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.

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.

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.

Improving the efficiency of quantitative (1)H NMR: an innovative external standard-internal reference approach.

PubMed

Huang, Yande; Su, Bao-Ning; Ye, Qingmei; Palaniswamy, Venkatapuram A; Bolgar, Mark S; Raglione, Thomas V

2014-01-01

The classical internal standard quantitative NMR (qNMR) method determines the purity of an analyte by the determination of a solution containing the analyte and a standard. Therefore, the standard must meet the requirements of chemical compatibility and lack of resonance interference with the analyte as well as a known purity. The identification of such a standard can be time consuming and must be repeated for each analyte. In contrast, the external standard qNMR method utilizes a standard with a known purity to calibrate the NMR instrument. The external standard and the analyte are measured separately, thereby eliminating the matter of chemical compatibility and resonance interference between the standard and the analyte. However, the instrumental factors, including the quality of NMR tubes, must be kept the same. Any deviations will compromise the accuracy of the results. An innovative qNMR method reported herein utilizes an internal reference substance along with an external standard to assume the role of the standard used in the traditional internal standard qNMR method. In this new method, the internal reference substance must only be chemically compatible and be free of resonance-interference with the analyte or external standard whereas the external standard must only be of a known purity. The exact purity or concentration of the internal reference substance is not required as long as the same quantity is added to the external standard and the analyte. The new method reduces the burden of searching for an appropriate standard for each analyte significantly. Therefore the efficiency of the qNMR purity assay increases while the precision of the internal standard method is retained. Copyright © 2013 Elsevier B.V. All rights reserved.

Federal Lands Highway Construction Manual

DOT National Transportation Integrated Search

1996-12-01

The purpose of this manual is to assist field personnel engaged in administering contracts on projects undertaken directly by the Federal Highway Administration. It provides a framework for the Federal Lands construction contract administration proce...

Innovative railroad information displays : video guide

DOT National Transportation Integrated Search

1998-01-01

The objectives of this study were to explore the potential of advanced digital technology, : novel concepts of information management, geographic information databases and : display capabilities in order to enhance planning and decision-making proces...

Perspective: next generation isotope-aided methods for protein NMR spectroscopy.

PubMed

Kainosho, Masatsune; Miyanoiri, Yohei; Terauchi, Tsutomu; Takeda, Mitsuhiro

2018-06-22

In this perspective, we describe our efforts to innovate the current isotope-aided NMR methodology to investigate biologically important large proteins and protein complexes, for which only limited structural information could be obtained by conventional NMR approaches. At the present time, it is widely believed that only backbone amide and methyl signals are amenable for investigating such difficult targets. Therefore, our primary mission is to disseminate our novel knowledge within the biological NMR community; specifically, that any type of NMR signals other than methyl and amide groups can be obtained, even for quite large proteins, by optimizing the transverse relaxation properties by isotope labeling methods. The idea of "TROSY by isotope labeling" has been cultivated through our endeavors aiming to improve the original stereo-array isotope labeling (SAIL) method (Kainosho et al., Nature 440:52-57, 2006). The SAIL TROSY methods subsequently culminated in the successful observations of individual NMR signals for the side-chain aliphatic and aromatic 13 CH groups in large proteins, as exemplified by the 82 kDa single domain protein, malate synthase G. Meanwhile, the expected role of NMR spectroscopy in the emerging integrative structural biology has been rapidly shifting, from structure determination to the acquisition of biologically relevant structural dynamics, which are poorly accessible by X-ray crystallography or cryo-electron microscopy. Therefore, the newly accessible NMR probes, in addition to the methyl and amide signals, will open up a new horizon for investigating difficult protein targets, such as membrane proteins and supramolecular complexes, by NMR spectroscopy. We briefly introduce our latest results, showing that the protons attached to 12 C-atoms give profoundly narrow 1 H-NMR signals even for large proteins, by isolating them from the other protons using the selective deuteration. The direct 1 H observation methods exhibit the highest sensitivities, as compared to heteronuclear multidimensional spectroscopy, in which the 1 H-signals are acquired via the spin-coupled 13 C- and/or 15 N-nuclei. Although the selective deuteration method was launched a half century ago, as the first milestone in the following prosperous history of isotope-aided NMR methods, our results strongly imply that the low-dimensional 1 H-direct observation NMR methods should be revitalized in the coming era, featuring ultrahigh-field spectrometers beyond 1 GHz.

Toward a structure determination method for biomineral-associated protein using combined solid- state NMR and computational structure prediction.

PubMed

Masica, David L; Ash, Jason T; Ndao, Moise; Drobny, Gary P; Gray, Jeffrey J

2010-12-08

Protein-biomineral interactions are paramount to materials production in biology, including the mineral phase of hard tissue. Unfortunately, the structure of biomineral-associated proteins cannot be determined by X-ray crystallography or solution nuclear magnetic resonance (NMR). Here we report a method for determining the structure of biomineral-associated proteins. The method combines solid-state NMR (ssNMR) and ssNMR-biased computational structure prediction. In addition, the algorithm is able to identify lattice geometries most compatible with ssNMR constraints, representing a quantitative, novel method for investigating crystal-face binding specificity. We use this method to determine most of the structure of human salivary statherin interacting with the mineral phase of tooth enamel. Computation and experiment converge on an ensemble of related structures and identify preferential binding at three crystal surfaces. The work represents a significant advance toward determining structure of biomineral-adsorbed protein using experimentally biased structure prediction. This method is generally applicable to proteins that can be chemically synthesized. Copyright © 2010 Elsevier Ltd. All rights reserved.

In-cell NMR of intrinsically disordered proteins in prokaryotic cells.

PubMed

Ito, Yutaka; Mikawa, Tsutomu; Smith, Brian O

2012-01-01

In-cell NMR, i.e., the acquisition of heteronuclear multidimensional NMR of biomacromolecules inside living cells, is, to our knowledge, the only method for investigating the three-dimensional structure and dynamics of proteins at atomic detail in the intracellular environment. Since the inception of the method, intrinsically disordered proteins have been regarded as particular targets for in-cell NMR, due to their expected sensitivity to the molecular crowding in the intracellular environment. While both prokaryotic and eukaryotic cells can be used as host cells for in-cell NMR, prokaryotic in-cell NMR, particularly employing commonly used protein overexpression systems in Escherichia coli cells, is the most accessible approach. In this chapter we describe general procedures for obtaining in-cell NMR spectra in E. coli cells.

NMR crystallography of zeolites: How far can we go without diffraction data?

PubMed

Brouwer, Darren H; Van Huizen, Jared

2018-05-10

Nuclear magnetic resonance (NMR) crystallography-an approach to structure determination that seeks to integrate solid-state NMR spectroscopy, diffraction, and computation methods-has emerged as an effective strategy to determine structures of difficult-to-characterize materials, including zeolites and related network materials. This paper explores how far it is possible to go in determining the structure of a zeolite framework from a minimal amount of input information derived only from solid-state NMR spectroscopy. It is shown that the framework structure of the fluoride-containing and tetramethylammonium-templated octadecasil clathrasil material can be solved from the 1D 29 Si NMR spectrum and a single 2D 29 Si NMR correlation spectrum alone, without the space group and unit cell parameters normally obtained from diffraction data. The resulting NMR-solved structure is in excellent agreement with the structures determined previously by diffraction methods. It is anticipated that NMR crystallography strategies like this will be useful for structure determination of other materials, which cannot be solved from diffraction methods alone. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Initial Stage Reference Search : Behavioral Economics and Transportation

DOT National Transportation Integrated Search

2015-04-01

The initial stage investigation is the beginning step in the Exploratory Advanced Research (EAR) Program process for exploring ideas across traditional and nontraditional fields of research and stimulating new approaches to problem solving. The proce...

Hazardous materials programs in the fifty states.

DOT National Transportation Integrated Search

1988-01-01

This report describes the hazardous materials transportation safety programs, laws, and regulatory programs enacted by each of the fifty states. The report contains a brief description of common elements in the hazardous materials policy-making proce...

Airport Winter Safety And Operations

DOT National Transportation Integrated Search

1991-10-01

The purpose of this advisory circular (AC) is to provide guidance to assist : airport owners/operators in the development of an acceptable airport snow and : ice control program and to provide guidance on appropriate field condition : reporting proce...

Respiratory Toxicity Biomarkers

EPA Science Inventory

The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

Determination of barge impact probabilities for bridge design.

DOT National Transportation Integrated Search

2016-04-01

Waterway bridges in the United States are designed to resist vessel collision loads according to design provisions released by the American Association of State : Highway and Transportation Officials (AASHTO). These provisions provide detailed proced...

Mechanistic-empirical design concepts for continuously reinforced concrete pavements in Illinois.

DOT National Transportation Integrated Search

2009-04-01

The Illinois Department of Transportation (IDOT) currently has an existing jointed plain concrete pavement : (JPCP) design based on mechanistic-empirical (M-E) principles. However, their continuously reinforced concrete : pavement (CRCP) design proce...

Microwave-assisted synthesis of organics and nanomaterials

EPA Science Inventory

Microwave-assisted chemistry techniques and greener reaction media are dramatically reducing chemical waste and reaction times in several organic transformations and material synthesis. This presentation summarizes author’s own experience in developing MW-assisted chemical proces...

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.

Calibration of NMR well logs from carbonate reservoirs with laboratory NMR measurements and μXRCT

DOE PAGES

Mason, Harris E.; Smith, Megan M.; Hao, Yue; ...

2014-12-31

The use of nuclear magnetic resonance (NMR) well log data has the potential to provide in-situ porosity, pore size distributions, and permeability of target carbonate CO₂ storage reservoirs. However, these methods which have been successfully applied to sandstones have yet to be completely validated for carbonate reservoirs. Here, we have taken an approach to validate NMR measurements of carbonate rock cores with independent measurements of permeability and pore surface area to volume (S/V) distributions using differential pressure measurements and micro X-ray computed tomography (μXRCT) imaging methods, respectively. We observe that using standard methods for determining permeability from NMR data incorrectlymore » predicts these values by orders of magnitude. However, we do observe promise that NMR measurements provide reasonable estimates of pore S/V distributions, and with further independent measurements of the carbonate rock properties that universally applicable relationships between NMR measured properties may be developed for in-situ well logging applications of carbonate reservoirs.« less

Calibration of NMR well logs from carbonate reservoirs with laboratory NMR measurements and μXRCT

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

Mason, Harris E.; Smith, Megan M.; Hao, Yue

The use of nuclear magnetic resonance (NMR) well log data has the potential to provide in-situ porosity, pore size distributions, and permeability of target carbonate CO₂ storage reservoirs. However, these methods which have been successfully applied to sandstones have yet to be completely validated for carbonate reservoirs. Here, we have taken an approach to validate NMR measurements of carbonate rock cores with independent measurements of permeability and pore surface area to volume (S/V) distributions using differential pressure measurements and micro X-ray computed tomography (μXRCT) imaging methods, respectively. We observe that using standard methods for determining permeability from NMR data incorrectlymore » predicts these values by orders of magnitude. However, we do observe promise that NMR measurements provide reasonable estimates of pore S/V distributions, and with further independent measurements of the carbonate rock properties that universally applicable relationships between NMR measured properties may be developed for in-situ well logging applications of carbonate reservoirs.« less

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.

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.

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

NMR logging apparatus

DOEpatents

Walsh, David O; Turner, Peter

2014-05-27

Technologies including NMR logging apparatus and methods are disclosed. Example NMR logging apparatus may include surface instrumentation and one or more downhole probes configured to fit within an earth borehole. The surface instrumentation may comprise a power amplifier, which may be coupled to the downhole probes via one or more transmission lines, and a controller configured to cause the power amplifier to generate a NMR activating pulse or sequence of pulses. Impedance matching means may be configured to match an output impedance of the power amplifier through a transmission line to a load impedance of a downhole probe. Methods may include deploying the various elements of disclosed NMR logging apparatus and using the apparatus to perform NMR measurements.

Multinuclear NMR of CaSiO(3) glass: simulation from first-principles.

PubMed

Pedone, Alfonso; Charpentier, Thibault; Menziani, Maria Cristina

2010-06-21

An integrated computational method which couples classical molecular dynamics simulations with density functional theory calculations is used to simulate the solid-state NMR spectra of amorphous CaSiO(3). Two CaSiO(3) glass models are obtained by shell-model molecular dynamics simulations, successively relaxed at the GGA-PBE level of theory. The calculation of the NMR parameters (chemical shielding and quadrupolar parameters), which are then used to simulate solid-state 1D and 2D-NMR spectra of silicon-29, oxygen-17 and calcium-43, is achieved by the gauge including projector augmented-wave (GIPAW) and the projector augmented-wave (PAW) methods. It is shown that the limitations due to the finite size of the MD models can be overcome using a Kernel Estimation Density (KDE) approach to simulate the spectra since it better accounts for the disorder effects on the NMR parameter distribution. KDE allows reconstructing a smoothed NMR parameter distribution from the MD/GIPAW data. Simulated NMR spectra calculated with the present approach are found to be in excellent agreement with the experimental data. This further validates the CaSiO(3) structural model obtained by MD simulations allowing the inference of relationships between structural data and NMR response. The methods used to simulate 1D and 2D-NMR spectra from MD GIPAW data have been integrated in a package (called fpNMR) freely available on request.

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.

A fast field-cycling device for high-resolution NMR: Design and application to spin relaxation and hyperpolarization experiments

NASA Astrophysics Data System (ADS)

Kiryutin, Alexey S.; Pravdivtsev, Andrey N.; Ivanov, Konstantin L.; Grishin, Yuri A.; Vieth, Hans-Martin; Yurkovskaya, Alexandra V.

2016-02-01

A device for performing fast magnetic field-cycling NMR experiments is described. A key feature of this setup is that it combines fast switching of the external magnetic field and high-resolution NMR detection. The field-cycling method is based on precise mechanical positioning of the NMR probe with the mounted sample in the inhomogeneous fringe field of the spectrometer magnet. The device enables field variation over several decades (from 100 μT up to 7 T) within less than 0.3 s; progress in NMR probe design provides NMR linewidths of about 10-3 ppm. The experimental method is very versatile and enables site-specific studies of spin relaxation (NMRD, LLSs) and spin hyperpolarization (DNP, CIDNP, and SABRE) at variable magnetic field and at variable temperature. Experimental examples of such studies are demonstrated; advantages of the experimental method are described and existing challenges in the field are outlined.

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.

Understanding Ionic Liquid Pretreatment of Lignocellulosic Biomasses

USDA-ARS?s Scientific Manuscript database

Pretreatment of biomass is essential for breaking apart highly ordered and crystalline plant cell walls and loosening the lignin and hemicellulose conjugation to cellulose microfibrills, thereby facilitating enzyme accessibility and adsorption and reducing costs of downstream saccharification proces...

AN ULTRAVIOLET-VISIBLE SPECTROPHOTOMETER AUTOMATION SYSTEM. PART III: PROGRAM DOCUMENTATION

EPA Science Inventory

The Ultraviolet-Visible Spectrophotometer (UVVIS) automation system accomplishes 'on-line' spectrophotometric quality assurance determinations, report generations, plot generations and data reduction for chlorophyll or color analysis. This system also has the capability to proces...

Cost analysis of Virginia system for processing accident data.

DOT National Transportation Integrated Search

1984-01-01

The objectives of this study were to identify present system costs and deficiencies, determine the economic feasibility of alternative system configurations, and make recommendations for improvements. The study focused on the procedures used to proce...

Proton Nuclear Magnetic Resonance Spectroscopy as a Technique for Gentamicin Drug Susceptibility Studies with Escherichia coli ATCC 25922

PubMed Central

García-Álvarez, Lara; Busto, Jesús H.; Avenoza, Alberto; Sáenz, Yolanda; Peregrina, Jesús Manuel

2015-01-01

Antimicrobial drug susceptibility tests involving multiple time-consuming steps are still used as reference methods. Today, there is a need for the development of new automated instruments that can provide faster results and reduce operating time, reagent costs, and labor requirements. Nuclear magnetic resonance (NMR) spectroscopy meets those requirements. The metabolism and antimicrobial susceptibility of Escherichia coli ATCC 25922 in the presence of gentamicin have been analyzed using NMR and compared with a reference method. Direct incubation of the bacteria (with and without gentamicin) into the NMR tube has also been performed, and differences in the NMR spectra were obtained. The MIC, determined by the reference method found in this study, would correspond with the termination of the bacterial metabolism observed with NMR. Experiments carried out directly into the NMR tube enabled the development of antimicrobial drug susceptibility tests to assess the effectiveness of the antibiotic. NMR is an objective and reproducible method for showing the effects of a drug on the subject bacterium and can emerge as an excellent tool for studying bacterial activity in the presence of different antibiotic concentrations. PMID:25972417

Proton Nuclear Magnetic Resonance Spectroscopy as a Technique for Gentamicin Drug Susceptibility Studies with Escherichia coli ATCC 25922.

PubMed

García-Álvarez, Lara; Busto, Jesús H; Avenoza, Alberto; Sáenz, Yolanda; Peregrina, Jesús Manuel; Oteo, José A

2015-08-01

Antimicrobial drug susceptibility tests involving multiple time-consuming steps are still used as reference methods. Today, there is a need for the development of new automated instruments that can provide faster results and reduce operating time, reagent costs, and labor requirements. Nuclear magnetic resonance (NMR) spectroscopy meets those requirements. The metabolism and antimicrobial susceptibility of Escherichia coli ATCC 25922 in the presence of gentamicin have been analyzed using NMR and compared with a reference method. Direct incubation of the bacteria (with and without gentamicin) into the NMR tube has also been performed, and differences in the NMR spectra were obtained. The MIC, determined by the reference method found in this study, would correspond with the termination of the bacterial metabolism observed with NMR. Experiments carried out directly into the NMR tube enabled the development of antimicrobial drug susceptibility tests to assess the effectiveness of the antibiotic. NMR is an objective and reproducible method for showing the effects of a drug on the subject bacterium and can emerge as an excellent tool for studying bacterial activity in the presence of different antibiotic concentrations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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.

ENVIRONMENTAL COMPARISON METRICS FOR LIFE CYCLE IMPACT ASSESSMENT AND PROCESS DESIGN

EPA Science Inventory

Metrics (potentials, potency factors, equivalency factors or characterization factors) are available to support the environmental comparison of alternatives in application domains like proces design and product life-cycle assessment (LCA). These metrics typically provide relative...

State of Idaho Port of Entry Study

DOT National Transportation Integrated Search

2016-05-01

The purpose of this study was to evaluate Idaho's Ports of Entry (POE) Program to identify its strengths and weaknesses, and provide recommendations for future program development and operations. As part of the study, current Idaho POE business proce...

Engineering properties of brittle repair materials : final report : volume I.

DOT National Transportation Integrated Search

1992-09-01

Most codes of practice prescribe procedures for selecting patch configuration and materials based on tests devised for evaluating new pavement materials. This study is aimed at examining the special consideration to be given to such evaluation proced...

Engineering properties of brittle repair materials : final report : volume II.

DOT National Transportation Integrated Search

1992-09-01

Most codes of practice prescribe procedures for selecting patch configuration and materials based on tests devised for evaluating new pavement materials. This study is aimed at examining the special consideration to be given to such evaluation proced...

Three dimensional geometric modeling of processing-tomatoes

USDA-ARS?s Scientific Manuscript database

Characterizing tomato geometries with different shapes and sizes would facilitate the design of tomato processing equipments and promote computer-based engineering simulations. This research sought to develop a three-dimensional geometric model that can describe the morphological attributes of proce...

Project inspection using mobile technology - phase II : assessing the impacts of mobile technology on project inspection.

DOT National Transportation Integrated Search

2015-01-01

As mobile technology becomes widely available and affordable, transportation agencies can use this : technology to streamline operations involved within project inspection. This research, conducted in two : phases, identified opportunities for proces...

ALTERNATIVE TO CHROME ETCHING PROCESSES FOR METALS

EPA Science Inventory

Several industries, including the National Center for Manufacturing Science have initiated programs for chrome abatement. The programs, however, generally focus on chrome reduction by use of existing technologies and do not address the elimination of chrome in pretreatment proces...

Variable dynamic testbed vehicle : safety plan

DOT National Transportation Integrated Search

1997-02-01

This safety document covers the entire safety process from inception to delivery of the Variable Dynamic Testbed Vehicle. In addition to addressing the process of safety on the vehicle , it should provide a basis on which to build future safety proce...

On the Analytical Superiority of 1D NMR for Fingerprinting the Higher Order Structure of Protein Therapeutics Compared to Multidimensional NMR Methods.

PubMed

Poppe, Leszek; Jordan, John B; Rogers, Gary; Schnier, Paul D

2015-06-02

An important aspect in the analytical characterization of protein therapeutics is the comprehensive characterization of higher order structure (HOS). Nuclear magnetic resonance (NMR) is arguably the most sensitive method for fingerprinting HOS of a protein in solution. Traditionally, (1)H-(15)N or (1)H-(13)C correlation spectra are used as a "structural fingerprint" of HOS. Here, we demonstrate that protein fingerprint by line shape enhancement (PROFILE), a 1D (1)H NMR spectroscopy fingerprinting approach, is superior to traditional two-dimensional methods using monoclonal antibody samples and a heavily glycosylated protein therapeutic (Epoetin Alfa). PROFILE generates a high resolution structural fingerprint of a therapeutic protein in a fraction of the time required for a 2D NMR experiment. The cross-correlation analysis of PROFILE spectra allows one to distinguish contributions from HOS vs protein heterogeneity, which is difficult to accomplish by 2D NMR. We demonstrate that the major analytical limitation of two-dimensional methods is poor selectivity, which renders these approaches problematic for the purpose of fingerprinting large biological macromolecules.

Reducing acquisition times in multidimensional NMR with a time-optimized Fourier encoding algorithm

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

Zhang, Zhiyong; Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005; Smith, Pieter E. S.

Speeding up the acquisition of multidimensional nuclear magnetic resonance (NMR) spectra is an important topic in contemporary NMR, with central roles in high-throughput investigations and analyses of marginally stable samples. A variety of fast NMR techniques have been developed, including methods based on non-uniform sampling and Hadamard encoding, that overcome the long sampling times inherent to schemes based on fast-Fourier-transform (FFT) methods. Here, we explore the potential of an alternative fast acquisition method that leverages a priori knowledge, to tailor polychromatic pulses and customized time delays for an efficient Fourier encoding of the indirect domain of an NMR experiment. Bymore » porting the encoding of the indirect-domain to the excitation process, this strategy avoids potential artifacts associated with non-uniform sampling schemes and uses a minimum number of scans equal to the number of resonances present in the indirect dimension. An added convenience is afforded by the fact that a usual 2D FFT can be used to process the generated data. Acquisitions of 2D heteronuclear correlation NMR spectra on quinine and on the anti-inflammatory drug isobutyl propionic phenolic acid illustrate the new method's performance. This method can be readily automated to deal with complex samples such as those occurring in metabolomics, in in-cell as well as in in vivo NMR applications, where speed and temporal stability are often primary concerns.« less

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.

