary Natural Products1234

PubMed Central

Kulakowski, Daniel; Lankin, David C; McAlpine, James B; Chen, Shao-Nong

2016-01-01

In the field of food and nutrition, complex natural products (NPs) are typically obtained from cells/tissues of diverse organisms such as plants, mushrooms, and animals. Among them, edible fruits, grains, and vegetables represent most of the human diet. Because of an important dietary dependence, the comprehensive metabolomic analysis of dietary NPs, performed holistically via the assessment of as many metabolites as possible, constitutes a fundamental building block for understanding the human diet. Both mass spectrometry (MS) and nuclear magnetic resonance (NMR) are important complementary analytic techniques, covering a wide range of metabolites at different concentrations. Particularly, 1-dimensional 1H-NMR offers an unbiased overview of all metabolites present in a sample without prior knowledge of its composition, thereby leading to an untargeted analysis. In the past decade, NMR-based metabolomics in plant and food analyses has evolved considerably. The scope of the present review, covering literature of the past 5 y, is to address the relevance of 1H-NMR–based metabolomics in food plant studies, including a comparison with MS-based techniques. Major applications of NMR-based metabolomics for the quality control of dietary NPs and assessment of their nutritional values are presented. PMID:27180381

Understanding the NMR properties and conformational behavior of indole vs. azaindole group in protoberberines: NICS and NCS analysis

NASA Astrophysics Data System (ADS)

Kadam, Shivaji S.; Toušek, Jaromír; Maier, Lukáš; Pipíška, Matej; Sklenář, Vladimír; Marek, Radek

2012-11-01

We report here the preparation and the structural investigation into a series of 8-(indol-1-yl)-7,8-dihydroprotoberberine derivatives derived from berberine, palmatine, and coptisine. Structures of these new compounds were characterized mainly by 2D NMR spectroscopy and the conformational behavior was investigated by using methods of density-functional theory (DFT). PBE0/6-311+G** calculated NMR chemical shifts for selected derivatives correlate excellently with the experimental NMR data and support the structural conclusions drawn from the NMR experiments. An interesting role of the nitrogen atom in position N7' of the indole moiety in 8-(7-azaindol-1-yl)-7,8-dihydroprotoberberines as compared to other 8-indolyl derivatives is investigated in detail. The experimentally observed trends in NMR chemical shifts are rationalized by DFT calculations and analysis based on the nucleus-independent chemical shifts (NICS) and natural localized molecular orbitals (NLMOs).

Online low-field NMR spectroscopy for process control of an industrial lithiation reaction-automated data analysis.

PubMed

Kern, Simon; Meyer, Klas; Guhl, Svetlana; Gräßer, Patrick; Paul, Andrea; King, Rudibert; Maiwald, Michael

2018-05-01

Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential for enabling closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies. We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (indirect hard modeling-IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union's Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analyzed by IHM with low calibration effort, compared to a multivariate PLS-R (partial least squares regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy. Graphical abstract NMR sensor module for monitoring of the aromatic coupling of 1-fluoro-2-nitrobenzene (FNB) with aniline to 2-nitrodiphenylamine (NDPA) using lithium-bis(trimethylsilyl) amide (Li-HMDS) in continuous operation. Online 43.5 MHz low-field NMR (LF) was compared to 500 MHz high-field NMR spectroscopy (HF) as reference method.

Metabolic changes in different developmental stages of Vanilla planifolia pods.

PubMed

Palama, Tony Lionel; Khatib, Alfi; Choi, Young Hae; Payet, Bertrand; Fock, Isabelle; Verpoorte, Robert; Kodja, Hippolyte

2009-09-09

The metabolomic analysis of developing Vanilla planifolia green pods (between 3 and 8 months after pollination) was carried out by nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis. Multivariate data analysis of the (1)H NMR spectra, such as principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA), showed a trend of separation of those samples based on the metabolites present in the methanol/water (1:1) extract. Older pods had a higher content of glucovanillin, vanillin, p-hydroxybenzaldehyde glucoside, p-hydroxybenzaldehyde, and sucrose, while younger pods had more bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-isopropyltartrate (glucoside A), bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-(2-butyl)tartrate (glucoside B), glucose, malic acid, and homocitric acid. A liquid chromatography-mass spectrometry (LC-MS) analysis targeted at phenolic compound content was also performed on the developing pods and confirmed the NMR results. Ratios of aglycones/glucosides were estimated and thus allowed for detection of more minor metabolites in the green vanilla pods. Quantification of compounds based on both LC-MS and NMR analyses showed that free vanillin can reach 24% of the total vanillin content after 8 months of development in the vanilla green pods.

A new Schiff base compound N,N'-(2,2-dimetylpropane)-bis(dihydroxylacetophenone): synthesis, experimental and theoretical studies on its crystal structure, FTIR, UV-visible, 1H NMR and 13C NMR spectra.

PubMed

Saheb, Vahid; Sheikhshoaie, Iran

2011-10-15

The Schiff base compound, N,N'-(2,2-dimetylpropane)-bis(dihydroxylacetophenone) (NDHA) is synthesized through the condensation of 2-hydroxylacetophenone and 2,2-dimethyl 1,3-amino propane in methanol at ambient temperature. The yellow crystalline precipitate is used for X-ray single-crystal determination and measuring Fourier transform infrared (FTIR), UV-visible, (1)H NMR and (13)C NMR spectra. Electronic structure calculations at the B3LYP, PBEPBE and PW91PW91 levels of theory are performed to optimize the molecular geometry and to calculate the FTIR, (1)H NMR and (13)C NMR spectra of the compound. Time-dependent density functional theory (TDDFT) method is used to calculate the UV-visible spectrum of NDHA. Vibrational frequencies are determined experimentally and compared with those obtained theoretically. Vibrational assignments and analysis of the fundamental modes of the compound are also performed. All theoretical methods can well reproduce the structure of the compound. The (1)H NMR and (13)C NMR chemical shifts calculated by all DFT methods are consistent with the experimental data. However, the NMR shielding tensors computed at the B3LYP/6-31+G(d,p) level of theory are in better agreement with experimental (1)H NMR and (13)C NMR spectra. The electronic absorption spectrum calculated at the B3LYP/6-31+G(d,p) level by using TD-DFT method is in accordance with the observed UV-visible spectrum of NDHA. In addition, some quantum descriptors of the molecule are calculated and conformational analysis is performed and the results were compared with the crystallographic data. Copyright © 2011 Elsevier B.V. All rights reserved.

Metabolic discrimination of sea buckthorn from different Hippophaë species by 1H NMR based metabolomics.

PubMed

Liu, Yue; Fan, Gang; Zhang, Jing; Zhang, Yi; Li, Jingjian; Xiong, Chao; Zhang, Qi; Li, Xiaodong; Lai, Xianrong

2017-05-08

Sea buckthorn (Hippophaë; Elaeagnaceae) berries are widely consumed in traditional folk medicines, nutraceuticals, and as a source of food. The growing demand of sea buckthorn berries and morphological similarity of Hippophaë species leads to confusions, which might cause misidentification of plants used in natural products. Detailed information and comparison of the complete set of metabolites of different Hippophaë species are critical for their objective identification and quality control. Herein, the variation among seven species and seven subspecies of Hippophaë was studied using proton nuclear magnetic resonance ( 1 H NMR) metabolomics combined with multivariate data analysis, and the important metabolites were quantified by quantitative 1 H NMR (qNMR) method. The results showed that different Hippophaë species can be clearly discriminated and the important interspecific discriminators, including organic acids, L-quebrachitol, and carbohydrates were identified. Statistical differences were found among most of the Hippophaë species and subspecies at the content levels of the aforementioned interspecific discriminators via qNMR and one-way analysis of variance (ANOVA) test. These findings demonstrated that 1 H NMR-based metabolomics is an applicable and effective approach for simultaneous metabolic profiling, species differentiation and quality assessment.

Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis

PubMed Central

2016-01-01

NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many “unwanted” or “undesirable” compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment. PMID:26745651

Potential effect of diaper and cotton ball contamination on NMR- and LC/MS-based metabonomics studies of urine from newborn babies.

PubMed

Goodpaster, Aaron M; Ramadas, Eshwar H; Kennedy, Michael A

2011-02-01

Nuclear magnetic resonance (NMR) and liquid chromatography/mass spectrometry (LC/MS) based metabonomics screening of urine has great potential for discovery of biomarkers for diseases that afflict newborn and preterm infants. However, urine collection from newborn infants presents a potential confounding problem due to the possibility that contaminants might leach from materials used for urine collection and influence statistical analysis of metabonomics data. In this manuscript, we have analyzed diaper and cotton ball contamination using synthetic urine to assess its potential to influence the outcome of NMR- and LC/MS-based metabonomics studies of human infant urine. Eight diaper brands were examined using the "diaper plus cotton ball" technique. Data were analyzed using conventional principal components analysis, as well as a statistical significance algorithm developed for, and applied to, NMR data. Results showed most diaper brands had distinct contaminant profiles that could potentially influence NMR- and LC/MS-based metabonomics studies. On the basis of this study, it is recommended that diaper and cotton ball brands be characterized using metabonomics methodologies prior to initiating a metabonomics study to ensure that contaminant profiles are minimal or manageable and that the same diaper and cotton ball brands be used throughout a study to minimize variation.

Accurate Identification of Unknown and Known Metabolic Mixture Components by Combining 3D NMR with Fourier Transform Ion Cyclotron Resonance Tandem Mass Spectrometry.

PubMed

Wang, Cheng; He, Lidong; Li, Da-Wei; Bruschweiler-Li, Lei; Marshall, Alan G; Brüschweiler, Rafael

2017-10-06

Metabolite identification in metabolomics samples is a key step that critically impacts downstream analysis. We recently introduced the SUMMIT NMR/mass spectrometry (MS) hybrid approach for the identification of the molecular structure of unknown metabolites based on the combination of NMR, MS, and combinatorial cheminformatics. Here, we demonstrate the feasibility of the approach for an untargeted analysis of both a model mixture and E. coli cell lysate based on 2D/3D NMR experiments in combination with Fourier transform ion cyclotron resonance MS and MS/MS data. For 19 of the 25 model metabolites, SUMMIT yielded complete structures that matched those in the mixture independent of database information. Of those, seven top-ranked structures matched those in the mixture, and four of those were further validated by positive ion MS/MS. For five metabolites, not part of the 19 metabolites, correct molecular structural motifs could be identified. For E. coli, SUMMIT MS/NMR identified 20 previously known metabolites with three or more 1 H spins independent of database information. Moreover, for 15 unknown metabolites, molecular structural fragments were determined consistent with their spin systems and chemical shifts. By providing structural information for entire metabolites or molecular fragments, SUMMIT MS/NMR greatly assists the targeted or untargeted analysis of complex mixtures of unknown compounds.

Isolation and structure elucidation of the nucleoside antibiotic strepturidin from Streptomyces albus DSM 40763.

PubMed

Pesic, Alexander; Steinhaus, Britta; Kemper, Sebastian; Nachtigall, Jonny; Kutzner, Hans Jürgen; Höfle, Gerhard; Süssmuth, Roderich D

2014-06-01

The antibiotic strepturidin (1) was isolated from the microorganism Streptomyces albus DSM 40763, and its structure elucidated by spectroscopic methods and chemical degradation studies. The determination of the relative and absolute stereocenters was partially achieved using chiral GC/EI-MS analysis and microderivatization by acetal ring formation and subsequent 2D-NMR analysis of key (1)H,(1)H-NOESY NMR correlations and extraction of (1)H,(13)C coupling constants from (1)H,(13)C-HMBC NMR spectra. Based on these results, a biosynthesis model was proposed.

A novel tridentate Schiff base dioxo-molybdenum(VI) complex: synthesis, experimental and theoretical studies on its crystal structure, FTIR, UV-visible, ¹H NMR and ¹³C NMR spectra.

PubMed

Saheb, Vahid; Sheikhshoaie, Iran; Stoeckli-Evans, Helen

2012-09-01

A new dioxo-molybdenum(VI) complex [MoO(2)(L)(H(2)O)] has been synthesized, using 5-methoxy 2-[(2-hydroxypropylimino)methyl]phenol as tridentate ONO donor Schiff base ligand (H(2)L) and MoO(2)(acac)(2). The yellow crystals of the compound are used for single-crystal X-ray analysis and measuring Fourier Transform Infrared (FTIR), UV-visible, (1)H NMR and (13)C NMR spectra. Electronic structure calculations at the B3LYP and PW91PW91 levels of theory are performed to optimize the molecular geometry and to calculate the UV-visible, FTIR, (1)H NMR and (13)C NMR spectra of the compound. Vibrational assignments and analysis of the fundamental modes of the compound are performed. Time-dependent density functional theory (TDDFT) method is used to calculate the electronic transitions of the complex. All theoretical methods can well reproduce the structure of the compound. The (1)H NMR shielding tensors computed at the B3LYP/DGDZVP level of theory is in agreement with experimental (1)H NMR spectra. However, the (13)C NMR shielding tensors computed at the B3LYP level, employing a combined basis set of DGDZVP for Mo and 6-31+G(2df,p) for other atoms, are in better agreement with experimental (13)C NMR spectra. The electronic transitions calculated at the B3LYP/DGDZVP level by using TD-DFT method is in accordance with the observed UV-visible spectrum of the compound. Copyright © 2012 Elsevier B.V. All rights reserved.

Epoxy monomers derived from tung oil fatty acids and its regulable thermosets cured in two synergistic ways

USDA-ARS?s Scientific Manuscript database

A new bio-based epoxy monomer with conjugated double bonds, glycidyl ester of eleostearic acid (GEEA), was synthesized from tung oil fatty acids and characterized by 1H-NMR, 13C-NMR and Mass Spectrometry Analysis (MSA). Differential Scanning Calorimetry (DSC) analysis and FT-IR were utilized to inve...

Automatic 1H-NMR Screening of Fatty Acid Composition in Edible Oils

PubMed Central

Castejón, David; Fricke, Pascal; Cambero, María Isabel; Herrera, Antonio

2016-01-01

In this work, we introduce an NMR-based screening method for the fatty acid composition analysis of edible oils. We describe the evaluation and optimization needed for the automated analysis of vegetable oils by low-field NMR to obtain the fatty acid composition (FAC). To achieve this, two scripts, which automatically analyze and interpret the spectral data, were developed. The objective of this work was to drive forward the automated analysis of the FAC by NMR. Due to the fact that this protocol can be carried out at low field and that the complete process from sample preparation to printing the report only takes about 3 min, this approach is promising to become a fundamental technique for high-throughput screening. To demonstrate the applicability of this method, the fatty acid composition of extra virgin olive oils from various Spanish olive varieties (arbequina, cornicabra, hojiblanca, manzanilla, and picual) was determined by 1H-NMR spectroscopy according to this protocol. PMID:26891323

Nuclear magnetic resonance (NMR)-based metabolomics for cancer research.

PubMed

Ranjan, Renuka; Sinha, Neeraj

2018-05-07

Nuclear magnetic resonance (NMR) has emerged as an effective tool in various spheres of biomedical research, amongst which metabolomics is an important method for the study of various types of disease. Metabolomics has proved its stronghold in cancer research by the development of different NMR methods over time for the study of metabolites, thus identifying key players in the aetiology of cancer. A plethora of one-dimensional and two-dimensional NMR experiments (in solids, semi-solids and solution phases) are utilized to obtain metabolic profiles of biofluids, cell extracts and tissue biopsy samples, which can further be subjected to statistical analysis. Any alteration in the assigned metabolite peaks gives an indication of changes in metabolic pathways. These defined changes demonstrate the utility of NMR in the early diagnosis of cancer and provide further measures to combat malignancy and its progression. This review provides a snapshot of the trending NMR techniques and the statistical analysis involved in the metabolomics of diseases, with emphasis on advances in NMR methodology developed for cancer research. Copyright © 2018 John Wiley & Sons, Ltd.

[superscript 1]H NMR Spectroscopy-Based Configurational Analysis of Mono- and Disaccharides and Detection of ß-Glucosidase Activity: An Undergraduate Biochemistry Laboratory

ERIC Educational Resources Information Center

Periyannan, Gopal R.; Lawrence, Barbara A.; Egan, Annie E.

2015-01-01

A [superscript 1]H NMR spectroscopy-based laboratory experiment explores mono- and disaccharide structural chemistry, and the enzyme-substrate specificity of glycosidic bond cleavage by ß-glucosidase towards cellobiose (ß-linked gluco-disaccharide) and maltose (a-linked gluco-disaccharide). Structural differences between cellobiose, maltose, and…

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Theoretical NMR correlations based Structure Discussion.

PubMed

Junker, Jochen

2011-07-28

The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. The actual difficulty of the structure elucidation problem depends more on the type of the investigated molecule than on its size. The moment HMBC data is involved in the process or a large number of heteroatoms is present, a possibility of multiple solutions fitting the same data set exists. A structure elucidation software can be used to find such alternative constitutional assignments and help in the discussion in order to find the correct solution. But this is rarely done. This article describes the use of theoretical NMR correlation data in the structure elucidation process with WEBCOCON, not for the initial constitutional assignments, but to define how well a suggested molecule could have been described by NMR correlation data. The results of this analysis can be used to decide on further steps needed to assure the correctness of the structural assignment. As first step the analysis of the deviation of carbon chemical shifts is performed, comparing chemical shifts predicted for each possible solution with the experimental data. The application of this technique to three well known compounds is shown. Using NMR correlation data alone for the description of the constitutions is not always enough, even when including 13C chemical shift prediction.

STD-NMR-Based Protein Engineering of the Unique Arylpropionate-Racemase AMDase G74C.

PubMed

Gaßmeyer, Sarah Katharina; Yoshikawa, Hiroyuki; Enoki, Junichi; Hülsemann, Nadine; Stoll, Raphael; Miyamoto, Kenji; Kourist, Robert

2015-06-23

Structure-guided protein engineering achieved a variant of the unique racemase AMDase G74C, with 40-fold increased activity in the racemisation of several arylaliphatic carboxylic acids. Substrate binding during catalysis was investigated by saturation-transfer-difference NMR (STD-NMR) spectroscopy. All atoms of the substrate showed interactions with the enzyme. STD-NMR measurements revealed distinct nuclear Overhauser effects in experiments with and without molecular conversion. The spectroscopic analysis led to the identification of several amino acid residues whose substitutions increased the activity of G74C. Single amino acid exchanges increased the activity moderately; structure-guided saturation mutagenesis yielded a quadruple mutant with a 40 times higher reaction rate. This study presents STD-NMR as versatile tool for the analysis of enzyme-substrate interactions in catalytically competent systems and for the guidance of protein engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syntheses, characterisation and crystal structures of ferrocenyl β-diketones and their Schiff base Nsbnd Nsbnd O ligand derivatives with 2-picolylamine

NASA Astrophysics Data System (ADS)

Artigas, Vania; González, Deborah; Fuentealba, Mauricio

2017-02-01

Ferrocenyl β-diketones compounds β3-4 were synthesised by Claisen condensation reaction between acetylferrocene and ethyl benzoate or 4-bromoethyl benzoate. We also synthesised four new Schiff base ligands L1-4 by condensation reaction between β1-4 and 2-picolylamine. Identities of all these compounds were confirmed by satisfactory elemental analysis, 1H nuclear magnetic resonance (NMR) correlation and infrared (IR) spectroscopy. In addition, all these compounds were authenticated by a single-crystal X-ray diffraction analysis. In solution, 1H NMR spectra of β3 and β4 exhibit a mixture of keto:enol tautomer ratios of 12:88 and 8:92, respectively, calculated by the integration of the free cyclopentadienyl ring. In contrast, the proton NMR spectra of L1-4 showed only the keto-enamine tautomer displacements. In addition, decoupled 13C NMR spectrum clearly confirmed the existence of these tautomers. These results are in accordance with X-ray crystallographic studies, in which the enol and keto-enamine forms were elucidated for β-diketones and Schiff base ligands, respectively.

Unconventional Tight Reservoirs Characterization with Nuclear Magnetic Resonance

NASA Astrophysics Data System (ADS)

Santiago, C. J. S.; Solatpour, R.; Kantzas, A.

2017-12-01

The increase in tight reservoir exploitation projects causes producing many papers each year on new, modern, and modified methods and techniques on estimating characteristics of these reservoirs. The most ambiguous of all basic reservoir property estimations deals with permeability. One of the logging methods that is advertised to predict permeability but is always met by skepticism is Nuclear Magnetic Resonance (NMR). The ability of NMR to differentiate between bound and movable fluids and providing porosity increased the capability of NMR as a permeability prediction technique. This leads to a multitude of publications and the motivation of a review paper on this subject by Babadagli et al. (2002). The first part of this presentation is dedicated to an extensive review of the existing correlation models for NMR based estimates of tight reservoir permeability to update this topic. On the second part, the collected literature information is used to analyze new experimental data. The data are collected from tight reservoirs from Canada, the Middle East, and China. A case study is created to apply NMR measurement in the prediction of reservoir characterization parameters such as porosity, permeability, cut-offs, irreducible saturations etc. Moreover, permeability correlations are utilized to predict permeability. NMR experiments were conducted on water saturated cores. NMR T2 relaxation times were measured. NMR porosity, the geometric mean relaxation time (T2gm), Irreducible Bulk Volume (BVI), and Movable Bulk Volume (BVM) were calculated. The correlation coefficients were computed based on multiple regression analysis. Results are cross plots of NMR permeability versus the independently measured Klinkenberg corrected permeability. More complicated equations are discussed. Error analysis of models is presented and compared. This presentation is beneficial in understanding existing tight reservoir permeability models. The results can be used as a guide for choosing the best permeability estimation model for tight reservoirs data.

An introduction to NMR-based approaches for measuring protein dynamics

PubMed Central

Kleckner, Ian R; Foster, Mark P

2010-01-01

Proteins are inherently flexible at ambient temperature. At equilibrium, they are characterized by a set of conformations that undergo continuous exchange within a hierarchy of spatial and temporal scales ranging from nanometers to micrometers and femtoseconds to hours. Dynamic properties of proteins are essential for describing the structural bases of their biological functions including catalysis, binding, regulation and cellular structure. Nuclear magnetic resonance (NMR) spectroscopy represents a powerful technique for measuring these essential features of proteins. Here we provide an introduction to NMR-based approaches for studying protein dynamics, highlighting eight distinct methods with recent examples, contextualized within a common experimental and analytical framework. The selected methods are (1) Real-time NMR, (2) Exchange spectroscopy, (3) Lineshape analysis, (4) CPMG relaxation dispersion, (5) Rotating frame relaxation dispersion, (6) Nuclear spin relaxation, (7) Residual dipolar coupling, (8) Paramagnetic relaxation enhancement. PMID:21059410

Quantitative analysis of amygdalin and prunasin in Prunus serotina Ehrh. using (1) H-NMR spectroscopy.

PubMed

Santos Pimenta, Lúcia P; Schilthuizen, Menno; Verpoorte, Robert; Choi, Young Hae

2014-01-01

Prunus serotina is native to North America but has been invasively introduced in Europe since the seventeenth century. This plant contains cyanogenic glycosides that are believed to be related to its success as an invasive plant. For these compounds, chromatographic- or spectrometric-based (targeting on HCN hydrolysis) methods of analysis have been employed so far. However, the conventional methods require tedious preparation steps and a long measuring time. To develop a fast and simple method to quantify the cyanogenic glycosides, amygdalin and prunasin in dried Prunus serotina leaves without any pre-purification steps using (1) H-NMR spectroscopy. Extracts of Prunus serotina leaves using CH3 OH-d4 and KH2 PO4 buffer in D2 O (1:1) were quantitatively analysed for amygdalin and prunasin using (1) H-NMR spectroscopy. Different internal standards were evaluated for accuracy and stability. The purity of quantitated (1) H-NMR signals was evaluated using several two-dimensional NMR experiments. Trimethylsilylpropionic acid sodium salt-d4 proved most suitable as the internal standard for quantitative (1) H-NMR analysis. Two-dimensional J-resolved NMR was shown to be a useful tool to confirm the structures and to check for possible signal overlapping with the target signals for the quantitation. Twenty-two samples of P. serotina were subsequently quantitatively analysed for the cyanogenic glycosides prunasin and amygdalin. The NMR method offers a fast, high-throughput analysis of cyanogenic glycosides in dried leaves permitting simultaneous quantification and identification of prunasin and amygdalin in Prunus serotina. Copyright © 2013 John Wiley & Sons, Ltd.

Comprehensive NMR analysis of compositional changes of black garlic during thermal processing.

PubMed

Liang, Tingfu; Wei, Feifei; Lu, Yi; Kodani, Yoshinori; Nakada, Mitsuhiko; Miyakawa, Takuya; Tanokura, Masaru

2015-01-21

Black garlic is a processed food product obtained by subjecting whole raw garlic to thermal processing that causes chemical reactions, such as the Maillard reaction, which change the composition of the garlic. In this paper, we report a nuclear magnetic resonance (NMR)-based comprehensive analysis of raw garlic and black garlic extracts to determine the compositional changes resulting from thermal processing. (1)H NMR spectra with a detailed signal assignment showed that 38 components were altered by thermal processing of raw garlic. For example, the contents of 11 l-amino acids increased during the first step of thermal processing over 5 days and then decreased. Multivariate data analysis revealed changes in the contents of fructose, glucose, acetic acid, formic acid, pyroglutamic acid, cycloalliin, and 5-(hydroxymethyl)furfural (5-HMF). Our results provide comprehensive information on changes in NMR-detectable components during thermal processing of whole garlic.

Paramagnetic NMR Investigation of Dendrimer-Based Host-Guest Interactions

PubMed Central

Wang, Fei; Shao, Naimin; Cheng, Yiyun

2013-01-01

In this study, the host-guest behavior of poly(amidoamine) (PAMAM) dendrimers bearing amine, hydroxyl, or carboxylate surface functionalities were investigated by paramagnetic NMR studies. 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO) derivatives were used as paramagnetic guest molecules. The results showed that TEMPO-COOH significantly broaden the 1H NMR peaks of amine- and hydroxyl-terminated PAMAM dendrimers. In comparison, no paramagnetic relaxation enhancement (PRE) was observed between TEMPO-NH2, TEMPO-OH and the three types of PAMAM dendrimers. The PRE phenomenon observed is correlated with the encapsulation of TEMPO-COOH within dendrimer pockets. Protonation of the tertiary amine groups within PAMAM dendrimers plays an important role during this process. Interestingly, the absence of TEMPO-COOH encapsulation within carboxylate-terminated PAMAM dendrimer is observed due to the repulsion of TEMPO-COO- anion and anionic dendrimer surface. The combination of paramagnetic probes and 1H NMR linewidth analysis can be used as a powerful tool in the analysis of dendrimer-based host-guest systems. PMID:23762249

Analysis of the interface variability in NMR structure ensembles of protein-protein complexes.

PubMed

Calvanese, Luisa; D'Auria, Gabriella; Vangone, Anna; Falcigno, Lucia; Oliva, Romina

2016-06-01

NMR structures consist in ensembles of conformers, all satisfying the experimental restraints, which exhibit a certain degree of structural variability. We analyzed here the interface in NMR ensembles of protein-protein heterodimeric complexes and found it to span a wide range of different conservations. The different exhibited conservations do not simply correlate with the size of the systems/interfaces, and are most probably the result of an interplay between different factors, including the quality of experimental data and the intrinsic complex flexibility. In any case, this information is not to be missed when NMR structures of protein-protein complexes are analyzed; especially considering that, as we also show here, the first NMR conformer is usually not the one which best reflects the overall interface. To quantify the interface conservation and to analyze it, we used an approach originally conceived for the analysis and ranking of ensembles of docking models, which has now been extended to directly deal with NMR ensembles. We propose this approach, based on the conservation of the inter-residue contacts at the interface, both for the analysis of the interface in whole ensembles of NMR complexes and for the possible selection of a single conformer as the best representative of the overall interface. In order to make the analyses automatic and fast, we made the protocol available as a web tool at: https://www.molnac.unisa.it/BioTools/consrank/consrank-nmr.html. Copyright © 2016 Elsevier Inc. All rights reserved.

A review of whole cell wall NMR by the direct-dissolution of biomass

DOE PAGES

Foston, Marcus B.; Samuel, Reichel; He, Jian; ...

2016-01-19

To fully realize the potential of lignocellulosic biomass as a renewable resource for the production of fuels, chemicals, and materials, an improved understanding of the chemical and molecular structures within biomass and how those structures are formed during biosynthesis and transformed during (thermochemical and biological) conversion must be developed. This effort will require analytical techniques which are not only in-depth, rapid, and cost-effective, but also leave native cell wall features intact. Whole plant cell wall nuclear magnetic resonance (NMR) analysis facilitates unparalleled structural characterization of lignocellulosic biomass without causing (or with minimal) structural modification. The objective of this review ismore » to summarize research pertaining to solution- or gel-state whole plant cell wall NMR analysis of biomass, demonstrating the capability of NMR to delineate the structural features and transformations of biomass. In particular, this review will focus on the application of a two-dimensional solution-state NMR technique and perdeuterated ionic liquid based organic electrolyte solvents for the direct dissolution and analysis of biomass. Furthermore, we believe this type of analysis will be critical to advancing biofuel research, improving bioprocessing methodology, and enhancing plant bioengineering efforts.« less

A review of whole cell wall NMR by the direct-dissolution of biomass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foston, Marcus B.; Samuel, Reichel; He, Jian

To fully realize the potential of lignocellulosic biomass as a renewable resource for the production of fuels, chemicals, and materials, an improved understanding of the chemical and molecular structures within biomass and how those structures are formed during biosynthesis and transformed during (thermochemical and biological) conversion must be developed. This effort will require analytical techniques which are not only in-depth, rapid, and cost-effective, but also leave native cell wall features intact. Whole plant cell wall nuclear magnetic resonance (NMR) analysis facilitates unparalleled structural characterization of lignocellulosic biomass without causing (or with minimal) structural modification. The objective of this review ismore » to summarize research pertaining to solution- or gel-state whole plant cell wall NMR analysis of biomass, demonstrating the capability of NMR to delineate the structural features and transformations of biomass. In particular, this review will focus on the application of a two-dimensional solution-state NMR technique and perdeuterated ionic liquid based organic electrolyte solvents for the direct dissolution and analysis of biomass. Furthermore, we believe this type of analysis will be critical to advancing biofuel research, improving bioprocessing methodology, and enhancing plant bioengineering efforts.« less

Structural Analysis of N- and O-glycans Using ZIC-HILIC/Dialysis Coupled to NMR Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Yi; Feng, Ju; Deng, Shuang

2014-11-19

Protein glycosylation, an important and complex post-translational modification (PTM), is involved in various biological processes including the receptor-ligand and cell-cell interaction, and plays a crucial role in many biological functions. However, little is known about the glycan structures of important biological complex samples, and the conventional glycan enrichment strategy (i.e., size-exclusion column [SEC] separation,) prior to nuclear magnetic resonance (NMR) detection is time-consuming and tedious. In this study, we employed SEC, Zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC), and ZIC-HILIC coupled with dialysis strategies to enrich the glycopeptides from the pronase E digests of RNase B, followed by NMR analysis ofmore » the glycoconjugate. Our results suggest that the ZIC-HILIC enrichment coupled with dialysis is the most efficient, which was thus applied to the analysis of biological complex sample, the pronase E digest of the secreted proteins from the fungi Aspergillus niger. The NMR spectra revealed that the secreted proteins from A. niger contain both N-linked glycans with a high-mannose core and O-linked glycans bearing mannose and glucose with 1->3 and 1->6 linkages. In all, our study provides compelling evidence that ZIC-HILIC separation coupled to dialysis is superior to the commonly used SEC separation to prepare glycopeptides for the downstream NMR analysis, which could greatly facilitate the future NMR-based glycoproteomics research.« less

The influence of a sports drink on the postexercise metabolism of elite athletes as investigated by NMR-based metabolomics.

PubMed

Miccheli, Alfredo; Marini, Federico; Capuani, Giorgio; Miccheli, Alberta Tomassini; Delfini, Maurizio; Di Cocco, Maria Enrica; Puccetti, Caterina; Paci, Maurizio; Rizzo, Marta; Spataro, Antonio

2009-10-01

The aim of this study is to evaluate the systemic effects of an isotonic sports drink on the metabolic status of athletes of the Italian Olympic rowing team during recovery after strenuous and prolonged physical exercise by means of nuclear magnetic resonance (NMR)-based metabolomics analysis on plasma and urine. Forty-four male athletes of the Italian Olympic rowing team were enrolled in a double-blind crossover study. All subjects underwent 2 evaluations at 1-week intervals. The evaluation was performed on a rowing ergometer after strenuous physical exercise to produce a state of dehydration. Afterward, the athletes were rehydrated either with a green tea-based carbohydrate-hydroelectrolyte drink or with oligomineral water. Three blood samples were drawn for each subject: at rest, after the exercise, and following rehydratation, while 2 urine samples were collected: at rest and after the rehydratation period. Biofluid samples were analyzed by high-resolution (1)H NMR metabolic profiling combined with multilevel simultaneous data-analysis (MSCA) and partial-least squares-discriminant analysis (PLS-DA). The between-subject variations, as evaluated by MSCA, reflected the variations of lactate levels induced by the physical exercise. Analysis of the within-individual variance using multilevel PLS-DA models of plasma and urine metabolic profiles showed an effect of the green tea-based sports drink on glucose, citrate, and lactate levels in plasma and on acetone, 3-OH-butyrate, and lactate levels in urine. The increase of caffeine and hippuric acid levels in urine indicated the absorption of green tea extract components. NMR-based metabolomics allowed the complex effects of a green tea extract-based carbohydrate/hydroelectrolyte beverage on the energy metabolism of athletes during recovery by postexercise rehydration to be evaluated.

Certified Reference Material for Use in 1H, 31P, and 19F Quantitative NMR, Ensuring Traceability to the International System of Units.

PubMed

Rigger, Romana; Rück, Alexander; Hellriegel, Christine; Sauermoser, Robert; Morf, Fabienne; Breitruck, KathrinBreitruck; Obkircher, Markus

2017-09-01

In recent years, quantitative NMR (qNMR) spectroscopy has become one of the most important tools for content determination of organic substances and quantitative evaluation of impurities. Using Certified Reference Materials (CRMs) as internal or external standards, the extensively used qNMR method can be applied for purity determination, including unbroken traceability to the International System of Units (SI). The implementation of qNMR toward new application fields, e.g., metabolomics, environmental analysis, and physiological pathway studies, brings along more complex molecules and systems, thus making use of 1H qNMR challenging. A smart workaround is possible by the use of other NMR active nuclei, namely 31P and 19F. This article presents the development of three classes of qNMR CRMs based on different NMR active nuclei (1H, 31P, and 19F), and the corresponding approaches to establish traceability to the SI through primary CRMs from the National Institute of Standards and Technology and the National Metrology Institute of Japan. These TraceCERT® qNMR CRMs are produced under ISO/IEC 17025 and ISO Guide 34 using high-performance qNMR.

Metabolite profiling of Clinacanthus nutans leaves extracts obtained from different drying methods by 1H NMR-based metabolomics

NASA Astrophysics Data System (ADS)

Hashim, Noor Haslinda Noor; Latip, Jalifah; Khatib, Alfi

2016-11-01

The metabolites of Clinacanthus nutans leaves extracts and their dependence on drying process were systematically characterized using 1H nuclear magnetic resonance spectroscopy (NMR) multivariate data analysis. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were able to distinguish the leaves extracts obtained from different drying methods. The identified metabolites were carbohydrates, amino acid, flavonoids and sulfur glucoside compounds. The major metabolites responsible for the separation in PLS-DA loading plots were lupeol, cycloclinacosides, betulin, cerebrosides and choline. The results showed that the combination of 1H NMR spectroscopy and multivariate data analyses could act as an efficient technique to understand the C. nutans composition and its variation.

Application of quantitative 1H NMR for the calibration of protoberberine alkaloid reference standards.

PubMed

Wu, Yan; He, Yi; He, Wenyi; Zhang, Yumei; Lu, Jing; Dai, Zhong; Ma, Shuangcheng; Lin, Ruichao

2014-03-01

Quantitative nuclear magnetic resonance spectroscopy (qNMR) has been developed into an important tool in the drug analysis, biomacromolecule detection, and metabolism study. Compared with mass balance method, qNMR method bears some advantages in the calibration of reference standard (RS): it determines the absolute amount of a sample; other chemical compound and its certified reference material (CRM) can be used as internal standard (IS) to obtain the purity of the sample. Protoberberine alkaloids have many biological activities and have been used as reference standards for the control of many herbal drugs. In present study, the qNMR methods were developed for the calibration of berberine hydrochloride, palmatine hydrochloride, tetrahydropalmatine, and phellodendrine hydrochloride with potassium hydrogen phthalate as IS. Method validation was carried out according to the guidelines for the method validation of Chinese Pharmacopoeia. The results of qNMR were compared with those of mass balance method and the differences between the results of two methods were acceptable based on the analysis of estimated measurement uncertainties. Therefore, qNMR is an effective and reliable analysis method for the calibration of RS and can be used as a good complementarity to the mass balance method. Copyright © 2013 Elsevier B.V. All rights reserved.

The application of NMR-based milk metabolite analysis in milk authenticity identification.

PubMed

Li, Qiangqiang; Yu, Zunbo; Zhu, Dan; Meng, Xianghe; Pang, Xiumei; Liu, Yue; Frew, Russell; Chen, He; Chen, Gang

2017-07-01

Milk is an important food component in the human diet and is a target for fraud, including many unsafe practices. For example, the unscrupulous adulteration of soymilk into bovine and goat milk or of bovine milk into goat milk in order to gain profit without declaration is a health risk, as the adulterant source and sanitary history are unknown. A robust and fit-for-purpose technique is required to enforce market surveillance and hence protect consumer health. Nuclear magnetic resonance (NMR) is a powerful technique for characterization of food products based on measuring the profile of metabolites. In this study, 1D NMR in conjunction with multivariate chemometrics as well as 2D NMR was applied to differentiate milk types and to identify milk adulteration. Ten metabolites were found which differed among milk types, hence providing characteristic markers for identifying the milk. These metabolites were used to establish mathematical models for milk type differentiation. The limit of quantification (LOQ) of adulteration was 2% (v/v) for soymilk in bovine milk, 2% (v/v) for soymilk in goat milk and 5% (v/v) for bovine milk in goat milk, with relative standard deviation (RSD) less than 10%, which can meet the needs of daily inspection. The NMR method described here is effective for milk authenticity identification, and the study demonstrates that the NMR-based milk metabolite analysis approach provides a means of detecting adulteration at expected levels and can be used for dairy quality monitoring. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, R.E.

This report describes the analysis of carbonxyl-terminated butadiene (CTB), carboxyl-terminated butadiene/acrylonitrile (CTBN), and a CTBN adduct prepared by reaction with Epon 828. Data from gel permeation chromatography, nuclear magnetic resonance spectroscopy, high performance liquid chromatography, and ion chromatography are presented and discussed. Quantitative methods based on carbon-13 and proton NMR for analyzing CTBN are described. Proton NMR was found to be useful in identifying lots that have an abnormal amount of CTBN protons. One such lot exhibited a phase separation of a polybutadiene impurity. Carbon-13 NMR was found to be capable of determining nitrile content directly. Carbon-13 NMR had amore » relative standard deviation of 8.3% and a proton NMR of 3.9%. Proton NMR was found to be useful in identifying lots that have 5% more CTBN protons than other lots. 3 refs., 11 figs., 4 tabs.« less

A Preliminary Investigation of NSCL/P Plasma and Urine in Guizhou Province in China Using NMR-Based Metabonomics.

PubMed

Lei, Huang Guang; Hong, Luo; Kun, Song Ju; Hai, Yin Xin; Dong, Wang Ya; Ke, Zhao; Ping, Xu; Hao, Chen

2013-09-01

Objective : To assess the feasibility of metabonomics in clinical studies. This is a pilot study introducing nuclear magnetic resonance (NMR)-based metabonomics to elucidate and compare the metabolism of patients with nonsyndromic cleft lip and/or palate (NSCL/P) and children without orofacial clefts. Methods : High-resolution (1)H NMR spectroscopy was performed on plasma and urine samples obtained from NSCL/P and healthy children. The (1)H NMR spectra were further analyzed with principal component analysis. Results : Compared to the control group, the level of low-molecular-weight metabolites in plasma such as asparagine was higher in NSCL/P patients, while arginine, lysine, acetate, lactate, proline, glutamine, pyruvate, creatinine, choline, and β-glucose were lower. The carnitine, citrate, and formate excretion in urine appeared to be higher in the healthy children, while the NSCL/P group excreted higher concentrations of aspartic acid and phenylalanine in urine. Conclusion : The present study clearly demonstrated the great potential of NMR-based metabonomics in elucidating NSCL/P plasma metabolism and the possible application of this technology in clinical diagnosis and screening.

Spectroscopic and Statistical Techniques for Information Recovery in Metabonomics and Metabolomics

NASA Astrophysics Data System (ADS)

Lindon, John C.; Nicholson, Jeremy K.

2008-07-01

Methods for generating and interpreting metabolic profiles based on nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and chemometric analysis methods are summarized and the relative strengths and weaknesses of NMR and chromatography-coupled MS approaches are discussed. Given that all data sets measured to date only probe subsets of complex metabolic profiles, we describe recent developments for enhanced information recovery from the resulting complex data sets, including integration of NMR- and MS-based metabonomic results and combination of metabonomic data with data from proteomics, transcriptomics, and genomics. We summarize the breadth of applications, highlight some current activities, discuss the issues relating to metabonomics, and identify future trends.

Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics.

PubMed

Lindon, John C; Nicholson, Jeremy K

2008-01-01

Methods for generating and interpreting metabolic profiles based on nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and chemometric analysis methods are summarized and the relative strengths and weaknesses of NMR and chromatography-coupled MS approaches are discussed. Given that all data sets measured to date only probe subsets of complex metabolic profiles, we describe recent developments for enhanced information recovery from the resulting complex data sets, including integration of NMR- and MS-based metabonomic results and combination of metabonomic data with data from proteomics, transcriptomics, and genomics. We summarize the breadth of applications, highlight some current activities, discuss the issues relating to metabonomics, and identify future trends.

Comparative NMR analysis of the decadeoxynucleotide d-(GCATTAATGC)2 and an analogue containing 2-aminoadenine.

PubMed Central

Chazin, W J; Rance, M; Chollet, A; Leupin, W

1991-01-01

The dodecadeoxynucleotide duplex d-(GCATTAATGC)2 has been prepared with all adenine bases replaced by 2-NH2-adenine. This modified duplex has been characterized by nuclear magnetic resonance (NMR) spectroscopy. Complete sequence-specific 1H resonance assignments have been obtained by using a variety of 2D NMR methods. Multiple quantum-filtered and multiple quantum experiments have been used to completely assign all sugar ring protons, including 5'H and 5'H resonances. The assignments form the basis for a detailed comparative analysis of the 1H NMR parameters of the modified and parent duplex. The structural features of both decamer duplexes in solution are characteristic of the B-DNA family. The spin-spin coupling constants in the sugar rings and the relative spatial proximities of protons in the bases and sugars (as determined from the comparison of corresponding nuclear Overhauser effects) are virtually identical in the parent and modified duplexes. Thus, substitution by this adenine analogue in oligonucleotides appears not to disturb the global or local conformation of the DNA duplex. PMID:1945828

A Multidisciplinary Approach to High Throughput Nuclear Magnetic Resonance Spectroscopy

PubMed Central

Pourmodheji, Hossein; Ghafar-Zadeh, Ebrahim; Magierowski, Sebastian

2016-01-01

Nuclear Magnetic Resonance (NMR) is a non-contact, powerful structure-elucidation technique for biochemical analysis. NMR spectroscopy is used extensively in a variety of life science applications including drug discovery. However, existing NMR technology is limited in that it cannot run a large number of experiments simultaneously in one unit. Recent advances in micro-fabrication technologies have attracted the attention of researchers to overcome these limitations and significantly accelerate the drug discovery process by developing the next generation of high-throughput NMR spectrometers using Complementary Metal Oxide Semiconductor (CMOS). In this paper, we examine this paradigm shift and explore new design strategies for the development of the next generation of high-throughput NMR spectrometers using CMOS technology. A CMOS NMR system consists of an array of high sensitivity micro-coils integrated with interfacing radio-frequency circuits on the same chip. Herein, we first discuss the key challenges and recent advances in the field of CMOS NMR technology, and then a new design strategy is put forward for the design and implementation of highly sensitive and high-throughput CMOS NMR spectrometers. We thereafter discuss the functionality and applicability of the proposed techniques by demonstrating the results. For microelectronic researchers starting to work in the field of CMOS NMR technology, this paper serves as a tutorial with comprehensive review of state-of-the-art technologies and their performance levels. Based on these levels, the CMOS NMR approach offers unique advantages for high resolution, time-sensitive and high-throughput bimolecular analysis required in a variety of life science applications including drug discovery. PMID:27294925

Quantitative analysis of protein-ligand interactions by NMR.

PubMed

Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

2016-08-01

Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used to analyze population-averaged NMR quantities. Essentially, to apply NMR successfully, both the type of experiment and equation to fit the data must be carefully and specifically chosen for the protein-ligand interaction under analysis. In this review, we first explain the exchange regimes and kinetic models of protein-ligand interactions, and then describe the NMR methods that quantitatively analyze these specific interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Establishing ¹H nuclear magnetic resonance based metabonomics fingerprinting profile for spinal cord injury: a pilot study.

PubMed

Jiang, Hua; Peng, Jin; Zhou, Zhi-yuan; Duan, Yu; Chen, Wei; Cai, Bin; Yang, Hao; Zhang, Wei

2010-09-01

Spinal cord injury (SCI) is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using (1)H nuclear magnetic resonance (NMR) based metabonomics methodology and principal component analysis techniques. Nine Sprague-Dawley (SD) male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for (1)H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software. Metabonomics analysis was able to distinguish the three groups (SCI, normal control, sham-operation). The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component: it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), triglyceride (TG), glucose, and 3-methyl-histamine. The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on (1)H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual.

Synthesis of metal complexes involving Schiff base ligand with methylenedioxy moiety: spectral, thermal, XRD and antimicrobial studies.

PubMed

Sundararajan, M L; Jeyakumar, T; Anandakumaran, J; Karpanai Selvan, B

2014-10-15

Metal complexes of Zn(II), Cd(II), Ni(II), Cu(II), Fe(III), Co(II), Mn(II) Hg(II), and Ag(I) have been synthesized from Schiff base ligand, prepared by the condensation of 3,4-(methylenedioxy)aniline and 5-bromo salicylaldehyde. All the compounds have been characterized by using elemental analysis, molar conductance, FT-IR, UV-Vis, (1)H NMR, (13)C NMR, mass spectra, powder XRD and thermal analysis (TG/DTA) technique. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). The FT-IR, (1)H NMR, (13)C NMR and UV-Vis spectral data suggest that the ligand coordinate to the metal atom by imino nitrogen and phenolic oxygen as bidentate manner. Mass spectral data further support the molecular mass of the compounds and their structure. Powder XRD indicates the crystalline state and morphology of the ligand and its metal complexes. The thermal behaviors of the complexes prove the presence of lattice as well as coordinated water molecules in the complexes. Melting point supports the thermal stability of all the compounds. The in vitro antimicrobial effects of the synthesized compounds were tested against five bacterial and three fungal species by well diffusion method. Antioxidant activities have also been performed for all the compounds. Metal complexes show more biological activity than the Schiff base. Copyright © 2014 Elsevier B.V. All rights reserved.

Thermal heterogeneity within aqueous materials quantified by 1H NMR spectroscopy: Multiparametric validation in silico and in vitro

NASA Astrophysics Data System (ADS)

Lutz, Norbert W.; Bernard, Monique

2018-02-01

We recently suggested a new paradigm for statistical analysis of thermal heterogeneity in (semi-)aqueous materials by 1H NMR spectroscopy, using water as a temperature probe. Here, we present a comprehensive in silico and in vitro validation that demonstrates the ability of this new technique to provide accurate quantitative parameters characterizing the statistical distribution of temperature values in a volume of (semi-)aqueous matter. First, line shape parameters of numerically simulated water 1H NMR spectra are systematically varied to study a range of mathematically well-defined temperature distributions. Then, corresponding models based on measured 1H NMR spectra of agarose gel are analyzed. In addition, dedicated samples based on hydrogels or biological tissue are designed to produce temperature gradients changing over time, and dynamic NMR spectroscopy is employed to analyze the resulting temperature profiles at sub-second temporal resolution. Accuracy and consistency of the previously introduced statistical descriptors of temperature heterogeneity are determined: weighted median and mean temperature, standard deviation, temperature range, temperature mode(s), kurtosis, skewness, entropy, and relative areas under temperature curves. Potential and limitations of this method for quantitative analysis of thermal heterogeneity in (semi-)aqueous materials are discussed in view of prospective applications in materials science as well as biology and medicine.

Nicotine Metabolite Ratio (3-hydroxycotinine/cotinine) in Plasma and Urine by Different Analytical Methods and Laboratories: Implications for Clinical Implementation

PubMed Central

Tanner, Julie-Anne; Novalen, Maria; Jatlow, Peter; Huestis, Marilyn A.; Murphy, Sharon E.; Kaprio, Jaakko; Kankaanpää, Aino; Galanti, Laurence; Stefan, Cristiana; George, Tony P.; Benowitz, Neal L.; Lerman, Caryn; Tyndale, Rachel F.

2015-01-01

Background The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3′-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers. Methods Plasma (n=35) and urine (n=35) samples were sent to eight different laboratories, which employed similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods. Results Measures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios 0.82–1.16) and were highly correlated (all Pearson r>0.96, P<0.0001). Measures of urinary NMR were in relatively weaker agreement (ratios 0.62–1.71) and less strongly correlated (Pearson r values of 0.66–0.98, P<0.0001) between different methods. Plasma and urinary COT and 3HC concentrations, while weaker than NMR, also showed good agreement in plasma, which was better than in urine, as was observed for NMR. Conclusions Plasma is a very reliable biological source for the determination of NMR, robust to differences in these analytical protocols or assessment site. Impact Together this indicates a reduced need for differential interpretation of plasma NMR results based on the approach used, allowing for direct comparison of different studies. PMID:26014804

Effect of genetic and phenotypic factors on the composition of commercial marmande type tomatoes studied through HRMAS NMR spectroscopy.

PubMed

Iglesias, María José; García López, Jesús; Collados Luján, Juan Fernando; López Ortiz, Fernando; Bojórquez Pereznieto, Humberto; Toresano, Fernando; Camacho, Francisco

2014-01-01

The effects of genetic, technological and environmental factors on the chemical composition of four marmande type tomato varieties have been investigated. The study is based on the analysis of (1)H HRMAS NMR spectra of tomato purée using a combination of partial least squares (PLS) and assigned signal analysis (ASA). In agreement with genetic, morphological and taste characteristics of the tomatoes studied, the analysis of the NMR data allows two groups of samples to be differentiated. The type of culture and climatic conditions can reduce the compositional differences. The extension of the compositional changes produced by climatic conditions is variety-depend. Neither grafting nor perlite affect significantly the relative content of primary metabolites. This was not the case for tomatoes grown using the pure hydroponic production system based on the recirculation of nutrient solution, New Growing System NGS®, which seems to be an effective agricultural approach to improve tomato quality. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

DOE PAGES

Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.; ...

2018-01-17

Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boiteau, Rene M.; Hoyt, David W.; Nicora, Carrie D.

Here, we introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS 2), and NMR in a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS 2 approach is well suited for discovery ofmore » new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases.« less

Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and MS/MS Prediction

PubMed Central

Hoyt, David W.; Nicora, Carrie D.; Kinmonth-Schultz, Hannah A.; Ward, Joy K.

2018-01-01

We introduce a cheminformatics approach that combines highly selective and orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR into a single analysis platform to accurately identify unknown metabolites in untargeted studies. The approach starts with an unknown LC-MS feature, and then combines the experimental MS/MS and NMR information of the unknown to effectively filter out the false positive candidate structures based on their predicted MS/MS and NMR spectra. We demonstrate the approach on a model mixture, and then we identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The NMR/MS2 approach is well suited to the discovery of new metabolites in plant extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and biomedical samples, facilitating the identification of metabolites that are not present in experimental NMR and MS metabolomics databases. PMID:29342073

Solid-state NMR and IR for the analysis of pharmaceutical solids: polymorphs of fosinopril sodium.

PubMed

Brittain, H G; Morris, K R; Bugay, D E; Thakur, A B; Serajuddin, A T

1993-01-01

The two polymorphic modifications of fosinopril sodium have been characterized as to their differences in melting behaviour, powder X-ray diffraction patterns, Fourier transform infrared spectra (FTIR), and solid-state 31P- and 13C-NMR spectra. The polymorphs were found to be enantiotropically related based upon melting point, heat of fusion, and solution mediated transformation data. Analysis of the solid-state FTIR and 13C-NMR data indicated that the environment of the acetal side chain of fosinopril sodium differed in two polymorphs, and that there might be cis-trans isomerization about the C6-N peptide bond. These conformational differences are postulated as the origin of the observed polymorphism.

Contaminations of herbal products determined by NMR fingerprint.

PubMed

Nicoletti, Marcello; Petitto, Valentina

2010-09-01

The utilisation of NMR fingerprinting is proposed as a rapid, available and reliable method to determine the contamination of herbal products. The presence of nimesulide has been reported recently as the contaminant of P.C. 28 Plus, a product based on herbal drugs marketed by the Italian company Cosval. The presence of the substance, as well as its relevant concentration (5%), was first reported by HPLC/MS analysis by other authors. The use of an NMR fingerprint confirmed the previous contamination with nimesulide in P.C. 28 Plus. The same contaminant was also found in P.C. 28 Pink. Furthermore, an analysis of Alergix Plus, another product of the same factory, evidenced the presence of bromhexin.

31P NMR Chemical Shifts of Solvents and Products Impurities in Biomass Pretreatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Mi; Yoo, Chang Geun; Pu, Yunqiao

The identification of chemical impurities is crucial in elucidating the structures of biorefinery products using nuclear magnetic resonance (NMR) spectroscopic analysis. In the current biorefinery platform, contaminants derived from pretreatment solvents and decomposition byproducts may lead to misassignment of the NMR spectra of biorefinery products (e.g, lignin and bio-oils). Therefore, we investigated in this paper 54 commonly reported compounds including alcohols, carbohydrates, organic acids, aromatics, aldehydes, and ionic liquids associated with biomass pretreatment using 31P NMR. The chemical shifts of these chemicals after derivatizing with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane (TMDP) were provided. Finally, the 31P NMR signals of these derivatives could serve asmore » valuable and informative spectral data in characterizing lignocellulose-based compounds.« less

31P NMR Chemical Shifts of Solvents and Products Impurities in Biomass Pretreatments

DOE PAGES

Li, Mi; Yoo, Chang Geun; Pu, Yunqiao; ...

2017-12-05

The identification of chemical impurities is crucial in elucidating the structures of biorefinery products using nuclear magnetic resonance (NMR) spectroscopic analysis. In the current biorefinery platform, contaminants derived from pretreatment solvents and decomposition byproducts may lead to misassignment of the NMR spectra of biorefinery products (e.g, lignin and bio-oils). Therefore, we investigated in this paper 54 commonly reported compounds including alcohols, carbohydrates, organic acids, aromatics, aldehydes, and ionic liquids associated with biomass pretreatment using 31P NMR. The chemical shifts of these chemicals after derivatizing with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane (TMDP) were provided. Finally, the 31P NMR signals of these derivatives could serve asmore » valuable and informative spectral data in characterizing lignocellulose-based compounds.« less

Use of NMR Metabolomics to Analyze the Targets of D-cycloserine in Mycobacteria: Role of D-Alanine Racemase

PubMed Central

Halouska, Steven; Chacon, Ofelia; Fenton, Robert J.; Zinniel, Denise K.; Barletta, Raul G.; Powers, Robert

2008-01-01

D-cycloserine (DCS) is only used with multi-drug resistant strains of tuberculosis because of serious side-effects. DCS is known to inhibit cell wall biosynthesis, but the in vivo lethal target is still unknown. We have applied NMR-based metabolomics combined with principal component analysis to monitor the in vivo affect of DCS on M. smegmatis. Our analysis suggests DCS functions by inhibiting multiple protein targets. PMID:17979227

NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds

PubMed Central

Yu, Jun-lan; Chen, Tian-tian; Zhou, Chen; Lian, Fu-lin; Tang, Xu-long; Wen, Yi; Shen, Jing-kang; Xu, Ye-chun; Xiong, Bing; Zhang, Nai-xia

2016-01-01

Aim: Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein. Methods: 1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein. Results: An NMR-based fragment library containing 539 compounds was established, which were clustered into 56 groups (8–10 compounds in each group). Eight hits with new scaffolds were found to inhibit BRD4(I). Four out of the 8 hits (compounds 1, 2, 8 and 9) had IC50 values of 100–260 μmol/L, demonstrating their potential for further BRD4-targeted hit-to-lead optimization. Analysis of the binding interactions revealed that compounds 1 and 2 shared a common quinazolin core structure and bound to BRD4(I) in a non-acetylated lysine mimetic mode. Conclusion: An NMR-based platform for FBLD was established and used in discovery of BRD4-targeted compounds. Four potential hit-to-lead optimization candidates have been found, two of them bound to BRD4(I) in a non-acetylated lysine mimetic mode, being selective BRD4(I) inhibitors. PMID:27238211

An epoxy monomer derived from Tung oil fatty acids and its products cured by two synergistic reactions

USDA-ARS?s Scientific Manuscript database

A new bio-based epoxy monomer containing conjugated double bonds, the glycidyl ester of eleostearic acid (GEEA), was synthesized from tung oil fatty acids. It was characterized using 1H-NMR, 13C-NMR and mass spectrometric analysis. Differential scanning calorimetry (DSC) and FT-IR spectroscopy were ...

Automated Solid Phase Extraction (SPE) LC/NMR Applied to the Structural Analysis of Extractable Compounds from a Pharmaceutical Packaging Material of Construction.

PubMed

Norwood, Daniel L; Mullis, James O; Davis, Mark; Pennino, Scott; Egert, Thomas; Gonnella, Nina C

2013-01-01

The structural analysis (i.e., identification) of organic chemical entities leached into drug product formulations has traditionally been accomplished with techniques involving the combination of chromatography with mass spectrometry. These include gas chromatography/mass spectrometry (GC/MS) for volatile and semi-volatile compounds, and various forms of liquid chromatography/mass spectrometry (LC/MS or HPLC/MS) for semi-volatile and relatively non-volatile compounds. GC/MS and LC/MS techniques are complementary for structural analysis of leachables and potentially leachable organic compounds produced via laboratory extraction of pharmaceutical container closure/delivery system components and corresponding materials of construction. Both hyphenated analytical techniques possess the separating capability, compound specific detection attributes, and sensitivity required to effectively analyze complex mixtures of trace level organic compounds. However, hyphenated techniques based on mass spectrometry are limited by the inability to determine complete bond connectivity, the inability to distinguish between many types of structural isomers, and the inability to unambiguously determine aromatic substitution patterns. Nuclear magnetic resonance spectroscopy (NMR) does not have these limitations; hence it can serve as a complement to mass spectrometry. However, NMR technology is inherently insensitive and its ability to interface with chromatography has been historically challenging. This article describes the application of NMR coupled with liquid chromatography and automated solid phase extraction (SPE-LC/NMR) to the structural analysis of extractable organic compounds from a pharmaceutical packaging material of construction. The SPE-LC/NMR technology combined with micro-cryoprobe technology afforded the sensitivity and sample mass required for full structure elucidation. Optimization of the SPE-LC/NMR analytical method was achieved using a series of model compounds representing the chemical diversity of extractables. This study demonstrates the complementary nature of SPE-LC/NMR with LC/MS for this particular pharmaceutical application. The identification of impurities leached into drugs from the components and materials associated with pharmaceutical containers, packaging components, and materials has historically been done using laboratory techniques based on the combination of chromatography with mass spectrometry. Such analytical techniques are widely recognized as having the selectivity and sensitivity required to separate the complex mixtures of impurities often encountered in such identification studies, including both the identification of leachable impurities as well as potential leachable impurities produced by laboratory extraction of packaging components and materials. However, while mass spectrometry-based analytical techniques have limitations for this application, newer analytical techniques based on the combination of chromatography with nuclear magnetic resonance spectroscopy provide an added dimension of structural definition. This article describes the development, optimization, and application of an analytical technique based on the combination of chromatography and nuclear magnetic resonance spectroscopy to the identification of potential leachable impurities from a pharmaceutical packaging material. The complementary nature of the analytical techniques for this particular pharmaceutical application is demonstrated.

Solid-state NMR studies of form I of atorvastatin calcium.

PubMed

Wang, Wei David; Gao, Xudong; Strohmeier, Mark; Wang, Wei; Bai, Shi; Dybowski, Cecil

2012-03-22

Solid-state (13)C, (19)F, and (15)N magic angle spinning NMR studies of Form I of atorvastatin calcium are reported, including chemical shift tensors of all resolvable carbon sites and fluorine sites. The complete (13)C and (19)F chemical shift assignments are given based on an extensive analysis of (13)C-(1)H HETCOR and (13)C-(19)F HETCOR results. The solid-state NMR data indicate that the asymmetric unit of this material contains two atorvastatin molecules. A possible structure of Form I of atorvastatin calcium (ATC-I), derived from solid-state NMR data and density functional theory calculations of various structures, is proposed for this important active pharmaceutical ingredient (API).

Influence of Freezing and Storage Procedure on Human Urine Samples in NMR-Based Metabolomics

PubMed Central

Rist, Manuela J.; Muhle-Goll, Claudia; Görling, Benjamin; Bub, Achim; Heissler, Stefan; Watzl, Bernhard; Luy, Burkhard

2013-01-01

It is consensus in the metabolomics community that standardized protocols should be followed for sample handling, storage and analysis, as it is of utmost importance to maintain constant measurement conditions to identify subtle biological differences. The aim of this work, therefore, was to systematically investigate the influence of freezing procedures and storage temperatures and their effect on NMR spectra as a potentially disturbing aspect for NMR-based metabolomics studies. Urine samples were collected from two healthy volunteers, centrifuged and divided into aliquots. Urine aliquots were frozen either at −20 °C, on dry ice, at −80 °C or in liquid nitrogen and then stored at −20 °C, −80 °C or in liquid nitrogen vapor phase for 1–5 weeks before NMR analysis. Results show spectral changes depending on the freezing procedure, with samples frozen on dry ice showing the largest deviations. The effect was found to be based on pH differences, which were caused by variations in CO2 concentrations introduced by the freezing procedure. Thus, we recommend that urine samples should be frozen at −20 °C and transferred to lower storage temperatures within one week and that freezing procedures should be part of the publication protocol. PMID:24957990

Influence of Freezing and Storage Procedure on Human Urine Samples in NMR-Based Metabolomics.

PubMed

Rist, Manuela J; Muhle-Goll, Claudia; Görling, Benjamin; Bub, Achim; Heissler, Stefan; Watzl, Bernhard; Luy, Burkhard

2013-04-09

It is consensus in the metabolomics community that standardized protocols should be followed for sample handling, storage and analysis, as it is of utmost importance to maintain constant measurement conditions to identify subtle biological differences. The aim of this work, therefore, was to systematically investigate the influence of freezing procedures and storage temperatures and their effect on NMR spectra as a potentially disturbing aspect for NMR-based metabolomics studies. Urine samples were collected from two healthy volunteers, centrifuged and divided into aliquots. Urine aliquots were frozen either at -20 °C, on dry ice, at -80 °C or in liquid nitrogen and then stored at -20 °C, -80 °C or in liquid nitrogen vapor phase for 1-5 weeks before NMR analysis. Results show spectral changes depending on the freezing procedure, with samples frozen on dry ice showing the largest deviations. The effect was found to be based on pH differences, which were caused by variations in CO2 concentrations introduced by the freezing procedure. Thus, we recommend that urine samples should be frozen at -20 °C and transferred to lower storage temperatures within one week and that freezing procedures should be part of the publication protocol.

New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

PubMed

Sanchon-Lopez, Beatriz; Everett, Jeremy R

2016-09-02

A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

1H NMR spectroscopic analysis detects metabolic disturbances in rat urine on acute exposure to heavy metal tungsten alloy based metals salt.