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.

Evaluation of phosphorus characterization in broiler ileal digesta, manure, and litter samples: (31)P-NMR vs. HPLC.

PubMed

Leytem, A B; Kwanyuen, P; Plumstead, P W; Maguire, R O; Brake, J

2008-01-01

Using 31-phosphorus nuclear magnetic resonance spectroscopy ((31)P-NMR) to characterize phosphorus (P) in animal manures and litter has become a popular technique in the area of nutrient management. To date, there has been no published work evaluating P quantification in manure/litter samples with (31)P-NMR compared to other accepted methods such as high performance liquid chromatography (HPLC). To evaluate the use of (31)P-NMR to quantify myo-inositol hexakisphosphate (phytate) in ileal digesta, manure, and litter from broilers, we compared results obtained from both (31)P-NMR and a more traditional HPLC method. The quantification of phytate in all samples was very consistent between the two methods, with linear regressions having slopes ranging from 0.94 to 1.07 and r(2) values of 0.84 to 0.98. We compared the concentration of total monoester P determined with (31)P-NMR with the total inositol P content determined with HPLC and found a strong linear relationship between the two measurements having slopes ranging from 0.91 to 1.08 and r(2) values of 0.73 to 0.95. This suggests that (31)P-NMR is a very reliable method for quantifying P compounds in manure/litter samples.

Metrics and experimental data for assessing unbalanced disassembly lines.

DOT National Transportation Integrated Search

2011-01-01

Disassembly lines are inherently multi-criteria, with balance having the possibility of : being one of the lower priorities. This is due to the fact that other criteria for example, : removing valuable or hazardous materials early on in the proce...

Speak Up Speak Out Coalition Survey Results

EPA Science Inventory

Comprehensive planning is a visionary planning process that integrates community values and land use policy. The Mayor of Duluth, Minnesota, directed the inclusion of two new values into the City’s comprehensive planning process to direct the community’s future, proce...

Documenting Public Values for River Ecosystem Services

EPA Science Inventory

The value to society of environmental changes is difficult to assess, and thus challenging to include in environmental management decisions. This presentation will first provide an overview of how framing these values in an ecosystem services perspective can facilitate the proces...

Predicting driver distraction using computed occlusion task times : estimation of task element times and distributions.

DOT National Transportation Integrated Search

2015-04-01

To determine conformance with NHTSAs visual-manual interface distraction guidelines and to : reduce the associated number of crashes, NHTSA recommends a visual-occlusion test : procedure. As an alternative to testing subjects following that proced...

Emerging evidence of ozone metabolic effects and potential mechanisms

EPA Science Inventory

SOT 2014 Abstract: Invitational Emerging evidence of ozone metabolic effects and potential mechanisms U.P. Kodavanti NHEERL, USEPA, Research Triangle Park, NC Recent evidence suggests that air pollutants are linked to metabolic syndrome and impact several key metabolic proce...

ENVIRONMENTAL CHAMBER STUDIES OF MERCURY REACTIONS IN THE ATMOSPHERE

EPA Science Inventory

Mercury is released into the environment through both natural and anthropogenic pathways. The cycling and fate of mercury in atmospheric, soil, and water ecosystems is impacted by various factors, including chemical transformation and transport. An understanding of these proces...

Potential use and applications for reclaimed millings.

DOT National Transportation Integrated Search

2015-06-01

The purpose of this project was to provide support to PennDOT District 1-0 in the effective use of milled asphalt material. Specifically, : District 1-0 has a shortage of high-quality available coarse aggregate and has developed the innovative proced...

Method and apparatus for measuring the NMR spectrum of an orientationally disordered sample

DOEpatents

Pines, Alexander; Samoson, Ago

1990-01-01

An improved NMR probe and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise oreintationally disordered samples. The apparatus mechanically varies the orientation of the sample such that the time average of two or more sets of spherical harmonic functions is zero.

Development of an 19F NMR method for the analysis of fluorinated acids in environmental water samples.

PubMed

Ellis, D A; Martin, J W; Muir, D C; Mabury, S A

2000-02-15

This investigation was carried out to evaluate 19F NMR as an analytical tool for the measurement of trifluoroacetic acid (TFA) and other fluorinated acids in the aquatic environment. A method based upon strong anionic exchange (SAX) chromatography was also optimized for the concentration of the fluoro acids prior to NMR analysis. Extraction of the analyte from the SAX column was carried out directly in the NMR solvent in the presence of the strong organic base, DBU. The method allowed the analysis of the acid without any prior cleanup steps being involved. Optimal NMR sensitivity based upon T1 relaxation times was investigated for seven fluorinated compounds in four different NMR solvents. The use of the relaxation agent chromium acetylacetonate, Cr(acac)3, within these solvent systems was also evaluated. Results show that the optimal NMR solvent differs for each fluorinated analyte. Cr(acac)3 was shown to have pronounced effects on the limits of detection of the analyte. Generally, the optimal sensitivity condition appears to be methanol-d4/2M DBU in the presence of 4 mg/mL of Cr-(acac)3. The method was validated through spike and recovery for five fluoro acids from environmentally relevant waters. Results are presented for the analysis of TFA in Toronto rainwater, which ranged from < 16 to 850 ng/L. The NMR results were confirmed by GC-MS selected-ion monitoring of the fluoroanalide derivative.

Possible 6-qubit NMR quantum computer device material; simulator of the NMR line width

NASA Astrophysics Data System (ADS)

Hashi, K.; Kitazawa, H.; Shimizu, T.; Goto, A.; Eguchi, S.; Ohki, S.

2002-12-01

For an NMR quantum computer, splitting of an NMR spectrum must be larger than a line width. In order to find a best device material for a solid-state NMR quantum computer, we have made a simulation program to calculate the NMR line width due to the nuclear dipole field by the 2nd moment method. The program utilizes the lattice information prepared by commercial software to draw a crystal structure. By applying this program, we can estimate the NMR line width due to the nuclear dipole field without measurements and find a candidate material for a 6-qubit solid-state NMR quantum computer device.

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.

Quantification of terpene trilactones in Ginkgo biloba with a 1H NMR method.

PubMed

Liang, Tingfu; Miyakawa, Takuya; Yang, Jinwei; Ishikawa, Tsutomu; Tanokura, Masaru

2018-06-01

Ginkgo biloba L. has been used as a herbal medicine in the traditional treatment of insufficient blood flow, memory deficits, and cerebral insufficiency. The terpene trilactone components, the bioactive agents of Ginkgo biloba L., have also been reported to exhibit useful functionality such as anti-inflammatory and neuroprotective effects. Therefore, in the present research, we attempted to analyze quantitatively the terpene trilactone components in Ginkgo biloba leaf extract, with quantitative 1 H NMR (qNMR) and obtained almost identical results to data reported using HPLC. Application of the qNMR method for the analysis of the terpene trilactone contents in commercial Ginkgo extract products, such as soft gel capsules and tablets, produced the same levels noted in package labels. Thus, qNMR is an alternative method for quantification of the terpene trilactone components in commercial Ginkgo extract products.

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.

Hypothesis driven assessment of an NMR curriculum

NASA Astrophysics Data System (ADS)

Cossey, Kimberly

The goal of this project was to develop a battery of assessments to evaluate an undergraduate NMR curriculum at Penn State University. As a chemical education project, we sought to approach the problem of curriculum assessment from a scientific perspective, while remaining grounded in the education research literature and practices. We chose the phrase hypothesis driven assessment to convey this process of relating the scientific method to the study of educational methods, modules, and curricula. We began from a hypothesis, that deeper understanding of one particular analytical technique (NMR) will increase undergraduate students' abilities to solve chemical problems. We designed an experiment to investigate this hypothesis, and data collected were analyzed and interpreted in light of the hypothesis and several related research questions. The expansion of the NMR curriculum at Penn State was funded through the NSF's Course, Curriculum, and Laboratory Improvement (CCLI) program, and assessment was required. The goal of this project, as stated in the grant proposal, was to provide NMR content in greater depth by integrating NMR modules throughout the curriculum in physical chemistry, instrumental, and organic chemistry laboratory courses. Hands-on contact with the NMR spectrometer and NMR data and repeated exposure of the analytical technique within different contexts (courses) were unique factors of this curriculum. Therefore, we maintained a focus on these aspects throughout the evaluation process. The most challenging and time-consuming aspect of any assessment is the development of testing instruments and methods to provide useful data. After key variables were defined, testing instruments were designed to measure these variables based on educational literature (Chapter 2). The primary variables measured in this assessment were: depth of understanding of NMR, basic NMR knowledge, problem solving skills (HETCOR problem), confidence for skills used in class (within the hands-on NMR modules), confidence for NMR tasks (not practiced), and confidence for general science tasks. Detailed discussion of the instruments, testing methods and experimental design used in this assessment are provided (Chapter 3). All data were analyzed quantitatively using methods adapted from the educational literature (Chapter 4). Data were analyzed and the descriptive statistics, independent t-tests between the experimental and control groups, and correlation statistics were calculated for each variable. In addition, for those variables included on the pretest, dependent t-tests between pretest and posttest scores were also calculated. The results of study 1 and study 2 were used to draw conclusions based on the hypothesis and research questions proposed in this work (Chapter 4). Data collected in this assessment were used to answer the following research questions: (1) Primary research question: Is depth of understanding of NMR linked to problem solving skills? (2) Are the NMR modules working as intended? Do they promote depth of understanding of NMR? (a) Will students who complete NMR modules have a greater depth of understanding of NMR than students who do not complete the modules? (b) Is depth of understanding increasing over the course of the experiment? (3) Is confidence an intermediary between depth of understanding and problem solving skills? Is it linked to both variables? (4) What levels of confidence are affected by the NMR modules? (a) Will confidence for the NMR class skills used in the modules themselves be greater for those who have completed the modules? (b) Will confidence for NMR tasks not practiced in the course be affected? (c) Will confidence for general science tasks be affected? (d) Are different levels of confidence (class skills, NMR tasks, general science tasks) linked to each other? Results from this NMR curriculum assessment could also have implications outside of the courses studied, and so there is potential to impact the chemical education community (section 5.2.1). In addition to providing reliable testing instruments/measures that could be used outside the university, the results of this research contribute to the study of problem solving in chemistry, learner characteristics within the context of chemical education studies, and NMR specific educational evaluations. Valuable information was gathered through the current method of evaluation for the NMR curriculum. However, improvements could be made to the existing assessment, and an alternate assessment that could supplement the information found in this study has been proposed (Chapter 5).

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.

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.

NMR shielding calculations across the periodic table: diamagnetic uranium compounds. 2. Ligand and metal NMR.

PubMed

Schreckenbach, Georg

2002-12-16

In this and a previous article (J. Phys. Chem. A 2000, 104, 8244), the range of application for relativistic density functional theory (DFT) is extended to the calculation of nuclear magnetic resonance (NMR) shieldings and chemical shifts in diamagnetic actinide compounds. Two relativistic DFT methods are used, ZORA ("zeroth-order regular approximation") and the quasirelativistic (QR) method. In the given second paper, NMR shieldings and chemical shifts are calculated and discussed for a wide range of compounds. The molecules studied comprise uranyl complexes, [UO(2)L(n)](+/-)(q); UF(6); inorganic UF(6) derivatives, UF(6-n)Cl(n), n = 0-6; and organometallic UF(6) derivatives, UF(6-n)(OCH(3))(n), n = 0-5. Uranyl complexes include [UO(2)F(4)](2-), [UO(2)Cl(4)](2-), [UO(2)(OH)(4)](2-), [UO(2)(CO(3))(3)](4-), and [UO(2)(H(2)O)(5)](2+). For the ligand NMR, moderate (e.g., (19)F NMR chemical shifts in UF(6-n)Cl(n)) to excellent agreement [e.g., (19)F chemical shift tensor in UF(6) or (1)H NMR in UF(6-n)(OCH(3))(n)] has been found between theory and experiment. The methods have been used to calculate the experimentally unknown (235)U NMR chemical shifts. A large chemical shift range of at least 21,000 ppm has been predicted for the (235)U nucleus. ZORA spin-orbit appears to be the most accurate method for predicting actinide metal chemical shifts. Trends in the (235)U NMR chemical shifts of UF(6-n)L(n) molecules are analyzed and explained in terms of the calculated electronic structure. It is argued that the energy separation and interaction between occupied and virtual orbitals with f-character are the determining factors.

Assessment of 1H NMR-based metabolomics analysis for normalization of urinary metals against creatinine.

PubMed

Cassiède, Marc; Nair, Sindhu; Dueck, Meghan; Mino, James; McKay, Ryan; Mercier, Pascal; Quémerais, Bernadette; Lacy, Paige

2017-01-01

Proton nuclear magnetic resonance ( 1 H NMR, or NMR) spectroscopy and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for metabolomics and metal analysis in urine samples. However, creatinine quantification by NMR for the purpose of normalization of urinary metals has not been validated. We assessed the validity of using NMR analysis for creatinine quantification in human urine samples in order to allow normalization of urinary metal concentrations. NMR and ICP-MS techniques were used to measure metabolite and metal concentrations in urine samples from 10 healthy subjects. For metabolite analysis, two magnetic field strengths (600 and 700MHz) were utilized. In addition, creatinine concentrations were determined by using the Jaffe method. Creatinine levels were strongly correlated (R 2 =0.99) between NMR and Jaffe methods. The NMR spectra were deconvoluted with a target database containing 151 metabolites that are present in urine. A total of 50 metabolites showed good correlation (R 2 =0.7-1.0) at 600 and 700MHz. Metal concentrations determined after NMR-measured creatinine normalization were comparable to previous reports. NMR analysis provided robust urinary creatinine quantification, and was sufficient for normalization of urinary metal concentrations. We found that NMR-measured creatinine-normalized urinary metal concentrations in our control subjects were similar to general population levels in Canada and the United Kingdom. Copyright © 2016 Elsevier B.V. All rights reserved.

Glyceollin I reverses epithelial to mesenchymal transition in letrozole resistance

USDA-ARS?s Scientific Manuscript database

Although aromatase inhibitors, such as letrozole; are standard endocrine therapy for postmenopausal women with early stage metastatic estrogen-dependent breast cancer, the major limitation in managing this disease is the development of drug resistance; therefore, a better understanding of this proce...

Production of Value-added Products by Lactic Acid Bacteria

USDA-ARS?s Scientific Manuscript database

Lactic acid bacteria (LAB) are a group of facultative anaerobic, catalase negative, nonmotile and nonsporeforming–Gram positive bacteria. Most LAB utilize high energy C sources including monomer sugars to produce energy to maintain cellular structure and function. This anaerobic fermentation proce...

Project inspection using mobile technology - phase I : an investigation into existing business processes and areas for improvement using mobile technology.

DOT National Transportation Integrated Search

2013-08-01

As mobile technology becomes widely available and affordable, transportation agencies can use this technology to : streamline operations involved within project inspection. This research, conducted in two phases, identified : opportunities for proces...

Monitoring Process Streams Towards Understanding Ionic Liquid Pretreatment of Switchgrass and Corn Stover

USDA-ARS?s Scientific Manuscript database

Pretreatment of Biomass is essential for breaking apart highly ordered and crystalline plant cell walls and loosening the lignin and hemicellulose conjugation to cellulose microfibrils, thereby facilitating enzyme accessibility and adsorption and reducing cotsts of downstream saccharification proces...

NMR Spectra through the Eyes of a Student: Eye Tracking Applied to NMR Items

ERIC Educational Resources Information Center

Topczewski, Joseph J.; Topczewski, Anna M.; Tang, Hui; Kendhammer, Lisa K.; Pienta, Norbert J.

2017-01-01

Nuclear magnetic resonance spectroscopy (NMR) plays a key role in introductory organic chemistry, spanning theory, concepts, and experimentation. Therefore, it is imperative that the instruction methods for NMR are both efficient and effective. By utilizing eye tracking equipment, the researchers were able to monitor how second-semester organic…

Method and sample spinning apparatus for measuring the NMR spectrum of an orientationally disordered sample

DOEpatents

Pines, Alexander; Samoson, Ago

1990-01-01

An improved NMR apparatus and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise orientationally disordered samples. The apparatus spins the sample about an axis. The angle of the axis is mechanically varied such that the time average of two or more Legendre polynomials are zero.

NMR system and method having a permanent magnet providing a rotating magnetic field

DOEpatents

Schlueter, Ross D [Berkeley, CA; Budinger, Thomas F [Berkeley, CA

2009-05-19

Disclosed herein are systems and methods for generating a rotating magnetic field. The rotating magnetic field can be used to obtain rotating-field NMR spectra, such as magic angle spinning spectra, without having to physically rotate the sample. This result allows magic angle spinning NMR to be conducted on biological samples such as live animals, including humans.

Determination of free fatty acids in pharmaceutical lipids by ¹H NMR and comparison with the classical acid value.

PubMed

Skiera, Christina; Steliopoulos, Panagiotis; Kuballa, Thomas; Diehl, Bernd; Holzgrabe, Ulrike

2014-05-01

Indices like acid value, peroxide value, and saponification value play an important role in quality control and identification of lipids. Requirements on these parameters are given by the monographs of the European pharmacopeia. (1)H NMR spectroscopy provides a fast and simple alternative to these classical approaches. In the present work a new (1)H NMR approach to determine the acid value is described. The method was validated using a statistical approach based on a variance components model. The performance under repeatability and in-house reproducibility conditions was assessed. We applied this (1)H NMR assay to a wide range of different fatty oils. A total of 305 oil and fat samples were examined by both the classical and the NMR method. Except for hard fat, the data obtained by the two methods were in good agreement. The (1)H NMR method was adapted to analyse waxes and oleyloleat. Furthermore, the effect of solvent and in the case of castor oil the effect of the oil matrix on line broadening and chemical shift of the carboxyl group signal are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Understanding Unimer Exchange Processes in Block Copolymer Micelles using NMR Diffusometry, Time-Resolved NMR, and SANS

NASA Astrophysics Data System (ADS)

Madsen, Louis; Kidd, Bryce; Li, Xiuli; Miller, Katherine; Cooksey, Tyler; Robertson, Megan

Our team seeks to understand dynamic behaviors of block copolymer micelles and their interplay with encapsulated cargo molecules. Quantifying unimer and cargo exchange rates micelles can provide critical information for determining mechanisms of unimer exchange as well as designing systems for specific cargo release dynamics. We are exploring the utility of NMR spectroscopy and diffusometry techniques as complements to existing SANS and fluorescence methods. One promising new method involves time-resolved NMR spin relaxation measurements, wherein mixing of fully protonated and 2H-labeled PEO-b-PCL micelles solutions shows an increase in spin-lattice relaxation time (T1) with time after mixing. This is due to a weakening in magnetic environment surrounding 1H spins as 2H-bearing unimers join fully protonated micelles. We are measuring time constants for unimer exchange of minutes to hours, and we expect to resolve times of <1 min. This method can work on any solution NMR spectrometer and with minimal perturbation to chemical structure (as in dye-labelled fluorescence methods). Multimodal NMR can complement existing characterization tools, expanding and accelerating dynamics measurements for polymer micelle, nanogel, and nanoparticle developers.

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.

High-resolution detection of 13C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy

PubMed Central

Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Jeffrey, F. Mark; Malloy, Craig R.; Pascual, Juan M.

2011-01-01

Glucose readily supplies the brain with the majority of carbon needed to sustain neurotransmitter production and utilization., The rate of brain glucose metabolism can be computed using 13C nuclear magnetic resonance (NMR) spectroscopy by detecting changes in 13C contents of products generated by cerebral metabolism. As previously observed, scalar coupling between adjacent 13C carbons (multiplets) can provide additional information to 13C contents for the computation of metabolic rates. Most NMR studies have been conducted in large animals (often under anesthesia) because the mass of the target organ is a limiting factor for NMR. Yet, despite the challengingly small size of the mouse brain, NMR studies are highly desirable because the mouse constitutes a common animal model for human neurological disorders. We have developed a method for the ex vivo resolution of NMR multiplets arising from the brain of an awake mouse after the infusion of [1,6-13C2]glucose. NMR spectra obtained by this method display favorable signal-to-noise ratios. With this protocol, the 13C multiplets of glutamate, glutamine, GABA and aspartate achieved steady state after 150 min. The method enables the accurate resolution of multiplets over time in the awake mouse brain. We anticipate that this method can be broadly applicable to compute brain fluxes in normal and transgenic mouse models of neurological disorders. PMID:21946227

Knowns and unknowns in metabolomics identified by multidimensional NMR and hybrid MS/NMR methods

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

Bingol, Kerem; Brüschweiler, Rafael

Metabolomics continues to make rapid progress through the development of new and better methods and their applications to gain insight into the metabolism of a wide range of different biological systems from a systems biology perspective. Customization of NMR databases and search tools allows the faster and more accurate identification of known metabolites, whereas the identification of unknowns, without a need for extensive purification, requires new strategies to integrate NMR with mass spectrometry, cheminformatics, and computational methods. For some applications, the use of covalent and non-covalent attachments in the form of labeled tags or nanoparticles can significantly reduce the complexitymore » of these tasks.« less

1H NMR investigation of thermally triggered insulin release from poly(N-isopropylacrylamide) microgels.

PubMed

Nolan, Christine M; Gelbaum, Leslie T; Lyon, L Andrew

2006-10-01

We describe investigations of insulin release from thermoresponsive microgels using variable temperature (1)H NMR. Microgel particles composed of poly(N-isopropylacrylamide) were loaded with the peptide via a swelling technique, and this method was compared to simple equilibrium partitioning. Variable temperature (1)H NMR studies suggest that the swelling loading method results in enhanced entrapment of the peptide versus equilibrium partitioning. A centrifugation-loading assay supports this finding. Pseudo-temperature jump (1)H NMR measurements suggest that the insulin release rate is partially decoupled from microgel collapse. These types of direct release investigations could prove to be useful methods in the future design of controlled macromolecule drug delivery devices.

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.

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.

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.

E-tool for business processes to improve travel time reliability.

DOT National Transportation Integrated Search

2015-01-01

The etool can be found on the TRB website by following this link: http://www.trb.org/Main/Blurbs/170579.aspx The research team developed an e-tool that can be used by practitioners for planning, implementing, integrating, and analyzing business proce...

SUMMARY REVIEW OF HEALTH EFFECTS ASSOCIATED WITH HYDROGEN FLUORIDE AND RELATED COMPOUNDS: HEALTH ISSUE ASSESSMENT

EPA Science Inventory

The major natural sources of airborne hydrogen fluoride (HF) are volcanic activity, ocean spray, and crustal weathering of fluoride-containing rocks. Anthropogenic sources include emissions from industrial operations such as aluminum and fluorocarbon production, and uranium proce...