PubMed

Tyagi, Ritu; Rana, Poonam; Gupta, Mamta; Bhatnagar, Deepak; Srivastava, Shatakshi; Roy, Raja; Khushu, Subash

2014-03-25

Heavy metal tungsten alloys (HMTAs) have been found to be safer alternatives for making military munitions. Recently, some studies demonstrating the toxic potential of HMTAs have raised concern over the safety issues, and further propose that HMTAs exposure may lead to physiological disturbances as well. To look for the systemic effect of acute toxicity of HMTA based metals salt, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic profiling of rat urine was carried out. Male Sprague Dawley rats were administered (intraperitoneal) low and high dose of mixture of HMTA based metals salt and NMR spectroscopy was carried out in urine samples collected at 8, 24, 72 and 120 h post dosing (p.d.). Serum biochemical parameters and liver histopathology were also conducted. The (1)H NMR spectra were analysed using multivariate analysis techniques to show the time- and dose-dependent biochemical variations in post HMTA based metals salt exposure. Urine metabolomic analysis showed changes associated with energy metabolism, amino acids, N-methyl nicotinamide, membrane and gut flora metabolites. Multivariate analysis showed maximum variation with best classification of control and treated groups at 24h p.d. At the end of the study, for the low dose group most of the changes at metabolite level reverted to control except for the energy metabolites; whereas, in the high dose group some of the changes still persisted. The observations were well correlated with histopathological and serum biochemical parameters. Further, metabolic pathway analysis clarified that amongst all the metabolic pathways analysed, tricarboxylic acid cycle was most affected at all the time points indicating a switchover in energy metabolism from aerobic to anaerobic. These results suggest that exposure of rats to acute doses of HMTA based metals salt disrupts physiological metabolism with moderate injury to the liver, which might indirectly result from heavy metals induced oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Diagnosis of coinfection by schistosomiasis and viral hepatitis B or C using 1H NMR-based metabonomics.

PubMed

Gouveia, Liana Ribeiro; Santos, Joelma Carvalho; Silva, Ronaldo Dionísio; Batista, Andrea Dória; Domingues, Ana Lúcia Coutinho; Lopes, Edmundo Pessoa de Almeida; Silva, Ricardo Oliveira

2017-01-01

Diagnosis of liver involvement due to schistosomiasis in asymptomatic patients from endemic areas previously diagnosed with chronic hepatitis B (HBV) or C (HCV) and periportal fibrosis is challenging. H-1 Nuclear Magnetic Resonance (NMR)-based metabonomics strategy is a powerful tool for providing a profile of endogenous metabolites of low molecular weight in biofluids in a non-invasive way. The aim of this study was to diagnose periportal fibrosis due to schistosomiasis mansoni in patients with chronic HBV or HCV infection through NMR-based metabonomics models. The study included 40 patients divided into two groups: (i) 18 coinfected patients with schistosomiasis mansoni and HBV or HCV; and (ii) 22 HBV or HCV monoinfected patients. The serum samples were analyzed through H-1 NMR spectroscopy and the models were based on Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Ultrasonography examination was used to ascertain the diagnosis of periportal fibrosis. Exploratory analysis showed a clear separation between coinfected and monoinfected samples. The supervised model built from PLS-DA showed accuracy, R2 and Q2 values equal to 100%, 98.1% and 97.5%, respectively. According to the variable importance in the projection plot, lactate serum levels were higher in the coinfected group, while the signals attributed to HDL serum cholesterol were more intense in the monoinfected group. The metabonomics models constructed in this study are promising as an alternative tool for diagnosis of periportal fibrosis by schistosomiasis in patients with chronic HBV or HCV infection from endemic areas for Schistosoma mansoni.

FoodPro: A Web-Based Tool for Evaluating Covariance and Correlation NMR Spectra Associated with Food Processes

PubMed Central

Chikayama, Eisuke; Yamashina, Ryo; Komatsu, Keiko; Tsuboi, Yuuri; Sakata, Kenji; Kikuchi, Jun; Sekiyama, Yasuyo

2016-01-01

Foods from agriculture and fishery products are processed using various technologies. Molecular mixture analysis during food processing has the potential to help us understand the molecular mechanisms involved, thus enabling better cooking of the analyzed foods. To date, there has been no web-based tool focusing on accumulating Nuclear Magnetic Resonance (NMR) spectra from various types of food processing. Therefore, we have developed a novel web-based tool, FoodPro, that includes a food NMR spectrum database and computes covariance and correlation spectra to tasting and hardness. As a result, FoodPro has accumulated 236 aqueous (extracted in D2O) and 131 hydrophobic (extracted in CDCl3) experimental bench-top 60-MHz NMR spectra, 1753 tastings scored by volunteers, and 139 hardness measurements recorded by a penetrometer, all placed into a core database. The database content was roughly classified into fish and vegetable groups from the viewpoint of different spectrum patterns. FoodPro can query a user food NMR spectrum, search similar NMR spectra with a specified similarity threshold, and then compute estimated tasting and hardness, covariance, and correlation spectra to tasting and hardness. Querying fish spectra exemplified specific covariance spectra to tasting and hardness, giving positive covariance for tasting at 1.31 ppm for lactate and 3.47 ppm for glucose and a positive covariance for hardness at 3.26 ppm for trimethylamine N-oxide. PMID:27775560

FoodPro: A Web-Based Tool for Evaluating Covariance and Correlation NMR Spectra Associated with Food Processes.

PubMed

Chikayama, Eisuke; Yamashina, Ryo; Komatsu, Keiko; Tsuboi, Yuuri; Sakata, Kenji; Kikuchi, Jun; Sekiyama, Yasuyo

2016-10-19

Foods from agriculture and fishery products are processed using various technologies. Molecular mixture analysis during food processing has the potential to help us understand the molecular mechanisms involved, thus enabling better cooking of the analyzed foods. To date, there has been no web-based tool focusing on accumulating Nuclear Magnetic Resonance (NMR) spectra from various types of food processing. Therefore, we have developed a novel web-based tool, FoodPro, that includes a food NMR spectrum database and computes covariance and correlation spectra to tasting and hardness. As a result, FoodPro has accumulated 236 aqueous (extracted in D₂O) and 131 hydrophobic (extracted in CDCl₃) experimental bench-top 60-MHz NMR spectra, 1753 tastings scored by volunteers, and 139 hardness measurements recorded by a penetrometer, all placed into a core database. The database content was roughly classified into fish and vegetable groups from the viewpoint of different spectrum patterns. FoodPro can query a user food NMR spectrum, search similar NMR spectra with a specified similarity threshold, and then compute estimated tasting and hardness, covariance, and correlation spectra to tasting and hardness. Querying fish spectra exemplified specific covariance spectra to tasting and hardness, giving positive covariance for tasting at 1.31 ppm for lactate and 3.47 ppm for glucose and a positive covariance for hardness at 3.26 ppm for trimethylamine N -oxide.

Synthesis, crystal structure and redox properties of dihydropyrazole-bridged ferrocene-based derivatives

NASA Astrophysics Data System (ADS)

Li, Heng-Dong; Ma, Zai-He; Yang, Kun; Xie, Li-Li; Yuan, Yao-Feng

2012-09-01

Dihydropyrazole-bridged ferrocene-based derivatives were prepared by corresponding chalcones with hydrazine hydrate, then acylation with 3-(ethoxycarbonyl)propionyl chloride directly in high yields and purity. All of these compounds were characterized by MS, IR, 1H NMR, 13C NMR and elemental analysis. The relationship between the structure and redox properties was investigated based on the results of single crystal X-ray structure determinations and cyclic voltammetry. The mechanism of the electron transfer for representative compound 4b was verified by density functional theory (DFT) calculations.

Expedited Selection of NMR Chiral Solvating Agents for Determination of Enantiopurity

PubMed Central

2016-01-01

The use of NMR chiral solvating agents (CSAs) for the analysis of enantiopurity has been known for decades, but has been supplanted in recent years by chromatographic enantioseparation technology. While chromatographic methods for the analysis of enantiopurity are now commonplace and easy to implement, there are still individual compounds and entire classes of analytes where enantioseparation can prove extremely difficult, notably, compounds that are chiral by virtue of very subtle differences such as isotopic substitution or small differences in alkyl chain length. NMR analysis using CSAs can often be useful for such problems, but the traditional approach to selection of an appropriate CSA and the development of an NMR-based analysis method often involves a trial-and-error approach that can be relatively slow and tedious. In this study we describe a high-throughput experimentation approach to the selection of NMR CSAs that employs automation-enabled screening of prepared libraries of CSAs in a systematic fashion. This approach affords excellent results for a standard set of enantioenriched compounds, providing a valuable comparative data set for the effectiveness of CSAs for different classes of compounds. In addition, the technique has been successfully applied to challenging pharmaceutical development problems that are not amenable to chromatographic solutions. Overall, this methodology provides a rapid and powerful approach for investigating enantiopurity that compliments and augments conventional chromatographic approaches. PMID:27280168

Determinants of Ligand Subtype-Selectivity at α1A-Adrenoceptor Revealed Using Saturation Transfer Difference (STD) NMR.

PubMed

Yong, Kelvin J; Vaid, Tasneem M; Shilling, Patrick J; Wu, Feng-Jie; Williams, Lisa M; Deluigi, Mattia; Plückthun, Andreas; Bathgate, Ross A D; Gooley, Paul R; Scott, Daniel J

2018-04-20

α 1A - and α 1B -adrenoceptors (α 1A -AR and α 1B -AR) are closely related G protein-coupled receptors (GPCRs) that modulate the cardiovascular and nervous systems in response to binding epinephrine and norepinephrine. The GPCR gene superfamily is made up of numerous subfamilies that, like α 1A -AR and α 1B -AR, are activated by the same endogenous agonists but may modulate different physiological processes. A major challenge in GPCR research and drug discovery is determining how compounds interact with receptors at the molecular level, especially to assist in the optimization of drug leads. Nuclear magnetic resonance spectroscopy (NMR) can provide great insight into ligand-binding epitopes, modes, and kinetics. Ideally, ligand-based NMR methods require purified, well-behaved protein samples. The instability of GPCRs upon purification in detergents, however, makes the application of NMR to study ligand binding challenging. Here, stabilized α 1A -AR and α 1B -AR variants were engineered using Cellular High-throughput Encapsulation, Solubilization, and Screening (CHESS), allowing the analysis of ligand binding with Saturation Transfer Difference NMR (STD NMR). STD NMR was used to map the binding epitopes of epinephrine and A-61603 to both receptors, revealing the molecular determinants for the selectivity of A-61603 for α 1A -AR over α 1B -AR. The use of stabilized GPCRs for ligand-observed NMR experiments will lead to a deeper understanding of binding processes and assist structure-based drug design.

NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

PubMed

Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

2017-01-01

The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of NMR-Based Metabolomics To Chemically Characterize the Roasting Process of Chicory Root.

PubMed

Wei, Feifei; Furihata, Kazuo; Zhang, Mimin; Miyakawa, Takuya; Tanokura, Masaru

2016-08-16

Roasted chicory root (Cichorium intybus) has been widely accepted as the most important coffee substitute. In this study, a nuclear magnetic resonance (NMR)-based comprehensive analysis was performed to monitor the substantial changes in the composition of chicory root during the roasting process. A detailed signal assignment of dried raw and roasted chicory roots was carried out using 1 H, 13 C, 1 H- 1 H DQF-COSY, 1 H- 13 C edited-HSQC, 1 H- 13 C CT-HMBC, and 1 H- 13 C HSQC-TOCSY NMR spectra. On the basis of the signal assignments, 36 NMR-visible components were monitored simultaneously during roasting. Inulins, sucrose, and most of the amino acids were largely degraded during the roasting process, whereas monosaccharides decreased at the beginning and then increased until the dark roasting stage. Acetamide, 5-hydroxymethylfurfural, di-d-fructose dianhydride, and norfuraneol were newly formed during roasting. Furthermore, a principal component analysis score plot indicated that similar chemical composition profiles could be achieved by roasting the chicory root either at a higher firepower for a shorter time or at a lower firepower for a longer time.

NMR spectroscopy of filtered serum of prostate cancer: A new frontier in metabolomics.

PubMed

Kumar, Deepak; Gupta, Ashish; Mandhani, Anil; Sankhwar, Satya Narain

2016-09-01

To address the shortcomings of digital rectal examinations (DRE), serum prostate-specific antigen (PSA), and trans-rectal ultrasound (TRUS) for precise determination of prostate cancer (PC) and differentiation from benign prostatic hyperplasia (BPH), we applied (1) H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate tactic for probing and prediction of PC and BPH. The study comprises 210 filtered sera from suspected PC, BPH, and a healthy subjects' cohort (HC). The filtered serum approach delineates to identify and quantify 52 metabolites using (1) H NMR spectroscopy. All subjects had undergone clinical evaluations (DRE, PSA, and TRUS) followed by biopsy for Gleason score, if needed. NMR-measured metabolites and clinical evaluation data were examined separately using linear multivariate discriminant function analysis (DFA) to probe the signature descriptors for each cohort. DFA indicated that glycine, sarcosine, alanine, creatine, xanthine, and hypoxanthine were able to determine abnormal prostate (BPH + PC). DFA-based classification presented high precision (86.2% by NMR and 68.1% by clinical laboratory method) in discriminating HC from BPH + PC. DFA reveals that alanine, sarcosine, creatinine, glycine, and citrate were able to discriminate PC from BPH. DFA-based categorization exhibited high accuracy (88.3% by NMR and 75.2% by clinical laboratory method) to differentiate PC from BPH. (1) H NMR-based metabolic profiling of filtered-serum sample appears to be assuring, swift, and least-invasive for probing and prediction of PC and BPH with its signature metabolic profile. This novel technique is not only on a par with histopathological evaluation of PC determination but is also comparable to liquid chromatography-based mass spectrometry to identify the metabolites. Prostate 76:1106-1119, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Monitoring Metabolite Profiles of Cannabis sativa L. Trichomes during Flowering Period Using 1H NMR-Based Metabolomics and Real-Time PCR.

PubMed

Happyana, Nizar; Kayser, Oliver

2016-08-01

Cannabis sativa trichomes are glandular structures predominantly responsible for the biosynthesis of cannabinoids, the biologically active compounds unique to this plant. To the best of our knowledge, most metabolomic works on C. sativa that have been reported previously focused their investigations on the flowers and leaves of this plant. In this study, (1)H NMR-based metabolomics and real-time PCR analysis were applied for monitoring the metabolite profiles of C. sativa trichomes, variety Bediol, during the last 4 weeks of the flowering period. Partial least squares discriminant analysis models successfully classified metabolites of the trichomes based on the harvest time. Δ (9)-Tetrahydrocannabinolic acid (1) and cannabidiolic acid (2) constituted the vital differential components of the organic preparations, while asparagine, glutamine, fructose, and glucose proved to be their water-extracted counterparts. According to RT-PCR analysis, gene expression levels of olivetol synthase and olivetolic acid cyclase influenced the accumulation of cannabinoids in the Cannabis trichomes during the monitoring time. Moreover, quantitative (1)H NMR and RT-PCR analysis of the Cannabis trichomes suggested that the gene regulation of cannabinoid biosynthesis in the C. sativa variety Bediol is unique when compared with other C. sativa varieties. Georg Thieme Verlag KG Stuttgart · New York.

Sonochemical synthesis and DFT studies of nano novel Schiff base cadmium complexes: Green, efficient, recyclable catalysts and precursors of Cd NPs

NASA Astrophysics Data System (ADS)

Parsaee, Zohreh

2017-10-01

Novel asymmetric (N4) Schiff bases (Ln, n = 1-3) and their nanosized cadmium complexes derived of 4,4'-(pentylazanediyl) dibenzaldehyde and aminobenzaldehyde are synthesized by sonochemical method and characterized based on physicochemical analysis including 1H NMR, 13C NMR, SEM, TGA, Mass, FT-IR, UV-Vis spectroscopy, elemental analysis, magnetic moment and molar conductance measurements. According to the analytic results of the NMR, UV-Vis and magnetic moment studies, it is found that the geometrical structures of these complexes [CdII2LnCl4], (L = C45H40N5X, X = CH3, Cl, OH) are square planer. The synthesized complexes were so effective as nanocatalyst on the oxidation of primary and secondary alcohols. The oxidation reactions were carried out in ethyl-methyl-imidazolium ionic liquid in presence of NaOCl. In addition Cd NPs were synthesized through the thermal decomposition of mentioned complexes and characterized by using FT-IR, SEM, TEM, EDX and XRD methods, which indicated close accordance to the standard pattern of CdO nanoparticles and an acceptable size at the nanorange (22-27 nm). Furthermore geometrical optimization of the Cd2LnCl4 calculated using DFT/B3LYP with LanL2DZ/6-311+G (d,p) level. The electronic parameter including HOMO-LUMO orbitals, bond gap, chemical hardness-softness, electronegativity, electrophilicity, NMR chemical shifts and IR frequencies were calculated. The calculated NMR shifts and vibrational frequencies showed excellent agreement with experimental data.

Improving reliability of chemometric models for authentication of species origin of heparin by switching from 1D to 2D NMR experiments.

PubMed

Monakhova, Yulia B; Fareed, Jawed; Yao, Yiming; Diehl, Bernd W K

2018-05-10

Nuclear magnetic resonance (NMR) spectroscopy is regarded as one of the most powerful and versatile analytical approaches to assure the quality of heparin preparations. In particular, it was recently demonstrated that by using 1 H NMR coupled with chemometrics heparin and low molecular weight heparin (LMWH) samples derived from three major animal species (porcine, ovine and bovine) can be differentiated [Y.B. Monakhova et al. J. Pharm. Anal. 149 (2018) 114-119]. In this study, significant improvement of existing chemometric models was achieved by switching to 2D NMR experiments (heteronuclear multiple-quantum correlation (HMQC) and diffusion-ordered spectroscopy (DOSY)). Two representative data sets (sixty-nine heparin and twenty-two LMWH) belonged to different batches and distributed by different commercial companies were investigated. A trend for animal species differentiation was observed in the principal component analysis (PCA) score plot built based on the DOSY data. A superior model was constructed using HMQC experiments, where individual heparin (LMWH) clusters as well as their blends were clearly differentiated. The predictive power of different classification methods as well as unsupervised techniques (independent components analysis, ICA) clearly proved applicability of the model for routine heparin and LMWH analysis. The switch from 1D to 2D NMR techniques provides a wealth of additional information, which is beneficial for multivariate modeling of NMR spectroscopic data for heparin preparations. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous 19F-1H medium resolution NMR spectroscopy for online reaction monitoring

NASA Astrophysics Data System (ADS)

Zientek, Nicolai; Laurain, Clément; Meyer, Klas; Kraume, Matthias; Guthausen, Gisela; Maiwald, Michael

2014-12-01

Medium resolution nuclear magnetic resonance (MR-NMR) spectroscopy is currently a fast developing field, which has an enormous potential to become an important analytical tool for reaction monitoring, in hyphenated techniques, and for systematic investigations of complex mixtures. The recent developments of innovative MR-NMR spectrometers are therefore remarkable due to their possible applications in quality control, education, and process monitoring. MR-NMR spectroscopy can beneficially be applied for fast, non-invasive, and volume integrating analyses under rough environmental conditions. Within this study, a simple 1/16″ fluorinated ethylene propylene (FEP) tube with an ID of 0.04″ (1.02 mm) was used as a flow cell in combination with a 5 mm glass Dewar tube inserted into a benchtop MR-NMR spectrometer with a 1H Larmor frequency of 43.32 MHz and 40.68 MHz for 19F. For the first time, quasi-simultaneous proton and fluorine NMR spectra were recorded with a series of alternating 19F and 1H single scan spectra along the reaction time coordinate of a homogeneously catalysed esterification model reaction containing fluorinated compounds. The results were compared to quantitative NMR spectra from a hyphenated 500 MHz online NMR instrument for validation. Automation of handling, pre-processing, and analysis of NMR data becomes increasingly important for process monitoring applications of online NMR spectroscopy and for its technical and practical acceptance. Thus, NMR spectra were automatically baseline corrected and phased using the minimum entropy method. Data analysis schemes were designed such that they are based on simple direct integration or first principle line fitting, with the aim that the analysis directly revealed molar concentrations from the spectra. Finally, the performance of 1/16″ FEP tube set-up with an ID of 1.02 mm was characterised regarding the limit of detection (LOQ (1H) = 0.335 mol L-1 and LOQ (19F) = 0.130 mol L-1 for trifluoroethanol in D2O (single scan)) and maximum quantitative flow rates up to 0.3 mL min-1. Thus, a series of single scan 19F and 1H NMR spectra acquired with this simple set-up already presents a valuable basis for quantitative reaction monitoring.

[Study on three different species tibetan medicine sea buckthorn by 1H-NMR-based metabonomics].

PubMed

Su, Yong-Wen; Tan, Er; Zhang, Jing; You, Jia-Li; Liu, Yue; Liu, Chuan; Zhou, Xiang-Dong; Zhang, Yi

2014-11-01

The 1H-NMR fingerprints of three different species tibetan medicine sea buckthorn were established by 1H-HMR metabolomics to find out different motablism which could provide a new method for the quality evaluation of sea buckthorn. The obtained free induction decay (FID) signal will be imported into MestReNova software and into divide segments. The data will be normalized and processed by principal component analysis and.partial least squares discriminant analysis to perform pattern recognition. The results showed that 25 metabolites belonging to different chemical types were detected from sea buckthorn,including flavonoids, triterpenoids, amino acids, carbohydrates, fatty acids, etc. PCA and PLS-DA analysis showed three different varietiest of sea buckthorn that can be clearly separated by the content of L-quebrachitol, malic acid and some unidentified sugars, which can be used as the differences metabolites of three species of sea buckthorn. 1H-NMR-based metabonomies method had a holistic characteristic with sample preparation and handling. The results of this study can offer an important reference for the species identification and quality control of sea buckthorn.

Classification of Ilex species based on metabolomic fingerprinting using nuclear magnetic resonance and multivariate data analysis.

PubMed

Choi, Young Hae; Sertic, Sarah; Kim, Hye Kyong; Wilson, Erica G; Michopoulos, Filippos; Lefeber, Alfons W M; Erkelens, Cornelis; Prat Kricun, Sergio D; Verpoorte, Robert

2005-02-23

The metabolomic analysis of 11 Ilex species, I. argentina, I. brasiliensis, I. brevicuspis, I. dumosavar. dumosa, I. dumosa var. guaranina, I. integerrima, I. microdonta, I. paraguariensis var. paraguariensis, I. pseudobuxus, I. taubertiana, and I. theezans, was carried out by NMR spectroscopy and multivariate data analysis. The analysis using principal component analysis and classification of the (1)H NMR spectra showed a clear discrimination of those samples based on the metabolites present in the organic and aqueous fractions. The major metabolites that contribute to the discrimination are arbutin, caffeine, phenylpropanoids, and theobromine. Among those metabolites, arbutin, which has not been reported yet as a constituent of Ilex species, was found to be a biomarker for I. argentina,I. brasiliensis, I. brevicuspis, I. integerrima, I. microdonta, I. pseudobuxus, I. taubertiana, and I. theezans. This reliable method based on the determination of a large number of metabolites makes the chemotaxonomical analysis of Ilex species possible.

Ultralow field NMR spectrometer with an atomic magnetometer near room temperature

NASA Astrophysics Data System (ADS)

Liu, Guobin; Li, Xiaofeng; Sun, Xianping; Feng, Jiwen; Ye, Chaohui; Zhou, Xin

2013-12-01

We present a Cs atomic magnetometer with a sensitivity of 150 fT/Hz1/2 operating near room temperature. The nuclear magnetic resonance (NMR) signal of 125 μL tap water was detected at an ultralow magnetic field down to 47 nT, with the signal-to-noise ratio (SNR) of the NMR signal approaching 50 after eight averages. Relaxivity experiments with a Gd(DTPA) contrast agent in zero field were performed, in order to show the magnetometer's ability to measure spin-lattice relaxation time with high accuracy. This demonstrates the feasibility of an ultralow field NMR spectrometer based on a Cs atomic magnetometer, which has a low working temperature, short data acquisition time and high sensitivity. This kind of NMR spectrometer has great potential in applications such as chemical analysis and magnetic relaxometry detection in ultralow or zero fields.

NPK NMR Sensor: Online Monitoring of Nitrogen, Phosphorus, and Potassium in Animal Slurry.

PubMed

Sørensen, Morten K; Jensen, Ole; Bakharev, Oleg N; Nyord, Tavs; Nielsen, Niels Chr

2015-07-07

Knowledge of the actual content of nitrogen, phosphorus, and potassium (NPK) in animal slurry is highly important to optimize crop production and avoid environmental pollution when slurry is spread on agricultural fields. Here, we present a mobile, low-field nuclear magnetic resonance (NMR) sensor suitable for online monitoring of the NPK content in animal slurry as an alternative to crude estimates or tedious nonspecific, off-site laboratory analysis. The sensor is based on (14)N, (17)O, (31)P, and (39)K NMR in a digital NMR instrument equipped with a 1.5 T Halbach magnet for direct detection of ammonium N, total P, and K and indirect evaluation of the organic N content, covering all practical components of NPK in animal slurry. In correlation studies, the obtained NMR measurements show good agreement with reference measurements from commercial laboratories.

Mathematical models of real geometrical factors in restricted blood vessels for the analysis of CAD (coronary artery diseases) using Legendre, Boubaker and Bessel polynomials.

PubMed

Awojoyogbe, O B; Faromika, O P; Dada, M; Boubaker, Karem; Ojambati, O S

2011-12-01

Most cardiovascular emergencies are directly caused by coronary artery disease. Coronary arteries can become clogged or occluded, leading to damage to the heart muscle supplied by the artery. Modem cardiovascular medicine can certainly be improved by meticulous analysis of geometrical factors closely associated with the degenerative disease that results in narrowing of the coronary arteries. There are, however, inherent difficulties in developing this type of mathematical models to completely describe the real or ideal geometries that are very critical in plaque formation and thickening of the vessel wall. Neither the mathematical models of the blood vessels with arthrosclerosis generated by the heart and blood flow or the NMR/MRI data to construct them are available. In this study, a mathematical formulation for the geometrical factors that are very critical for the understanding of coronary artery disease is presented. Based on the Bloch NMR flow equations, we derive analytical expressions to describe in detail the NMR transverse magnetizations and signals as a function of some NMR flow and geometrical parameters which are invaluable for the analysis of blood flow in restricted blood vessels. The procedure would apply to the situations in which the geometry of the fatty deposits, (plague) on the interior walls of the coronary arteries is spherical. The boundary conditions are introduced based on Bessel, Boubaker and Legendre polynomials.

The SPORT-NMR Software: A Tool for Determining Relaxation Times in Unresolved NMR Spectra

NASA Astrophysics Data System (ADS)

Geppi, Marco; Forte, Claudia

1999-03-01

A software package which allows the correct determination of individual relaxation times for all the nonequivalent nuclei in poorly resolved NMR spectra is described. The procedure used, based on the fitting of each spectrum in the series recorded in the relaxation experiment, should improve the analysis of relaxation data in terms of quantitative dynamic information, especially in anisotropic phases. Tests on simulated data and experimental examples concerning1H and13CT1ρmeasurement in a solid copolymer and2HT1ZandT1Qmeasurement in a liquid crystal are shown and discussed.

Automated Control of the Organic and Inorganic Composition of Aloe vera Extracts Using (1)H NMR Spectroscopy.

PubMed

Monakhova, Yulia B; Randel, Gabriele; Diehl, Bernd W K

2016-09-01

Recent classification of Aloe vera whole-leaf extract by the International Agency for Research and Cancer as a possible carcinogen to humans as well as the continuous adulteration of A. vera's authentic material have generated renewed interest in controlling A. vera. The existing NMR spectroscopic method for the analysis of A. vera, which is based on a routine developed at Spectral Service, was extended. Apart from aloverose, glucose, malic acid, lactic acid, citric acid, whole-leaf material (WLM), acetic acid, fumaric acid, sodium benzoate, and potassium sorbate, the quantification of Mg(2+), Ca(2+), and fructose is possible with the addition of a Cs-EDTA solution to sample. The proposed methodology was automated, which includes phasing, baseline-correction, deconvolution (based on the Lorentzian function), integration, quantification, and reporting. The NMR method was applied to 41 A. vera preparations in the form of liquid A. vera juice and solid A. vera powder. The advantages of the new NMR methodology over the previous method were discussed. Correlation between the new and standard NMR methodologies was significant for aloverose, glucose, malic acid, lactic acid, citric acid, and WLM (P < 0.0001, R(2) = 0.99). NMR was found to be suitable for the automated simultaneous quantitative determination of 13 parameters in A. vera.

Analysis of salivary phenotypes of generalized aggressive and chronic periodontitis through nuclear magnetic resonance-based metabolomics.

PubMed

Romano, Federica; Meoni, Gaia; Manavella, Valeria; Baima, Giacomo; Tenori, Leonardo; Cacciatore, Stefano; Aimetti, Mario

2018-06-07

Recent findings about the differential gene expression signature of periodontal lesions have raised the hypothesis of distinctive biological phenotypes expressed by generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients. Therefore, this cross-sectional investigation was planned, primarily, to determine the ability of nuclear magnetic resonance (NMR) spectroscopic analysis of unstimulated whole saliva to discriminate GCP and GAgP disease-specific metabolomic fingerprint and, secondarily, to assess potential metabolites discriminating periodontitis patients from periodontally healthy individuals (HI). NMR-metabolomics spectra were acquired from salivary samples of patients with a clinical diagnosis of GCP (n = 33) or GAgP (n = 28) and from HI (n = 39). The clustering of HI, GCP and GAgP patients was achieved by using a combination of the Principal Component Analysis and Canonical Correlation Analysis on the NMR profiles. These analyses revealed a significant predictive accuracy discriminating HI from GCP, and discriminating HI from GAgP patients (both 81%). In contrast, the GAgP and GCP saliva samples seem to belong to the same metabolic space (60% predictive accuracy). Significantly lower levels (P < 0.05) of pyruvate, N-acetyl groups and lactate and higher levels (P < 0.05) of proline, phenylalanine, and tyrosine were found in GCP and GAgP patients compared with HI. Within the limitations of this study, CGP and GAgP metabolomic profiles were not unequivocally discriminated through a NMR-based spectroscopic analysis of saliva. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

NMR-based metabolomic analysis of spatial variation in soft corals.

PubMed

He, Qing; Sun, Ruiqi; Liu, Huijuan; Geng, Zhufeng; Chen, Dawei; Li, Yinping; Han, Jiao; Lin, Wenhan; Du, Shushan; Deng, Zhiwei

2014-03-28

Soft corals are common marine organisms that inhabit tropical and subtropical oceans. They are shown to be rich source of secondary metabolites with biological activities. In this work, soft corals from two geographical locations were investigated using ¹H-NMR spectroscopy coupled with multivariate statistical analysis at the metabolic level. A partial least-squares discriminant analysis showed clear separation among extracts of soft corals grown in Sanya Bay and Weizhou Island. The specific markers that contributed to discrimination between soft corals in two origins belonged to terpenes, sterols and N-containing compounds. The satisfied precision of classification obtained indicates this approach using combined ¹H-NMR and chemometrics is effective to discriminate soft corals collected in different geographical locations. The results revealed that metabolites of soft corals evidently depended on living environmental condition, which would provide valuable information for further relevant coastal marine environment evaluation.

Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars.

PubMed

Hu, Boran; Yue, Yaqing; Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W

2015-01-01

Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach.

Determination of 13C/12C Isotope Ratio in Alcohols of Different Origin by 1н Nuclei NMR-Spectroscopy

NASA Astrophysics Data System (ADS)

Dzhimak, S. S.; Basov, A. A.; Buzko, V. Yu.; Kopytov, G. F.; Kashaev, D. V.; Shashkov, D. I.; Shlapakov, M. S.; Baryshev, M. G.

2017-02-01

A new express method of indirect assessment of 13C/12C isotope ratio on 1H nuclei is developed to verify the authenticity of ethanol origin in alcohol-water-based fluids and assess the facts of various alcoholic beverages falsification. It is established that in water-based alcohol-containing systems, side satellites for the signals of ethanol methyl and methylene protons in the NMR spectra on 1H nuclei, correspond to the protons associated with 13C nuclei. There is a direct correlation between the intensities of the signals of ethanol methyl and methylene protons' 1H- NMR and their side satellites, therefore, the data obtained can be used to assess 13C/12C isotope ratio in water-based alcohol-containing systems. The analysis of integrated intensities of main and satellite signals of methyl and methylene protons of ethanol obtained by NMR on 1H nuclei makes it possible to differentiate between ethanol of synthetic and natural origin. Furthermore, the method proposed made it possible to differentiate between wheat and corn ethanol.

PGI chicory (Cichorium intybus L.) traceability by means of HRMAS-NMR spectroscopy: a preliminary study.

PubMed

Ritota, Mena; Casciani, Lorena; Valentini, Massimiliano

2013-05-01

Analytical traceability of PGI and PDO foods (Protected Geographical Indication and Protected Denomination Origin respectively) is one of the most challenging tasks of current applied research. Here we proposed a metabolomic approach based on the combination of (1)H high-resolution magic angle spinning-nuclear magnetic resonance (HRMAS-NMR) spectroscopy with multivariate analysis, i.e. PLS-DA, as a reliable tool for the traceability of Italian PGI chicories (Cichorium intybus L.), i.e. Radicchio Rosso di Treviso and Radicchio Variegato di Castelfranco, also known as red and red-spotted, respectively. The metabolic profile was gained by means of HRMAS-NMR, and multivariate data analysis allowed us to build statistical models capable of providing clear discrimination among the two varieties and classification according to the geographical origin. Based on Variable Importance in Projection values, the molecular markers for classifying the different types of red chicories analysed were found accounting for both the cultivar and the place of origin. © 2012 Society of Chemical Industry.

Authentication of beef versus horse meat using 60 MHz 1H NMR spectroscopy

PubMed Central

Jakes, W.; Gerdova, A.; Defernez, M.; Watson, A.D.; McCallum, C.; Limer, E.; Colquhoun, I.J.; Williamson, D.C.; Kemsley, E.K.

2015-01-01

This work reports a candidate screening protocol to distinguish beef from horse meat based upon comparison of triglyceride signatures obtained by 60 MHz 1H NMR spectroscopy. Using a simple chloroform-based extraction, we obtained classic low-field triglyceride spectra from typically a 10 min acquisition time. Peak integration was sufficient to differentiate samples of fresh beef (76 extractions) and horse (62 extractions) using Naïve Bayes classification. Principal component analysis gave a two-dimensional “authentic” beef region (p = 0.001) against which further spectra could be compared. This model was challenged using a subset of 23 freeze–thawed training samples. The outcomes indicated that storing samples by freezing does not adversely affect the analysis. Of a further collection of extractions from previously unseen samples, 90/91 beef spectra were classified as authentic, and 16/16 horse spectra as non-authentic. We conclude that 60 MHz 1H NMR represents a feasible high-throughput approach for screening raw meat. PMID:25577043

Application of chemometrics in quality control of Turmeric (Curcuma longa) based on Ultra-violet, Fourier transform-infrared and 1H NMR spectroscopy.

PubMed

Gad, Haidy A; Bouzabata, Amel

2017-12-15

Turmeric (Curcuma longa L.) belongs to the family Zingiberaceae that is widely used as a spice in food preparations in addition to its biological activities. UV, FT-IR, 1 H NMR in addition to HPLC were applied to construct a metabolic fingerprint for Turmeric in an attempt to assess its quality. 30 samples were analyzed, and then principal component analysis (PCA) and hierarchical clustering analysis (HCA) were utilized to assess the differences and similarities between collected samples. PCA score plot based on both HPLC and UV spectroscopy showed the same discriminatory pattern, where the samples were segregated into four main groups depending on their total curcuminoids content. The results revealed that UV could be utilized as a simple and rapid alternative for HPLC. However, FT-IR failed to discriminate between the same species. By applying 1 H NMR, the metabolic variability between samples was more evident in the essential oils/fatty acid region. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical analysis of bleach and hydroxide-based solutions after decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX).

PubMed

Hopkins, F B; Gravett, M R; Self, A J; Wang, M; Chua, Hoe-Chee; Hoe-Chee, C; Lee, H S Nancy; Sim, N Lee Hoi; Jones, J T A; Timperley, C M; Riches, J R

2014-08-01

Detailed chemical analysis of solutions used to decontaminate chemical warfare agents can be used to support verification and forensic attribution. Decontamination solutions are amongst the most difficult matrices for chemical analysis because of their corrosive and potentially emulsion-based nature. Consequently, there are relatively few publications that report their detailed chemical analysis. This paper describes the application of modern analytical techniques to the analysis of decontamination solutions following decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX). We confirm the formation of N,N-diisopropylformamide and N,N-diisopropylamine following decontamination of VX with hypochlorite-based solution, whereas they were not detected in extracts of hydroxide-based decontamination solutions by nuclear magnetic resonance (NMR) spectroscopy or gas chromatography-mass spectrometry. We report the electron ionisation and chemical ionisation mass spectroscopic details, retention indices, and NMR spectra of N,N-diisopropylformamide and N,N-diisopropylamine, as well as analytical methods suitable for their analysis and identification in solvent extracts and decontamination residues.

The structure of poly(carbonsuboxide) on the atomic scale: a solid-state NMR study.

PubMed

Schmedt auf der Günne, Jörn; Beck, Johannes; Hoffbauer, Wilfried; Krieger-Beck, Petra

2005-07-18

In this contribution we present a study of the structure of amorphous poly(carbonsuboxide) (C3O2)x by 13C solid-state NMR spectroscopy supported by infrared spectroscopy and chemical analysis. Poly(carbonsuboxide) was obtained by polymerization of carbonsuboxide C3O2, which in turn was synthesized from malonic acid bis(trimethylsilylester). Two different 13C labeling schemes were applied to probe inter- and intramonomeric bonds in the polymer by dipolar solid-state NMR methods and also to allow quantitative 13C MAS NMR spectra. Four types of carbon environments can be distinguished in the NMR spectra. Double-quantum and triple-quantum 2D correlation experiments were used to assign the observed peaks using the through-space and through-bond dipolar coupling. In order to obtain distance constraints for the intermonomeric bonds, double-quantum constant-time experiments were performed. In these experiments an additional filter step was applied to suppress contributions from not directly bonded 13C,13C spin pairs. The 13C NMR intensities, chemical shifts, connectivities and distances gave constraints for both the polymerization mechanism and the short-range order of the polymer. The experimental results were complemented by bond lengths predicted by density functional theory methods for several previously suggested models. Based on the presented evidence we can unambiguously exclude models based on gamma-pyronic units and support models based on alpha-pyronic units. The possibility of planar ladder- and bracelet-like alpha-pyronic structures is discussed.

General order parameter based correlation analysis of protein backbone motions between experimental NMR relaxation measurements and molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qing; Shi, Chaowei; Yu, Lu

Internal backbone dynamic motions are essential for different protein functions and occur on a wide range of time scales, from femtoseconds to seconds. Molecular dynamic (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation measurements are valuable tools to gain access to fast (nanosecond) internal motions. However, there exist few reports on correlation analysis between MD and NMR relaxation data. Here, backbone relaxation measurements of {sup 15}N-labeled SH3 (Src homology 3) domain proteins in aqueous buffer were used to generate general order parameters (S{sup 2}) using a model-free approach. Simultaneously, 80 ns MD simulations of SH3 domain proteins in amore » defined hydrated box at neutral pH were conducted and the general order parameters (S{sup 2}) were derived from the MD trajectory. Correlation analysis using the Gromos force field indicated that S{sup 2} values from NMR relaxation measurements and MD simulations were significantly different. MD simulations were performed on models with different charge states for three histidine residues, and with different water models, which were SPC (simple point charge) water model and SPC/E (extended simple point charge) water model. S{sup 2} parameters from MD simulations with charges for all three histidines and with the SPC/E water model correlated well with S{sup 2} calculated from the experimental NMR relaxation measurements, in a site-specific manner. - Highlights: • Correlation analysis between NMR relaxation measurements and MD simulations. • General order parameter (S{sup 2}) as common reference between the two methods. • Different protein dynamics with different Histidine charge states in neutral pH. • Different protein dynamics with different water models.« less

Chemometric Methods to Quantify 1D and 2D NMR Spectral Differences Among Similar Protein Therapeutics.

PubMed

Chen, Kang; Park, Junyong; Li, Feng; Patil, Sharadrao M; Keire, David A

2018-04-01

NMR spectroscopy is an emerging analytical tool for measuring complex drug product qualities, e.g., protein higher order structure (HOS) or heparin chemical composition. Most drug NMR spectra have been visually analyzed; however, NMR spectra are inherently quantitative and multivariate and thus suitable for chemometric analysis. Therefore, quantitative measurements derived from chemometric comparisons between spectra could be a key step in establishing acceptance criteria for a new generic drug or a new batch after manufacture change. To measure the capability of chemometric methods to differentiate comparator NMR spectra, we calculated inter-spectra difference metrics on 1D/2D spectra of two insulin drugs, Humulin R® and Novolin R®, from different manufacturers. Both insulin drugs have an identical drug substance but differ in formulation. Chemometric methods (i.e., principal component analysis (PCA), 3-way Tucker3 or graph invariant (GI)) were performed to calculate Mahalanobis distance (D M ) between the two brands (inter-brand) and distance ratio (D R ) among the different lots (intra-brand). The PCA on 1D inter-brand spectral comparison yielded a D M value of 213. In comparing 2D spectra, the Tucker3 analysis yielded the highest differentiability value (D M  = 305) in the comparisons made followed by PCA (D M  = 255) then the GI method (D M  = 40). In conclusion, drug quality comparisons among different lots might benefit from PCA on 1D spectra for rapidly comparing many samples, while higher resolution but more time-consuming 2D-NMR-data-based comparisons using Tucker3 analysis or PCA provide a greater level of assurance for drug structural similarity evaluation between drug brands.

Parsimony and goodness-of-fit in multi-dimensional NMR inversion

NASA Astrophysics Data System (ADS)

Babak, Petro; Kryuchkov, Sergey; Kantzas, Apostolos

2017-01-01

Multi-dimensional nuclear magnetic resonance (NMR) experiments are often used for study of molecular structure and dynamics of matter in core analysis and reservoir evaluation. Industrial applications of multi-dimensional NMR involve a high-dimensional measurement dataset with complicated correlation structure and require rapid and stable inversion algorithms from the time domain to the relaxation rate and/or diffusion domains. In practice, applying existing inverse algorithms with a large number of parameter values leads to an infinite number of solutions with a reasonable fit to the NMR data. The interpretation of such variability of multiple solutions and selection of the most appropriate solution could be a very complex problem. In most cases the characteristics of materials have sparse signatures, and investigators would like to distinguish the most significant relaxation and diffusion values of the materials. To produce an easy to interpret and unique NMR distribution with the finite number of the principal parameter values, we introduce a new method for NMR inversion. The method is constructed based on the trade-off between the conventional goodness-of-fit approach to multivariate data and the principle of parsimony guaranteeing inversion with the least number of parameter values. We suggest performing the inversion of NMR data using the forward stepwise regression selection algorithm. To account for the trade-off between goodness-of-fit and parsimony, the objective function is selected based on Akaike Information Criterion (AIC). The performance of the developed multi-dimensional NMR inversion method and its comparison with conventional methods are illustrated using real data for samples with bitumen, water and clay.

Portable, low-cost NMR with laser-lathe lithography produced microcoils.

PubMed

Demas, Vasiliki; Herberg, Julie L; Malba, Vince; Bernhardt, Anthony; Evans, Lee; Harvey, Christopher; Chinn, Sarah C; Maxwell, Robert S; Reimer, Jeffrey

2007-11-01

Nuclear Magnetic Resonance (NMR) is unsurpassed in its ability to non-destructively probe chemical identity. Portable, low-cost NMR sensors would enable on-site identification of potentially hazardous substances, as well as the study of samples in a variety of industrial applications. Recent developments in RF microcoil construction (i.e. coils much smaller than the standard 5mm NMR RF coils), have dramatically increased NMR sensitivity and decreased the limits-of-detection (LOD). We are using advances in laser pantographic microfabrication techniques, unique to LLNL, to produce RF microcoils for field deployable, high sensitivity NMR-based detectors. This same fabrication technique can be used to produce imaging coils for MRI as well as for standard hardware shimming or "ex-situ" shimming of field inhomogeneities typically associated with inexpensive magnets. This paper describes a portable NMR system based on the use of a 2 kg hand-held permanent magnet, laser-fabricated microcoils, and a compact spectrometer. The main limitations for such a system are the low resolution and sensitivity associated with the low field values and quality of small permanent magnets, as well as the lack of large amounts of sample of interest in most cases. The focus of the paper is on the setting up of this system, initial results, sensitivity measurements, discussion of the limitations and future plans. The results, even though preliminary, are promising and provide the foundation for developing a portable, inexpensive NMR system for chemical analysis. Such a system will be ideal for chemical identification of trace substances on site.

Differentiation of Organically and Conventionally Grown Tomatoes by Chemometric Analysis of Combined Data from Proton Nuclear Magnetic Resonance and Mid-infrared Spectroscopy and Stable Isotope Analysis.

PubMed

Hohmann, Monika; Monakhova, Yulia; Erich, Sarah; Christoph, Norbert; Wachter, Helmut; Holzgrabe, Ulrike

2015-11-04

Because the basic suitability of proton nuclear magnetic resonance spectroscopy ((1)H NMR) to differentiate organic versus conventional tomatoes was recently proven, the approach to optimize (1)H NMR classification models (comprising overall 205 authentic tomato samples) by including additional data of isotope ratio mass spectrometry (IRMS, δ(13)C, δ(15)N, and δ(18)O) and mid-infrared (MIR) spectroscopy was assessed. Both individual and combined analytical methods ((1)H NMR + MIR, (1)H NMR + IRMS, MIR + IRMS, and (1)H NMR + MIR + IRMS) were examined using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), linear discriminant analysis (LDA), and common components and specific weight analysis (ComDim). With regard to classification abilities, fused data of (1)H NMR + MIR + IRMS yielded better validation results (ranging between 95.0 and 100.0%) than individual methods ((1)H NMR, 91.3-100%; MIR, 75.6-91.7%), suggesting that the combined examination of analytical profiles enhances authentication of organically produced tomatoes.

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

PubMed

Tyagi, Ritu; Rana, Poonam; Khan, Ahmad Raza; Bhatnagar, Deepak; Devi, M Memita; Chaturvedi, Shubhra; Tripathi, Rajendra P; Khushu, Subash

2011-10-01

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity. Copyright © 2011 John Wiley & Sons, Ltd.

NMR metabolomics of ripened and developing oilseed rape (Brassica napus) and turnip rape (Brassica rapa).

PubMed

Kortesniemi, Maaria; Vuorinen, Anssi L; Sinkkonen, Jari; Yang, Baoru; Rajala, Ari; Kallio, Heikki

2015-04-01

The oilseeds of the commercially important oilseed rape (Brassica napus) and turnip rape (Brassica rapa) were investigated with (1)H NMR metabolomics. The compositions of ripened (cultivated in field trials) and developing seeds (cultivated in controlled conditions) were compared in multivariate models using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Differences in the major lipids and the minor metabolites between the two species were found. A higher content of polyunsaturated fatty acids and sucrose were observed in turnip rape, while the overall oil content and sinapine levels were higher in oilseed rape. The genotype traits were negligible compared to the effect of the growing site and concomitant conditions on the oilseed metabolome. This study demonstrates the applicability of NMR-based analysis in determining the species, geographical origin, developmental stage, and quality of oilseed Brassicas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for quantification of inflammatory lung injury

PubMed Central

Serkova, Natalie J.; Van Rheen, Zachary; Tobias, Meghan; Pitzer, Joshua E.; Wilkinson, J. Erby; Stringer, Kathleen A.

2008-01-01

Magnetic resonance imaging (MRI) and metabolic nuclear magnetic resonance (NMR) spectroscopy are clinically available but have had little application in the quantification of experimental lung injury. There is a growing and unfulfilled need for predictive animal models that can improve our understanding of disease pathogenesis and therapeutic intervention. Integration of MRI and NMR could extend the application of experimental data into the clinical setting. This study investigated the ability of MRI and metabolic NMR to detect and quantify inflammation-mediated lung injury. Pulmonary inflammation was induced in male B6C3F1 mice by intratracheal administration of IL-1β and TNF-α under isoflurane anesthesia. Mice underwent MRI at 2, 4, 6, and 24 h after dosing. At 6 and 24 h lungs were harvested for metabolic NMR analysis. Data acquired from IL-1β+TNF-α-treated animals were compared with saline-treated control mice. The hyperintense-to-total lung volume (HTLV) ratio derived from MRI was higher in IL-1β+TNF-α-treated mice compared with control at 2, 4, and 6 h but returned to control levels by 24 h. The ability of MRI to detect pulmonary inflammation was confirmed by the association between HTLV ratio and histological and pathological end points. Principal component analysis of NMR-detectable metabolites also showed a temporal pattern for which energy metabolism-based biomarkers were identified. These data demonstrate that both MRI and metabolic NMR have utility in the detection and quantification of inflammation-mediated lung injury. Integration of these clinically available techniques into experimental models of lung injury could improve the translation of basic science knowledge and information to the clinic. PMID:18441091

A solid-phase extraction procedure coupled to 1H NMR, with chemometric analysis, to seek reliable markers of the botanical origin of honey.

PubMed

Beretta, Giangiacomo; Caneva, Enrico; Regazzoni, Luca; Bakhtyari, Nazanin Golbamaki; Maffei Facino, Roberto

2008-07-14

The aim of this work was to establish an analytical method for identifying the botanical origin of honey, as an alternative to conventional melissopalynological, organoleptic and instrumental methods (gas-chromatography coupled to mass spectrometry (GC-MS), high-performance liquid chromatography HPLC). The procedure is based on the (1)H nuclear magnetic resonance (NMR) profile coupled, when necessary, with electrospray ionisation-mass spectrometry (ESI-MS) and two-dimensional NMR analyses of solid-phase extraction (SPE)-purified honey samples, followed by chemometric analyses. Extracts of 44 commercial Italian honeys from 20 different botanical sources were analyzed. Honeydew, chestnut and linden honeys showed constant, specific, well-resolved resonances, suitable for use as markers of origin. Honeydew honey contained the typical resonances of an aliphatic component, very likely deriving from the plant phloem sap or excreted into it by sap-sucking aphids. Chestnut honey contained the typical signals of kynurenic acid and some structurally related metabolite. In linden honey the (1)H NMR profile gave strong signals attributable to the mono-terpene derivative cyclohexa-1,3-diene-1-carboxylic acid (CDCA) and to its 1-O-beta-gentiobiosyl ester (CDCA-GBE). These markers were not detectable in the other honeys, except for the less common nectar honey from rosa mosqueta. We compared and analyzed the data by multivariate techniques. Principal component analysis found different clusters of honeys based on the presence of these specific markers. The results, although obviously only preliminary, suggest that the (1)H NMR profile (with HPLC-MS analysis when necessary) can be used as a reference framework for identifying the botanical origin of honey.

Solution NMR Spectroscopy in Target-Based Drug Discovery.

PubMed

Li, Yan; Kang, Congbao

2017-08-23

Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important roles in multiple steps of the drug discovery process. In a fragment-based drug discovery process, ligand-observed and protein-observed NMR spectroscopy can be applied to screen fragments with low binding affinities. The screened fragments can be further optimized into drug-like molecules. In combination with other biophysical techniques, NMR will guide structure-based drug discovery. In this review, we describe the possible roles of NMR spectroscopy in drug discovery. We also illustrate the challenges encountered in the drug discovery process. We include several examples demonstrating the roles of NMR in target-based drug discoveries such as hit identification, ranking ligand binding affinities, and mapping the ligand binding site. We also speculate the possible roles of NMR in target engagement based on recent processes in in-cell NMR spectroscopy.

Determination of the purity of pharmaceutical reference materials by 1H NMR using the standardless PULCON methodology.

PubMed

Monakhova, Yulia B; Kohl-Himmelseher, Matthias; Kuballa, Thomas; Lachenmeier, Dirk W

2014-11-01

A fast and reliable nuclear magnetic resonance spectroscopic method for quantitative determination (qNMR) of targeted molecules in reference materials has been established using the ERETIC2 methodology (electronic reference to access in vivo concentrations) based on the PULCON principle (pulse length based concentration determination). The developed approach was validated for the analysis of pharmaceutical samples in the context of official medicines control, including ibandronic acid, amantadine, ambroxol and lercanidipine. The PULCON recoveries were above 94.3% and coefficients of variation (CVs) obtained by quantification of different targeted resonances ranged between 0.7% and 2.8%, demonstrating that the qNMR method is a precise tool for rapid quantification (approximately 15min) of reference materials and medicinal products. Generally, the values were within specification (certified values) provided by the manufactures. The results were in agreement with NMR quantification using an internal standard and validated reference HPLC analysis. The PULCON method was found to be a practical alternative with competitive precision and accuracy to the classical internal reference method and it proved to be applicable to different solvent conditions. The method can be recommended for routine use in medicines control laboratories, especially when the availability and costs of reference compounds are problematic. Copyright © 2014 Elsevier B.V. All rights reserved.

Metabolic profiling and predicting the free radical scavenging activity of guava (Psidium guajava L.) leaves according to harvest time by 1H-nuclear magnetic resonance spectroscopy.

PubMed

Kim, So-Hyun; Cho, Somi K; Hyun, Sun-Hee; Park, Hae-Eun; Kim, Young-Suk; Choi, Hyung-Kyoon

2011-01-01

Guava leaves were classified and the free radical scavenging activity (FRSA) evaluated according to different harvest times by using the (1)H-NMR-based metabolomic technique. A principal component analysis (PCA) of (1)H-NMR data from the guava leaves provided clear clusters according to the harvesting time. A partial least squares (PLS) analysis indicated a correlation between the metabolic profile and FRSA. FRSA levels of the guava leaves harvested during May and August were high, and those leaves contained higher amounts of 3-hydroxybutyric acid, acetic acid, glutamic acid, asparagine, citric acid, malonic acid, trans-aconitic acid, ascorbic acid, maleic acid, cis-aconitic acid, epicatechin, protocatechuic acid, and xanthine than the leaves harvested during October and December. Epicatechin and protocatechuic acid among those compounds seem to have enhanced FRSA of the guava leaf samples harvested in May and August. A PLS regression model was established to predict guava leaf FRSA at different harvesting times by using a (1)H-NMR data set. The predictability of the PLS model was then tested by internal and external validation. The results of this study indicate that (1)H-NMR-based metabolomic data could usefully characterize guava leaves according to their time of harvesting.

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

PubMed

Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

2011-01-15

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Cytotoxic Effects of Sarcophyton sp. Soft Corals—Is There a Correlation to Their NMR Fingerprints?

PubMed Central

Farag, Mohamed A.; Fekry, Mostafa I.; Al-Hammady, Montasser A.; Khalil, Mohamed N.; El-Seedi, Hesham R.; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A.

2017-01-01

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton, with (ent)sarcophines as major components (17–100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC50 values ranging from 10–60 µg/mL. No obvious correlation between the extracts’ IC50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels. PMID:28677625

Cytotoxic Effects of Sarcophyton sp. Soft Corals-Is There a Correlation to Their NMR Fingerprints?

PubMed

Farag, Mohamed A; Fekry, Mostafa I; Al-Hammady, Montasser A; Khalil, Mohamed N; El-Seedi, Hesham R; Meyer, Achim; Porzel, Andrea; Westphal, Hildegard; Wessjohann, Ludger A

2017-07-04

Sarcophyton sp. soft corals are rich in cembranoid diterpenes, which represent the main chemical defense of corals against their natural predators in addition to their myriad biological effects in humans. Quantitative NMR (qNMR) was applied for assessing the diterpene variation in 16 soft coral specimens in the context of their genotype, origin, and growing habitat. qNMR revealed high diterpene levels in Sarcophyton sp. compared to Sinularia and Lobophyton , with (ent)sarcophines as major components (17-100 µg/mg) of the coral tissues. Multivariate data analysis was employed to classify samples based on the quantified level of diterpenes, and compared to the untargeted NMR approach. Results revealed that qNMR provided a stronger classification model of Sarcophyton sp. than untargeted NMR fingerprinting. Additionally, cytotoxicity of soft coral crude extracts was assessed against androgen-dependent prostate cancer cell lines (PC3) and androgen-independent colon cancer cell lines (HT-29), with IC 50 values ranging from 10-60 µg/mL. No obvious correlation between the extracts' IC 50 values and their diterpene levels was found using either Spearman or Pearson correlations. This suggests that this type of bioactivity may not be easily predicted by NMR metabolomics in soft corals, or is not strongly correlated to measured diterpene levels.

Analysis of the temperature and pressure dependence of the 129Xe NMR chemical shift and signal intensity for the derivation of basic parameters of adsorption as applied to zeolite ZSM-5.

PubMed

Kawata, Yoko; Adachi, Yuko; Haga, Saori; Fukutomi, Junko; Imai, Hirohiko; Kimura, Atsuomi; Fujiwara, Hideaki

2007-12-01

Temperature and pressure dependences of the 129Xe NMR chemical shift and the signal intensity have been investigated using ZSM-5 as an adsorbent under routine conditions without using any high-pressure or especially high-temperature facilities. The use of a rigorously shielded system and a calibration sample for the signal intensity was found to be valuable to obtain reliable data about the chemical shift and the signal intensity. The 129Xe NMR data obtained between 0.05 and 1.5 atm and from 24 to 80 degrees C were analyzed based on the Dubinin-Radushkevich equation as well as the Langmuir type equation. In both analyses, chemical shift data succeeded only partially in providing the profile of adsorption, such as energetic aspects, surface area, saturated amount of Xe adsorption and specific parameters of 129Xe chemical shift. It was shown that the reliable total analysis was achieved when the chemical shift data were used together with the intensity data. Such an analysis of the chemical shift data, aided by the intensity data, will be useful in performing nano-material analysis on 129Xe NMR without invoking the traditional methodology of gravimetric or volumetric adsorption experiments.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid Identification of Candida Species by Using Nuclear Magnetic Resonance Spectroscopy and a Statistical Classification Strategy

PubMed Central

Himmelreich, Uwe; Somorjai, Ray L.; Dolenko, Brion; Lee, Ok Cha; Daniel, Heide-Marie; Murray, Ronan; Mountford, Carolyn E.; Sorrell, Tania C.

2003-01-01

Nuclear magnetic resonance (NMR) spectra were acquired from suspensions of clinically important yeast species of the genus Candida to characterize the relationship between metabolite profiles and species identification. Major metabolites were identified by using two-dimensional correlation NMR spectroscopy. One-dimensional proton NMR spectra were analyzed by using a staged statistical classification strategy. Analysis of NMR spectra from 442 isolates of Candida albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis resulted in rapid, accurate identification when compared with conventional and DNA-based identification. Spectral regions used for the classification of the five yeast species revealed species-specific differences in relative amounts of lipids, trehalose, polyols, and other metabolites. Isolates of C. parapsilosis and C. glabrata with unusual PCR fingerprinting patterns also generated atypical NMR spectra, suggesting the possibility of intraspecies discontinuity. We conclude that NMR spectroscopy combined with a statistical classification strategy is a rapid, nondestructive, and potentially valuable method for identification and chemotaxonomic characterization that may be broadly applicable to fungi and other microorganisms. PMID:12902244

The structure investigations of dehydroacetic acid and 1,8-diaminonaphthalene condensation product by NMR, MS, and X-ray measurements

NASA Astrophysics Data System (ADS)

Kołodziej, B.; Morawiak, M.; Kamieński, B.; Schilf, W.

2016-05-01

A new unexpected product of condensation reaction of 1,8-diaminonaphthalene (DAN) and carbonyl compound (here: dehydroacetic acid (dha)) was synthesized. Discussion about the molecular structure of possible products of this reaction was done on the base of NMR studies. The structure of the titled product in both DMSO solution and in the solid state was resolved by analysis of its spectral data (X-ray structure analysis, multinuclear NMR in solution and solid state spectra) and MS measurements. The presented studies provided clear evidence that the titled product exists in diluted DMSO solution as the mixture of two kinetic free ionic species whereas in concentrated DMSO solution as well as in the solid state this system forms associated ionic pairs bonded together by hydrogen bonds.

Combined chemometric analysis of (1)H NMR, (13)C NMR and stable isotope data to differentiate organic and conventional milk.

PubMed

Erich, Sarah; Schill, Sandra; Annweiler, Eva; Waiblinger, Hans-Ulrich; Kuballa, Thomas; Lachenmeier, Dirk W; Monakhova, Yulia B

2015-12-01

The increased sales of organically produced food create a strong need for analytical methods, which could authenticate organic and conventional products. Combined chemometric analysis of (1)H NMR-, (13)C NMR-spectroscopy data, stable-isotope data (IRMS) and α-linolenic acid content (gas chromatography) was used to differentiate organic and conventional milk. In total 85 raw, pasteurized and ultra-heat treated (UHT) milk samples (52 organic and 33 conventional) were collected between August 2013 and May 2014. The carbon isotope ratios of milk protein and milk fat as well as the α-linolenic acid content of these samples were determined. Additionally, the milk fat was analyzed by (1)H and (13)C NMR spectroscopy. The chemometric analysis of combined data (IRMS, GC, NMR) resulted in more precise authentication of German raw and retail milk with a considerably increased classification rate of 95% compared to 81% for NMR and 90% for IRMS using linear discriminate analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

1H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients.

PubMed

Amin, Arwa M; Sheau Chin, Lim; Teh, Chin-Hoe; Mostafa, Hamza; Mohamed Noor, Dzul Azri; Sk Abdul Kader, Muhamad Ali; Kah Hay, Yuen; Ibrahim, Baharudin

2017-11-30

Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance ( 1 H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using 1 H NMR analysis to phenotype clopidogrel HTPR in urine. Urine samples were collected from 71 coronary artery disease (CAD) patients who were planned for interventional angiographic procedure prior to taking 600mg clopidogrel loading dose (LD) and 6h post LD. Patients' platelets function testing was assessed with the VerifyNow ® P2Y12 assay at 6h after LD. Urine samples were analysed using 1 H NMR. Multivariate statistical analysis was used to identify metabolites associated with clopidogrel HTPR. In pre-dose samples, 16 metabolites were associated with clopidogrel HTPR. However, 18 metabolites were associated with clopidogrel HTPR in post-dose samples. The pathway analysis of the identified biomarkers reflected that multifactorial conditions are associated with clopidogrel HTPR. It also revealed the implicated role of gut microbiota in clopidogrel HTPR. Pharmacometabolomics not only discovered novel biomarkers of clopidogrel HTPR but also revealed implicated pathways and conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

In Situ Flow MAS NMR Spectroscopy and Synchrotron PDF Analyses of the Local Response of the Brønsted Acidic Site in SAPO-34 during Hydration at Elevated Temperatures.

PubMed

Kalantzopoulos, Georgios N; Lundvall, Fredrik; Checchia, Stefano; Lind, Anna; Wragg, David S; Fjellvåg, Helmer; Arstad, Bjørnar

2018-02-19

In situ flow magic-angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy and synchrotron-based pair distribution function (PDF) analyses were applied to study water's interactions with the Brønsted acidic site and the surrounding framework in the SAPO-34 catalyst at temperatures up to 300 °C for NMR spectroscopy and 700 °C for PDF. 29 Si enrichment of the sample enabled detailed NMR spectroscopy investigations of the T-atom generating the Brønsted site. By NMR spectroscopy, we observed dehydration above 100 °C and a coalescence of Si peaks due to local framework adjustments. Towards 300 °C, the NMR spectroscopy data indicated highly mobile acidic protons. In situ total X-ray scattering measurements analyzed by PDF showed clear changes in the Al local environment in the 250-300 °C region, as the Al-O bond lengths showed a sudden change. This fell within the same temperature range as the increased Brønsted proton mobility. We suggest that the active site in this catalyst under industrial conditions comprises not only the Brønsted proton but also SiO 4 . To the best of our knowledge, this is the first work proposing a structural model of a SAPO catalyst by atomic PDF analysis. The combination of synchrotron PDF analysis with in situ NMR spectroscopy is promising in revealing the dynamic features of a working catalyst. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

MeRy-B: a web knowledgebase for the storage, visualization, analysis and annotation of plant NMR metabolomic profiles

PubMed Central

2011-01-01

Background Improvements in the techniques for metabolomics analyses and growing interest in metabolomic approaches are resulting in the generation of increasing numbers of metabolomic profiles. Platforms are required for profile management, as a function of experimental design, and for metabolite identification, to facilitate the mining of the corresponding data. Various databases have been created, including organism-specific knowledgebases and analytical technique-specific spectral databases. However, there is currently no platform meeting the requirements for both profile management and metabolite identification for nuclear magnetic resonance (NMR) experiments. Description MeRy-B, the first platform for plant 1H-NMR metabolomic profiles, is designed (i) to provide a knowledgebase of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata, (ii) for queries and visualization of the data, (iii) to discriminate between profiles with spectrum visualization tools and statistical analysis, (iv) to facilitate compound identification. It contains lists of plant metabolites and unknown compounds, with information about experimental conditions, the factors studied and metabolite concentrations for several plant species, compiled from more than one thousand annotated NMR profiles for various organs or tissues. Conclusion MeRy-B manages all the data generated by NMR-based plant metabolomics experiments, from description of the biological source to identification of the metabolites and determinations of their concentrations. It is the first database allowing the display and overlay of NMR metabolomic profiles selected through queries on data or metadata. MeRy-B is available from http://www.cbib.u-bordeaux2.fr/MERYB/index.php. PMID:21668943

A novel in situ electrochemical NMR cell with a palisade gold film electrode

NASA Astrophysics Data System (ADS)

Ni, Zu-Rong; Cui, Xiao-Hong; Cao, Shuo-Hui; Chen, Zhong

2017-08-01

In situ electrochemical nuclear magnetic resonance (EC-NMR) has attracted considerable attention because of its ability to directly observe real-time electrochemical processes. Therefore, minimizing the incompatibility between the electrochemical device and NMR detection has become an important challenge. A circular thin metal film deposited on the outer surface of a glass tube with a thickness considerably less than the metal skin depth is considered to be the ideal working electrode. In this study, we demonstrate that such a thin film electrode still has a great influence on the radio frequency field homogeneity in the detective zone of the NMR spectrometer probe and provide theoretical and experimental confirmation of its electromagnetic shielding. Furthermore, we propose a novel palisade gold film device to act as the working electrode. The NMR nutation behavior of protons shows that the uniformity of the radio frequency field is greatly improved, increasing the sensitivity in NMR detection. Another advantage of the proposed device is that an external reference standard adapted to the reaction compound can be inserted as a probe to determine the fluctuation of the physico-chemical environment and achieve high-accuracy quantitative NMR analysis. A three-chamber electrochemical device based on the palisade gold film design was successfully fabricated and the in situ electrochemical NMR performance was validated in a standard 5 mm NMR probe by acquiring voltammograms and high-resolution NMR spectra to characterize the electrochemically generated species. The evolution of in situ EC-NMR spectrum monitoring of the redox transformation between p-benzoquinone and hydroquinone demonstrates the ability of the EC-NMR device to simultaneously quantitatively determine the reactants and elucidate the reaction mechanism at the molecular level.

Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.

PubMed

Emwas, Abdul-Hamid; Luchinat, Claudio; Turano, Paola; Tenori, Leonardo; Roy, Raja; Salek, Reza M; Ryan, Danielle; Merzaban, Jasmeen S; Kaddurah-Daouk, Rima; Zeri, Ana Carolina; Nagana Gowda, G A; Raftery, Daniel; Wang, Yulan; Brennan, Lorraine; Wishart, David S

The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

Rapid NMR method for the quantification of organic compounds in thin stillage.

PubMed

Ratanapariyanuch, Kornsulee; Shen, Jianheng; Jia, Yunhua; Tyler, Robert T; Shim, Youn Young; Reaney, Martin J T

2011-10-12

Thin stillage contains organic and inorganic compounds, some of which may be valuable fermentation coproducts. This study describes a thorough analysis of the major solutes present in thin stillage as revealed by NMR and HPLC. The concentration of charged and neutral organic compounds in thin stillage was determined by excitation sculpting NMR methods (double pulse field gradient spin echo). Compounds identified by NMR included isopropanol, ethanol, lactic acid, 1,3-propanediol, acetic acid, succinic acid, glycerophosphorylcholine, betaine, glycerol, and 2-phenylethanol. The concentrations of lactic and acetic acid determined with NMR were comparable to those determined using HPLC. HPLC and NMR were complementary, as more compounds were identified using both methods. NMR analysis revealed that stillage contained the nitrogenous organic compounds betaine and glycerophosphorylcholine, which contributed as much as 24% of the nitrogen present in the stillage. These compounds were not observed by HPLC analysis.

A rapid NMR-based method for discrimination of strain-specific cell wall teichoic acid structures reveals a third backbone type in Lactobacillus plantarum.

PubMed

Tomita, Satoru; Tanaka, Naoto; Okada, Sanae

2017-03-01

The lactic acid bacterium Lactobacillus plantarum is capable of producing strain-specific structures of cell wall teichoic acid (WTA), an anionic polysaccharide found in the Gram-positive bacterial cell wall. In this study, we established a rapid, NMR-based procedure to discriminate WTA structures in this species, and applied it to 94 strains of L. plantarum. Six previously reported glycerol- and ribitol-containing WTA subtypes were successfully identified from 78 strains, suggesting that these were the dominant structures. However, the level of structural variety differed markedly among bacterial sources, possibly reflecting differences in strain-level microbial diversity. WTAs from eight strains were not identified based on NMR spectra and were classified into three groups. Structural analysis of a partial degradation product of an unidentified WTA produced by strain TUA 1496L revealed that the WTA was 1-O-β-d-glucosylglycerol. Two-dimensional NMR analysis of the polymer structure showed phosphodiester bonds between C-3 and C-6 of the glycerol and glucose residues, suggesting a polymer structure of 3,6΄-linked poly(1-O-β-d-glucosyl-sn-glycerol phosphate). This is the third WTA backbone structure in L. plantarum, following 3,6΄-linked poly(1-O-α-d-glucosyl-sn-glycerol phosphate) and 1,5-linked poly(ribitol phosphate). © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High-throughput authentication of edible oils with benchtop Ultrafast 2D NMR.

PubMed

Gouilleux, B; Marchand, J; Charrier, B; Remaud, G S; Giraudeau, P

2018-04-01

We report the use of an Ultrafast 2D NMR approach applied on a benchtop NMR system (43 MHz) for the authentication of edible oils. Our results demonstrate that a profiling strategy based on fast 2D NMR spectra recorded in 2.4 min is more efficient than the standard 1D experiments to classify oils from different botanical origins, since 1D spectra on the same samples suffer from strong peak overlaps. Six edible oils with different botanical origins (olive, hazelnut, sesame, rapeseed, corn and sunflower) have been clearly discriminated by PCA analysis. Furthermore, we show how this approach combined with a PLS model can detect adulteration processes such as the addition of hazelnut oil into olive oil, a common fraud in food industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review of NMR characterization of pyrolysis oils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Naijia; Ben, Haoxi; Yoo, Chang Geun

Here, pyrolysis of renewable biomass has been developed as a method to produce green fuels and chemicals in response to energy security concerns as well as to alleviate environmental issues incurred with fossil fuel usage. However, pyrolysis oils still have limited commercial application, mainly because unprocessed oils cannot be readily blended with current petroleum-based transportation fuels. To better understand these challenges, researchers have applied diverse characterization techniques in the development of bio-oil studies. In particular, nuclear magnetic resonance (NMR) is a key spectroscopic characterization method through analysis of bio-oil components. This review highlights the NMR strategies for pyrolysis oil characterizationmore » and critically discusses the applications of 1H, 13C, 31P, 19F, and two-dimensional (2-D NMR) analyses such as heteronuclear single quantum correlation (HSQC) in representative pyrolysis oil studies.« less

Review of NMR characterization of pyrolysis oils

DOE PAGES

Hao, Naijia; Ben, Haoxi; Yoo, Chang Geun; ...

2016-08-24

Here, pyrolysis of renewable biomass has been developed as a method to produce green fuels and chemicals in response to energy security concerns as well as to alleviate environmental issues incurred with fossil fuel usage. However, pyrolysis oils still have limited commercial application, mainly because unprocessed oils cannot be readily blended with current petroleum-based transportation fuels. To better understand these challenges, researchers have applied diverse characterization techniques in the development of bio-oil studies. In particular, nuclear magnetic resonance (NMR) is a key spectroscopic characterization method through analysis of bio-oil components. This review highlights the NMR strategies for pyrolysis oil characterizationmore » and critically discusses the applications of 1H, 13C, 31P, 19F, and two-dimensional (2-D NMR) analyses such as heteronuclear single quantum correlation (HSQC) in representative pyrolysis oil studies.« less

Interlaboratory Comparison Test as an Evaluation of Applicability of an Alternative Edible Oil Analysis by 1H NMR Spectroscopy.

PubMed

Zailer, Elina; Holzgrabe, Ulrike; Diehl, Bernd W K

2017-11-01

A proton (1H) NMR spectroscopic method was established for the quality assessment of vegetable oils. To date, several research studies have been published demonstrating the high potential of the NMR technique in lipid analysis. An interlaboratory comparison was organized with the following main objectives: (1) to evaluate an alternative analysis of edible oils by using 1H NMR spectroscopy; and (2) to determine the robustness and reproducibility of the method. Five different edible oil samples were analyzed by evaluating 15 signals (free fatty acids, peroxides, aldehydes, double bonds, and linoleic and linolenic acids) in each spectrum. A total of 21 NMR data sets were obtained from 17 international participant laboratories. The performance of each laboratory was assessed by their z-scores. The test was successfully passed by 90.5% of the participants. Results showed that NMR spectroscopy is a robust alternative method for edible oil analysis.

Metabolomic Fingerprinting of Romaneschi Globe Artichokes by NMR Spectroscopy and Multivariate Data Analysis.

PubMed

de Falco, Bruna; Incerti, Guido; Pepe, Rosa; Amato, Mariana; Lanzotti, Virginia

2016-09-01

Globe artichoke (Cynara cardunculus L. var. scolymus L. Fiori) and cardoon (Cynara cardunculus L. var. altilis DC) are sources of nutraceuticals and bioactive compounds. To apply a NMR metabolomic fingerprinting approach to Cynara cardunculus heads to obtain simultaneous identification and quantitation of the major classes of organic compounds. The edible part of 14 Globe artichoke populations, belonging to the Romaneschi varietal group, were extracted to obtain apolar and polar organic extracts. The analysis was also extended to one species of cultivated cardoon for comparison. The (1) H-NMR of the extracts allowed simultaneous identification of the bioactive metabolites whose quantitation have been obtained by spectral integration followed by principal component analysis (PCA). Apolar organic extracts were mainly based on highly unsaturated long chain lipids. Polar organic extracts contained organic acids, amino acids, sugars (mainly inulin), caffeoyl derivatives (mainly cynarin), flavonoids, and terpenes. The level of nutraceuticals was found to be highest in the Italian landraces Bianco di Pertosa zia E and Natalina while cardoon showed the lowest content of all metabolites thus confirming the genetic distance between artichokes and cardoon. Metabolomic approach coupling NMR spectroscopy with multivariate data analysis allowed for a detailed metabolite profile of artichoke and cardoon varieties to be obtained. Relevant differences in the relative content of the metabolites were observed for the species analysed. This work is the first application of (1) H-NMR with multivariate statistics to provide a metabolomic fingerprinting of Cynara scolymus. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

{sup 1}H NMR spectroscopic studies establish that heparanase is a retaining glycosidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Jennifer C., E-mail: jennifer.wilson@griffith.edu.au; Laloo, Andrew Elohim; Singh, Sanjesh

2014-01-03

Highlights: •{sup 1}H and {sup 13}C NMR chemical shifts of fondaparinux were fully assigned by 1D and 2D NMR techniques. •Hydrolysis of fondaparinux by heparanase was monitored by {sup 1}H NMR spectroscopy. •Heparanase is established to be a retaining glycosidase. -- Abstract: Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains of proteoglycans in basement membranes and the extracellular matrix (ECM). Heparanase is implicated in several diverse pathological processes associated with ECM degradation such as metastasis, inflammation and angiogenesis and is thus an important target for anti-cancer and anti-inflammatory drug discovery. Heparanase has been classed as belonging to themore » clan A glycoside hydrolase family 79 based on sequence analysis, secondary structure predictions and mutagenic analysis, and thus it has been inferred that it is a retaining glycosidase. However, there has been no direct experimental evidence to support this conclusion. Herein we describe {sup 1}H NMR spectroscopic studies of the hydrolysis of the pentasaccharide substrate fondaparinux by heparanase, and provide conclusive evidence that heparanase hydrolyses its substrate with retention of configuration and is thus established as a retaining glycosidase. Knowledge of the mechanism of hydrolysis may have implications for future design of inhibitors for this important drug target.« less

Implementation of picoSpin Benchtop NMR Instruments into Organic Chemistry Teaching Laboratories through Spectral Analysis of Fischer Esterification Products

ERIC Educational Resources Information Center

Yearty, Kasey L.; Sharp, Joseph T.; Meehan, Emma K.; Wallace, Doyle R.; Jackson, Douglas M.; Morrison, Richard W.

2017-01-01

[Superscript 1]H NMR analysis is an important analytical technique presented in introductory organic chemistry courses. NMR instrument access is limited for undergraduate organic chemistry students due to the size of the instrument, price of NMR solvents, and the maintenance level required for instrument upkeep. The University of Georgia Chemistry…

Structural and Biological Behaviour of Co(II), Cu(II) and Ni(II) Metal Complexes of Some Amino Acid Derived Schiff-Bases

PubMed Central

Chohan, Zahid H.; Praveen, M.; Ghaffar, A.

1997-01-01

Biologically active tridentate amino acid (Alanine, Glycine & Tyrosine) derived Schiff-bases and their Co(II), Cu(II) & Ni(II) complexes have been synthesised and characterised on the basis of their conductance and magnetic measurements, elemental analysis and 13C-NMR, 1H-NMR, IR and electronic spectral data. These Schiff-bases and their complexes have been evaluated for their antibacterial activity against bacterial species such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumonae, Proteus vulgarus and Pseudomonas aeruginosa and this activity data show the metal complexes to be more antibacterial than the Schiff-bases against one or more bacterial species. PMID:18475798

Metabolic changes associated with papillary thyroid carcinoma: A nuclear magnetic resonance-based metabolomics study.

PubMed

Li, Yanyun; Chen, Minjian; Liu, Cuiping; Xia, Yankai; Xu, Bo; Hu, Yanhui; Chen, Ting; Shen, Meiping; Tang, Wei

2018-05-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new insights into detailed metabolic changes of PTC, and hold great potential in the treatment of PTC.

Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries.

PubMed

Baurley, James W; Edlund, Christopher K; Pardamean, Carissa I; Conti, David V; Krasnow, Ruth; Javitz, Harold S; Hops, Hyman; Swan, Gary E; Benowitz, Neal L; Bergen, Andrew W

2016-09-01

Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3'-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed. Three hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status. African and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values < 5E-5). This meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan-continental population biomarkers for nicotine metabolism. This multiple ancestry meta-GWAS of the laboratory study-based NMR provides novel evidence and replication for genome-wide association of CYP2A6 single nucleotide and insertion-deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism from a recent GWAS of the NMR in Finnish smokers, identify a functional mechanism for this intronic variant from in silico analyses of RNA-seq data that is consistent with CYP2A6 expression measured in postmortem lung and liver, and provide additional support for the intergenic region between CYP2A6 and CYP2A7. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries

PubMed Central

Baurley, James W.; Edlund, Christopher K.; Pardamean, Carissa I.; Conti, David V.; Krasnow, Ruth; Javitz, Harold S.; Hops, Hyman; Swan, Gary E.; Benowitz, Neal L.

2016-01-01

Introduction: Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3′-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed. Methods: Three hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status. Results: African and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values < 5E-5). Conclusions: This meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan-continental population biomarkers for nicotine metabolism. Implications: This multiple ancestry meta-GWAS of the laboratory study-based NMR provides novel evidence and replication for genome-wide association of CYP2A6 single nucleotide and insertion–deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism from a recent GWAS of the NMR in Finnish smokers, identify a functional mechanism for this intronic variant from in silico analyses of RNA-seq data that is consistent with CYP2A6 expression measured in postmortem lung and liver, and provide additional support for the intergenic region between CYP2A6 and CYP2A7. PMID:27113016

Conformational analysis of a quinolonic ribonucleoside with anti-HSV-1 activity

NASA Astrophysics Data System (ADS)

Yoneda, Julliane D.; Velloso, Marcia Helena R.; Leal, Kátia Z.; Azeredo, Rodrigo B. de V.; Sugiura, Makiko; Albuquerque, Magaly G.; Santos, Fernanda da C.; Souza, Maria Cecília B. V. de; Cunha, Anna Claudia; Seidl, Peter R.; Alencastro, Ricardo B. de; Ferreira, Vitor F.

2011-01-01

The infections caused by the Herpes Simplex Virus are one of the most common sources of diseases in adults and several natural nucleoside analogues are currently used in the treatment of these infections. In vitro tests of a series of quinolonic ribonucleosides derivatives synthesized by part of our group indicated that some of them have antiviral activity against HSV-1. The conformational analysis of bioactive compounds is extremely important in order to better understand their chemical structures and biological activity. In this work, we have carried out a nuclear relaxation NMR study of 6-Me ribonucleoside derivative in order to determine if the syn or anti conformation is preferential. The NMR analysis permits the determination of inter-atomic distances by using techniques which are based on nuclear relaxation and related phenomena. Those techniques are non-selective longitudinal or spin-lattice relaxation rates and NULL pulse sequence, which allow the determination of distances between pairs of hydrogen atoms. The results of NMR studies were compared with those obtained by molecular modeling.

Comprehensive non-targeted analysis of contaminated groundwater of a former ammunition destruction site using 1H-NMR and HPLC-SPE-NMR/TOF-MS.

PubMed

Godejohann, Markus; Heintz, Lea; Daolio, Cristina; Berset, Jean-Daniel; Muff, Daniel

2009-09-15

The aim of the present study was to explore the capabilities of the combination of 1H NMR (proton nuclear magnetic resonance) mixture analysis and HPLC-SPE-NMR/TOF-MS (high-performance liquid chromatography coupled to solid-phase extraction and nuclear magnetic resonance and time-of-flight mass spectrometry) for the characterization of xenobiotic contaminants in groundwater samples. As an example, solid-phase extracts of two groundwater samples taken from a former ammunition destruction site in Switzerland were investigated. 1H NMR spectra of postcolumn SPE enriched compounds, together with accurate mass measurements, allowed the structural elucidation of unknowns. This untargeted approach allowed us to identify expected residues of explosives such as 2,4,6-trinitrotoluene (2,4,6-TNT), Hexogen (RDX) and Octogen (HMX), degradation products of TNT (1,3,5-trinitrobenzene (1,3,5-TNB), 2-amino-4,6-dinitrotoluene (2-A-4,6-DNT), 3,5-dinitrophenol (3,5-DNP), 3,5-dinitroaniline (3,5-DNA), 2,6-dinitroanthranite, and 2-Hydroxy-4,6-dinitrobenzonitrile), benzoic acid, Bisphenol A (a known endocrine disruptor compound), and some toxicologically relevant additives for propelling charges: Centralite I (1,3-diethyl-1,3-diphenylurea), DPU (N,N-diphenylurethane), N,N-diphenylcarbamate (Acardite II), and N-methyl-N-phenylurethane. To our knowledge, this is the first report of the presence of these additives in environmental samples. Extraction recoveries for Centralite I and DPU have been determined. Contaminants identified by our techniques were quantified based on HPLC-UV (HPLC-ultraviolet detection) and 1H NMR mixture analysis. The concentrations of the contaminants ranged between 0.1 and 48 microg/L assuming 100% recovery for the SPE step.

Synthesis, spectroscopy, X-ray crystallography, DFT calculations, DNA binding and molecular docking of a propargyl arms containing Schiff base.

PubMed

Balakrishnan, C; Subha, L; Neelakantan, M A; Mariappan, S S

2015-11-05

A propargyl arms containing Schiff base (L) was synthesized by the condensation of 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl]ethanone with trans-1,2-diaminocyclohexane. The structure of L was characterized by IR, (1)H NMR, (13)C NMR and UV-Vis spectroscopy and by single crystal X-ray diffraction analysis. The UV-Visible spectral behavior of L in different solvents exhibits positive solvatochromism. Density functional calculation of the L in gas phase was performed by using DFT (B3LYP) method with 6-31G basis set. The computed vibrational frequencies and NMR signals of L were compared with the experimental data. Tautomeric stability study inferred that the enolimine is more stable than the ketoamine form. The charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Electronic absorption and emission spectral studies were used to study the binding of L with CT-DNA. The molecular docking was done to identify the interaction of L with A-DNA and B-DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Authentication of beef versus horse meat using 60 MHz 1H NMR spectroscopy.

PubMed

Jakes, W; Gerdova, A; Defernez, M; Watson, A D; McCallum, C; Limer, E; Colquhoun, I J; Williamson, D C; Kemsley, E K

2015-05-15

This work reports a candidate screening protocol to distinguish beef from horse meat based upon comparison of triglyceride signatures obtained by 60 MHz (1)H NMR spectroscopy. Using a simple chloroform-based extraction, we obtained classic low-field triglyceride spectra from typically a 10 min acquisition time. Peak integration was sufficient to differentiate samples of fresh beef (76 extractions) and horse (62 extractions) using Naïve Bayes classification. Principal component analysis gave a two-dimensional "authentic" beef region (p=0.001) against which further spectra could be compared. This model was challenged using a subset of 23 freeze-thawed training samples. The outcomes indicated that storing samples by freezing does not adversely affect the analysis. Of a further collection of extractions from previously unseen samples, 90/91 beef spectra were classified as authentic, and 16/16 horse spectra as non-authentic. We conclude that 60 MHz (1)H NMR represents a feasible high-throughput approach for screening raw meat. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural investigations of Pu{sup III} phosphate by X-ray diffraction, MAS-NMR and XANES spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popa, Karin; Raison, Philippe E., E-mail: philippe.raison@ec.europa.eu; Martel, Laura

2015-10-15

PuPO{sub 4} was prepared by a solid state reaction method and its crystal structure at room temperature was solved by powder X-ray diffraction combined with Rietveld refinement. High resolution XANES measurements confirm the +III valence state of plutonium, in agreement with valence bond derivation. The presence of the americium (as β{sup −} decay product of plutonium) in the +III oxidation state was determined based on XANES spectroscopy. High resolution solid state {sup 31}P NMR agrees with the XANES results and the presence of a solid-solution. - Graphical abstract: A full structural analysis of PuPO{sub 4} based on Rietveld analysis ofmore » room temperature X-ray diffraction data, XANES and MAS NMR measurements was performed. - Highlights: • The crystal structure of PuPO{sub 4} monazite is solved. • In PuPO{sub 4} plutonium is strictly trivalent. • The presence of a minute amount of Am{sup III} is highlighted. • We propose PuPO{sub 4} as a potential reference material for spectroscopic and microscopic studies.« less

Theoretical DFT, vibrational and NMR studies of benzimidazole and alkyl derivatives

NASA Astrophysics Data System (ADS)

Infante-Castillo, Ricardo; Rivera-Montalvo, Luis A.; Hernández-Rivera, Samuel P.

2008-04-01

Benzimidazoles are heterocyclic compounds that have awaked great interest during the last few years because of their proven biological activity as antiviral, antimicrobial, and antitumoral agents. For this reason, the development of a systematic FT-IR, FT-Raman and NMR study of 1-substituted compounds in 2-methylbenzimidazole constitutes a significant tool in understanding the molecular dynamics and the structural parameters that govern their behavior. Two new 1-alkyl-2-methylbenzimidazoles compounds were synthesized from reaction of 2-methylbenzimidazole with primary and secondary alkyl halides using a strong base as a catalyst. These compounds were purified and characterized by elemental analysis and different spectroscopic methods. The comparative analysis of vibrational modes of benzimidazole and its alkyl derivatives show that regions of absorption are very similar in all of them. However, changes are produced at low frequencies specifically in the C-H out of plane deformations, ring breathing and ring skeletal vibrations. The ring out-of plane bending modes shift by 10-15 cm -1 in some cases as results of alkyl substitution. The theoretical calculated spectra, using Density Functional Theory (DFT) approximation, and experimental results were consistent with each other. The GIAO method was used to calculate absolute shieldings, which agree consistently with those measured by 1H and 13C NMR. The consistency and efficiency of the GIAO 13C and 1H NMR calculations were thoroughly checked by the analysis of statistical parameters concerning computed and experimental 13C and 1H NMR chemical shift values of the studied compounds.

PepsNMR for 1H NMR metabolomic data pre-processing.

PubMed

Martin, Manon; Legat, Benoît; Leenders, Justine; Vanwinsberghe, Julien; Rousseau, Réjane; Boulanger, Bruno; Eilers, Paul H C; De Tullio, Pascal; Govaerts, Bernadette

2018-08-17

In the analysis of biological samples, control over experimental design and data acquisition procedures alone cannot ensure well-conditioned 1 H NMR spectra with maximal information recovery for data analysis. A third major element affects the accuracy and robustness of results: the data pre-processing/pre-treatment for which not enough attention is usually devoted, in particular in metabolomic studies. The usual approach is to use proprietary software provided by the analytical instruments' manufacturers to conduct the entire pre-processing strategy. This widespread practice has a number of advantages such as a user-friendly interface with graphical facilities, but it involves non-negligible drawbacks: a lack of methodological information and automation, a dependency of subjective human choices, only standard processing possibilities and an absence of objective quality criteria to evaluate pre-processing quality. This paper introduces PepsNMR to meet these needs, an R package dedicated to the whole processing chain prior to multivariate data analysis, including, among other tools, solvent signal suppression, internal calibration, phase, baseline and misalignment corrections, bucketing and normalisation. Methodological aspects are discussed and the package is compared to the gold standard procedure with two metabolomic case studies. The use of PepsNMR on these data shows better information recovery and predictive power based on objective and quantitative quality criteria. Other key assets of the package are workflow processing speed, reproducibility, reporting and flexibility, graphical outputs and documented routines. Copyright © 2018 Elsevier B.V. All rights reserved.

Independent components analysis to increase efficiency of discriminant analysis methods (FDA and LDA): Application to NMR fingerprinting of wine.

PubMed

Monakhova, Yulia B; Godelmann, Rolf; Kuballa, Thomas; Mushtakova, Svetlana P; Rutledge, Douglas N

2015-08-15

Discriminant analysis (DA) methods, such as linear discriminant analysis (LDA) or factorial discriminant analysis (FDA), are well-known chemometric approaches for solving classification problems in chemistry. In most applications, principle components analysis (PCA) is used as the first step to generate orthogonal eigenvectors and the corresponding sample scores are utilized to generate discriminant features for the discrimination. Independent components analysis (ICA) based on the minimization of mutual information can be used as an alternative to PCA as a preprocessing tool for LDA and FDA classification. To illustrate the performance of this ICA/DA methodology, four representative nuclear magnetic resonance (NMR) data sets of wine samples were used. The classification was performed regarding grape variety, year of vintage and geographical origin. The average increase for ICA/DA in comparison with PCA/DA in the percentage of correct classification varied between 6±1% and 8±2%. The maximum increase in classification efficiency of 11±2% was observed for discrimination of the year of vintage (ICA/FDA) and geographical origin (ICA/LDA). The procedure to determine the number of extracted features (PCs, ICs) for the optimum DA models was discussed. The use of independent components (ICs) instead of principle components (PCs) resulted in improved classification performance of DA methods. The ICA/LDA method is preferable to ICA/FDA for recognition tasks based on NMR spectroscopic measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

speaq 2.0: A complete workflow for high-throughput 1D NMR spectra processing and quantification.

PubMed

Beirnaert, Charlie; Meysman, Pieter; Vu, Trung Nghia; Hermans, Nina; Apers, Sandra; Pieters, Luc; Covaci, Adrian; Laukens, Kris

2018-03-01

Nuclear Magnetic Resonance (NMR) spectroscopy is, together with liquid chromatography-mass spectrometry (LC-MS), the most established platform to perform metabolomics. In contrast to LC-MS however, NMR data is predominantly being processed with commercial software. Meanwhile its data processing remains tedious and dependent on user interventions. As a follow-up to speaq, a previously released workflow for NMR spectral alignment and quantitation, we present speaq 2.0. This completely revised framework to automatically analyze 1D NMR spectra uses wavelets to efficiently summarize the raw spectra with minimal information loss or user interaction. The tool offers a fast and easy workflow that starts with the common approach of peak-picking, followed by grouping, thus avoiding the binning step. This yields a matrix consisting of features, samples and peak values that can be conveniently processed either by using included multivariate statistical functions or by using many other recently developed methods for NMR data analysis. speaq 2.0 facilitates robust and high-throughput metabolomics based on 1D NMR but is also compatible with other NMR frameworks or complementary LC-MS workflows. The methods are benchmarked using a simulated dataset and two publicly available datasets. speaq 2.0 is distributed through the existing speaq R package to provide a complete solution for NMR data processing. The package and the code for the presented case studies are freely available on CRAN (https://cran.r-project.org/package=speaq) and GitHub (https://github.com/beirnaert/speaq).

speaq 2.0: A complete workflow for high-throughput 1D NMR spectra processing and quantification

PubMed Central

Pieters, Luc; Covaci, Adrian

2018-01-01

Nuclear Magnetic Resonance (NMR) spectroscopy is, together with liquid chromatography-mass spectrometry (LC-MS), the most established platform to perform metabolomics. In contrast to LC-MS however, NMR data is predominantly being processed with commercial software. Meanwhile its data processing remains tedious and dependent on user interventions. As a follow-up to speaq, a previously released workflow for NMR spectral alignment and quantitation, we present speaq 2.0. This completely revised framework to automatically analyze 1D NMR spectra uses wavelets to efficiently summarize the raw spectra with minimal information loss or user interaction. The tool offers a fast and easy workflow that starts with the common approach of peak-picking, followed by grouping, thus avoiding the binning step. This yields a matrix consisting of features, samples and peak values that can be conveniently processed either by using included multivariate statistical functions or by using many other recently developed methods for NMR data analysis. speaq 2.0 facilitates robust and high-throughput metabolomics based on 1D NMR but is also compatible with other NMR frameworks or complementary LC-MS workflows. The methods are benchmarked using a simulated dataset and two publicly available datasets. speaq 2.0 is distributed through the existing speaq R package to provide a complete solution for NMR data processing. The package and the code for the presented case studies are freely available on CRAN (https://cran.r-project.org/package=speaq) and GitHub (https://github.com/beirnaert/speaq). PMID:29494588

LC-UV-solid-phase extraction-NMR-MS combined with a cryogenic flow probe and its application to the identification of compounds present in Greek oregano.

PubMed

Exarchou, Vassiliki; Godejohann, Markus; van Beek, Teris A; Gerothanassis, Ioannis P; Vervoort, Jacques

2003-11-15

Structure elucidation of natural products usually relies on a combination of NMR spectroscopy with mass spectrometry whereby NMR trails MS in terms of the minimum sample amount required. In the present study, the usefulness of on-line solid-phase extraction (SPE) in LC-NMR for peak storage after the LC separation prior to NMR analysis is demonstrated. The SPE unit allows the use of normal protonated solvents for the LC separation and fully deuterated solvents for flushing the trapped compounds to the NMR probe. Thus, solvent suppression is no longer necessary. Multiple trapping of the same analyte from repeated LC injections was utilized to solve the problem of low concentration and to obtain 2D heteronuclear NMR spectra. In addition, a combination of the SPE unit with a recently developed cryoflow NMR probe and an MS was evaluated. This on-line LC-UV-SPE-NMR-MS system was used for the automated analysis of a Greek oregano extract. Combining the data provided by the UV, MS, and NMR spectra, the flavonoids taxifolin, aromadendrin, eriodictyol, naringenin, and apigenin, the phenolic acid rosmarinic acid, and the monoterpene carvacrol were identified. This automated technique is very useful for natural product analysis, and the large sensitivity improvement leads to significantly reduced NMR acquisition times.

NMR/MS Translator for the Enhanced Simultaneous Analysis of Metabolomics Mixtures by NMR Spectroscopy and Mass Spectrometry: Application to Human Urine.

PubMed

Bingol, Kerem; Brüschweiler, Rafael

2015-06-05

A novel metabolite identification strategy is presented for the combined NMR/MS analysis of complex metabolite mixtures. The approach first identifies metabolite candidates from 1D or 2D NMR spectra by NMR database query, which is followed by the determination of the masses (m/z) of their possible ions, adducts, fragments, and characteristic isotope distributions. The expected m/z ratios are then compared with the MS(1) spectrum for the direct assignment of those signals of the mass spectrum that contain information about the same metabolites as the NMR spectra. In this way, the mass spectrum can be assigned with very high confidence, and it provides at the same time validation of the NMR-derived metabolites. The method was first demonstrated on a model mixture, and it was then applied to human urine collected from a pool of healthy individuals. A number of metabolites could be detected that had not been reported previously, further extending the list of known urine metabolites. The new analysis approach, which is termed NMR/MS Translator, is fully automated and takes only a few seconds on a computer workstation. NMR/MS Translator synergistically uses the power of NMR and MS, enhancing the accuracy and efficiency of the identification of those metabolites compiled in databases.

Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars

PubMed Central

Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W.

2015-01-01

Background and Aims Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. Methods and Results We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Conclusions Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. Significance of the Study The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach. PMID:26658757

Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

PubMed

Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

2015-01-01

Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Identification of Imitation Cheese and Imitation Ice Cream Based on Vegetable Fat Using NMR Spectroscopy and Chemometrics

PubMed Central

Monakhova, Yulia B.; Godelmann, Rolf; Andlauer, Claudia; Kuballa, Thomas; Lachenmeier, Dirk W.

2013-01-01

Vegetable oils and fats may be used as cheap substitutes for milk fat to manufacture imitation cheese or imitation ice cream. In this study, 400 MHz nuclear magnetic resonance (NMR) spectroscopy of the fat fraction of the products was used in the context of food surveillance to validate the labeling of milk-based products. For sample preparation, the fat was extracted using an automated Weibull-Stoldt methodology. Using principal component analysis (PCA), imitation products can be easily detected. In both cheese and ice cream, a differentiation according to the type of raw material (milk fat and vegetable fat) was possible. The loadings plot shows that imitation products were distinguishable by differences in their fatty acid ratios. Furthermore, a differentiation of several types of cheese (Edamer, Gouda, Emmentaler, and Feta) was possible. Quantitative data regarding the composition of the investigated products can also be predicted from the same spectra using partial least squares (PLS) regression. The models obtained for 13 compounds in cheese (R 2 0.75–0.95) and 17 compounds in ice cream (R 2 0.83–0.99) (e.g., fatty acids and esters) were suitable for a screening analysis. NMR spectroscopy was judged as suitable for the routine analysis of dairy products based on milk or on vegetable fat substitutes. PMID:26904597

CRAFT (complete reduction to amplitude frequency table)--robust and time-efficient Bayesian approach for quantitative mixture analysis by NMR.

PubMed

Krishnamurthy, Krish

2013-12-01

The intrinsic quantitative nature of NMR is increasingly exploited in areas ranging from complex mixture analysis (as in metabolomics and reaction monitoring) to quality assurance/control. Complex NMR spectra are more common than not, and therefore, extraction of quantitative information generally involves significant prior knowledge and/or operator interaction to characterize resonances of interest. Moreover, in most NMR-based metabolomic experiments, the signals from metabolites are normally present as a mixture of overlapping resonances, making quantification difficult. Time-domain Bayesian approaches have been reported to be better than conventional frequency-domain analysis at identifying subtle changes in signal amplitude. We discuss an approach that exploits Bayesian analysis to achieve a complete reduction to amplitude frequency table (CRAFT) in an automated and time-efficient fashion - thus converting the time-domain FID to a frequency-amplitude table. CRAFT uses a two-step approach to FID analysis. First, the FID is digitally filtered and downsampled to several sub FIDs, and secondly, these sub FIDs are then modeled as sums of decaying sinusoids using the Bayesian approach. CRAFT tables can be used for further data mining of quantitative information using fingerprint chemical shifts of compounds of interest and/or statistical analysis of modulation of chemical quantity in a biological study (metabolomics) or process study (reaction monitoring) or quality assurance/control. The basic principles behind this approach as well as results to evaluate the effectiveness of this approach in mixture analysis are presented. Copyright © 2013 John Wiley & Sons, Ltd.

1H and 31P benchtop NMR of liquids and solids used in and/or produced during the manufacture of methamphetamine by the HI reduction of pseudoephedrine/ephedrine.

PubMed

Bogun, Ben; Moore, Sarah

2017-09-01

In this study, the use of benchtop NMR spectroscopy in the analysis of solids and liquids used and/or produced during the HI reduction of pseudoephedrine was evaluated. The study focused on identifying organic precursors and phosphorus containing compounds used in and/or produced during the manufacturing process. Samples taken from clandestine laboratories, where this synthesis process was suspected of occurring, were also analysed and evaluated. Benchtop NMR was able to distinguish between ephedrine, pseudoephedrine and methamphetamine as the free base and hydrochloride salt. This technique was also effective at identifying and distinguishing between phosphorus containing compounds used and/or produced during the manufacture of methamphetamine. Benchtop NMR was also determined to be effective at analysing samples from suspected clandestine laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization and automation of quantitative NMR data extraction.

PubMed

Bernstein, Michael A; Sýkora, Stan; Peng, Chen; Barba, Agustín; Cobas, Carlos

2013-06-18

NMR is routinely used to quantitate chemical species. The necessary experimental procedures to acquire quantitative data are well-known, but relatively little attention has been applied to data processing and analysis. We describe here a robust expert system that can be used to automatically choose the best signals in a sample for overall concentration determination and determine analyte concentration using all accepted methods. The algorithm is based on the complete deconvolution of the spectrum which makes it tolerant of cases where signals are very close to one another and includes robust methods for the automatic classification of NMR resonances and molecule-to-spectrum multiplets assignments. With the functionality in place and optimized, it is then a relatively simple matter to apply the same workflow to data in a fully automatic way. The procedure is desirable for both its inherent performance and applicability to NMR data acquired for very large sample sets.

Toward nanomolar detection by NMR through SABRE hyperpolarization.

PubMed

Eshuis, Nan; Hermkens, Niels; van Weerdenburg, Bram J A; Feiters, Martin C; Rutjes, Floris P J T; Wijmenga, Sybren S; Tessari, Marco

2014-02-19

SABRE is a nuclear spin hyperpolarization technique based on the reversible association of a substrate molecule and para-hydrogen (p-H2) to a metal complex. During the lifetime of such a complex, generally fractions of a second, the spin order of p-H2 is transferred to the nuclear spins of the substrate molecule via a transient scalar coupling network, resulting in strongly enhanced NMR signals. This technique is generally applied at relatively high concentrations (mM), in large excess of substrate with respect to metal complex. Dilution of substrate ligands below stoichiometry results in progressive decrease of signal enhancement, which precludes the direct application of SABRE to the NMR analysis of low concentration (μM) solutions. Here, we show that the efficiency of SABRE at low substrate concentrations can be restored by addition of a suitable coordinating ligand to the solution. The proposed method allowed NMR detection below 1 μM in a single scan.

Combined In Situ Illumination-NMR-UV/Vis Spectroscopy: A New Mechanistic Tool in Photochemistry.

PubMed

Seegerer, Andreas; Nitschke, Philipp; Gschwind, Ruth M

2018-06-18

Synthetic applications in photochemistry are booming. Despite great progress in the development of new reactions, mechanistic investigations are still challenging. Therefore, we present a fully automated in situ combination of NMR spectroscopy, UV/Vis spectroscopy, and illumination to allow simultaneous and time-resolved detection of paramagnetic and diamagnetic species. This optical fiber-based setup enables the first acquisition of combined UV/Vis and NMR spectra in photocatalysis, as demonstrated on a conPET process. Furthermore, the broad applicability of combined UVNMR spectroscopy for light-induced processes is demonstrated on a structural and quantitative analysis of a photoswitch, including rate modulation and stabilization of transient species by temperature variation. Owing to the flexibility regarding the NMR hardware, temperature, and light sources, we expect wide-ranging applications of this setup in various research fields. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

NMR signal analysis to attribute the components to the solid/liquid phases present in mixes and ice creams.

PubMed

Mariette, François; Lucas, Tiphaine

2005-03-09

The NMR relaxation signals from complex products such as ice cream are hard to interpret because of the multiexponential behavior of the relaxation signal and the difficulty of attributing the NMR relaxation components to specific molecule fractions. An attribution of the NMR relaxation parameters is proposed, however, based on an approach that combines quantitative analysis of the spin-spin and spin-lattice relaxation times and the signal intensities with characterization of the ice cream components. We have been able to show that NMR can be used to describe the crystallized and liquid phases separately. The first component of the spin-spin and spin-lattice relaxation describes the behavior of the protons of the crystallized fat in the mix. The amount of fat crystals can then be estimated. In the case of ice cream, only the spin-lattice relaxation signal from the crystallized fraction is relevant. However, it enables the ice protons and the protons of the crystallized fat to be distinguished. The spin-lattice relaxation time can be used to describe the mobility of the protons in the different crystallized phases and also to quantify the amount of ice crystals and fat crystals in the ice cream. The NMR relaxation of the liquid phase of the mix has a biexponential behavior. A first component is attributable to the liquid fraction of the fat and to the sugars, while a second component is attributable to the aqueous phase. Overall, the study shows that despite the complexity of the NMR signal from ice cream, a number of relevant parameters can be extracted to study the influence of the formulation and of the process stages on the ice fraction, the crystallized fat fraction, and the liquid aqueous fraction.

PDBStat: a universal restraint converter and restraint analysis software package for protein NMR.

PubMed

Tejero, Roberto; Snyder, David; Mao, Binchen; Aramini, James M; Montelione, Gaetano T

2013-08-01

The heterogeneous array of software tools used in the process of protein NMR structure determination presents organizational challenges in the structure determination and validation processes, and creates a learning curve that limits the broader use of protein NMR in biology. These challenges, including accurate use of data in different data formats required by software carrying out similar tasks, continue to confound the efforts of novices and experts alike. These important issues need to be addressed robustly in order to standardize protein NMR structure determination and validation. PDBStat is a C/C++ computer program originally developed as a universal coordinate and protein NMR restraint converter. Its primary function is to provide a user-friendly tool for interconverting between protein coordinate and protein NMR restraint data formats. It also provides an integrated set of computational methods for protein NMR restraint analysis and structure quality assessment, relabeling of prochiral atoms with correct IUPAC names, as well as multiple methods for analysis of the consistency of atomic positions indicated by their convergence across a protein NMR ensemble. In this paper we provide a detailed description of the PDBStat software, and highlight some of its valuable computational capabilities. As an example, we demonstrate the use of the PDBStat restraint converter for restrained CS-Rosetta structure generation calculations, and compare the resulting protein NMR structure models with those generated from the same NMR restraint data using more traditional structure determination methods. These results demonstrate the value of a universal restraint converter in allowing the use of multiple structure generation methods with the same restraint data for consensus analysis of protein NMR structures and the underlying restraint data.

PDBStat: A Universal Restraint Converter and Restraint Analysis Software Package for Protein NMR

PubMed Central

Tejero, Roberto; Snyder, David; Mao, Binchen; Aramini, James M.; Montelione, Gaetano T

2013-01-01

The heterogeneous array of software tools used in the process of protein NMR structure determination presents organizational challenges in the structure determination and validation processes, and creates a learning curve that limits the broader use of protein NMR in biology. These challenges, including accurate use of data in different data formats required by software carrying out similar tasks, continue to confound the efforts of novices and experts alike. These important issues need to be addressed robustly in order to standardize protein NMR structure determination and validation. PDBStat is a C/C++ computer program originally developed as a universal coordinate and protein NMR restraint converter. Its primary function is to provide a user-friendly tool for interconverting between protein coordinate and protein NMR restraint data formats. It also provides an integrated set of computational methods for protein NMR restraint analysis and structure quality assessment, relabeling of prochiral atoms with correct IUPAC names, as well as multiple methods for analysis of the consistency of atomic positions indicated by their convergence across a protein NMR ensemble. In this paper we provide a detailed description of the PDBStat software, and highlight some of its valuable computational capabilities. As an example, we demonstrate the use of the PDBStat restraint converter for restrained CS-Rosetta structure generation calculations, and compare the resulting protein NMR structure models with those generated from the same NMR restraint data using more traditional structure determination methods. These results demonstrate the value of a universal restraint converter in allowing the use of multiple structure generation methods with the same restraint data for consensus analysis of protein NMR structures and the underlying restraint data. PMID:23897031

Tunable Thermosetting Epoxies Based on Fractionated and Well-Characterized Lignins.

PubMed

Gioia, Claudio; Lo Re, Giada; Lawoko, Martin; Berglund, Lars

2018-03-21

Here we report the synthesis of thermosetting resins from low molar mass Kraft lignin fractions of high functionality, refined by solvent extraction. Such fractions were fully characterized by 31 P NMR, 2D-HSQC NMR, SEC, and DSC in order to obtain a detailed description of the structures. Reactive oxirane moieties were introduced on the lignin backbone under mild reaction conditions and quantified by simple 1 H NMR analysis. The modified fractions were chemically cross-linked with a flexible polyether diamine ( M n ≈ 2000), in order to obtain epoxy thermosets. Epoxies from different lignin fractions, studied by DSC, DMA, tensile tests, and SEM, demonstrated substantial differences in terms of thermo-mechanical properties. For the first time, strong relationships between lignin structures and epoxy properties could be demonstrated. The suggested approach provides unprecedented possibilities to tune network structure and properties of thermosets based on real lignin fractions, rather than model compounds.

1H-NMR and UPLC-MS metabolomics: Functional tools for exploring chemotypic variation in Sceletium tortuosum from two provinces in South Africa.

PubMed

Zhao, Jianping; Khan, Ikhlas A; Combrinck, Sandra; Sandasi, Maxleene; Chen, Weiyang; Viljoen, Alvaro M

2018-05-17

Sceletium tortuosum (Aizoaceae) is widely recognised for the treatment of stress, anxiety and depression, as well as for obsessive compulsive disorders. A comprehensive intraspecies chemotypic variation study, using samples harvested from two distinct regions of South Africa, was done using both proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy of methanol extracts (N = 145) and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) of acid/base extracts (N = 289). Chemometric analysis of the 1 H-NMR data indicated two main clusters that were region-specific (Northern Cape and Western Cape provinces). Two dimensional (2D) NMR was used to identify analytes that contributed to the clustering as revealed by the S-plot. The sceletium alkaloids, pinitol and two alkylamines, herein reported for the first time from S. tortuosum, were identified as markers that distinguished the two groups. Relative quantification of the marker analytes conducted by qNMR indicated that samples from the Northern Cape generally contained higher concentrations of all the markers than samples from the Western Cape. Quantitative analysis of the four mesembrine alkaloids using a validated UPLC-photo diode array (PDA) detection method confirmed the results of qNMR with regard to the total alkaloid concentrations. Samples from the Northern Cape Province were found to contain, on average, very high total alkaloids, ranging from 4938.0 to 9376.8 mg/kg dry w. Regarding the Western Cape samples, the total yields of the four mesembrine alkaloids were substantially lower (averages 16.4-4143.2 mg/kg). Hierarchical cluster analysis of the UPLC-MS data, based on the alkaloid chemistry, revealed three branches, with one branch comprising samples primarily from the Northern Cape that seemed somewhat chemically conserved, while the other two branches represented mainly samples from the Western Cape. The construction of an orthogonal projections to latent structures-discriminant analysis model and subsequent loadings plot, allowed alkaloid markers to be identified for each cluster. The diverse sceletium alkaloid chemistry of samples from the three clusters may facilitate the recognition of alkaloid profiles, rather than individual compounds, that exert targeted effects on various brain receptors involved in stress, anxiety or depression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

NASA Astrophysics Data System (ADS)

Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

In this contribution the ability of 19F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T1(1H) and T1ρ(1H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in 19F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around 19F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded 19F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way 19F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

Classification of edible oils by employing 31P and 1H NMR spectroscopy in combination with multivariate statistical analysis. A proposal for the detection of seed oil adulteration in virgin olive oils.

PubMed

Vigli, Georgia; Philippidis, Angelos; Spyros, Apostolos; Dais, Photis

2003-09-10

A combination of (1)H NMR and (31)P NMR spectroscopy and multivariate statistical analysis was used to classify 192 samples from 13 types of vegetable oils, namely, hazelnut, sunflower, corn, soybean, sesame, walnut, rapeseed, almond, palm, groundnut, safflower, coconut, and virgin olive oils from various regions of Greece. 1,2-Diglycerides, 1,3-diglycerides, the ratio of 1,2-diglycerides to total diglycerides, acidity, iodine value, and fatty acid composition determined upon analysis of the respective (1)H NMR and (31)P NMR spectra were selected as variables to establish a classification/prediction model by employing discriminant analysis. This model, obtained from the training set of 128 samples, resulted in a significant discrimination among the different classes of oils, whereas 100% of correct validated assignments for 64 samples were obtained. Different artificial mixtures of olive-hazelnut, olive-corn, olive-sunflower, and olive-soybean oils were prepared and analyzed by (1)H NMR and (31)P NMR spectroscopy. Subsequent discriminant analysis of the data allowed detection of adulteration as low as 5% w/w, provided that fresh virgin olive oil samples were used, as reflected by their high 1,2-diglycerides to total diglycerides ratio (D > or = 0.90).

Configurational assignments of conformationally restricted bis-monoterpene hydroquinones: utility in exploration of endangered plants.

PubMed

Oh, Joonseok; Bowling, John J; Zou, Yike; Chittiboyina, Amar G; Doerksen, Robert J; Ferreira, Daneel; Leininger, Theodor D; Hamann, Mark T

2013-08-01

Endangered plant species are an important resource for new chemistry. Lindera melissifolia is native to the Southeastern U.S. and scarcely populates the edges of lakes and ponds. Quantum mechanics (QM) used in combination with NMR/ECD is a powerful tool for the assignment of absolute configuration in lieu of X-ray crystallography. The EtOAc extract of L. melissifolia was subject to chromatographic analysis by VLC and HPLC. Spin-spin coupling constant (SSCC) were calculated using DFT at the MPW1PW91/6-31G(d,p) level for all staggered rotamers. ECD calculations employed Amber* force fields followed by PM6 semi-empirical optimizations. Hetero- and homo-nuclear coupling constants were extracted from 1D (1)H, E.COSY and HETLOC experiments. Two meroterpenoids, melissifolianes A (1) and B (2) were purified and their 2-D structures elucidated using NMR and HRESIMS. The relative configuration of 1 was established using the combination of NOE-based distance restraints and the comparisons of experimental and calculated SSCCs. The comparison of calculated and experimental ECD assigned the absolute configuration of 1. The relative configuration of a racemic mixture, melissifoliane B (2) was established utilizing J-based analysis combined with QM and NMR techniques.Conclusion Our study of the Lindera melissifolia metabolome exemplifies how new chemistry remains undiscovered among the numerous endangered plant species and demonstrates how analysis by ECD and NMR combined with various QM calculations is a sensible approach to support the stereochemical assignment of molecules with conformationally restricted conformations. QM-NMR/ECD combined approaches are of utility for unambiguous assignment of 3-D structures, especially with limited plant material and when a molecule is conformationally restricted. Conservation of an endangered plant species can be supported through identification of its new chemistry and utilization of that chemistry for commercial purposes. Copyright © 2013. Published by Elsevier B.V.

NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Chunfeng; Department of Pharmacology, Basic Medical College, Jiamusi University, Jiamusi 154007; Wang Yimei

2010-11-01

A metabonomic approach using {sup 1}H NMR spectroscopy was adopted to investigate the metabonomic pattern of rat urine after oral administration of environmental endocrine disruptors (EDs) polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) alone or in combination and to explore the possible hepatotoxic mechanisms of combined exposure to PCBs and TCDD. {sup 1}H NMR spectra of urines collected 24 h before and after exposure were analyzed via pattern recognition by using principal component analysis (PCA). Serum biochemistry and liver histopathology indicated significant hepatotoxicity in the rats of the combined group. The PCA scores plots of urinary {sup 1}H NMR datamore » showed that all the treatment groups could be easily distinguished from the control group, so could the PCBs or TCDD group and the combined group. The loadings plots of the PCA revealed remarkable increases in the levels of lactate, glucose, taurine, creatine, and 2-hydroxy-isovaleric acid and reductions in the levels of 2-oxoglutarate, citrate, succinate, hippurate, and trimethylamine-N-oxide in rat urine after exposure. These changes were more striking in the combined group. The changed metabolites may be considered possible biomarker for the hepatotoxicity. The present study demonstrates that combined exposure to PCBs and TCDD induced significant hepatotoxicity in rats, and mitochondrial dysfunction and fatty acid metabolism perturbations might contribute to the hepatotoxicity. There was good conformity between changes in the urine metabonomic pattern and those in serum biochemistry and liver histopathology. These results showed that the NMR-based metabonomic approach may provide a promising technique for the evaluation of the combined toxicity of EDs.« less

Rapid acquisition of data dense solid-state CPMG NMR spectral sets using multi-dimensional statistical analysis

DOE PAGES

Mason, H. E.; Uribe, E. C.; Shusterman, J. A.

2018-01-01

Tensor-rank decomposition methods have been applied to variable contact time 29 Si{ 1 H} CP/CPMG NMR data sets to extract NMR dynamics information and dramatically decrease conventional NMR acquisition times.

Rapid acquisition of data dense solid-state CPMG NMR spectral sets using multi-dimensional statistical analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mason, H. E.; Uribe, E. C.; Shusterman, J. A.

Tensor-rank decomposition methods have been applied to variable contact time 29 Si{ 1 H} CP/CPMG NMR data sets to extract NMR dynamics information and dramatically decrease conventional NMR acquisition times.

Using NMR to Determine Protein Structure in Solution

NASA Astrophysics Data System (ADS)

Cavagnero, Silvia

2003-02-01

Nuclear magnetic resonance (NMR) is a marvelous spectroscopic technique that chemists, physicists, and biochemists routinely employ for their research around the world. This year half of the Nobel Prize for chemistry went to Kurt Wüthrich, who was recognized for the development of NMR-based techniques that lead to the structure determination of biomolecules in solution. In addition to implementing novel pulse sequences and software packages, Wüthrich also applied his methods to several biological systems of key importance to human health. These include the prion protein, which is heavily involved in the spongiform encephalopathy (best known as 'mad cow disease'), which recently caused numerous human deaths, particularly in the UK, due to ingestion of contaminated meat. Transverse relaxation optimized spectroscopy (TROSY) is the most intriguing new NMR method recently developed by Wüthrich and coworkers. This and other closely related pulse sequences promise to play a pivotal role in the extension of NMR to the conformational analysis of very large (up to the megadalton range) macromolecules and macromolecular complexes. More exciting new developments are expected in the near future.

Pentacyclic antibiotics from a tidal mud flat-derived actinomycete.

PubMed

Moon, Kyuho; Chung, Beomkoo; Shin, Yoonho; Rheingold, Arnold L; Moore, Curtis E; Park, Sung Jean; Park, Sunghyouk; Lee, Sang Kook; Oh, Ki-Bong; Shin, Jongheon; Oh, Dong-Chan

2015-03-27

The combination of investigating a unique source of chemically prolific bacterium with an LC/MS-based bacterial strain selection approach resulted in the discovery of two new secondary metabolites, buanmycin (1) and buanquinone (2), from the culture of a marine Streptomyces strain, which was isolated from a tidal mudflat in Buan, Republic of Korea. The carbon backbone of buanmycin (1), comprising 20 quaternary carbons out of 30 total carbons, was determined via (13)C-(13)C COSY NMR analysis after labeling 1 with (13)C by culturing the bacterium with (13)C-glucose. The complete structure of 1 was confidently elucidated, primarily based on 1D and 2D NMR spectroscopic and X-ray crystallographic analysis, as that of a new pentacyclic xanthone. The absolute configuration of the α-methyl serine unit in 1 was established by applying the advanced Marfey's method. The structure of buanquinone (2) was determined to be a new pentacyclic quinone based on NMR and MS spectroscopic data. Buanmycin exhibited potent cytotoxicity against colorectal carcinoma cells (HCT-116) and gastric carcinoma cells (SNU-638) with submicromolar IC50 values and strongly inhibited the pathogenic Gram-negative bacterium Salmonella enterica (MIC = 0.7 μM). In particular, buanmycin demonstrated inhibition of sortase A, which is a promising target for antibiotic discovery.

Acid-base equilibrium in aqueous solutions of 1,3-dimethylbarbituric acid as studied by 13C NMR spectroscopy

NASA Astrophysics Data System (ADS)

Gryff-Keller, A.; Kraska-Dziadecka, A.

2011-12-01

13C NMR spectra of 1,3-dimethylbarbituric acid in aqueous solutions of various acidities and for various solute concentrations have been recorded and interpreted. The spectra recorded at pH = 2 and below contain the signals of the neutral solute molecule exclusively, while the ones recorded at pH = 7 and above only the signals of the appropriate anion, which has been confirmed by theoretical GIAO-DFT calculations. The signals in the spectra recorded for solutions of pH < 7 show dynamic broadenings. The lineshape analysis of these signals has provided information on the kinetics of the processes running in the dynamic acid-base equilibrium. The kinetic data determined this way have been used to clarify the mechanisms of these processes. The numerical analysis has shown that under the investigated conditions deprotonation of the neutral solute molecules undergoes not only via a simple transfer of the C-H proton to water molecules but also through a process with participation of the barbiturate anions. Moreover, the importance of tautomerism, or association, or both these phenomena for the kinetics of the acid-base transformations in the investigated system has been shown. Qualitatively similar changes of 13C NMR spectra with the solution pH variation have been observed for the parent barbituric acid.

Can NMR solve some significant challenges in metabolomics?

PubMed Central

Gowda, G.A. Nagana; Raftery, Daniel

2015-01-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact biospecimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. PMID:26476597

Can NMR solve some significant challenges in metabolomics?

NASA Astrophysics Data System (ADS)

Nagana Gowda, G. A.; Raftery, Daniel

2015-11-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory.

Rapid discrimination of strain-dependent fermentation characteristics among Lactobacillus strains by NMR-based metabolomics of fermented vegetable juice

PubMed Central

Nakamura, Toshihide; Sekiyama, Yasuyo; Kikuchi, Jun

2017-01-01

In this study, we investigated the applicability of NMR-based metabolomics to discriminate strain-dependent fermentation characteristics of lactic acid bacteria (LAB), which are important microorganisms for fermented food production. To evaluate the discrimination capability, six type strains of Lactobacillus species and six additional L. brevis strains were used focusing on i) the difference between homo- and hetero-lactic fermentative species and ii) strain-dependent characteristics within L. brevis. Based on the differences in the metabolite profiles of fermented vegetable juices, non-targeted principal component analysis (PCA) clearly separated the samples into those inoculated with homo- and hetero-lactic fermentative species. The separation was primarily explained by the different levels of dominant metabolites (lactic acid, acetic acid, ethanol, and mannitol). Orthogonal partial least squares discrimination analysis, based on a regions-of-interest (ROIs) approach, revealed the contribution of low-abundance metabolites: acetoin, phenyllactic acid, p-hydroxyphenyllactic acid, glycerophosphocholine, and succinic acid for homolactic fermentation; and ornithine, tyramine, and γ-aminobutyric acid (GABA) for heterolactic fermentation. Furthermore, ROIs-based PCA of seven L. brevis strains separated their strain-dependent fermentation characteristics primarily based on their ability to utilize sucrose and citric acid, and convert glutamic acid and tyrosine into GABA and tyramine, respectively. In conclusion, NMR metabolomics successfully discriminated the fermentation characteristics of the tested strains and provided further information on metabolites responsible for these characteristics, which may impact the taste, aroma, and functional properties of fermented foods. PMID:28759594

NMR-Fragment Based Virtual Screening: A Brief Overview.

PubMed

Singh, Meenakshi; Tam, Benjamin; Akabayov, Barak

2018-01-25

Fragment-based drug discovery (FBDD) using NMR has become a central approach over the last twenty years for development of small molecule inhibitors against biological macromolecules, to control a variety of cellular processes. Yet, several considerations should be taken into account for obtaining a therapeutically relevant agent. In this review, we aim to list the considerations that make NMR fragment screening a successful process for yielding potent inhibitors. Factors that may govern the competence of NMR in fragment based drug discovery are discussed, as well as later steps that involve optimization of hits obtained by NMR-FBDD.

NMR solution structure study of one saturated sulphur-containing amides from Glycosmis lucida.

PubMed

Geng, Zhu-Feng; Yang, Kai; Li, Yin-Ping; Guo, Shan-Shan; You, Chun-Xue; Zhang, Wen-Juan; Zhang, Zhe; Du, Shu-Shan

2017-04-01

One sulphur-containing amide (N-[2-(4-Hydroxyphenyl)-ethyl]-3-methanesulfonyl-N-methyl-propionamide) which was isolated from Glycosmis lucida Wall ex Huang had a different NMR profile with this kind of compounds' normal case. Based on the information obtained by nuclear magnetic resonance pectroscopy (NMR) and mass spectrometry (MS), its configurations in solution were investigated. The results indicated that the compound would have two stable configurations in solution as the double bond switched between C-N and C-O in an appropriate rate. This phenomenon was clearly exposed by the one dimension selective NOE (1D-NOE) experiments. This conclusion would play an active role in the structure analysis work of this kind of compounds.

Fourier Analysis and Structure Determination. Part II: Pulse NMR and NMR Imaging.

ERIC Educational Resources Information Center

Chesick, John P.

1989-01-01

Uses simple pulse NMR experiments to discuss Fourier transforms. Studies the generation of spin echoes used in the imaging procedure. Shows that pulse NMR experiments give signals that are additions of sinusoids of differing amplitudes, frequencies, and phases. (MVL)

Long-range anisotropic effects in a V-shaped Tröger's base diformanilide: Conformational study by NMR assignment and DFT calculations

NASA Astrophysics Data System (ADS)

Trupp, Leandro; Laurella, Sergio L.; Tettamanzi, M. Cristina; Barja, Beatriz C.; Bruttomesso, Andrea C.

2018-04-01

Herein we describe the synthesis and conformational analysis of a Tröger's base diformanilide whose distinctive NMR spectra was fully assigned via DFT calculations. The complexity of the spectra originated by the presence of three conformers in equilibrium shows that the nuclei in each side of the molecule are sensitive to the configuration not only of the closest formamide moiety but also of the farthest one, due to long-range anisotropic effects. The temperature and the solvent polarity influence were analyzed to determine the different conformer populations and the corresponding rotational activation parameters.

Effects of CO2 injection and Kerogen Maturation on Low-Field Nuclear Magnetic Resonance Response

NASA Astrophysics Data System (ADS)

Prasad, M.; Livo, K.

2017-12-01

Low-field Nuclear Magnetic Resonance (NMR) is commonly used in petrophysical analysis of petroleum reservoir rocks. NMR experiments record the relaxation and polarization of in-situ hydrogen protons present in gaseous phases such as free-gas intervals and solution gas fluids, bulk fluid phases such as oil and aquifer intervals, and immovable fractions of kerogen and bitumen. Analysis of NMR relaxation spectra is performed to record how fluid composition, maturity, and viscosity change NMR experimental results. We present T1-T2 maps as thermal maturity of a water-saturated, sub-mature Woodford shale is increased at temperatures from 125 to 400 degrees Celsius. Experiments with applied fluid pressure in paraffinic mineral oil and DI water with varying fluid pH have been performed to mimic reservoir conditions in analysis of the relaxation of bulk fluid phases. We have recorded NMR spectra, T1-T2 maps, and fluid diffusion coefficients using a low-field (2 MHz) MagritekTM NMR. CO2 was injected at a pressure of 900 psi in an in house developed NMR pressure vessel made of torlon plastic. Observable 2D NMR shifts in immature kerogen formations as thermal maturity is increased show generation of lighter oils with increased maturity. CO2 injection leads to a decrease in bulk fluid relaxation time that is attributed to viscosity modification with gas presence. pH variation with increased CO2 presence were shown to not effect NMR spectra. From this, fluid properties have been shown to greatly affect NMR readings and must be taken into account for more accurate NMR reservoir characterization.

Nmrglue: an open source Python package for the analysis of multidimensional NMR data.

PubMed

Helmus, Jonathan J; Jaroniec, Christopher P

2013-04-01

Nmrglue, an open source Python package for working with multidimensional NMR data, is described. When used in combination with other Python scientific libraries, nmrglue provides a highly flexible and robust environment for spectral processing, analysis and visualization and includes a number of common utilities such as linear prediction, peak picking and lineshape fitting. The package also enables existing NMR software programs to be readily tied together, currently facilitating the reading, writing and conversion of data stored in Bruker, Agilent/Varian, NMRPipe, Sparky, SIMPSON, and Rowland NMR Toolkit file formats. In addition to standard applications, the versatility offered by nmrglue makes the package particularly suitable for tasks that include manipulating raw spectrometer data files, automated quantitative analysis of multidimensional NMR spectra with irregular lineshapes such as those frequently encountered in the context of biomacromolecular solid-state NMR, and rapid implementation and development of unconventional data processing methods such as covariance NMR and other non-Fourier approaches. Detailed documentation, install files and source code for nmrglue are freely available at http://nmrglue.com. The source code can be redistributed and modified under the New BSD license.

Nmrglue: An Open Source Python Package for the Analysis of Multidimensional NMR Data

PubMed Central

Helmus, Jonathan J.; Jaroniec, Christopher P.