COMPUTERIZED FGD BYPRODUCT PRODUCTION AND MARKETING SYSTEM: USERS MANUAL

EPA Science Inventory

The users manual describes a computerized system--consisting of a number of integrated programs, models, and data bases--that has been developed to compare the costs of power plant strategies designed to meet clean air regulations. It describes the data bases, programs, and proce...

User Interface Technology Survey.

DTIC Science & Technology

1987-04-01

malon abc * Owl proces and it dch9anget be reprmeet property to be communicated eff-ctivly Today, larg displays k cupael0 grapics, color. animnation and...have gone trugh a similar evolution. Thee ae hldaaltd sstes [273 sytem geeraedfrom formal deecrptione [77, and aye- ternmtdored Is rspid prottpligby

NHEXAS PHASE I MARYLAND STUDY--LIST OF AVAILABLE DOCUMENTS: PROTOCOLS AND SOPS

EPA Science Inventory

This document lists available protocols and SOPs for the NHEXAS Phase I Maryland study. It identifies protocols and SOPs for the following study components: (1) Sample collection and field operations, (2) Sample analysis and general laboratory procedures, (3) Data Analysis Proced...

THE BEAR BROOK WATERSHED MANIPULATION PROJECT: WATERSHED SCIENCE IN A POLICY PERSPECTIVE

EPA Science Inventory

The Bear Brook Watershed Manipulation in Maine is a paired watershed experiment. Monitoring of the paired catchments (East Bear Brook - reference; West Bear Brook - experimental) began in early 1987. Chemical manipulation of West Bear Brook catchment began in November 1989. Proce...

COMPARING FUNCTIONAL ASSESSMENTS OF WETLANDS TO MEASUREMENTS OF SOIL CHARACTERISTICS AND NITROGEN PROCESSING

EPA Science Inventory

One beneficial service of wetland ecosystems is the improvement of water quality through nitrogen (N) removal. However, one important N-removal process, denitrification, can produce the atmospheric pollutant nitrous oxide (N2O). Wetland biogeochemical functions, such as N proce...

Physical properties of select explosive components for assessing their fate and transport in the environment

USDA-ARS?s Scientific Manuscript database

Information on physical properties of munitions compounds is necessary for assessing their environmental distribution and transport, and predict potential hazards. This information is also needed for selection and design of successful physical, chemical or biological environmental remediation proces...

Development of Performance Indicators for DOTD programs : technical summary.

DOT National Transportation Integrated Search

1998-05-01

The objective of the research was to evaluate the performance indicators currently in use at DOTD and determine if any deficiencies exist with those that are sent forward as a part of the executive budget. A further objective was to examine the proce...

NMR characterization of thin films

DOEpatents

Gerald II, Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

2010-06-15

A method, apparatus, and system for characterizing thin film materials. The method, apparatus, and system includes a container for receiving a starting material, applying a gravitational force, a magnetic force, and an electric force or combinations thereof to at least the starting material, forming a thin film material, sensing an NMR signal from the thin film material and analyzing the NMR signal to characterize the thin film of material.

NMR characterization of thin films

DOEpatents

Gerald, II, Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

2008-11-25

A method, apparatus, and system for characterizing thin film materials. The method, apparatus, and system includes a container for receiving a starting material, applying a gravitational force, a magnetic force, and an electric force or combinations thereof to at least the starting material, forming a thin film material, sensing an NMR signal from the thin film material and analyzing the NMR signal to characterize the thin film of material.

Screening of Small Molecule Interactor Library by Using In-Cell NMR Spectroscopy (SMILI-NMR)

PubMed Central

Xie, Jingjing; Thapa, Rajiv; Reverdatto, Sergey; Burz, David S.; Shekhtman, Alexander

2011-01-01

We developed an in-cell NMR assay for screening small molecule interactor libraries (SMILI-NMR) for compounds capable of disrupting or enhancing specific interactions between two or more components of a biomolecular complex. The method relies on the formation of a well-defined biocomplex and utilizes in-cell NMR spectroscopy to identify the molecular surfaces involved in the interaction at atomic scale resolution. Changes in the interaction surface caused by a small molecule interfering with complex formation are used as a read-out of the assay. The in-cell nature of the experimental protocol insures that the small molecule is capable of penetrating the cell membrane and specifically engaging the target molecule(s). Utility of the method was demonstrated by screening a small dipeptide library against the FKBP–FRB protein complex involved in cell cycle arrest. The dipeptide identified by SMILI-NMR showed biological activity in a functional assay in yeast. PMID:19422228

The PAW/GIPAW approach for computing NMR parameters: a new dimension added to NMR study of solids.

PubMed

Charpentier, Thibault

2011-07-01

In 2001, Mauri and Pickard introduced the gauge including projected augmented wave (GIPAW) method that enabled for the first time the calculation of all-electron NMR parameters in solids, i.e. accounting for periodic boundary conditions. The GIPAW method roots in the plane wave pseudopotential formalism of the density functional theory (DFT), and avoids the use of the cluster approximation. This method has undoubtedly revitalized the interest in quantum chemical calculations in the solid-state NMR community. It has quickly evolved and improved so that the calculation of the key components of NMR interactions, namely the shielding and electric field gradient tensors, has now become a routine for most of the common nuclei studied in NMR. Availability of reliable implementations in several software packages (CASTEP, Quantum Espresso, PARATEC) make its usage more and more increasingly popular, maybe indispensable in near future for all material NMR studies. The majority of nuclei of the periodic table have already been investigated by GIPAW, and because of its high accuracy it is quickly becoming an essential tool for interpreting and understanding experimental NMR spectra, providing reliable assignments of the observed resonances to crystallographic sites or enabling a priori prediction of NMR data. The continuous increase of computing power makes ever larger (and thus more realistic) systems amenable to first-principles analysis. In the near future perspectives, as the incorporation of dynamical effects and/or disorder are still at their early developments, these areas will certainly be the prime target. Copyright © 2011 Elsevier Inc. All rights reserved.

HPLC & NMR-based forced degradation studies of ifosfamide: The potential of NMR in stability studies.

PubMed

Salman, D; Peron, J-M R; Goronga, T; Barton, S; Swinden, J; Nabhani-Gebara, S

2016-03-01

The aim of this study is to conduct a forced degradation study on ifosfamide under several stress conditions to investigate the robustness of the developed HPLC method. It also aims to provide further insight into the stability of ifosfamide and its degradation profile using both HPLC and NMR. Ifosfamide solutions (20mg/mL; n=15, 20mL) were stressed in triplicate by heating (70°C), under acidic (pH 1 & 4) and alkaline (pH 10 & 12) conditions. Samples were analysed periodically using HPLC and FT-NMR. Ifosfamide was most stable under weakly acidic conditions (pH 4). NMR results suggested that the mechanism of ifosfamide degradation involves the cleavage of the PN bond. For all stress conditions, HPLC was not able to detect ifosfamide degradation products that were detected by NMR. These results suggest that the developed HPLC method for ifosfamide did not detect the degradation products shown by NMR. It is possible that degradation products co-elute with ifosfamide, do not elute altogether or are not amenable to the detection method employed. Therefore, investigation of ifosfamide stability requires additional techniques that do not suffer from the aforementioned shortcomings. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

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.

Validated ¹H and 13C Nuclear Magnetic Resonance Methods for the Quantitative Determination of Glycerol in Drug Injections.

PubMed

Lu, Jiaxi; Wang, Pengli; Wang, Qiuying; Wang, Yanan; Jiang, Miaomiao

2018-05-15

In the current study, we employed high-resolution proton and carbon nuclear magnetic resonance spectroscopy (¹H and 13 C NMR) for quantitative analysis of glycerol in drug injections without any complex pre-treatment or derivatization on samples. The established methods were validated with good specificity, linearity, accuracy, precision, stability, and repeatability. Our results revealed that the contents of glycerol were convenient to calculate directly via the integration ratios of peak areas with an internal standard in ¹H NMR spectra, while the integration of peak heights were proper for 13 C NMR in combination with an external calibration of glycerol. The developed methods were both successfully applied in drug injections. Quantitative NMR methods showed an extensive prospect for glycerol determination in various liquid samples.

Sensitivity of ab Initio vs Empirical Methods in Computing Structural Effects on NMR Chemical Shifts for the Example of Peptides.

PubMed

Sumowski, Chris Vanessa; Hanni, Matti; Schweizer, Sabine; Ochsenfeld, Christian

2014-01-14

The structural sensitivity of NMR chemical shifts as computed by quantum chemical methods is compared to a variety of empirical approaches for the example of a prototypical peptide, the 38-residue kaliotoxin KTX comprising 573 atoms. Despite the simplicity of empirical chemical shift prediction programs, the agreement with experimental results is rather good, underlining their usefulness. However, we show in our present work that they are highly insensitive to structural changes, which renders their use for validating predicted structures questionable. In contrast, quantum chemical methods show the expected high sensitivity to structural and electronic changes. This appears to be independent of the quantum chemical approach or the inclusion of solvent effects. For the latter, explicit solvent simulations with increasing number of snapshots were performed for two conformers of an eight amino acid sequence. In conclusion, the empirical approaches neither provide the expected magnitude nor the patterns of NMR chemical shifts determined by the clearly more costly ab initio methods upon structural changes. This restricts the use of empirical prediction programs in studies where peptide and protein structures are utilized for the NMR chemical shift evaluation such as in NMR refinement processes, structural model verifications, or calculations of NMR nuclear spin relaxation rates.

Natural Computing: Its Impact on Software Development

DTIC Science & Technology

2000-02-01

liars) Hanieuually ------. - ------ hadirline and single 1________N *ha c ea I coal C.oke loand . SIt thtan I other 0 Boxohead cutoff rule...user can develop new proce- dures by copying objects from documents and connecting them. These procedures can be saved for future use. Figure 27 shows

Practical Strategies for Integrating Final Ecosystem Goods and Services into Community Decision-Making.

EPA Science Inventory

The concept of Final Ecosystem Goods and Services (FEGS) explicitly connects ecosystem services to the people that benefit from them. This report presents a number of practical strategies for incorporating FEGS, and more broadly ecosystem services, into the decision-making proces...

MODELING THE FORMATION OF SECONDARY ORGANIC AEROSOL WITHIN A COMPREHENSIVE AIR QUALITY MODEL SYSTEM

EPA Science Inventory

The aerosol component of the CMAQ model is designed to be an efficient and economical depiction of aerosol dynamics in the atmosphere. The approach taken represents the particle size distribution as the superposition of three lognormal subdistributions, called modes. The proces...

TEST RESULTS FOR FUEL CELL OPERATION ON ANAEROBIC DIGESTER GAS

EPA Science Inventory

EPA, in conjunction with ONSI Corp., embarked on a project to define, design, test, and assess a fuel cell energy recovery system for application at anaerobic digester waste water (sewage) treatment plants. Anaerobic digester gas (ADG) is produced at these plants during the proce...

Work zone impacts assessment : an approach to assess and management work zone safety and mobility impacts of road projects

DOT National Transportation Integrated Search

2006-05-01

To help transportation agencies understand and implement the provisions of the Rule, FHWA has : developed four guidance documents. This Guide is designed to help transportation agencies : develop and/or update their own policies, processes, and proce...

Analysis of Florida Department Of Transportation Transit Corridor Program/Projects: Technical Memorandum Number Three - General Recommendations

DOT National Transportation Integrated Search

2001-03-01

CUTR interviewed FDOT personnel at both the Central Office and Distict Offices and agency personnel to discuss the strengths and weaknesses of the overall Transit Corridor Program, including the results of specific projects, as well as the FDOT proce...

Leaves as composites of latent developmental and evolutionary shapes

USDA-ARS?s Scientific Manuscript database

Across plants, leaves exhibit profound diversity in shape. As a single leaf expands, its shape is in constant flux. Additionally, plants may also produce leaves with different shapes at successive nodes. Because leaf shape can vary in many different ways, theoretically the effects of distinct proces...

Drought and heat stress effects on soybean fatty acid composition and oil stability

USDA-ARS?s Scientific Manuscript database

Previous studies have shown that oil concentration and fatty acid profile (composition) change with genotype, environment (mainly heat and drought), and geographical location. The changes in fatty acid composition under these conditions affect fatty acid stability, creating a challenge to oil proces...

Development of a remote sensing network for time-sensitive detection of fine scale damage to transportation infrastructure : [final report].

DOT National Transportation Integrated Search

2015-09-23

This research project aimed to develop a remote sensing system capable of rapidly identifying fine-scale damage to critical transportation infrastructure following hazard events. Such a system must be pre-planned for rapid deployment, automate proces...

Pore size distribution calculation from 1H NMR signal and N2 adsorption-desorption techniques

NASA Astrophysics Data System (ADS)

Hassan, Jamal

2012-09-01

The pore size distribution (PSD) of nano-material MCM-41 is determined using two different approaches: N2 adsorption-desorption and 1H NMR signal of water confined in silica nano-pores of MCM-41. The first approach is based on the recently modified Kelvin equation [J.V. Rocha, D. Barrera, K. Sapag, Top. Catal. 54(2011) 121-134] which deals with the known underestimation in pore size distribution for the mesoporous materials such as MCM-41 by introducing a correction factor to the classical Kelvin equation. The second method employs the Gibbs-Thompson equation, using NMR, for melting point depression of liquid in confined geometries. The result shows that both approaches give similar pore size distribution to some extent, and also the NMR technique can be considered as an alternative direct method to obtain quantitative results especially for mesoporous materials. The pore diameter estimated for the nano-material used in this study was about 35 and 38 Å for the modified Kelvin and NMR methods respectively. A comparison between these methods and the classical Kelvin equation is also presented.

Fast acquisition of multidimensional NMR spectra of solids and mesophases using alternative sampling methods.

PubMed

Lesot, Philippe; Kazimierczuk, Krzysztof; Trébosc, Julien; Amoureux, Jean-Paul; Lafon, Olivier

2015-11-01

Unique information about the atom-level structure and dynamics of solids and mesophases can be obtained by the use of multidimensional nuclear magnetic resonance (NMR) experiments. Nevertheless, the acquisition of these experiments often requires long acquisition times. We review here alternative sampling methods, which have been proposed to circumvent this issue in the case of solids and mesophases. Compared to the spectra of solutions, those of solids and mesophases present some specificities because they usually display lower signal-to-noise ratios, non-Lorentzian line shapes, lower spectral resolutions and wider spectral widths. We highlight herein the advantages and limitations of these alternative sampling methods. A first route to accelerate the acquisition time of multidimensional NMR spectra consists in the use of sparse sampling schemes, such as truncated, radial or random sampling ones. These sparsely sampled datasets are generally processed by reconstruction methods differing from the Discrete Fourier Transform (DFT). A host of non-DFT methods have been applied for solids and mesophases, including the G-matrix Fourier transform, the linear least-square procedures, the covariance transform, the maximum entropy and the compressed sensing. A second class of alternative sampling consists in departing from the Jeener paradigm for multidimensional NMR experiments. These non-Jeener methods include Hadamard spectroscopy as well as spatial or orientational encoding of the evolution frequencies. The increasing number of high field NMR magnets and the development of techniques to enhance NMR sensitivity will contribute to widen the use of these alternative sampling methods for the study of solids and mesophases in the coming years. Copyright © 2015 John Wiley & Sons, Ltd.

Earth field NMR with chemical shift spectral resolution: theory and proof of concept.

PubMed

Katz, Itai; Shtirberg, Lazar; Shakour, Gubrail; Blank, Aharon

2012-06-01

A new method for obtaining an NMR signal in the Earth's magnetic field (EF) is presented. The method makes use of a simple pulse sequence with only DC fields which is much less demanding than previous approaches in terms of the pulses' rise and fall times. Furthermore, it offers the possibility of obtaining NMR data with enough spectral resolution to allow retrieving high resolution molecular chemical shift (CS) information - a capability that was not considered possible in EF NMR until now. Details of the pulse sequence, the experimental system, and our specially tailored EF NMR probe are provided. The experimental results demonstrate the capability to differentiate between three types of samples made of common fluorine compounds, based on their CS data. Copyright © 2012 Elsevier Inc. All rights reserved.

Detection of acoustic waves by NMR using a radiofrequency field gradient

NASA Astrophysics Data System (ADS)

Madelin, Guillaume; Baril, Nathalie; Lewa, Czeslaw J.; Franconi, Jean-Michel; Canioni, Paul; Thiaudiére, Eric; de Certaines, Jacques D.

2003-03-01

A B1 field gradient-based method previously described for the detection of mechanical vibrations has been applied to detect oscillatory motions in condensed matter originated from acoustic waves. A ladder-shaped coil generating a quasi-constant RF-field gradient was associated with a motion-encoding NMR sequence consisting in a repetitive binomial 1 3¯3 1¯ RF pulse train (stroboscopic acquisition). The NMR response of a gel phantom subject to acoustic wave excitation in the 20-200 Hz range was investigated. Results showed a linear relationship between the NMR signal and the wave amplitude and a spectroscopic selectivity of the NMR sequence with respect to the input acoustic frequency. Spin displacements as short as a few tens of nanometers were able to be detected with this method.

Detection of acoustic waves by NMR using a radiofrequency field gradient.

PubMed

Madelin, Guillaume; Baril, Nathalie; Lewa, Czeslaw J; Franconi, Jean Michel; Canioni, Paul; Thiaudiére, Eric; de Certaines, Jacques D

2003-03-01

A B(1) field gradient-based method previously described for the detection of mechanical vibrations has been applied to detect oscillatory motions in condensed matter originated from acoustic waves. A ladder-shaped coil generating a quasi-constant RF-field gradient was associated with a motion-encoding NMR sequence consisting in a repetitive binomial 13;31; RF pulse train (stroboscopic acquisition). The NMR response of a gel phantom subject to acoustic wave excitation in the 20-200 Hz range was investigated. Results showed a linear relationship between the NMR signal and the wave amplitude and a spectroscopic selectivity of the NMR sequence with respect to the input acoustic frequency. Spin displacements as short as a few tens of nanometers were able to be detected with this method.

Recent developments and applications of saturation transfer difference nuclear magnetic resonance (STD NMR) spectroscopy.

PubMed

Wagstaff, Jane L; Taylor, Samantha L; Howard, Mark J

2013-04-05

This review aims to illustrate that STD NMR is not simply a method for drug screening and discovery, but has qualitative and quantitative applications that can answer fundamental and applied biological and biomedical questions involving molecular interactions between ligands and proteins. We begin with a basic introduction to the technique of STD NMR and report on recent advances and biological applications of STD including studies to follow the interactions of non-steroidal anti-inflammatories, minimum binding requirements for virus infection and understating inhibition of amyloid fibre formation. We expand on this introduction by reporting recent STD NMR studies of live-cell receptor systems, new methodologies using scanning STD, magic-angle spinning STD and approaches to use STD NMR in a quantitative fashion for dissociation constants and group epitope mapping (GEM) determination. We finish by outlining new approaches that have potential to influence future applications of the technique; NMR isotope-editing, heteronuclear multidimensional STD and (19)F STD methods that are becoming more amenable due to the latest NMR equipment technologies.

Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of Protein-Ligand Contacts.

PubMed

Monaco, Serena; Tailford, Louise E; Juge, Nathalie; Angulo, Jesus

2017-11-27

Saturation transfer difference (STD) NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, thereby revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Herein, we report the development of the novel method differential epitope mapping by STD NMR (DEEP-STD NMR) for identifying the type of protein residues contacting the ligand. The method produces differential epitope maps through 1) differential frequency STD NMR and/or 2) differential solvent (D 2 O/H 2 O) STD NMR experiments. The two approaches provide different complementary information on the binding pocket. We demonstrate that DEEP-STD NMR can be used to readily obtain pharmacophore information on the protein. Furthermore, if the 3D structure of the protein is known, this information also helps in orienting the ligand in the binding pocket. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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.

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.

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.

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

PSYCHE Pure Shift NMR Spectroscopy.

PubMed

Foroozandeh, Mohammadali; Morris, Gareth; Nilsson, Mathias

2018-03-13

Broadband homodecoupling techniques in NMR, also known as "pure shift" methods, aim to enhance spectral resolution by suppressing the effects of homonuclear coupling interactions to turn multiplet signals into singlets. Such techniques typically work by selecting a subset of "active" nuclear spins to observe, and selectively inverting the remaining, "passive", spins to reverse the effects of coupling. Pure Shift Yielded by Chirp Excitation (PSYCHE) is one such method; it is relatively recent, but has already been successfully implemented in a range of different NMR experiments. Paradoxically, PSYCHE is one of the trickiest of pure shift NMR techniques to understand but one of the easiest to use. Here we offer some insights into theoretical and practical aspects of the method, and into the effects and importance of the experimental parameters. Some recent improvements that enhance the spectral purity of PSYCHE spectra will be presented, and some experimental frameworks including examples in 1D and 2D NMR spectroscopy, for the implementation of PSYCHE will be introduced. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Quick and Easy Simplification of Benzocaine's NMR Spectrum

NASA Astrophysics Data System (ADS)

Carpenter, Suzanne R.; Wallace, Richard H.

2006-04-01

The preparation of benzocaine is a common experiment used in sophomore-level organic chemistry. Its straightforward procedure and predictable good yields make it ideal for the beginning organic student. Analysis of the product via NMR spectroscopy, however, can be confusing to the novice interpreter. An inexpensive, quick, and effective method for simplifying the NMR spectrum is reported. The method results in a spectrum that is cleanly integrated and more easily interpreted.

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.

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.

CHARACTERIZATION OF EMISSIONS FROM THE SIMULATED OPEN-BURNING OF NON-METALLIC AUTOMOBILE SHREDDER RESIDUE

EPA Science Inventory

The report gives results of a study in which the open combustion of a nonmetallic waste product called "fluff" was simulated and the resulting emissions collected and characterized to gain insight into the types and quantities of these air pollutants. (NOTE: The reclamation proce...

Jane Jacobs and ‘The Need for Aged Buildings’: Neighbourhood Historical Development Pace and Community Social Relations

EPA Science Inventory

Jacobs argued that grand planning schemes intending to redevelop large swaths of a city according to a central theoretical framework fail because planners do not understand that healthy cities are organic, spontaneous, messy, complex systems that result from evolutionary proces...

Ruthenium on chitosan: A recyclable heterogeneous catalyst for aqueous hydration of nitriles to amides

EPA Science Inventory

Ruthenium has been immobilized over chitosan by simply stirring an aqueous suspension of chitosan in water with ruthenium chloride and has been utilized for the oxidation of nitriles to amides; the hydration of nitriles occurs in high yield and excellent selectivity, which procee...

NBS/EPA (NATIONAL BUREAU OF STANDARDS/ENVIRONMENTAL PROTECTION AGENCY) CERTIFIED REFERENCE MATERIAL PERFORMANCE AUDIT PROGRAM: STATUS REPORT 1

EPA Science Inventory

A traceability procedure has been established which allows specialty gas producers to prepare gaseous pollutant Certified Reference Materials (CRMs). The accuracy, stability and homogeneity of the CRMs approach those of NBS Standard Reference Materials (SRMs). Part of this proced...