2013-01-01

Nmrglue, an open source Python package for working with multidimensional NMR data, is described. When used in combination with other Python scientific libraries, nmrglue provides a highly flexible and robust environment for spectral processing, analysis and visualization and includes a number of common utilities such as linear prediction, peak picking and lineshape fitting. The package also enables existing NMR software programs to be readily tied together, currently facilitating the reading, writing and conversion of data stored in Bruker, Agilent/Varian, NMRPipe, Sparky, SIMPSON, and Rowland NMR Toolkit file formats. In addition to standard applications, the versatility offered by nmrglue makes the package particularly suitable for tasks that include manipulating raw spectrometer data files, automated quantitative analysis of multidimensional NMR spectra with irregular lineshapes such as those frequently encountered in the context of biomacromolecular solid-state NMR, and rapid implementation and development of unconventional data processing methods such as covariance NMR and other non-Fourier approaches. Detailed documentation, install files and source code for nmrglue are freely available at http://nmrglue.com. The source code can be redistributed and modified under the New BSD license. PMID:23456039

1H-NMR METABONOMICS ANALYSIS OF SERA DIFFERENTIATES BETWEEN MAMMARY TUMOR-BEARING MICE AND HEALTHY CONTROLS

EPA Science Inventory

Global analysis of 1H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1H-NMR metabonomic analyses on serum samples ob...

Spectral analysis, vibrational assignments, NBO analysis, NMR, UV-Vis, hyperpolarizability analysis of 2-aminofluorene by density functional theory.

PubMed

Jone Pradeepa, S; Sundaraganesan, N

2014-05-05

In this present investigation, the collective experimental and theoretical study on molecular structure, vibrational analysis and NBO analysis has been reported for 2-aminofluorene. FT-IR spectrum was recorded in the range 4000-400 cm(-1). FT-Raman spectrum was recorded in the range 4000-50 cm(-1). The molecular geometry, vibrational spectra, and natural bond orbital analysis (NBO) were calculated for 2-aminofluorene using Density Functional Theory (DFT) based on B3LYP/6-31G(d,p) model chemistry. (13)C and (1)H NMR chemical shifts of 2-aminofluorene were calculated using GIAO method. The computed vibrational and NMR spectra were compared with the experimental results. The total energy distribution (TED) was derived to deepen the understanding of different modes of vibrations contributed by respective wavenumber. The experimental UV-Vis spectra was recorded in the region of 400-200 nm and correlated with simulated spectra by suitably solvated B3LYP/6-31G(d,p) model. The HOMO-LUMO energies were measured with time dependent DFT approach. The nonlinearity of the title compound was confirmed by hyperpolarizabilty examination. Using theoretical calculation Molecular Electrostatic Potential (MEP) was investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Biological variation of Vanilla planifolia leaf metabolome.

PubMed

Palama, Tony Lionel; Fock, Isabelle; Choi, Young Hae; Verpoorte, Robert; Kodja, Hippolyte

2010-04-01

The metabolomic analysis of Vanilla planifolia leaves collected at different developmental stages was carried out using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis in order to evaluate their variation. Ontogenic changes of the metabolome were considered since leaves of different ages were collected at two different times of the day and in two different seasons. Principal component analysis (PCA) and partial least square modeling discriminate analysis (PLS-DA) of (1)H NMR data provided a clear separation according to leaf age, time of the day and season of collection. Young leaves were found to have higher levels of glucose, bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-isopropyltartrate (glucoside A) and bis[4-(beta-D-glucopyranosyloxy)-benzyl]-2-(2-butyl)-tartrate (glucoside B), whereas older leaves had more sucrose, acetic acid, homocitric acid and malic acid. Results obtained from PLS-DA analysis showed that leaves collected in March 2008 had higher levels of glucosides A and B as compared to those collected in August 2007. However, the relative standard deviation (RSD) exhibited by the individual values of glucosides A and B showed that those compounds vary more according to their developmental stage (50%) than to the time of day or the season in which they were collected (19%). Although morphological variations of the V. planifolia accessions were observed, no clear separation of the accessions was determined from the analysis of the NMR spectra. The results obtained in this study, show that this method based on the use of (1)H NMR spectroscopy in combination with multivariate analysis has a great potential for further applications in the study of vanilla leaf metabolome. Copyright 2009 Elsevier Ltd. All rights reserved.

Synthesis of palm oil fatty acid and trimethylolpropane based ester for biolubricant base stocks

NASA Astrophysics Data System (ADS)

Nor, Nurazira Mohd; Derawi, Darfizzi; Salimon, Jumat

2018-04-01

RBD palm oil become one of the interesting renewable resources in biolubricant application. However, palm oil cannot be used directly as lubricant due to some performance limitations such as thermal and oxidative stability. This drawback can be overcome by chemical modification through esterification with polyhydric alcohol such as trimethylolpropane (TMP). The synthesis of ester was carried out via esterification of palm oil fatty acid (POFA) with TMP in the presence of 2% sulphuric acid as catalyst at 150 °C for 5 hours. Gas Chromatography equipped with a Flame Ionization Detector (GC-FID) was used to determine the percentage composition of POTMP ester. The structure confirmation of POTMP ester was proven by Fourier Transformation Infra-Red (FTIR), proton and carbon Nuclear Magnetic Resonance (1H-NMR and 13C-NMR) spectroscopy analysis. The result showed that POTMP ester has successfully synthesized with 97.7% composition of triesters (TE), proved by GC chromatogram. Presence of ester group also evidenced by 1H NMR at 2.27-2.30 ppm and 13C NMR at 173.52-173.54 ppm. The percentage yield of POTMP ester produced was 82% and exist in liquid form at room temperature.

NMR-Based Metabolomic Study on Isatis tinctoria: Comparison of Different Accessions, Harvesting Dates, and the Effect of Repeated Harvesting.

PubMed

Guldbrandsen, Niels; Kostidis, Sarantos; Schäfer, Hartmut; De Mieri, Maria; Spraul, Manfred; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Hamburger, Matthias

2015-05-22

Isatis tinctoria is an ancient dye and medicinal plant with potent anti-inflammatory and antiallergic properties. Metabolic differences were investigated by NMR spectroscopy of accessions from different origins that were grown under identical conditions on experimental plots. For these accessions, metabolite profiles at different harvesting dates were analyzed, and single and repeatedly harvested plants were compared. Leaf samples were shock-frozen in liquid N2 immediately after being harvested, freeze-dried, and cryomilled prior to extraction. Extracts were prepared by pressurized liquid extraction with ethyl acetate and 70% aqueous methanol. NMR spectra were analyzed using a combination of different methods of multivariate data analysis such as principal component analysis (PCA), canonical analysis (CA), and k-nearest neighbor concept (k-NN). Accessions and harvesting dates were well separated in the PCA/CA/k-NN analysis in both extracts. Pairwise statistical total correlation spectroscopy (STOCSY) revealed unsaturated fatty acids, porphyrins, carbohydrates, indole derivatives, isoprenoids, phenylpropanoids, and minor aromatic compounds as the cause of these differences. In addition, the metabolite profile was affected by the repeated harvest regime, causing a decrease of 1,5-anhydroglucitol, sucrose, unsaturated fatty acids, porphyrins, isoprenoids, and a flavonoid.

Robust and transferable quantification of NMR spectral quality using IROC analysis

NASA Astrophysics Data System (ADS)

Zambrello, Matthew A.; Maciejewski, Mark W.; Schuyler, Adam D.; Weatherby, Gerard; Hoch, Jeffrey C.

2017-12-01

Non-Fourier methods are increasingly utilized in NMR spectroscopy because of their ability to handle nonuniformly-sampled data. However, non-Fourier methods present unique challenges due to their nonlinearity, which can produce nonrandom noise and render conventional metrics for spectral quality such as signal-to-noise ratio unreliable. The lack of robust and transferable metrics (i.e. applicable to methods exhibiting different nonlinearities) has hampered comparison of non-Fourier methods and nonuniform sampling schemes, preventing the identification of best practices. We describe a novel method, in situ receiver operating characteristic analysis (IROC), for characterizing spectral quality based on the Receiver Operating Characteristic curve. IROC utilizes synthetic signals added to empirical data as "ground truth", and provides several robust scalar-valued metrics for spectral quality. This approach avoids problems posed by nonlinear spectral estimates, and provides a versatile quantitative means of characterizing many aspects of spectral quality. We demonstrate applications to parameter optimization in Fourier and non-Fourier spectral estimation, critical comparison of different methods for spectrum analysis, and optimization of nonuniform sampling schemes. The approach will accelerate the discovery of optimal approaches to nonuniform sampling experiment design and non-Fourier spectrum analysis for multidimensional NMR.

Studies on the biosynthesis of vitamin B sub 2 and vitamin B sub 12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, H.C.

1988-01-01

Feeding experiments with Ashbya gossypii followed by NMR analysis of the resulting riboflavin showed incorporation of deuterium from D-(2-{sup 2}H)ribose at C-2{prime} and from D-(1-{sup 2}H)ribose in the pro-R position at C-1{prime} of the ribityl side chain. The results rule out an Amadori rearrangement mechanism for the reduction of the ribosylamino to the ribitylamino linkage and point to formation of a Schiff base that is reduced stereospecifically opposite to the face from which the oxygen has departed. As prerequisite for the analysis, the {sup 1}H NMR signals for the pro-R and pro-S hydrogens at C-1{prime} of riboflavin and its tetraacetatemore » were assigned with the aid of synthetic stereospecifically deuteriated samples. Feeding experiments with Propionibacterium shermianii followed by NMR analysis of the resulting vitamin B{sub 12} showed: (1) 5-methylbenzimidazole (5MBI) incorporated and only one regioisomer (B6-demethylcyanocobalamin)formed. (2) 8-demethylriboflavin incorporated and the same regioisomer was obtained as 5MBI experiment. (3) (1{prime}-{sup 13}C, 5-{sup 15}N)riboflavin incorporated and {sup 13}C-NMR showed that {sup 13}C at the B2 position of cyanocobalamin coupled to both adjacent nitrogen-15 atoms at about the same ratio.« less

Time-Domain Nuclear Magnetic Resonance (TD-NMR) and Chemometrics for Determination of Fat Content in Commercial Products of Milk Powder.

PubMed

Nascimento, Paloma Andrade Martins; Barsanelli, Paulo Lopes; Rebellato, Ana Paula; Pallone, Juliana Azevedo Lima; Colnago, Luiz Alberto; Pereira, Fabíola Manhas Verbi

2017-03-01

This study shows the use of time-domain (TD)-NMR transverse relaxation (T2) data and chemometrics in the nondestructive determination of fat content for powdered food samples such as commercial dried milk products. Most proposed NMR spectroscopy methods for measuring fat content correlate free induction decay or echo intensities with the sample's mass. The need for the sample's mass limits the analytical frequency of NMR determination, because weighing the samples is an additional step in this procedure. Therefore, the method proposed here is based on a multivariate model of T2 decay, measured with Carr-Purcell-Meiboom-Gill pulse sequence and reference values of fat content. The TD-NMR spectroscopy method shows high correlation (r = 0.95) with the lipid content, determined by the standard extraction method of Bligh and Dyer. For comparison, fat content determination was also performed using a multivariate model with near-IR (NIR) spectroscopy, which is also a nondestructive method. The advantages of the proposed TD-NMR method are that it (1) minimizes toxic residue generation, (2) performs measurements with high analytical frequency (a few seconds per analysis), and (3) does not require sample preparation (such as pelleting, needed for NIR spectroscopy analyses) or weighing the samples.

Publication of nuclear magnetic resonance experimental data with semantic web technology and the application thereof to biomedical research of proteins.

PubMed

Yokochi, Masashi; Kobayashi, Naohiro; Ulrich, Eldon L; Kinjo, Akira R; Iwata, Takeshi; Ioannidis, Yannis E; Livny, Miron; Markley, John L; Nakamura, Haruki; Kojima, Chojiro; Fujiwara, Toshimichi

2016-05-05

The nuclear magnetic resonance (NMR) spectroscopic data for biological macromolecules archived at the BioMagResBank (BMRB) provide a rich resource of biophysical information at atomic resolution. The NMR data archived in NMR-STAR ASCII format have been implemented in a relational database. However, it is still fairly difficult for users to retrieve data from the NMR-STAR files or the relational database in association with data from other biological databases. To enhance the interoperability of the BMRB database, we present a full conversion of BMRB entries to two standard structured data formats, XML and RDF, as common open representations of the NMR-STAR data. Moreover, a SPARQL endpoint has been deployed. The described case study demonstrates that a simple query of the SPARQL endpoints of the BMRB, UniProt, and Online Mendelian Inheritance in Man (OMIM), can be used in NMR and structure-based analysis of proteins combined with information of single nucleotide polymorphisms (SNPs) and their phenotypes. We have developed BMRB/XML and BMRB/RDF and demonstrate their use in performing a federated SPARQL query linking the BMRB to other databases through standard semantic web technologies. This will facilitate data exchange across diverse information resources.

NMR conformational properties of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vourtsis, Dionysios J.; Chasapis, Christos T.; Pairas, George

2014-07-18

Highlights: • A polypeptide, N-ALF{sub 233}, was overexpressed in E. coli and successfully isolated. • We produced {sup 2}H/{sup 15}N/{sup 13}C labeled protein samples. • Amino acid selective approaches were applied. • We acquired several heteronuclear NMR spectra, to complete the backbone assignment. • Prediction of the secondary structure was performed. - Abstract: NMR-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution NMR spectra and their subsequent analysis. Especially for bigger proteins (>20 kDa) selective labeling is a frequently used means of sequence-specific assignment. In this work we present the successfulmore » overexpression of a polypeptide of 233 residues, corresponding to the structured part of the N-terminal domain of Anthrax Lethal Factor, using Escherichia coli expression system. The polypeptide was subsequently isolated in pure, soluble form and analyzed structurally by solution NMR spectroscopy. Due to the non-satisfying quality and resolution of the spectra of this 27 kDa protein, an almost complete backbone assignment became feasible only by the combination of uniform and novel amino acid-selective labeling schemes. Moreover, amino acid-type selective triple-resonance NMR experiments proved to be very helpful.« less

Micro-structural characterization of the hydration products of bauxite-calcination-method red mud-coal gangue based cementitious materials.

PubMed

Liu, Xiaoming; Zhang, Na; Yao, Yuan; Sun, Henghu; Feng, Huan

2013-11-15

In this research, the micro-structural characterization of the hydration products of red mud-coal gangue based cementitious materials has been investigated through SEM-EDS, (27)Al MAS NMR and (29)Si MAS NMR techniques, in which the used red mud was derived from the bauxite calcination method. The results show that the red mud-coal gangue based cementitious materials mainly form fibrous C-A-S-H gel, needle-shaped/rod-like AFt in the early hydration period. With increasing of the hydration period, densification of the pastes were promoted resulting in the development of strength. EDS analysis shows that with the Ca/Si of red mud-coal gangue based cementitious materials increases, the average Ca/Si and Ca/(Si+Al) atomic ratio of C-A-S-H gel increases, while the average Al/Si atomic ratio of C-A-S-H gel decreases. MAS NMR analysis reveals that Al in the hydration products of red mud-coal gangue based cementitious materials exists in the forms of Al(IV) and Al(VI), but mainly in the form of Al(VI). Increasing the Ca/Si ratio of raw material promotes the conversion of [AlO4] to [AlO6] and inhibits the combination between [AlO4] and [SiO4] to form C-A-S-H gel. Meanwhile, the polymerization degree of [SiO4] in the hydration products declines. Published by Elsevier B.V.

NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer.

PubMed

Lin, Yan; Ma, Changchun; Liu, Chengkang; Wang, Zhening; Yang, Jurong; Liu, Xinmu; Shen, Zhiwei; Wu, Renhua

2016-05-17

Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its earlier detection for optimal disease management. A metabolomics based approach provides potential for noninvasive identification of biomarkers of colorectal carcinogenesis, as well as dissection of molecular pathways of pathophysiological conditions. Here, proton nuclear magnetic resonance spectroscopy (1HNMR) -based metabolomic approach was used to profile fecal metabolites of 68 CRC patients (stage I/II=20; stage III=25 and stage IV=23) and 32 healthy controls (HC). Pattern recognition through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied on 1H-NMR processed data for dimension reduction. OPLS-DA revealed that each stage of CRC could be clearly distinguished from HC based on their metabolomic profiles. Successive analyses identified distinct disturbances to fecal metabolites of CRC patients at various stages, compared with those in cancer free controls, including reduced levels of acetate, butyrate, propionate, glucose, glutamine, and elevated quantities of succinate, proline, alanine, dimethylglycine, valine, glutamate, leucine, isoleucine and lactate. These altered fecal metabolites potentially involved in the disruption of normal bacterial ecology, malabsorption of nutrients, increased glycolysis and glutaminolysis. Our findings revealed that the fecal metabolic profiles of healthy controls can be distinguished from CRC patients, even in the early stage (stage I/II), highlighting the potential utility of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients.

NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer

PubMed Central

Lin, Yan; Ma, Changchun; Liu, Chengkang; Wang, Zhening; Yang, Jurong; Liu, Xinmu; Shen, Zhiwei; Wu, Renhua

2016-01-01

Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its earlier detection for optimal disease management. A metabolomics based approach provides potential for noninvasive identification of biomarkers of colorectal carcinogenesis, as well as dissection of molecular pathways of pathophysiological conditions. Here, proton nuclear magnetic resonance spectroscopy (1HNMR) -based metabolomic approach was used to profile fecal metabolites of 68 CRC patients (stage I/II=20; stage III=25 and stage IV=23) and 32 healthy controls (HC). Pattern recognition through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied on 1H-NMR processed data for dimension reduction. OPLS-DA revealed that each stage of CRC could be clearly distinguished from HC based on their metabolomic profiles. Successive analyses identified distinct disturbances to fecal metabolites of CRC patients at various stages, compared with those in cancer free controls, including reduced levels of acetate, butyrate, propionate, glucose, glutamine, and elevated quantities of succinate, proline, alanine, dimethylglycine, valine, glutamate, leucine, isoleucine and lactate. These altered fecal metabolites potentially involved in the disruption of normal bacterial ecology, malabsorption of nutrients, increased glycolysis and glutaminolysis. Our findings revealed that the fecal metabolic profiles of healthy controls can be distinguished from CRC patients, even in the early stage (stage I/II), highlighting the potential utility of NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in CRC patients. PMID:27107423

The GNAT: A new tool for processing NMR data.

PubMed

Castañar, Laura; Poggetto, Guilherme Dal; Colbourne, Adam A; Morris, Gareth A; Nilsson, Mathias

2018-06-01

The GNAT (General NMR Analysis Toolbox) is a free and open-source software package for processing, visualising, and analysing NMR data. It supersedes the popular DOSY Toolbox, which has a narrower focus on diffusion NMR. Data import of most common formats from the major NMR platforms is supported, as well as a GNAT generic format. Key basic processing of NMR data (e.g., Fourier transformation, baseline correction, and phasing) is catered for within the program, as well as more advanced techniques (e.g., reference deconvolution and pure shift FID reconstruction). Analysis tools include DOSY and SCORE for diffusion data, ROSY T 1 /T 2 estimation for relaxation data, and PARAFAC for multilinear analysis. The GNAT is written for the MATLAB® language and comes with a user-friendly graphical user interface. The standard version is intended to run with a MATLAB installation, but completely free-standing compiled versions for Windows, Mac, and Linux are also freely available. © 2018 The Authors Magnetic Resonance in Chemistry Published by John Wiley & Sons Ltd.

NMR Analysis of Unknowns: An Introduction to 2D NMR Spectroscopy

ERIC Educational Resources Information Center

Alonso, David E.; Warren, Steven E.

2005-01-01

A study combined 1D (one-dimensional) and 2D (two-dimensional) NMR spectroscopy to solve structural organic problems of three unknowns, which include 2-, 3-, and 4-heptanone. Results showed [to the first power]H NMR and [to the thirteenth power]C NMR signal assignments for 2- and 3-heptanone were more challenging than for 4-heptanone owing to the…

1H NMR and PCA-based analysis revealed variety dependent changes in phenolic contents of apple fruit after drying.

PubMed

Francini, Alessandra; Romeo, Stefania; Cifelli, Mario; Gori, Daniele; Domenici, Valentina; Sebastiani, Luca

2017-04-15

Dry and fresh apples have been studied monitoring their polyphenolic profiles through 1 H NMR, antioxidant capacity and total polyphenol content. Six ancient and underutilized apple varieties (Mantovana, Mora, Nesta, Cipolla, Ruggina, Sassola) and a commercial one (Golden Delicious) were dried with an air-drying system at 45°C for 19h. Although some of their polyphenol constituents were lost during drying, the antioxidant capacity of some apple varieties remained higher compared to Golden Delicious. This result is very important for ancient and underutilized varieties that are not consumed on large scale as fresh product since they have low attractiveness, due to their ugly appearance. Combining quantitative NMR spectroscopy with principal component analysis we have identified and quantified several polyphenols (such as catechin, epicathechin, and chlorogenic acid) that are important to establish the nutraceutical value of the different investigated apple varieties. Copyright © 2016 Elsevier Ltd. All rights reserved.

NMR analysis of biodiesel

USDA-ARS?s Scientific Manuscript database

Biodiesel is usually analyzed by the various methods called for in standards such as ASTM D6751 and EN 14214. Nuclear magnetic resonance (NMR) is not one of these methods. However, NMR, with 1H-NMR commonly applied, can be useful in a variety of applications related to biodiesel. These include monit...

qHNMR Analysis of Purity of Common Organic Solvents--An Undergraduate Quantitative Analysis Laboratory Experiment

ERIC Educational Resources Information Center

Bell, Peter T.; Whaley, W. Lance; Tochterman, Alyssa D.; Mueller, Karl S.; Schultz, Linda D.

2017-01-01

NMR spectroscopy is currently a premier technique for structural elucidation of organic molecules. Quantitative NMR (qNMR) methodology has developed more slowly but is now widely accepted, especially in the areas of natural product and medicinal chemistry. However, many undergraduate students are not routinely exposed to this important concept.…

The ratio of acetate-to-glucose oxidation in astrocytes from a single 13C NMR spectrum of cerebral cortex.

PubMed

Marin-Valencia, Isaac; Hooshyar, M Ali; Pichumani, Kumar; Sherry, A Dean; Malloy, Craig R

2015-01-01

The (13) C-labeling patterns in glutamate and glutamine from brain tissue are quite different after infusion of a mixture of (13) C-enriched glucose and acetate. Two processes contribute to this observation, oxidation of acetate by astrocytes but not neurons, and preferential incorporation of α-ketoglutarate into glutamate in neurons, and incorporation of α-ketoglutarate into glutamine in astrocytes. The acetate:glucose ratio, introduced previously for analysis of a single (13) C NMR spectrum, provides a useful index of acetate and glucose oxidation in the brain tissue. However, quantitation of relative substrate oxidation at the cell compartment level has not been reported. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes, based on the standard assumption that neurons do not oxidize acetate. Mice were infused with [1,2-(13) C]acetate and [1,6-(13) C]glucose, and proton decoupled (13) C NMR spectra of cortex extracts were acquired. A fit of those spectra to the model indicated that (13) C-labeled acetate and glucose contributed approximately equally to acetyl-CoA (0.96) in astrocytes. As this method relies on a single (13) C NMR spectrum, it can be readily applied to multiple physiologic and pathologic conditions. Differences in (13) C labeling of brain glutamate and glutamine have been attributed to metabolic compartmentation. The acetate:glucose ratio, introduced for description of a (13) C NMR (nuclear magnetic resonance) spectrum, is an index of glucose and acetate oxidation in brain tissue. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes from a single NMR spectrum. As kinetic analysis is not required, the method is readily applicable to analysis of tissue extracts. α-KG = alpha-ketoglutarate; CAC = citric acid cycle; GLN = glutamine; GLU = glutamate. © 2014 International Society for Neurochemistry.

Reconstruction of interatomic vectors by principle component analysis of nuclear magnetic resonance data in multiple alignments

NASA Astrophysics Data System (ADS)

Hus, Jean-Christophe; Bruschweiler, Rafael

2002-07-01

A general method is presented for the reconstruction of interatomic vector orientations from nuclear magnetic resonance (NMR) spectroscopic data of tensor interactions of rank 2, such as dipolar coupling and chemical shielding anisotropy interactions, in solids and partially aligned liquid-state systems. The method, called PRIMA, is based on a principal component analysis of the covariance matrix of the NMR parameters collected for multiple alignments. The five nonzero eigenvalues and their eigenvectors efficiently allow the approximate reconstruction of the vector orientations of the underlying interactions. The method is demonstrated for an isotropic distribution of sample orientations as well as for finite sets of orientations and internuclear vectors encountered in protein systems.

Study of mixed Ca-Zn hydroxyapatite surface modified by lactic acid

NASA Astrophysics Data System (ADS)

Turki, Thouraya; Aissa, Abdallah; Bac, Christophe Goze; Rachdi, Férid; Debbabi, Mongi

2012-07-01

The new hybrid inorganic-organic composites, Ca(10-x)Znx(PO4)6(OH)2-lactic acid, at different amounts of zinc and lactic acid were prepared by dissolution of the organic compound in an hydroxyapatite suspension. They were characterized by XRD, IR, MAS NMR (13C and 1H) and chemical analysis. The crystallinity was slightly affected by the presence of organic fragments. IR and (13C and 1H) MAS NMR measurements indicate that the carboxylic groups of the acid interact with calcium and zinc ions of hydroxyapatite surface. Chemical analysis displays that zinc promotes the acid grafting. A mechanism of surface modification is proposed based on the obtained results.

NMR-based metabolomic urinalysis: a rapid screening test for urinary tract infection.

PubMed

Lam, Ching-Wan; Law, Chun-Yiu; To, Kelvin Kai-Wang; Cheung, Stanley Kwok-Kuen; Lee, Kim-Chung; Sze, Kong-Hung; Leung, Ka-Fai; Yuen, Kwok-Yung

2014-09-25

Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker. We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples. The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA. Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative analysis of NMR spectra with chemometrics

NASA Astrophysics Data System (ADS)

Winning, H.; Larsen, F. H.; Bro, R.; Engelsen, S. B.

2008-01-01

The number of applications of chemometrics to series of NMR spectra is rapidly increasing due to an emerging interest for quantitative NMR spectroscopy e.g. in the pharmaceutical and food industries. This paper gives an analysis of advantages and limitations of applying the two most common chemometric procedures, Principal Component Analysis (PCA) and Multivariate Curve Resolution (MCR), to a designed set of 231 simple alcohol mixture (propanol, butanol and pentanol) 1H 400 MHz spectra. The study clearly demonstrates that the major advantage of chemometrics is the visualisation of larger data structures which adds a new exploratory dimension to NMR research. While robustness and powerful data visualisation and exploration are the main qualities of the PCA method, the study demonstrates that the bilinear MCR method is an even more powerful method for resolving pure component NMR spectra from mixtures when certain conditions are met.

Optimized slice-selective 1H NMR experiments combined with highly accurate quantitative 13C NMR using an internal reference method

NASA Astrophysics Data System (ADS)

Jézéquel, Tangi; Silvestre, Virginie; Dinis, Katy; Giraudeau, Patrick; Akoka, Serge

2018-04-01

Isotope ratio monitoring by 13C NMR spectrometry (irm-13C NMR) provides the complete 13C intramolecular position-specific composition at natural abundance. It represents a powerful tool to track the (bio)chemical pathway which has led to the synthesis of targeted molecules, since it allows Position-specific Isotope Analysis (PSIA). Due to the very small composition range (which represents the range of variation of the isotopic composition of a given nuclei) of 13C natural abundance values (50‰), irm-13C NMR requires a 1‰ accuracy and thus highly quantitative analysis by 13C NMR. Until now, the conventional strategy to determine the position-specific abundance xi relies on the combination of irm-MS (isotopic ratio monitoring Mass Spectrometry) and 13C quantitative NMR. However this approach presents a serious drawback since it relies on two different techniques and requires to measure separately the signal of all the carbons of the analyzed compound, which is not always possible. To circumvent this constraint, we recently proposed a new methodology to perform 13C isotopic analysis using an internal reference method and relying on NMR only. The method combines a highly quantitative 1H NMR pulse sequence (named DWET) with a 13C isotopic NMR measurement. However, the recently published DWET sequence is unsuited for samples with short T1, which forms a serious limitation for irm-13C NMR experiments where a relaxing agent is added. In this context, we suggest two variants of the DWET called Multi-WET and Profiled-WET, developed and optimized to reach the same accuracy of 1‰ with a better immunity towards T1 variations. Their performance is evaluated on the determination of the 13C isotopic profile of vanillin. Both pulse sequences show a 1‰ accuracy with an increased robustness to pulse miscalibrations compared to the initial DWET method. This constitutes a major advance in the context of irm-13C NMR since it is now possible to perform isotopic analysis with high relaxing agent concentrations, leading to a strong reduction of the overall experiment time.

nmrML: A Community Supported Open Data Standard for the Description, Storage, and Exchange of NMR Data.

PubMed

Schober, Daniel; Jacob, Daniel; Wilson, Michael; Cruz, Joseph A; Marcu, Ana; Grant, Jason R; Moing, Annick; Deborde, Catherine; de Figueiredo, Luis F; Haug, Kenneth; Rocca-Serra, Philippe; Easton, John; Ebbels, Timothy M D; Hao, Jie; Ludwig, Christian; Günther, Ulrich L; Rosato, Antonio; Klein, Matthias S; Lewis, Ian A; Luchinat, Claudio; Jones, Andrew R; Grauslys, Arturas; Larralde, Martin; Yokochi, Masashi; Kobayashi, Naohiro; Porzel, Andrea; Griffin, Julian L; Viant, Mark R; Wishart, David S; Steinbeck, Christoph; Salek, Reza M; Neumann, Steffen

2018-01-02

NMR is a widely used analytical technique with a growing number of repositories available. As a result, demands for a vendor-agnostic, open data format for long-term archiving of NMR data have emerged with the aim to ease and encourage sharing, comparison, and reuse of NMR data. Here we present nmrML, an open XML-based exchange and storage format for NMR spectral data. The nmrML format is intended to be fully compatible with existing NMR data for chemical, biochemical, and metabolomics experiments. nmrML can capture raw NMR data, spectral data acquisition parameters, and where available spectral metadata, such as chemical structures associated with spectral assignments. The nmrML format is compatible with pure-compound NMR data for reference spectral libraries as well as NMR data from complex biomixtures, i.e., metabolomics experiments. To facilitate format conversions, we provide nmrML converters for Bruker, JEOL and Agilent/Varian vendor formats. In addition, easy-to-use Web-based spectral viewing, processing, and spectral assignment tools that read and write nmrML have been developed. Software libraries and Web services for data validation are available for tool developers and end-users. The nmrML format has already been adopted for capturing and disseminating NMR data for small molecules by several open source data processing tools and metabolomics reference spectral libraries, e.g., serving as storage format for the MetaboLights data repository. The nmrML open access data standard has been endorsed by the Metabolomics Standards Initiative (MSI), and we here encourage user participation and feedback to increase usability and make it a successful standard.

Kim Magrini | NREL

Science.gov Websites

Developing char-based soil amendments Soil carbon and char analysis via molecular beam mass spectrometry depth profiling, Fourier transform infrared [FTIR]) Rapid soil carbon analysis using analytical DRIFTS, 13C NMR, and py-MBMS to Characterize the Effects of Soil Science Oxidation Assays on Soil Organic

Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics.

PubMed

Marchev, Andrey; Yordanova, Zhenya; Alipieva, Kalina; Zahmanov, Georgi; Rusinova-Videva, Snezhana; Kapchina-Toteva, Veneta; Simova, Svetlana; Popova, Milena; Georgiev, Milen I

2016-09-01

To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside.

Chemical characterization of a prominent phosphomonoester resonance from mammalian brain. 31P and 1H NMR analysis at 4.7 and 14.1 tesla

NASA Astrophysics Data System (ADS)

Pettegrew, J. W.; Kopp, S. J.; Dadok, J.; Minshew, N. J.; Feliksik, J. M.; Glonek, T.; Cohen, M. M.

A prominent 31P NMR resonance at 3.84 ppm in mammalian brain has been identified as ethanolamine phosphate. The identification was based on 1H and 31P NMR findings (including pH titrations) at 4.7 and 14.1 T, as well as thin-layer chromatography studies. We previously incorrectly assigned the 3.84 ppm resonance to ribose-5-phosphate. The incorrect assignment occurred because the two compounds have very similar 31P chemical shifts, and because we did not carefully consider the effects of counter ions and ionic strengths when interpreting the 31P chemical shifts. In separate preliminary studies we have demonstrated ethanolamine phosphate to be high in immature developing brain and in the degenerating brain of Alzheimer's and Huntington's disease patients. Ethanolamine phosphate may therefore serve as a sensitive marker of membrane phospholipid turnover for both in vitro and in vivo31P NMR studies.

Can NMR solve some significant challenges in metabolomics?

PubMed

Nagana Gowda, G A; Raftery, Daniel

2015-11-01

The field of metabolomics continues to witness rapid growth driven by fundamental studies, methods development, and applications in a number of disciplines that include biomedical science, plant and nutrition sciences, drug development, energy and environmental sciences, toxicology, etc. NMR spectroscopy is one of the two most widely used analytical platforms in the metabolomics field, along with mass spectrometry (MS). NMR's excellent reproducibility and quantitative accuracy, its ability to identify structures of unknown metabolites, its capacity to generate metabolite profiles using intact bio-specimens with no need for separation, and its capabilities for tracing metabolic pathways using isotope labeled substrates offer unique strengths for metabolomics applications. However, NMR's limited sensitivity and resolution continue to pose a major challenge and have restricted both the number and the quantitative accuracy of metabolites analyzed by NMR. Further, the analysis of highly complex biological samples has increased the demand for new methods with improved detection, better unknown identification, and more accurate quantitation of larger numbers of metabolites. Recent efforts have contributed significant improvements in these areas, and have thereby enhanced the pool of routinely quantifiable metabolites. Additionally, efforts focused on combining NMR and MS promise opportunities to exploit the combined strength of the two analytical platforms for direct comparison of the metabolite data, unknown identification and reliable biomarker discovery that continue to challenge the metabolomics field. This article presents our perspectives on the emerging trends in NMR-based metabolomics and NMR's continuing role in the field with an emphasis on recent and ongoing research from our laboratory. Copyright © 2015 Elsevier Inc. All rights reserved.

J-GFT NMR for precise measurement of mutually correlated nuclear spin-spin couplings.

PubMed

Atreya, Hanudatta S; Garcia, Erwin; Shen, Yang; Szyperski, Thomas

2007-01-24

G-matrix Fourier transform (GFT) NMR spectroscopy is presented for accurate and precise measurement of chemical shifts and nuclear spin-spin couplings correlated according to spin system. The new approach, named "J-GFT NMR", is based on a largely extended GFT NMR formalism and promises to have a broad impact on projection NMR spectroscopy. Specifically, constant-time J-GFT (6,2)D (HA-CA-CO)-N-HN was implemented for simultaneous measurement of five mutually correlated NMR parameters, that is, 15N backbone chemical shifts and the four one-bond spin-spin couplings 13Calpha-1Halpha, 13Calpha-13C', 15N-13C', and 15N-1HNu. The experiment was applied for measuring residual dipolar couplings (RDCs) in an 8 kDa protein Z-domain aligned with Pf1 phages. Comparison with RDC values extracted from conventional NMR experiments reveals that RDCs are measured with high precision and accuracy, which is attributable to the facts that (i) the use of constant time evolution ensures that signals do not broaden whenever multiple RDCs are jointly measured in a single dimension and (ii) RDCs are multiply encoded in the multiplets arising from the joint sampling. This corresponds to measuring the couplings multiple times in a statistically independent manner. A key feature of J-GFT NMR, i.e., the correlation of couplings according to spin systems without reference to sequential resonance assignments, promises to be particularly valuable for rapid identification of backbone conformation and classification of protein fold families on the basis of statistical analysis of dipolar couplings.

Synthesis and spectral characterization of Zn(II) microsphere series for antimicrobial application

NASA Astrophysics Data System (ADS)

Singh, Ajay K.; Pandey, Sarvesh K.; Pandey, O. P.; Sengupta, S. K.

2014-09-01

Microsphere series have been synthesized by reacting zinc(II) acetate dihydrate with Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole/oxadiazole/triazole with salicylaldehyde. Elemental analysis suggests that the complexes have 1:2 and 1:1 stoichiometry of the type [Zn(L)2(H2O)2] and [Zn(L‧)(H2O)2]; LH = Schiff bases derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thia/oxadiazole with salicylaldehyde; L‧H2 = Schiff bases derived from 3-(substituted phenyl)-4-amino-5-hydrazino-1,2,4-triazole and salicylaldehyde and were characterized by elemental analyses, IR, 1H NMR and 13C NMR spectral data. Scanning electron microscopy (SEM) showed that synthesized materials have microsphere like structure and there EDX analysis comparably matches with elemental analysis. For the antimicrobial application Schiff bases and their zinc(II) complexes were screened for four bacteria e.g. Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, Streptococcus pyogenes and four fungi e.g. Cyrtomium falcatum, Aspergillus niger, Fusarium oxysporium and Curvularia pallescence by the reported method. Schiff base and Zn(II) compounds showed significant antimicrobial activities. However, activities increase upon chelation. Thermal analysis (TGA) data of compound (10) showed its stability up to 300 °C.

Theoretical and experimental NMR study of protopine hydrochloride isomers.

PubMed

Tousek, Jaromír; Malináková, Katerina; Dostál, Jirí; Marek, Radek

2005-07-01

The 1H and 13C NMR chemical shifts of cis- and trans-protopinium salts were measured and calculated. The calculations of the chemical shifts consisted of conformational analysis, geometry optimization (RHF/6-31G** method) and shielding constants calculations (B3LYP/6-31G** method). Based on the results of the quantum chemical calculations, two sets of experimental chemical shifts were assigned to the particular isomers. According to the experimental results, the trans-isomer is more stable and its population is approximately 68%. Copyright 2005 John Wiley & Sons, Ltd

Separation and analysis of trace degradants in a pharmaceutical formulation using on-line capillary isotachophoresis-NMR.

PubMed

Eldridge, Stacie L; Almeida, Valentino K; Korir, Albert K; Larive, Cynthia K

2007-11-15

NMR spectroscopy is widely used in the pharmaceutical industry for the structure elucidation of pharmaceutical impurities, especially when coupled to a separation method, such as HPLC. However, NMR has relatively poor sensitivity compared with other techniques such as mass spectrometry, limiting its applicability in impurity analyses. This limitation is addressed here through the on-line coupling of microcoil NMR with capillary isotachophoresis (cITP), a separation method that can concentrate dilute components by 2-3 orders of magnitude. With this approach, 1H NMR spectra can be acquired for microgram (nanomole) quantities of trace impurities in a complex sample matrix. cITP-NMR was used in this work to isolate and detect 4-aminophenol (PAP) in an acetaminophen sample spiked at the 0.1% level, with no interference from the parent compound. Analysis of an acetaminophen thermal degradation sample revealed resonances of several degradation products in addition to PAP, confirming the effectiveness of on-line cITP-NMR for trace analyses of pharmaceutical formulations. Subsequent LC-MS/MS analysis provided complementary information for the structure elucidation of the unknown degradation products, which were dimers formed during the degradation process.

Unilateral NMR applied to the conservation of works of art.

PubMed

Del Federico, Eleonora; Centeno, Silvia A; Kehlet, Cindie; Currier, Penelope; Stockman, Denise; Jerschow, Alexej

2010-01-01

In conventional NMR, samples from works of art in sizes above those considered acceptable in the field of art conservation would have to be removed to place them into the bore of large superconducting magnets. The portable permanent-magnet-based systems, by contrast, can be used in situ to study works of art, in a noninvasive manner. One of these portable NMR systems, NMR-MOUSE(R), measures the information contained in one pixel in an NMR image from a region of about 1 cm(2), which can be as thin as 2-3 microm. With such a high depth resolution, profiles through the structures of art objects can be measured to characterize the materials, the artists' techniques, and the deterioration processes. A novel application of the technique to study a deterioration process and to follow up a conservation treatment is presented in which micrometer-thick oil stains on paper are differentiated and characterized. In this example, the spin-spin relaxation T (2) of the stain is correlated to the iodine number and to the degree of cross-linking of the oil, parameters that are crucial in choosing an appropriate conservation treatment to remove them. It is also shown that the variation of T (2) over the course of treatments with organic solvents can be used to monitor the progress of the conservation interventions. It is expected that unilateral NMR in combination with multivariate data analysis will fill a gap within the set of high-spatial-resolution techniques currently available for the noninvasive analysis of materials in works of art, where procedures to study the inorganic components are currently far more developed than those suitable for the study of the organic components.

Focus: a robust workflow for one-dimensional NMR spectral analysis.

PubMed

Alonso, Arnald; Rodríguez, Miguel A; Vinaixa, Maria; Tortosa, Raül; Correig, Xavier; Julià, Antonio; Marsal, Sara

2014-01-21

One-dimensional (1)H NMR represents one of the most commonly used analytical techniques in metabolomic studies. The increase in the number of samples analyzed as well as the technical improvements involving instrumentation and spectral acquisition demand increasingly accurate and efficient high-throughput data processing workflows. We present FOCUS, an integrated and innovative methodology that provides a complete data analysis workflow for one-dimensional NMR-based metabolomics. This tool will allow users to easily obtain a NMR peak feature matrix ready for chemometric analysis as well as metabolite identification scores for each peak that greatly simplify the biological interpretation of the results. The algorithm development has been focused on solving the critical difficulties that appear at each data processing step and that can dramatically affect the quality of the results. As well as method integration, simplicity has been one of the main objectives in FOCUS development, requiring very little user input to perform accurate peak alignment, peak picking, and metabolite identification. The new spectral alignment algorithm, RUNAS, allows peak alignment with no need of a reference spectrum, and therefore, it reduces the bias introduced by other alignment approaches. Spectral alignment has been tested against previous methodologies obtaining substantial improvements in the case of moderate or highly unaligned spectra. Metabolite identification has also been significantly improved, using the positional and correlation peak patterns in contrast to a reference metabolite panel. Furthermore, the complete workflow has been tested using NMR data sets from 60 human urine samples and 120 aqueous liver extracts, reaching a successful identification of 42 metabolites from the two data sets. The open-source software implementation of this methodology is available at http://www.urr.cat/FOCUS.

Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

PubMed Central

Kim, So-Hyun; K. Cho, Somi; Min, Tae-Sun; Kim, Yujin; Yang, Seung-Ok; Kim, Hee-Su; Hyun, Sun-Hee; Kim, Hana; Kim, Young-Suk; Choi, Hyung-Kyoon

2011-01-01

The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake. PMID:21562641

NMR-based metabolic study of fruits of Physalis peruviana L. grown in eight different Peruvian ecosystems.

PubMed

Maruenda, Helena; Cabrera, Rodrigo; Cañari-Chumpitaz, Cristhian; Lopez, Juan M; Toubiana, David

2018-10-01

The berry of Physalis peruviana L. (Solanaceae) represents an important socio-economical commodity for Latin America. The absence of a clear phenotype renders it difficult to trace its place of origin. In this study, Cape gooseberries from eight different regions within the Peruvian Andes were profiled for their metabolism implementing a NMR platform. Twenty-four compounds could be unequivocally identified and sixteen quantified. One-way ANOVA and post-hoc Tukey test revealed that all of the quantified metabolites changed significantly among regions: Bambamarca I showed the most accumulated significant differences. The coefficient of variation demonstrated high phenotypic plasticity for amino acids, while sugars displayed low phenotypic plasticity. Correlation analysis highlighted the closely coordinated behavior of the amino acid profile. Finally, PLS-DA revealed a clear separation among the regions based on their metabolic profiles, accentuating the discriminatory capacity of NMR in establishing significant phytochemical differences between producing regions of the fruit of P. peruviana L. Copyright © 2018 Elsevier Ltd. All rights reserved.

NMR spectrum analysis for CrAs at ambient pressure

NASA Astrophysics Data System (ADS)

Kotegawa, H.; Nakahara, S.; Matsushima, K.; Tou, H.; Matsuoka, E.; Sugawara, H.; Harima, H.

2018-05-01

We report NMR spectrum analysis for CrAs, which was recently reported to be superconducting under pressure. The NMR spectrum obtained by the powdered single crystals shows a typical powder pattern reproduced by the electric field gradient (EFG) parameters and isotropic Knight shift, indicating anisotropy of Knight shift is not remarkable in CrAs. For the oriented sample, the spectrum can be understood by considering that the crystals are aligned for H ∥ b . The temperature dependence of Knight shift was successfully obtained from NMR spectrum with large nuclear quadrupole interaction.

CONNJUR R: An annotation strategy for fostering reproducibility in bio-NMR: protein spectral assignment

PubMed Central

Fenwick, Matthew; Hoch, Jeffrey C.; Ulrich, Eldon; Gryk, Michael R.

2015-01-01

Reproducibility is a cornerstone of the scientific method, essential for validation of results by independent laboratories and the sine qua non of scientific progress. A key step toward reproducibility of biomolecular NMR studies was the establishment of public data repositories (PDB and BMRB). Nevertheless, bio-NMR studies routinely fall short of the requirement for reproducibility that all the data needed to reproduce the results are published. A key limitation is that considerable metadata goes unpublished, notably manual interventions that are typically applied during the assignment of multidimensional NMR spectra. A general solution to this problem has been elusive, in part because of the wide range of approaches and software packages employed in the analysis of protein NMR spectra. Here we describe an approach for capturing missing metadata during the assignment of protein NMR spectra that can be generalized to arbitrary workflows, different software packages, other biomolecules, or other stages of data analysis in bio-NMR. We also present extensions to the NMR-STAR data dictionary that enable machine archival and retrieval of the “missing” metadata. PMID:26253947

Fragment-Based Drug Discovery Using NMR Spectroscopy

PubMed Central

Harner, Mary J.; Frank, Andreas O.; Fesik, Stephen W.

2013-01-01

Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool for fragment-based drug discovery over the last two decades. While NMR has been traditionally used to elucidate the three-dimensional structures and dynamics of biomacromolecules and their interactions, it can also be a very valuable tool for the reliable identification of small molecules that bind to proteins and for hit-to-lead optimization. Here, we describe the use of NMR spectroscopy as a method for fragment-based drug discovery and how to most effectively utilize this approach for discovering novel therapeutics based on our experience. PMID:23686385

Sensitivity enhancement by chromatographic peak concentration with ultra-high performance liquid chromatography-nuclear magnetic resonance spectroscopy for minor impurity analysis.

PubMed

Tokunaga, Takashi; Akagi, Ken-Ichi; Okamoto, Masahiko

2017-07-28

High performance liquid chromatography can be coupled with nuclear magnetic resonance (NMR) spectroscopy to give a powerful analytical method known as liquid chromatography-nuclear magnetic resonance (LC-NMR) spectroscopy, which can be used to determine the chemical structures of the components of complex mixtures. However, intrinsic limitations in the sensitivity of NMR spectroscopy have restricted the scope of this procedure, and resolving these limitations remains a critical problem for analysis. In this study, we coupled ultra-high performance liquid chromatography (UHPLC) with NMR to give a simple and versatile analytical method with higher sensitivity than conventional LC-NMR. UHPLC separation enabled the concentration of individual peaks to give a volume similar to that of the NMR flow cell, thereby maximizing the sensitivity to the theoretical upper limit. The UHPLC concentration of compound peaks present at typical impurity levels (5.0-13.1 nmol) in a mixture led to at most three-fold increase in the signal-to-noise ratio compared with LC-NMR. Furthermore, we demonstrated the use of UHPLC-NMR for obtaining structural information of a minor impurity in a reaction mixture in actual laboratory-scale development of a synthetic process. Using UHPLC-NMR, the experimental run times for chromatography and NMR were greatly reduced compared with LC-NMR. UHPLC-NMR successfully overcomes the difficulties associated with analyses of minor components in a complex mixture by LC-NMR, which are problematic even when an ultra-high field magnet and cryogenic probe are used. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative analysis of sitagliptin using the (19)F-NMR method: a universal technique for fluorinated compound detection.

PubMed

Zhang, Fen-Fen; Jiang, Meng-Hong; Sun, Lin-Lin; Zheng, Feng; Dong, Lei; Shah, Vishva; Shen, Wen-Bin; Ding, Ya

2015-01-07

To expand the application scope of nuclear magnetic resonance (NMR) technology in quantitative analysis of pharmaceutical ingredients, (19)F nuclear magnetic resonance ((19)F-NMR) spectroscopy has been employed as a simple, rapid, and reproducible approach for the detection of a fluorine-containing model drug, sitagliptin phosphate monohydrate (STG). ciprofloxacin (Cipro) has been used as the internal standard (IS). Influential factors, including the relaxation delay time (d1) and pulse angle, impacting the accuracy and precision of spectral data are systematically optimized. Method validation has been carried out in terms of precision and intermediate precision, linearity, limit of detection (LOD) and limit of quantification (LOQ), robustness, and stability. To validate the reliability and feasibility of the (19)F-NMR technology in quantitative analysis of pharmaceutical analytes, the assay result has been compared with that of (1)H-NMR. The statistical F-test and student t-test at 95% confidence level indicate that there is no significant difference between these two methods. Due to the advantages of (19)F-NMR, such as higher resolution and suitability for biological samples, it can be used as a universal technology for the quantitative analysis of other fluorine-containing pharmaceuticals and analytes.

A personal computer-based nuclear magnetic resonance spectrometer

NASA Astrophysics Data System (ADS)

Job, Constantin; Pearson, Robert M.; Brown, Michael F.

1994-11-01

Nuclear magnetic resonance (NMR) spectroscopy using personal computer-based hardware has the potential of enabling the application of NMR methods to fields where conventional state of the art equipment is either impractical or too costly. With such a strategy for data acquisition and processing, disciplines including civil engineering, agriculture, geology, archaeology, and others have the possibility of utilizing magnetic resonance techniques within the laboratory or conducting applications directly in the field. Another aspect is the possibility of utilizing existing NMR magnets which may be in good condition but unused because of outdated or nonrepairable electronics. Moreover, NMR applications based on personal computer technology may open up teaching possibilities at the college or even secondary school level. The goal of developing such a personal computer (PC)-based NMR standard is facilitated by existing technologies including logic cell arrays, direct digital frequency synthesis, use of PC-based electrical engineering software tools to fabricate electronic circuits, and the use of permanent magnets based on neodymium-iron-boron alloy. Utilizing such an approach, we have been able to place essentially an entire NMR spectrometer console on two printed circuit boards, with the exception of the receiver and radio frequency power amplifier. Future upgrades to include the deuterium lock and the decoupler unit are readily envisioned. The continued development of such PC-based NMR spectrometers is expected to benefit from the fast growing, practical, and low cost personal computer market.

Socioeconomic inequality in neonatal mortality in countries of low and middle income: a multicountry analysis.

PubMed

McKinnon, Britt; Harper, Sam; Kaufman, Jay S; Bergevin, Yves

2014-03-01

Neonatal mortality rates (NMRs) in countries of low and middle income have been only slowly decreasing; coverage of essential maternal and newborn health services needs to increase, particularly for disadvantaged populations. Our aim was to produce comparable estimates of changes in socioeconomic inequalities in NMR in the past two decades across these countries. We used data from Demographic and Health Surveys (DHS) for countries in which a survey was done in 2008 or later and one about 10 years previously. We measured absolute inequalities with the slope index of inequality and relative inequalities with the relative index of inequality. We used an asset-based wealth index and maternal education as measures of socioeconomic position and summarised inequality estimates for all included countries with random-effects meta-analysis. 24 low-income and middle-income countries were eligible for inclusion. In most countries, absolute and relative wealth-related and educational inequalities in NMR decreased between survey 1 and survey 2. In five countries (Cameroon, Nigeria, Malawi, Mozambique, and Uganda), the difference in NMR between the top and bottom of the wealth distribution was reduced by more than two neonatal deaths per 1000 livebirths per year. By contrast, wealth-related inequality increased by more than 1·5 neonatal deaths per 1000 livebirths per year in Ethiopia and Cambodia. Patterns of change in absolute and relative educational inequalities in NMR were similar to those of wealth-related NMR inequalities, although the size of educational inequalities tended to be slightly larger. Socioeconomic inequality in NMR seems to have decreased in the past two decades in most countries of low and middle income. However, a substantial survival advantage remains for babies born into wealthier households with a high educational level, which should be considered in global efforts to further reduce NMR. Canadian Institutes of Health Research. Copyright © 2014 McKinnon et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

icoshift: A versatile tool for the rapid alignment of 1D NMR spectra

NASA Astrophysics Data System (ADS)

Savorani, F.; Tomasi, G.; Engelsen, S. B.

2010-02-01

The increasing scientific and industrial interest towards metabonomics takes advantage from the high qualitative and quantitative information level of nuclear magnetic resonance (NMR) spectroscopy. However, several chemical and physical factors can affect the absolute and the relative position of an NMR signal and it is not always possible or desirable to eliminate these effects a priori. To remove misalignment of NMR signals a posteriori, several algorithms have been proposed in the literature. The icoshift program presented here is an open source and highly efficient program designed for solving signal alignment problems in metabonomic NMR data analysis. The icoshift algorithm is based on correlation shifting of spectral intervals and employs an FFT engine that aligns all spectra simultaneously. The algorithm is demonstrated to be faster than similar methods found in the literature making full-resolution alignment of large datasets feasible and thus avoiding down-sampling steps such as binning. The algorithm uses missing values as a filling alternative in order to avoid spectral artifacts at the segment boundaries. The algorithm is made open source and the Matlab code including documentation can be downloaded from www.models.life.ku.dk.

A novel method for the investigation of liquid/liquid distribution coefficients and interface permeabilities applied to the water-octanol-drug system.

PubMed

Stein, Paul C; di Cagno, Massimiliano; Bauer-Brandl, Annette

2011-09-01

In this work a new, accurate and convenient technique for the measurement of distribution coefficients and membrane permeabilities based on nuclear magnetic resonance (NMR) is described. This method is a novel implementation of localized NMR spectroscopy and enables the simultaneous analysis of the drug content in the octanol and in the water phase without separation. For validation of the method, the distribution coefficients at pH = 7.4 of four active pharmaceutical ingredients (APIs), namely ibuprofen, ketoprofen, nadolol, and paracetamol (acetaminophen), were determined using a classical approach. These results were compared to the NMR experiments which are described in this work. For all substances, the respective distribution coefficients found with the two techniques coincided very well. Furthermore, the NMR experiments make it possible to follow the distribution of the drug between the phases as a function of position and time. Our results show that the technique, which is available on any modern NMR spectrometer, is well suited to the measurement of distribution coefficients. The experiments present also new insight into the dynamics of the water-octanol interface itself and permit measurement of the interface permeability.

Discrimination of three Pegaga (Centella) varieties and determination of growth-lighting effects on metabolites content based on the chemometry of 1H nuclear magnetic resonance spectroscopy.

PubMed

H, Maulidiani; Khatib, Alfi; Shaari, Khozirah; Abas, Faridah; Shitan, Mahendran; Kneer, Ralf; Neto, Victor; Lajis, Nordin H

2012-01-11

The metabolites of three species of Apiaceae, also known as Pegaga, were analyzed utilizing (1)H NMR spectroscopy and multivariate data analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) resolved the species, Centella asiatica, Hydrocotyle bonariensis, and Hydrocotyle sibthorpioides, into three clusters. The saponins, asiaticoside and madecassoside, along with chlorogenic acids were the metabolites that contributed most to the separation. Furthermore, the effects of growth-lighting condition to metabolite contents were also investigated. The extracts of C. asiatica grown in full-day light exposure exhibited a stronger radical scavenging activity and contained more triterpenes (asiaticoside and madecassoside), flavonoids, and chlorogenic acids as compared to plants grown in 50% shade. This study established the potential of using a combination of (1)H NMR spectroscopy and multivariate data analyses in differentiating three closely related species and the effects of growth lighting, based on their metabolite contents and identification of the markers contributing to their differences.

A fast and efficient python library for interfacing with the Biological Magnetic Resonance Data Bank.

PubMed

Smelter, Andrey; Astra, Morgan; Moseley, Hunter N B

2017-03-17

The Biological Magnetic Resonance Data Bank (BMRB) is a public repository of Nuclear Magnetic Resonance (NMR) spectroscopic data of biological macromolecules. It is an important resource for many researchers using NMR to study structural, biophysical, and biochemical properties of biological macromolecules. It is primarily maintained and accessed in a flat file ASCII format known as NMR-STAR. While the format is human readable, the size of most BMRB entries makes computer readability and explicit representation a practical requirement for almost any rigorous systematic analysis. To aid in the use of this public resource, we have developed a package called nmrstarlib in the popular open-source programming language Python. The nmrstarlib's implementation is very efficient, both in design and execution. The library has facilities for reading and writing both NMR-STAR version 2.1 and 3.1 formatted files, parsing them into usable Python dictionary- and list-based data structures, making access and manipulation of the experimental data very natural within Python programs (i.e. "saveframe" and "loop" records represented as individual Python dictionary data structures). Another major advantage of this design is that data stored in original NMR-STAR can be easily converted into its equivalent JavaScript Object Notation (JSON) format, a lightweight data interchange format, facilitating data access and manipulation using Python and any other programming language that implements a JSON parser/generator (i.e., all popular programming languages). We have also developed tools to visualize assigned chemical shift values and to convert between NMR-STAR and JSONized NMR-STAR formatted files. Full API Reference Documentation, User Guide and Tutorial with code examples are also available. We have tested this new library on all current BMRB entries: 100% of all entries are parsed without any errors for both NMR-STAR version 2.1 and version 3.1 formatted files. We also compared our software to three currently available Python libraries for parsing NMR-STAR formatted files: PyStarLib, NMRPyStar, and PyNMRSTAR. The nmrstarlib package is a simple, fast, and efficient library for accessing data from the BMRB. The library provides an intuitive dictionary-based interface with which Python programs can read, edit, and write NMR-STAR formatted files and their equivalent JSONized NMR-STAR files. The nmrstarlib package can be used as a library for accessing and manipulating data stored in NMR-STAR files and as a command-line tool to convert from NMR-STAR file format into its equivalent JSON file format and vice versa, and to visualize chemical shift values. Furthermore, the nmrstarlib implementation provides a guide for effectively JSONizing other older scientific formats, improving the FAIRness of data in these formats.

A Routine Experimental Protocol for qHNMR Illustrated with Taxol⊥

PubMed Central

Pauli, Guido F.; Jaki, Birgit U.; Lankin, David C.

2012-01-01

Quantitative 1H NMR (qHNMR) provides a value-added dimension to the standard spectroscopic data set involved in structure analysis, especially when analyzing bioactive molecules and elucidating new natural products. The qHNMR method can be integrated into any routine qualitative workflow without much additional effort by simply establishing quantitative conditions for the standard solution 1H NMR experiments. Moreover, examination of different chemical lots of taxol and a Taxus brevifolia extract as working examples led to a blueprint for a generic approach to performing a routinely practiced 13C-decoupled qHNMR experiment, and for recognizing its potential and main limitations. The proposed protocol is based on a newly assembled 13C GARP broadband decoupled proton acquisition sequence that reduces spectroscopic complexity by removal of carbon satellites. The method is capable of providing qualitative and quantitative NMR data simultaneously and covers various analytes from pure compounds to complex mixtures such as metabolomes. Due to a routinely achievable dynamic range of 300:1 (0.3%) or better, qHNMR qualifies for applications ranging from reference standards to biologically active compounds to metabolome analysis. Providing a “cookbook” approach to qHNMR, acquisition conditions are described that can be adapted for contemporary NMR spectrometers of all major manufacturers. PMID:17298095

Synthesis of Pyridine– and Pyrazine–BF 3 Complexes and Their Characterization in Solution and Solid State

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chénard, Etienne; Sutrisno, Andre; Zhu, Lingyang

2016-03-31

Following the discovery of the redox-active 1,4- bis-BF 3-quinoxaline complex, we undertook a structure- activity study with the objective to understand the active nature of the quinoxaline complex. Through systematic synthesis and characterization, we have compared complexes prepared from pyridine and pyrazine derivatives, as heterocyclic core analogues. This paper reports the structural requirements that give rise to the electrochemical features of the 1,4-bis-BF 3-quinoxaline adduct. Using solution and solidstate NMR spectroscopy, the role of aromatic ring fusion and nitrogen incorporation in bonding and electronics was elucidated. We establish the boron atom location and its interaction with its environment from 1Dmore » and 2D solution NMR, X-ray diffraction analysis, and 11B solid-state NMR experiments. Crystallographic analysis of single crystals helped to correlate the boron geometry with 11B quadrupolar coupling constant (CQ) and asymmetry parameter (ηQ), extracted from 11B solid-state NMR spectra. Additionally, computations based on density functional theory were performed to predict electrochemical behavior of the BF 3-heteroaromatic complexes. We then experimentally measured electrochemical potential using cyclic voltammetry and found that the redox potentials and CQ values are similarly affected by electronic changes in the complexes.« less

¹H and ¹³C NMR-based sugar profiling with chemometric analysis and antioxidant activity of herbhoneys and honeys.

PubMed

Jamróz, Marta K; Paradowska, Katarzyna; Zawada, Katarzyna; Makarova, Katerina; Kaźmierski, Sławomir; Wawer, Iwona

2014-01-30

Herbhoneys, relatively new bee products, are expected to have interesting medicinal properties. However, there is still a lack of data concerning their composition and antioxidant properties. ¹H and ¹³C NMR spectroscopy coupled with chemometric analysis (PCA and PLS-DA) and antioxidant assays (DPPH-ESR and ORAC-FL) were used to study 25 samples of Polish herbhoneys and honeys. Antioxidant activity varied among the samples. The best properties were exhibited by cocoa and instant coffee herbhoneys. The contents of total polyphenols and total carotenoids in the studied samples were found to be 70-1340 mg GAE kg⁻¹ and 0-28.05 mg kg⁻¹ respectively. No significant differences between herbhoney and honey samples were found in their sugar profiles. The PCA of ¹³C NMR spectra of the samples in DMSO-d6 resulted in sample clustering due to sucrose content. Herbhoneys have similar antioxidant properties to traditional honeys, being therefore of equal nutritional value. There was a noticeable influence of the extract concentration on the observed antioxidant effect. For samples with high antioxidant activity, polyphenols were responsible for the observed effect. Sample clustering due to sucrose content in the NMR-PCA study allowed effortless detection of adulteration. © 2013 Society of Chemical Industry.

LC-NMR Technique in the Analysis of Phytosterols in Natural Extracts

PubMed Central

Horník, Štěpán; Sajfrtová, Marie; Sýkora, Jan; Březinová, Anna; Wimmer, Zdeněk

2013-01-01

The ability of LC-NMR to detect simultaneously free and conjugated phytosterols in natural extracts was tested. The advantages and disadvantages of a gradient HPLC-NMR method were compared to the fast composition screening using SEC-NMR method. Fractions of free and conjugated phytosterols were isolated and analyzed by isocratic HPLC-NMR methods. The results of qualitative and quantitative analyses were in a good agreement with the literature data. PMID:24455424

Structures of glycans bound to receptors from saturation transfer difference (STD) NMR spectroscopy: quantitative analysis by using CORCEMA-ST.

PubMed

Enríquez-Navas, Pedro M; Guzzi, Cinzia; Muñoz-García, Juan C; Nieto, Pedro M; Angulo, Jesús

2015-01-01

Glycan-receptor interactions are of fundamental relevance for a large number of biological processes, and their kinetics properties (medium/weak binding affinities) make them appropriated to be studied by ligand observed NMR techniques, among which saturation transfer difference (STD) NMR spectroscopy has been shown to be a very robust and powerful approach. The quantitative analysis of the results from a STD NMR study of a glycan-receptor interaction is essential to be able to translate the resulting spectral intensities into a 3D molecular model of the complex. This chapter describes how to carry out such a quantitative analysis by means of the Complete Relaxation and Conformational Exchange Matrix Approach for STD NMR (CORCEMA-ST), in general terms, and an example of a previous work on an antibody-glycan interaction is also shown.

Substituent effect study on experimental ¹³C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives.

PubMed

Kara, Yesim S

2015-12-05

Eleven novel (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives were synthesized in the present study. These dihydroisoxazole derivatives were characterized by IR, (1)H NMR, (13)C NMR and elemental analyses. Their (13)C NMR spectra were measured in Deuterochloroform (CDCl3). The correlation analysis for the substituent-induced chemical shift (SCS) with Hammett substituent constant (σ), inductive substituent constant (σI), different of resonance substituent constants (σR, σR(o)) and Swain-Lupton substituent parameters (F, R) were performed using SSP (single substituent parameter), and DSP (dual substituent parameter) methods, as well as single and multiple regression analysis. From the result of regression analysis, the effect of substituent on the (13)C NMR chemical shifts was explained. Copyright © 2015 Elsevier B.V. All rights reserved.

Coupling HPLC-SPE-NMR with a microplate-based high-resolution antioxidant assay for efficient analysis of antioxidants in food--validation and proof-of-concept study with caper buds.

PubMed

Wiese, Stefanie; Wubshet, Sileshi G; Nielsen, John; Staerk, Dan

2013-12-15

This work describes the coupling of a microplate-based antioxidant assay with a hyphenated system consisting of high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HPLC-SPE-NMR/high-resolution antioxidant assay, for the analysis of complex food extracts. The applicability of the microplate-based antioxidant assay for high-resolution screening of common food phenolics as well as parameters related to their trapping efficiency, elution behavior, and recovery on/from SPE cartridges are described. It was found that the microplate-based high-resolution antioxidant assay is an attractive and easy implementable alternative to direct on-line screening methods. Furthermore, it was shown that Resin SH and Resin GP SPE material are superior to RP C18HD for trapping of phenolic compounds. Proof-of-concept study was performed with caper bud extract, revealing the most important antioxidants to be quercetin, kaempferol, rutin, kaempferol-3-O-β-rutinoside and N(1),N(5),N(10)-triphenylpropenoyl spermidine amides. Targeted isolation of the latter, and comprehensive NMR experiments showed them to be N(1),N(10)-di-(E)-caffeoyl-N(5)-p-(E)-coumaroyl spermidine, N(1)-(E)-caffeoyl-N(5),N(10)-di-p-(E)-coumaroyl spermidine, N(10)-(E)-caffeoyl-N(1),N(5)-di-p-(E)-coumaroyl spermidine, and N(1),N(5),N(10)-tri-p-(E)-coumaroyl spermidine amides. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coordination Polymer: Synthesis, Spectral Characterization and Thermal Behaviour of Starch-Urea Based Biodegradable Polymer and Its Polymer Metal Complexes

PubMed Central

Malik, Ashraf; Parveen, Shadma; Ahamad, Tansir; Alshehri, Saad M.; Singh, Prabal Kumar; Nishat, Nahid

2010-01-01

A starch-urea-based biodegradable coordination polymer modified by transition metal Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) was prepared by polycondensation of starch and urea. All the synthesized polymeric compounds were characterized by Fourier transform-infrared spectroscopy (FT-IR), 1H-NMR spectroscopy, 13C-NMR spectroscopy, UV-visible spectra, magnetic moment measurements, differential scanning calorimeter (DSC), and thermogravimetric analysis (TGA). The results of electronic spectra and magnetic moment measurements indicate that Mn(II), Co(II), and Ni(II) complexes show octahedral geometry, while Cu(II) and Zn(II) complexes show square planar and tetrahedral geometry, respectively. The thermogravimetric analysis revealed that all the polymeric metal complexes are more thermally stable than the parental ligand. In addition, biodegradable studies of all the polymeric compounds were also carried out through ASTM standards of biodegradable polymers by CO2 evolution method. PMID:20414461

Highly Accurate Quantitative Analysis Of Enantiomeric Mixtures from Spatially Frequency Encoded 1H NMR Spectra.

PubMed

Plainchont, Bertrand; Pitoux, Daisy; Cyrille, Mathieu; Giraud, Nicolas

2018-02-06

We propose an original concept to measure accurately enantiomeric excesses on proton NMR spectra, which combines high-resolution techniques based on a spatial encoding of the sample, with the use of optically active weakly orienting solvents. We show that it is possible to simulate accurately dipolar edited spectra of enantiomers dissolved in a chiral liquid crystalline phase, and to use these simulations to calibrate integrations that can be measured on experimental data, in order to perform a quantitative chiral analysis. This approach is demonstrated on a chemical intermediate for which optical purity is an essential criterion. We find that there is a very good correlation between the experimental and calculated integration ratios extracted from G-SERF spectra, which paves the way to a general method of determination of enantiomeric excesses based on the observation of 1 H nuclei.

One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schiff bases and pyrimido[1,2-a]benzimidazol-3(4H)-ones.

PubMed

Neochoritis, Constantinos G; Zarganes-Tzitzikas, Tryfon; Tsoleridis, Constantinos A; Stephanidou-Stephanatou, Julia; Kontogiorgis, Christos A; Hadjipavlou-Litina, Dimitra J; Choli-Papadopoulou, Theodora

2011-01-01

The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts. Compounds 3 and 4 were evaluated as inhibitors of lipoxygenase (LOX) and of lipid peroxidation (LPO). All the tested derivatives showed inhibition of lipid peroxidation, whereas most of them were found to have higher activation than the reference compound trolox; The Schiff bases 3e, 3h, and 3i, and the pyrimidobenzimidazoles 4a, 4e and 4f were found to be the most potent. The most potent LOX inhibitor within the subset of Schiff bases was found compound 3i, followed by 3f, whereas compounds 4a and 4g were found the most potent of the 3-oxo-pyrimido[1,2-a]benzimidazole group. Moreover, some cytotoxicity assessments were undertaken, whereupon it was found that Schiff base 3i and pyrimidobenzimidazoles 4e and 4f did not exhibit cytotoxicity at similar concentrations resembling thus the inhibitory activity of lipid peroxidation. The most cytotoxic Schiff base and pyrimidobenzimidazole were found to be 3d and 4c, respectively. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

NMR-based metabonomics and correlation analysis reveal potential biomarkers associated with chronic atrophic gastritis.

PubMed

Cui, Jiajia; Liu, Yuetao; Hu, Yinghuan; Tong, Jiayu; Li, Aiping; Qu, Tingli; Qin, Xuemei; Du, Guanhua

2017-01-05

Chronic atrophic gastritis (CAG) is one of the most important pre-cancerous states with a high prevalence. Exploring of the underlying mechanism and potential biomarkers is of significant importance for CAG. In the present work, 1 H NMR-based metabonomics with correlative analysis was performed to analyze the metabolic features of CAG. 19 plasma metabolites and 18 urine metabolites were enrolled to construct the circulatory and excretory metabolome of CAG, which was in response to alterations of energy metabolism, inflammation, immune dysfunction, as well as oxidative stress. 7 plasma biomarkers and 7 urine biomarkers were screened to elucidate the pathogenesis of CAG based on the further correlation analysis with biochemical indexes. Finally, 3 plasma biomarkers (arginine, succinate and 3-hydroxybutyrate) and 2 urine biomarkers (α-ketoglutarate and valine) highlighted the potential to indicate risks of CAG in virtue of correlation with pepsin activity and ROC analysis. Here, our results paved a way for elucidating the underlying mechanisms in the development of CAG, and provided new avenues for the diagnosis of CAG and presented potential drug targets for treatment of CAG. Copyright © 2016 Elsevier B.V. All rights reserved.

Orthogonal analytical methods for botanical standardization: Determination of green tea catechins by qNMR and LC-MS/MS

PubMed Central

Napolitano, José G.; Gödecke, Tanja; Lankin, David C.; Jaki, Birgit U.; McAlpine, James B.; Chen, Shao-Nong; Pauli, Guido F.

2013-01-01

The development of analytical methods for parallel characterization of multiple phytoconstituents is essential to advance the quality control of herbal products. While chemical standardization is commonly carried out by targeted analysis using gas or liquid chromatography-based methods, more universal approaches based on quantitative 1H NMR (qHNMR) measurements are being used increasingly in the multi-targeted assessment of these complex mixtures. The present study describes the development of a 1D qHNMR-based method for simultaneous identification and quantification of green tea constituents. This approach utilizes computer-assisted 1H iterative Full Spin Analysis (HiFSA) and enables rapid profiling of seven catechins in commercial green tea extracts. The qHNMR results were cross-validated against quantitative profiles obtained with an orthogonal LC-MS/MS method. The relative strengths and weaknesses of both approaches are discussed, with special emphasis on the role of identical reference standards in qualitative and quantitative analyses. PMID:23870106

Synthesis and characterization of boric acid mediated metal-organic frameworks based on trimesic acid and terephthalic acid

NASA Astrophysics Data System (ADS)

Ozer, Demet; Köse, Dursun A.; Şahin, Onur; Oztas, Nursen Altuntas

2017-08-01

The new metal-organic framework materials based on boric acid reported herein. Sodium and boron containing metal-organic frameworks were synthesized by one-pot self-assembly reaction in the presence of trimesic acid and terephthalic acid in water/ethanol solution. Boric acid is a relatively cheap boron source and boric acid mediated metal-organic framework prepared mild conditions compared to the other boron source based metal-organic framework. The synthesized compounds were characterized by FT-IR, p-XRD, TGA/DTA, elemental analysis, 13C-MAS NMR, 11B-NMR and single crystal measurements. The molecular formulas of compounds were estimated as C18H33B2Na5O28 and C8H24B2Na2O17 according to the structural analysis. The obtained complexes were thermally stable. Surface properties of inorganic polymer complexes were investigated by BET analyses and hydrogen storage properties of compound were also calculated.

13C cell wall enrichment and ionic liquid NMR analysis: progress towards a high-throughput detailed chemical analysis of the whole plant cell wall.

PubMed

Foston, Marcus; Samuel, Reichel; Ragauskas, Arthur J

2012-09-07

The ability to accurately and rapidly measure plant cell wall composition, relative monolignol content and lignin-hemicellulose inter-unit linkage distributions has become essential to efforts centered on reducing the recalcitrance of biomass by genetic engineering. Growing (13)C enriched transgenic plants is a viable route to achieve the high-throughput, detailed chemical analysis of whole plant cell wall before and after pretreatment and microbial or enzymatic utilization by (13)C nuclear magnetic resonance (NMR) in a perdeuterated ionic liquid solvent system not requiring component isolation. 1D (13)C whole cell wall ionic liquid NMR of natural abundant and (13)C enriched corn stover stem samples suggest that a high level of uniform labeling (>97%) can significantly reduce the total NMR experiment times up to ~220 times. Similarly, significant reduction in total NMR experiment time (~39 times) of the (13)C enriched corn stover stem samples for 2D (13)C-(1)H heteronuclear single quantum coherence NMR was found.

Multispectral Analysis of NMR Imagery

NASA Technical Reports Server (NTRS)

Butterfield, R. L.; Vannier, M. W. And Associates; Jordan, D.

1985-01-01

Conference paper discusses initial efforts to adapt multispectral satellite-image analysis to nuclear magnetic resonance (NMR) scans of human body. Flexibility of these techniques makes it possible to present NMR data in variety of formats, including pseudocolor composite images of pathological internal features. Techniques do not have to be greatly modified from form in which used to produce satellite maps of such Earth features as water, rock, or foliage.

78 FR 22151 - Fees for Official Inspection and Official Weighing Services Under the United States Grain...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... kit) \\5\\ 17.50 (v) NIR or NMR Analysis (protein, oil, starch, etc.) 2.40 (vi) Waxy corn (per test) 2...) (d) All other Mycotoxins (rapid test kit 38.50 method-applicant provides kit) \\3\\ (e) NIR or NMR... kit) \\3\\ (e) NIR or NMR Analysis (protein, oil, starch, 18.60 etc.) (f) Sunflower oil (per test) 18.60...

Reliability of ^1^H NMR analysis for assessment of lipid oxidation at frying temperatures

USDA-ARS?s Scientific Manuscript database

The reliability of a method using ^1^H NMR analysis for assessment of oil oxidation at a frying temperature was examined. During heating and frying at 180 °C, changes of soybean oil signals in the ^1^H NMR spectrum including olefinic (5.16-5.30 ppm), bisallylic (2.70-2.88 ppm), and allylic (1.94-2.1...

Evidence for altered metabolic pathways during environmental stress: (1)H-NMR spectroscopy based metabolomics and clinical studies on subjects of sea-voyage and Antarctic-stay.

PubMed

Yadav, Anand Prakash; Chaturvedi, Shubhra; Mishra, Kamla Prasad; Pal, Sunil; Ganju, Lilly; Singh, Shashi Bala

2014-08-01

The Antarctic context is an analogue of space travel, with close similarity in ambience of extreme climate, isolation, constrained living spaces, disrupted sleep cycles, and environmental stress. The present study examined the impact of the harsh habitat of Antarctica on human physiology and its metabolic pathways, by analyzing human serum samples, using (1)H-NMR spectroscopy for identification of metabolites; and quantifying other physiological and clinical parameters for correlation between expression data and metabolite data. Sera from seven adult males (of median age 36years) who participated in this study, from the 28th Indian Expeditionary group to the Antarctica station Maitri, were collected in chronological sequence. These included: i) baseline control; ii) during ship journey; iii) at Antarctica, in the months of March, May, August and November; to enable study of temporal evolution of monitored physiological states. 29 metabolites in serum were identified from the 400MHz (1)H-NMR spectra. Out of these, 19 metabolites showed significant variations in levels, during the ship journey and the stay at Maitri, compared to the base-line levels. Further biochemical analysis also supported these results, indicating that the ship journey, and the long-term Antarctic exposure, affected kidney and liver functioning. Our metabolite data highlights for the first time the effect of environmental stress on the patho-physiology of the human system. Multivariate analysis tools were employed for this metabonomics study, using (1)H-NMR spectroscopy. Copyright © 2014. Published by Elsevier Inc.

A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods.

PubMed

Liu, Shu-Yu; Hu, Chang-Qin

2007-10-17

This study introduces the general method of quantitative nuclear magnetic resonance (qNMR) for the calibration of reference standards of macrolide antibiotics. Several qNMR experimental conditions were optimized including delay, which is an important parameter of quantification. Three kinds of macrolide antibiotics were used to validate the accuracy of the qNMR method by comparison with the results obtained by the high performance liquid chromatography (HPLC) method. The purities of five common reference standards of macrolide antibiotics were measured by the 1H qNMR method and the mass balance method, respectively. The analysis results of the two methods were compared. The qNMR is quick and simple to use. In a new medicine research and development process, qNMR provides a new and reliable method for purity analysis of the reference standard.

CHARACTERIZATION OF METABOLITES IN SMALL FISH BIOFLUIDS AND TISSUES BY NMR SPECTROSCOPY

EPA Science Inventory

Nuclear magnetic resonance (NMR) spectroscopy has been utilized for assessing ecotoxicity in small fish models by means of metabolomics. Two fundamental challenges of NMR-based metabolomics are the detection limit and characterization of metabolites (or NMR resonance assignments...

Science meets regulation.

PubMed

Bilia, Anna Rita

2014-12-02

The European Pharmacopoeia (Ph. Eur.) is a standard reference for both European and non-European countries and defines requirements for the qualitative and quantitative composition of medicines. Herbal drug (HD) monographs state which aspects have to be considered for quality assurance through the relevant chapters "Definition", "Characters", "Identification", "Tests", and "Assay". Identification of botanical material is achieved by macroscopic and microscopic morphology, generally examined by a trained expert. Content or assay is the most difficult area of quality control to perform, since in most herbal drugs the active constituents are unknown and markers should be used which cannot be really related to the quality. The other critical points are represented by the purity tests, in particular some tests such as heavy metals, aflatoxins and pesticides are laborious and time intensive, requiring a significant investment in equipment, materials, and maintenance. A literature survey concerning alternative and/or complementary tools for quality control of botanicals has been performed by searching the scientific databases Pubmed, SciFinder, Scopus and Web of Science. Diverse analytical methods including DNA fingerprinting, Nuclear Magnetic Resonance (NMR), Near Infra Red (NIR) and (bio)sensors have been reported in the literature to evaluate the quality of botanical products. Identification of plants at the species level can be successfully based on genome-based methods, using DNA barcodes, the nucleotide sequence of a short DNA fragment. NMR can provide direct NMR fingerprint determination (complete assignment of the signals by 1D and 2D experiments), quantitative NMR and chemometric analysis (the metabolite fingerprint is based on the distribution of intensity in the NMR spectrum to provide sample classification). NIR spectroscopy is a fast qualitative and quantitative analytical method, getting knowledge about plant species and/or its geographic origin. Finally, the development of chemical and biological sensors is currently one of the most active areas of analytical research. Immobilization of specific enzymes led to recognize definite class of compounds such as cysteine sulfoxides, glucosinolates, cyanogenic glycosides, and polyphenols. Other recognition elements are nucleic acids to evaluate the ability of different molecules to bind DNA. Sensors have also been developed for the detection of heavy metals in botanicals. Moreover, the analysis of mycotoxins and pesticides, could represent another field of possible application. These alternative/complementary analytical methods represent tools which appear to be an analyst's dream: they are able to give rapid analysis responses; to operate directly on complex matrices, in many cases; to be selective and sensitive enough for the required application; to be portable and sometimes also disposable; and to have fast analysis times. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A pilot study of NMR-based sensory prediction of roasted coffee bean extracts.

PubMed

Wei, Feifei; Furihata, Kazuo; Miyakawa, Takuya; Tanokura, Masaru

2014-01-01

Nuclear magnetic resonance (NMR) spectroscopy can be considered a kind of "magnetic tongue" for the characterisation and prediction of the tastes of foods, since it provides a wealth of information in a nondestructive and nontargeted manner. In the present study, the chemical substances in roasted coffee bean extracts that could distinguish and predict the different sensations of coffee taste were identified by the combination of NMR-based metabolomics and human sensory test and the application of the multivariate projection method of orthogonal projection to latent structures (OPLS). In addition, the tastes of commercial coffee beans were successfully predicted based on their NMR metabolite profiles using our OPLS model, suggesting that NMR-based metabolomics accompanied with multiple statistical models is convenient, fast and accurate for the sensory evaluation of coffee. Copyright © 2013 Elsevier Ltd. All rights reserved.

Early Prediction of Lupus Nephritis Using Advanced Proteomics

DTIC Science & Technology

2010-06-01

SELDI-TOF-MS. Additional proteomic profiling studies using NMR- and MS-based metabonomics have been completed, and LC/MS based protein profiling using...Flight mass spectrometry (SELDI-TOF-MS). Changes in proteomic profiles will be confirmed and enhanced using NMR- and MS-based metabonomics , by Dr...performed using NMR- and MS-based metabonomics at Miami University, in the laboratory of Dr. Michael Kennedy. Initial spectra and profiles obtained show

Residue-level global and local ensemble-ensemble comparisons of protein domains.

PubMed

Clark, Sarah A; Tronrud, Dale E; Karplus, P Andrew

2015-09-01

Many methods of protein structure generation such as NMR-based solution structure determination and template-based modeling do not produce a single model, but an ensemble of models consistent with the available information. Current strategies for comparing ensembles lose information because they use only a single representative structure. Here, we describe the ENSEMBLATOR and its novel strategy to directly compare two ensembles containing the same atoms to identify significant global and local backbone differences between them on per-atom and per-residue levels, respectively. The ENSEMBLATOR has four components: eePREP (ee for ensemble-ensemble), which selects atoms common to all models; eeCORE, which identifies atoms belonging to a cutoff-distance dependent common core; eeGLOBAL, which globally superimposes all models using the defined core atoms and calculates for each atom the two intraensemble variations, the interensemble variation, and the closest approach of members of the two ensembles; and eeLOCAL, which performs a local overlay of each dipeptide and, using a novel measure of local backbone similarity, reports the same four variations as eeGLOBAL. The combination of eeGLOBAL and eeLOCAL analyses identifies the most significant differences between ensembles. We illustrate the ENSEMBLATOR's capabilities by showing how using it to analyze NMR ensembles and to compare NMR ensembles with crystal structures provides novel insights compared to published studies. One of these studies leads us to suggest that a "consistency check" of NMR-derived ensembles may be a useful analysis step for NMR-based structure determinations in general. The ENSEMBLATOR 1.0 is available as a first generation tool to carry out ensemble-ensemble comparisons. © 2015 The Protein Society.

Residue-level global and local ensemble-ensemble comparisons of protein domains

PubMed Central

Clark, Sarah A; Tronrud, Dale E; Andrew Karplus, P

2015-01-01

Many methods of protein structure generation such as NMR-based solution structure determination and template-based modeling do not produce a single model, but an ensemble of models consistent with the available information. Current strategies for comparing ensembles lose information because they use only a single representative structure. Here, we describe the ENSEMBLATOR and its novel strategy to directly compare two ensembles containing the same atoms to identify significant global and local backbone differences between them on per-atom and per-residue levels, respectively. The ENSEMBLATOR has four components: eePREP (ee for ensemble-ensemble), which selects atoms common to all models; eeCORE, which identifies atoms belonging to a cutoff-distance dependent common core; eeGLOBAL, which globally superimposes all models using the defined core atoms and calculates for each atom the two intraensemble variations, the interensemble variation, and the closest approach of members of the two ensembles; and eeLOCAL, which performs a local overlay of each dipeptide and, using a novel measure of local backbone similarity, reports the same four variations as eeGLOBAL. The combination of eeGLOBAL and eeLOCAL analyses identifies the most significant differences between ensembles. We illustrate the ENSEMBLATOR's capabilities by showing how using it to analyze NMR ensembles and to compare NMR ensembles with crystal structures provides novel insights compared to published studies. One of these studies leads us to suggest that a “consistency check” of NMR-derived ensembles may be a useful analysis step for NMR-based structure determinations in general. The ENSEMBLATOR 1.0 is available as a first generation tool to carry out ensemble-ensemble comparisons. PMID:26032515

Introducing Undergraduate Students to Metabolomics Using a NMR-Based Analysis of Coffee Beans

ERIC Educational Resources Information Center

Sandusky, Peter Olaf

2017-01-01

Metabolomics applies multivariate statistical analysis to sets of high-resolution spectra taken over a population of biologically derived samples. The objective is to distinguish subpopulations within the overall sample population, and possibly also to identify biomarkers. While metabolomics has become part of the standard analytical toolbox in…

Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study.

PubMed

Du, Shanshan; Sun, Shuhong; Liu, Liyan; Zhang, Qiao; Guo, Fuchuan; Li, Chunlong; Feng, Rennan; Sun, Changhao

2017-06-02

The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine 1 H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum 1 H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-glucose were exhibited after histidine supplement. In urine 1 H NMR metabolic profiles, citrate, creatinine/creatine, methylguanidine, and betaine + TMAO were higher, while hippurate was lower in histidine supplement group. In serum AA profiles, 10 AAs changed after histidine supplementation, including increased histidine, glycine, alanine, lysine, asparagine, and tyrosine and decreased leucine, isoleucine, ornithine, and citrulline. The study showed a systemic metabolic response in serum and urine metabolomics and AA profiles to histidine supplementation, showing significantly changed metabolism in AAs, lipid, and glucose in obese women with MetS.

Synthesis, crystal structure and biological activity of the Schiff base organotin(IV) complexes based on salicylaldehyde-o-aminophenol

NASA Astrophysics Data System (ADS)

Tan, Yu-Xing; Zhang, Zhi-Jian; Liu, Yang; Yu, Jiang-Xi; Zhu, Xiao-Ming; Kuang, Dai-Zhi; Jiang, Wu-Jiu

2017-12-01

Schiff base organotin(IV) complexes C1 ∼ C5b have been synthesized via the reaction of the substituted salicylaldehyde-o-aminophenol Schiff base ligands (L1 ∼ L3) with the dibenzyltin dichloride, n-butyltin trichloride or dibutyltin oxide, respectively. The complexes have been characterized by IR, UV-Vis, 1H NMR, 13C NMR spectra, elemental analysis and the crystal structures have been determined by X-ray diffraction. The anticancer activity of the Schiff base ligand and complexes C1 ∼ C5b against five species of cancer cell which are Hela, MCF7, HepG2, Colo205, NCIsbnd H460 were tested respectively, the tests showed that C1 ∼ C5b exhibited significant anticancer activity for the cancer cells in comparison with the ligand, and the activity was greater than carboplatin.

Nuclear magnetic resonance (NMR) study of the effect of cisplatin on the metabolic profile of MG-63 osteosarcoma cells.

PubMed

Duarte, Iola F; Lamego, Ines; Marques, Joana; Marques, M Paula M; Blaise, Benjamin J; Gil, Ana M

2010-11-05

In the present study, (1)H HRMAS NMR spectroscopy was used to assess the changes in the intracellular metabolic profile of MG-63 human osteosarcoma (OS) cells induced by the chemotherapy agent cisplatin (CDDP) at different times of exposure. Multivariate analysis was applied to the cells spectra, enabling consistent variation patterns to be detected and drug-specific metabolic effects to be identified. Statistical recoupling of variables (SRV) analysis and spectral integration enabled the most relevant spectral changes to be evaluated, revealing significant time-dependent alterations in lipids, choline-containing compounds, some amino acids, polyalcohols, and nitrogenated bases. The metabolic relevance of these compounds in the response of MG-63 cells to CDDP treatment is discussed.

Hydrogenation of Carbon Dioxide Catalyzed by Ruthenium Trimethylphosphine Complexes: A Mechanistic Investigation using High-Pressure NMR Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Getty, April D.; Tai, Chih-Cheng; Linehan, John C.

2009-08-26

The previously reported complex, cis-(PMe3)4RuCl(OAc) (1) acts as a catalyst for CO2 hydrogenation into formic acid in the presence of a base and an alcohol co-catalyst. NMR spectroscopy has revealed that 1 exists in solution in equilibrium with fac-(PMe3)3RuCl(h2-OAc) (2), [(PMe3)4Ru(h2-OAc)]Cl (3a), and free PMe3. Complex 2 has been isolated and characterized by elemental analysis, NMR spectroscopy, and X-ray crystallography. 2 has been tested as a CO2 hydrogenation catalyst, however, it performed poorly under the conditions of catalysis used for 1. Complex 3a can be prepared by adding certain alcohols, such as MeOH, EtOH, or o-C6H5OH, to a solution ofmore » 1 in CDCl3. The chloride ion of 3a has been exchanged for the non-coordinating anions BPh4 or B(ArF )4 (B(ArF)4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) to produce [(PMe3)4Ru(h2-OAc)]BPh4 (3b) and [(PMe3)4Ru(h2-OAc)]B(ArF)4 (3c). Both of these complexes have been isolated and characterized by elemental analysis, NMR spectroscopy, and in the case of 3b, X-ray crystallography. Complexes 3b and 3c perform just as well as 1 for CO2 hydrogenation to formic acid in the presence of an alcohol co-catalyst; however, 3b,c perform equally well without the added alcohol. High-pressure NMR has been used to investigate the mechanism of CO2 hydrogenation via 3a,b in the presence of base. Two of the intermediates involved have been identified as cis-(PMe3)4RuH2 (5) and cis-(PMe3)4Ru(H)O2CH (6), and the role of the base includes not only trapping of the formic acid product, but also initiation of the catalysis by aiding the conversion of 3b,c to 5.« less

MAS-NMR investigations of the crystallization behaviour of lithium aluminum silicate (LAS) glasses containing P 2O 5 and TiO 2 nucleants

NASA Astrophysics Data System (ADS)

Ananthanarayanan, A.; Kothiyal, G. P.; Montagne, L.; Revel, B.

2010-06-01

Lithium aluminum silicate (LAS) glass of composition (mol%) 20.4Li 2O-4.0Al 2O 3-68.6SiO 2-3.0K 2O-2.6B 2O 3-0.5P 2O 5-0.9TiO 2 was prepared by melt quenching. The glass was then nucleated and crystallized based on differential thermal analysis (DTA) data and was characterized by 29Si, 31P, 11B and 27Al MAS-NMR. XRD and 29Si NMR showed that lithium metasilicate (Li 2SiO 3) is the first phase to c form followed by cristobalite (SiO 2) and lithium disilicate (Li 2Si 2O 5). 29Si MAS-NMR revealed a change in the network structure already for the glasses nucleated at 550 °C. Since crystalline Li 3PO 4, as observed by 31P MAS-NMR, forms concurrently with the silicate phases, we conclude that crystalline Li 3PO 4 does not act as a nucleating agent for lithium silicate phases. Moreover, 31P NMR indicates the formation of M-PO 4 ( M=B, Al or Ti) complexes. The presence of BO 3 and BO 4 structural units in all the glass/glass-ceramic samples is revealed through 11B MAS-NMR. B remains in the residual glass and the crystallization of silicate phases causes a reduction in the number of alkali ions available for charge compensation. As a result, the number of trigonally coordinated B (BO 3) increases at the expense of tetrahedrally coordinated B (BO 4). The 27Al MAS-NMR spectra indicate the presence of tetrahedrally coordinated Al species, which are only slightly perturbed by the crystallization.

Optimized slice-selective 1H NMR experiments combined with highly accurate quantitative 13C NMR using an internal reference method.

PubMed

Jézéquel, Tangi; Silvestre, Virginie; Dinis, Katy; Giraudeau, Patrick; Akoka, Serge

2018-04-01

Isotope ratio monitoring by 13 C NMR spectrometry (irm- 13 C NMR) provides the complete 13 C intramolecular position-specific composition at natural abundance. It represents a powerful tool to track the (bio)chemical pathway which has led to the synthesis of targeted molecules, since it allows Position-specific Isotope Analysis (PSIA). Due to the very small composition range (which represents the range of variation of the isotopic composition of a given nuclei) of 13 C natural abundance values (50‰), irm- 13 C NMR requires a 1‰ accuracy and thus highly quantitative analysis by 13 C NMR. Until now, the conventional strategy to determine the position-specific abundance x i relies on the combination of irm-MS (isotopic ratio monitoring Mass Spectrometry) and 13 C quantitative NMR. However this approach presents a serious drawback since it relies on two different techniques and requires to measure separately the signal of all the carbons of the analyzed compound, which is not always possible. To circumvent this constraint, we recently proposed a new methodology to perform 13 C isotopic analysis using an internal reference method and relying on NMR only. The method combines a highly quantitative 1 H NMR pulse sequence (named DWET) with a 13 C isotopic NMR measurement. However, the recently published DWET sequence is unsuited for samples with short T 1 , which forms a serious limitation for irm- 13 C NMR experiments where a relaxing agent is added. In this context, we suggest two variants of the DWET called Multi-WET and Profiled-WET, developed and optimized to reach the same accuracy of 1‰ with a better immunity towards T 1 variations. Their performance is evaluated on the determination of the 13 C isotopic profile of vanillin. Both pulse sequences show a 1‰ accuracy with an increased robustness to pulse miscalibrations compared to the initial DWET method. This constitutes a major advance in the context of irm- 13 C NMR since it is now possible to perform isotopic analysis with high relaxing agent concentrations, leading to a strong reduction of the overall experiment time. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization and quantification of N-(3-aminopropyl)-N-dodecyl-1,3-propanediamine biocide by NMR, HPLC/MS and titration techniques.

PubMed

Mondin, Andrea; Bogialli, Sara; Venzo, Alfonso; Favaro, Gabriella; Badocco, Denis; Pastore, Paolo

2014-01-01

The present paper reports the determination of the tri-amine N-(3-aminopropyl)-N-dodecyl-1,3-propanediamine (TA) present in a raw material called LONZABAC used to formulate various, widely used commercial biocides. The active principle, TA, is present in LONZABAC together with other molecules at lower concentration levels. Three independent analytical approaches, namely solution NMR spectroscopy, liquid chromatography coupled to high resolution mass spectrometry (LC/HRMS) and acid-base titration in mixed solvent, were used to overcome the problem of the non-availability of the active principle as high purity standard. NMR analysis of raw material, using a suitable internal standard, evidenced in all analyzed lots the presence of the active principle, the N-dodecyl-1,3-propanediamine (DA) and the n-dodecylamine (MA) and the absence of non-organic, NMR-inactive species. NMR peak integration led to a rough composition of the MA:DA:TA as 1:9:90. The LC/HRMS analysis allowed the accurate determination of DA and MA and confirmed in all samples the presence of the TA, which was estimated by difference: MA=1.4±0.3%, DA=11.1±0.7%, TA=87.5±1.3%. The obtained results were used to setup an easy, rapid and cheap acid-base titration method able to furnish a sufficiently accurate evaluation of the active principle both in the raw material and in diluted commercial products. For the raw material the results were: TA+MA=91.1±0.8% and DA-MA=8.9±0.8%, statistically coherent with LC/MS ones. The LC/MS approach demonstrated also its great potentialities to recognize trace of the biocide components both in environmental samples and in the formulated commercial products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recommendations of the wwPDB NMR Validation Task Force

PubMed Central

Montelione, Gaetano T.; Nilges, Michael; Bax, Ad; Güntert, Peter; Herrmann, Torsten; Richardson, Jane S.; Schwieters, Charles; Vranken, Wim F.; Vuister, Geerten W.; Wishart, David S.; Berman, Helen M.; Kleywegt, Gerard J.; Markley, John L.

2013-01-01

As methods for analysis of biomolecular structure and dynamics using nuclear magnetic resonance spectroscopy (NMR) continue to advance, the resulting 3D structures, chemical shifts, and other NMR data are broadly impacting biology, chemistry, and medicine. Structure model assessment is a critical area of NMR methods development, and is an essential component of the process of making these structures accessible and useful to the wider scientific community. For these reasons, the Worldwide Protein Data Bank (wwPDB) has convened an NMR Validation Task Force (NMR-VTF) to work with the wwPDB partners in developing metrics and policies for biomolecular NMR data harvesting, structure representation, and structure quality assessment. This paper summarizes the recommendations of the NMR-VTF, and lays the groundwork for future work in developing standards and metrics for biomolecular NMR structure quality assessment. PMID:24010715

High-throughput microcoil NMR of compound libraries using zero-dispersion segmented flow analysis.

PubMed

Kautz, Roger A; Goetzinger, Wolfgang K; Karger, Barry L

2005-01-01

An automated system for loading samples into a microcoil NMR probe has been developed using segmented flow analysis. This approach enhanced 2-fold the throughput of the published direct injection and flow injection methods, improved sample utilization 3-fold, and was applicable to high-field NMR facilities with long transfer lines between the sample handler and NMR magnet. Sample volumes of 2 microL (10-30 mM, approximately 10 microg) were drawn from a 96-well microtiter plate by a sample handler, then pumped to a 0.5-microL microcoil NMR probe as a queue of closely spaced "plugs" separated by an immiscible fluorocarbon fluid. Individual sample plugs were detected by their NMR signal and automatically positioned for stopped-flow data acquisition. The sample in the NMR coil could be changed within 35 s by advancing the queue. The fluorocarbon liquid wetted the wall of the Teflon transfer line, preventing the DMSO samples from contacting the capillary wall and thus reducing sample losses to below 5% after passage through the 3-m transfer line. With a wash plug of solvent between samples, sample-to-sample carryover was <1%. Significantly, the samples did not disperse into the carrier liquid during loading or during acquisitions of several days for trace analysis. For automated high-throughput analysis using a 16-second acquisition time, spectra were recorded at a rate of 1.5 min/sample and total deuterated solvent consumption was <0.5 mL (1 US dollar) per 96-well plate.

Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy.

PubMed

Egner, John M; Jensen, Davin R; Olp, Michael D; Kennedy, Nolan W; Volkman, Brian F; Peterson, Francis C; Smith, Brian C; Hill, R Blake

2018-03-02

An academic chemical screening approach was developed by using 2D protein-detected NMR, and a 352-chemical fragment library was screened against three different protein targets. The approach was optimized against two protein targets with known ligands: CXCL12 and BRD4. Principal component analysis reliably identified compounds that induced nonspecific NMR crosspeak broadening but did not unambiguously identify ligands with specific affinity (hits). For improved hit detection, a novel scoring metric-difference intensity analysis (DIA)-was devised that sums all positive and negative intensities from 2D difference spectra. Applying DIA quickly discriminated potential ligands from compounds inducing nonspecific NMR crosspeak broadening and other nonspecific effects. Subsequent NMR titrations validated chemotypes important for binding to CXCL12 and BRD4. A novel target, mitochondrial fission protein Fis1, was screened, and six hits were identified by using DIA. Screening these diverse protein targets identified quinones and catechols that induced nonspecific NMR crosspeak broadening, hampering NMR analyses, but are currently not computationally identified as pan-assay interference compounds. The results established a streamlined screening workflow that can easily be scaled and adapted as part of a larger screening pipeline to identify fragment hits and assess relative binding affinities in the range of 0.3-1.6 mm. DIA could prove useful in library screening and other applications in which NMR chemical shift perturbations are measured. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An efficient algorithm for automatic phase correction of NMR spectra based on entropy minimization

NASA Astrophysics Data System (ADS)

Chen, Li; Weng, Zhiqiang; Goh, LaiYoong; Garland, Marc

2002-09-01

A new algorithm for automatic phase correction of NMR spectra based on entropy minimization is proposed. The optimal zero-order and first-order phase corrections for a NMR spectrum are determined by minimizing entropy. The objective function is constructed using a Shannon-type information entropy measure. Entropy is defined as the normalized derivative of the NMR spectral data. The algorithm has been successfully applied to experimental 1H NMR spectra. The results of automatic phase correction are found to be comparable to, or perhaps better than, manual phase correction. The advantages of this automatic phase correction algorithm include its simple mathematical basis and the straightforward, reproducible, and efficient optimization procedure. The algorithm is implemented in the Matlab program ACME—Automated phase Correction based on Minimization of Entropy.

Real-time analysis of multiple anion mixtures in aqueous media using a single receptor.

PubMed

Havel, Vaclav; Yawer, Mirza Arfan; Sindelar, Vladimir

2015-03-18

Bambusuril-based receptors have been used in conjunction with (1)H NMR spectroscopy to recognize mixtures of inorganic anions in aqueous solutions. This was achieved by examining complexation-induced changes in the receptors' (1)H NMR fingerprints. This approach enables the simultaneous identification of up to 9 anions and the quantification of up to 5 anions using a single receptor in DMSO-d6 containing 5% D2O. Toxic perchlorate was recognized and quantified at 0.1 μM (1.8 ppb, mol mol(-1)) concentration in pure water.

On the microscopic fluctuations driving the NMR relaxation of quadrupolar ions in water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carof, Antoine; Salanne, Mathieu; Rotenberg, Benjamin, E-mail: benjamin.rotenberg@upmc.fr

Nuclear Magnetic Resonance (NMR) relaxation is sensitive to the local structure and dynamics around the probed nuclei. The Electric Field Gradient (EFG) is the key microscopic quantity to understand the NMR relaxation of quadrupolar ions, such as {sup 7}Li{sup +}, {sup 23}Na{sup +}, {sup 25}Mg{sup 2+}, {sup 35}Cl{sup −}, {sup 39}K{sup +}, or {sup 133}Cs{sup +}. Using molecular dynamics simulations, we investigate the statistical and dynamical properties of the EFG experienced by alkaline, alkaline Earth, and chloride ions at infinite dilution in water. Specifically, we analyze the effect of the ionic charge and size on the distribution of the EFGmore » tensor and on the multi-step decay of its auto-correlation function. The main contribution to the NMR relaxation time arises from the slowest mode, with a characteristic time on the picosecond time scale. The first solvation shell of the ion plays a dominant role in the fluctuations of the EFG, all the more that the ion radius is small and its charge is large. We propose an analysis based on a simplified charge distribution around the ion, which demonstrates that the auto-correlation of the EFG, hence the NMR relaxation time, reflects primarily the collective translational motion of water molecules in the first solvation shell of the cations. Our findings provide a microscopic route to the quantitative interpretation of NMR relaxation measurements and open the way to the design of improved analytical theories for NMR relaxation for small ionic solutes, which should focus on water density fluctuations around the ion.« less

Direct synthesis of acid-base bifunctionalized hexagonal mesoporous silica and its catalytic activity in cascade reactions.

PubMed

Shang, Fanpeng; Sun, Jianrui; Wu, Shujie; Liu, Heng; Guan, Jingqi; Kan, Qiubin

2011-03-01

A series of efficient acid-base bifunctionalized hexagonal mesoporous silica (HMS) catalysts contained aminopropyl and propanesulfonic acid have been synthesized through a simple co-condensation by protection of amino group. The results of small-angle XRD, TEM, and N(2) adsorption-desorption measurements show that the resultant materials have mesoscopic structures. X-ray photoelectron spectroscopies, elemental analysis (EA), back titration, (29)Si NMR and (13)C NMR confirm that the organosiloxanes were condensed as a part of the silica framework. The resultant catalysts exhibit excellent acid-basic properties, which make them possess high activity for one-pot deacetalization-Knoevenagel and deacetalization-nitroaldol (Henry) reactions. Copyright © 2010 Elsevier Inc. All rights reserved.

Modification of indole by electron-rich atoms and their application in novel electron donor materials

NASA Astrophysics Data System (ADS)

Zhang, Maolin; Qin, Guangjiong; Liu, Jialei; Zhen, Zhen; Fedorchuk, A. A.; Lakshminarayana, G.; Albassam, A. A.; El-Naggar, A. M.; Ozga, Katarzyna; Kityk, I. V.

2017-08-01

Novel nonlinear optical (NLO) chromophore based on 6-(pyrrolidin-1-yl)-1H-indole as the electron donor group was designed and synthesized. The molecular structure of this chromophore was characterized by 1H NMR spectra, 13C NMR spectra, and MS spectra. The delocalized energy level was estimated by UV-Vis. spectra. The thermal property was studied by thermogravimetric analysis (TGA). The poled films containing chromophores ZML-1 with a loading density of 10 wt% in amorphous polycarbonate (APC) afford an average electro-optic (EO) coefficient (r33) of 19 pm/V at 1310 nm. Compared to the reported aniline-based chromophore (r33 = 12 pm/V) analogues, chromophore ZML-1 exhibits enhanced electro-optical activity.

QM/MM methodology, docking and spectroscopic (FT-IR/FT-Raman, NMR, UV) and Fukui function analysis on adrenergic agonist

NASA Astrophysics Data System (ADS)

Uma Maheswari, J.; Muthu, S.; Sundius, Tom

2015-02-01

The Fourier transform infrared, FT-Raman, UV and NMR spectra of Ternelin have been recorded and analyzed. Harmonic vibrational frequencies have been investigated with the help of HF with 6-31G (d,p) and B3LYP with 6-31G (d,p) and LANL2DZ basis sets. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by GIAO method. The polarizability (α) and the first hyperpolarizability (β) values of the investigated molecule have been computed using DFT quantum mechanical calculations. Stability of the molecule arising from hyper conjugative interactions, and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The electron density-based local reactivity descriptors such as Fukui functions were calculated to explain the chemical selectivity or reactivity site in Ternelin. Finally the calculated results were compared to simulated infrared and Raman spectra of the title compound which show good agreement with observed spectra. Molecular docking studies have been carried out in the active site of Ternelin and reactivity with ONIOM was also investigated.

NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes

PubMed Central

Dias, David M.; Ciulli, Alessio

2014-01-01

Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets. PMID:25175337

NMR-based metabolomics approach to study the chronic toxicity of crude ricin from castor bean kernels on rats.

PubMed

Guo, Pingping; Wang, Junsong; Dong, Ge; Wei, Dandan; Li, Minghui; Yang, Minghua; Kong, Lingyi

2014-07-29

Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM.

Differential Attenuation of NMR Signals by Complementary Ion-Exchange Resin Beads for De Novo Analysis of Complex Metabolomics Mixtures.

PubMed

Zhang, Bo; Yuan, Jiaqi; Brüschweiler, Rafael

2017-07-12

A primary goal of metabolomics is the characterization of a potentially very large number of metabolites that are part of complex mixtures. Application to biofluids and tissue samples offers insights into biochemical metabolic pathways and their role in health and disease. 1D 1 H and 2D 13 C- 1 H HSQC NMR spectra are most commonly used for this purpose. They yield quantitative information about each proton of the mixture, but do not tell which protons belong to the same molecule. Interpretation requires the use of NMR spectral databases, which naturally limits these investigations to known metabolites. Here, a new method is presented that uses complementary ion exchange resin beads to differentially attenuate 2D NMR cross-peaks that belong to different metabolites. Based on their characteristic attenuation patterns, cross-peaks could be clustered and assigned to individual molecules, including unknown metabolites with multiple spin systems, as demonstrated for a metabolite model mixture and E. coli cell lysate. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automatic Assignment of Methyl-NMR Spectra of Supramolecular Machines Using Graph Theory.

PubMed

Pritišanac, Iva; Degiacomi, Matteo T; Alderson, T Reid; Carneiro, Marta G; Ab, Eiso; Siegal, Gregg; Baldwin, Andrew J

2017-07-19

Methyl groups are powerful probes for the analysis of structure, dynamics and function of supramolecular assemblies, using both solution- and solid-state NMR. Widespread application of the methodology has been limited due to the challenges associated with assigning spectral resonances to specific locations within a biomolecule. Here, we present Methyl Assignment by Graph Matching (MAGMA), for the automatic assignment of methyl resonances. A graph matching protocol examines all possibilities for each resonance in order to determine an exact assignment that includes a complete description of any ambiguity. MAGMA gives 100% accuracy in confident assignments when tested against both synthetic data, and 9 cross-validated examples using both solution- and solid-state NMR data. We show that this remarkable accuracy enables a user to distinguish between alternative protein structures. In a drug discovery application on HSP90, we show the method can rapidly and efficiently distinguish between possible ligand binding modes. By providing an exact and robust solution to methyl resonance assignment, MAGMA can facilitate significantly accelerated studies of supramolecular machines using methyl-based NMR spectroscopy.

Conventional sample enrichment strategies combined with high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance analysis allows analyte identification from a single minuscule Corydalis solida plant tuber.

PubMed

Sturm, Sonja; Seger, Christoph; Godejohann, Markus; Spraul, Manfred; Stuppner, Hermann

2007-09-07

Identification of putative biomarker molecules within the genus Corydalis (Papaveraceae) was pursued by combining conventional off-line sample enrichment with high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance (HPLC-SPE-NMR) based structure elucidation. Off-line reversed phase solid phase extraction (SPE) was used to enrich the desired analytes from a methanolic extract (93 mg dry weight) of a miniscule single tuber (233 mg dry weight) of C. solida. An aliquot of the SPE fraction (2.1 mg) was subjected to separation in the HPLC-SPE-NMR hyphenation. Chromatographic peaks bearing the metabolites under investigation were trapped in the SPE device in a single experiment and transferred to a 600 MHz NMR spectrometer equipped with a 30 microl cryofit insert fed into a 3 mm cryoprobe. Recorded homo- and heteronuclear 1D and 2D NMR data allowed the identification of the three analytes under investigation as protopine, allocryptopine, and N-methyl-laudanidinium acetate. The latter is a rare alkaloid, which has been isolated only once before.

[Determination of the Plant Origin of Licorice Oil Extract, a Natural Food Additive, by Principal Component Analysis Based on Chemical Components].

PubMed

Tada, Atsuko; Ishizuki, Kyoko; Sugimoto, Naoki; Yoshimatsu, Kayo; Kawahara, Nobuo; Suematsu, Takako; Arifuku, Kazunori; Fukai, Toshio; Tamura, Yukiyoshi; Ohtsuki, Takashi; Tahara, Maiko; Yamazaki, Takeshi; Akiyama, Hiroshi

2015-01-01

"Licorice oil extract" (LOE) (antioxidant agent) is described in the notice of Japanese food additive regulations as a material obtained from the roots and/or rhizomes of Glycyrrhiza uralensis, G. inflata or G. glabra. In this study, we aimed to identify the original Glycyrrhiza species of eight food additive products using LC/MS. Glabridin, a characteristic compound in G. glabra, was specifically detected in seven products, and licochalcone A, a characteristic compound in G. inflata, was detected in one product. In addition, Principal Component Analysis (PCA) (a kind of multivariate analysis) using the data of LC/MS or (1)H-NMR analysis was performed. The data of thirty-one samples, including LOE products used as food additives, ethanol extracts of various Glycyrrhiza species and commercially available Glycyrrhiza species-derived products were assessed. Based on the PCA results, the majority of LOE products was confirmed to be derived from G. glabra. This study suggests that PCA using (1)H-NMR analysis data is a simple and useful method to identify the plant species of origin of natural food additive products.

Reproducibility of NMR Analysis of Urine Samples: Impact of Sample Preparation, Storage Conditions, and Animal Health Status

PubMed Central

Schreier, Christina; Kremer, Werner; Huber, Fritz; Neumann, Sindy; Pagel, Philipp; Lienemann, Kai; Pestel, Sabine

2013-01-01

Introduction. Spectroscopic analysis of urine samples from laboratory animals can be used to predict the efficacy and side effects of drugs. This employs methods combining 1H NMR spectroscopy with quantification of biomarkers or with multivariate data analysis. The most critical steps in data evaluation are analytical reproducibility of NMR data (collection, storage, and processing) and the health status of the animals, which may influence urine pH and osmolarity. Methods. We treated rats with a solvent, a diuretic, or a nephrotoxicant and collected urine samples. Samples were titrated to pH 3 to 9, or salt concentrations increased up to 20-fold. The effects of storage conditions and freeze-thaw cycles were monitored. Selected metabolites and multivariate data analysis were evaluated after 1H NMR spectroscopy. Results. We showed that variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no effect on the quantification of the metabolites or on multivariate data analysis. Storage led to changes after 14 days at 4°C or after 12 months at −20°C, independent of sample composition. Multiple freeze-thaw cycles did not affect data analysis. Conclusion. Reproducibility of NMR measurements is not dependent on sample composition under physiological or pathological conditions. PMID:23865070

Reproducibility of NMR analysis of urine samples: impact of sample preparation, storage conditions, and animal health status.

PubMed

Schreier, Christina; Kremer, Werner; Huber, Fritz; Neumann, Sindy; Pagel, Philipp; Lienemann, Kai; Pestel, Sabine

2013-01-01

Spectroscopic analysis of urine samples from laboratory animals can be used to predict the efficacy and side effects of drugs. This employs methods combining (1)H NMR spectroscopy with quantification of biomarkers or with multivariate data analysis. The most critical steps in data evaluation are analytical reproducibility of NMR data (collection, storage, and processing) and the health status of the animals, which may influence urine pH and osmolarity. We treated rats with a solvent, a diuretic, or a nephrotoxicant and collected urine samples. Samples were titrated to pH 3 to 9, or salt concentrations increased up to 20-fold. The effects of storage conditions and freeze-thaw cycles were monitored. Selected metabolites and multivariate data analysis were evaluated after (1)H NMR spectroscopy. We showed that variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no effect on the quantification of the metabolites or on multivariate data analysis. Storage led to changes after 14 days at 4°C or after 12 months at -20°C, independent of sample composition. Multiple freeze-thaw cycles did not affect data analysis. Reproducibility of NMR measurements is not dependent on sample composition under physiological or pathological conditions.

Is Low-field NMR a Complementary Tool to GC-MS in Quality Control of Essential Oils? A Case Study: Patchouli Essential Oil.

PubMed

Krause, Andre; Wu, Yu; Tian, Runtao; van Beek, Teris A

2018-04-24

High-field NMR is an expensive and important quality control technique. In recent years, cheaper and simpler low-field NMR has become available as a new quality control technique. In this study, 60 MHz 1 H-NMR was compared with GC-MS and refractometry for the detection of adulteration of essential oils, taking patchouli essential oil as a test case. Patchouli essential oil is frequently adulterated, even today. In total, 75 genuine patchouli essential oils, 10 commercial patchouli essential oils, 10 other essential oils, 17 adulterants, and 1 patchouli essential oil, spiked at 20% with those adulterants, were measured. Visual inspection of the NMR spectra allowed for easy detection of 14 adulterants, while gurjun and copaiba balsams proved difficult and one adulterant could not be detected. NMR spectra of 10 random essential oils differed not only strongly from patchouli essential oil but also from one another, suggesting that fingerprinting by low-field NMR is not limited to patchouli essential oil. Automated chemometric evaluation of NMR spectra was possible by similarity analysis (Mahalanobis distance) based on the integration from 0.1 - 8.1 ppm in 0.01 ppm increments. Good quality patchouli essential oils were recognised as well as 15 of 17 deliberate adulterations. Visual qualitative inspection by GC-MS allowed for the detection of all volatile adulterants. Nonvolatile adulterants, and all but one volatile adulterant, could be detected by semiquantitation. Different chemometric approaches showed satisfactory results. Similarity analyses were difficult with nonvolatile adulterants. Refractive index measurements could detect only 8 of 17 adulterants. Due to advantages such as simplicity, rapidity, reproducibility, and ability to detect nonvolatile adulterants, 60 MHz 1 H-NMR is complimentary to GC-MS for quality control of essential oils. Georg Thieme Verlag KG Stuttgart · New York.

Impact of genetic strain on body fat loss, food consumption, metabolism, ventilation, and motor activity in free running female rats

EPA Science Inventory

Nuclear magnetic resonance (NMR) based body composition analysis is an idea means of assessing changes in relative proportions of fat, lean, and fluid in rodents non­ invasively. While the data are not as accurate as convent ional chemical analysis, the systems allow one to follo...

Solid-state NMR adiabatic TOBSY sequences provide enhanced sensitivity for multidimensional high-resolution magic-angle-spinning 1H MR spectroscopy

NASA Astrophysics Data System (ADS)

Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Struppe, Jochem; Black, Peter M.; Tzika, A. Aria

2008-08-01

We propose a solid-state NMR method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS) applied to intact biopsies when compared to more conventional liquid-state NMR approaches. Theoretical treatment, numerical simulations and experimental results on intact human brain biopsies are presented. Experimentally, it is proven that an optimized adiabatic TOBSY (TOtal through Bond correlation SpectroscopY) solid-state NMR pulse sequence for two-dimensional 1H- 1H homonuclear scalar-coupling longitudinal isotropic mixing provides a 20%-50% improvement in signal-to-noise ratio relative to its liquid-state analogue TOCSY (TOtal Correlation SpectroscopY). For this purpose we have refined the C9151 symmetry-based 13C TOBSY pulse sequence for 1H MRS use and compared it to MLEV-16 TOCSY sequence. Both sequences were rotor-synchronized and implemented using WURST-8 adiabatic inversion pulses. As discussed theoretically and shown in simulations, the improved magnetization-transfer comes from actively removing residual dipolar couplings from the average Hamiltonian. Importantly, the solid-state NMR techniques are tailored to perform measurements at low temperatures where sample degradation is reduced. This is the first demonstration of such a concept for HRMAS metabolic profiling of disease processes, including cancer, from biopsies requiring reduced sample degradation for further genomic analysis.

NMR absolute shielding scale and nuclear magnetic dipole moment of (207)Pb.

PubMed

Adrjan, Bożena; Makulski, Włodzimierz; Jackowski, Karol; Demissie, Taye B; Ruud, Kenneth; Antušek, Andrej; Jaszuński, Michał

2016-06-28

An absolute shielding scale is proposed for (207)Pb nuclear magnetic resonance (NMR) spectroscopy. It is based on ab initio calculations performed on an isolated tetramethyllead Pb(CH3)4 molecule and the assignment of the experimental resonance frequency from the gas-phase NMR spectra of Pb(CH3)4, extrapolated to zero density of the buffer gas to obtain the result for an isolated molecule. The computed (207)Pb shielding constant is 10 790 ppm for the isolated molecule, leading to a shielding of 10799.7 ppm for liquid Pb(CH3)4 which is the accepted reference standard for (207)Pb NMR spectra. The new experimental and theoretical data are used to determine μ((207)Pb), the nuclear magnetic dipole moment of (207)Pb, by applying the standard relationship between NMR frequencies, shielding constants and nuclear moments of two nuclei in the same external magnetic field. Using the gas-phase (207)Pb and (reference) proton results and the theoretical value of the Pb shielding in Pb(CH3)4, we find μ((207)Pb) = 0.59064 μN. The analysis of new experimental and theoretical data obtained for the Pb(2+) ion in water solutions provides similar values of μ((207)Pb), in the range of 0.59000-0.59131 μN.

C terminal retroviral-type zinc finger domain from the HIV-1 nucleocapsid protein is structurally similar to the N-terminal zinc finger domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

South, T.L.; Blake, P.R.; Hare, D.R.

Two-dimensional NMR spectroscopic and computational methods were employed for the structure determination of an 18-residue peptide with the amino acid sequence of the C-terminal retriviral-type (r.t.) zinc finger domain from the nucleocapsid protein (NCP) of HIV-1 (Zn(HIV1-F2)). Unlike results obtained for the first retroviral-type zinc finger peptide, Zn (HIV1-F1) broad signals indicative of confomational lability were observed in the {sup 1}H NMR spectrum of An(HIV1-F2) at 25 C. The NMR signals narrowed upon cooling to {minus}2 C, enabling complete {sup 1}H NMR signal assignment via standard two-dimensional (2D) NMR methods. Distance restraints obtained from qualitative analysis of 2D nuclear Overhausermore » effect (NOESY) data were sued to generate 30 distance geometry (DG) structures with penalties in the range 0.02-0.03 {angstrom}{sup 2}. All structures were qualitatively consistent with the experimental NOESY spectrum based on comparisons with 2D NOESY back-calculated spectra. These results indicate that the r.t. zinc finger sequences observed in retroviral NCPs, simple plant virus coat proteins, and in a human single-stranded nucleic acid binding protein share a common structural motif.« less

Probing the Carbonyl Functionality of a Petroleum Resin and Asphaltene through Oximation and Schiff Base Formation in Conjunction with N-15 NMR

PubMed Central

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected. PMID:26556054

Fingerprinting analysis of Rhizoma chuanxiong of commercial types using 1H nuclear magnetic resonance spectroscopy and high performance liquid chromatography method.

PubMed

Qin, Hai-Lin; Deng, An-Jun; Du, Guan-Hua; Wang, Peng; Zhang, Jin-Lan; Li, Zhi-Hong

2009-06-01

The (1)H nuclear magnetic resonance ((1)H NMR) fingerprints of fractionated non-polar extracts (control substance for a plant drug (CSPD) A) from Rhizoma chuanxiong, the rhizomes of Ligusticum chuanxiong Hort., of seven specimens from different sources were measured on Fourier Transform (FT)-NMR spectrometer and assigned by comparing them with the (1)H NMR spectra of the isolated pure compounds. The (1)H NMR fingerprints showed exclusively characteristic resonance signals of the major special constituents of the plant. Although the differences in the relative intensity of the (1)H NMR signals due to a discrepancy in the ratio of the major constituents among these samples could be confirmed by high performance liquid chromatography analysis, the general features of the (1)H NMR fingerprint established for an authentic sample of the rhizomes of L. chuanxiong exhibited exclusive data from those special compounds and can be used for authenticating L. Chuanxiong species.

Soil organic matter composition from correlated thermal analysis and nuclear magnetic resonance data in Australian national inventory of agricultural soils

NASA Astrophysics Data System (ADS)

Moore, T. S.; Sanderman, J.; Baldock, J.; Plante, A. F.

2016-12-01

National-scale inventories typically include soil organic carbon (SOC) content, but not chemical composition or biogeochemical stability. Australia's Soil Carbon Research Programme (SCaRP) represents a national inventory of SOC content and composition in agricultural systems. The program used physical fractionation followed by 13C nuclear magnetic resonance (NMR) spectroscopy. While these techniques are highly effective, they are typically too expensive and time consuming for use in large-scale SOC monitoring. We seek to understand if analytical thermal analysis is a viable alternative. Coupled differential scanning calorimetry (DSC) and evolved gas analysis (CO2- and H2O-EGA) yields valuable data on SOC composition and stability via ramped combustion. The technique requires little training to use, and does not require fractionation or other sample pre-treatment. We analyzed 300 agricultural samples collected by SCaRP, divided into four fractions: whole soil, coarse particulates (POM), untreated mineral associated (HUM), and hydrofluoric acid (HF)-treated HUM. All samples were analyzed by DSC-EGA, but only the POM and HF-HUM fractions were analyzed by NMR. Multivariate statistical analyses were used to explore natural clustering in SOC composition and stability based on DSC-EGA data. A partial least-squares regression (PLSR) model was used to explore correlations among the NMR and DSC-EGA data. Correlations demonstrated regions of combustion attributable to specific functional groups, which may relate to SOC stability. We are increasingly challenged with developing an efficient technique to assess SOC composition and stability at large spatial and temporal scales. Correlations between NMR and DSC-EGA may demonstrate the viability of using thermal analysis in lieu of more demanding methods in future large-scale surveys, and may provide data that goes beyond chemical composition to better approach quantification of biogeochemical stability.

Comprehensive analysis of commercial willow bark extracts by new technology platform: combined use of metabolomics, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy and high-resolution radical scavenging assay.

PubMed

Agnolet, Sara; Wiese, Stefanie; Verpoorte, Robert; Staerk, Dan

2012-11-02

Here, proof-of-concept of a new analytical platform used for the comprehensive analysis of a small set of commercial willow bark products is presented, and compared with a traditional standardization solely based on analysis of salicin and salicin derivatives. The platform combines principal component analysis (PCA) of two chemical fingerprints, i.e., HPLC and (1)H NMR data, and a pharmacological fingerprint, i.e., high-resolution 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(+)) reduction profile, with targeted identification of constituents of interest by hyphenated HPLC-solid-phase extraction-tube transfer NMR, i.e., HPLC-SPE-ttNMR. Score plots from PCA of HPLC and (1)H NMR fingerprints showed the same distinct grouping of preparations formulated as capsules of Salix alba bark and separation of S. alba cortex. Loading plots revealed this to be due to high amount of salicin in capsules and ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba cortex, respectively. PCA of high-resolution radical scavenging profiles revealed clear separation of preparations along principal component 1 due to the major radical scavengers (+)-catechin and ampelopsin. The new analytical platform allowed identification of 16 compounds in commercial willow bark extracts, and identification of ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, and 7-O-methyltaxifolin in S. alba bark extract is reported for the first time. The detection of the novel compound, ethyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate, is also described. Copyright © 2012 Elsevier B.V. All rights reserved.

Group type analysis of asphalt by column liquid chromatography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, C.; Yang, J.; Xue, Y.

2008-07-01

An improved analysis method for characterization of asphalt was established. The method is based on column chromatography technique. The asphalts were separated into four groups: saturates, aromatics, resins, and asphaltenes, quantitatively. About 0.1 g of sample was required in each analysis. About 20 mL of n-heptanes was used to separate out saturates first. Then about 35 mL of n-heptanes/dichloromethane (.5, v/v) mixture was used to separate out aromatics. About 30 mL of dichloromethane/tetrahydrofuran (1/3, v/v) mixture was used to separate out resin. The quality of the separation was confirmed by infrared spectra (IR) and {sup 1}H NMR analysis. The modelmore » compounds, tetracosan for saturates, dibenz(o)anthracen for aromatics, and acetanilide for resins were used for verification. The IR and {sup 1}H NMR analysis of the prepared fractions from the column liquid chromatography were in good agreement that of pure reagents.« less

Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy.

PubMed

Li, Z Jane; Abramov, Yuriy; Bordner, Jon; Leonard, Jason; Medek, Ales; Trask, Andrew V

2006-06-28

A cancer candidate, compound 1, is a weak base with two heterocyclic basic nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble in water rendering it unsuitable for pharmaceutical development. The crystalline acid-base pairs of 1, collectively termed solid acid-base complexes, provide significant increases in the solubility and bioavailability compared to the free base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3, and dimaleate 4, show the most favorable physicochemical profiles and are studied in greater detail. The structural analyses of the three complexes using crystal structure and solid-state NMR reveal that the proton-transfer behavior in these organic acid-base complexes vary successively correlating with Delta pKa. As a result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4 is an ionic salt. The addition of the acidic components leads to maximized hydrogen bond interactions forming extended three-dimensional networks. Although structurally similar, the packing arrangements of the three complexes are considerably different due to the presence of multiple functional groups and the flexible backbone of 1. The findings in this study provide insight into the structural characteristics of complexes involving heterocyclic bases and carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state NMR are truly complementary in elucidating hydrogen bonding interactions and the degree of proton transfer of these complexes.

1H NMR spectra dataset and solid-state NMR data of cowpea (Vigna unguiculata).

PubMed

Alves Filho, Elenilson G; Silva, Lorena M A; Teofilo, Elizita M; Larsen, Flemming H; de Brito, Edy S

2017-04-01

In this article the NMR data from chemical shifts, coupling constants, and structures of all the characterized compounds were provided, beyond a complementary PCA evaluation for the corresponding manuscript (E.G. Alves Filho, L.M.A. Silva, E.M. Teofilo, F.H. Larsen, E.S. de Brito, 2017) [3]. In addition, a complementary assessment from solid-state NMR data was provided. For further chemometric analysis, numerical matrices from the raw 1 H NMR data were made available in Microsoft Excel workbook format (.xls).

Novel dimeric metabolites from Alternaria tagetica.

PubMed

Gamboa-Angulo, M M; Alejos-González, F; Escalante-Erosa, F; García-Sosa, K; Delgado-Lamas, G; Peña-Rodríguez, L M

2000-08-01

Two novel polyketides, bis-7-O-8' '.8-O-7' '- and bis-7-O-7' '. 8-O-8' '-zinniol (2 and 3, respectively) were isolated from the organic crude extract of culture filtrates from Alternaria tagetica. Both structures were determined on the basis of their spectroscopic data (IR, MS, (1)H NMR, (13)C NMR, and 2D NMR experiments) and confirmed by chemical synthesis. Zinniol (1) was isolated as a major component, and its (13)C NMR data was correctly assigned after careful analysis of data from its 2D NMR experiments (HMQC and HMBC).

Application of 1H NMR spectroscopy-based metabonomics to feces of cervical cancer patients with radiation-induced acute intestinal symptoms.