49 CFR 611.101 - Purpose and contents.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Purpose and contents. 611.101 Section 611.101 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS General Provisions § 611.101 Purpose and contents. (a) This part prescribes the proces...

ENHANCED PRODUCTION OF CRYPTOSPORIDIUM PARVUM OOCYSTS IN IMMUNOSUPPRESSED MICE

EPA Science Inventory

Recently there has been an increase in the need for fresh C. parvum oocysts for engineering and biomedical research applications. In our laboratory the emphsis has shifted from the use of dairy calves to inbred C57BL/67n mice, primarily for reasons of ease of collection and proce...

COMMODITY SCALE SYNTHESIS OF 1-METHYLIMIDAZOLE BASED IONIC LIQUIDS USING A SPINNING TUBE-IN-TUBE REACTOR

EPA Science Inventory

The continuous large-scale preparation of several 1-methylimidazole based ionic liquids was carried out using a Spinning Tube-in-Tube (STT) reactor (manufactured by Kreido Laboratories). This reactor, which embodies and facilitates the use of Green Chemistry principles and Proce...

Detection of organic residues on poultry processing equipment surfaces by LED-induced fluorescence imaging

USDA-ARS?s Scientific Manuscript database

Organic residues on equipment surfaces in poultry processing plants can generate cross- contamination and increase the risk of unsafe food for consumers. This research was aimed to investigate the potential of LED-induced fluorescence imaging technique for rapid inspection of stainless steel proces...

Air Land Sea Bulletin

DTIC Science & Technology

2014-11-01

conducting multi-Service and joint force operations. Status: Current TACTICAL RADIOS Multi-Service Communications Procedures for Tactical Radios in a Joint...Techniques, and Proce- dures Package for Ultra High Frequency Military Satellite Communications Distribution Restricted 9 AUG 13 ATP 6-02.90 MCRP 3... Communicating within the Information Environment......................................................................30 IN HOUSE Current ALSA MTTP

Characterizing mercury concentrations and flux dynamics in a coastal plain watershed using multiple models and data

EPA Science Inventory

Mercury-related fish consumption advisories are widespread in the coastal plain of the southeastern U.S., where atmospherically deposited mercury interacts with an abundance of wetlands and high-dissolved organic carbon (DOC), acidic waters. Recent trends in decision making proce...

USING BAYESIAN SPATIAL MODELS TO FACILITATE WATER QUALITY MONITORING

EPA Science Inventory

The Clean Water Act of 1972 requires states to monitor the quality of their surface water. The number of sites sampled on streams and rivers varies widely by state. A few states are now using probability survey designs to select sites, while most continue to rely on other proce...

Botanical trash mixtures analyzed with near-infrared and attenuated total reflectance fourier transform spectroscopy and thermogravimetric analysis

USDA-ARS?s Scientific Manuscript database

Botanical cotton trash mixed with lint reduces cotton’s marketability and appearance. During cotton harvesting, ginning, and processing, trash size reduction occurs, thus complicating its removal and identification. This trash causes problems by increasing ends down in yarn formation and thus proce...

NMR-based investigations into target DNA search processes of proteins.

PubMed

Iwahara, Junji; Zandarashvili, Levani; Kemme, Catherine A; Esadze, Alexandre

2018-05-10

To perform their function, transcription factors and DNA-repair/modifying enzymes must first locate their targets in the vast presence of nonspecific, but structurally similar sites on genomic DNA. Before reaching their targets, these proteins stochastically scan DNA and dynamically move from one site to another on DNA. Solution NMR spectroscopy provides unique atomic-level insights into the dynamic DNA-scanning processes, which are difficult to gain by any other experimental means. In this review, we provide an introductory overview on the NMR methods for the structural, dynamic, and kinetic investigations of target DNA search by proteins. We also discuss advantages and disadvantages of these NMR methods over other methods such as single-molecule techniques and biochemical approaches. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Determination of Diethyl Phthalate and Polyhexamethylene Guanidine in Surrogate Alcohol from Russia

PubMed Central

Monakhova, Yulia B.; Kuballa, Thomas; Leitz, Jenny; Lachenmeier, Dirk W.

2011-01-01

Analytical methods based on spectroscopic techniques were developed and validated for the determination of diethyl phthalate (DEP) and polyhexamethylene guanidine (PHMG), which may occur in unrecorded alcohol. Analysis for PHMG was based on UV-VIS spectrophotometry after derivatization with Eosin Y and 1H NMR spectroscopy of the DMSO extract. Analysis of DEP was performed with direct UV-VIS and 1H NMR methods. Multivariate curve resolution and spectra computation methods were used to confirm the presence of PHMG and DEP in the investigated beverages. Of 22 analysed alcohol samples, two contained DEP or PHMG. 1H NMR analysis also revealed the presence of signals of hawthorn extract in three medicinal alcohols used as surrogate alcohol. The simple and cheap UV-VIS methods can be used for rapid screening of surrogate alcohol samples for impurities, while 1H NMR is recommended for specific confirmatory analysis if required. PMID:21647285

Determination of diethyl phthalate and polyhexamethylene guanidine in surrogate alcohol from Russia.

PubMed

Monakhova, Yulia B; Kuballa, Thomas; Leitz, Jenny; Lachenmeier, Dirk W

2011-01-01

Analytical methods based on spectroscopic techniques were developed and validated for the determination of diethyl phthalate (DEP) and polyhexamethylene guanidine (PHMG), which may occur in unrecorded alcohol. Analysis for PHMG was based on UV-VIS spectrophotometry after derivatization with Eosin Y and (1)H NMR spectroscopy of the DMSO extract. Analysis of DEP was performed with direct UV-VIS and (1)H NMR methods. Multivariate curve resolution and spectra computation methods were used to confirm the presence of PHMG and DEP in the investigated beverages. Of 22 analysed alcohol samples, two contained DEP or PHMG. (1)H NMR analysis also revealed the presence of signals of hawthorn extract in three medicinal alcohols used as surrogate alcohol. The simple and cheap UV-VIS methods can be used for rapid screening of surrogate alcohol samples for impurities, while (1)H NMR is recommended for specific confirmatory analysis if required.

High-pressure autoclave for multipurpose nuclear magnetic resonance measurements up to 10 MPa

NASA Astrophysics Data System (ADS)

Behr, W.; Haase, A.; Reichenauer, G.; Fricke, J.

1999-05-01

High-pressure nuclear magnetic resonance (NMR) is an established method in NMR spectroscopy: on-line coupling of high-performance liquid chromatography with NMR, for example, reveals structural information which cannot be obtained with any other method. However, applications has been focused solely on high-pressure NMR spectroscopy, even though high-pressure NMR imaging allows in situ studies of processes such as the fluid exchange in porous media. A versatile high-pressure autoclave for NMR imaging is described in this article. The autoclave allows measurements in any horizontal NMR imager using magnetic field coil systems with an inside diameter of more than 70 mm. Any sample with a diameter up to 28 mm and a length of about 200 mm can be investigated. The autoclave is constructed for operating pressures up to 10 MPa and is temperature controlled between 10 and 60 °C. The materials of the high-pressure cell which are the thermoplastic polyetheretherketon (PEEK) for the pressure tube and brass (63% Cu, 37% Zn) for the caps also permit investigations with aggressive fluids such as supercritical carbon dioxide. Inlet and outlet valves allow replacement of fluids and pressure variations in the autoclave during the NMR measurement. FLASH NMR images of the fluid exchange of methanol for liquid carbon dioxide in silica alcogels at 6.5 MPa are presented in order to demonstrate possible applications.

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…

Single-Scan Multidimensional NMR Analysis of Mixtures at Sub-Millimolar Concentrations by using SABRE Hyperpolarization.

PubMed

Daniele, Valeria; Legrand, François-Xavier; Berthault, Patrick; Dumez, Jean-Nicolas; Huber, Gaspard

2015-11-16

Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE-enhanced (1)H NMR signals are short lived, and SABRE is often used to record 1D NMR spectra only. When the sample of interest is a complex mixture, this results in severe overlaps for (1)H spectra. In addition, the use of a co-substrate, whose signals may obscure the (1) H spectra, is currently the most efficient way to lower the detection limit of SABRE experiments. Here, we describe an approach to obtain clean, SABRE-hyperpolarized 2D (1)H NMR spectra of mixtures of small molecules at sub-millimolar concentrations in a single scan. The method relies on the use of para-hydrogen together with a deuterated co-substrate for hyperpolarization and ultrafast 2D NMR for acquisition. It is applicable to all substrates that can be polarized with SABRE. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

PubMed

Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

2008-02-01

We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

Ultra-low field nuclear magnetic resonance and magnetic resonance imaging to discriminate and identify materials

DOEpatents

Matlashov, Andrei Nikolaevich; Urbaitis, Algis V.; Savukov, Igor Mykhaylovich; Espy, Michelle A.; Volegov, Petr Lvovich; Kraus, Jr., Robert Henry

2013-03-05

Method comprising obtaining an NMR measurement from a sample wherein an ultra-low field NMR system probes the sample and produces the NMR measurement and wherein a sampling temperature, prepolarizing field, and measurement field are known; detecting the NMR measurement by means of inductive coils; analyzing the NMR measurement to obtain at least one measurement feature wherein the measurement feature comprises T1, T2, T1.rho., or the frequency dependence thereof; and, searching for the at least one measurement feature within a database comprising NMR reference data for at least one material to determine if the sample comprises a material of interest.

Determination of NMR chemical shifts for cholesterol crystals from first-principles

NASA Astrophysics Data System (ADS)

Kucukbenli, Emine; de Gironcoli, Stefano

2011-03-01

Solid State Nuclear Magnetic Resonance (NMR) is a powerful tool in crystallography when combined with theoretical predictions. So far, empirical calculations of spectra have been employed for an unambiguous identification. However, many complex systems are outside the scope of these methods. Our implementation of ultrasoft and projector augmented wave pseudopotentials within ab initio gauge including projector augmented plane wave (GIPAW) method in Quantum Espresso simulation package allows affordable calculations of NMR spectra for systems of thousands of electrons. We report here the first ab initio determination of NMR spectra for several crystal structures of cholesterol. Cholesterol crystals, the main component of human gallstones, are of interest to medical research as their structural properties can shed light on the pathologies of gallbladder. With our application we show that ab initio calculations can be employed to aid NMR crystallography.

Anatomising proton NMR spectra with pure shift 2D J-spectroscopy: A cautionary tale

NASA Astrophysics Data System (ADS)

Kiraly, Peter; Foroozandeh, Mohammadali; Nilsson, Mathias; Morris, Gareth A.

2017-09-01

Analysis of proton NMR spectra has been a key tool in structure determination for over 60 years. A classic tool is 2D J-spectroscopy, but common problems are the difficulty of obtaining the absorption mode lineshapes needed for accurate results, and the need for a 45° shear of the final 2D spectrum. A novel 2D NMR method is reported here that allows straightforward determination of homonuclear couplings, using a modified version of the PSYCHE method to suppress couplings in the direct dimension. The method illustrates the need for care when combining pure shift data acquisition with multiple pulse methods.

Direct quantification of molar masses of copolymers by online liquid chromatography under critical conditions-nuclear magnetic resonance and size exclusion chromatography-nuclear magnetic resonance.

PubMed

Hehn, Mathias; Wagner, Thomas; Hiller, Wolf

2014-01-07

Online LCCC-NMR and SEC-NMR are compared regarding the determination of molar masses of block copolymers. Two different direct referencing methods are particularly demonstrated in LCCC-NMR for a detailed characterization of diblock copolymers and their co-monomers. First, an intramolecular reference group was used for the direct determination of block lengths and molar masses. For the first time, it was shown that LCCC-NMR can be used for an accurate determination of Mw and Mn of copolymers. These data were in perfect agreement with SEC-NMR measurements using the same intramolecular referencing method. In contrast, the determination of molar masses with common relative methods based on calibrations with homopolymers delivered inaccurate results for all investigated diblock copolymers due to different hydrodynamic volumes of the diblock copolymer compared to their homopolymers. The intramolecular referencing method provided detailed insights in the co-monomer behavior during the chromatographic separation of LCCC. Especially, accurate chain lengths and chemical compositions of the "invisible" and "visible" blocks were quantified during the elution under critical conditions and provided new aspects to the concept of critical conditions. Second, an external reference NMR signal was used to directly determine concentrations and molar masses of the block copolymers from the chromatographic elution profile. Consequently, the intensity axes of the resulting chromatograms were converted to molar amounts and masses, allowing for determination of the amount of polymer chains with respect to elution volume, the evaluation of the limiting magnitude of concentration for LCCC-NMR, and determination of the molar masses of copolymers.

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.

Magic Angle Spinning NMR Metabolomics

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

Zhi Hu, Jian

Nuclear Magnetic Resonance (NMR) spectroscopy is a non-destructive, quantitative, reproducible, untargeted and unbiased method that requires no or minimal sample preparation, and is one of the leading analytical tools for metabonomics research [1-3]. The easy quantification and the no need of prior knowledge about compounds present in a sample associated with NMR are advantageous over other techniques [1,4]. 1H NMR is especially attractive because protons are present in virtually all metabolites and its NMR sensitivity is high, enabling the simultaneous identification and monitoring of a wide range of low molecular weight metabolites.

Apparatus and method for generating a magnetic field by rotation of a charge holding object

DOEpatents

Gerald, II, Rex E.; Vukovic, Lela [Westchester, IL; Rathke, Jerome W [Homer Glenn, IL

2009-10-13

A device and a method for the production of a magnetic field using a Charge Holding Object that is mechanically rotated. In a preferred embodiment, a Charge Holding Object surrounding a sample rotates and subjects the sample to one or more magnetic fields. The one or more magnetic fields are used by NMR Electronics connected to an NMR Conductor positioned within the Charge Holding Object to perform NMR analysis of the sample.

On-line high-performance liquid chromatography-ultraviolet-nuclear magnetic resonance method of the markers of nerve agents for verification of the Chemical Weapons Convention.

PubMed

Mazumder, Avik; Gupta, Hemendra K; Garg, Prabhat; Jain, Rajeev; Dubey, Devendra K

2009-07-03

This paper details an on-flow liquid chromatography-ultraviolet-nuclear magnetic resonance (LC-UV-NMR) method for the retrospective detection and identification of alkyl alkylphosphonic acids (AAPAs) and alkylphosphonic acids (APAs), the markers of the toxic nerve agents for verification of the Chemical Weapons Convention (CWC). Initially, the LC-UV-NMR parameters were optimized for benzyl derivatives of the APAs and AAPAs. The optimized parameters include stationary phase C(18), mobile phase methanol:water 78:22 (v/v), UV detection at 268nm and (1)H NMR acquisition conditions. The protocol described herein allowed the detection of analytes through acquisition of high quality NMR spectra from the aqueous solution of the APAs and AAPAs with high concentrations of interfering background chemicals which have been removed by preceding sample preparation. The reported standard deviation for the quantification is related to the UV detector which showed relative standard deviations (RSDs) for quantification within +/-1.1%, while lower limit of detection upto 16mug (in mug absolute) for the NMR detector. Finally the developed LC-UV-NMR method was applied to identify the APAs and AAPAs in real water samples, consequent to solid phase extraction and derivatization. The method is fast (total experiment time approximately 2h), sensitive, rugged and efficient.

Quantification of taurine in energy drinks using ¹H NMR.

PubMed

Hohmann, Monika; Felbinger, Christine; Christoph, Norbert; Wachter, Helmut; Wiest, Johannes; Holzgrabe, Ulrike

2014-05-01

The consumption of so called energy drinks is increasing, especially among adolescents. These beverages commonly contain considerable amounts of the amino sulfonic acid taurine, which is related to a magnitude of various physiological effects. The customary method to control the legal limit of taurine in energy drinks is LC-UV/vis with postcolumn derivatization using ninhydrin. In this paper we describe the quantification of taurine in energy drinks by (1)H NMR as an alternative to existing methods of quantification. Variation of pH values revealed the separation of a distinct taurine signal in (1)H NMR spectra, which was applied for integration and quantification. Quantification was performed using external calibration (R(2)>0.9999; linearity verified by Mandel's fitting test with a 95% confidence level) and PULCON. Taurine concentrations in 20 different energy drinks were analyzed by both using (1)H NMR and LC-UV/vis. The deviation between (1)H NMR and LC-UV/vis results was always below the expanded measurement uncertainty of 12.2% for the LC-UV/vis method (95% confidence level) and at worst 10.4%. Due to the high accordance to LC-UV/vis data and adequate recovery rates (ranging between 97.1% and 108.2%), (1)H NMR measurement presents a suitable method to quantify taurine in energy drinks. Copyright © 2013 Elsevier B.V. All rights reserved.

BOOK REVIEW: NMR Imaging of Materials

NASA Astrophysics Data System (ADS)

Blümich, Bernhard

2003-09-01

Magnetic resonance imaging (MRI) of materials is a field of increasing importance. Applications extend from fundamental science like the characterization of fluid transport in porous rock, catalyst pellets and hemodialysers into various fields of engineering for process optimization and product quality control. While the results of MRI imaging are being appreciated by a growing community, the methods of imaging are far more diverse for materials applications than for medical imaging of human beings. Blümich has delivered the first book in this field. It was published in hardback three years ago and is now offered as a paperback for nearly half the price. The text provides an introduction to MRI imaging of materials covering solid-state NMR spectroscopy, imaging methods for liquid and solid samples, and unusual MRI in terms of specialized approaches to spatial resolution such as an MRI surface scanner. The book represents an excellent and thorough treatment which will help to grow research in materials MRI. Blümich developed the treatise over many years for his research students, graduates in chemistry, physics and engineering. But it may also be useful for medical students looking for a less formal discussion of solid-state NMR spectroscopy. The structure of this book is easy to perceive. The first three chapters cover an introduction, the fundamentals and methods of solid-state NMR spectroscopy. The book starts at the ground level where no previous knowledge about NMR is assumed. Chapter 4 discusses a wide variety of transformations beyond the Fourier transformation. In particular, the Hadamard transformation and the 'wavelet' transformation are missing from most related books. This chapter also includes a description of noise-correlation spectroscopy, which promises the imaging of large objects without the need for extremely powerful radio-frequency transmitters. Chapters 5 and 6 cover basic imaging methods. The following chapter about the use of relaxation and spectroscopic methods to weight or filter the spin signals represents the core of the book. This is a subject where Blümich is deeply involved with substantial contributions. The chapter includes a lot of ideas to provide MR contrast between different regions based on their mobility, diffusion, spin couplings or NMR spectra. After describing NMR imaging methods for solids with broad lines, Blümich spends time on applications in the last two chapters of the book. This part is really fun to read. It underlines the effort to bring NMR into many kinds of manufacturing. Car tyres and high-voltage cables are just two such areas. Elastomeric materials, green-state ceramics and food science represent other interesting fields of applications. This part of the book represents a personal but nevertheless extensive compilation of modern applications. As a matter of course the MOUSE is presented, a portable permanent-magnet based NMR developed by Blümich and his co-workers. Thus the book is not only of interest to NMR spectroscopists but also to people in material science and chemical engineering. The bibliography and indexing are excellent and may serve as an attractive reference source for NMR spectroscopists. The book is the first on the subject and likely to become the standard text for NMR imaging of materials as the books by Abragam, Slicher and Ernst et al are for NMR spectroscopy. The purchase of this beautiful book for people dealing with NMR spectroscopy or medical MRI is highly recommended. Ralf Ludwig

Refinement of NMR structures using implicit solvent and advanced sampling techniques.

PubMed

Chen, Jianhan; Im, Wonpil; Brooks, Charles L

2004-12-15

NMR biomolecular structure calculations exploit simulated annealing methods for conformational sampling and require a relatively high level of redundancy in the experimental restraints to determine quality three-dimensional structures. Recent advances in generalized Born (GB) implicit solvent models should make it possible to combine information from both experimental measurements and accurate empirical force fields to improve the quality of NMR-derived structures. In this paper, we study the influence of implicit solvent on the refinement of protein NMR structures and identify an optimal protocol of utilizing these improved force fields. To do so, we carry out structure refinement experiments for model proteins with published NMR structures using full NMR restraints and subsets of them. We also investigate the application of advanced sampling techniques to NMR structure refinement. Similar to the observations of Xia et al. (J.Biomol. NMR 2002, 22, 317-331), we find that the impact of implicit solvent is rather small when there is a sufficient number of experimental restraints (such as in the final stage of NMR structure determination), whether implicit solvent is used throughout the calculation or only in the final refinement step. The application of advanced sampling techniques also seems to have minimal impact in this case. However, when the experimental data are limited, we demonstrate that refinement with implicit solvent can substantially improve the quality of the structures. In particular, when combined with an advanced sampling technique, the replica exchange (REX) method, near-native structures can be rapidly moved toward the native basin. The REX method provides both enhanced sampling and automatic selection of the most native-like (lowest energy) structures. An optimal protocol based on our studies first generates an ensemble of initial structures that maximally satisfy the available experimental data with conventional NMR software using a simplified force field and then refines these structures with implicit solvent using the REX method. We systematically examine the reliability and efficacy of this protocol using four proteins of various sizes ranging from the 56-residue B1 domain of Streptococcal protein G to the 370-residue Maltose-binding protein. Significant improvement in the structures was observed in all cases when refinement was based on low-redundancy restraint data. The proposed protocol is anticipated to be particularly useful in early stages of NMR structure determination where a reliable estimate of the native fold from limited data can significantly expedite the overall process. This refinement procedure is also expected to be useful when redundant experimental data are not readily available, such as for large multidomain biomolecules and in solid-state NMR structure determination.

Modern NMR Spectroscopy.

ERIC Educational Resources Information Center

Jelinski, Lynn W.

1984-01-01

Discusses direct chemical information that can be obtained from modern nuclear magnetic resonance (NMR) methods, concentrating on the types of problems that can be solved. Shows how selected methods provide information about polymers, bipolymers, biochemistry, small organic molecules, inorganic compounds, and compounds oriented in a magnetic…

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.

Ensemble of single quadrupolar nuclei in rotating solids: sidebands in NMR spectrum.

PubMed

Kundla, Enn

2006-07-01

A novel way is proposed to describe the evolution of nuclear magnetic polarization and the induced NMR spectrum. In this method, the effect of a high-intensity external static magnetic field and the effects of proper Hamiltonian left over interaction components, which commute with the first, are taken into account simultaneously and equivalently. The method suits any concrete NMR problem. This brings forth the really existing details in the registered spectra, evoked by Hamiltonian secular terms, which may be otherwise smoothed due to approximate treatment of the effects of the secular terms. Complete analytical expressions are obtained describing the NMR spectra including the rotational sideband sets of single quadrupolar nuclei in rotating solids.

Solution state NMR of lignins

Treesearch

John Ralph; Jane M. Marita; Sally A. Ralph; Ronald D. Hatfield; Fachuang Lu; Richard M. Ede; Junpeng Peng; Larry L. Landucci

1999-01-01

Despite the rather random and heterogeneous nature of isolated lignins, many of their intimate structural details are revealed by diagnostic NMR experiments. 13C-NMR was recognized early-on as a high-resolution method for detailed structural characterization, aided by the almost exact agreement between chemical shifts of carbons in good low-molecular...

Using Cloud Storage for NMR Data Distribution

ERIC Educational Resources Information Center

Soulsby, David

2012-01-01

An approach using Google Groups as method for distributing student-acquired NMR data has been implemented. We describe how to configure NMR spectrometer software so that data is uploaded to a laboratory section specific Google Group, thereby removing bottlenecks associated with printing and processing at the spectrometer workstation. Outside of…

NMR Spectroscopy and Its Value: A Primer

ERIC Educational Resources Information Center

Veeraraghavan, Sudha

2008-01-01

Nuclear magnetic resonance (NMR) spectroscopy is widely used by chemists. Furthermore, the use of NMR spectroscopy to solve structures of macromolecules or to examine protein-ligand interactions is popular. Yet, few students entering graduate education in biological sciences have been introduced to this method or its utility. Over the last six…

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. ...

Probe for high resolution NMR with sample reorientation

DOEpatents

Pines, Alexander; Samoson, Ago

1990-01-01

An improved NMR probe and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise orientationally disordered samples. The apparatus mechanically varies the orientation of the sample such that the time average of two or more sets of spherical harmonic functions are zero.

The application of NMR and MS methods for detection of adulteration of wine, fruit juices, and olive oil. A review.

PubMed

Ogrinc, N; Kosir, I J; Spangenberg, J E; Kidric, J

2003-06-01

This review covers two important techniques, high resolution nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), used to characterize food products and detect possible adulteration of wine, fruit juices, and olive oil, all important products of the Mediterranean Basin. Emphasis is placed on the complementary use of SNIF-NMR (site-specific natural isotopic fractionation nuclear magnetic resonance) and IRMS (isotope-ratio mass spectrometry) in association with chemometric methods for detecting the adulteration.

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.

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.

Bayesian Peak Picking for NMR Spectra

PubMed Central

Cheng, Yichen; Gao, Xin; Liang, Faming

2013-01-01

Protein structure determination is a very important topic in structural genomics, which helps people to understand varieties of biological functions such as protein-protein interactions, protein–DNA interactions and so on. Nowadays, nuclear magnetic resonance (NMR) has often been used to determine the three-dimensional structures of protein in vivo. This study aims to automate the peak picking step, the most important and tricky step in NMR structure determination. We propose to model the NMR spectrum by a mixture of bivariate Gaussian densities and use the stochastic approximation Monte Carlo algorithm as the computational tool to solve the problem. Under the Bayesian framework, the peak picking problem is casted as a variable selection problem. The proposed method can automatically distinguish true peaks from false ones without preprocessing the data. To the best of our knowledge, this is the first effort in the literature that tackles the peak picking problem for NMR spectrum data using Bayesian method. PMID:24184964

Facilitated assignment of large protein NMR signals with covariance sequential spectra using spectral derivatives.

PubMed

Harden, Bradley J; Nichols, Scott R; Frueh, Dominique P

2014-09-24

Nuclear magnetic resonance (NMR) studies of larger proteins are hampered by difficulties in assigning NMR resonances. Human intervention is typically required to identify NMR signals in 3D spectra, and subsequent procedures depend on the accuracy of this so-called peak picking. We present a method that provides sequential connectivities through correlation maps constructed with covariance NMR, bypassing the need for preliminary peak picking. We introduce two novel techniques to minimize false correlations and merge the information from all original 3D spectra. First, we take spectral derivatives prior to performing covariance to emphasize coincident peak maxima. Second, we multiply covariance maps calculated with different 3D spectra to destroy erroneous sequential correlations. The maps are easy to use and can readily be generated from conventional triple-resonance experiments. Advantages of the method are demonstrated on a 37 kDa nonribosomal peptide synthetase domain subject to spectral overlap.

NMR-based diffusion pore imaging by double wave vector measurements.

PubMed

Kuder, Tristan Anselm; Laun, Frederik Bernd

2013-09-01

One main interest of nuclear magnetic resonance (NMR) diffusion experiments is the investigation of boundaries such as cell membranes hindering the diffusion process. NMR diffusion measurements allow collecting the signal from the whole sample. This mainly eliminates the problem of vanishing signal at increasing resolution. It has been a longstanding question if, in principle, the exact shape of closed pores can be determined by NMR diffusion measurements. In this work, we present a method using short diffusion gradient pulses only, which is able to reveal the shape of arbitrary closed pores without relying on a priori knowledge. In comparison to former approaches, the method has reduced demands on relaxation times due to faster convergence to the diffusion long-time limit and allows for a more flexible NMR sequence design, because, e.g., stimulated echoes can be used. Copyright © 2012 Wiley Periodicals, Inc.

Establishing resolution-improved NMR spectroscopy in high magnetic fields with unknown spatiotemporal variations

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

Zhang, Zhiyong; Cai, Shuhui; Zheng, Zhenyao

A half-century quest for higher magnetic fields has been an integral part of the progress undergone in the Nuclear Magnetic Resonance (NMR) study of materials’ structure and dynamics. Because 2D NMR relies on systematic changes in coherences’ phases as a function of an encoding time varied over a series of independent experiments, it generally cannot be applied in temporally unstable fields. This precludes most NMR methods from being used to characterize samples situated in hybrid or resistive magnets that are capable of achieving extremely high magnetic field strength. Recently, “ultrafast” NMR has been developed into an effective and widely applicablemore » methodology enabling the acquisition of a multidimensional NMR spectrum in a single scan; it can therefore be used to partially mitigate the effects of temporally varying magnetic fields. Nevertheless, the strong interference of fluctuating fields with the spatial encoding of ultrafast NMR still severely restricts measurement sensitivity and resolution. Here, we introduce a strategy for obtaining high resolution NMR spectra that exploits the immunity of intermolecular zero-quantum coherences (iZQCs) to field instabilities and inhomogeneities. The spatial encoding of iZQCs is combined with a J-modulated detection scheme that removes the influence of arbitrary field inhomogeneities during acquisition. This new method can acquire high-resolution one-dimensional NMR spectra in large inhomogeneous and fluctuating fields, and it is tested with fields experimentally modeled to mimic those of resistive and resistive-superconducting hybrid magnets.« less

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

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.

Prediction of recrystallization behavior of troglitazone/polyvinylpyrrolidone solid dispersion by solid-state NMR.

PubMed

Ito, Atsutoshi; Watanabe, Tomoyuki; Yada, Shuichi; Hamaura, Takeshi; Nakagami, Hiroaki; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2010-01-04

The purpose of this study was to elaborate the relationship between the (13)C CP/MAS NMR spectra and the recrystallization behavior during the storage of troglitazone solid dispersions. The solid dispersions were prepared by either the solvent method or by co-grinding. The recrystallization behavior under storage conditions at 40 degrees C/94% RH was evaluated by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. Solid dispersions prepared by the solvent method or by prolonged grinding brought about inhibition of the nucleation and the nuclei growth at the same time. No differences in the PXRD profiles were found in the samples prepared by the co-grinding and solvent methods, however, (13)C CP/MAS NMR showed significant differences in the spectra. The correlation coefficients using partial least square regression analysis between the PXRD profiles and the apparent nuclei-growth constant or induction period to nucleation were 0.1305 or 0.6350, respectively. In contrast, those between the (13)C CP/MAS NMR spectra and the constant or the period were 0.9916 or 0.9838, respectively. The (13)C CP/MAS NMR spectra had good correlation with the recrystallization kinetic parameters evaluated by the KJMA equation. Consequently, solid-state NMR was judged to be a useful tool for the prediction of the recrystallization behavior of solid dispersions.

Reflection in Education: A Kantian Epistemology

ERIC Educational Resources Information Center

Procee, Henk

2006-01-01

As even its defenders admit, reflection in education suffers from a lack of conceptual clarity. In this essay, Henk Procee provides a philosophical analysis of the central concepts in this domain. In the current literature, these concepts are usually taken from the pragmatic school of John Dewey and from critical social theory associated with…

A loop-mediated isothermal amplification assay and sample preparation procedure for sensitive detection of Xanthomonas fragariae in strawberry

USDA-ARS?s Scientific Manuscript database

Xanthomonas fragariae is a bacterium that causes angular leaf spot of strawberry. Asymptomatic infections are common and contribute to the difficulties in disease management. The aim of this study was to develop a loop-mediated isothermal amplification (LAMP) assay with a bacterial enrichment proced...

Coupling Computer-Aided Process Simulation and Estimations of Emissions and Land Use for Rapid Life Cycle Inventory Modeling

EPA Science Inventory

A methodology is described for developing a gate-to-gate life cycle inventory (LCI) of a chemical manufacturing process to support the application of life cycle assessment in the design and regulation of sustainable chemicals. The inventories were derived by first applying proces...

IRIS Toxicological Review of cis- & trans-1,2-Dichloroethylene (Interagency Science Discussion Draft)

EPA Science Inventory

EPA is releasing the draft report, Toxicological Review of cis-1,2-Dichloroethylene and trans-1,2-Dichloroethylene, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the Effect of toll-like receptor activation on thymosin beta-4 production by chicken macrophages

USDA-ARS?s Scientific Manuscript database

Thymosin beta 4 (Tb4) is an actin binding intracellular peptide that promotes wound healing, tissue remodeling, and angiogenesis. The regulation of Tb4 secretion to the extracellular environment is not understood. The macrophage is a rich source of Tb4 which also participates in wound healing proce...

Organogels of vegetable oil with plant wax – trans/saturated fat replacements

USDA-ARS?s Scientific Manuscript database

This featured article reviews recent advances on the development of trans fat-free, low saturated fat food products from organogels formed by a plant wax in a vegetable oil. Plant waxes are of great interest in this research area because they are obtained as by-products during the oil refining proce...

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.

Segmental Isotopic Labeling of Proteins for Nuclear Magnetic Resonance

PubMed Central

Dongsheng, Liu; Xu, Rong; Cowburn, David

2009-01-01

Nuclear Magnetic Resonance (NMR) spectroscopy has emerged as one of the principle techniques of structural biology. It is not only a powerful method for elucidating the 3D structures under near physiological conditions, but also a convenient method for studying protein-ligand interactions and protein dynamics. A major drawback of macromolecular NMR is its size limitation caused by slower tumbling rates and greater complexity of the spectra as size increases. Segmental isotopic labeling allows specific segment(s) within a protein to be selectively examined by NMR thus significantly reducing the spectral complexity for large proteins and allowing a variety of solution-based NMR strategies to be applied. Two related approaches are generally used in the segmental isotopic labeling of proteins: expressed protein ligation and protein trans-splicing. Here we describe the methodology and recent application of expressed protein ligation and protein trans-splicing for NMR structural studies of proteins and protein complexes. We also describe the protocol used in our lab for the segmental isotopic labeling of a 50 kDa protein Csk (C-terminal Src Kinase) using expressed protein ligation methods. PMID:19632474

Nuclear magnetic resonance, vibrational spectroscopic studies, physico-chemical properties and computational calculations on (nitrophenyl) octahydroquinolindiones by DFT method.

PubMed

Pasha, M A; Siddekha, Aisha; Mishra, Soni; Azzam, Sadeq Hamood Saleh; Umapathy, S

2015-02-05

In the present study, 2'-nitrophenyloctahydroquinolinedione and its 3'-nitrophenyl isomer were synthesized and characterized by FT-IR, FT-Raman, (1)H NMR and (13)C NMR spectroscopy. The molecular geometry, vibrational frequencies, (1)H and (13)C NMR chemical shift values of the synthesized compounds in the ground state have been calculated by using the density functional theory (DFT) method with the 6-311++G (d,p) basis set and compared with the experimental data. The complete vibrational assignments of wave numbers were made on the basis of potential energy distribution using GAR2PED programme. Isotropic chemical shifts for (1)H and (13)C NMR were calculated using gauge-invariant atomic orbital (GIAO) method. The experimental vibrational frequencies, (1)H and (13)C NMR chemical shift values were found to be in good agreement with the theoretical values. On the basis of vibrational analysis, molecular electrostatic potential and the standard thermodynamic functions have been investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Neuronal current detection with low-field magnetic resonance: simulations and methods.

PubMed

Cassará, Antonino Mario; Maraviglia, Bruno; Hartwig, Stefan; Trahms, Lutz; Burghoff, Martin

2009-10-01

The noninvasive detection of neuronal currents in active brain networks [or direct neuronal imaging (DNI)] by means of nuclear magnetic resonance (NMR) remains a scientific challenge. Many different attempts using NMR scanners with magnetic fields >1 T (high-field NMR) have been made in the past years to detect phase shifts or magnitude changes in the NMR signals. However, the many physiological (i.e., the contemporarily BOLD effect, the weakness of the neuronal-induced magnetic field, etc.) and technical limitations (e.g., the spatial resolution) in observing the weak signals have led to some contradicting results. In contrast, only a few attempts have been made using low-field NMR techniques. As such, this paper was aimed at reviewing two recent developments in this front. The detection schemes discussed in this manuscript, the resonant mechanism (RM) and the DC method, are specific to NMR instrumentations with main fields below the earth magnetic field (50 microT), while some even below a few microteslas (ULF-NMR). However, the experimental validation for both techniques, with differentiating sensitivity to the various neuronal activities at specific temporal and spatial resolutions, is still in progress and requires carefully designed magnetic field sensor technology. Additional care should be taken to ensure a stringent magnetic shield from the ambient magnetic field fluctuations. In this review, we discuss the characteristics and prospect of these two methods in detecting neuronal currents, along with the technical requirements on the instrumentation.

(1)H nuclear magnetic resonance (NMR) as a tool to measure dehydration in mice.

PubMed

Li, Matthew; Vassiliou, Christophoros C; Colucci, Lina A; Cima, Michael J

2015-08-01

Dehydration is a prevalent pathology, where loss of bodily water can result in variable symptoms. Symptoms can range from simple thirst to dire scenarios involving loss of consciousness. Clinical methods exist that assess dehydration from qualitative weight changes to more quantitative osmolality measurements. These methods are imprecise, invasive, and/or easily confounded, despite being practiced clinically. We investigate a non-invasive, non-imaging (1)H NMR method of assessing dehydration that attempts to address issues with existing clinical methods. Dehydration was achieved by exposing mice (n = 16) to a thermally elevated environment (37 °C) for up to 7.5 h (0.11-13% weight loss). Whole body NMR measurements were made using a Bruker LF50 BCA-Analyzer before and after dehydration. Physical lean tissue, adipose, and free water compartment approximations had NMR values extracted from relaxation data through a multi-exponential fitting method. Changes in before/after NMR values were compared with clinically practiced metrics of weight loss (percent dehydration) as well as blood and urine osmolality. A linear correlation between tissue relaxometry and both animal percent dehydration and urine osmolality was observed in lean tissue, but not adipose or free fluids. Calculated R(2) values for percent dehydration were 0.8619 (lean, P < 0.0001), 0.5609 (adipose, P = 0.0008), and 0.0644 (free fluids, P = 0.3445). R(2) values for urine osmolality were 0.7760 (lean, P < 0.0001), 0.5005 (adipose, P = 0.0022), and 0.0568 (free fluids, P = 0.3739). These results suggest that non-imaging (1)H NMR methods are capable of non-invasively assessing dehydration in live animals. Copyright © 2015 John Wiley & Sons, Ltd.

Indirect detection in solid state NMR: An illustrious history and a bright future

NASA Astrophysics Data System (ADS)

Tycko, Robert

2018-03-01

Many of us have a love/hate relationship with nuclear magnetic resonance (NMR). We love the information content of NMR data, which provides us with essential information about structure, dynamics, and material properties that is not available from any other measurement, and we love the fact that NMR methods can be applied to almost any problem in almost any area of science. But we hate the low sensitivity of NMR, which forces us to make big samples, spend many tedious hours or days taking data, or live with marginal signal-to-noise.

Relationship between pore geometric characteristics and SIP/NMR parameters observed for mudstones

NASA Astrophysics Data System (ADS)

Robinson, J.; Slater, L. D.; Keating, K.; Parker, B. L.; Robinson, T.

2017-12-01

The reliable estimation of permeability remains one of the most challenging problems in hydrogeological characterization. Cost effective, non-invasive geophysical methods such as spectral induced polarization (SIP) and nuclear magnetic resonance (NMR) offer an alternative to traditional sampling methods as they are sensitive to the mineral surfaces and pore spaces that control permeability. We performed extensive physical characterization, SIP and NMR geophysical measurements on fractured rock cores extracted from a mudstone site in an effort to compare 1) the pore size characterization determined from traditional and geophysical methods and 2) the performance of permeability models based on these methods. We focus on two physical characterizations that are well-correlated with hydraulic properties: the pore volume normalized surface area (Spor) and an interconnected pore diameter (Λ). We find the SIP polarization magnitude and relaxation time are better correlated with Spor than Λ, the best correlation of these SIP measures for our sample dataset was found with Spor divided by the electrical formation factor (F). NMR parameters are, similarly, better correlated with Spor than Λ. We implement previously proposed mechanistic and empirical permeability models using SIP and NMR parameters. A sandstone-calibrated SIP model using a polarization magnitude does not perform well while a SIP model using a mean relaxation time performs better in part by more sufficiently accounting for the effects of fluid chemistry. A sandstone-calibrated NMR permeability model using an average measure of the relaxation time does not perform well, presumably due to small pore sizes which are either not connected or contain water of limited mobility. An NMR model based on the laboratory determined portions of the bound versus mobile portions of the relaxation distribution performed reasonably well. While limitations exist, there are many opportunities to use geophysical data to predict permeability in mudstone formations.

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

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...

An Oil Spill in a Tube: An Accessible Approach for Teaching Environmental NMR Spectroscopy

ERIC Educational Resources Information Center

Simpson, Andre´ J.; Mitchell, Perry J.; Masoom, Hussain; Mobarhan, Yalda Liaghati; Adamo, Antonio; Dicks, Andrew P.

2015-01-01

NMR spectroscopy has great potential as an instrumental method for environmental chemistry research and monitoring but may be underused in teaching laboratories because of its complexity and the level of expertise required in operating the instrument and interpreting data. This laboratory experiment introduces environmental NMR spectroscopy to…

Probe for high resolution NMR with sample reorientation

DOEpatents

Pines, A.; Samoson, A.

1990-02-06

An improved NMR probe and method are described which substantially improve the resolution of NMR measurements made on powdered or amorphous or otherwise orientationally disordered samples. The apparatus mechanically varies the orientation of the sample such that the time average of two or more sets of spherical harmonic functions are zero. 8 figs.

NMR spectra of 3β-hydroxy-5α-cholane derivatives, zymosterol synthesis intermediates

NASA Astrophysics Data System (ADS)

Baranovsky, A. V.; Bolotin, A. A.; Kiselev, V. P.

2011-05-01

Proton and carbon resonances in NMR spectra of a number of derivatives of 3β-hydroxy-5α-cholanes, zymosterol synthesis intermediates, have been completely assigned using 2D NMR spectroscopy methods. The stereochemistry of the chiral centers and the structures of the molecules have been confirmed.

A "special perspectives" issue: Recent achievements and new directions in biomolecular solid state NMR

NASA Astrophysics Data System (ADS)

Tycko, Robert

2015-04-01

Twenty years ago, applications of solid state nuclear magnetic resonance (NMR) methods to real problems involving biological systems or biological materials were few and far between. Starting in the 1980s, a small number of research groups had begun to explore the possibility of obtaining structural and dynamical information about peptides, proteins, and other biopolymers from solid state NMR spectra. Progress was initially slow due to the relatively primitive state of solid state NMR probes, spectrometers, sample preparation methods, and pulse sequence techniques, coupled with the small number of people contributing to this research area. By the early 1990s, with the advent of new ideas about pulse sequence techniques such as dipolar recoupling, improvements in techniques for orienting membrane proteins and in technology for magic-angle spinning (MAS), improvements in the capabilities of commercial NMR spectrometers, and general developments in multidimensional spectroscopy, it began to appear that biomolecular solid state NMR might have a viable future. It was not until 1993 that the annual number of publications in this area crept above twenty.

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.

Using indirect covariance spectra to identify artifact responses in unsymmetrical indirect covariance calculated spectra.

PubMed

Martin, Gary E; Hilton, Bruce D; Blinov, Kirill A; Williams, Antony J

2008-02-01

Several groups of authors have reported studies in the areas of indirect and unsymmetrical indirect covariance NMR processing methods. Efforts have recently focused on the use of unsymmetrical indirect covariance processing methods to combine various discrete two-dimensional NMR spectra to afford the equivalent of the much less sensitive hyphenated 2D NMR experiments, for example indirect covariance (icv)-heteronuclear single quantum coherence (HSQC)-COSY and icv-HSQC-nuclear Overhauser effect spectroscopy (NOESY). Alternatively, unsymmetrical indirect covariance processing methods can be used to combine multiple heteronuclear 2D spectra to afford icv-13C-15N HSQC-HMBC correlation spectra. We now report the use of responses contained in indirect covariance processed HSQC spectra as a means for the identification of artifacts in both indirect covariance and unsymmetrical indirect covariance processed 2D NMR spectra. Copyright (c) 2007 John Wiley & Sons, Ltd.

Utilization of SABRE-derived hyperpolarization to detect low-concentration analytes via 1D and 2D NMR methods.

PubMed

Lloyd, Lyrelle S; Adams, Ralph W; Bernstein, Michael; Coombes, Steven; Duckett, Simon B; Green, Gary G R; Lewis, Richard J; Mewis, Ryan E; Sleigh, Christopher J

2012-08-08

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of (13)C, (13)C{(1)H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

Application of 13C NMR cross-polarization inversion recovery experiments for the analysis of solid dosage forms.

PubMed

Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz

2016-11-20

Solid-state nuclear magnetic resonance (ssNMR) is a powerful and unique method for analyzing solid forms of the active pharmaceutical ingredients (APIs) directly in their original formulations. Unfortunately, despite their wide range of application, the ssNMR experiments often suffer from low sensitivity and peaks overlapping between API and excipients. To overcome these limitations, the crosspolarization inversion recovery method was successfully used. The differences in the spin-lattice relaxation time constants for hydrogen atoms T1(H) between API and excipients were employed in order to separate and discriminate their peaks in ssNMR spectra as well as to increase the intensity of API signals in low-dose formulations. The versatility of this method was demonstrated by different examples, including the excipients mixture and commercial solid dosage forms (e.g. granules and tablets). Copyright © 2016 Elsevier B.V. All rights reserved.

Desktop NMR spectroscopy for real-time monitoring of an acetalization reaction in comparison with gas chromatography and NMR at 9.4 T.