PubMed

Chai, Yanlan; Wang, Juan; Wang, Tao; Yang, Yunyi; Su, Jin; Shi, Fan; Wang, Jiquan; Zhou, Xi; He, Bin; Ma, Hailin; Liu, Zi

2015-11-01

Radiation-induced acute intestinal symptoms (RIAISs) are a common complication of radiotherapy for cervical cancer. The aim of this study was to use (1)H nuclear magnetic resonance ((1)H NMR) combined with chemometric analysis to develop a metabolic profile of patients with RIAISs. Fecal samples were collected from 66 patients with cervical cancer before and after pelvic radiotherapy. After radiotherapy, RIAISs occurred in eleven patients. We selected another 11 patients from participants without RIAISs whose age, stage, histological type and treatment methods are matched with RIAIS patients as the control group. (1)H NMR spectroscopy combined with multivariate pattern recognition analysis was used to generate metabolic profile data, as well as to establish a RIAIS-specific metabolic phenotype. Orthogonal partial least-squares discriminant analysis was used to distinguish samples between the pre- and post-radiotherapy RIAIS patients and between RIAIS patients and controls. Fecal samples from RIAIS patients after pelvic radiotherapy were characterized by increased concentrations of α-ketobutyrate, valine, uracil, tyrosine, trimethylamine N-oxide, phenylalanine, lysine, isoleucine, glutamine, creatinine, creatine, bile acids, aminohippurate, and alanine, accompanied by reduced concentrations of α-glucose, n-butyrate, methylamine, and ethanol relative to samples from RIAIS patients before pelvic radiotherapy, while in RIAIS patients relative to controls, trimethylamine, n-butyrate, fumarate and acetate were down-regulated and valine, TMAO, taurine, phenylalanine, lactate, isoleucine and creatinine were up-regulated. We obtained the metabolic profile of RIAIS patients from fecal samples using NMR-based metabonomics. This profile has the potential to be developed into a novel clinical tool for RIAIS diagnosis or therapeutic monitoring, and could contribute to an improved understanding of the disease mechanism. However, because of the limitations of methods, technique, bacterial contamination of feces and small sample size, further research and verification are needed. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Enhanced NMR-based profiling of polyphenols in commercially available grape juices using solid-phase extraction.

PubMed

Savage, Angela K; van Duynhoven, John P M; Tucker, Gregory; Daykin, Clare A

2011-12-01

Grapes and related products, such as juices, and in particular, their polyphenols, have previously been associated with many health benefits, such as protection against cardiovascular disease. Within grapes, a large range of structurally diverse polyphenols can be present, and their characterisation stands as a challenge. (1)H NMR spectroscopy in principle would provide a rapid, nondestructive and straightforward method for profiling of polyphenols. However, polyphenol profiling and identification in grape juices is hindered because of signals of prevailing carbohydrates causing spectral overlap and compromising dynamic range. This study describes the development of an extraction method prior to analysis using (1)H NMR spectroscopy, which can, potentially, significantly increase the number of detectable polyphenols and aid their identification, by reduction of signal overlap and selective removal of heavily dominating compounds such as sugars. Copyright © 2012 John Wiley & Sons, Ltd.

Comparative structural analysis of cytidine, ethenocytidine and their protonated salts III. 1H, 13C and 15N NMR studies at natural isotope abundance.

PubMed Central

Kozerski, L; Sierzputowska-Gracz, H; Krzyzosiak, W; Bratek-Wiewiórowska, M; Jaskólski, M; Wiewiórowski, M

1984-01-01

The 1H, 13C, 15N NMR spectra of cytidine /Cyd/, ethenocytidine /epsilon Cyd/ and their hydrochlorides /Cyd X HC1/ and /epsilon Cyd X HC1/ have been analysed to compare structural differences observed in solution with those existing in the crystalline state. The effects of ethenobridging and protonation of the hertero-aromatic base on the intramolecular stereochemistry, intermolecular interactions and electronic structure of the whole molecule are discussed on the basis of the NMR studies in DMSO solutions. Particular interest is devoted to the discussion of the conformation of the ribose ring, the presence of the intramolecular C-5'-0...H-6-C hydrogen bond, unambiguous assignment of the site of protonation, the mechanism of the 5C-H deuterium exchange in Cyd X HC1, and the intermolecular interactions in solution. PMID:6701098

A new phase correction method in NMR imaging based on autocorrelation and histogram analysis.

PubMed

Ahn, C B; Cho, Z H

1987-01-01

A new statistical approach to phase correction in NMR imaging is proposed. The proposed scheme consists of first-and zero-order phase corrections each by the inverse multiplication of estimated phase error. The first-order error is estimated by the phase of autocorrelation calculated from the complex valued phase distorted image while the zero-order correction factor is extracted from the histogram of phase distribution of the first-order corrected image. Since all the correction procedures are performed on the spatial domain after completion of data acquisition, no prior adjustments or additional measurements are required. The algorithm can be applicable to most of the phase-involved NMR imaging techniques including inversion recovery imaging, quadrature modulated imaging, spectroscopic imaging, and flow imaging, etc. Some experimental results with inversion recovery imaging as well as quadrature spectroscopic imaging are shown to demonstrate the usefulness of the algorithm.

Generalised Spin Dynamics and Induced Bounds of Automorphic [A]nX, [AX]n NMR Systems via Dual Tensorial Sets: An Invariant Cardinality Role for CFP

NASA Astrophysics Data System (ADS)

Temme, Francis P.

For uniform spins and their indistinguishable point sets of tensorial bases defining automorphic group-based Liouvillian NMR spin dynamics, the role of recursively-derived coefficients of fractional parentage (CFP) bijections and Schur duality-defined CFP(0)(n) ≡ ¦GI¦(n) group invariant cardinality is central both to understanding the impact of time-reversal invariance(TRI) spin physics, and to analysis as density-matrix formalisms over democratic recoupled (DR) dual tensorial sets, {T{ṽ}k(11.1)(SU2 × ln)}. Over abstract spin space, these tensorial sets are (ṽ) invariant-theoretic forms which lie beyond the Liouvillian graph recoupling and Racah-forms envisaged by Sanctuary [1]. This is a direct consequence of the dominance of the ln group. It leads to new views on the value of projective group actions as mappings over specialised Liouvillian carrier spaces, and on the need for the replacement of Racah-Wigner (R-W) orthogonality for distinct point sets, by criteria based on explicit properties of invariants [J. Phys.: Math. & Theor. A 41, 015210 (2008)] for multiple invariant systems. Ũ × P group actions over disjoint (L) carrier subspaces, leading to exclusively combinatorial views of the nature of quantal completeness for indistinguishable point-based tensorial sets. Such generalised invariant-theoretic approaches lie beyond the range of Lévi-Civitá generator views, or of Lévy-Leblond and Lévy-Nahas [9] with its additional cyclic-commutators defining mono-invariant DR forms. Comparison of the latter with generalised multiple-invariant techniques provides an answer to the question of precisely why [A]n≥4(X) and [AX]n≥4 NMR system spin dynamics are not ameniable to conventional R-W analysis of recoupled discrete-point tensorial systems. Our work augments earlier Hilbert space views, both of Louck and Biedenharn [21] on boson pattern projective mapping, and of Corio [19]. The roles of recent ln group action and (λ ⊢ n)-Schur combinatorial concepts, as well as of polyhedral-combinatorial modelling over invariance algebras, contribute significantly to our understanding of invariant-based techniques of Liouville dual tensorial sets for automorphic NMR spin physics.1

27 Al MAS NMR Studies of HBEA Zeolite at Low to High Magnetic Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Jian Zhi; Wan, Chuan; Vjunov, Aleksei

27Al single pulse (SP) MAS NMR spectra of HBEA zeolites with high Si/Al ratios of 71 and 75 were obtained at three magnetic field strengths of 7.05, 11.75 and 19.97 T. High field 27Al MAS NMR spectra acquired at 19.97 T show significantly improved spectral resolution, resulting in at least two well-resolved tetrahedral-Al NMR peaks. Based on the results obtained from 27Al MAS and MQMAS NMR acquired at 19.97 T, four different quadrupole peaks are used to deconvolute the 27Al SP MAS spectra acquired at vari-ous fields by using the same set of quadrupole coupling constants, asymmetric parameters and relativemore » integrated peak intensities for the tetrahedral Al peaks. The line shapes of individual peaks change from typical quadrupole line shape at low field to essentially symmetrical line shapes at high field. We demonstrate that for fully hydrated HBEA zeolites the effect of second order quadrupole interaction can be ignored and quantitative spectral analysis can be performed by directly fitting the high field spectra using mixed Gaussian/Lorentzian line shapes. Also, the analytical steps described in our work allow direct assignment of spectral intensity to individual Al tetrahedral sites (T-sites) of zeolite HBEA. Finally, the proposed concept is suggested generally applicable to other zeo-lite framework types, thus, allowing a direct probing of Al distributions by NMR spectroscopic methods in zeolites with high confi-dence.« less

A sulfated alpha-L-fucan from sea cucumber.

PubMed

Ribeiro, A C; Vieira, R P; Mourão, P A; Mulloy, B

1994-03-04

A purified sulfated alpha-L-fucan from the sea cucumber body wall was studied, before and after almost complete desulfation, using methylation analysis and NMR spectroscopy. NMR analysis indicates that 2,4-di-O-sulfo-L-fucopyranose and unsubstituted fucopyranose are present in equal proportions, and that 2-O-sulfo-L-fucopyranose is present in twice that proportion. There is some NMR evidence that a regular repeating sequence of four residues comprises most or all of the polysaccharide chain.

Borrelidins C-E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

PubMed

Kim, Jungwoo; Shin, Daniel; Kim, Seong-Hwan; Park, Wanki; Shin, Yoonho; Kim, Won Kyung; Lee, Sang Kook; Oh, Ki-Bong; Shin, Jongheon; Oh, Dong-Chan

2017-06-06

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C-E ( 1 - 3 ), along with a previously reported borrelidin ( 4 ). The planar structures of borrelidins C-E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C-E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher's method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica , and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines.

Vicinal 1H-1H NMR coupling constants from density functional theory as reliable tools for stereochemical analysis of highly flexible multichiral center molecules.

PubMed

López-Vallejo, Fabian; Fragoso-Serrano, Mabel; Suárez-Ortiz, Gloria Alejandra; Hernández-Rojas, Adriana C; Cerda-García-Rojas, Carlos M; Pereda-Miranda, Rogelio

2011-08-05

A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal (1)H-(1)H NMR coupling constants, was developed and applied to a series of flexible compounds (1-8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the (1)H-C-C-(1)H vicinal coupling constants: f((sp3)-(sp3)) = 0.910, f((sp3)-(sp2)) = 0.929, and f((sp2)-(sp2))= 0.977. A remarkable correlation between the theoretical (J(pre)) and experimental (1)H-(1)H NMR (J(exp)) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2-4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1-8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.

Biodiversity in targeted metabolomics analysis of filamentous fungal pathogens by 1H NMR-based studies.

PubMed

Ząbek, Adam; Klimek-Ochab, Magdalena; Jawień, Ewa; Młynarz, Piotr

2017-07-01

The taxonomical classification among fungi kingdom in the last decades was evolved. In this work the targeted metabolomics study based on 1 H NMR spectroscopy combined with chemometrics tools was reported to be useful for differentiation of three model of fungal strains, which represent various genus of Ascomycota (Aspergillus pallidofulvus, Fusarium oxysporum, Geotrichum candidum) were selected in order to perform metabolomics studies. Each tested species, revealed specific metabolic profile of primary endo-metabolites. The species of A. pallidofulvus is represented by the highest concentration of glycerol, glucitol and Unk5. While, F. oxysporum species is characterised by increased level of propylene glycol, ethanol, 4-aminobutyrate, succinate, xylose, Unk1 and Unk4. In G. candidum, 3-methyl-2-oxovalerate, glutamate, pyruvate, glutamine and citrate were elevated. Additionally, a detailed analysis of metabolic changes among A. pallidofulvus, F. oxysporum and G. candidum showed that A. pallidofulvus seems to be the most pathogenic fungi. The obtained results demonstrated that targeted metabolomics analysis could be utilized in the future as a supporting taxonomical tool for currently methods.

Molecular and Silica-Supported Molybdenum Alkyne Metathesis Catalysts: Influence of Electronics and Dynamics on Activity Revealed by Kinetics, Solid-State NMR, and Chemical Shift Analysis.

PubMed

Estes, Deven P; Gordon, Christopher P; Fedorov, Alexey; Liao, Wei-Chih; Ehrhorn, Henrike; Bittner, Celine; Zier, Manuel Luca; Bockfeld, Dirk; Chan, Ka Wing; Eisenstein, Odile; Raynaud, Christophe; Tamm, Matthias; Copéret, Christophe

2017-12-06

Molybdenum-based molecular alkylidyne complexes of the type [MesC≡Mo{OC(CH 3 ) 3-x (CF 3 ) x } 3 ] (MoF 0 , x = 0; MoF 3 , x = 1; MoF 6 , x = 2; MoF 9 , x = 3; Mes = 2,4,6-trimethylphenyl) and their silica-supported analogues are prepared and characterized at the molecular level, in particular by solid-state NMR, and their alkyne metathesis catalytic activity is evaluated. The 13 C NMR chemical shift of the alkylidyne carbon increases with increasing number of fluorine atoms on the alkoxide ligands for both molecular and supported catalysts but with more shielded values for the supported complexes. The activity of these catalysts increases in the order MoF 0 < MoF 3 < MoF 6 before sharply decreasing for MoF 9 , with a similar effect for the supported systems (MoF 0 ≈ MoF 9 < MoF 6 < MoF 3 ). This is consistent with the different kinetic behavior (zeroth order in alkyne for MoF 9 derivatives instead of first order for the others) and the isolation of stable metallacyclobutadiene intermediates of MoF 9 for both molecular and supported species. Detailed solid-state NMR analysis of molecular and silica-supported metal alkylidyne catalysts coupled with DFT/ZORA calculations rationalize the NMR spectroscopic signatures and discernible activity trends at the frontier orbital level: (1) increasing the number of fluorine atoms lowers the energy of the π*(M≡C) orbital, explaining the more deshielded chemical shift values; it also leads to an increased electrophilicity and higher reactivity for catalysts up to MoF 6 , prior to a sharp decrease in reactivity for MoF 9 due to the formation of stable metallacyclobutadiene intermediates; (2) the silica-supported catalysts are less active than their molecular analogues because they are less electrophilic and dynamic, as revealed by their 13 C NMR chemical shift tensors.

NMR ANALYSIS OF MALE FATHEAD MINNOW URINARY METABOLITES: A POTENTIAL APPROACH FOR STUDYING IMPACTS OF CHEMICAL EXPOSURES

EPA Science Inventory

The potential for profiling endogenous metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one dimensional (1D) and two dimensional (2D) NMR spectroscopy w...

Push-through direct injection NMR: an optimized automation method applied to metabolomics

EPA Science Inventory

There is a pressing need to increase the throughput of NMR analysis in fields such as metabolomics and drug discovery. Direct injection (DI) NMR automation is recognized to have the potential to meet this need due to its suitability for integration with the 96-well plate format. ...

An Integrated Laboratory Project in NMR Spectroscopy.

ERIC Educational Resources Information Center

Hudson, Reggie L.; Pendley, Bradford D.

1988-01-01

Describes an advanced NMR project that can be done with a 60-MHz continuous-wave proton spectrometer. Points out the main purposes are to give students experience in second-order NMR analysis, the simplification of spectra by raising the frequency, and the effect of non-hydrogen nuclei on proton resonances. (MVL)

¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis.

PubMed

Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz; Wawer, Iwona

2016-04-15

Excipients used in the solid drug formulations differ in their NMR relaxation and (13)C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5 s to 1200 s) and T(1ρ)(I) parameters (from 2 ms to 73 ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-invasive NMR stratigraphy of a multi-layered artefact: an ancient detached mural painting.

PubMed

Di Tullio, Valeria; Capitani, Donatella; Presciutti, Federica; Gentile, Gennaro; Brunetti, Brunetto Giovanni; Proietti, Noemi

2013-10-01

NMR stratigraphy was used to investigate in situ, non-destructively and non-invasively, the stratigraphy of hydrogen-rich layers of an ancient Nubian detached mural painting. Because of the detachment procedure, a complex multi-layered artefact was obtained, where, besides layers of the original mural painting, also the materials used during the procedure all became constitutive parts of the artefact. NMR measurements in situ enabled monitoring of the state of conservation of the artefact and planning of minimum representative sampling to validate results obtained in situ by solid-state NMR analysis of the samples. This analysis enabled chemical characterization of all organic materials. Use of reference compounds and prepared specimens assisted data interpretation.

NMR analysis and chemical shift calculations of poly(lactic acid) dimer model compounds with different tacticities

USDA-ARS?s Scientific Manuscript database

In this work, PLA dimer model compounds with different tacticities were synthesized and studied in detail by 1H and 13C NMR in three solvents, CDCl3/CCl4 (20/80 v/v), CDCl3 and DMSO-d6. All the peaks in the 1H and 13C NMR spectra were assigned with the help of two-dimensional NMR. Although the solve...

Performance of the WeNMR CS-Rosetta3 web server in CASD-NMR.

PubMed

van der Schot, Gijs; Bonvin, Alexandre M J J

2015-08-01

We present here the performance of the WeNMR CS-Rosetta3 web server in CASD-NMR, the critical assessment of automated structure determination by NMR. The CS-Rosetta server uses only chemical shifts for structure prediction, in combination, when available, with a post-scoring procedure based on unassigned NOE lists (Huang et al. in J Am Chem Soc 127:1665-1674, 2005b, doi: 10.1021/ja047109h). We compare the original submissions using a previous version of the server based on Rosetta version 2.6 with recalculated targets using the new R3FP fragment picker for fragment selection and implementing a new annotation of prediction reliability (van der Schot et al. in J Biomol NMR 57:27-35, 2013, doi: 10.1007/s10858-013-9762-6), both implemented in the CS-Rosetta3 WeNMR server. In this second round of CASD-NMR, the WeNMR CS-Rosetta server has demonstrated a much better performance than in the first round since only converged targets were submitted. Further, recalculation of all CASD-NMR targets using the new version of the server demonstrates that our new annotation of prediction quality is giving reliable results. Predictions annotated as weak are often found to provide useful models, but only for a fraction of the sequence, and should therefore only be used with caution.

Chiral discrimination of sibutramine enantiomers by capillary electrophoresis and proton nuclear magnetic resonance spectroscopy.

PubMed

Lee, Yong-Jae; Choi, Seungho; Lee, Jinhoo; Nguyen, NgocVan Thi; Lee, Kyungran; Kang, Jong Seong; Mar, Woongchon; Kim, Kyeong Ho

2012-03-01

Capillary electrophoresis (CE) and proton nuclear magnetic resonance spectroscopy ((1)H-NMR) have been used to discriminate the enantiomers of sibutramine using cyclodextrin derivatives. Possible correlation between CE and (1)H-NMR was examined. Good correlation between the (1)H-NMR shift non-equivalence data for sibutramine and the degree of enantioseparation in CE was observed. In CE study, a method of enantiomeric separation and quantitation of sibutramine was developed using enantiomeric standards. The method was based on the use of 50 mM of phosphate buffer of pH 3.0 with 10 mM of methyl-beta-cyclodextrin (M-β-CD). 0.05% of LOD, 0.2% of LOQ for S-sibutramine enantiomer was achieved, and the method was validated and applied to the quantitative determination of sibutramine enantiomers in commercial drugs. On a 600 MHz (1)H-NMR analysis, enantiomer signal separation of sibutramine was obtained by fast diastereomeric interaction with a chiral selector M-β-CD. For chiral separation and quantification, N-methyl proton peaks (at 2.18 ppm) were selected because of its being singlet and simple for understanding of diastereomeric interaction. Effects of temperature and concentration of chiral selector on enantiomer signal separation were investigated. The optimum condition was 0.5 mg/mL of sibutramine and 10 mg/mL of M-β-CD at 10°C. Distinguishment of 0.5% of S-sibutramine in R-sibutramine was found to be possible by (1)H-NMR with M-β-CD as chiral selector. Host-guest interaction between sibutramine and M-β-CD was confirmed by (1)H-NMR studies and CE studies. A Structure of the inclusion complex was proposed considering (1)H-NMR and 2D ROESY studies.

1H NMR Metabolomics Study of Spleen from C57BL/6 Mice Exposed to Gamma Radiation

PubMed Central

Xiao, X; Hu, M; Liu, M; Hu, JZ

2016-01-01

Due to the potential risk of accidental exposure to gamma radiation, it’s critical to identify the biomarkers of radiation exposed creatures. In the present study, NMR based metabolomics combined with multivariate data analysis to evaluate the metabolites changed in the C57BL/6 mouse spleen after 4 days whole body exposure to 3.0 Gy and 7.8 Gy gamma radiations. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification potential biomarkers associated with gamma irradiation. Two different strategies for NMR spectral data reduction (i.e., spectral binning and spectral deconvolution) are combined with normalize to constant sum and unit weight before multivariate data analysis, respectively. The combination of spectral deconvolution and normalization to unit weight is the best way for identifying discriminatory metabolites between the irradiation and control groups. Normalized to the constant sum may achieve some pseudo biomarkers. PCA and OPLS results shown that the exposed groups can be well separated from the control group. Leucine, 2-aminobutyrate, valine, lactate, arginine, glutathione, 2-oxoglutarate, creatine, tyrosine, phenylalanine, π-methylhistidine, taurine, myoinositol, glycerol and uracil are significantly elevated while ADP is decreased significantly. These significantly changed metabolites are associated with multiple metabolic pathways and may be potential biomarkers in the spleen exposed to gamma irradiation. PMID:27019763

1H NMR metabolomics study of spleen from C57BL/6 mice exposed to gamma radiation

DOE PAGES

Xiao, Xiongjie; Hu, M.; Liu, M.; ...

2016-01-27

Due to the potential risk of accidental exposure to gamma radiation, it’s critical to identify the biomarkers of radiation exposed creatures. In the present study, NMR based metabolomics combined with multivariate data analysis to evaluate the metabolites changed in the C57BL/6 mouse spleen after 4 days whole body exposure to 3.0 Gy and 7.8 Gy gamma radiations. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification potential biomarkers associated with gamma irradiation. Two different strategies for NMR spectral data reduction (i.e., spectral binning and spectral deconvolution) are combined with normalize tomore » constant sum and unit weight before multivariate data analysis, respectively. The combination of spectral deconvolution and normalization to unit weight is the best way for identifying discriminatory metabolites between the irradiation and control groups. Normalized to the constant sum may achieve some pseudo biomarkers. PCA and OPLS results shown that the exposed groups can be well separated from the control group. Leucine, 2-aminobutyrate, valine, lactate, arginine, glutathione, 2-oxoglutarate, creatine, tyrosine, phenylalanine, π-methylhistidine, taurine, myoinositol, glycerol and uracil are significantly elevated while ADP is decreased significantly. As a result, these significantly changed metabolites are associated with multiple metabolic pathways and may be potential biomarkers in the spleen exposed to gamma irradiation.« less

Teaching NMR spectra analysis with nmr.cheminfo.org.

PubMed

Patiny, Luc; Bolaños, Alejandro; Castillo, Andrés M; Bernal, Andrés; Wist, Julien

2018-06-01

Teaching spectra analysis and structure elucidation requires students to get trained on real problems. This involves solving exercises of increasing complexity and when necessary using computational tools. Although desktop software packages exist for this purpose, nmr.cheminfo.org platform offers students an online alternative. It provides a set of exercises and tools to help solving them. Only a small number of exercises are currently available, but contributors are invited to submit new ones and suggest new types of problems. Copyright © 2018 John Wiley & Sons, Ltd.

Functional Characteristics of Tumor Associated Protein Spot14 and Interacting Proteins in Mouse Mammary Epithelial and Breast Cancer Cell Lines

DTIC Science & Technology

2012-03-01

enhanced accumulation of total lipids evaluated by Bodipy staining and NMR analysis. A major finding in this report is that glycolytic and lipogenic enzyme...total lipid component using NMR Metabolomics showed significant increases in the quantity of intracellular (CH2)n and (CH3) acyl chains (i.e. fatty...Mass Spectrometry (GC-MS) methods were developed. GC-MS differs from NMR analysis of lipid fractions in that GC-MS distinguishes between fatty acids

Soft Corals Biodiversity in the Egyptian Red Sea: A Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species.

PubMed

Farag, Mohamed A; Porzel, Andrea; Al-Hammady, Montasser A; Hegazy, Mohamed-Elamir F; Meyer, Achim; Mohamed, Tarik A; Westphal, Hildegard; Wessjohann, Ludger A

2016-04-01

Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via (1)H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC-MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of S. ehrenbergi from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC-MS data sets was found equally effective in predicting the species origin of unknown Sarcophyton. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids.

Lithological controls on gas hydrate saturation: Insights from signal classification of NMR downhole data

NASA Astrophysics Data System (ADS)

Bauer, Klaus; Kulenkampff, Johannes; Henninges, Jan; Spangenberg, Erik

2016-04-01

Nuclear magnetic resonance (NMR) downhole data are analyzed with a new strategy to study gas hydrate-bearing sediments in the Mackenzie Delta (NW Canada). NMR logging is a powerful tool to study geological reservoir formations. The measurements are based on interactions between the magnetic moments of protons in geological formation water and an external magnetic field. Inversion of the measured raw data provides so-called transverse relaxation time (T2) distribution curves or spectra. Different parts of the T2 curve are related with distinct pore radii and corresponding fluid components. A common practice in the analysis of T2 distribution curves is to extract single-valued parameters such as apparent total porosity. Moreover, the derived total NMR apparent porosity and the gamma-gamma density log apparent porosity can be combined to estimate gas hydrate saturation in hydrate-bearing sediments. To avoid potential loss of information, in our new approach we analyze the entire T2 distribution curves as quasi-continuous signals to characterize the rock formation. The approach is applied to NMR data measured in gas hydrate research well Mallik 5L-38. We use self-organizing maps, a neural network clustering technique, to subdivide the data set of NMR T2 distribution curves into classes with a similar and distinctive signal shape. The method includes (1) preparation of data vectors, (2) unsupervised learning, (3) cluster definition, and (4) classification and depth mapping of all NMR signals. Each signal class thus represents a specific pore size distribution which can be interpreted in terms of distinct lithologies and reservoir types. A key step in the interpretation strategy is to reconcile the NMR classes with other log data not considered in the clustering analysis, such as gamma ray, photo-electric factor, hydrate saturation, and other logs. Our results defined six main lithologies within the target zone. Gas hydrate layers were recognized by their low signal amplitudes for all relaxation times. Highly concentrated methane hydrates occur in sand and shaly sand. Most importantly, two subtypes of hydrate-bearing sands and shaly sands were identified. They show distinct NMR signals and differ in hydrate saturation and gamma ray values. An inverse linear relationship between hydrate saturation and clay content was concluded. Finally, we infer that the gas hydrate is not grain coating, but rather, pore filling with matrix support is the preferred growth habit model for the studied formation.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

PubMed

MacRae, Sheila L; Zhang, Quanwei; Lemetre, Christophe; Seim, Inge; Calder, Robert B; Hoeijmakers, Jan; Suh, Yousin; Gladyshev, Vadim N; Seluanov, Andrei; Gorbunova, Vera; Vijg, Jan; Zhang, Zhengdong D

2015-04-01

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Structure simulation with calculated NMR parameters - integrating COSMOS into the CCPN framework.

PubMed

Schneider, Olaf; Fogh, Rasmus H; Sternberg, Ulrich; Klenin, Konstantin; Kondov, Ivan

2012-01-01

The Collaborative Computing Project for NMR (CCPN) has build a software framework consisting of the CCPN data model (with APIs) for NMR related data, the CcpNmr Analysis program and additional tools like CcpNmr FormatConverter. The open architecture allows for the integration of external software to extend the abilities of the CCPN framework with additional calculation methods. Recently, we have carried out the first steps for integrating our software Computer Simulation of Molecular Structures (COSMOS) into the CCPN framework. The COSMOS-NMR force field unites quantum chemical routines for the calculation of molecular properties with a molecular mechanics force field yielding the relative molecular energies. COSMOS-NMR allows introducing NMR parameters as constraints into molecular mechanics calculations. The resulting infrastructure will be made available for the NMR community. As a first application we have tested the evaluation of calculated protein structures using COSMOS-derived 13C Cα and Cβ chemical shifts. In this paper we give an overview of the methodology and a roadmap for future developments and applications.

ImatraNMR: Novel software for batch integration and analysis of quantitative NMR spectra

NASA Astrophysics Data System (ADS)

Mäkelä, A. V.; Heikkilä, O.; Kilpeläinen, I.; Heikkinen, S.

2011-08-01

Quantitative NMR spectroscopy is a useful and important tool for analysis of various mixtures. Recently, in addition of traditional quantitative 1D 1H and 13C NMR methods, a variety of pulse sequences aimed for quantitative or semiquantitative analysis have been developed. To obtain actual usable results from quantitative spectra, they must be processed and analyzed with suitable software. Currently, there are many processing packages available from spectrometer manufacturers and third party developers, and most of them are capable of analyzing and integration of quantitative spectra. However, they are mainly aimed for processing single or few spectra, and are slow and difficult to use when large numbers of spectra and signals are being analyzed, even when using pre-saved integration areas or custom scripting features. In this article, we present a novel software, ImatraNMR, designed for batch analysis of quantitative spectra. In addition to capability of analyzing large number of spectra, it provides results in text and CSV formats, allowing further data-analysis using spreadsheet programs or general analysis programs, such as Matlab. The software is written with Java, and thus it should run in any platform capable of providing Java Runtime Environment version 1.6 or newer, however, currently it has only been tested with Windows and Linux (Ubuntu 10.04). The software is free for non-commercial use, and is provided with source code upon request.

Fragment based drug discovery: practical implementation based on ¹⁹F NMR spectroscopy.

PubMed

Jordan, John B; Poppe, Leszek; Xia, Xiaoyang; Cheng, Alan C; Sun, Yax; Michelsen, Klaus; Eastwood, Heather; Schnier, Paul D; Nixey, Thomas; Zhong, Wenge

2012-01-26

Fragment based drug discovery (FBDD) is a widely used tool for discovering novel therapeutics. NMR is a powerful means for implementing FBDD, and several approaches have been proposed utilizing (1)H-(15)N heteronuclear single quantum coherence (HSQC) as well as one-dimensional (1)H and (19)F NMR to screen compound mixtures against a target of interest. While proton-based NMR methods of fragment screening (FBS) have been well documented and are widely used, the use of (19)F detection in FBS has been only recently introduced (Vulpetti et al. J. Am. Chem. Soc.2009, 131 (36), 12949-12959) with the aim of targeting "fluorophilic" sites in proteins. Here, we demonstrate a more general use of (19)F NMR-based fragment screening in several areas: as a key tool for rapid and sensitive detection of fragment hits, as a method for the rapid development of structure-activity relationship (SAR) on the hit-to-lead path using in-house libraries and/or commercially available compounds, and as a quick and efficient means of assessing target druggability.

NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes.

PubMed

Dias, David M; Ciulli, Alessio

2014-01-01

Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

MULTIVARIATE CURVE RESOLUTION OF NMR SPECTROSCOPY METABONOMIC DATA

EPA Science Inventory

Sandia National Laboratories is working with the EPA to evaluate and develop mathematical tools for analysis of the collected NMR spectroscopy data. Initially, we have focused on the use of Multivariate Curve Resolution (MCR) also known as molecular factor analysis (MFA), a tech...

Squid detected NMR and MRI at ultralow fields

DOEpatents

Clarke, John [Berkeley, CA; McDermott, Robert [Louisville, CO; Pines, Alexander [Berkeley, CA; Trabesinger, Andreas Heinz [CH-8006 Zurich, CH

2007-05-15

Nuclear magnetic resonance (NMR) signals are detected in microtesla fields. Prepolarization in millitesla fields is followed by detection with an untuned dc superconducting quantum interference device (SQUID) magnetometer. Because the sensitivity of the SQUID is frequency independent, both signal-to-noise ratio (SNR) and spectral resolution are enhanced by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. MRI in ultralow magnetic field is based on the NMR at ultralow fields. Gradient magnetic fields are applied, and images are constructed from the detected NMR signals.

Squid detected NMR and MRI at ultralow fields

DOEpatents

Clarke, John; McDermott, Robert; Pines, Alexander; Trabesinger, Andreas Heinz

2006-05-30

Nuclear magnetic resonance (NMR) signals are detected in microtesla fields. Prepolarization in millitesla fields is followed by detection with an untuned dc superconducting quantum interference device (SQUID) magnetometer. Because the sensitivity of the SQUID is frequency independent, both signal-to-noise ratio (SNR) and spectral resolution are enhanced by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. MRI in ultralow magnetic field is based on the NMR at ultralow fields. Gradient magnetic fields are applied, and images are constructed from the detected NMR signals.

Squid detected NMR and MRI at ultralow fields

DOEpatents

Clarke, John [Berkeley, CA; Pines, Alexander [Berkeley, CA; McDermott, Robert F [Monona, WI; Trabesinger, Andreas H [London, GB

2008-12-16

Nuclear magnetic resonance (NMR) signals are detected in microtesla fields. Prepolarization in millitesla fields is followed by detection with an untuned dc superconducting quantum interference device (SQUID) magnetometer. Because the sensitivity of the SQUID is frequency independent, both signal-to-noise ratio (SNR) and spectral resolution are enhanced by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. MRI in ultralow magnetic field is based on the NMR at ultralow fields. Gradient magnetic fields are applied, and images are constructed from the detected NMR signals.

SQUID detected NMR and MRI at ultralow fields

DOEpatents

Clarke, John; McDermott, Robert; Pines, Alexander; Trabesinger, Andreas Heinz

2006-10-03

Nuclear magnetic resonance (NMR) signals are detected in microtesla fields. Prepolarization in millitesla fields is followed by detection with an untuned dc superconducting quantum interference device (SQUID) magnetometer. Because the sensitivity of the SQUID is frequency independent, both signal-to-noise ratio (SNR) and spectral resolution are enhanced by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. MRI in ultralow magnetic field is based on the NMR at ultralow fields. Gradient magnetic fields are applied, and images are constructed from the detected NMR signals.

Quantitative analysis of Earth's field NMR spectra of strongly-coupled heteronuclear systems.

PubMed

Halse, Meghan E; Callaghan, Paul T; Feland, Brett C; Wasylishen, Roderick E

2009-09-01

In the Earth's magnetic field, it is possible to observe spin systems consisting of unlike spins that exhibit strongly coupled second-order NMR spectra. Such spectra result when the J-coupling between two unlike spins is of the same order of magnitude as the difference in their Larmor precession frequencies. Although the analysis of second-order spectra involving only spin-(1/2) nuclei has been discussed since the early days of NMR spectroscopy, NMR spectra involving spin-(1/2) nuclei and quadrupolar (I>(1/2)) nuclei have rarely been treated. Two examples are presented here, the tetrahydroborate anion, BH4-, and the ammonium cation, NH4+. For the tetrahydroborate anion, (1)J((11)B,(1)H)=80.9Hz, and in an Earth's field of 53.3microT, nu((1)H)=2269Hz and nu((11)B)=728Hz. The (1)H NMR spectra exhibit features that both first- and second-order perturbation theory are unable to reproduce. On the other hand, second-order perturbation theory adequately describes (1)H NMR spectra of the ammonium anion, (14)NH4+, where (1)J((14)N,(1)H)=52.75Hz when nu((1)H)=2269Hz and nu((14)N)=164Hz. Contrary to an early report, we find that the (1)H NMR spectra are independent of the sign of (1)J((14)N,(1)H). Exact analysis of two-spin systems consisting of quadrupolar nuclei and spin-(1/2) nuclei are also discussed.

High-field 95 Mo and 183 W static and MAS NMR study of polyoxometalates.

PubMed

Haouas, Mohamed; Trébosc, Julien; Roch-Marchal, Catherine; Cadot, Emmanuel; Taulelle, Francis; Martineau-Corcos, Charlotte

2017-10-01

The potential of high-field NMR to measure solid-state 95 Mo and 183 W NMR in polyoxometalates (POMs) is explored using some archetypical structures like Lindqvist, Keggin and Dawson as model compounds that are well characterized in solution. NMR spectra in static and under magic angle spinning (MAS) were obtained, and their analysis allowed extraction of the NMR parameters, including chemical shift anisotropy and quadrupolar coupling parameters. Despite the inherent difficulties of measurement in solid state of these low-gamma NMR nuclei, due mainly to the low spectral resolution and poor signal-to-noise ratio, the observed global trends compare well with the solution-state NMR data. This would open an avenue for application of solid-state NMR to POMs, especially when liquid-state NMR is not possible, e.g., for poorly soluble or unstable compounds in solution, and for giant molecules with slow tumbling motion. This is the case of Keplerate where we provide here the first NMR characterization of this class of POMs in the solid state. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Automatic NMR-Based Identification of Chemical Reaction Types in Mixtures of Co-Occurring Reactions

PubMed Central

Latino, Diogo A. R. S.; Aires-de-Sousa, João

2014-01-01

The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the 1H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the 1H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of the molecules in the mixtures. PMID:24551112

Automatic NMR-based identification of chemical reaction types in mixtures of co-occurring reactions.

PubMed

Latino, Diogo A R S; Aires-de-Sousa, João

2014-01-01

The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the (1)H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the (1)H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of the molecules in the mixtures.

NMR screening in fragment-based drug design: a practical guide.

PubMed

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Bayesian reconstruction of projection reconstruction NMR (PR-NMR).

PubMed

Yoon, Ji Won

2014-11-01

Projection reconstruction nuclear magnetic resonance (PR-NMR) is a technique for generating multidimensional NMR spectra. A small number of projections from lower-dimensional NMR spectra are used to reconstruct the multidimensional NMR spectra. In our previous work, it was shown that multidimensional NMR spectra are efficiently reconstructed using peak-by-peak based reversible jump Markov chain Monte Carlo (RJMCMC) algorithm. We propose an extended and generalized RJMCMC algorithm replacing a simple linear model with a linear mixed model to reconstruct close NMR spectra into true spectra. This statistical method generates samples in a Bayesian scheme. Our proposed algorithm is tested on a set of six projections derived from the three-dimensional 700 MHz HNCO spectrum of a protein HasA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural and cytotoxic studies of cationic thiosemicarbazones

NASA Astrophysics Data System (ADS)

Sinniah, Saravana Kumar; Sim, Kae Shin; Ng, Seik Weng; Tan, Kong Wai

2017-06-01

Schiff bases from the thiosemicarbazones family with variable N4 substituents are known to show enhanced growth inhibitory properties. In view of these facts and as a part of our continuous interest in cationic Schiff bases, we have developed several Schiff base ligands from (3-formyl-4-hydroxyphenyl)methyltriphenylphosphonium (T) in present study. The compounds were characterized by various spectroscopic methods (infrared spectra, 1H NMR, 13C NMR, HRESIMS and X-ray crystallography). Three of the N4 substituents, namely P(tsc)T, FP(tsc)T and EP(tsc)T exerted strong growth inhibitory properties by inhibiting the highly metastasis prostate cancer growth (PC-3). The thiosemicarbazone with ethylphenyl (EP) moiety displayed most potent activity against all cell lines tested. The MTT data obtained from analysis establishes that phenyl substituent enhances the growth inhibitory properties of the compound. The result affirms that EP(tsc)T would serve as a lead scaffold for rational anticancer agent development.

Volatile-Compound Fingerprinting by Headspace-Gas-Chromatography Ion-Mobility Spectrometry (HS-GC-IMS) as a Benchtop Alternative to 1H NMR Profiling for Assessment of the Authenticity of Honey.

PubMed

Gerhardt, Natalie; Birkenmeier, Markus; Schwolow, Sebastian; Rohn, Sascha; Weller, Philipp

2018-02-06

This work describes a simple approach for the untargeted profiling of volatile compounds for the authentication of the botanical origins of honey based on resolution-optimized HS-GC-IMS combined with optimized chemometric techniques, namely PCA, LDA, and kNN. A direct comparison of the PCA-LDA models between the HS-GC-IMS and 1 H NMR data demonstrated that HS-GC-IMS profiling could be used as a complementary tool to NMR-based profiling of honey samples. Whereas NMR profiling still requires comparatively precise sample preparation, pH adjustment in particular, HS-GC-IMS fingerprinting may be considered an alternative approach for a truly fully automatable, cost-efficient, and in particular highly sensitive method. It was demonstrated that all tested honey samples could be distinguished on the basis of their botanical origins. Loading plots revealed the volatile compounds responsible for the differences among the monofloral honeys. The HS-GC-IMS-based PCA-LDA model was composed of two linear functions of discrimination and 10 selected PCs that discriminated canola, acacia, and honeydew honeys with a predictive accuracy of 98.6%. Application of the LDA model to an external test set of 10 authentic honeys clearly proved the high predictive ability of the model by correctly classifying them into three variety groups with 100% correct classifications. The constructed model presents a simple and efficient method of analysis and may serve as a basis for the authentication of other food types.

Coal liquefaction process streams characterization and evaluation: Analysis of Black Thunder coal and liquefaction products from HRI Bench Unit Run CC-15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pugmire, R.J.; Solum, M.S.

This study was designed to apply {sup 13}C-nuclear magnetic resonance (NMR) spectrometry to the analysis of direct coal liquefaction process-stream materials. {sup 13}C-NMR was shown to have a high potential for application to direct coal liquefaction-derived samples in Phase II of this program. In this Phase III project, {sup 13}C-NMR was applied to a set of samples derived from the HRI Inc. bench-scale liquefaction Run CC-15. The samples include the feed coal, net products and intermediate streams from three operating periods of the run. High-resolution {sup 13}C-NMR data were obtained for the liquid samples and solid-state CP/MAS {sup 13}C-NMR datamore » were obtained for the coal and filter-cake samples. The {sup 1}C-NMR technique is used to derive a set of twelve carbon structural parameters for each sample (CONSOL Table A). Average molecular structural descriptors can then be derived from these parameters (CONSOL Table B).« less

Metabolic fingerprint of Brazilian maize landraces silk (stigma/styles) using NMR spectroscopy and chemometric methods.

PubMed

Kuhnen, Shirley; Bernardi Ogliari, Juliana; Dias, Paulo Fernando; da Silva Santos, Maiara; Ferreira, Antônio Gilberto; Bonham, Connie C; Wood, Karl Vernon; Maraschin, Marcelo

2010-02-24

Aqueous extract from maize silks is used by traditional medicine for the treatment of several ailments, mainly related to the urinary system. This work focuses on the application of NMR spectroscopy and chemometric analysis for the determination of metabolic fingerprint and pattern recognition of silk extracts from seven maize landraces cultivated in southern Brazil. Principal component analysis (PCA) of the (1)H NMR data set showed clear discrimination among the maize varieties by PC1 and PC2, pointing out three distinct metabolic profiles. Target compounds analysis showed significant differences (p < 0.05) in the contents of protocatechuic acid, gallic acid, t-cinnamic acid, and anthocyanins, corroborating the discrimination of the genotypes in this study as revealed by PCA analysis. Thus the combination of (1)H NMR and PCA is a useful tool for the discrimination of maize silks in respect to their chemical composition, including rapid authentication of the raw material of current pharmacological interest.

Statistical total correlation spectroscopy scaling for enhancement of metabolic information recovery in biological NMR spectra.

PubMed

Maher, Anthony D; Fonville, Judith M; Coen, Muireann; Lindon, John C; Rae, Caroline D; Nicholson, Jeremy K

2012-01-17

The high level of complexity in nuclear magnetic resonance (NMR) metabolic spectroscopic data sets has fueled the development of experimental and mathematical techniques that enhance latent biomarker recovery and improve model interpretability. We previously showed that statistical total correlation spectroscopy (STOCSY) can be used to edit NMR spectra to remove drug metabolite signatures that obscure metabolic variation of diagnostic interest. Here, we extend this "STOCSY editing" concept to a generalized scaling procedure for NMR data that enhances recovery of latent biochemical information and improves biological classification and interpretation. We call this new procedure STOCSY-scaling (STOCSY(S)). STOCSY(S) exploits the fixed proportionality in a set of NMR spectra between resonances from the same molecule to suppress or enhance features correlated with a resonance of interest. We demonstrate this new approach using two exemplar data sets: (a) a streptozotocin rat model (n = 30) of type 1 diabetes and (b) a human epidemiological study utilizing plasma NMR spectra of patients with metabolic syndrome (n = 67). In both cases significant biomarker discovery improvement was observed by using STOCSY(S): the approach successfully suppressed interfering NMR signals from glucose and lactate that otherwise dominate the variation in the streptozotocin study, which then allowed recovery of biomarkers such as glycine, which were otherwise obscured. In the metabolic syndrome study, we used STOCSY(S) to enhance variation from the high-density lipoprotein cholesterol peak, improving the prediction of individuals with metabolic syndrome from controls in orthogonal projections to latent structures discriminant analysis models and facilitating the biological interpretation of the results. Thus, STOCSY(S) is a versatile technique that is applicable in any situation in which variation, either biological or otherwise, dominates a data set at the expense of more interesting or important features. This approach is generally appropriate for many types of NMR-based complex mixture analyses and hence for wider applications in bioanalytical science.

Chemical behavior of methylpyranomalvidin-3-O-glucoside in aqueous solution studied by NMR and UV-visible spectroscopy.

PubMed

Oliveira, Joana; Petrov, Vesselin; Parola, A Jorge; Pina, Fernando; Azevedo, Joana; Teixeira, Natércia; Brás, Natércia F; Fernandes, Pedro A; Mateus, Nuno; Ramos, Maria João; de Freitas, Victor

2011-02-17

In the present work, the proton-transfer reactions of the methylpyranomalvidin-3-O-glucoside pigment in water with different pH values was studied by NMR and UV-visible spectroscopies. The results showed four equilibrium forms: the methylpyranomalvidin-3-O-glucoside cation, the neutral quinoidal base, the respective anionic quinoidal base, and a dianionic base unprotonated at the methyl group. According to the NMR data, it seems that for methylpyranomalvidin-3-O-glucoside besides the acid-base equilibrium between the pyranoflavylium cation and the neutral quinoidal base, a new species is formed at pD 4.88-6.10. This is corroborated by the appearance of a new set of signals in the NMR spectrum that may be assigned to the formation of hemiketal/cis-chalcone species to a small extent. The two ionization constants (pK(a1) and pK(a2)) obtained by both methods (NMR and UV-visible) for methylpyranomalvidin-3-O-glucoside are in agreement (pK(a1) = 5.17 ± 0.03; pK(a2) = 8.85 ± 0.08; and pK(a1) = 4.57 ± 0.07; pK(a2) = 8.23 ± 0.04 obtained by NMR and UV-visible spectroscopies, respectively). Moreover, the fully dianionic unprotonated form (at the methyl group) of the methylpyranomalvidin-3-O-glucoside is converted slowly into a new structure that displays a yellow color at basic pH. On the basis of the results obtained through LC-MS and NMR, the proposed structure was found to correspond to the flavonol syringetin-3-glucoside.

Synthesis and characterization of an octaimidazolium-based polyhedral oligomeric silsesquioxanes ionic liquid by an ion-exchange reaction.

PubMed

Tan, Jinglin; Ma, Depeng; Sun, Xingrong; Feng, Shengyu; Zhang, Changqiao

2013-04-07

Preparation of POSS-min-DS, an octaimidazolium-based polyhedral oligomeric silsesquioxanes (POSS) room temperature ionic liquid, by an ion-exchange reaction between POSS and sodium dodecyl sulfate was reported. Octaimidazolium-based POSS was synthesized with more than 98% yield within 3 h. POSS-min-DS and octaimidazolium-based POSS were confirmed by (1)H, (13)C, and (29)Si NMR, FT-IR and elemental analysis.

Probing the carbonyl functionality of a petroleum resin and asphaltene through oximation and schiff base formation in conjunction with N-15 NMR

USGS Publications Warehouse

Thorn, Kevin A.; Cox, Larry G.

2015-01-01

Despite recent advances in spectroscopic techniques, there is uncertainty regarding the nature of the carbonyl groups in the asphaltene and resin fractions of crude oil, information necessary for an understanding of the physical properties and environmental fate of these materials. Carbonyl and hydroxyl group functionalities are not observed in natural abundance 13C nuclear magnetic resonance (NMR) spectra of asphaltenes and resins and therefore require spin labeling techniques for detection. In this study, the carbonyl functionalities of the resin and asphaltene fractions from a light aliphatic crude oil that is the source of groundwater contamination at the long term USGS study site near Bemidji, Minnesota, have been examined through reaction with 15N-labeled hydroxylamine and aniline in conjunction with analysis by solid and liquid state 15N NMR. Ketone groups were revealed through 15N NMR detection of their oxime and Schiff base derivatives, and esters through their hydroxamic acid derivatives. Anilinohydroquinone adducts provided evidence for quinones. Some possible configurations of the ketone groups in the resin and asphaltene fractions can be inferred from a consideration of the likely reactions that lead to heterocyclic condensation products with aniline and to the Beckmann reaction products from the initially formed oximes. These include aromatic ketones and ketones adjacent to quaternary carbon centers, β-hydroxyketones, β-diketones, and β-ketoesters. In a solid state cross polarization/magic angle spinning (CP/MAS) 15N NMR spectrum recorded on the underivatized asphaltene as a control, carbazole and pyrrole-like nitrogens were the major naturally abundant nitrogens detected.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

NASA Astrophysics Data System (ADS)

Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

2010-03-01

As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Protein-RNA specificity by high-throughput principal component analysis of NMR spectra.

PubMed

Collins, Katherine M; Oregioni, Alain; Robertson, Laura E; Kelly, Geoff; Ramos, Andres

2015-03-31

Defining the RNA target selectivity of the proteins regulating mRNA metabolism is a key issue in RNA biology. Here we present a novel use of principal component analysis (PCA) to extract the RNA sequence preference of RNA binding proteins. We show that PCA can be used to compare the changes in the nuclear magnetic resonance (NMR) spectrum of a protein upon binding a set of quasi-degenerate RNAs and define the nucleobase specificity. We couple this application of PCA to an automated NMR spectra recording and processing protocol and obtain an unbiased and high-throughput NMR method for the analysis of nucleobase preference in protein-RNA interactions. We test the method on the RNA binding domains of three important regulators of RNA metabolism. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

NMR data-driven structure determination using NMR-I-TASSER in the CASD-NMR experiment

PubMed Central

Jang, Richard; Wang, Yan

2015-01-01

NMR-I-TASSER, an adaption of the I-TASSER algorithm combining NMR data for protein structure determination, recently joined the second round of the CASD-NMR experiment. Unlike many molecular dynamics-based methods, NMR-I-TASSER takes a molecular replacement-like approach to the problem by first threading the target through the PDB to identify structural templates which are then used for iterative NOE assignments and fragment structure assembly refinements. The employment of multiple templates allows NMR-I-TASSER to sample different topologies while convergence to a single structure is not required. Retroactive and blind tests of the CASD-NMR targets from Rounds 1 and 2 demonstrate that even without using NOE peak lists I-TASSER can generate correct structure topology with 15 of 20 targets having a TM-score above 0.5. With the addition of NOE-based distance restraints, NMR-I-TASSER significantly improved the I-TASSER models with all models having the TM-score above 0.5. The average RMSD was reduced from 5.29 to 2.14 Å in Round 1 and 3.18 to 1.71 Å in Round 2. There is no obvious difference in the modeling results with using raw and refined peak lists, indicating robustness of the pipeline to the NOE assignment errors. Overall, despite the low-resolution modeling the current NMR-I-TASSER pipeline provides a coarse-grained structure folding approach complementary to traditional molecular dynamics simulations, which can produce fast near-native frameworks for atomic-level structural refinement. PMID:25737244

Regioselective Hydration of an Alkene and Analysis of the Alcohol Product by Remote Access NMR: A Classroom Demonstration

ERIC Educational Resources Information Center

Smith, Maureen E.; Johnson, Sara L.; Masterson, Douglas S.

2013-01-01

A two-part demonstration was conducted in our first-semester organic chemistry course designed to introduce students to the formation of alcohols, regioselective reactions, and analysis of organic products by NMR analysis. This demonstration utilized the oxymercuration-demercuration sequence to prepare an alcohol from an alkene in a Markovnikov…

High-performance liquid chromatography with nuclear magnetic resonance detection applied to organosilicon polymers. Part 2. Comparison with other methods.

PubMed

Blechta, Vratislav; Kurfürst, Milan; Sýkora, Jan; Schraml, Jan

2007-03-23

LC-NMR utilizing (1)H and (29)Si NMR spectroscopy is ideally suited for the analysis of silicones. It is shown that reversed phase gradient LC-NMR surpasses standard gel permeation chromatography (GPC) and diffusion ordered spectroscopy (DOSY) in the analysis of model hydride terminated polydimethylsiloxane. (1)H and (29)Si NMR in the stopped-flow arrangement leads to full identification of the components. Concentration gradient introduces a dependence of the (29)Si shifts on solvent composition, this dependence can be substantially reduced by a proposed method of referencing. It is shown that the ADEQUATE version of powerful but insensitive 2D INADEQUATE experiment can be used for complete line assignment.

Proton-Based Ultrafast Magic Angle Spinning Solid-State NMR Spectroscopy.

PubMed

Zhang, Rongchun; Mroue, Kamal H; Ramamoorthy, Ayyalusamy

2017-04-18

Protons are vastly abundant in a wide range of exciting macromolecules and thus can be a powerful probe to investigate the structure and dynamics at atomic resolution using solid-state NMR (ssNMR) spectroscopy. Unfortunately, the high signal sensitivity, afforded by the high natural-abundance and high gyromagnetic ratio of protons, is greatly compromised by severe line broadening due to the very strong 1 H- 1 H dipolar couplings. As a result, protons are rarely used, in spite of the desperate need for enhancing the sensitivity of ssNMR to study a variety of systems that are not amenable for high resolution investigation using other techniques including X-ray crystallography, cryo-electron microscopy, and solution NMR spectroscopy. Thanks to the remarkable improvement in proton spectral resolution afforded by the significant advances in magic-angle-spinning (MAS) probe technology, 1 H ssNMR spectroscopy has recently attracted considerable attention in the structural and dynamics studies of various molecular systems. However, it still remains a challenge to obtain narrow 1 H spectral lines, especially from proteins, without resorting to deuteration. In this Account, we review recent proton-based ssNMR strategies that have been developed in our laboratory to further improve proton spectral resolution without resorting to chemical deuteration for the purposes of gaining atomistic-level insights into molecular structures of various crystalline solid systems, using small molecules and peptides as illustrative examples. The proton spectral resolution enhancement afforded by the ultrafast MAS frequencies up to 120 kHz is initially discussed, followed by a description of an ensemble of multidimensional NMR pulse sequences, all based on proton detection, that have been developed to obtain in-depth information from dipolar couplings and chemical shift anisotropy (CSA). Simple single channel multidimensional proton NMR experiments could be performed to probe the proximity of protons for structure determination using 1 H- 1 H dipolar couplings and to evaluate the changes in chemical environments as well as the relative orientation to the external magnetic field using proton CSA. Due to the boost in signal sensitivity enabled by proton detection under ultrafast MAS, by virtue of high proton natural abundance and gyromagnetic ratio, proton-detected multidimensional experiments involving low-γ nuclei can now be accomplished within a reasonable time, while the higher dimension also offers additional resolution enhancement. In addition, the application of proton-based ssNMR spectroscopy under ultrafast MAS in various challenging and crystalline systems is also presented. Finally, we briefly discuss the limitations and challenges pertaining to proton-based ssNMR spectroscopy under ultrafast MAS conditions, such as the presence of high-order dipolar couplings, friction-induced sample heating, and limited sample volume. Although there are still a number of challenges that must be circumvented by further developments in radio frequency pulse sequences, MAS probe technology and approaches to prepare NMR-friendly samples, proton-based ssNMR has already gained much popularity in various research domains, especially in proteins where uniform or site-selective deuteration can be relatively easily achieved. In addition, implementation of the recently developed fast data acquisition approaches would also enable further developments in the design and applications of proton-based ultrafast MAS multidimensional ssNMR techniques.

1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing.

PubMed

Jawień, Ewa; Ząbek, Adam; Deja, Stanisław; Łukaszewicz, Marcin; Młynarz, Piotr

2015-12-01

Poppy seeds are widely used in household and commercial confectionery. The aim of this study was to demonstrate the application of metabolic profiling for industrial monitoring of the molecular changes which occur during minced poppy seed rancidity and brewing processes performed on raw seeds. Both forms of poppy seeds were obtained from a confectionery company. Proton nuclear magnetic resonance (1H NMR) was applied as the analytical method of choice together with multivariate statistical data analysis. Metabolic fingerprinting was applied as a bioprocess control tool to monitor rancidity with the trajectory of change and brewing progressions. Low molecular weight compounds were found to be statistically significant biomarkers of these bioprocesses. Changes in concentrations of chemical compounds were explained relative to the biochemical processes and external conditions. The obtained results provide valuable and comprehensive information to gain a better understanding of the biology of rancidity and brewing processes, while demonstrating the potential for applying NMR spectroscopy combined with multivariate data analysis tools for quality control in food industries involved in the processing of oilseeds. This precious and versatile information gives a better understanding of the biology of these processes.

Two dimensional distribution measurement of electric current generated in a polymer electrolyte fuel cell using 49 NMR surface coils.

PubMed

Ogawa, Kuniyasu; Sasaki, Tatsuyoshi; Yoneda, Shigeki; Tsujinaka, Kumiko; Asai, Ritsuko

2018-05-17

In order to increase the current density generated in a PEFC (polymer electrolyte fuel cell), a method for measuring the spatial distribution of both the current and the water content of the MEA (membrane electrode assembly) is necessary. Based on the frequency shifts of NMR (nuclear magnetic resonance) signals acquired from the water contained in the MEA using 49 NMR coils in a 7 × 7 arrangement inserted in the PEFC, a method for measuring the two-dimensional spatial distribution of electric current generated in a unit cell with a power generation area of 140 mm × 160 mm was devised. We also developed an inverse analysis method to determine the two-dimensional electric current distribution that can be applied to actual PEFC connections. Two analytical techniques, namely coarse graining of segments and stepwise search, were used to shorten the calculation time required for inverse analysis of the electric current map. Using this method and techniques, spatial distributions of electric current and water content in the MEA were obtained when the PEFC generated electric power at 100 A. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic Profiling and Classification of Propolis Samples from Southern Brazil: An NMR-Based Platform Coupled with Machine Learning.

PubMed

Maraschin, Marcelo; Somensi-Zeggio, Amélia; Oliveira, Simone K; Kuhnen, Shirley; Tomazzoli, Maíra M; Raguzzoni, Josiane C; Zeri, Ana C M; Carreira, Rafael; Correia, Sara; Costa, Christopher; Rocha, Miguel

2016-01-22

The chemical composition of propolis is affected by environmental factors and harvest season, making it difficult to standardize its extracts for medicinal usage. By detecting a typical chemical profile associated with propolis from a specific production region or season, certain types of propolis may be used to obtain a specific pharmacological activity. In this study, propolis from three agroecological regions (plain, plateau, and highlands) from southern Brazil, collected over the four seasons of 2010, were investigated through a novel NMR-based metabolomics data analysis workflow. Chemometrics and machine learning algorithms (PLS-DA and RF), including methods to estimate variable importance in classification, were used in this study. The machine learning and feature selection methods permitted construction of models for propolis sample classification with high accuracy (>75%, reaching ∼90% in the best case), better discriminating samples regarding their collection seasons comparatively to the harvest regions. PLS-DA and RF allowed the identification of biomarkers for sample discrimination, expanding the set of discriminating features and adding relevant information for the identification of the class-determining metabolites. The NMR-based metabolomics analytical platform, coupled to bioinformatic tools, allowed characterization and classification of Brazilian propolis samples regarding the metabolite signature of important compounds, i.e., chemical fingerprint, harvest seasons, and production regions.

Confirming the 3D Solution Structure of a Short Double-Stranded DNA Sequence Using NMR Spectroscopy

ERIC Educational Resources Information Center

Ruhayel, Rasha A.; Berners-Price, Susan J.

2010-01-01

2D [superscript 1]H NOESY NMR spectroscopy is routinely used to give information on the closeness of hydrogen atoms through space. This work is based on a 2D [superscript 1]H NOESY NMR spectrum of a 12 base-pair DNA duplex. This 6-h laboratory workshop aims to provide advanced-level chemistry students with a basic, yet solid, understanding of how…

Interaction of the replication terminator protein of Bacillus subtilis with DNA probed by NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hastings, Adam F.; Otting, Gottfried; Folmer, Rutger H.A.

2005-09-23

Termination of DNA replication in Bacillus subtilis involves the polar arrest of replication forks by a specific complex formed between the dimeric 29 kDa replication terminator protein (RTP) and DNA terminator sites. We have used NMR spectroscopy to probe the changes in {sup 1}H-{sup 15}N correlation spectra of a {sup 15}N-labelled RTP.C110S mutant upon the addition of a 21 base pair symmetrical DNA binding site. Assignment of the {sup 1}H-{sup 15}N correlations was achieved using a suite of triple resonance NMR experiments with {sup 15}N,{sup 13}C,70% {sup 2}H enriched protein recorded at 800 MHz and using TROSY pulse sequences. Perturbationsmore » to {sup 1}H-{sup 15}N spectra revealed that the N-termini, {alpha}3-helices and several loops are affected by the binding interaction. An analysis of this data in light of the crystallographically determined apo- and DNA-bound forms of RTP.C110S revealed that the NMR spectral perturbations correlate more closely to protein structural changes upon complex formation rather than to interactions at the protein-DNA interface.« less

Linear free energy relationships of the 1H and 13C NMR chemical shifts of 3-methylene-2-substituted-1,4-pentadienes

NASA Astrophysics Data System (ADS)

Valentić, Nataša V.; Vitnik, Željko; Kozhushkov, Sergei I.; de Meijere, Armin; Ušćumlić, Gordana S.; Juranić, Ivan O.

2005-06-01

Linear free energy relationships (LFER) were applied to the 1H and 13C NMR chemical shifts ( δN, N= 1H and 13C, respectively) in the unsaturated backbone of cross-conjugated trienes 3-methylene-2-substituted-1,4-pentadienes. The NMR data were correlated using five different LFER models, based on the mono, the dual and the triple substituent parameter (MSP, DSP and TSP, respectively) treatment. The simple and extended Hammett equations, and the three postulated unconventional LFER models obtained by adaptation of the later, were used. The geometry data, which are needed in Karplus-type and McConnell-type analysis, were obtained using semi-empirical MNDO-PM3 calculations. In correlating the data the TSP approach was more successful than the MSP and DSP approaches. The fact that the calculated molecular geometries allow accurate prediction of the NMR data confirms the validity of unconventional LFER models used. These results suggest the s- cis conformation of the cross-conjugated triene as the preferred one. Postulated unconventional DSP and TSP equations enable the assessment of electronic substituent effects in the presence of other interfering influences.

Metabolites Re-programming and Physiological Changes Induced in Scenedesmus regularis under Nitrate Treatment.

PubMed

Ma, Nyuk-Ling; Aziz, Ahmad; Teh, Kit-Yinn; Lam, Su Shiung; Cha, Thye-San

2018-06-27

Nitrate is required to maintain the growth and metabolism of plant and animals. Nevertheless, in excess amount such as polluted water, its concentration can be harmful to living organisms such as microalgae. Recently, studies on microalgae response towards nutrient fluctuation are usually limited to lipid accumulation for the production of biofuels, disregarding the other potential of microalgae to be used in wastewater treatments and as source of important metabolites. Our study therefore captures the need to investigate overall metabolite changes via NMR spectroscopy approach coupled with multivariate data to understand the complex molecular process under high (4X) and low (1/4X) concentrations of nitrate ([Formula: see text]). NMR spectra with the aid of chemometric analysis revealed contrasting metabolites makeup under abundance and limited nitrate treatment. By using NMR technique, 43 types of metabolites and 8 types of fatty acid chains were detected. Nevertheless, only 20 key changes were observed and 16 were down regulated in limited nitrate condition. This paper has demonstrated the feasibility of NMR-based metabolomics approach to study the physiological impact of changing environment such as pollution to the implications for growth and productivity of microalgae population.

Conformational heterogeneity in the Hsp70 chaperone-substrate ensemble identified from analysis of NMR-detected titration data.

PubMed

Sekhar, Ashok; Nagesh, Jayashree; Rosenzweig, Rina; Kay, Lewis E

2017-11-01

The Hsp70 chaperone system plays a critical role in cellular homeostasis by binding to client protein molecules. We have recently shown by methyl-TROSY NMR methods that the Escherichia coli Hsp70, DnaK, can form multiple bound complexes with a small client protein, hTRF1. In an effort to characterize the interactions further we report here the results of an NMR-based titration study of hTRF1 and DnaK, where both molecular components are monitored simultaneously, leading to a binding model. A central finding is the formation of a previously undetected 3:1 hTRF1-DnaK complex, suggesting that under heat shock conditions, DnaK might be able to protect cytosolic proteins whose net concentrations would exceed that of the chaperone. Moreover, these results provide new insight into the heterogeneous ensemble of complexes formed by DnaK chaperones and further emphasize the unique role of NMR spectroscopy in obtaining information about individual events in a complex binding scheme by exploiting a large number of probes that report uniquely on distinct binding processes. © 2017 The Protein Society.

Improved Spin-Echo-Edited NMR Diffusion Measurements

NASA Astrophysics Data System (ADS)

Otto, William H.; Larive, Cynthia K.