PubMed

Singh, Kawarpal; Danieli, Ernesto; Blümich, Bernhard

2017-12-01

Monitoring of chemical reactions in real-time is in demand for process control. Different methods such as gas chromatography (GC), mass spectroscopy, infrared spectroscopy, and nuclear magnetic resonance (NMR) are used for that purpose. The current state-of-the-art compact NMR systems provide a useful method to employ with various reaction conditions for studying chemical reactions inside the fume hood at the chemical workplace. In the present study, an acetalization reaction was investigated with compact NMR spectroscopy in real-time. Acetalization is used for multistep synthesis of the variety of organic compounds to protect particular chemical groups. A compact 1 T NMR spectrometer with a permanent magnet was employed to monitor the acid catalyzed acetalization of the p-nitrobenzaldehyde with ethylene glycol. The concentrations of both reactant and product were followed by peak integrals in single-scan 1 H NMR spectra as a function of time. The reaction conditions were varied in terms of temperature, agitation speed, catalyst loading, and feed concentrations in order to determine the activation energy with the help of a pseudo-homogeneous kinetic model. For low molar ratios of aldehyde and glycol, the equilibrium conversions were lower than for the stoichiometric ratio. Increasing catalyst concentration leads to faster conversion. The data obtained with low-field NMR spectroscopy were compared with data from GC and NMR spectroscopy at 9.4 T acquired in batch mode by extracting samples at regular time intervals. The reaction kinetics followed by either method agreed well. The activation energies for forward and backward reactions were determined by real-time monitoring with compact NMR at 1 T were 48 ± 5 and 60 ± 4 kJ/mol, respectively. The activation energies obtained with gas chromatography for forward and backward reactions were 48 ± 4 and 51 ± 4 kJ/mol. The equilibrium constant decreases with increasing temperature as expected for an exothermic reaction. The impact of dense sampling with online NMR and sparse sampling with GC was observed on the kinetic outcome using the same kinetic model. Graphical abstract Acetalization reaction kinetics were monitored with real-time desktop NMR spectroscopy at 1 T. Each data point was obtained at regular intervals with a single shot in 15 s. The kinetics was compared with sparsely sampled data obtained with GC and NMR at 9.4 T.

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.

Protein folding on the ribosome studied using NMR spectroscopy

PubMed Central

Waudby, Christopher A.; Launay, Hélène; Cabrita, Lisa D.; Christodoulou, John

2013-01-01

NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome–nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity. PMID:24083462

Structure analysis and spectroscopic characterization of 2-Fluoro-3-Methylpyridine-5-Boronic Acid with experimental (FT-IR, Raman, NMR and XRD) techniques and quantum chemical calculations

NASA Astrophysics Data System (ADS)

Alver, Özgür; Dikmen, Gökhan

2016-03-01

Possible stable conformers, geometrical molecular structures, vibrational properties as well as band assignments, nuclear magnetic shielding tensors of 2-Fluoro-3-Methylpyridine-5-Boronic Acid (2F3MP5BA) were studied experimentally and theoretically using FT-IR, Raman, (CP/MAS) NMR and XRD spectroscopic methods. FT-IR and Raman spectra were evaluated in the region of 3500-400 cm-1, and 3200-400 cm-1, respectively. The optimized geometric structures, vibrational wavenumbers and nuclear magnetic shielding tensors were examined using Becke-3-Lee-Yang-Parr (B3LYP) hybrid density functional theory method with 6-311++G(d, p) basis set. 1H, 13C NMR chemical shifts were calculated using the gauge invariant atomic orbital (GIAO) method. 1H, 13C, APT and HETCOR NMR experiments of title molecule were carried out in DMSO solution. 13C CP/MAS NMR measurement was done with 4 mm zirconium rotor and glycine was used as an external standard. Single crystal of 2F3MP5BA was also prepared for XRD measurements. Assignments of vibrational wavenumbers were also strengthened by calculating the total energy distribution (TED) values using scaled quantum mechanical (SQM) method.

NMR shieldings from density functional perturbation theory: GIPAW versus all-electron calculations

NASA Astrophysics Data System (ADS)

de Wijs, G. A.; Laskowski, R.; Blaha, P.; Havenith, R. W. A.; Kresse, G.; Marsman, M.

2017-02-01

We present a benchmark of the density functional linear response calculation of NMR shieldings within the gauge-including projector-augmented-wave method against all-electron augmented-plane-wave+local-orbital and uncontracted Gaussian basis set results for NMR shieldings in molecular and solid state systems. In general, excellent agreement between the aforementioned methods is obtained. Scalar relativistic effects are shown to be quite large for nuclei in molecules in the deshielded limit. The small component makes up a substantial part of the relativistic corrections.

NMR shieldings from density functional perturbation theory: GIPAW versus all-electron calculations.

PubMed

de Wijs, G A; Laskowski, R; Blaha, P; Havenith, R W A; Kresse, G; Marsman, M

2017-02-14

We present a benchmark of the density functional linear response calculation of NMR shieldings within the gauge-including projector-augmented-wave method against all-electron augmented-plane-wave+local-orbital and uncontracted Gaussian basis set results for NMR shieldings in molecular and solid state systems. In general, excellent agreement between the aforementioned methods is obtained. Scalar relativistic effects are shown to be quite large for nuclei in molecules in the deshielded limit. The small component makes up a substantial part of the relativistic corrections.

Comparative study of inversion methods of three-dimensional NMR and sensitivity to fluids

NASA Astrophysics Data System (ADS)

Tan, Maojin; Wang, Peng; Mao, Keyu

2014-04-01

Three-dimensional nuclear magnetic resonance (3D NMR) logging can simultaneously measure transverse relaxation time (T2), longitudinal relaxation time (T1), and diffusion coefficient (D). These parameters can be used to distinguish fluids in the porous reservoirs. For 3D NMR logging, the relaxation mechanism and mathematical model, Fredholm equation, are introduced, and the inversion methods including Singular Value Decomposition (SVD), Butler-Reeds-Dawson (BRD), and Global Inversion (GI) methods are studied in detail, respectively. During one simulation test, multi-echo CPMG sequence activation is designed firstly, echo trains of the ideal fluid models are synthesized, then an inversion algorithm is carried on these synthetic echo trains, and finally T2-T1-D map is built. Futhermore, SVD, BRD, and GI methods are respectively applied into a same fluid model, and the computing speed and inversion accuracy are compared and analyzed. When the optimal inversion method and matrix dimention are applied, the inversion results are in good aggreement with the supposed fluid model, which indicates that the inversion method of 3D NMR is applieable for fluid typing of oil and gas reservoirs. Additionally, the forward modeling and inversion tests are made in oil-water and gas-water models, respectively, the sensitivity to the fluids in different magnetic field gradients is also examined in detail. The effect of magnetic gradient on fluid typing in 3D NMR logging is stuied and the optimal manetic gradient is choosen.

Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for ¹⁹F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation.

PubMed

Asada, Mamiko Nasu; Nemoto, Takayuki; Mimura, Hisashi

2016-03-01

We recently developed several new relaxation filter-selective signal excitation (RFS) methods for (13)C solid-state nuclear magnetic resonance (NMR) that allow (13)C signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to (19)F solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with (19)F solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with (19)F solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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, ...

North Jetty Performance and Entrance Navigation Channel Maintenance, Grays Harbor, Washington. Volume 2. Appendices

DTIC Science & Technology

2004-06-01

Rectified Infrared Aerial Photos Image112-4 flown on 9/9/01. F22 Appendix F Shoreline and Bathymetry Data Map registration and digitizing...Division 108( WW2 ), 163-179. Soulsby, R. L., and Whitehouse, R. J. S. W. (1997). “Threshold of sediment motion in coastal environments,” Proceeings

Guayule (parthenium argentatum) pyrolysis biorefining: production of hydrocarbon compatible bio-oils from guayule bagasse via tail-gas reactive pyrolysis

USDA-ARS?s Scientific Manuscript database

Guayule (Parthenium argentatum) is a woody desert shrub grown in the southwestern United States as a source of natural rubber, organic resins, and high energy biofuel feedstock from crop residues. We used guayule bagasse, the residual biomass after latex extraction as feedstock in a pyrolysis proces...

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR BATCHING OF LAB DATA (UA-C-7.0)

EPA Science Inventory

The purpose of this SOP is to describe the steps involved in batching the physical laboratory data forms generated by NHEXAS Arizona and slated for data entry at the primary NHEXAS Arizona office. It applies to all physical laboratory data forms entered at this site. This proced...

A comprehensive NMR methodology to assess the composition of biobased and biodegradable polymers in contact with food.

PubMed

Gratia, Audrey; Merlet, Denis; Ducruet, Violette; Lyathaud, Cédric

2015-01-01

A nuclear magnetic resonance (NMR) methodology was assessed regarding the identification and quantification of additives in three types of polylactide (PLA) intended as food contact materials. Additives were identified using the LNE/NMR database which clusters NMR datasets on more than 130 substances authorized by European Regulation No. 10/2011. Of the 12 additives spiked in the three types of PLA pellets, 10 were rapidly identified by the database and correlated with spectral comparison. The levels of the 12 additives were estimated using quantitative NMR combined with graphical computation. A comparison with chromatographic methods tended to prove the sensitivity of NMR by demonstrating an analytical difference of less than 15%. Our results therefore demonstrated the efficiency of the proposed NMR methodology for rapid assessment of the composition of PLA. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Ultrafast-based projection-reconstruction three-dimensional nuclear magnetic resonance spectroscopy.

PubMed

Mishkovsky, Mor; Kupce, Eriks; Frydman, Lucio

2007-07-21

Recent years have witnessed increased efforts toward the accelerated acquisition of multidimensional nuclear magnetic resonance (nD NMR) spectra. Among the methods proposed to speed up these NMR experiments is "projection reconstruction," a scheme based on the acquisition of a reduced number of two-dimensional (2D) NMR data sets constituting cross sections of the nD time domain being sought. Another proposition involves "ultrafast" spectroscopy, capable of completing nD NMR acquisitions within a single scan. Potential limitations of these approaches include the need for a relatively slow 2D-type serial data collection procedure in the former case, and a need for at least n high-performance, linearly independent gradients and a sufficiently high sensitivity in the latter. The present study introduces a new scheme that comes to address these limitations, by combining the basic features of the projection reconstruction and the ultrafast approaches into a single, unified nD NMR experiment. In the resulting method each member within the series of 2D cross sections required by projection reconstruction to deliver the nD NMR spectrum being sought, is acquired within a single scan with the aid of the 2D ultrafast protocol. Full nD NMR spectra can thus become available by backprojecting a small number of 2D sets, collected using a minimum number of scans. Principles, opportunities, and limitations of the resulting approach, together with demonstrations of its practical advantages, are here discussed and illustrated with a series of three-dimensional homo- and heteronuclear NMR correlation experiments.

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.

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.

Scalable NMR spectroscopy with semiconductor chips

PubMed Central

Ha, Dongwan; Paulsen, Jeffrey; Sun, Nan; Song, Yi-Qiao; Ham, Donhee

2014-01-01

State-of-the-art NMR spectrometers using superconducting magnets have enabled, with their ultrafine spectral resolution, the determination of the structure of large molecules such as proteins, which is one of the most profound applications of modern NMR spectroscopy. Many chemical and biotechnological applications, however, involve only small-to-medium size molecules, for which the ultrafine resolution of the bulky, expensive, and high-maintenance NMR spectrometers is not required. For these applications, there is a critical need for portable, affordable, and low-maintenance NMR spectrometers to enable in-field, on-demand, or online applications (e.g., quality control, chemical reaction monitoring) and co-use of NMR with other analytical methods (e.g., chromatography, electrophoresis). As a critical step toward NMR spectrometer miniaturization, small permanent magnets with high field homogeneity have been developed. In contrast, NMR spectrometer electronics capable of modern multidimensional spectroscopy have thus far remained bulky. Complementing the magnet miniaturization, here we integrate the NMR spectrometer electronics into 4-mm2 silicon chips. Furthermore, we perform various multidimensional NMR spectroscopies by operating these spectrometer electronics chips together with a compact permanent magnet. This combination of the spectrometer-electronics-on-a-chip with a permanent magnet represents a useful step toward miniaturization of the overall NMR spectrometer into a portable platform. PMID:25092330

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

Bayesian peak picking for NMR spectra.

PubMed

Cheng, Yichen; Gao, Xin; Liang, Faming

2014-02-01

Protein structure determination is a very important topic in structural genomics, which helps people to understand varieties of biological functions such as protein-protein interactions, protein-DNA interactions and so on. Nowadays, nuclear magnetic resonance (NMR) has often been used to determine the three-dimensional structures of protein in vivo. This study aims to automate the peak picking step, the most important and tricky step in NMR structure determination. We propose to model the NMR spectrum by a mixture of bivariate Gaussian densities and use the stochastic approximation Monte Carlo algorithm as the computational tool to solve the problem. Under the Bayesian framework, the peak picking problem is casted as a variable selection problem. The proposed method can automatically distinguish true peaks from false ones without preprocessing the data. To the best of our knowledge, this is the first effort in the literature that tackles the peak picking problem for NMR spectrum data using Bayesian method. Copyright © 2013. Production and hosting by Elsevier Ltd.

A general algorithm for peak-tracking in multi-dimensional NMR experiments.

PubMed

Ravel, P; Kister, G; Malliavin, T E; Delsuc, M A

2007-04-01

We present an algorithmic method allowing automatic tracking of NMR peaks in a series of spectra. It consists in a two phase analysis. The first phase is a local modeling of the peak displacement between two consecutive experiments using distance matrices. Then, from the coefficients of these matrices, a value graph containing the a priori set of possible paths used by these peaks is generated. On this set, the minimization under constraint of the target function by a heuristic approach provides a solution to the peak-tracking problem. This approach has been named GAPT, standing for General Algorithm for NMR Peak Tracking. It has been validated in numerous simulations resembling those encountered in NMR spectroscopy. We show the robustness and limits of the method for situations with many peak-picking errors, and presenting a high local density of peaks. It is then applied to the case of a temperature study of the NMR spectrum of the Lipid Transfer Protein (LTP).

NMR Spectroscopy in Glass Science: A Review of the Elements

PubMed Central

2018-01-01

The study of inorganic glass structure is critically important for basic glass science and especially the commercial development of glasses for a variety of technological uses. One of the best means by which to achieve this understanding is through application of solid-state nuclear magnetic resonance (NMR) spectroscopy, which has a long and interesting history. This technique is element specific, but highly complex, and thus, one of the many inquiries made by non-NMR specialists working in glass science is what type of information and which elements can be studied by this method. This review presents a summary of the different elements that are amenable to the study of glasses by NMR spectroscopy and provides examples of the type of atomic level structural information that can be achieved. It serves to inform the non-specialist working in glass science and technology about some of the benefits and challenges involved in the study of inorganic glass structure using modern, readily-available NMR methods. PMID:29565328

LEGO-NMR spectroscopy: a method to visualize individual subunits in large heteromeric complexes.

PubMed

Mund, Markus; Overbeck, Jan H; Ullmann, Janina; Sprangers, Remco

2013-10-18

Seeing the big picture: Asymmetric macromolecular complexes that are NMR active in only a subset of their subunits can be prepared, thus decreasing NMR spectral complexity. For the hetero heptameric LSm1-7 and LSm2-8 rings NMR spectra of the individual subunits of the complete complex are obtained, showing a conserved RNA binding site. This LEGO-NMR technique makes large asymmetric complexes accessible to detailed NMR spectroscopic studies. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons the Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Organic Spectroscopy Laboratory: Utilizing IR and NMR in the Identification of an Unknown Substance

ERIC Educational Resources Information Center

Glagovich, Neil M.; Shine, Timothy D.

2005-01-01

A laboratory experiment that emphasizes the interpretation of both infrared (IR) and nuclear magnetic resonance (NMR) spectra in the elucidation of the structure of an unknown compound was developed. The method helps students determine [to the first power]H- and [to the thirteenth power]C-NMR spectra from the structures of compounds and to…

A First Laboratory Utilizing NMR for Undergraduate Education: Characterization of Edible Fats and Oils by Quantitative [superscript 13]C NMR

ERIC Educational Resources Information Center

Fry, Charles G.; Hofstetter, Heike; Bowman, Matthew D.

2017-01-01

Quantitative [superscript 13]C NMR provides a straightforward method of analyzing edible oils in undergraduate chemistry laboratories. [superscript 13]C spectra are relatively easy to understand, and are much simpler to analyze and workup than corresponding [superscript 1]H spectra. Average chain length, degree of saturation, and average…

A Robust Magnetic Resonance Imager For Ground and Flight Based Measurements of Fluid Physics Phenomena

NASA Technical Reports Server (NTRS)

2002-01-01

Nuclear magnetic resonance (NMR) is a powerful and versatile, noninvasive method for studying fluid transport problems, However, its applications to these types of investigations have been limited. A primary factor that limits the application of NMR has been the lack of a user-friendly, versatile, and inexpensive NMR imaging apparatus that can be used by scientists who are not familiar with sophisticated NMR. To rectify this situation, we developed a user-friendly, NMR imager for projects of relevance to the MRD science community. To that end, we performed preliminary collaborative experiments between NASA, NCMR, and New Mexico Resonance in the high field NMR set up at New Mexico Resonance to track wetting front dynamics in foams under gravity. The experiments were done in a 30 cm, 1.9T Oxford magnet with a TECMAG Libra spectrometer (Tecmag, Inc., Houston, TX). We used two different imaging strategies depending on whether the water in the foam sample was static or moving. Stationary water distributions were imaged with the standard Fourier imaging method, as used in medical MRI, in which data are acquired from all parts of the region of interest at all times and Fourier transformed into a static spatial image.

Chirp echo Fourier transform EPR-detected NMR

NASA Astrophysics Data System (ADS)

Wili, Nino; Jeschke, Gunnar

2018-04-01

A new ultra-wide band (UWB) pulse EPR method is introduced for observing all nuclear frequencies of a paramagnetic center in a single shot. It is based on burning spectral holes with a high turning angle (HTA) pulse that excites forbidden transitions and subsequent detection of the hole pattern by a chirp echo. We term this method Chirp Echo Epr SpectroscopY (CHEESY)-detected NMR. The approach is a revival of FT EPR-detected NMR. It yields similar spectra and the same type of information as electron-electron double resonance (ELDOR)-detected NMR, but with a multiplex advantage. We apply CHEESY-detected NMR in Q band to nitroxides and correlate the hyperfine spectrum to the EPR spectrum by varying the frequency of the HTA pulse. Furthermore, a selective π pulse before the HTA pulse allows for detecting hyperfine sublevel correlations between transitions of one nucleus and for elucidating the coupling regime, the same information as revealed by the HYSCORE experiment. This is demonstrated on hexaaquamanganese(II). We expect that CHEESY-detected NMR is generally applicable to disordered systems and that our results further motivate the development of EPR spectrometers capable of coherent UWB excitation and detection, especially at higher fields and frequencies.

Multicomponent analysis of fat- and water-soluble vitamins and auxiliary substances in multivitamin preparations by qNMR.

PubMed

Eiff, Julia; Monakhova, Yulia B; Diehl, Bernd W K

2015-04-01

A nuclear magnetic resonance (NMR) spectroscopic method was tested to control 12 vitamins and accompanying substances in multivitamin preparations. The limits of detection (LODs) and limits of quantification (LOQs) varied in the 9.0-77.0 mg/kg and in the 34.5-93.5 mg/kg range, respectively. The coefficients of variation (CVs) ranged between 0.9% and 12%. The (1)H NMR spectra showed linearity for the 140-260 mg sample weight (R(2) > 0.918). The NMR spectra of multivitamin preparations showed the presence of different degradation products of ascorbic acid. The NMR method was applied to 13 different multivitamin preparations including tablets, capsules, and effervescent tablets with average recovery rates between 85% and 132%. A number of accompanying substances (citric acid, mannitol, saccharin, cyclamate, sum of steviol glycosides, and butylhydroxytoluene) were additionally identified and quantified. NMR was found to be suitable for the simultaneous qualitative measurement of water- and fat-soluble vitamins and accompanying substances and shows some promise for quantitative determination of at least 5 vitamins (B1, B3, B5, B6, and E) in multivitamin preparations.

Curcuminoid content of Curcuma longa L. and Curcuma xanthorrhiza rhizome based on drying method with NMR and HPLC-UVD

NASA Astrophysics Data System (ADS)

Hadi, S.; Artanti, A. N.; Rinanto, Y.; Wahyuni, D. S. C.

2018-04-01

Curcuminoid, consisting of curcumin, demethoxycurcumin and bis demethoxycurcumin, is the major compound in Curcuma longa L. and Curcuma xanthorrhiza rhizome. It has been known to have a potent antioxidants, anticancer, antibacteria activity. Those rhizomes needs to be dried beforehand which influenced the active compounds concentration. The present work was conducted to assess the curcuminoid content of C. longa L. and C. xanthorrhiza based on drying method with Nuclear Magnetic Resonance (NMR) and High Pressure Liquid Chromatography (HPLC)-UVD. Samples were collected and dried using freeze-drying and oven method. The latter is the common method applied in most drying method at herbal medicine preparation procedure. All samples were extracted using 96% ethanol and analyzed using NMR and HPLC-UVD. Curcuminoid as a bioactive compound in the sample exhibited no significant difference and weak significant difference in C. xanthorrhiza and C. longa L., respectively. HLPC-UVD as a reliable analytical method for the quantification is subsequently used to confirm of the data obtained by NMR. It resulted that curcuminoid content showed no significant difference in both samples. This replied that curcuminoids content in both samples were stable into heating process. These results are useful information for simplicia standardization method in pharmaceutical products regarding to preparation procedure.

A Noninvasive Method to Study Regulation of Extracellular Fluid Volume in Rats Using Nuclear Magnetic Resonance

EPA Science Inventory

Time-domain nuclear magnetic resonance (TD-NMR)-based measurement of body composition of rodents is an effective method to quickly and repeatedly measure proportions of fat, lean, and fluid without anesthesia. TD-NMR provides a measure of free water in a living animal, termed % f...

Comparison of Flow Injection MS, NMR, and DNA Sequencing: Methods for Identification and Authentication of Black Cohosh (Actaea racemosa)

USDA-ARS?s Scientific Manuscript database

Flow injection mass spectrometry (FIMS) and proton nuclear magnetic resonance spectrometry (1H-NMR), two metabolic fingerprinting methods, and DNA sequencing were used to identify and authenticate Actaea species. Initially, samples of Actaea racemosa L. from a single source were distinguished from ...

Building blocks for automated elucidation of metabolites: machine learning methods for NMR prediction.