2001-12-01

The need for simple and robust schemes for the analysis of ligand-protein binding has resulted in the development of diffusion-based NMR techniques that can be used to assay binding in protein solutions containing a mixture of several ligands. As a means of gaining spectral selectivity in NMR diffusion measurements, a simple experiment, the gradient modified spin-echo (GOSE), has been developed to reject the resonances of coupled spins and detect only the singlets in the 1H NMR spectrum. This is accomplished by first using a spin echo to null the resonances of the coupled spins. Following the spin echo, the singlet magnetization is flipped out of the transverse plane and a dephasing gradient is applied to reduce the spectral artifacts resulting from incomplete cancellation of the J-coupled resonances. The resulting modular sequence is combined here with the BPPSTE pulse sequence; however, it could be easily incorporated into any pulse sequence where additional spectral selectivity is desired. Results obtained with the GOSE-BPPSTE pulse sequence are compared with those obtained with the BPPSTE and CPMG-BPPSTE experiments for a mixture containing the ligands resorcinol and tryptophan in a solution of human serum albumin.

Squid-based CW NMR system for measuring the magnetization of helium-3 films

NASA Astrophysics Data System (ADS)

White, Kevin Spencer

This thesis describes the design and construction of a SQUID-based CW NMR system together with its application in a study of the two dimensional magnetism of 3He. 3He provides an exemplary system for the study of two-dimensional magnetism. Two-dimensional 3He films of varying coverages may be formed by plating 3He on relatively uniform two-dimensional substrates, such as GTA Grafoil and ZYX graphite substrates. At coverages above approximately 20 atoms/nm. 2 on these substrates, the second layer of 3He exhibits a strong ferromagnetic ordering tendency. The ferromagnetic ordering presents as a rapid onset of measured magnetization that becomes independent of the applied magnetic field as film temperatures approach 1 mK. Very low applied magnetic fields are used to probe the ferromagnetic ordering in order to minimize masking of the measured magnetization and to stay within the available bandwidth of the SQUID. Commensurate with the ferromagnetic ordering, the NMR linewidth increases dramatically at these coverages and temperatures. An increasing linewidth equates to a short decay time with respect to pulsed NMR probing of the two-dimensional 3He magnetization. The decay times at these coverages and temperatures become so short that they fall below the minimum recovery time necessary for a SQUID-based pulsed NMR system to recover from the relatively large tipping pulse and acquire meaningful data. To address this problem, we have designed a SQUID-based CW NMR system to leverage as much of an already-existing pulsed NMR system as possible but allow accurate measurement of the rapid onset of ferromagnetic ordering of the 3He films below the approximate 1 mK temperature limit of the pulsed NMR system.

Direct metabolic fingerprinting of commercial herbal tinctures by nuclear magnetic resonance spectroscopy and mass spectrometry.

PubMed

Politi, Matteo; Zloh, Mire; Pintado, Manuela E; Castro, Paula M L; Heinrich, Michael; Prieto, Jose M

2009-01-01

Tinctures are widely used liquid pharmaceutical preparations traditionally obtained by maceration of one or more medicinal plants in ethanol-water solutions. Such a process results in the extraction of virtually hundreds of structurally diverse compounds with different polarities. Owing to the large chemical diversity of the constituents present in the herbal tinctures, the analytical tools used for the quality control of tinctures are usually optimised only for the detection of single chemical entities or specific class of compounds. In order to overcome the major limitations of the current methods used for analysis of tinctures, a new methodological approach based on NMR spectroscopy and MS spectrometry has been tested with different commercial tinctures. Diffusion-edited 1H-NMR (1D DOSY) and 1H-NMR with suppression of the ethanol and water signals have been applied here for the first time to the direct analysis of commercial herbal tinctures derived from Echinacea purpurea, Hypericum perforatum, Ginkgo biloba and Valeriana officinalis. The direct injection of the tinctures in the MS detector in order to obtain the corresponding metabolic profiles was also performed. Using both NMR and MS methods it was possible, without evaporation or separation steps, to obtain a metabolic fingerprint able to distinguish between tinctures prepared with different plants. Batch-to-batch homogeneity, as well as degradation after the expiry date of a batch, was also investigated. The techniques proposed here represent fast and convenient direct analyses of medicinal herbal tinctures.

Toward Reliable Lipoprotein Particle Predictions from NMR Spectra of Human Blood: An Interlaboratory Ring Test.

PubMed

Monsonis Centelles, Sandra; Hoefsloot, Huub C J; Khakimov, Bekzod; Ebrahimi, Parvaneh; Lind, Mads V; Kristensen, Mette; de Roo, Niels; Jacobs, Doris M; van Duynhoven, John; Cannet, Claire; Fang, Fang; Humpfer, Eberhard; Schäfer, Hartmut; Spraul, Manfred; Engelsen, Søren B; Smilde, Age K

2017-08-01

Lipoprotein profiling of human blood by 1 H nuclear magnetic resonance (NMR) spectroscopy is a rapid and promising approach to monitor health and disease states in medicine and nutrition. However, lack of standardization of measurement protocols has prevented the use of NMR-based lipoprotein profiling in metastudies. In this study, a standardized NMR measurement protocol was applied in a ring test performed across three different laboratories in Europe on plasma and serum samples from 28 individuals. Data was evaluated in terms of (i) spectral differences, (ii) differences in LPD predictions obtained using an existing prediction model, and (iii) agreement of predictions with cholesterol concentrations in high- and low-density lipoproteins (HDL and LDL) particles measured by standardized clinical assays. ANOVA-simultaneous component analysis (ASCA) of the ring test spectral ensemble that contains methylene and methyl peaks (1.4-0.6 ppm) showed that 97.99% of the variance in the data is related to subject, 1.62% to sample type (serum or plasma), and 0.39% to laboratory. This interlaboratory variation is in fact smaller than the maximum acceptable intralaboratory variation on quality control samples. It is also shown that the reproducibility between laboratories is good enough for the LPD predictions to be exchangeable when the standardized NMR measurement protocol is followed. With the successful implementation of this protocol, which results in reproducible prediction of lipoprotein distributions across laboratories, a step is taken toward bringing NMR more into scope of prognostic and diagnostic biomarkers, reducing the need for less efficient methods such as ultracentrifugation or high-performance liquid chromatography (HPLC).

Unusual open chain quinolinyl peroxol and its alcohol counterpart obtained through a modified Skraup-Doebner-Von Miller quinoline synthesis: theoretical studies and complete (1) H- and (13) C-NMR assignments.

PubMed

Fotie, Jean; Kemami Wangun, Hilaire V; Dreux, Katelyn; Sommerfeld, Thomas; Pittman, Jacob

2012-01-01

Because of their extreme instability, it is generally difficult to synthesize and fully characterize open chain peroxides, also known as peroxols. In our attempt to investigate the mechanism of the Skraup-Doebner-Von Miller quinoline synthesis, we were able to obtain an unusual open chain peroxy-quinoline, namely, 4-(8-ethoxy-2,3-dihydro-1H-cyclopenta[c]quinolin-4-yl)butane-1-peroxol (1), and its alcohol counterpart, namely 4-(8-ethoxy-2,3-dihydro-1H-cyclopenta[c]quinolin-4-yl)butan-1-ol (2) obtained as a side product during the same reaction. Although structurally similar, these two compounds appeared to display some very distinct physical and spectroscopic characteristics. This work reports detailed NMR studies and full (1) H and (13)  C NMR assignments for these two compounds. These assignments are based upon the analysis of the NMR spectra of these compounds including (1) H, (13)  C, COSY, gHSQC and gHMBC. The effect of the peroxide functional group on the chemical shift of neighboring carbons and protons was also investigated by comparing the NMR data of these two compounds. Furthermore, the effects of potential hydrogen bondings in 1, 2, and possible 1-1 dimer, 2-2 dimer and in prototypical model systems, as well as the stability of these compounds, were investigated computationally. The computed dissociation energies and NMR data support the interpretation of the experimental data. Copyright © 2012 John Wiley & Sons, Ltd.

NMR reaction monitoring in flow synthesis

PubMed Central

Gomez, M Victoria

2017-01-01

Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is reviewed. Some recent selected applications have been collected, including synthetic applications, the determination of the kinetic and thermodynamic parameters and reaction optimization, even in single experiments and on the μL scale. Finally, software that allows automatic reaction monitoring and optimization is discussed. PMID:28326137

Beyond Fourier

NASA Astrophysics Data System (ADS)

Hoch, Jeffrey C.

2017-10-01

Non-Fourier methods of spectrum analysis are gaining traction in NMR spectroscopy, driven by their utility for processing nonuniformly sampled data. These methods afford new opportunities for optimizing experiment time, resolution, and sensitivity of multidimensional NMR experiments, but they also pose significant challenges not encountered with the discrete Fourier transform. A brief history of non-Fourier methods in NMR serves to place different approaches in context. Non-Fourier methods reflect broader trends in the growing importance of computation in NMR, and offer insights for future software development.

NMR reaction monitoring in flow synthesis.

PubMed

Gomez, M Victoria; de la Hoz, Antonio

2017-01-01

Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is reviewed. Some recent selected applications have been collected, including synthetic applications, the determination of the kinetic and thermodynamic parameters and reaction optimization, even in single experiments and on the μL scale. Finally, software that allows automatic reaction monitoring and optimization is discussed.

Development of LC-13C NMR

NASA Technical Reports Server (NTRS)

Dorn, H. C.; Wang, J. S.; Glass, T. E.

1986-01-01

This study involves the development of C-13 nuclear resonance as an on-line detector for liquid chromatography (LC-C-13 NMR) for the chemical characterization of aviation fuels. The initial focus of this study was the development of a high sensitivity flow C-13 NMR probe. Since C-13 NMR sensitivity is of paramount concern, considerable effort during the first year was directed at new NMR probe designs. In particular, various toroid coil designs were examined. In addition, corresponding shim coils for correcting the main magnetic field (B sub 0) homogeneity were examined. Based on these initial probe design studies, an LC-C-13 NMR probe was built and flow C-13 NMR data was obtained for a limited number of samples.

Using nuclear magnetic resonance and transient electromagnetics to characterise water distribution beneath an ice covered volcanic crater: the case of Sherman Crater Mt. Baker Washington.

USGS Publications Warehouse

Irons, Trevor P.; Martin, Kathryn; Finn, Carol A.; Bloss, Benjamin; Horton, Robert J.

2014-01-01

Surface and laboratory Nuclear Magnetic Resonance (NMR) measurements combined with transient electromagnetic (TEM) data are powerful tools for subsurface water detection. Surface NMR (sNMR) and TEM soundings, laboratory NMR, complex resistivity, and X-Ray Diffraction (XRD) analysis were all conducted to characterise the distribution of water within Sherman Crater on Mt. Baker, WA. Clay rich rocks, particularly if water saturated, can weaken volcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-travelled, destructive debris flows. Detecting the presence and volume of shallow groundwater is critical for evaluating these landslide hazards. The TEM data identified a low resistivity layer (<10 ohm-m), under 60 m of glacial ice related to water saturated clays. The TEM struggles to resolve the presence or absence of a plausible thin layer of bulk liquid water on top of the clay. The sNMR measurements did not produce any observable signal, indicating the lack of substantial accumulated bulk water below the ice. Laboratory analysis on a sample from the crater wall that likely represented the clays beneath the ice confirmed that the controlling factor for the lack of sNMR signal was the fine-grained nature of the media. The laboratory measurements further indicated that small pores in clays detected by the XRD contain as much as 50% water, establishing an upper bound on the water content in the clay layer. Forward modelling of geologic scenarios revealed that bulk water layers as thin as ½ m between the ice and clay layer would have been detectable using sNMR. The instrumentation conditions which would allow for sNMR detection of the clay layer are investigated. Using current instrumentation the combined analysis of the TEM and sNMR data allow for valuable characterisation of the groundwater system in the crater. The sNMR is able to reduce the uncertainty of the TEM in regards to the presence of a bulk water layer, a valuable piece of information in hazard assessment.

Advanced solid-state NMR spectroscopy of natural organic matter.

PubMed

Mao, Jingdong; Cao, Xiaoyan; Olk, Dan C; Chu, Wenying; Schmidt-Rohr, Klaus

2017-05-01

Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially a systematic approach to NOM characterization, and their applications to the study of NOM. We discuss some basics of how to acquire high-quality and quantitative solid-state 13 C NMR spectra, and address some common technical mistakes that lead to unreliable spectra of NOM. The identification of specific functional groups in NOM, primarily based on 13 C spectral-editing techniques, is described and the theoretical background of some recently-developed spectral-editing techniques is provided. Applications of solid-state NMR to investigating nitrogen (N) in NOM are described, focusing on limitations of the widely used 15 N CP/MAS experiment and the potential of improved advanced NMR techniques for characterizing N forms in NOM. Then techniques used for identifying proximities, heterogeneities and domains are reviewed, and some examples provided. In addition, NMR techniques for studying segmental dynamics in NOM are reviewed. We also briefly discuss applications of solid-state NMR to NOM from various sources, including soil organic matter, aquatic organic matter, organic matter in atmospheric particulate matter, carbonaceous meteoritic organic matter, and fossil fuels. Finally, examples of NMR-based structural models and an outlook are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel high performance nano chemosensor for copper (II) ion based on an ultrasound-assisted synthesized diphenylamine-based Schiff base: Design, fabrication and density functional theory calculations.

PubMed

Parsaee, Zohreh; Haratipour, Pouya; Lariche, Milad Janghorban; Vojood, Arash

2018-03-01

A novel high selective colorimetric chemosensor was introduced based on a nano diphenyl-based Schiff base (H 2 L), 2,2'-((1E,1'E)-(((hexylazanediyl)bis(4,1-phenylene))bis(methanylylidene))bis(azanylylidene))bis(4-methylphenol) that synthesized using sonochemical method. H 2 L was characterized by FT-IR, MS, TGA, 1 H NMR, 13 C NMR, SEM and elemental analysis techniques, then fabricated as the portable strips for sensing copper (II) ions in aqueous media. The binding interaction between H 2 L and various metal ions was investigated by UV-Vis spectroscopic that showed favorable coordination toward Cu 2+ ion. H 2 L exhibited binding-induced color changes from yellow to pink and practically no interference in the presence of other metal ions, i.e., Cr 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Zn 2+ , Cd 2+ , Hg 2+ , Pb 2+ , Mg 2+ and Ca 2+ . The chemsensor showd the color change from yellow to pink in presence of copper (II) ion in aqueous media due to binging of H 2 L and Cu (II). This sensor can determine the copper (II) at in the rang of 7.5 × 10 -8 -1.8 × 10 -5  mol L -1 with a correlation equation: Absorbance = 0.0450[Cu 2+ ] × 10 -6  + 0.71 and R 2  = 0.975 and low detection limit of 1.89 × 10 -8  mol L -1 . Density functional theory (DFT) calculations were carried out at the B3LYP levels of theory with B3LYP/6-311+G(d,p) and LANL2DZ/6-311+G(d,p) basis sets for chemosensor and its copper complex respectively. The optimized geometry, harmonic vibrational frequencies, 1 H NMR and 13 C NMR chemical, Molecular orbital (M.O.), Mulliken population analysis (MPA), contour of Electrostatic Potential (ESP) and Molecular Electrostatic Potential (MEP) map of H 2 L were calculated which show good agreement with behavior of sensor for detection of Cu 2+ ion. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical Characterization and Water Content Determination of Bio-Oils Obtained from Various Biomass Species using 31P NMR Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

David, K.; Ben, H.; Muzzy, J.

2012-03-01

Pyrolysis is a promising approach to utilize biomass for biofuels. One of the key challenges for this conversion is how to analyze complicated components in the pyrolysis oils. Water contents of pyrolysis oils are normally analyzed by Karl Fischer titration. The use of 2-chloro-4,4,5,5,-tetramethyl-1,3,2-dioxaphospholane followed by {sup 31}P NMR analysis has been used to quantitatively analyze the structure of hydroxyl groups in lignin and whole biomass. Results: {sup 31}P NMR analysis of pyrolysis oils is a novel technique to simultaneously characterize components and analyze water contents in pyrolysis oils produced from various biomasses. The water contents of various pyrolysis oilsmore » range from 16 to 40 wt%. The pyrolysis oils obtained from Loblolly pine had higher guaiacyl content, while that from oak had a higher syringyl content. Conclusion: The comparison with Karl Fischer titration shows that {sup 31}P NMR could also reliably be used to measure the water content of pyrolysis oils. Simultaneously with analysis of water content, quantitative characterization of hydroxyl groups, including aliphatic, C-5 substituted/syringyl, guaiacyl, p-hydroxyl phenyl and carboxylic hydroxyl groups, could also be provided by {sup 31}P NMR analysis.« less

DOSY Analysis of Micromolar Analytes: Resolving Dilute Mixtures by SABRE Hyperpolarization.

PubMed

Reile, Indrek; Aspers, Ruud L E G; Tyburn, Jean-Max; Kempf, James G; Feiters, Martin C; Rutjes, Floris P J T; Tessari, Marco

2017-07-24

DOSY is an NMR spectroscopy technique that resolves resonances according to the analytes' diffusion coefficients. It has found use in correlating NMR signals and estimating the number of components in mixtures. Applications of DOSY in dilute mixtures are, however, held back by excessively long measurement times. We demonstrate herein, how the enhanced NMR sensitivity provided by SABRE hyperpolarization allows DOSY analysis of low-micromolar mixtures, thus reducing the concentration requirements by at least 100-fold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A chiral aluminum solvating agent (CASA) for 1H NMR chiral analysis of alcohols at low temperature.

PubMed

Seo, Min-Seob; Jang, Sumin; Kim, Hyunwoo

2018-03-16

A chiral aluminum solvating agent (CASA) was demonstrated to be a general and efficient reagent for 1H NMR chiral analysis of alcohols. The sodium salt of the CASA (CASA-Na) showed a complete baseline peak separation of the hydroxyl group for various chiral alcohols including primary, secondary, and tertiary alcohols with alkyl and aryl substituents in CD3CN. Due to the weak intermolecular interaction, 1H NMR measurement at low temperature (-40 to 10 °C) was required.

Characterization and elimination of undesirable protein residues in plant cell walls for enhancing lignin analysis by solution-state 2D gel-NMR methods

USDA-ARS?s Scientific Manuscript database

Proteins exist in every plant cell wall. Certain protein residues interfere with lignin characterization and quantification. The current solution-state 2D-NMR technique (gel-NMR) for whole plant cell wall structural profiling provides detailed information regarding cell walls and proteins. However, ...

Why Is It so? The [superscript 1]H-NMR CH[subscript 2] Splitting in Substituted Propanes

ERIC Educational Resources Information Center

Lim, Kieran F.; Dereani, Marino

2010-01-01

Nuclear magnetic resonance (NMR) spectroscopy is an important tool in the structural analysis of both organic and inorganic molecules. Proton NMR spectra can yield information about the chemical or bonding environment surrounding various protons, the number of protons in those environments, and the number of neighbouring protons around each…

Dipeptide Structural Analysis Using Two-Dimensional NMR for the Undergraduate Advanced Laboratory

ERIC Educational Resources Information Center

Gonzalez, Elizabeth; Dolino, Drew; Schwartzenburg, Danielle; Steiger, Michelle A.

2015-01-01

A laboratory experiment was developed to introduce students in either an organic chemistry or biochemistry lab course to two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy using simple biomolecules. The goal of this experiment is for students to understand and interpret the information provided by a 2D NMR spectrum. Students are…

Combining Two-Dimensional Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy, Imaging Desorption Electrospray Ionization Mass Spectrometry, and Direct Analysis in Real-Time Mass Spectrometry for the Integral Investigation of Counterfeit Pharmaceuticals

PubMed Central

Nyadong, Leonard; Harris, Glenn A.; Balayssac, Stéphane; Galhena, Asiri S.; Malet-Martino, Myriam; Martino, Robert; Parry, R. Mitchell; Wang, May Dongmei; Fernández, Facundo M.; Gilard, Véronique

2016-01-01

During the past decade, there has been a marked increase in the number of reported cases involving counterfeit medicines in developing and developed countries. Particularly, artesunate-based antimalarial drugs have been targeted, because of their high demand and cost. Counterfeit antimalarials can cause death and can contribute to the growing problem of drug resistance, particularly in southeast Asia. In this study, the complementarity of two-dimensional diffusion-ordered 1H nuclear magnetic resonance spectroscopy (2D DOSY 1H NMR) with direct analysis in real-time mass spectrometry (DART MS) and desorption electrospray ionization mass spectrometry (DESI MS) was assessed for pharmaceutical forensic purposes. Fourteen different artesunate tablets, representative of what can be purchased from informal sources in southeast Asia, were investigated with these techniques. The expected active pharmaceutical ingredient was detected in only five formulations via both nuclear magnetic resonance (NMR) and mass spectrometry (MS) methods. Common organic excipients such as sucrose, lactose, stearate, dextrin, and starch were also detected. The graphical representation of DOSY 1H NMR results proved very useful for establishing similarities among groups of samples, enabling counterfeit drug “chemotyping”. In addition to bulk- and surface-average analyses, spatially resolved information on the surface composition of counterfeit and genuine antimalarial formulations was obtained using DESI MS that was performed in the imaging mode, which enabled one to visualize the homogeneity of both genuine and counterfeit drug samples. Overall, this study suggests that 2D DOSY 1H NMR, combined with ambient MS, comprises a powerful suite of instrumental analysis methodologies for the integral characterization of counterfeit antimalarials. PMID:19453162

Combining two-dimensional diffusion-ordered nuclear magnetic resonance spectroscopy, imaging desorption electrospray ionization mass spectrometry, and direct analysis in real-time mass spectrometry for the integral investigation of counterfeit pharmaceuticals.

PubMed

Nyadong, Leonard; Harris, Glenn A; Balayssac, Stéphane; Galhena, Asiri S; Malet-Martino, Myriam; Martino, Robert; Parry, R Mitchell; Wang, May Dongmei; Fernández, Facundo M; Gilard, Véronique

2009-06-15

During the past decade, there has been a marked increase in the number of reported cases involving counterfeit medicines in developing and developed countries. Particularly, artesunate-based antimalarial drugs have been targeted, because of their high demand and cost. Counterfeit antimalarials can cause death and can contribute to the growing problem of drug resistance, particularly in southeast Asia. In this study, the complementarity of two-dimensional diffusion-ordered (1)H nuclear magnetic resonance spectroscopy (2D DOSY (1)H NMR) with direct analysis in real-time mass spectrometry (DART MS) and desorption electrospray ionization mass spectrometry (DESI MS) was assessed for pharmaceutical forensic purposes. Fourteen different artesunate tablets, representative of what can be purchased from informal sources in southeast Asia, were investigated with these techniques. The expected active pharmaceutical ingredient was detected in only five formulations via both nuclear magnetic resonance (NMR) and mass spectrometry (MS) methods. Common organic excipients such as sucrose, lactose, stearate, dextrin, and starch were also detected. The graphical representation of DOSY (1)H NMR results proved very useful for establishing similarities among groups of samples, enabling counterfeit drug "chemotyping". In addition to bulk- and surface-average analyses, spatially resolved information on the surface composition of counterfeit and genuine antimalarial formulations was obtained using DESI MS that was performed in the imaging mode, which enabled one to visualize the homogeneity of both genuine and counterfeit drug samples. Overall, this study suggests that 2D DOSY (1)H NMR, combined with ambient MS, comprises a powerful suite of instrumental analysis methodologies for the integral characterization of counterfeit antimalarials.

ImatraNMR: novel software for batch integration and analysis of quantitative NMR spectra.

PubMed

Mäkelä, A V; Heikkilä, O; Kilpeläinen, I; Heikkinen, S

2011-08-01

Quantitative NMR spectroscopy is a useful and important tool for analysis of various mixtures. Recently, in addition of traditional quantitative 1D (1)H and (13)C NMR methods, a variety of pulse sequences aimed for quantitative or semiquantitative analysis have been developed. To obtain actual usable results from quantitative spectra, they must be processed and analyzed with suitable software. Currently, there are many processing packages available from spectrometer manufacturers and third party developers, and most of them are capable of analyzing and integration of quantitative spectra. However, they are mainly aimed for processing single or few spectra, and are slow and difficult to use when large numbers of spectra and signals are being analyzed, even when using pre-saved integration areas or custom scripting features. In this article, we present a novel software, ImatraNMR, designed for batch analysis of quantitative spectra. In addition to capability of analyzing large number of spectra, it provides results in text and CSV formats, allowing further data-analysis using spreadsheet programs or general analysis programs, such as Matlab. The software is written with Java, and thus it should run in any platform capable of providing Java Runtime Environment version 1.6 or newer, however, currently it has only been tested with Windows and Linux (Ubuntu 10.04). The software is free for non-commercial use, and is provided with source code upon request. Copyright © 2011 Elsevier Inc. All rights reserved.

Measurement of Solution Viscosity via Diffusion-Ordered NMR Spectroscopy (DOSY)

ERIC Educational Resources Information Center

Li, Weibin; Kagan, Gerald; Hopson, Russell; Williard, Paul G.

2011-01-01

Increasingly, the undergraduate chemistry curriculum includes nuclear magnetic resonance (NMR) spectroscopy. Advanced NMR techniques are often taught including two-dimensional gradient-based experiments. An investigation of intermolecular forces including viscosity, by a variety of methods, is often integrated in the undergraduate physical and…

Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

PubMed

Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted

2016-04-28

Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

NMRe: a web server for NMR protein structure refinement with high-quality structure validation scores.

PubMed

Ryu, Hyojung; Lim, GyuTae; Sung, Bong Hyun; Lee, Jinhyuk

2016-02-15

Protein structure refinement is a necessary step for the study of protein function. In particular, some nuclear magnetic resonance (NMR) structures are of lower quality than X-ray crystallographic structures. Here, we present NMRe, a web-based server for NMR structure refinement. The previously developed knowledge-based energy function STAP (Statistical Torsion Angle Potential) was used for NMRe refinement. With STAP, NMRe provides two refinement protocols using two types of distance restraints. If a user provides NOE (Nuclear Overhauser Effect) data, the refinement is performed with the NOE distance restraints as a conventional NMR structure refinement. Additionally, NMRe generates NOE-like distance restraints based on the inter-hydrogen distances derived from the input structure. The efficiency of NMRe refinement was validated on 20 NMR structures. Most of the quality assessment scores of the refined NMR structures were better than those of the original structures. The refinement results are provided as a three-dimensional structure view, a secondary structure scheme, and numerical and graphical structure validation scores. NMRe is available at http://psb.kobic.re.kr/nmre/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Investigation of anti-cancer mechanisms by comparative analysis of naked mole rat and rat

PubMed Central

2013-01-01

Background The naked mole rats (NMRs) are small-sized underground rodents with plenty of unusual traits. Their life expectancy can be up to thirty years, more than seven times longer than laboratory rat. Furthermore, they are resistant to both congenital and experimentally induced cancer genesis. These peculiar physiological and pathological characteristics allow them to become a suitable model for cancer and aging research. Results In this paper, we carried out a genome-wide comparative analysis of rat and NMR using the recently published genome sequence of NMR. First, we identified all the rat-NMR orthologous genes and specific genes within each of them. The expanded and contracted numbers of protein families in NMR were also analyzed when compared to rat. Seven cancer-related protein families appeared to be significantly expanded, whereas several receptor families were found to be contracted in NMR. We then chose those rat genes that were inexistent in NMR and adopted KEGG pathway database to investigate the metabolic processes in which their proteins may be involved. These genes were significantly enriched in two rat cancer pathways, "Pathway in cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths leading to evading apoptosis appeared to be affected in NMR. In addition, a significant number of other NMR-missing genes enriched in several cancer-related pathways have been known to be related to a variety of cancers, implying that many of them may be also related to tumorigenesis in mammals. Finally, investigation of sequence variations among orthologous proteins between rat and NMR revealed that significant fragment insertions/deletions within important functional domains were present in some NMR proteins, which might lead to expressional and/or functional changes of these genes in different species. Conclusions Overall, this study provides insights into understanding the possible anti-cancer mechanisms of NMR as well as searching for new cancer-related candidate genes. PMID:24565050

Introducing NMR to a General Chemistry Audience: A Structural-Based Instrumental Laboratory Relating Lewis Structures, Molecular Models, and [superscript 13]C NMR Data

ERIC Educational Resources Information Center

Pulliam, Curtis R.; Pfeiffer, William F.; Thomas, Alyssa C.

2015-01-01

This paper describes a first-year general chemistry laboratory that uses NMR spectroscopy and model building to emphasize molecular shape and structure. It is appropriate for either a traditional or an atoms-first curriculum. Students learn the basis of structure and the use of NMR data through a cooperative learning hands-on laboratory…

Saturation-Transfer Difference (STD) NMR: A Simple and Fast Method for Ligand Screening and Characterization of Protein Binding

ERIC Educational Resources Information Center

Viegas, Aldino; Manso, Joao; Nobrega, Franklin L.; Cabrita, Eurico J.

2011-01-01

Saturation transfer difference (STD) NMR has emerged as one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. The success of this technique is a consequence of its robustness and the fact that it is focused on the signals of the ligand, without any need of processing NMR information about the receptor…

Micromixer-based time-resolved NMR: applications to ubiquitin protein conformation.

PubMed

Kakuta, Masaya; Jayawickrama, Dimuthu A; Wolters, Andrew M; Manz, Andreas; Sweedler, Jonathan V

2003-02-15

Time-resolved NMR spectroscopy is used to studychanges in protein conformation based on the elapsed time after a change in the solvent composition of a protein solution. The use of a micromixer and a continuous-flow method is described where the contents of two capillary flows are mixed rapidly, and then the NMR spectra of the combined flow are recorded at precise time points. The distance after mixing the two fluids and flow rates define the solvent-protein interaction time; this method allows the measurement of NMR spectra at precise mixing time points independent of spectral acquisition time. Integration of a micromixer and a microcoil NMR probe enables low-microliter volumes to be used without losing significant sensitivity in the NMR measurement. Ubiquitin, the model compound, changes its conformation from native to A-state at low pH and in 40% or higher methanol/water solvents. Proton NMR resonances of the His-68 and the Tyr-59 of ubiquitin are used to probe the conformational changes. Mixing ubiquitin and methanol solutions under low pH at microliter per minute flow rates yields both native and A-states. As the flow rate decreases, yielding longer reaction times, the population of the A-state increases. The micromixer-NMR system can probe reaction kinetics on a time scale of seconds.

Extraction and [superscript 1]H NMR Analysis of Fats from Convenience Foods: A Laboratory Experiment for Organic Chemistry

ERIC Educational Resources Information Center

Hartel, Aaron M.; Moore, Amy C.

2014-01-01

The extraction and analysis of fats from convenience foods (crackers, cookies, chips, candies) has been developed as an experiment for a second-year undergraduate organic chemistry laboratory course. Students gravimetrically determine the fat content per serving and then perform a [superscript 1]H NMR analysis of the recovered fat to determine the…

Comparative study of single/combination use of Huang-Lian-Jie-Du decoction and berberine on their protection on sepsis induced acute liver injury by NMR metabolic profiling.

PubMed

Lv, Yan; Wang, Junsong; Xu, Dingqiao; Liao, Shanting; Li, Pei; Zhang, Qian; Yang, Minghua; Kong, Lingyi

2017-10-25

Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, 1 H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

A 1H-NMR based metabolomics study of the intervention effect of mangiferin on hyperlipidemia hamsters induced by a high-fat diet.

PubMed

Guo, Fuchuan; Zi, Tianqi; Liu, Liyan; Feng, Rennan; Sun, Changhao

2017-07-19

It has been demonstrated that mangiferin can ameliorate hypertriglyceridemia by modulating the expression levels of genes involved in lipid metabolism in animal experiments, but its effects on the serum metabolic fingerprinting of hyperlipidemia animal models have not been reported. Thus, a NMR-based metabolomics approach was conducted to explore the effects of mangiferin on hyperlipidemia hamsters and to gain a better understanding of the involved metabolic pathways. Hamsters fed with a high-fat diet were orally administered with mangiferin 150 mg per kg BW once a day for 8 weeks. Serum samples were analysed by 1 H NMR, and multivariate statistical analysis was applied to the data to identify potential biomarkers. In total, 20 discriminating metabolites were identified. It turned out that mangiferin administration can partly reverse the metabolism disorders induced by a high-fat diet and exerted a good anti-hypertriglyceridemia effect. Mangiferin ameliorated hyperlipidemia by intervening in some major metabolic pathways, involving glycolysis, the TCA cycle, synthesis of ketone bodies, and BCAAs as well as choline and lipid metabolism. These findings provided new essential information on the effects of mangiferin and demonstrated the great potential of this nutrimetabolomics approach.

Microplate assay for screening the antibacterial activity of Schiff bases derived from substituted benzopyran-4-one.

PubMed

Amin, Rehab M; Abdel-Kader, Nora S; El-Ansary, Aida L

2012-09-01

Schiff bases (SB(1)-SB(3)) were synthesized from the condensation of 6-formyl-7-hydroxy-5-methoxy-2-methylbenzopyran-4-one with 2-aminopyridine (SB(1)), p-phenylenediamine (SB(2)) and o-phenylenediamine (SB(3)), while Schiff bases (SB(4)-SB(6)) were synthesized by condensation of 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one with 2-aminopyridine (SB(4)), p-phenylenediamine (SB(5)) and o-phenylenediamine (SB(6)). Schiff bases were characterized using elemental analysis, IR, UV-Vis, (1)H NMR, (13)C NMR and mass spectroscopy. These compounds were screened for antibacterial activities by micro-plate assay technique. Escherichia coli and Staphylococcus capitis were exposed to different concentrations of the Schiff bases. Results showed that the antibacterial effect of these Schiff bases on Gram-negative bacteria were higher than that on Gram-positive bacteria moreover, the Schiff bases containing substituent OCH(3) on position five have higher antibacterial activity than that containing hydroxy group on the same position. Copyright © 2012 Elsevier B.V. All rights reserved.

A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

PubMed Central

Everett, Jeremy R.

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field. PMID:25750701

A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

PubMed

Everett, Jeremy R

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

Kinetic analysis of reactions of Si-based epoxy resins by near-infrared spectroscopy, 13C NMR and soft-hard modelling.

PubMed

Garrido, Mariano; Larrechi, Maria Soledad; Rius, F Xavier; Mercado, Luis Adolfo; Galià, Marina

2007-02-05

Soft- and hard-modelling strategy was applied to near-infrared spectroscopy data obtained from monitoring the reaction between glycidyloxydimethylphenyl silane, a silicon-based epoxy monomer, and aniline. On the basis of the pure soft-modelling approach and previous chemical knowledge, a kinetic model for the reaction was proposed. Then, multivariate curve resolution-alternating least squares optimization was carried out under a hard constraint, that compels the concentration profiles to fulfil the proposed kinetic model at each iteration of the optimization process. In this way, the concentration profiles of each species and the corresponding kinetic rate constants of the reaction, unpublished until now, were obtained. The results obtained were contrasted with 13C NMR. The joint interval test of slope and intercept for detecting bias was not significant (alpha=5%).

Design of arbitrarily homogeneous permanent magnet systems for NMR and MRI: theory and experimental developments of a simple portable magnet.

PubMed

Hugon, Cedric; D'Amico, Francesca; Aubert, Guy; Sakellariou, Dimitris

2010-07-01

Starting from general results of magnetostatics, we give fundamental considerations on the design and characterization of permanent magnets for NMR based on harmonic analysis and symmetry. We then propose a simple geometry that takes advantage of some of these considerations and discuss the practical aspects of the assembly of a real magnet based on this geometry, involving the characterization of its elements, the optimization of the layout and the correction of residual inhomogeneities due to material and geometry imperfections. We report with this low-cost, light-weight magnet (100 euros and 1.8 kg including the aluminum frame) a field of 120 mT (5.1 MHz proton) with a 10 ppm natural homogeneity over a sphere of 1.5 mm in diameter. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Spectroscopic [FT-IR and FT-Raman] and theoretical [UV-Visible and NMR] analysis on α-Methylstyrene by DFT calculations

NASA Astrophysics Data System (ADS)

Karthikeyan, N.; Joseph Prince, J.; Ramalingam, S.; Periandy, S.

2015-05-01

In the present research work, the FT-IR, FT-Raman and 13C and 1H NMR spectra of the α-Methylstyrene were recorded. The observed fundamental frequencies in finger print as well as functional group regions were assigned according to their uniqueness region. The Gaussian computational calculations are carried out by HF and DFT (B3LYP and B3PW91) methods with 6-31++G(d,p) and 6-311++G(d,p) basis sets and the corresponding results were tabulated. The impact of the presence of vinyl group in phenyl structure of the compound is investigated. The modified vibrational pattern of the molecule associated vinyl group was analyzed. Moreover, 13C NMR and 1H NMR were calculated by using the gauge independent atomic orbital (GIAO) method with B3LYP methods and the 6-311++G(d,p) basis set and their spectra were simulated and the chemical shifts linked to TMS were compared. A study on the electronic and optical properties; absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies were carried out. The kubo gap of the present compound was calculated related to HOMO and LUMO energies which confirm the occurring of charge transformation between the base and ligand. Besides frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) was performed. The NLO properties related to Polarizability and hyperpolarizability based on the finite-field approach were also discussed.

Fractional motion model for characterization of anomalous diffusion from NMR signals.

PubMed

Fan, Yang; Gao, Jia-Hong

2015-07-01

Measuring molecular diffusion has been used to characterize the properties of living organisms and porous materials. NMR is able to detect the diffusion process in vivo and noninvasively. The fractional motion (FM) model is appropriate to describe anomalous diffusion phenomenon in crowded environments, such as living cells. However, no FM-based NMR theory has yet been established. Here, we present a general formulation of the FM-based NMR signal under the influence of arbitrary magnetic field gradient waveforms. An explicit analytic solution of the stretched exponential decay format for NMR signals with finite-width Stejskal-Tanner bipolar pulse magnetic field gradients is presented. Signals from a numerical simulation matched well with the theoretical prediction. In vivo diffusion-weighted brain images were acquired and analyzed using the proposed theory, and the resulting parametric maps exhibit remarkable contrasts between different brain tissues.

Fractional motion model for characterization of anomalous diffusion from NMR signals

NASA Astrophysics Data System (ADS)

Fan, Yang; Gao, Jia-Hong

2015-07-01

Measuring molecular diffusion has been used to characterize the properties of living organisms and porous materials. NMR is able to detect the diffusion process in vivo and noninvasively. The fractional motion (FM) model is appropriate to describe anomalous diffusion phenomenon in crowded environments, such as living cells. However, no FM-based NMR theory has yet been established. Here, we present a general formulation of the FM-based NMR signal under the influence of arbitrary magnetic field gradient waveforms. An explicit analytic solution of the stretched exponential decay format for NMR signals with finite-width Stejskal-Tanner bipolar pulse magnetic field gradients is presented. Signals from a numerical simulation matched well with the theoretical prediction. In vivo diffusion-weighted brain images were acquired and analyzed using the proposed theory, and the resulting parametric maps exhibit remarkable contrasts between different brain tissues.

Recent Advances in Characterization of Lignin Polymer by Solution-State Nuclear Magnetic Resonance (NMR) Methodology

PubMed Central

Wen, Jia-Long; Sun, Shao-Long; Xue, Bai-Liang; Sun, Run-Cang

2013-01-01

The demand for efficient utilization of biomass induces a detailed analysis of the fundamental chemical structures of biomass, especially the complex structures of lignin polymers, which have long been recognized for their negative impact on biorefinery. Traditionally, it has been attempted to reveal the complicated and heterogeneous structure of lignin by a series of chemical analyses, such as thioacidolysis (TA), nitrobenzene oxidation (NBO), and derivatization followed by reductive cleavage (DFRC). Recent advances in nuclear magnetic resonance (NMR) technology undoubtedly have made solution-state NMR become the most widely used technique in structural characterization of lignin due to its versatility in illustrating structural features and structural transformations of lignin polymers. As one of the most promising diagnostic tools, NMR provides unambiguous evidence for specific structures as well as quantitative structural information. The recent advances in two-dimensional solution-state NMR techniques for structural analysis of lignin in isolated and whole cell wall states (in situ), as well as their applications are reviewed. PMID:28809313

Structural and Nutritional Properties of Pasta from Triticum monococcum and Triticum durum Species. A Combined ¹H NMR, MRI, and Digestibility Study.

PubMed

Pasini, Gabriella; Greco, Fulvia; Cremonini, Mauro A; Brandolini, Andrea; Consonni, Roberto; Gussoni, Maristella

2015-05-27

The aim of the present study was to characterize the structure of two different types of pasta, namely Triticum turgidum ssp. durum (cv. Saragolla) and Triticum monococcum ssp. monococcum (cv. Monlis), under different processing conditions. MRI analysis and NMR spectroscopy (i.e., T1 and T2 NMR relaxation times and diffusion parameters) were conducted on pasta, and (1)H NMR spectroscopic analysis of the chemical compounds released by pasta samples during the cooking process was performed. In addition, starch digestibility (enzimatically determined) was also investigated. The NMR results indicated that Saragolla pasta has a more compact structure, ascribed to pasta network and in particular to different technological gluten properties, that mainly determine the lower ability of Monlis pasta in binding water. These results correlate well with the lower rate of starch hydrolysis measured for Monlis pasta compared to Saragolla when both are dried at high temperature.

Improving the analysis of NMR spectra tracking pH-induced conformational changes: removing artefacts of the electric field on the NMR chemical shift.

PubMed

Kukić, Predrag; Farrell, Damien; Søndergaard, Chresten R; Bjarnadottir, Una; Bradley, John; Pollastri, Gianluca; Nielsen, Jens Erik

2010-03-01

pH-induced chemical shift perturbations (CSPs) can be used to study pH-dependent conformational transitions in proteins. Recently, an elegant principal component analysis (PCA) algorithm was developed and used to study the pH-dependent structural transitions in bovine beta-lactoglobulin (betaLG) by analyzing its NMR pH-titration spectra. Here, we augment this analysis method by filtering out changes in the NMR chemical shift that stem from effects that are electrostatic in nature. Specifically, we examine how many CSPs can be explained by purely electrostatic effects arising from titrational events in betaLG. The results show that around 20% of the amide nuclei CSPs in betaLG originate exclusively from "through-space" electric field effects. A PCA of NMR data where electric field artefacts have been removed gives a different picture of the pH-dependent structural transitions in betaLG. The method implemented here is well suited to be applied on a whole range of proteins, which experience at least one pH-dependent conformational change. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood.

PubMed

Gee, Michael S; Ghazani, Arezou A; Haq, Rizwan; Wargo, Jennifer A; Sebas, Matthew; Sullivan, Ryan J; Lee, Hakho; Weissleder, Ralph

2017-04-01

This study evaluates μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. μNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with μNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate that μNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients. Copyright © 2016 Elsevier Inc. All rights reserved.

PREdator: a python based GUI for data analysis, evaluation and fitting

PubMed Central

2014-01-01

The analysis of a series of experimental data is an essential procedure in virtually every field of research. The information contained in the data is extracted by fitting the experimental data to a mathematical model. The type of the mathematical model (linear, exponential, logarithmic, etc.) reflects the physical laws that underlie the experimental data. Here, we aim to provide a readily accessible, user-friendly python script for data analysis, evaluation and fitting. PREdator is presented at the example of NMR paramagnetic relaxation enhancement analysis.

Study on 1H-NMR fingerprinting of Rhodiolae Crenulatae Radix et Rhizoma.

PubMed

Wen, Shi-yuan; Zhou, Jiang-tao; Chen, Yan-yan; Ding, Li-qin; Jiang, Miao-miao

2015-07-01

Nuclear magnetic resonance (1H-NMR) fingerprint of Rhodiola rosea medicinal materials was established, and used to distinguish the quality of raw materials from different sources. Pulse sequence for water peak inhibition was employed to acquire 1H-NMR spectra with the temperature at 298 K and spectrometer frequency of 400.13 MHz. Through subsection integral method, the obtained NMR data was subjected to similarity analysis and principal component analysis (PCA). 10 batches raw materials of Rhodiola rosea from different origins were successfully distinguished by PCA. The statistical results indicated that rhodiola glucoside, butyl alcohol, maleic acid and alanine were the main differential ingredients. This method provides an auxiliary method of Chinese quality approach to evaluate the quality of Rhodiola crenulata without using natural reference substances.

Multidimensional NMR approaches towards highly resolved, sensitive and high-throughput quantitative metabolomics.

PubMed

Marchand, Jérémy; Martineau, Estelle; Guitton, Yann; Dervilly-Pinel, Gaud; Giraudeau, Patrick

2017-02-01

Multi-dimensional NMR is an appealing approach for dealing with the challenging complexity of biological samples in metabolomics. This article describes how spectroscopists have recently challenged their imagination in order to make 2D NMR a powerful tool for quantitative metabolomics, based on innovative pulse sequences combined with meticulous analytical chemistry approaches. Clever time-saving strategies have also been explored to make 2D NMR a high-throughput tool for metabolomics, relying on alternative data acquisition schemes such as ultrafast NMR. Currently, much work is aimed at drastically boosting the NMR sensitivity thanks to hyperpolarisation techniques, which have been used in combination with fast acquisition methods and could greatly expand the application potential of NMR metabolomics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparing pharmacophore models derived from crystallography and NMR ensembles

NASA Astrophysics Data System (ADS)

Ghanakota, Phani; Carlson, Heather A.

2017-11-01

NMR and X-ray crystallography are the two most widely used methods for determining protein structures. Our previous study examining NMR versus X-Ray sources of protein conformations showed improved performance with NMR structures when used in our Multiple Protein Structures (MPS) method for receptor-based pharmacophores (Damm, Carlson, J Am Chem Soc 129:8225-8235, 2007). However, that work was based on a single test case, HIV-1 protease, because of the rich data available for that system. New data for more systems are available now, which calls for further examination of the effect of different sources of protein conformations. The MPS technique was applied to Growth factor receptor bound protein 2 (Grb2), Src SH2 homology domain (Src-SH2), FK506-binding protein 1A (FKBP12), and Peroxisome proliferator-activated receptor-γ (PPAR-γ). Pharmacophore models from both crystal and NMR ensembles were able to discriminate between high-affinity, low-affinity, and decoy molecules. As we found in our original study, NMR models showed optimal performance when all elements were used. The crystal models had more pharmacophore elements compared to their NMR counterparts. The crystal-based models exhibited optimum performance only when pharmacophore elements were dropped. This supports our assertion that the higher flexibility in NMR ensembles helps focus the models on the most essential interactions with the protein. Our studies suggest that the "extra" pharmacophore elements seen at the periphery in X-ray models arise as a result of decreased protein flexibility and make very little contribution to model performance.

Establishment and optimization of NMR-based cell metabonomics study protocols for neonatal Sprague-Dawley rat cardiomyocytes.

PubMed

Zhang, Ming; Sun, Bo; Zhang, Qi; Gao, Rong; Liu, Qiao; Dong, Fangting; Fang, Haiqin; Peng, Shuangqing; Li, Famei; Yan, Xianzhong

2017-01-15

A quenching, harvesting, and extraction protocol was optimized for cardiomyocytes NMR metabonomics analysis in this study. Trypsin treatment and direct scraping cells in acetonitrile were compared for sample harvesting. The results showed trypsin treatment cause normalized concentration increasing of phosphocholine and metabolites leakage, since the trypsin-induced membrane broken and long term harvesting procedures. Then the intracellular metabolite extraction efficiency of methanol and acetonitrile were compared. As a result, washing twice with phosphate buffer, direct scraping cells and extracting with acetonitrile were chosen to prepare cardiomyocytes extracts samples for metabonomics studies. This optimized protocol is rapid, effective, and exhibits greater metabolite retention. Copyright © 2016 Elsevier Inc. All rights reserved.

Non-Linear Signal Detection Improvement by Radiation Damping in Single-Pulse NMR Spectra

PubMed Central

Schlagnitweit, Judith; Morgan, Steven W; Nausner, Martin; Müller, Norbert; Desvaux, Hervé

2012-01-01

When NMR lines overlap and at least one of them is affected by radiation damping, the resonance line shapes of all lines are no longer Lorentzian. We report the appearance of narrow signal distortions, which resemble hole-burnt spectra. This new experimental phenomenon facilitates the detection of tiny signals hidden below the main resonance. Theoretical analysis based on modified Maxwell–Bloch equations shows that the presence of strong transverse magnetization creates a feedback through the coil, which influences the magnetization of all spins with overlapping resonance lines. In the time domain this leads to cross-precession terms between magnetization densities, which ultimately cause non-linear behavior. Numerical simulations corroborate this interpretation. PMID:22266720

A Solid-State NMR Experiment: Analysis of Local Structural Environments in Phosphate Glasses

ERIC Educational Resources Information Center

Anderson, Stanley E.; Saiki, David; Eckert, Hellmut; Meise-Gresch, Karin

2004-01-01

An experiment that can be used to directly study the local chemical environments of phosphorus in solid amorphous materials is demonstrated. The experiment aims at familiarizing the students of chemistry with the principles of solid-state NMR, by having them synthesize a simple phosphate glass, and making them observe the (super 31)P NMR spectrum,…

NMR and MRI apparatus and method

DOEpatents

Clarke, John; Kelso, Nathan; Lee, SeungKyun; Moessle, Michael; Myers, Whittier; McDermott, Robert; ten Haken, Bernard; Pines, Alexander; Trabesinger, Andreas

2007-03-06

Nuclear magnetic resonance (NMR) signals are detected in microtesla fields. Prepolarization in millitesla fields is followed by detection with an untuned dc superconducting quantum interference device (SQUID) magnetometer. Because the sensitivity of the SQUID is frequency independent, both signal-to-noise ratio (SNR) and spectral resolution are enhanced by detecting the NMR signal in extremely low magnetic fields, where the NMR lines become very narrow even for grossly inhomogeneous measurement fields. Additional signal to noise benefits are obtained by use of a low noise polarization coil, comprising litz wire or superconducting materials. MRI in ultralow magnetic field is based on the NMR at ultralow fields. Gradient magnetic fields are applied, and images are constructed from the detected NMR signals.

Protein Structural Information Derived from NMR Chemical Shift with the Neural Network Program TALOS-N

PubMed Central

Shen, Yang; Bax, Ad

2015-01-01

Summary Chemical shifts are obtained at the first stage of any protein structural study by NMR spectroscopy. Chemical shifts are known to be impacted by a wide range of structural factors and the artificial neural network based TALOS-N program has been trained to extract backbone and sidechain torsion angles from 1H, 15N and 13C shifts. The program is quite robust, and typically yields backbone torsion angles for more than 90% of the residues, and sidechain χ1 rotamer information for about half of these, in addition to reliably predicting secondary structure. The use of TALOS-N is illustrated for the protein DinI, and torsion angles obtained by TALOS-N analysis from the measured chemical shifts of its backbone and 13Cβ nuclei are compared to those seen in a prior, experimentally determined structure. The program is also particularly useful for generating torsion angle restraints, which then can be used during standard NMR protein structure calculations. PMID:25502373

Nonlinear Behavior of a Shim Coil in an LTS/HTS NMR Magnet With an HTS Insert Comprising Double-Pancake HTS-Tape Coils

PubMed Central

Hahn, Seung-yong; Ahn, Min Cheol; Bascuñán, Juan; Yao, Weijun; Iwasa, Yukikazu

2010-01-01

This paper reports results, experimental and analytical, of the nonlinear behavior of a shim coil in the presence of an HTS coil assembled with double-pancake (DP) HTS-tape coils. The experimental results are from: 1) operation of a 700 MHz LTS/HTS NMR magnet (LH700) consisting of a 600 MHz LTS NMR magnet (L600) equipped with superconducting shim coils and a 100 MHz DP-assembled HTS insert (H100) and; 2) an experiment with a room-temperature (RT) Z1 shim coil coupled to a 50 MHz DP-as-sembled HTS insert (H50). A field mapping theory with a harmonic analysis is applied to interpret both results. Based on experimental results and analyses, we conclude that the screening-current-induced field (SCF) generated by a DP-assembled HTS insert is primarily responsible for the nonlinear behavior, including strength degradation, of a shim coil. PMID:20383282

Synthesis, X-ray diffraction method, spectroscopic characterization (FT-IR, 1H and 13C NMR), antimicrobial activity, Hirshfeld surface analysis and DFT computations of novel sulfonamide derivatives

NASA Astrophysics Data System (ADS)

Demircioğlu, Zeynep; Özdemir, Fethi Ahmet; Dayan, Osman; Şerbetçi, Zafer; Özdemir, Namık

2018-06-01

Synthesized compounds of N-(2-aminophenyl)benzenesulfonamide 1 and (Z)-N-(2-((2-nitrobenzylidene)amino)phenyl)benzenesulfonamide 2 were characterized by antimicrobial activity, FT-IR, 1H and 13C NMR. Two new Schiff base ligands containing aromatic sulfonamide fragment of (Z)-N-(2-((3-nitrobenzylidene)amino)phenyl)benzenesulfonamide 3 and (Z)-N-(2-((4-nitrobenzylidene)amino)phenyl)benzenesulfonamide 4 were synthesized and investigated by spectroscopic techniques including 1H and 13C NMR, FT-IR, single crystal X-ray diffraction, Hirshfeld surface, theoretical method analyses and by antimicrobial activity. The molecular geometry obtained from the X-ray structure determination was optimized Density Functional Theory (DFT/B3LYP) method with the 6-311++G(d,p) basis set in ground state. From the optimized geometry of the molecules of 3 and 4, the geometric parameters, vibrational wavenumbers and chemical shifts were computed. The optimized geometry results, which were well represented the X-ray data, were shown that the chosen of DFT/B3LYP 6-311G++(d,p) was a successful choice. After a successful optimization, frontier molecular orbitals, chemical activity, non-linear optical properties (NLO), molecular electrostatic mep (MEP), Mulliken population method, natural population analysis (NPA) and natural bond orbital analysis (NBO), which cannot be obtained experimentally, were calculated and investigated.

Antimicrobial Applications of Transition Metal Complexes of Benzothiazole Based Terpolymer: Synthesis, Characterization, and Effect on Bacterial and Fungal Strains

PubMed Central

Riswan Ahamed, Mohamed A.; Azarudeen, Raja S.; Kani, N. Mujafar

2014-01-01

Terpolymer of 2-amino-6-nitro-benzothiazole-ethylenediamine-formaldehyde (BEF) has been synthesized and characterized by elemental analysis and various spectral techniques like FTIR, UV-Visible, and 1H and 13C-NMR. The terpolymer metal complexes were prepared with Cu2+, Ni2+, and Zn2+ metal ions using BEF terpolymer as a ligand. The complexes have been characterized by elemental analysis and IR, UV-Visible, ESR, 1H-NMR, and 13C-NMR spectral studies. Gel permeation chromatography was used to determine the molecular weight of the ligand. The surface features and crystalline behavior of the ligand and its complexes were analyzed by scanning electron microscope and X-ray diffraction methods. Thermogravimetric analysis was used to analyze the thermal stability of the ligand and its metal complexes. Kinetic parameters such as activation energy (E a) and order of reaction (n) and thermodynamic parameters, namely, ΔS, ΔF, S*, and Z, were calculated using Freeman-Carroll (FC), Sharp-Wentworth (SW), and Phadnis-Deshpande (PD) methods. Thermal degradation model of the terpolymer and its metal complexes was also proposed using PD method. Biological activities of the ligand and its complexes were tested against Shigella sonnei, Escherichia coli, Klebsiella species, Staphylococcus aureus, Bacillus subtilis, and Salmonella typhimurium bacteria and Aspergillus flavus, Aspergillus niger, Penicillium species, Candida albicans, Cryptococcus neoformans, Mucor species fungi. PMID:25298760

Investigation into adamantane-based M2 inhibitors with FB-QSAR.

PubMed

Wei, Hang; Wang, Cheng-Hua; Du, Qi-Shi; Meng, Jianzong; Chou, Kuo-Chen

2009-07-01

Because of their high resistance rate to the existing drugs, influenza A viruses have become a threat to human beings. It is known that the replication of influenza A viruses needs a pH-gated proton channel, the so-called M2 channel. Therefore, to develop effective drugs against influenza A, the most logic strategy is to inhibit the M2 channel. Recently, the atomic structure of the M2 channel was determined by NMR spectroscopy (Schnell, J.R. and Chou, J.J., Nature, 2008, 451, 591-595). The high-resolution NMR structure has provided a solid basis for structure-based drug design approaches. In this study, a benchmark dataset has been constructed that contains 34 newly-developed adamantane-based M2 inhibitors and covers considerable structural diversities and wide range of bioactivities. Based on these compounds, an in-depth analysis was performed with the newly developed fragment-based quantitative structure-activity relationship (FB-QSAR) algorithm. The results thus obtained provide useful insights for dealing with the drug-resistant problem and designing effective adamantane-based antiflu drugs.

Beyond Fourier.

PubMed

Hoch, Jeffrey C

2017-10-01

Non-Fourier methods of spectrum analysis are gaining traction in NMR spectroscopy, driven by their utility for processing nonuniformly sampled data. These methods afford new opportunities for optimizing experiment time, resolution, and sensitivity of multidimensional NMR experiments, but they also pose significant challenges not encountered with the discrete Fourier transform. A brief history of non-Fourier methods in NMR serves to place different approaches in context. Non-Fourier methods reflect broader trends in the growing importance of computation in NMR, and offer insights for future software development. Copyright © 2017 Elsevier Inc. All rights reserved.

6C.04: INTEGRATED SNP ANALYSIS AND METABOLOMIC PROFILES OF METABOLIC SYNDROME.

PubMed

Marrachelli, V; Monleon, D; Morales, J M; Rentero, P; Martínez, F; Chaves, F J; Martin-Escudero, J C; Redon, J

2015-06-01

Metabolic syndrome (MS) has become a health and financial burden worldwide. Susceptibility of genetically determined metabotype of MS has not yet been investigated. We aimed to identify a distinctive metabolic profile of blood serum which might correlates to the early detection of the development of MS associated to genetic polymorphism. We applied high resolution NMR spectroscopy to profile blood serum from patients without MS (n = 945) or with (n = 291). Principal component analysis (PCA) and projection to latent structures for discriminant analysis (PLS-DA) were applied to NMR spectral datasets. Results were cross-validated using the Venetian Blinds approach. Additionally, five SNPs previously associated with MS were genotyped with SNPlex and tested for associations between the metabolic profiles and the genetic variants. Statistical analysis was performed using in-house MATLAB scripts and the PLS Toolbox statistical multivariate analysis library. Our analysis provided a PLS-DA Metabolic Syndrome discrimination model based on NMR metabolic profile (AUC = 0.86) with 84% of sensitivity and 72% specificity. The model identified 11 metabolites differentially regulated in patients with MS. Among others, fatty acids, glucose, alanine, hydroxyisovalerate, acetone, trimethylamine, 2-phenylpropionate, isobutyrate and valine, significantly contributed to the model. The combined analysis of metabolomics and SNP data revealed an association between the metabolic profile of MS and genes polymorphism involved in the adiposity regulation and fatty acids metabolism: rs2272903_TT (TFAP2B), rs3803_TT (GATA2), rs174589_CC (FADS2) and rs174577_AA (FADS2). In addition, individuals with the rs2272903-TT genotype seem to develop MS earlier than general population. Our study provides new insights on the metabolic alterations associated with a MS high-risk genotype. These results could help in future development of risk assessment and predictive models for subclinical cardiovascular disease.

High-resolution NMR study of light and heavy crude oils: “structure-property” analysis

NASA Astrophysics Data System (ADS)

Rakhmatullin, I.; Efimov, S.; Varfolomeev, M.; Klochkov, V.

2018-05-01

Measurements of three light and one heavy crude oil samples were carried out by high-resolution nuclear magnetic resonance (NMR) spectroscopy methods. Quantitative fractions of aromatic molecules and functional groups constituting oil hydrocarbons were determined, and comparative analysis of the oil samples of different viscosity and origin was done.

NMR in the SPINE Structural Proteomics project.

PubMed

Ab, E; Atkinson, A R; Banci, L; Bertini, I; Ciofi-Baffoni, S; Brunner, K; Diercks, T; Dötsch, V; Engelke, F; Folkers, G E; Griesinger, C; Gronwald, W; Günther, U; Habeck, M; de Jong, R N; Kalbitzer, H R; Kieffer, B; Leeflang, B R; Loss, S; Luchinat, C; Marquardsen, T; Moskau, D; Neidig, K P; Nilges, M; Piccioli, M; Pierattelli, R; Rieping, W; Schippmann, T; Schwalbe, H; Travé, G; Trenner, J; Wöhnert, J; Zweckstetter, M; Kaptein, R

2006-10-01

This paper describes the developments, role and contributions of the NMR spectroscopy groups in the Structural Proteomics In Europe (SPINE) consortium. Focusing on the development of high-throughput (HTP) pipelines for NMR structure determinations of proteins, all aspects from sample preparation, data acquisition, data processing, data analysis to structure determination have been improved with respect to sensitivity, automation, speed, robustness and validation. Specific highlights are protonless (13)C-direct detection methods and inferential structure determinations (ISD). In addition to technological improvements, these methods have been applied to deliver over 60 NMR structures of proteins, among which are five that failed to crystallize. The inclusion of NMR spectroscopy in structural proteomics pipelines improves the success rate for protein structure determinations.

Design and UV-curable behaviour of boron based reactive diluent for epoxy acrylate oligomer used for flame retardant wood coating

PubMed Central

Chambhare, Sachin U.; Lokhande, Gunawant P.; Jagtap, Ramanand N.

2017-01-01

Abstract Difunctional boron-containing reactive flame retardant for UV-curable epoxy acrylate oligomer was synthesized from phenyl boronic acid and glycidyl methacrylate. The synthesized reactive diluent was utilized to formulate ultraviolet (UV)-curable wood coatings. The weight fractions of reactive diluent in coatings formulation was varied from 5 to 25 wt % with constant photoinitiator concentration. The molecular structure of reactive flame retardant was confirmed by Fourier-transform infrared, Nuclear magnetic resonance (NMR) and 11B NMR spectral analysis. Further, the efficacy of flame retardant behaviour of coatings was evaluated using limiting oxygen index and UL-94 vertical burning test. Thermal stability of cured coatings films were estimated from thermogravimetric and differential scanning calorimetry analysis. The effects of varying concentration of reactive diluent on the viscosity of coatings formulation along with optical, mechanical and chemical resistance properties of coatings were also evaluated. The coatings gel content, water absorption behaviour, contact angle analysis and stain resistance were also studied. PMID:29491786

1H NMR quantification in very dilute toxin solutions: application to anatoxin-a analysis.

PubMed

Dagnino, Denise; Schripsema, Jan

2005-08-01

A complete procedure is described for the extraction, detection and quantification of anatoxin-a in biological samples. Anatoxin-a is extracted from biomass by a routine acid base extraction. The extract is analysed by GC-MS, without the need of derivatization, with a detection limit of 0.5 ng. A method was developed for the accurate quantification of anatoxin-a in the standard solution to be used for the calibration of the GC analysis. 1H NMR allowed the accurate quantification of microgram quantities of anatoxin-a. The accurate quantification of compounds in standard solutions is rarely discussed, but for compounds like anatoxin-a (toxins with prices in the range of a million dollar a gram), of which generally only milligram quantities or less are available, this factor in the quantitative analysis is certainly not trivial. The method that was developed can easily be adapted for the accurate quantification of other toxins in very dilute solutions.

Composition and Quantitation of Microalgal Lipids by ERETIC 1H NMR Method

PubMed Central

Nuzzo, Genoveffa; Gallo, Carmela; d’Ippolito, Giuliana; Cutignano, Adele; Sardo, Angela; Fontana, Angelo

2013-01-01

Accurate characterization of biomass constituents is a crucial aspect of research in the biotechnological application of natural products. Here we report an efficient, fast and reproducible method for the identification and quantitation of fatty acids and complex lipids (triacylglycerols, glycolipids, phospholipids) in microalgae under investigation for the development of functional health products (probiotics, food ingredients, drugs, etc.) or third generation biofuels. The procedure consists of extraction of the biological matrix by modified Folch method and direct analysis of the resulting material by proton nuclear magnetic resonance (1H NMR). The protocol uses a reference electronic signal as external standard (ERETIC method) and allows assessment of total lipid content, saturation degree and class distribution in both high throughput screening of algal collection and metabolic analysis during genetic or culturing studies. As proof of concept, the methodology was applied to the analysis of three microalgal species (Thalassiosira weissflogii, Cyclotella cryptica and Nannochloropsis salina) which drastically differ for the qualitative and quantitative composition of their fatty acid-based lipids. PMID:24084790

¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations, Part I: Chemical shifts assignment.

PubMed

Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika Agnieszka; Szeleszczuk, Łukasz; Wawer, Iwona

2016-04-15

Solid-state NMR is an excellent and useful method for analyzing solid-state forms of drugs. In the (13)C CP/MAS NMR spectra of the solid dosage forms many of the signals originate from the excipients and should be distinguished from those of active pharmaceutical ingredient (API). In this work the most common pharmaceutical excipients used in the solid drug formulations: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. Their (13)C CP/MAS NMR spectra were recorded and the signals were assigned, employing the results (R(2): 0.948-0.998) of GIPAW calculations and theoretical chemical shifts. The (13)C ssNMR spectra for some of the studied excipients have not been published before while for the other signals in the spectra they were not properly assigned or the assignments were not correct. The results summarize and complement the data on the (13)C ssNMR analysis of the most common pharmaceutical excipients and are essential for further NMR studies of API-excipient interactions in the pharmaceutical formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

International NMR-based Environmental Metabolomics Intercomparison Exercise

EPA Science Inventory

Several fundamental requirements must be met so that NMR-based metabolomics and the related technique of metabonomics can be formally adopted into environmental monitoring and chemical risk assessment. Here we report an intercomparison exercise which has evaluated the effectivene...

Synthesis, spectroscopic, thermal and electrical conductivity studies of three charge transfer complexes formed between 1,3-di[( E)-1-(2-hydroxyphenyl)methylideneamino]-2-propanol Schiff base and different acceptors

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Ibrahim, Mohamed M.; Moussa, Mohamed A. A.

2012-01-01

Charge-transfer complexes (CTC) resulting from interactions of 1,3-di[( E)-1-(2-hydroxyphenyl) methylideneamino]-2-propanol Schiff base with some acceptors such as iodine (I2), bromine (Br2), and picric acid (PiA) have been isolated in the solid state in a chloroform solvent at room temperature. Based on elemental analysis, UV-Vis, infrared, and 1H NMR spectra, and thermogravimetric analysis (TG/DTG) of the solid CTC, [(Schiff)(I2)] (1), [(Schiff)(Br2)] complexes with a ratio of 1:1 and [(Schiff)(PiA)3] complexes with 1:3 have been prepared. In the picric acid complex, infrared and 1H NMR spectroscopic data indicate that the charge-transfer interaction is associated with a hydrogen bonding, whereas the iodine and bromine complexes were interpreted in terms of the formation of dative ion pairs [Schiff+, I{2/•-}] and [Schiff+, Br{2/•-}], respectively. Kinetic parameters were obtained for each stage of thermal degradation of the CT complexes using Coats-Redfern and Horowitz-Metzger methods. DC electrical properties as a function of temperature of these charge transfer complexes have been studied.

NMR data (ppm) from liver cells exposed to surfactant-wrapped (SDS) and oxidized (-OH) multi-walled carbon nanotubes (MWCNTs)

EPA Pesticide Factsheets

Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic properties. CNTs are commonly oxidized or treated with surfactants to facilitate aqueous solution processing, and these CNT surface modifications also increase possible human and ecological exposures to nanoparticle-contaminated waters. To determine the exposure outcomes of oxidized and surfactant-wrapped multiwalled carbon nanotubes (MWCNTs) on biochemical processes, metabolomics based profiling of human liver cells (C3A) was utilized. Cells were exposed to 0, 10, or 100 ng/mL of MWCNTs for 24 and 48 hr. MWCNT particle size distribution, charge, and aggregation were monitored concurrently during exposures. Following MWCNT exposure, cellular metabolites were extracted, lyophilized, and buffered for 1H NMR analysis. Acquired spectra were subjected to both multivariate and univariate analysis to determine the consequences of nanotube exposure on the metabolite profile of C3A cells. Resulting scores plots illustrated temporal and dose-dependent metabolite responses to all MWCNTs tested. Loadings plots coupled with t-test filtered spectra identified metabolites of interest. XPS analysis revealed the presence of hydroxyl and carboxyl functionalities on both MWCNTs surfaces. Metal content analysis by ICP-AES indicated that the total mass concentration of the potentially toxic impurities in the exposure exper

NMR-based conformational analysis of perezone and analogues.

PubMed

Zepeda, L Gerardo; Burgueño-Tapia, Eleuterio; Pérez-Hernández, Nury; Cuevas, Gabriel; Joseph-Nathan, Pedro

2013-04-01

Complete assignment of the (1)H NMR chemical shift and coupling constant values of perezone (1), O-methylperezone (2) and 6-hydroxyperezone (3) was carried out by total-line-shape-fitting calculations using the PERCH iterative spectra analysis software (PERCH Solutions Ltd., Kuopio, Finland). The resulting simulated spectra for the three compounds showed strong similarity to their corresponding experimental spectra. Particularly, all vicinal, allylic and homoallylic coupling constant values for the side chain of the three compounds were very similar, thus revealing that the conformation of these three molecules in solution is indeed almost identical. This fact is in agreement with extended side chain conformations over folded chain conformations because 1, 2 and 3 undergo completely different intramolecular cycloaddition reactions. In addition, results of double pulsed field gradient spin echo NOESY 1D experiments performed on perezone (1) were unable to provide evidence for folded conformers. Copyright © 2013 John Wiley & Sons, Ltd.

NMR Based Cerebrum Metabonomic Analysis Reveals Simultaneous Interconnected Changes during Chick Embryo Incubation.

PubMed

Feng, Yue; Zhu, Hang; Zhang, Xu; Wang, Xuxia; Xu, Fuqiang; Tang, Huiru; Ye, Chaohui; Liu, Maili

2015-01-01

To find out if content changes of the major functional cerebrum metabolites are interconnected and formed a network during the brain development, we obtained high-resolution magic-angle-spinning (HR-MAS) 1H NMR spectra of cerebrum tissues of chick embryo aged from incubation day 10 to 20, and postnatal day 1, and analyzed the data with principal component analysis (PCA). Within the examined time window, 26 biological important molecules were identified and 12 of them changed their relative concentration significantly in a time-dependent manner. These metabolites are generally belonged to three categories, neurotransmitters, nutrition sources, and neuronal or glial markers. The relative concentration changes of the metabolites were interconnected among/between the categories, and, more interestingly, associated with the number and size of Nissl-positive neurons. These results provided valuable biochemical and neurochemical information to understand the development of the embryonic brain.

NMR Based Cerebrum Metabonomic Analysis Reveals Simultaneous Interconnected Changes during Chick Embryo Incubation

PubMed Central

Feng, Yue; Zhu, Hang; Zhang, Xu; Wang, Xuxia; Xu, Fuqiang; Tang, Huiru; Ye, Chaohui; Liu, Maili

2015-01-01

To find out if content changes of the major functional cerebrum metabolites are interconnected and formed a network during the brain development, we obtained high-resolution magic-angle-spinning (HR-MAS) 1H NMR spectra of cerebrum tissues of chick embryo aged from incubation day 10 to 20, and postnatal day 1, and analyzed the data with principal component analysis (PCA). Within the examined time window, 26 biological important molecules were identified and 12 of them changed their relative concentration significantly in a time-dependent manner. These metabolites are generally belonged to three categories, neurotransmitters, nutrition sources, and neuronal or glial markers. The relative concentration changes of the metabolites were interconnected among/between the categories, and, more interestingly, associated with the number and size of Nissl-positive neurons. These results provided valuable biochemical and neurochemical information to understand the development of the embryonic brain. PMID:26485040

Evaluating the quality of NMR structures by local density of protons.

PubMed

Ban, Yih-En Andrew; Rudolph, Johannes; Zhou, Pei; Edelsbrunner, Herbert

2006-03-01

Evaluating the quality of experimentally determined protein structural models is an essential step toward identifying potential errors and guiding further structural refinement. Herein, we report the use of proton local density as a sensitive measure to assess the quality of nuclear magnetic resonance (NMR) structures. Using 256 high-resolution crystal structures with protons added and optimized, we show that the local density of different proton types display distinct distributions. These distributions can be characterized by statistical moments and are used to establish local density Z-scores for evaluating both global and local packing for individual protons. Analysis of 546 crystal structures at various resolutions shows that the local density Z-scores increase as the structural resolution decreases and correlate well with the ClashScore (Word et al. J Mol Biol 1999;285(4):1711-1733) generated by all atom contact analysis. Local density Z-scores for NMR structures exhibit a significantly wider range of values than for X-ray structures and demonstrate a combination of potentially problematic inflation and compression. Water-refined NMR structures show improved packing quality. Our analysis of a high-quality structural ensemble of ubiquitin refined against order parameters shows proton density distributions that correlate nearly perfectly with our standards derived from crystal structures, further validating our approach. We present an automated analysis and visualization tool for proton packing to evaluate the quality of NMR structures. 2005 Wiley-Liss, Inc.

Detection of poly(ethylene glycol) residues from nonionic surfactants in surface water by1h and13c nuclear magnetic resonance spectrometry

USGS Publications Warehouse

Leenheer, J.A.; Wershaw, R. L.; Brown, P.A.; Noyes, T.I.

1991-01-01

??? Poly(ethylene glycol) (PEG) residues were detected in organic solute isolates from surface water by 1H nuclear magnetic resonance spectrometry (NMR), 13C NMR spectrometry, and colorimetric assay. PEG residues were separated from natural organic solutes in Clear Creek, CO, by a combination of methylation and chromatographic procedures. The isolated PEG residues, characterized by NMR spectrometry, were found to consist of neutral and acidic residues that also contained poly(propylene glycol) moieties. The 1H NMR and the colorimetric assays for poly(ethylene glycol) residues were done on samples collected in the lower Mississippi River and tributaries between St. Louis, MO, and New Orleans, LA, in July-August and November-December 1987. Aqueous concentrations for poly(ethylene glycol) residues based on colorimetric assay ranged from undetectable to ???28 ??g/L. Concentrations based on 1H NMR spectrometry ranged from undetectable to 145 ??g/L.

Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Ju; Isern, Nancy G.; Burton, Sarah D.

2013-10-31

NMR metabolomics, consisting of solid state high resolution (hr) magic angle spinning (MAS) 1H NMR (1H hr-MAS), liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver . The melanoma group can be differentiated from its control group by PCA analysis of the absolute concentrations or by the absolute peak intensities of metabolites from either 1H hr-MAS NMR data on intact liver tissues or liquid state 1H-NMR spectra on liver tissue extracts. In particular, we found that the absolute concentrations of alanine, glutamate, creatine, creatinine, fumarate andmore » cholesterol are elevated in the melanoma group as compared to controls, while the absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acylglycerol are decreased. The ratio of glycerophosphocholine to phosphocholine is increased by about 1.5 fold in the melanoma group, while the absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.« less

Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment.

PubMed

Doskocz, Marek; Marchewka, Zofia; Jeż, Magdalena; Passowicz-Muszyńska, Ewa; Długosz, Anna

2015-01-01

Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p≤0.05, p≤0.01). There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program.

An overview of methods using (13)C for improved compound identification in metabolomics and natural products.

PubMed

Clendinen, Chaevien S; Stupp, Gregory S; Ajredini, Ramadan; Lee-McMullen, Brittany; Beecher, Chris; Edison, Arthur S

2015-01-01

Compound identification is a major bottleneck in metabolomics studies. In nuclear magnetic resonance (NMR) investigations, resonance overlap often hinders unambiguous database matching or de novo compound identification. In liquid chromatography-mass spectrometry (LC-MS), discriminating between biological signals and background artifacts and reliable determination of molecular formulae are not always straightforward. We have designed and implemented several NMR and LC-MS approaches that utilize (13)C, either enriched or at natural abundance, in metabolomics applications. For LC-MS applications, we describe a technique called isotopic ratio outlier analysis (IROA), which utilizes samples that are isotopically labeled with 5% (test) and 95% (control) (13)C. This labeling strategy leads to characteristic isotopic patterns that allow the differentiation of biological signals from artifacts and yield the exact number of carbons, significantly reducing possible molecular formulae. The relative abundance between the test and control samples for every IROA feature can be determined simply by integrating the peaks that arise from the 5 and 95% channels. For NMR applications, we describe two (13)C-based approaches. For samples at natural abundance, we have developed a workflow to obtain (13)C-(13)C and (13)C-(1)H statistical correlations using 1D (13)C and (1)H NMR spectra. For samples that can be isotopically labeled, we describe another NMR approach to obtain direct (13)C-(13)C spectroscopic correlations. These methods both provide extensive information about the carbon framework of compounds in the mixture for either database matching or de novo compound identification. We also discuss strategies in which (13)C NMR can be used to identify unknown compounds from IROA experiments. By combining technologies with the same samples, we can identify important biomarkers and corresponding metabolites of interest.

[Non-invasive analysis of proteins in living cells using NMR spectroscopy].

PubMed

Tochio, Hidehito; Murayama, Shuhei; Inomata, Kohsuke; Morimoto, Daichi; Ohno, Ayako; Shirakawa, Masahiro

2015-01-01

NMR spectroscopy enables structural analyses of proteins and has been widely used in the structural biology field in recent decades. NMR spectroscopy can be applied to proteins inside living cells, allowing characterization of their structures and dynamics in intracellular environments. The simplest "in-cell NMR" approach employs bacterial cells; in this approach, live Escherichia coli cells overexpressing a specific protein are subjected to NMR. The cells are grown in an NMR active isotope-enriched medium to ensure that the overexpressed proteins are labeled with the stable isotopes. Thus the obtained NMR spectra, which are derived from labeled proteins, contain atomic-level information about the structure and dynamics of the proteins. Recent progress enables us to work with higher eukaryotic cells such as HeLa and HEK293 cells, for which a number of techniques have been developed to achieve isotope labeling of the specific target protein. In this review, we describe successful use of electroporation for in-cell NMR. In addition, (19)F-NMR to characterize protein-ligand interactions in cells is presented. Because (19)F nuclei rarely exist in natural cells, when (19)F-labeled proteins are delivered into cells and (19)F-NMR signals are observed, one can safely ascertain that these signals originate from the delivered proteins and not other molecules.

Development of a micro nuclear magnetic resonance system

NASA Astrophysics Data System (ADS)

Goloshevsky, Artem

Application of Nuclear Magnetic Resonance (NMR) to on-line/in-line control of industrial processes is currently limited by equipment costs and requirements for installation. A superconducting magnet generating strong fields is the most expensive part of a typical NMR instrument. In industrial environments, fringe magnetic fields make accommodation of NMR instruments difficult. However, a portable, low-cost and low-field magnetic resonance system can be used in virtually any environment. Development of a number of hardware components for a portable, low-cost NMR instrument is reported in this dissertation. Chapter one provides a discussion on a miniaturized Helmholtz spiral radio-frequency (RF) coil (average diameter equal to 3.5 mm) and an NMR probe built around a capillary (outer diameter = 1.59 mm and inner diameter = 1.02 mm) for flow imaging. Experiments of NMR spectroscopy, static and dynamic (flow) imaging, conducted with the use of the miniaturized coil, are described. Chapter two presents a microfabricated package of two biaxial gradient coils and a Helmholtz RF coil. Planar configuration of discrete wires was used to create magnetic field gradients. Performance of the microfabricated gradient coils while imaging water flow compared well with a commercial gradient set of much larger size. Chapter three reports on flow imaging experiments with power law fluids (aqueous solutions of sodium salt of carboxymethyl cellulose (CMC)) of different viscosities, carried out in the NMR probe with the miniaturized RF coil and capillary. Viscosities of the CMC solutions were determined based on the curve fits of the velocity profiles and simultaneous measurements of the flow rates. The curve fits were carried out according to the power law model equations. The NMR viscosity measurements compared well with measurements of the same CMC samples, performed on a conventional rotational rheometer. A portable, home-built transceiver, designed for NMR applications utilizing a miniaturized RF coil, is described in chapter four. The maximum RF power, occurring in the transceiver, was 21.5 dBm. Two transistor-transistor logic (TTL) switches functioned as an active duplexer. A quadrature detection scheme was used. The transceiver, combined with a filter/amplifier module, data acquisition (DAQ and RF generating PC boards, was successfully tested in NMR spectroscopy experiments at low magnetic field. It was demonstrated that, starting with the RF probe, a typical, large size NMR instrument can be miniaturized without impairment to the quality of the data. Such an instrument will be readily used in many industrial process control applications (e.g. for analysis of material properties and identification of chemicals).

Targeted Molecular Imaging of Cancer Cells Using MS2-Based 129 Xe NMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Keunhong; Netirojjanakul, Chawita; Munch, Henrik K.

Targeted, selective, and highly sensitive 129Xe NMR nanoscale biosensors have been synthesized using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized 129Xe NMR signal contrast and hyper-CEST 129Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized 129Xe NMR nanoscale biosensor for future applications in cancer detection in vivo.

NMR crystallography: structure and properties of materials from solid-state nuclear magnetic resonance observables

PubMed Central

Bryce, David L.

2017-01-01

This topical review provides a brief overview of recent developments in NMR crystallography and related NMR approaches to studying the properties of molecular and ionic solids. Areas of complementarity with diffraction-based methods are underscored. These include the study of disordered systems, of dynamic systems, and other selected examples where NMR can provide unique insights. Highlights from the literature as well as recent work from my own group are discussed. PMID:28875022

Development of 19F-NMR chemical shift detection of DNA B-Z equilibrium using 19F-NMR.

PubMed

Nakamura, S; Yang, H; Hirata, C; Kersaudy, F; Fujimoto, K

2017-06-28

Various DNA conformational changes are in correlation with biological events. In particular, DNA B-Z equilibrium showed a high correlation with translation and transcription. In this study, we developed a DNA probe containing 5-trifluoromethylcytidine or 5-trifluoromethylthymidine to detect DNA B-Z equilibrium using 19 F-NMR. Its probe enabled the quantitative detection of B-, Z-, and ss-DNA based on 19 F-NMR chemical shift change.

Observation of NMR noise from solid samples.

PubMed

Schlagnitweit, Judith; Dumez, Jean-Nicolas; Nausner, Martin; Jerschow, Alexej; Elena-Herrmann, Bénédicte; Müller, Norbert

2010-11-01

We demonstrate that proton NMR noise signals, i.e. NMR spectra without excitation by radio frequency, can be obtained from solid samples. Experimental results are shown for static and magic-angle spinning conditions. In addition, a tuning procedure based on the probes' NMR noise characteristics and similar to the one described previously for liquids probes can also be used to optimize signal-to-noise ratios in ¹H-MAS experiments. Copyright © 2010 Elsevier Inc. All rights reserved.

1H nuclear magnetic resonance-based metabolomic characterization of wines by grape varieties and production areas.

PubMed

Son, Hong-Seok; Kim, Ki Myong; van den Berg, Frans; Hwang, Geum-Sook; Park, Won-Mok; Lee, Cherl-Ho; Hong, Young-Shick

2008-09-10

(1)H NMR spectroscopy was used to investigate the metabolic differences in wines produced from different grape varieties and different regions. A significant separation among wines from Campbell Early, Cabernet Sauvignon, and Shiraz grapes was observed using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The metabolites contributing to the separation were assigned to be 2,3-butanediol, lactate, acetate, proline, succinate, malate, glycerol, tartarate, glucose, and phenolic compounds by PCA and PLS-DA loading plots. Wines produced from Cabernet Sauvignon grapes harvested in the continental areas of Australia, France, and California were also separated. PLS-DA loading plots revealed that the level of proline in Californian Cabernet Sauvignon wines was higher than that in Australian and French Cabernet Sauvignon, Australian Shiraz, and Korean Campbell Early wines, showing that the chemical composition of the grape berries varies with the variety and growing area. This study highlights the applicability of NMR-based metabolomics with multivariate statistical data sets in determining wine quality and product origin.

Quantification of oil and water in preserved reservoir rock by NMR spectroscopy and imaging.

PubMed

Davies, S; Hardwick, A; Roberts, D; Spowage, K; Packer, K J

1994-01-01

Reservoir rock analysis by proton NMR requires separation of the response into brine and crude oil components. Tests on preserved core from a North Sea chalk reservoir show that spin-lattice relaxation time distributions can be used to distinguish the two fluids. NMR estimates of oil and water saturations for 1.5" diameter core examined in a 10 MHz Bruker Minispec spectrometer closely match fluid contents determined by distillation. The spin-lattice relaxation contrast mechanism developed for core samples can be applied in the quantitative analysis of NMR images. The relaxation data are compared with data from chemical shift imaging on the same core sample. The results indicate that it will be possible to monitor changes in fluid distributions, in this and similar systems, under dynamic conditions such as in a waterflood.

High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

PubMed

Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

High-throughput screening by Nuclear Magnetic Resonance (HTS by NMR) for the identification of PPIs antagonists

PubMed Central

Wu, Bainan; Barile, Elisa; De, Surya K.; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications. PMID:25986689

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrell, Jack R; Ware, Anne E

Two catalytic fast pyrolysis (CFP) oils (bottom/heavy fraction) were analyzed in various solvents that are used in common analytical methods (nuclear magnetic resonance - NMR, gas chromatography - GC, gel permeation chromatography - GPC, thermogravimetric analysis - TGA) for oil characterization and speciation. A more accurate analysis of the CFP oils can be obtained by identification and exploitation of solvent miscibility characteristics. Acetone and tetrahydrofuran can be used to completely solubilize CFP oils for analysis by GC and tetrahydrofuran can be used for traditional organic GPC analysis of the oils. DMSO-d6 can be used to solubilize CFP oils for analysismore » by 13C NMR. The fractionation of oils into solvents that did not completely solubilize the whole oils showed that miscibility can be related to the oil properties. This allows for solvent selection based on physico-chemical properties of the oils. However, based on semi-quantitative comparisons of the GC chromatograms, the organic solvent fractionation schemes did not speciate the oils based on specific analyte type. On the other hand, chlorinated solvents did fractionate the oils based on analyte size to a certain degree. Unfortunately, like raw pyrolysis oil, the matrix of the CFP oils is complicated and is not amenable to simple liquid-liquid extraction (LLE) or solvent fractionation to separate the oils based on the chemical and/or physical properties of individual components. For reliable analyses, for each analytical method used, it is critical that the bio-oil sample is both completely soluble and also not likely to react with the chosen solvent. The adoption of the standardized solvent selection protocols presented here will allow for greater reproducibility of analysis across different users and facilities.« less

In-plane anisotropy of the electric field gradient in Ba(Fe 1 -xCox)2As2 observed by 75As NMR

NASA Astrophysics Data System (ADS)

Toyoda, Masayuki; Ichikawa, Akihiro; Kobayashi, Yoshiaki; Sato, Masatoshi; Itoh, Masayuki

2018-05-01

We have performed 75As NMR measurements on single crystals to investigate the nematic behavior via the in-plane anisotropy of the electronic state at the As site far from Co impurities in the representative iron arsenides Ba (Fe1-xCox) 2As2 . From the analysis of the angular dependence of the NMR satellites in the c plane using the binominal distribution, we find that there is the in-plane fourfold symmetry breaking, namely, the orthorhombic-type anisotropy in the electric field gradient (EFG) at the As site with no Co atom at the nearest neighboring Fe sites even in the tetragonal phase of both BaFe2As2 and Ba (Fe1-xCox) 2As2(x ≠0 ) . The NMR spectrum in the antiferromagnetically ordered state of BaFe2As2 is shown not to support a nanotwin model on the basis of the nematic order proposed from the pair-distribution analysis of neutron scattering data. Based on results of the x and temperature T dependences of the in-plane anisotropy in the wide x and T ranges, the symmetry breaking is concluded to come from the local orthorhombic domains induced by disorder such as Co impurities or lattice imperfections. Furthermore, we find that the asymmetry parameter of EFG η obeys the Curie-Weiss law which may be governed by nematic susceptibility, and the Weiss temperature becomes zero at xc˜0.05 in Ba (Fe1-xCox) 2As2 .

An NMR Experiment Based on Off-the-Shelf Digital Data-Acquisition Equipment

ERIC Educational Resources Information Center

Hilty, Christian; Bowen, Sean

2010-01-01

Nuclear magnetic resonance (NMR) poses significant challenges for teaching in the context of an undergraduate laboratory, foremost because of high equipment cost. Current off-the-shelf data-acquisition hardware, however, is sufficiently powerful to constitute the core of a fully digital NMR spectrometer operating at the earth's field. We present…

Interactive NMR: A Simulation Based Teaching Tool for Fundamentals to Applications with Tangible Analogies

NASA Astrophysics Data System (ADS)

Griesse-Nascimento, Sarah; Bridger, Joshua; Brown, Keith; Westervelt, Robert

2011-03-01

Interactive computer simulations increase students' understanding of difficult concepts and their ability to explain complex ideas. We created a module of eight interactive programs and accompanying lesson plans for teaching the fundamental concepts of Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) that we call interactive NMR (iNMR). We begin with an analogy between nuclear spins and metronomes to start to build intuition about the dynamics of spins in a magnetic field. We continue to explain T1, T2, and pulse sequences with the metronome analogy. The final three programs are used to introduce and explain the Magnetic Resonance Switch, a recent diagnostic technique based on NMR. A modern relevant application is useful to generate interest in the topic and confidence in the students' ability to apply their knowledge. The iNMR module was incorporated into a high school AP physics class. In a preliminary evaluation of implementation, students expressed enthusiasm and demonstrated enhanced understanding of the material relative to the previous year. Funded by NSF PHY-0646094 grant.

Accuracy and precision of protein-ligand interaction kinetics determined from chemical shift titrations.

PubMed

Markin, Craig J; Spyracopoulos, Leo

2012-12-01

NMR-monitored chemical shift titrations for the study of weak protein-ligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K ( D )) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods wherein co-variation of the total protein and ligand concentrations gives increased precision for the K ( D ) value of a 1:1 protein-ligand interaction (Markin and Spyracopoulos in J Biomol NMR 53: 125-138, 2012). In this study, we demonstrate that classical line shape analysis applied to a single set of (1)H-(15)N 2D HSQC NMR spectra acquired using precise protein-ligand chemical shift titration methods we developed, produces accurate and precise kinetic parameters such as the off-rate (k ( off )). For experimentally determined kinetics in the fast exchange regime on the NMR timescale, k ( off ) ~ 3,000 s(-1) in this work, the accuracy of classical line shape analysis was determined to be better than 5 % by conducting quantum mechanical NMR simulations of the chemical shift titration methods with the magnetic resonance toolkit GAMMA. Using Monte Carlo simulations, the experimental precision for k ( off ) from line shape analysis of NMR spectra was determined to be 13 %, in agreement with the theoretical precision of 12 % from line shape analysis of the GAMMA simulations in the presence of noise and protein concentration errors. In addition, GAMMA simulations were employed to demonstrate that line shape analysis has the potential to provide reasonably accurate and precise k ( off ) values over a wide range, from 100 to 15,000 s(-1). The validity of line shape analysis for k ( off ) values approaching intermediate exchange (~100 s(-1)), may be facilitated by more accurate K ( D ) measurements from NMR-monitored chemical shift titrations, for which the dependence of K ( D ) on the chemical shift difference (Δω) between free and bound states is extrapolated to Δω = 0. The demonstrated accuracy and precision for k ( off ) will be valuable for the interpretation of biological kinetics in weakly interacting protein-protein networks, where a small change in the magnitude of the underlying kinetics of a given pathway may lead to large changes in the associated downstream signaling cascade.

Polymeric material prepared from Schiff base based on O-carboxymethyl chitosan and its Cu(II) and Pd(II) complexes

NASA Astrophysics Data System (ADS)

Baran, Talat; Menteş, Ayfer

2016-07-01

In this study, a new eco-friendly Schiff base based on O-carboxymethyl chitosan ([OCMCS-7a]) and its copper(II) and palladium(II) complexes were synthesized. Characterizations of [OCMCS-7a] and its metal complexes were conducted using FTIR, 1H NMR, 13C NMR, TG/DTG, XRD, SEM-EDAX, ICP, UV-VIS, GC-MS, elemental analysis, magnetic moment and molar conductivity measurements. The degree of substitution (DS) of [OCMCS-7a] was determined by elemental analysis to be 0.44. It was shown by the solubility test that [OCMCS-7a] was completely soluble in water. Surface images of chitosan, [OCMCS-7a] and its Cu(II) and Pd(II) complexes were investigated using the SEM-EDAX technique. Their thermal behaviors and crystallinities of the synthesized complexes were determined by TG/DTG and X-ray powder diffraction techniques, respectively. The metal contents of the obtained complexes were determined using an ICP-OES instrument. From the analyses, it was noted that the thermal stabilities and crystallinities of [OCMCS-7a] and its complexes decreased compared to chitosan. As a consequence of surface screening, it was also noted that the surface structure of the chitosan was smoother than that of the obtained compounds.

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia

PubMed Central

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100–300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making. PMID:29095932

Metabolomics based predictive biomarker model of ARDS: A systemic measure of clinical hypoxemia.

PubMed

Viswan, Akhila; Singh, Chandan; Rai, Ratan Kumar; Azim, Afzal; Sinha, Neeraj; Baronia, Arvind Kumar

2017-01-01

Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100-300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making.

Synthesis, spectroscopic characterization, DFT optimization and biological activities of Schiff bases and their metal (II) complexes

NASA Astrophysics Data System (ADS)

Rauf, Abdur; Shah, Afzal; Munawar, Khurram Shahzad; Khan, Abdul Aziz; Abbasi, Rashda; Yameen, Muhammad Arfat; Khan, Asad Muhammad; Khan, Abdur Rahman; Qureshi, Irfan Zia; Kraatz, Heinz-Bernhard; Zia-ur-Rehman

2017-10-01

A Novel Schiff base, 3-(((4-chlorophenyl)imino)methyl)benzene-1,2-diol (HL1) was successfully synthesized along with a structurally similar Schiff base 3-(((4-bromophenyl)imino)methyl)benzene-1,2-diol (HL2). Both the Schiff bases were used to synthesize their zinc (II) and cobalt (II) complexes. These compounds were characterized by FTIR, 1H NMR, 13C NMR and elemental analysis. Metal complexes were confirmed by TGA. Crystals of Schiff bases were also characterized by X-ray analysis and experimental parameters were found in line with the theoretical parameters. Quantum mechanical approach was also used to fine useful structural parameters and to ensure the geometry of metal complexes. The photometric behaviors of all the synthesized compounds were investigated in a wide pH range using BR buffers. The appearance of isosbestic points indicated the existence of Schiff bases in more than one isomeric form. Moreover, these compounds were screened for enzyme inhibition; antibacterial, cytotoxic and in vivo antidiabetic activities and compounds were found active against one or other activity. Results indicate that ZnL22 is a good inhibitor of alkaline phosphatase enzyme and possess highest potential against diabetes, blood cholesterol level and cancer cells. This effort just provides preliminary data for some biological properties. Further investigations are required to precisely determine mechanistic pathways of their use towards drug development.

An integrated analysis for determining the geographical origin of medicinal herbs using ICP-AES/ICP-MS and (1)H NMR analysis.

PubMed

Kwon, Yong-Kook; Bong, Yeon-Sik; Lee, Kwang-Sik; Hwang, Geum-Sook

2014-10-15

ICP-MS and (1)H NMR are commonly used to determine the geographical origin of food and crops. In this study, data from multielemental analysis performed by ICP-AES/ICP-MS and metabolomic data obtained from (1)H NMR were integrated to improve the reliability of determining the geographical origin of medicinal herbs. Astragalus membranaceus and Paeonia albiflora with different origins in Korea and China were analysed by (1)H NMR and ICP-AES/ICP-MS, and an integrated multivariate analysis was performed to characterise the differences between their origins. Four classification methods were applied: linear discriminant analysis (LDA), k-nearest neighbour classification (KNN), support vector machines (SVM), and partial least squares-discriminant analysis (PLS-DA). Results were compared using leave-one-out cross-validation and external validation. The integration of multielemental and metabolomic data was more suitable for determining geographical origin than the use of each individual data set alone. The integration of the two analytical techniques allowed diverse environmental factors such as climate and geology, to be considered. Our study suggests that an appropriate integration of different types of analytical data is useful for determining the geographical origin of food and crops with a high degree of reliability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of ethanol-soluble extractives in southern pine wood by low-field proton NMR

Treesearch

Thomas L. Eberhardt; Thomas Elder; Nicole Labbe

2007-01-01

Low-field portion NMR was evaluated as a nondestructive and rapid technique for measuring ethanol-soluble extractives in southern pine wood. Matchstick-sized wood specimens were steeped in extractive-containing solutions to generate extractive-enriched samples for analysis. decay curves obtained by the Carr-Purcell-Meiboom-gill (CPMG) pulse sequence were analyzed with...

Discrimination of Aurantii Fructus Immaturus and Fructus Poniciri Trifoliatae Immaturus by Flow Injection UV Spectroscopy (FIUV) and 1H NMR using Partial Least-squares Discriminant Analysis (PLS-DA)

USDA-ARS?s Scientific Manuscript database

Two simple fingerprinting methods, flow-injection UV spectroscopy (FIUV) and 1H nuclear magnetic resonance (NMR), for discrimination of Aurantii FructusImmaturus and Fructus Poniciri TrifoliataeImmaturususing were described. Both methods were combined with partial least-squares discriminant analysis...

Fraction of boroxol rings in vitreous boron oxide from a first-principles analysis of Raman and NMR spectra.

PubMed

Umari, P; Pasquarello, Alfredo

2005-09-23

We determine the fraction f of B atoms belonging to boroxol rings in vitreous boron oxide through a first-principles analysis. After generating a model structure of vitreous B2O3 by first-principles molecular dynamics, we address a large set of properties, including the neutron structure factor, the neutron density of vibrational states, the infrared spectra, the Raman spectra, and the 11B NMR spectra, and find overall good agreement with corresponding experimental data. From the analysis of Raman and 11B NMR spectra, we yield consistently for both probes a fraction f of approximately 0.75. This result indicates that the structure of vitreous boron oxide is largely dominated by boroxol rings.

Mechanistic insights into lithium ion battery electrolyte degradation - a quantitative NMR study.

PubMed

Wiemers-Meyer, S; Winter, M; Nowak, S

2016-09-29

The changes in electrolyte composition on the molecular level and the reaction mechanisms of electrolyte degradation upon thermal aging are monitored by quantitative NMR spectroscopy, revealing similar rates of degradation for pristine and already aged electrolytes. The data analysis is not in favor of an autocatalytic reaction mechanism based on OPF 3 but rather indicates that the degradation of LiPF 6 in carbonate based solvents proceeds via a complex sequence of "linear" reactions rather than a cyclic reaction pattern which is determined by the amount of water present in the samples. All investigated electrolytes are reasonably stable at temperatures of up to 60 °C in the presence of minor amounts or absence of water hence indicating that chemical instability of electrolyte components against water is decisive for degradation and an increase in temperature ("thermal aging") just accelerates the degradation impact of water.

NMR Chemical Exchange as a Probe for Ligand-Binding Kinetics in a Theophylline-Binding RNA Aptamer

PubMed Central

Latham, Michael P.; Zimmermann, Grant R.; Pardi, Arthur

2009-01-01

The apparent on- and off-rate constants for theophylline binding to its RNA aptamer in the absence of Mg2+ were determined here by 2D 1H-1H NMR ZZ-exchange spectroscopy. Analysis of the build-up rate of the exchange cross peaks for several base-paired imino protons in the RNA yielded an apparent kon of 600 M-1 s-1. This small apparent kon results from the free RNA existing as a dynamic equilibrium of inactive states rapidly interconverting with a low population of active species. The data here indicate that the RNA aptamer employs a conformational selection mechanism for binding theophylline in the absence of Mg2+. The kinetic data here also explain a very unusual property of this RNA-theophylline system, slow exchange on the NMR chemical shift timescale for a weak-binding complex. To our knowledge, it is unprecedented to have such a weak binding complex (Kd ≈ 3.0 mM at 15 °C) show slow exchange on the NMR chemical shift timescale, but the results clearly demonstrate that slow exchange and weak binding are readily rationalized by a small kon. Comparisons with other ligand-receptor interactions are presented. PMID:19317486

A new method of evaluating tight gas sands pore structure from nuclear magnetic resonance (NMR) logs

NASA Astrophysics Data System (ADS)

Xiao, Liang; Mao, Zhi-qiang; Xie, Xiu-hong

2016-04-01

Tight gas sands always display such characteristics of ultra-low porosity, permeability, high irreducible water, low resistivity contrast, complicated pore structure and strong heterogeneity, these make that the conventional methods are invalid. Many effective gas bearing formations are considered as dry zones or water saturated layers, and cannot be identified and exploited. To improve tight gas sands evaluation, the best method is quantitative characterizing rock pore structure. The mercury injection capillary pressure (MICP) curves are advantageous in predicting formation pore structure. However, the MICP experimental measurements are limited due to the environment and economy factors, this leads formation pore structure cannot be consecutively evaluated. Nuclear magnetic resonance (NMR) logs are considered to be promising in evaluating rock pore structure. Generally, to consecutively quantitatively evaluate tight gas sands pore structure, the best method is constructing pseudo Pc curves from NMR logs. In this paper, based on the analysis of lab experimental results for 20 core samples, which were drilled from tight gas sandstone reservoirs of Sichuan basin, and simultaneously applied for lab MICP and NMR measurements, the relationships of piecewise power function between nuclear magnetic resonance (NMR) transverse relaxation T2 time and pore-throat radius Rc are established. A novel method, which is used to transform NMR reverse cumulative curve as pseudo capillary pressure (Pc) curve is proposed, and the corresponding model is established based on formation classification. By using this model, formation pseudo Pc curves can be consecutively synthesized. The pore throat radius distribution, and pore structure evaluation parameters, such as the average pore throat radius (Rm), the threshold pressure (Pd), the maximum pore throat radius (Rmax) and so on, can also be precisely extracted. After this method is extended into field applications, several tight gas sandstone reservoirs are processed, and the predicted results are compared with core derived results. Good consistency between evaluated results with core derived results illustrates the dependability of the proposed method. Comparing with the previous methods, this presented model is much more theoretical, and the applicability is much improved. Combining with the evaluated results, our target tight gas sands are well evaluated, and many potential gas-bearing layers are effectively identified.

Citrus Quality Control: An NMR/MRI Problem-Based Experiment

ERIC Educational Resources Information Center

Erhart, Sarah E.; McCarrick, Robert M.; Lorigan, Gary A.; Yezierski, Ellen J.

2016-01-01

An experiment seated in an industrial context can provide an engaging framework and unique learning opportunity for an upper-division physical chemistry laboratory. An experiment that teaches NMR/MRI through a problem-based quality control of citrus products was developed. In this experiment, using a problem-based learning (PBL) approach, students…

Ionic polysaccharide hydrogels via the Passerini and Ugi multicomponent condensations: synthesis, behavior and solid-state NMR characterization.

PubMed

de Nooy, A E; Capitani, D; Masci, G; Crescenzi, V

2000-01-01

Original data are provided demonstrating that the title condensations are simple and versatile methods for the synthesis of hydrogels based on a variety of carboxylated polysaccharides. In this work, the biopolymers considered are sodium hyaluronate and sodium alginate. Nonnatural carboxylated polysaccharides were commercial (carboxymethyl)cellulose or were obtained by carboxymethylation or selective oxidation of primary alcohol groups of scleroglucan and dextran. Hydrogels prepared via the Passerini reaction were transparent, alkali labile materials whereas the transparency of the Ugi gels depended on the polysaccharide, the cross-linker, and the degree of cross-linking. The Ugi gels were stable for several months at a pH ranging from 1.3 to 11 and up to temperatures over 90 degrees C. The structure of the networks was studied by means of 13C CP-MAS and 15N CP-MAS NMR spectroscopy. A quantitative NMR analysis and elemental analysis of the dry gels allowed us to estimate the efficiency of the reactions, i.e., the actual degree of cross-linking, which appeared to be about 80% of theoretical. The influence of added salt and pH on the swelling of several Ugi gels with different degrees of cross-linking was studied in a qualitative manner.

Simultaneous Gaussian and exponential inversion for improved analysis of shales by NMR relaxometry

USGS Publications Warehouse

Washburn, Kathryn E.; Anderssen, Endre; Vogt, Sarah J.; Seymour, Joseph D.; Birdwell, Justin E.; Kirkland, Catherine M.; Codd, Sarah L.

2014-01-01

Nuclear magnetic resonance (NMR) relaxometry is commonly used to provide lithology-independent porosity and pore-size estimates for petroleum resource evaluation based on fluid-phase signals. However in shales, substantial hydrogen content is associated with solid and fluid signals and both may be detected. Depending on the motional regime, the signal from the solids may be best described using either exponential or Gaussian decay functions. When the inverse Laplace transform, the standard method for analysis of NMR relaxometry results, is applied to data containing Gaussian decays, this can lead to physically unrealistic responses such as signal or porosity overcall and relaxation times that are too short to be determined using the applied instrument settings. We apply a new simultaneous Gaussian-Exponential (SGE) inversion method to simulated data and measured results obtained on a variety of oil shale samples. The SGE inversion produces more physically realistic results than the inverse Laplace transform and displays more consistent relaxation behavior at high magnetic field strengths. Residuals for the SGE inversion are consistently lower than for the inverse Laplace method and signal overcall at short T2 times is mitigated. Beyond geological samples, the method can also be applied in other fields where the sample relaxation consists of both Gaussian and exponential decays, for example in material, medical and food sciences.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Naijia; Bezerra, Tais Lacerda; Wu, Qiong

Pyrolysis is a promising method for converting biomass to biofuels. However, some of pyrolysis oil's physiochemical properties still limit its commercial applications. Here, the autohydrolysis pretreatment at 175 ± 3 °C for 40 min was conducted to improve the resulting pine pyrolysis oil’s properties as a fuel. During autohydrolysis, deacetylation and decomposition of hemicellulose was observed by ion-exchange chromatography and Fourier transform infrared spectroscopy (FT-IR). Additionally, the cleavage of lignin ether bonds was clearly determined by 13C cross-polarization/magic angle spinning (CP/MAS) nuclear magnetic resonance (NMR). Phosphitylation followed by 31P NMR analysis of the heavy oils gave detailed structural information ofmore » the hydroxyl groups; the results revealed that autohydrolysis pretreatment led to a reduction of carboxyl acids in the heavy oils generated at all three pyrolysis temperatures (400, 500, and 600 °C). The 31P NMR analysis also revealed that autohydrolysis pretreatment led to a reduction of condensed phenolic hydroxyl groups in the heavy oils produced at 600 °C. 1H- 13C heteronuclear single-quantum correlation (HSQC) NMR analysis showed that at a pyrolysis temperature of 600 °C, the pretreated pine produced lower methoxy group constituents. In both 31P and HSQC NMR results indicated that autohydrolysis pretreatment increased levoglucosan yields in the bio-oils.« less

Unexpected Solubility Enhancement of Drug Bases in the Presence of a Dimethylaminoethyl Methacrylate Copolymer.

PubMed

Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2018-01-02

The methacrylate copolymer Eudragit EPO (EPO) has previously shown to greatly enhance solubilization of acidic drugs via ionic interactions and by multiple hydrophobic contacts with polymeric side chains. The latter type of interaction could also play a role for solubilization of other compounds than acids. The aim of this study was therefore to investigate the solubility of six poorly soluble bases in presence and absence of EPO by quantitative ultrapressure liquid chromatography with concomitant X-ray powder diffraction analysis of the solid state. For a better mechanistic understanding, spectra and diffusion data were obtained by 1 H nuclear magnetic resonance (NMR) spectroscopy. Unexpected high solubility enhancement (up to 360-fold) was evidenced in the presence of EPO despite the fact that bases and polymer were both carrying positive charges. This exceptional and unexpected solubilization was not due to a change in the crystalline solid state. NMR spectra and measured diffusion coefficients indicated both strong drug-polymer interactions in the bulk solution, and diffusion data suggested conformational changes of the polymer in solution. Such conformational changes may have increased the accessibility and extent of hydrophobic contacts thereby leading to increased overall molecular interactions. These initially surprising solubilization results demonstrate that excipient selection should not be based solely on simple considerations of, for example, opposite charges of drug and excipient, but it requires a more refined molecular view. Different solution NMR techniques are especially promising tools to gain such mechanistic insights.

A novel fluorescence probe based on triphenylamine Schiff base for bioimaging and responding to pH and Fe3.

PubMed

Wang, Lei; Yang, Xiaodong; Chen, Xiuli; Zhou, Yuping; Lu, Xiaodan; Yan, Chenggong; Xu, Yikai; Liu, Ruiyuan; Qu, Jinqing

2017-03-01

A novel fluorescence probe 1 based on triphenylamine was synthesized and characterized by NMR, IR, high resolution mass spectrometry and elemental analysis. Its fluorescence was quenched when pH below 2. There was a linear relationship between the fluorescence intensity and pH value ranged from 2 to 7. And its fluorescence emission was reversibility in acidic and alkaline solution. Furthermore, it exhibited remarkable selectivity and high sensitivity to Fe 3+ and was able to detect Fe 3+ in aqueous solution with low detection limit of 0.511μM. Job plot showed that the binding stoichiometry of 1 with Fe 3+ was 1:1. Further observations of 1 H NMR titration suggested that coordination interaction between Fe 3+ and nitrogen atom on CN bond promoted the intramolecular charge transfer (ICT) or energy transfer process causing fluorescence quenching. Additionally, 1 was also able to be applied for detecting Fe 3+ in living cell and bioimaging. Copyright © 2016. Published by Elsevier B.V.

Zn(II), Ni(II), Cu(II) and Pb(II) complexes of tridentate asymmetrical Schiff base ligands: Synthesis, characterization, properties and biological activity

NASA Astrophysics Data System (ADS)

Şahin, Mustafa; Koçak, Nuriye; Erdenay, Damla; Arslan, Uğur

2013-02-01

New asymmetrical tridentate Schiff base ligands were synthesized using 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde, 9-anthracenecarboxaldehyde. Schiff base ligands and their metal complexes were synthesised and characterized by using FT-IR, 1H NMR, 13C NMR, UV-Vis, XRD, ESR, elemental analysis and fluorescence studies. The antimicrobial activity of the ligands and their metal complexes were studied against Staphylococcus aureus ATCC 29213, S. aureus ATCC 25923, Streptococcus mutans RSHM 676, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853. The determination of the antibacterial activity was done using the broth microdilution methods. In general, it has been determined that the studied compounds have MIC values similar to Gram-positive and Gram-negative bacteria. It has been found that Ni, Pb, Zn derivatives of HL1A and ZnL2A has lower MIC values than ampicillin for P. aeruginosa ATCC 27853 strain.

Synthesis of Schiff base 24-membered trivalent transition metal derivatives with their anti-inflammation and antimicrobial evaluation

NASA Astrophysics Data System (ADS)

Kumar, Gajendra; Devi, Shoma; Kumar, Dharmendra

2016-03-01

The paper presents the synthesis of macrocyclic complexes [{M(C52H36N12O4)X}X2] of Cr(III), Mn(III) and Fe(III) with Schiff base ligand (C52H36N12O4) obtained through the condensation of 1,4-dicarbonyl phenyl dihydrazide with 1,2-di(1H-indol-1-yl)ethane-1,2-dione. The newly formed Schiff base and its complexes have been characterized with the help of elemental analysis, condensation measurements, magnetic measurements and their structure configuration have been determined by various spectroscopic (electronic, IR, 1H NMR, 13C NMR, GCMS) techniques. The electronic spectra of the complexes indicate a five coordinate square pyramidal geometry of the center metal ion. These metal complexes and ligand were tested for their anti-inflammation and antimicrobial inhibiting potential and compared with standard drugs Phenyl butazone (anti-inflammation), Imipenem (antibacterial) and Miconazole (antifungal).

Synthesis of new Schiff bases bearing 1,2,4-triazole, thiazolidine and chloroazetidine moieties and their pharmacological evaluation.

PubMed

Kandile, Nadia G; Mohamed, Mansoura I; Ismaeel, Hind M

2017-12-01

New compounds based on oxindole moiety were synthesized via the reaction of 5-substitued isatins 1a-e with different nucleophiles such as benzidine, 3,3'-dimethoxybenzidine 2a,b and 2,6-diaminopyridine 3 to afford three different classes of bis-Schiff bases 4a-e, 5a-e and 6a-e, respectively. The structures of the new compounds were elucidated on the basis of their FTIR, 1 H NMR, 13 C NMR, GC/MS spectral data and elemental analysis. The in vitro antimicrobial activity of the new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration (MIC) against four bacterial and two fungal pathogens and anticancer activities against HELA cervix. The revealed data showed that compound 9d has excellent activity against Gram + ve and Gram -ve bacteria, and compounds 11b presented promising anticancer activity against HELA cervix. [Formula: see text].

Capillary toroid cavity detector for high pressure NMR

DOEpatents

Gerald, II, Rex E.; Chen, Michael J.; Klingler, Robert J.; Rathke, Jerome W.; ter Horst, Marc

2007-09-11

A Toroid Cavity Detector (TCD) is provided for implementing nuclear magnetic resonance (NMR) studies of chemical reactions under conditions of high pressures and temperatures. A toroid cavity contains an elongated central conductor extending within the toroid cavity. The toroid cavity and central conductor generate an RF magnetic field for NMR analysis. A flow-through capillary sample container is located within the toroid cavity adjacent to the central conductor to subject a sample material flowing through the capillary to a static magnetic field and to enable NMR spectra to be recorded of the material in the capillary under a temperature and high pressure environment.

Application of ChemDraw NMR Tool: Correlation of Program-Generated 13C Chemical Shifts and pKa Values of para-Substituted Benzoic Acids

NASA Astrophysics Data System (ADS)

Wang, Hongyi

2005-09-01

An application of ChemDraw NMR Tool was demonstrated by correlation of program-generated 13 C NMR chemical shifts and p K a values of para-substituted benzoic acids. Experimental 13 C NMR chemical shifts were analyzed in the same way for comparison. The project can be used as an assignment at the end of the first-year organic chemistry course to review topics or explore new techniques: Hammett equation, acid base equilibrium theory, electronic nature of functional groups, inductive and resonance effects, structure reactivity relationship, NMR spectroscopy, literature search, database search, and ChemDraw software.

NMRPro: an integrated web component for interactive processing and visualization of NMR spectra.

PubMed

Mohamed, Ahmed; Nguyen, Canh Hao; Mamitsuka, Hiroshi

2016-07-01

The popularity of using NMR spectroscopy in metabolomics and natural products has driven the development of an array of NMR spectral analysis tools and databases. Particularly, web applications are well used recently because they are platform-independent and easy to extend through reusable web components. Currently available web applications provide the analysis of NMR spectra. However, they still lack the necessary processing and interactive visualization functionalities. To overcome these limitations, we present NMRPro, a web component that can be easily incorporated into current web applications, enabling easy-to-use online interactive processing and visualization. NMRPro integrates server-side processing with client-side interactive visualization through three parts: a python package to efficiently process large NMR datasets on the server-side, a Django App managing server-client interaction, and SpecdrawJS for client-side interactive visualization. Demo and installation instructions are available at http://mamitsukalab.org/tools/nmrpro/ mohamed@kuicr.kyoto-u.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

(13)C NMR substituent-induced chemical shifts in 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-ones (thiones).

PubMed

Kara, Yesim Saniye

2015-01-01

In the present, study mostly novel ten 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-ones and ten 4-(substituted phenyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-thiones were synthesized. These oxadiazole derivatives were characterized by IR, (1)H NMR, (13)C NMR and elemental analyses. Their (13)C NMR spectra were measured in Deuterochloroform (CDCl3). The correlation analysis for the substituent-induced chemical shift (SCS) with Hammett substituent constants (σ), Brown Okamoto substituent constants (σ(+), σ(-)), inductive substituent constants (σI) and different of resonance substituent constants (σR, σR(o)) were performed using SSP (single substituent parameter), DSP (dual substituent parameter) and DSP-NLR (dual substituent parameter-non-linear resonance) methods, as well as single and multiple regression analysis. Negative ρ values were found for all correlations (reverse substituent effect). The results of all statistical analyses, (13)C NMR chemical shift of CN, CO and CS carbon of oxadiazole rings have shown satisfactory correlation. Copyright © 2015 Elsevier B.V. All rights reserved.

Perspectives on NMR in drug discovery: a technique comes of age

PubMed Central

Pellecchia, Maurizio; Bertini, Ivano; Cowburn, David; Dalvit, Claudio; Giralt, Ernest; Jahnke, Wolfgang; James, Thomas L.; Homans, Steve W.; Kessler, Horst; Luchinat, Claudio; Meyer, Bernd; Oschkinat, Hartmut; Peng, Jeff; Schwalbe, Harald; Siegal, Gregg

2009-01-01

In the past decade, the potential of harnessing the ability of nuclear magnetic resonance (NMR) spectroscopy to monitor intermolecular interactions as a tool for drug discovery has been increasingly appreciated in academia and industry. In this Perspective, we highlight some of the major applications of NMR in drug discovery, focusing on hit and lead generation, and provide a critical analysis of its current and potential utility. PMID:19172689

Assessment of higher order structure comparability in therapeutic proteins using nuclear magnetic resonance spectroscopy.

PubMed

Amezcua, Carlos A; Szabo, Christina M

2013-06-01

In this work, we applied nuclear magnetic resonance (NMR) spectroscopy to rapidly assess higher order structure (HOS) comparability in protein samples. Using a variation of the NMR fingerprinting approach described by Panjwani et al. [2010. J Pharm Sci 99(8):3334-3342], three nonglycosylated proteins spanning a molecular weight range of 6.5-67 kDa were analyzed. A simple statistical method termed easy comparability of HOS by NMR (ECHOS-NMR) was developed. In this method, HOS similarity between two samples is measured via the correlation coefficient derived from linear regression analysis of binned NMR spectra. Applications of this method include HOS comparability assessment during new product development, manufacturing process changes, supplier changes, next-generation products, and the development of biosimilars to name just a few. We foresee ECHOS-NMR becoming a routine technique applied to comparability exercises used to complement data from other analytical techniques. Copyright © 2013 Wiley Periodicals, Inc.

Purity assessment of organic calibration standards using a combination of quantitative NMR and mass balance.

PubMed

Davies, Stephen R; Jones, Kai; Goldys, Anna; Alamgir, Mahuiddin; Chan, Benjamin K H; Elgindy, Cecile; Mitchell, Peter S R; Tarrant, Gregory J; Krishnaswami, Maya R; Luo, Yawen; Moawad, Michael; Lawes, Douglas; Hook, James M

2015-04-01

Quantitative NMR spectroscopy (qNMR) has been examined for purity assessment using a range of organic calibration standards of varying structural complexities, certified using the traditional mass balance approach. Demonstrated equivalence between the two independent purity values confirmed the accuracy of qNMR and highlighted the benefit of using both methods in tandem to minimise the potential for hidden bias, thereby conferring greater confidence in the overall purity assessment. A comprehensive approach to purity assessment is detailed, utilising, where appropriate, multiple peaks in the qNMR spectrum, chosen on the basis of scientific reason and statistical analysis. Two examples are presented in which differences between the purity assignment by qNMR and mass balance are addressed in different ways depending on the requirement of the end user, affording fit-for-purpose calibration standards in a cost-effective manner.

Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles.

PubMed

Bendahan, David; Chatel, Benjamin; Jue, Thomas

2017-12-01

Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O 2 Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O 2 requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb. In contrast, 1 H NMR has only detected the Mb signal in contracting muscle, and comparative NIRS and NMR experiments indicate a predominant Mb contribution. The present study has examined the question of the NIRS signal origin by measuring simultaneously the 1 H NMR, 31 P NMR, and NIRS signals in finger flexor muscles during the transition from rest to contraction, recovery, ischemia, and reperfusion. The experiment results confirm a predominant Mb contribution to the NIRS signal from muscle. Given the NMR and NIRS corroborated changes in the intracellular O 2 , the analysis shows that at the onset of muscle contraction, O 2 declines immediately and reaches new steady states as contraction intensity rises. Moreover, lactate formation increases even under quite aerobic condition. Copyright © 2017 the American Physiological Society.

Crystallinity and compositional changes in carbonated apatites: Evidence from 31P solid-state NMR, Raman, and AFM analysis

NASA Astrophysics Data System (ADS)

McElderry, John-David P.; Zhu, Peizhi; Mroue, Kamal H.; Xu, Jiadi; Pavan, Barbara; Fang, Ming; Zhao, Guisheng; McNerny, Erin; Kohn, David H.; Franceschi, Renny T.; Holl, Mark M. Banaszak; Tecklenburg, Mary M. J.; Ramamoorthy, Ayyalusamy; Morris, Michael D.

2013-10-01

Solid-state (magic-angle spinning) NMR spectroscopy is a useful tool for obtaining structural information on bone organic and mineral components and synthetic model minerals at the atomic-level. Raman and 31P NMR spectral parameters were investigated in a series of synthetic B-type carbonated apatites (CAps). Inverse 31P NMR linewidth and inverse Raman PO43-ν1 bandwidth were both correlated with powder XRD c-axis crystallinity over the 0.3-10.3 wt% CO32- range investigated. Comparison with bone powder crystallinities showed agreement with values predicted by NMR and Raman calibration curves. Carbonate content was divided into two domains by the 31P NMR chemical shift frequency and the Raman phosphate ν1 band position. These parameters remain stable except for an abrupt transition at 6.5 wt% carbonate, a composition which corresponds to an average of one carbonate per unit cell. This near-binary distribution of spectroscopic properties was also found in AFM-measured particle sizes and Ca/P molar ratios by elemental analysis. We propose that this transition differentiates between two charge-balancing ion-loss mechanisms as measured by Ca/P ratios. These results define a criterion for spectroscopic characterization of B-type carbonate substitution in apatitic minerals.

A guide to the identification of metabolites in NMR-based metabonomics/metabolomics experiments.

PubMed

Dona, Anthony C; Kyriakides, Michael; Scott, Flora; Shephard, Elizabeth A; Varshavi, Dorsa; Veselkov, Kirill; Everett, Jeremy R

2016-01-01

Metabonomics/metabolomics is an important science for the understanding of biological systems and the prediction of their behaviour, through the profiling of metabolites. Two technologies are routinely used in order to analyse metabolite profiles in biological fluids: nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), the latter typically with hyphenation to a chromatography system such as liquid chromatography (LC), in a configuration known as LC-MS. With both NMR and MS-based detection technologies, the identification of the metabolites in the biological sample remains a significant obstacle and bottleneck. This article provides guidance on methods for metabolite identification in biological fluids using NMR spectroscopy, and is illustrated with examples from recent studies on mice.

Application of the double relaxation oscillation superconducting quantum interference device sensor to micro-tesla 1H nuclear magnetic resonance experiments

NASA Astrophysics Data System (ADS)

Kang, Chan Seok; Kim, Kiwoong; Lee, Seong-Joo; Hwang, Seong-min; Kim, Jin-Mok; Yu, Kwon Kyu; Kwon, Hyukchan; Lee, Sang Kil; Lee, Yong-Ho

2011-09-01

We developed an ultra-low field (ULF)-nuclear magnetic resonance (NMR) measurement system capable of working with a measurement field (Bm) of several micro-tesla and performed basic NMR studies with a double relaxation oscillation superconducting quantum interference device (DROS) instead of conventional dc-SQUIDs. DROS is a SQUID sensor utilizing a relaxation oscillation between a dc-SQUID and a relaxation circuit; the new unit consists of an inductor and a resistor, and is connected in parallel with the SQUID. DROS has a 10 times larger flux-to-voltage transfer coefficient (˜mV/ϕ0) than that of the dc-SQUID, and this large transfer coefficient enables the acquisition of the SQUID signal with a simple flux-locked-loop (FLL) circuit using room temperature pre-amplifiers. The DROS second-order gradiometer showed average field noise of 9.2 μϕ0/√Hz in a magnetically shielded room (MSR). In addition, a current limiter formed of a Josephson junction array was put in a flux-transformer of DROS to prevent excessive currents that can be generated from the high pre-polarization field (Bp). Using this system, we measured an 1H NMR signal in water under 2.8 μT Bm field and reconstructed a one-dimensional MR image from the 1H NMR signal under a gradient field BG of 4.09 nT/mm. In addition, we confirmed that the ULF-NMR system can measure the NMR signal in the presence of metal without any distortion by measuring the NMR signal of a sample wrapped with metal. Lastly, we have measured the scalar J-coupling of trimethylphosphate and were able to confirm a clear doublet NMR signal with the coupling strength J3[P,H] = 10.4 ± 0.8 Hz. Finally, because the existing ULF-NMR/MRI studies were almost all performed with dc-SQUID based systems, we constructed a dc-SQUID-based ULF-NMR system in addition to the DROS based system and compared the characteristics of the two different systems by operating the two systems under identical experimental conditions.

Spectroscopic [FT-IR and FT-Raman] and theoretical [UV-Visible and NMR] analysis on α-Methylstyrene by DFT calculations.

PubMed

Karthikeyan, N; Joseph Prince, J; Ramalingam, S; Periandy, S

2015-05-15

In the present research work, the FT-IR, FT-Raman and (13)C and (1)H NMR spectra of the α-Methylstyrene were recorded. The observed fundamental frequencies in finger print as well as functional group regions were assigned according to their uniqueness region. The Gaussian computational calculations are carried out by HF and DFT (B3LYP and B3PW91) methods with 6-31++G(d,p) and 6-311++G(d,p) basis sets and the corresponding results were tabulated. The impact of the presence of vinyl group in phenyl structure of the compound is investigated. The modified vibrational pattern of the molecule associated vinyl group was analyzed. Moreover, (13)C NMR and (1)H NMR were calculated by using the gauge independent atomic orbital (GIAO) method with B3LYP methods and the 6-311++G(d,p) basis set and their spectra were simulated and the chemical shifts linked to TMS were compared. A study on the electronic and optical properties; absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies were carried out. The kubo gap of the present compound was calculated related to HOMO and LUMO energies which confirm the occurring of charge transformation between the base and ligand. Besides frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) was performed. The NLO properties related to Polarizability and hyperpolarizability based on the finite-field approach were also discussed. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

A flavone derivative from Sesbania sesban leaves and its cytotoxicity against murine leukemia P-388 cells

NASA Astrophysics Data System (ADS)

Dianhar, Hanhan; Syah, Yana Maolana; Mujahidin, Didin; Hakim, Euis Holisotan; Juliawaty, Lia Dewi

2014-03-01

Sesbania sesban, locally named as Jayanti, is one of Indonesia plants belonging to Fabaceae family. This species is traditionally used by Indonesian people to cure digestive disorders, fever, or headache. Jayanti can grow well in tropical to subtropical region, such as in Asia and Africa. Based on literature, qualitative analysis of the methanol extract of leaves of S. sesban showed that it contained flavonoids, alkaloids, saponins and glycosides. In addition, the activity assay of extracts of different tissues of this species showed antitumor, antimalarial, and antidiabetic activityies (leaves and seed extracts), antioxidants (flower extract), and analgesic (wood extract). Though the extracts of S. sesban parts showed interesting activities, chemical study of those extracts have not been widely reported. Therefore, the objective of this research was to isolate the secondary metabolites from methanol extract of leaves of S. sesban and to determine their cytotoxicity against murine leukemia P-388 cells. One compound has been obtained and identified as 3-hydroxy-4',7-dimethoxyflavone (1), a new isolated compound from nature. This compound was obtained through separation of methanol extract using various chromatographic techniques, such as vacuum liquid chromatography and radial chromatography. The structure elucidation of isolated compound was based on 1D NMR (1H-NMR and 13C-NMR) and 2D NMR (HMBC). The cytotoxicity of methanol extract and compound 1 against murine leukemia P-388 cells examined through MTT assay showed IC50 value of 60.04 μg/mL and 5.40 μg/mL, respectively.

A flavone derivative from Sesbania sesban leaves and its cytotoxicity against murine leukemia P-388 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dianhar, Hanhan, E-mail: liadewi@chem.itb.ac.id; Syah, Yana Maolana, E-mail: liadewi@chem.itb.ac.id; Mujahidin, Didin, E-mail: liadewi@chem.itb.ac.id

2014-03-24

Sesbania sesban, locally named as Jayanti, is one of Indonesia plants belonging to Fabaceae family. This species is traditionally used by Indonesian people to cure digestive disorders, fever, or headache. Jayanti can grow well in tropical to subtropical region, such as in Asia and Africa. Based on literature, qualitative analysis of the methanol extract of leaves of S. sesban showed that it contained flavonoids, alkaloids, saponins and glycosides. In addition, the activity assay of extracts of different tissues of this species showed antitumor, antimalarial, and antidiabetic activityies (leaves and seed extracts), antioxidants (flower extract), and analgesic (wood extract). Though themore » extracts of S. sesban parts showed interesting activities, chemical study of those extracts have not been widely reported. Therefore, the objective of this research was to isolate the secondary metabolites from methanol extract of leaves of S. sesban and to determine their cytotoxicity against murine leukemia P-388 cells. One compound has been obtained and identified as 3-hydroxy-4',7-dimethoxyflavone (1), a new isolated compound from nature. This compound was obtained through separation of methanol extract using various chromatographic techniques, such as vacuum liquid chromatography and radial chromatography. The structure elucidation of isolated compound was based on 1D NMR ({sup 1}H-NMR and {sup 13}C-NMR) and 2D NMR (HMBC). The cytotoxicity of methanol extract and compound 1 against murine leukemia P-388 cells examined through MTT assay showed IC{sub 50} value of 60.04 μg/mL and 5.40 μg/mL, respectively.« less