PubMed

Kuhn, Stefan; Egert, Björn; Neumann, Steffen; Steinbeck, Christoph

2008-09-25

Current efforts in Metabolomics, such as the Human Metabolome Project, collect structures of biological metabolites as well as data for their characterisation, such as spectra for identification of substances and measurements of their concentration. Still, only a fraction of existing metabolites and their spectral fingerprints are known. Computer-Assisted Structure Elucidation (CASE) of biological metabolites will be an important tool to leverage this lack of knowledge. Indispensable for CASE are modules to predict spectra for hypothetical structures. This paper evaluates different statistical and machine learning methods to perform predictions of proton NMR spectra based on data from our open database NMRShiftDB. A mean absolute error of 0.18 ppm was achieved for the prediction of proton NMR shifts ranging from 0 to 11 ppm. Random forest, J48 decision tree and support vector machines achieved similar overall errors. HOSE codes being a notably simple method achieved a comparatively good result of 0.17 ppm mean absolute error. NMR prediction methods applied in the course of this work delivered precise predictions which can serve as a building block for Computer-Assisted Structure Elucidation for biological metabolites.

Solvent signal suppression for high-resolution MAS-DNP

NASA Astrophysics Data System (ADS)

Lee, Daniel; Chaudhari, Sachin R.; De Paëpe, Gaël

2017-05-01

Dynamic nuclear polarization (DNP) has become a powerful tool to substantially increase the sensitivity of high-field magic angle spinning (MAS) solid-state NMR experiments. The addition of dissolved hyperpolarizing agents usually results in the presence of solvent signals that can overlap and obscure those of interest from the analyte. Here, two methods are proposed to suppress DNP solvent signals: a Forced Echo Dephasing experiment (FEDex) and TRAnsfer of Populations in DOuble Resonance Echo Dephasing (TRAPDORED) NMR. These methods reintroduce a heteronuclear dipolar interaction that is specific to the solvent, thereby forcing a dephasing of recoupled solvent spins and leaving acquired NMR spectra free of associated resonance overlap with the analyte. The potency of these methods is demonstrated on sample types common to MAS-DNP experiments, namely a frozen solution (of L-proline) and a powdered solid (progesterone), both containing deuterated glycerol as a DNP solvent. The proposed methods are efficient, simple to implement, compatible with other NMR experiments, and extendable past spectral editing for just DNP solvents. The sensitivity gains from MAS-DNP in conjunction with FEDex or TRAPDORED then permits rapid and uninterrupted sample analysis.

Analytical challenges in drug counterfeiting and falsification-The NMR approach.

PubMed

Holzgrabe, Ulrike; Malet-Martino, Myriam

2011-06-25

Counterfeiting of products is a global problem. As long as clothes, clocks, leather wear, etc. are faked there is no danger, but when it comes to drugs, counterfeiting can be life-threatening. In the last years sub-standard active pharmaceutical ingredients (APIs) were found more often even though the use of the quality-ensuring methods of international pharmacopoeias should have detected additional impurities and the low content of the API. Methods orthogonal to the separating methods used in the pharmacopoeias are necessary to find counterfeits. Beside Raman and NIR spectroscopies as well as powder X-ray analysis, NMR spectroscopy being a primary ratio method of measurement is highly suitable to identify and quantify a drug and its related substances as well as to recognize a drug of sub-standard quality. DOSY experiments are suitable to identify the ingredients of formulations and therefore to identify wrong and/or additional ingredients. This review gives an overview of the application of quantitative NMR spectroscopy and DOSY NMR in anticounterfeiting. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of 13C Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy for estimating humification and aromatization of soil organic matter

NASA Astrophysics Data System (ADS)

Rogers, K.; Cooper, W. T.; Hodgkins, S. B.; Verbeke, B. A.; Chanton, J.

2017-12-01

Solid state direct polarization 13C NMR spectroscopy (DP-NMR) is generally considered the most quantitatively reliable method for soil organic matter (SOM) characterization, including determination of the relative abundances of carbon functional groups. These functional abundances can then be used to calculate important soil parameters such as degree of humification and extent of aromaticity that reveal differences in reactivity or compositional changes along gradients (e.g. thaw chronosequence in permafrost). Unfortunately, the 13C NMR DP-NMR experiment is time-consuming, with a single sample often requiring over 24 hours of instrument time. Alternatively, solid state cross polarization 13C NMR (CP-NMR) can circumvent this problem, reducing analyses times to 4-6 hours but with some loss of quantitative reliability. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) is a quick and relatively inexpensive method for characterizing solid materials, and has been suggested as an alternative to NMR for analysis of soil organic matter and determination of humification (HI) and aromatization (AI) indices. However, the quantitative reliability of ATR-FTIR for SOM analyses has never been verified, nor have any ATR-FTIR data been compared to similar measurements by NMR. In this work we focused on FTIR vibrational bands that correspond to the three functional groups used to calculate HI and AI values: carbohydrates (1030 cm-1), aromatics (1510, 1630 cm-1), and aliphatics (2850, 2920 cm-1). Data from ATR-FTIR measurements were compared to analogous quantitation by DP- and CP-NMR using peat samples from Sweden, Minnesota, and North Carolina. DP- and CP-NMR correlate very strongly, although the correlations are not always 1:1. Direct comparison of relative abundances of the three functional groups determined by NMR and ATR-FTIR yielded satisfactory results for carbohydrates (r2= 0.78) and aliphatics (r2=0.58), but less so for aromatics (r2= 0.395). ATR-FTIR has to this point been used primarily for relative abundance analyses (e.g. calculating HI and AI values), but these results suggest FTIR can provide quantitative reliability that approaches that of NMR.

NMR study of the gelation of a designed gelator.

PubMed

Brand, Torsten; Nolis, Pau; Richter, Sven; Berger, Stefan

2008-06-01

The gelation of a designed gelator was investigated by different NMR methods, which showed a clear thermal hysteresis. Two very simple approaches for the NMR determination of the gelation point are suggested. One involves the observation of the NMR integral, and the other records the ratio of the diffusion coefficients between the gelator and the solvent. Differential behavior of the gelator protons are interpreted as a hint that a part of the gelator molecule might still be flexible as in the dissolved state. Copyright (c) 2008 John Wiley & Sons, Ltd

13C CP MAS NMR and GIAO-CHF calculations of coumarins.

PubMed

Zolek, Teresa; Paradowska, Katarzyna; Wawer, Iwona

2003-01-01

13C cross-polarization magic-angle spinning NMR spectra were recorded for a series of solid coumarins. Ab initio calculations of shielding constants were performed with the use of GIAO-CHF method. The combined CPMAS NMR and theoretical approach was successful in characterizing solid-state conformations of coumarins; a relationship sigma (ppm) = -1.032 xdelta + 205.28 (R(2) = 0.9845) can be used to obtain structural information for coumarins, for which solid-state NMR or crystal structure data are not available. Copyright 2002 Elsevier Science (USA)

Quantitative structure parameters from the NMR spectroscopy of quadrupolar nuclei

DOE PAGES

Perras, Frederic A.

2015-12-15

Here, nuclear magnetic resonance (NMR) spectroscopy is one of the most important characterization tools in chemistry, however, 3/4 of the NMR active nuclei are underutilized due to their quadrupolar nature. This short review centers on the development of methods that use solid-state NMR of quadrupolar nuclei for obtaining quantitative structural information. Namely, techniques using dipolar recoupling as well as the resolution afforded by double-rotation are presented for the measurement of spin–spin coupling between quadrupoles, enabling the measurement of internuclear distances and connectivities.

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.

Enhancing NMR of insensitive nuclei by transfer of SABRE spin hyperpolarization

NASA Astrophysics Data System (ADS)

Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Zimmermann, Herbert; Vieth, Hans-Martin; Ivanov, Konstantin L.

2016-09-01

We describe the performance of methods for enhancing NMR (Nuclear Magnetic Resonance) signals of "insensitive", but important NMR nuclei, which are based on the SABRE (Signal Amplification By Reversible Exchange) technique, i.e., on spin order transfer from parahydrogen (H2 molecule in its nuclear singlet spin state) to a substrate in a transient organometallic complex. Here such transfer is performed at high magnetic fields by INEPT-type NMR pulse sequences, modified for SABRE. Signal enhancements up to three orders of magnitude are obtained for 15N nuclei; the possibility of sensitive detection of 2D-NMR 1H-15N spectra of SABRE complexes and substrates is demonstrated.

Reliable resonance assignments of selected residues of proteins with known structure based on empirical NMR chemical shift prediction

NASA Astrophysics Data System (ADS)

Li, Da-Wei; Meng, Dan; Brüschweiler, Rafael

2015-05-01

A robust NMR resonance assignment method is introduced for proteins whose 3D structure has previously been determined by X-ray crystallography. The goal of the method is to obtain a subset of correct assignments from a parsimonious set of 3D NMR experiments of 15N, 13C labeled proteins. Chemical shifts of sequential residue pairs are predicted from static protein structures using PPM_One, which are then compared with the corresponding experimental shifts. Globally optimized weighted matching identifies the assignments that are robust with respect to small changes in NMR cross-peak positions. The method, termed PASSPORT, is demonstrated for 4 proteins with 100-250 amino acids using 3D NHCA and a 3D CBCA(CO)NH experiments as input producing correct assignments with high reliability for 22% of the residues. The method, which works best for Gly, Ala, Ser, and Thr residues, provides assignments that serve as anchor points for additional assignments by both manual and semi-automated methods or they can be directly used for further studies, e.g. on ligand binding, protein dynamics, or post-translational modification, such as phosphorylation.

Reliable Resonance Assignments of Selected Residues of Proteins with Known Structure Based on Empirical NMR Chemical Shift Prediction

PubMed Central

Li, Da-Wei; Meng, Dan; Brüschweiler, Rafael

2015-01-01

A robust NMR resonance assignment method is introduced for proteins whose 3D structure has previously been determined by X-ray crystallography. The goal of the method is to obtain a subset of correct assignments from a parsimonious set of 3D NMR experiments of 15N, 13C labeled proteins. Chemical shifts of sequential residue pairs are predicted from static protein structures using PPM_One, which are then compared with the corresponding experimental shifts. Globally optimized weighted matching identifies the assignments that are robust with respect to small changes in NMR cross-peak positions. The method, termed PASSPORT, is demonstrated for 4 proteins with 100 – 250 amino acids using 3D NHCA and a 3D CBCA(CO)NH experiments as input producing correct assignments with high reliability for 22% of the residues. The method, which works best for Gly, Ala, Ser, and Thr residues, provides assignments that serve as anchor points for additional assignments by both manual and semi-automated methods or they can be directly used for further studies, e.g. on ligand binding, protein dynamics, or post-translational modification, such as phosphorylation. PMID:25863893

Using optimal control methods with constraints to generate singlet states in NMR

NASA Astrophysics Data System (ADS)

Rodin, Bogdan A.; Kiryutin, Alexey S.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L.; Yamamoto, Satoru; Sato, Kazunobu; Takui, Takeji

2018-06-01

A method is proposed for optimizing the performance of the APSOC (Adiabatic-Passage Spin Order Conversion) technique, which can be exploited in NMR experiments with singlet spin states. In this technique magnetization-to-singlet conversion (and singlet-to-magnetization conversion) is performed by using adiabatically ramped RF-fields. Optimization utilizes the GRAPE (Gradient Ascent Pulse Engineering) approach, in which for a fixed search area we assume monotonicity to the envelope of the RF-field. Such an approach allows one to achieve much better performance for APSOC; consequently, the efficiency of magnetization-to-singlet conversion is greatly improved as compared to simple model RF-ramps, e.g., linear ramps. We also demonstrate that the optimization method is reasonably robust to possible inaccuracies in determining NMR parameters of the spin system under study and also in setting the RF-field parameters. The present approach can be exploited in other NMR and EPR applications using adiabatic switching of spin Hamiltonians.

Orphan spin operators enable the acquisition of multiple 2D and 3D magic angle spinning solid-state NMR spectra

NASA Astrophysics Data System (ADS)

Gopinath, T.; Veglia, Gianluigi

2013-05-01

We propose a general method that enables the acquisition of multiple 2D and 3D solid-state NMR spectra for U-13C, 15N-labeled proteins. This method, called MEIOSIS (Multiple ExperIments via Orphan SpIn operatorS), makes it possible to detect four coherence transfer pathways simultaneously, utilizing orphan (i.e., neglected) spin operators of nuclear spin polarization generated during 15N-13C cross polarization (CP). In the MEIOSIS experiments, two phase-encoded free-induction decays are decoded into independent nuclear polarization pathways using Hadamard transformations. As a proof of principle, we show the acquisition of multiple 2D and 3D spectra of U-13C, 15N-labeled microcrystalline ubiquitin. Hadamard decoding of CP coherences into multiple independent spin operators is a new concept in solid-state NMR and is extendable to many other multidimensional experiments. The MEIOSIS method will increase the throughput of solid-state NMR techniques for microcrystalline proteins, membrane proteins, and protein fibrils.

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.

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

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...

Comparison of phytate and other organic P forms in Mehlich-3 and Alkaline-EDTA matrices by ICP, NMR and mass spectrometry

USDA-ARS?s Scientific Manuscript database

The favored method of organic P identification over the last few decades has been 31P NMR. While this technique has the distinct advantage of speciating the organic P fraction, it has a relatively poor detection threshold (0.05 mg/ml), which typically limits 31P NMR to qualitative or confirmative ap...

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

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

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.

49 CFR 40.129 - What are the MRO's functions in reviewing laboratory confirmed non-negative drug test results?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false What are the MRO's functions in reviewing laboratory confirmed non-negative drug test results? 40.129 Section 40.129 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the Verification Proces...

Exploring pima and upland cross-combinations to identify fusarium oxysporum f. sp. vasinfectum race 4 resistant cottons by combining ability of superior cultivars

USDA-ARS?s Scientific Manuscript database

A cotton breeding program strives to identify the best performance cultivars or breeding lines which can be used as parents in crosses. Multi-cross combinations provide the means of performance of each parent and assess the combining ability or productivity of parents through the hybridization proce...

Development of a User-Defined Stressor in the Improved Performance Research Integration Tool (IMPRINT) for Conducting Tasks in a Moving Vehicle

DTIC Science & Technology

2007-03-01

task termine if in travel la ons, visual recognitio nd information proce visual recognitio uation will yiee Δ = (0accuracy .37 * 06463) + (0.63 * 0.11...mission Figure 2. User-defined stresso err int face . 8 Figure 3. Stressor levels in IMPRINT. Figure 4. Accuracy stressor definition

JPRS Report, Environmental Issues

DTIC Science & Technology

1990-06-13

in settlements in valley locations, with the simultaneous application of efficient waste- gas purification proce- dures (dedusting, desulfurization ...Slaughtered [RUDE PRAVO 1 JunJ 17 Power Plant Desulfurization Technology, Funding Explored [ZEMEDELSKE NOVINY 29 Apr] . 17 GERMAN DEMOCRATIC...the Soviet Union, it is a question of money and a shortage of foreign currency but apparently also an attempt to develop its own pollution control

Macroeconomics and Public Policy.

DTIC Science & Technology

1982-12-01

now outmoded cottage system. They were joined by the growing commercial class who sought to dissolve the exclusive State franchises in foreign trade...providing gas, electricity, water and other such services generally operate with monopoly franchises in their geographical areas of operation. In...exchange for exclusive franchises , they submit to regulation of the pricing structure for their output as well as their operational proce- dures. Monopoly

Hydraulic Conductivity Calibration of Logging NMR in a Granite Aquifer, Laramie Range, Wyoming.

PubMed

Ren, Shuangpo; Parsekian, Andrew D; Zhang, Ye; Carr, Bradley J

2018-05-15

In granite aquifers, fractures can provide both storage volume and conduits for groundwater. Characterization of fracture hydraulic conductivity (K) in such aquifers is important for predicting flow rate and calibrating models. Nuclear magnetic resonance (NMR) well logging is a method to quickly obtain near-borehole hydraulic conductivity (i.e., K NMR ) at high-vertical resolution. On the other hand, FLUTe flexible liner technology can produce a K profile at comparable resolution but requires a fluid driving force between borehole and formation. For three boreholes completed in a fractured granite, we jointly interpreted logging NMR data and FLUTe K estimates to calibrate an empirical equation for translating borehole NMR data to K estimates. For over 90% of the depth intervals investigated from these boreholes, the estimated K NMR are within one order of magnitude of K FLUTe . The empirical parameters obtained from calibrating the NMR data suggest that "intermediate diffusion" and/or "slow diffusion" during the NMR relaxation time may occur in the flowing fractures when hydraulic aperture are sufficiently large. For each borehole, "intermediate diffusion" dominates the relaxation time, therefore assuming "fast diffusion" in the interpretation of NMR data from fractured rock may lead to inaccurate K NMR estimates. We also compare calibrations using inexpensive slug tests that suggest reliable K NMR estimates for fractured rock may be achieved using limited calibration against borehole hydraulic measurements. © 2018, National Ground Water Association.

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.

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.

Development of high resolution NMR spectroscopy as a structural tool

NASA Astrophysics Data System (ADS)

Feeney, James

1992-06-01

The discovery of the nuclear magnetic resonance (NMR) phenomenon and its development and exploitation as a scientific tool provide an excellent basis for a case-study for examining the factors which control the evolution of scientific techniques. Since the detection of the NMR phenomenon and the subsequent rapid discovery of all the important NMR spectral parameters in the late 1940s, the method has emerged as one of the most powerful techniques for determining structures of molecules in solution and for analysis of complex mixtures. The method has made a dramatic impact on the development of structural chemistry over the last 30 years and is now one of the key techniques in this area. Support for NMR instrumentation attracts a dominant slice of public funding in most scientifically developed countries. The technique is an excellent example of how instrumentation and technology have revolutionised structural chemistry and it is worth exploring how it has been developed so successfully. Clearly its wide range of application and the relatively direct connection between the NMR data and molecular structure has created a major market for the instrumentation. This has provided several competing manufacturers with the incentive to develop better and better instruments. Understanding the complexity of the basics of NMR spectroscopy has been an ongoing challenge attracting the attention of physicists. The well-organised specialist NMR literature and regular scientific meetings have ensured rapid exploitation of any theoretical advances that have a practical relevance. In parallel, the commercial development of the technology has allowed the fruits of such theoretical advances to be enjoyed by the wider scientific community.

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.

Label-free quantitative 1H NMR spectroscopy to study low-affinity ligand–protein interactions in solution: A contribution to the mechanism of polyphenol-mediated astringency

PubMed Central

Delius, Judith; Frank, Oliver

2017-01-01

Nuclear magnetic resonance (NMR) spectroscopy is well-established in assessing the binding affinity between low molecular weight ligands and proteins. However, conventional NMR-based binding assays are often limited to small proteins of high purity and may require elaborate isotopic labeling of one of the potential binding partners. As protein–polyphenol complexation is assumed to be a key event in polyphenol-mediated oral astringency, here we introduce a label-free, ligand-focused 1H NMR titration assay to estimate binding affinities and characterize soluble complex formation between proteins and low molecular weight polyphenols. The method makes use of the effects of NMR line broadening due to protein–ligand interactions and quantitation of the non-bound ligand at varying protein concentrations by quantitative 1H NMR spectroscopy (qHNMR) using electronic reference to access in vivo concentration (ERETIC 2). This technique is applied to assess the interaction kinetics of selected astringent tasting polyphenols and purified mucin, a major lubricating glycoprotein of human saliva, as well as human whole saliva. The protein affinity values (BC50) obtained are subsequently correlated with the intrinsic mouth-puckering, astringent oral sensation imparted by these compounds. The quantitative NMR method is further exploited to study the effect of carboxymethyl cellulose, a candidate “anti-astringent” protein binding antagonist, on the polyphenol–protein interaction. Consequently, the NMR approach presented here proves to be a versatile tool to study the interactions between proteins and low-affinity ligands in solution and may find promising applications in the discovery of bioactives. PMID:28886151

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

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...

Superstatistics model for T₂ distribution in NMR experiments on porous media.

PubMed

Correia, M D; Souza, A M; Sinnecker, J P; Sarthour, R S; Santos, B C C; Trevizan, W; Oliveira, I S

2014-07-01

We propose analytical functions for T2 distribution to describe transverse relaxation in high- and low-fields NMR experiments on porous media. The method is based on a superstatistics theory, and allows to find the mean and standard deviation of T2, directly from measurements. It is an alternative to multiexponential models for data decay inversion in NMR experiments. We exemplify the method with q-exponential functions and χ(2)-distributions to describe, respectively, data decay and T2 distribution on high-field experiments of fully water saturated glass microspheres bed packs, sedimentary rocks from outcrop and noisy low-field experiment on rocks. The method is general and can also be applied to biological systems. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

RNA unrestrained molecular dynamics ensemble improves agreement with experimental NMR data compared to single static structure: a test case

NASA Astrophysics Data System (ADS)

Beckman, Robert A.; Moreland, David; Louise-May, Shirley; Humblet, Christine

2006-05-01

Nuclear magnetic resonance (NMR) provides structural and dynamic information reflecting an average, often non-linear, of multiple solution-state conformations. Therefore, a single optimized structure derived from NMR refinement may be misleading if the NMR data actually result from averaging of distinct conformers. It is hypothesized that a conformational ensemble generated by a valid molecular dynamics (MD) simulation should be able to improve agreement with the NMR data set compared with the single optimized starting structure. Using a model system consisting of two sequence-related self-complementary ribonucleotide octamers for which NMR data was available, 0.3 ns particle mesh Ewald MD simulations were performed in the AMBER force field in the presence of explicit water and counterions. Agreement of the averaged properties of the molecular dynamics ensembles with NMR data such as homonuclear proton nuclear Overhauser effect (NOE)-based distance constraints, homonuclear proton and heteronuclear 1H-31P coupling constant ( J) data, and qualitative NMR information on hydrogen bond occupancy, was systematically assessed. Despite the short length of the simulation, the ensemble generated from it agreed with the NMR experimental constraints more completely than the single optimized NMR structure. This suggests that short unrestrained MD simulations may be of utility in interpreting NMR results. As expected, a 0.5 ns simulation utilizing a distance dependent dielectric did not improve agreement with the NMR data, consistent with its inferior exploration of conformational space as assessed by 2-D RMSD plots. Thus, ability to rapidly improve agreement with NMR constraints may be a sensitive diagnostic of the MD methods themselves.

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.

Compressed NMR: Combining compressive sampling and pure shift NMR techniques.

PubMed

Aguilar, Juan A; Kenwright, Alan M

2017-12-26

Historically, the resolution of multidimensional nuclear magnetic resonance (NMR) has been orders of magnitude lower than the intrinsic resolution that NMR spectrometers are capable of producing. The slowness of Nyquist sampling as well as the existence of signals as multiplets instead of singlets have been two of the main reasons for this underperformance. Fortunately, two compressive techniques have appeared that can overcome these limitations. Compressive sensing, also known as compressed sampling (CS), avoids the first limitation by exploiting the compressibility of typical NMR spectra, thus allowing sampling at sub-Nyquist rates, and pure shift techniques eliminate the second issue "compressing" multiplets into singlets. This paper explores the possibilities and challenges presented by this combination (compressed NMR). First, a description of the CS framework is given, followed by a description of the importance of combining it with the right pure shift experiment. Second, examples of compressed NMR spectra and how they can be combined with covariance methods will be shown. Copyright © 2017 John Wiley & Sons, Ltd.

Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

PubMed

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

2010-09-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

Effect of hydrocarbon to nuclear magnetic resonance (NMR) logging in tight sandstone reservoirs and method for hydrocarbon correction

NASA Astrophysics Data System (ADS)

Xiao, Liang; Mao, Zhi-qiang; Xie, Xiu-hong

2017-04-01

It is crucial to understand the behavior of the T2 distribution in the presence of hydrocarbon to properly interpret pore size distribution from NMR logging. The NMR T2 spectrum is associated with pore throat radius distribution under fully brine saturated. However, when the pore space occupied by hydrocarbon, the shape of NMR spectrum is changed due to the bulk relaxation of hydrocarbon. In this study, to understand the effect of hydrocarbon to NMR logging, the kerosene and transformer oil are used to simulate borehole crude oils with different viscosity. 20 core samples, which were separately drilled from conventional, medium porosity and permeability and tight sands are saturated with four conditions of irreducible water saturation, fully saturated with brine, hydrocarbon-bearing condition and residual oil saturation, and the corresponding NMR experiments are applied to acquire NMR measurements. The residual oil saturation is used to simulate field NMR logging due to the shallow investigation depth of NMR logging. The NMR spectra with these conditions are compared, the results illustrate that for core samples drilled from tight sandstone reservoirs, the shape of NMR spectra have much change once they pore space occupied by hydrocarbon. The T2 distributions are wide, and they are bimodal due to the effect of bulk relaxation of hydrocarbon, even though the NMR spectra are unimodal under fully brine saturated. The location of the first peaks are similar with those of the irreducible water, and the second peaks are close to the bulk relaxation of viscosity oils. While for core samples drilled from conventional formations, the shape of T2 spectra have little changes. The T2 distributions overlap with each other under these three conditions of fully brine saturated, hydrocarbon-bearing and residual oil. Hence, in tight sandstone reservoirs, the shape of NMR logging should be corrected. In this study, based on the lab experiments, seven T2 times of 1ms, 3ms, 10ms, 33ms, 100ms, 300ms and 1000ms are first used to separate the T2 distributions of the residual oil saturation as 8 parts, and 8 pore components percentage compositions are calculated, second, an optimal T2 cutoff is determined to cut the T2 spectra of fully brine saturated conditions into two parts, the left parts (with short T2 time) represent to the irreducible water, and they do not need to be corrected, only the shape for the right parts of the T2 spectra needed to be corrected. Third the relationships among the amplitudes corresponding to the T2 times large than the optimal T2 cut off and 8 pore components percentage compositions are established, and they are used to predict corrected T2 amplitudes from NMR logging under residual oil saturation. Finally, the amplitudes corresponding to the left parts and the estimated amplitudes are spliced as the corrected NMR amplitudes, and a corrected T2 spectrum can be obtained. The reliability of this method is verified by comparing the corrected results and the experimental measurements. This method is extended to field application, fully water saturated T2 distributions are extracted from field NMR logging, and they are used to precisely evaluate hydrocarbon-bearing formations pore structure.

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.

Correction of erroneously packed protein's side chains in the NMR structure based on ab initio chemical shift calculations.

PubMed

Zhu, Tong; Zhang, John Z H; He, Xiao

2014-09-14

In this work, protein side chain (1)H chemical shifts are used as probes to detect and correct side-chain packing errors in protein's NMR structures through structural refinement. By applying the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of chemical shifts, incorrect side chain packing was detected in the NMR structures of the Pin1 WW domain. The NMR structure is then refined by using molecular dynamics simulation and the polarized protein-specific charge (PPC) model. The computationally refined structure of the Pin1 WW domain is in excellent agreement with the corresponding X-ray structure. In particular, the use of the PPC model yields a more accurate structure than that using the standard (nonpolarizable) force field. For comparison, some of the widely used empirical models for chemical shift calculations are unable to correctly describe the relationship between the particular proton chemical shift and protein structures. The AF-QM/MM method can be used as a powerful tool for protein NMR structure validation and structural flaw detection.

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.

AssignFit: a program for simultaneous assignment and structure refinement from solid-state NMR spectra

PubMed Central

Tian, Ye; Schwieters, Charles D.; Opella, Stanley J.; Marassi, Francesca M.

2011-01-01

AssignFit is a computer program developed within the XPLOR-NIH package for the assignment of dipolar coupling (DC) and chemical shift anisotropy (CSA) restraints derived from the solid-state NMR spectra of protein samples with uniaxial order. The method is based on minimizing the difference between experimentally observed solid-state NMR spectra and the frequencies back calculated from a structural model. Starting with a structural model and a set of DC and CSA restraints grouped only by amino acid type, as would be obtained by selective isotopic labeling, AssignFit generates all of the possible assignment permutations and calculates the corresponding atomic coordinates oriented in the alignment frame, together with the associated set of NMR frequencies, which are then compared with the experimental data for best fit. Incorporation of AssignFit in a simulated annealing refinement cycle provides an approach for simultaneous assignment and structure refinement (SASR) of proteins from solid-state NMR orientation restraints. The methods are demonstrated with data from two integral membrane proteins, one α-helical and one β-barrel, embedded in phospholipid bilayer membranes. PMID:22036904

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

Application of the AMPLE cluster-and-truncate approach to NMR structures for molecular replacement

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

Bibby, Jaclyn; Keegan, Ronan M.; Mayans, Olga

2013-11-01

Processing of NMR structures for molecular replacement by AMPLE works well. AMPLE is a program developed for clustering and truncating ab initio protein structure predictions into search models for molecular replacement. Here, it is shown that its core cluster-and-truncate methods also work well for processing NMR ensembles into search models. Rosetta remodelling helps to extend success to NMR structures bearing low sequence identity or high structural divergence from the target protein. Potential future routes to improved performance are considered and practical, general guidelines on using AMPLE are provided.

MAS NMR of HIV-1 protein assemblies

NASA Astrophysics Data System (ADS)

Suiter, Christopher L.; Quinn, Caitlin M.; Lu, Manman; Hou, Guangjin; Zhang, Huilan; Polenova, Tatyana

2015-04-01

The negative global impact of the AIDS pandemic is well known. In this perspective article, the utility of magic angle spinning (MAS) NMR spectroscopy to answer pressing questions related to the structure and dynamics of HIV-1 protein assemblies is examined. In recent years, MAS NMR has undergone major technological developments enabling studies of large viral assemblies. We discuss some of these evolving methods and technologies and provide a perspective on the current state of MAS NMR as applied to the investigations into structure and dynamics of HIV-1 assemblies of CA capsid protein and of Gag maturation intermediates.

Solution conformation of carbohydrates: a view by using NMR assisted by modeling.

PubMed

Díaz, Dolores; Canales-Mayordomo, Angeles; Cañada, F Javier; Jiménez-Barbero, Jesús

2015-01-01

Structural elucidation of complex carbohydrates in solution is not a trivial task. From the NMR view point, the limited chemical shift dispersion of sugar NMR spectra demands the combination of a variety of NMR techniques as well as the employment of molecular modeling methods. Herein, a general protocol for assignment of resonances and determination of inter-proton distances within the saccharides by homonuclear and heteronuclear experiments (i.e., (1)H and (13)C) is described. In addition, several computational tools and procedures for getting a final ensemble of geometries that represent the structure in solution are presented.

An improved 13C-tracer method for the study of lignin structure and reactions : differential 13C-NMR

Treesearch

Noritsugu Terashima; Dmitry Evtuguin; Carlos Pascoal Neto; Jim Parkas; Magnus Paulsson; Ulla Westermark; Sally Ralph; John Ralph

2003-01-01

The technique of selective 13C-enrichment of specific carbons in lignin combined with 13C-NMR differential spectrometry between spectra of 13C-enriched and unenriched lignins (Ä13C-NMR) provides definitive information on the structure of the lignin macromolecule. Improvements were made on, (1) specific 13C-enrichment of almost all carbons involved in inter-unit bonds...

Improved in-cell structure determination of proteins at near-physiological concentration

PubMed Central

Ikeya, Teppei; Hanashima, Tomomi; Hosoya, Saori; Shimazaki, Manato; Ikeda, Shiro; Mishima, Masaki; Güntert, Peter; Ito, Yutaka

2016-01-01

Investigating three-dimensional (3D) structures of proteins in living cells by in-cell nuclear magnetic resonance (NMR) spectroscopy opens an avenue towards understanding the structural basis of their functions and physical properties under physiological conditions inside cells. In-cell NMR provides data at atomic resolution non-invasively, and has been used to detect protein-protein interactions, thermodynamics of protein stability, the behavior of intrinsically disordered proteins, etc. in cells. However, so far only a single de novo 3D protein structure could be determined based on data derived only from in-cell NMR. Here we introduce methods that enable in-cell NMR protein structure determination for a larger number of proteins at concentrations that approach physiological ones. The new methods comprise (1) advances in the processing of non-uniformly sampled NMR data, which reduces the measurement time for the intrinsically short-lived in-cell NMR samples, (2) automatic chemical shift assignment for obtaining an optimal resonance assignment, and (3) structure refinement with Bayesian inference, which makes it possible to calculate accurate 3D protein structures from sparse data sets of conformational restraints. As an example application we determined the structure of the B1 domain of protein G at about 250 μM concentration in living E. coli cells. PMID:27910948

Chirp echo Fourier transform EPR-detected NMR.

PubMed

Wili, Nino; Jeschke, Gunnar

2018-04-01

A new ultra-wide band (UWB) pulse EPR method is introduced for observing all nuclear frequencies of a paramagnetic center in a single shot. It is based on burning spectral holes with a high turning angle (HTA) pulse that excites forbidden transitions and subsequent detection of the hole pattern by a chirp echo. We term this method Chirp Echo Epr SpectroscopY (CHEESY)-detected NMR. The approach is a revival of FT EPR-detected NMR. It yields similar spectra and the same type of information as electron-electron double resonance (ELDOR)-detected NMR, but with a multiplex advantage. We apply CHEESY-detected NMR in Q band to nitroxides and correlate the hyperfine spectrum to the EPR spectrum by varying the frequency of the HTA pulse. Furthermore, a selective π pulse before the HTA pulse allows for detecting hyperfine sublevel correlations between transitions of one nucleus and for elucidating the coupling regime, the same information as revealed by the HYSCORE experiment. This is demonstrated on hexaaquamanganese(II). We expect that CHEESY-detected NMR is generally applicable to disordered systems and that our results further motivate the development of EPR spectrometers capable of coherent UWB excitation and detection, especially at higher fields and frequencies. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

NMR studies of cation transport across membranes

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

Shochet, N.R.

1985-01-01

/sup 23/Na NMR Studies of cation transport across membranes were conducted both on model and biological membranes. Two ionophores, the carrier monensin and the channel-former gramicidin, were chosen to induce cation transport in large unilamellar phosphatidylcholine vesicles. The distinction between the NMR signals arising from the two sides of the membrane was achieved by the addition of an anionic paramagnetic shift reagent to the outer solution. The kinetics of the cation transport across the membrane was observed simultaneously monitoring the changes in the /sup 23/Na NMR signals of both compartments. Two mathematical models were developed for the estimation of themore » transport parameters of the monensin- and gramicidin-induced cation transport. The models were able to fit the experimental data very well. A new method for the estimation of the volume trapped inside the vesicles was developed. The method uses the relative areas of the intra- and extravesicular NMR signals arising from a suspension of vesicles bathed in the same medium they contain, as a measure for the relative volumes of these compartments. Sodium transport across biological membranes was studied by /sup 23/ NMR, using suspensions of cultured nerve cells. The sodium influx through voltage-gated channels was studied using the channel modifier batrachotoxin in combination with scorpion toxin.« less

Nuclear magnetic resonance of laser-polarized noble gases in molecules, materials and organisms

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

Goodson, Boyd McLean

1999-12-01

Conventional nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) are fundamentally challenged by the insensitivity that stems from the ordinarily low spin polarization achievable in even the strongest NMR magnets. However, by transferring angular momentum from laser light to electronic and nuclear spins, optical pumping methods can increase the nuclear spin polarization of noble gases by several orders of magnitude, thereby greatly enhancing their NMR sensitivity. This dissertation is primarily concerned with the principles and practice of optically pumped nuclear magnetic resonance (OPNMR). The enormous sensitivity enhancement afforded by optical pumping noble gases can be exploited to permitmore » a variety of novel NMR experiments across many disciplines. Many such experiments are reviewed, including the void-space imaging of organisms and materials, NMR and MRI of living tissues, probing structure and dynamics of molecules in solution and on surfaces, and zero-field NMR and MRI.« less

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).

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.

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.

Mathematical Development and Computational Analysis of Harmonic Phase-Magnetic Resonance Imaging (HARP-MRI) Based on Bloch Nuclear Magnetic Resonance (NMR) Diffusion Model for Myocardial Motion.

PubMed

Dada, Michael O; Jayeoba, Babatunde; Awojoyogbe, Bamidele O; Uno, Uno E; Awe, Oluseyi E

2017-09-13

Harmonic Phase-Magnetic Resonance Imaging (HARP-MRI) is a tagged image analysis method that can measure myocardial motion and strain in near real-time and is considered a potential candidate to make magnetic resonance tagging clinically viable. However, analytical expressions of radially tagged transverse magnetization in polar coordinates (which is required to appropriately describe the shape of the heart) have not been explored because the physics required to directly connect myocardial deformation of tagged Nuclear Magnetic Resonance (NMR) transverse magnetization in polar geometry and the appropriate harmonic phase parameters are not yet available. The analytical solution of Bloch NMR diffusion equation in spherical geometry with appropriate spherical wave tagging function is important for proper analysis and monitoring of heart systolic and diastolic deformation with relevant boundary conditions. In this study, we applied Harmonic Phase MRI method to compute the difference between tagged and untagged NMR transverse magnetization based on the Bloch NMR diffusion equation and obtained radial wave tagging function for analysis of myocardial motion. The analytical solution of the Bloch NMR equations and the computational simulation of myocardial motion as developed in this study are intended to significantly improve healthcare for accurate diagnosis, prognosis and treatment of cardiovascular related deceases at the lowest cost because MRI scan is still one of the most expensive anywhere. The analysis is fundamental and significant because all Magnetic Resonance Imaging techniques are based on the Bloch NMR flow equations.

NMR crystallography of α-poly(L-lactide).

PubMed

Pawlak, Tomasz; Jaworska, Magdalena; Potrzebowski, Marek J

2013-03-07

A complementary approach that combines NMR measurements, analysis of X-ray and neutron powder diffraction data and advanced quantum mechanical calculations was employed to study the α-polymorph of L-polylactide. Such a strategy, which is known as NMR crystallography, to the best of our knowledge, is used here for the first time for the fine refinement of the crystal structure of a synthetic polymer. The GIPAW method was used to compute the NMR shielding parameters for the different models, which included the α-PLLA structure obtained by 2-dimensional wide-angle X-ray diffraction (WAXD) at -150 °C (model M1) and at 25 °C (model M2), neutron diffraction (WAND) measurements (model M3) and the fully optimized geometry of the PLLA chains in the unit cell with defined size (model M4). The influence of changes in the chain conformation on the (13)C σ(ii) NMR shielding parameters is shown. The correlation between the σ(ii) and δ(ii) values for the M1-M4 models revealed that the M4 model provided the best fit. Moreover, a comparison of the experimental (13)C NMR spectra with the spectra calculated using the M1-M4 models strongly supports the data for the M4 model. The GIPAW method, via verification using NMR measurements, was shown to be capable of the fine refinement of the crystal structures of polymers when coarse X-ray diffraction data for powdered samples are available.

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.

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.

Optimization of cell disruption methods for efficient recovery of bioactive metabolites via NMR of three freshwater microalgae (chlorophyta).

PubMed

Ma, Nyuk Ling; Teh, Kit Yinn; Lam, Su Shiung; Kaben, Anne Marie; Cha, Thye San

2015-08-01

This study demonstrates the use of NMR techniques coupled with chemometric analysis as a high throughput data mining method to identify and examine the efficiency of different disruption techniques tested on microalgae (Chlorella variabilis, Scenedesmus regularis and Ankistrodesmus gracilis). The yield and chemical diversity from the disruptions together with the effects of pre-oven and pre-freeze drying prior to disruption techniques were discussed. HCl extraction showed the highest recovery of oil compounds from the disrupted microalgae (up to 90%). In contrast, NMR analysis showed the highest intensity of bioactive metabolites obtained for homogenized extracts pre-treated with freeze-drying, indicating that homogenizing is a more favorable approach to recover bioactive substances from the disrupted microalgae. The results show the potential of NMR as a useful metabolic fingerprinting tool for assessing compound diversity in complex microalgae extracts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automatic analysis of quantitative NMR data of pharmaceutical compound libraries.

PubMed

Liu, Xuejun; Kolpak, Michael X; Wu, Jiejun; Leo, Gregory C

2012-08-07

In drug discovery, chemical library compounds are usually dissolved in DMSO at a certain concentration and then distributed to biologists for target screening. Quantitative (1)H NMR (qNMR) is the preferred method for the determination of the actual concentrations of compounds because the relative single proton peak areas of two chemical species represent the relative molar concentrations of the two compounds, that is, the compound of interest and a calibrant. Thus, an analyte concentration can be determined using a calibration compound at a known concentration. One particularly time-consuming step in the qNMR analysis of compound libraries is the manual integration of peaks. In this report is presented an automated method for performing this task without prior knowledge of compound structures and by using an external calibration spectrum. The script for automated integration is fast and adaptable to large-scale data sets, eliminating the need for manual integration in ~80% of the cases.

1H NMR determination of beta-N-methylamino-L-alanine (L-BMAA) in environmental and biological samples.

PubMed

Moura, Sidnei; Ultramari, Mariah de Almeida; de Paula, Daniela Mendes Louzada; Yonamine, Mauricio; Pinto, Ernani

2009-04-01

A nuclear magnetic resonance (1H NMR) method for the determination of beta-N-methylamino-L-alanine (L-BMAA) in environmental aqueous samples was developed and validated. L-BMAA is a neurotoxic modified amino acid that can be produced by cyanobacteria in aqueous environments. This toxin was extracted from samples by means of solid-phase extraction (SPE) and identified and quantified by 1H NMR without further derivatization steps. The lower limit of quantification (LLOQ) was 5 microg/mL. Good inter and intra-assay precision was also observed (relative standard deviation <8.5%) with the use of 4-nitro-DL-phenylalanine as an internal standard (IS). This method of 1H NMR analysis is not time consuming and can be readily utilized to monitor L-BMAA and confirm its presence in environmental and biological samples.

Remote NMR/MRI detection of laser polarized gases

DOEpatents

Pines, Alexander; Saxena, Sunil; Moule, Adam; Spence, Megan; Seeley, Juliette A.; Pierce, Kimberly L.; Han, Song-I; Granwehr, Josef

2006-06-13

An apparatus and method for remote NMR/MRI spectroscopy having an encoding coil with a sample chamber, a supply of signal carriers, preferably hyperpolarized xenon and a detector allowing the spatial and temporal separation of signal preparation and signal detection steps. This separation allows the physical conditions and methods of the encoding and detection steps to be optimized independently. The encoding of the carrier molecules may take place in a high or a low magnetic field and conventional NMR pulse sequences can be split between encoding and detection steps. In one embodiment, the detector is a high magnetic field NMR apparatus. In another embodiment, the detector is a superconducting quantum interference device. A further embodiment uses optical detection of Rb--Xe spin exchange. Another embodiment uses an optical magnetometer using non-linear Faraday rotation. Concentration of the signal carriers in the detector can greatly improve the signal to noise ratio.

Assessment of a 1H high-resolution magic angle spinning NMR spectroscopy procedure for free sugars quantification in intact plant tissue.

PubMed

Delgado-Goñi, Teresa; Campo, Sonia; Martín-Sitjar, Juana; Cabañas, Miquel E; San Segundo, Blanca; Arús, Carles

2013-08-01

In most plants, sucrose is the primary product of photosynthesis, the transport form of assimilated carbon, and also one of the main factors determining sweetness in fresh fruits. Traditional methods for sugar quantification (mainly sucrose, glucose and fructose) require obtaining crude plant extracts, which sometimes involve substantial sample manipulation, making the process time-consuming and increasing the risk of sample degradation. Here, we describe and validate a fast method to determine sugar content in intact plant tissue by using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). The HR-MAS NMR method was used for quantifying sucrose, glucose and fructose in mesocarp tissues from melon fruits (Cucumis melo var. reticulatus and Cucumis melo var. cantalupensis). The resulting sugar content varied among individual melons, ranging from 1.4 to 7.3 g of sucrose, 0.4-2.5 g of glucose; and 0.73-2.83 g of fructose (values per 100 g fw). These values were in agreement with those described in the literature for melon fruit tissue, and no significant differences were found when comparing them with those obtained using the traditional, enzymatic procedure, on melon tissue extracts. The HR-MAS NMR method offers a fast (usually <30 min) and sensitive method for sugar quantification in intact plant tissues, it requires a small amount of tissue (typically 50 mg fw) and avoids the interferences and risks associated with obtaining plant extracts. Furthermore, this method might also allow the quantification of additional metabolites detectable in the plant tissue NMR spectrum.

Nuclear magnetic resonance and high-performance liquid chromatography techniques for the characterization of bioactive compounds from Humulus lupulus L. (hop).

PubMed

Bertelli, Davide; Brighenti, Virginia; Marchetti, Lucia; Reik, Anna; Pellati, Federica

2018-06-01

Humulus lupulus L. (hop) represents one of the most cultivated crops, it being a key ingredient in the brewing process. Many health-related properties have been described for hop extracts, making this plant gain more interest in the field of pharmaceutical and nutraceutical research. Among the analytical tools available for the phytochemical characterization of plant extracts, quantitative nuclear magnetic resonance (qNMR) represents a new and powerful technique. In this ambit, the present study was aimed at the development of a new, simple, and efficient qNMR method for the metabolite fingerprinting of bioactive compounds in hop cones, taking advantage of the novel ERETIC 2 tool. To the best of our knowledge, this is the first attempt to apply this method to complex matrices of natural origin, such as hop extracts. The qNMR method set up in this study was applied to the quantification of both prenylflavonoids and bitter acids in eight hop cultivars. The performance of this analytical method was compared with that of HPLC-UV/DAD, which represents the most frequently used technique in the field of natural product analysis. The quantitative data obtained for hop samples by means of the two aforementioned techniques highlighted that the amount of bioactive compounds was slightly higher when qNMR was applied, although the order of magnitude of the values was the same. The accuracy of qNMR was comparable to that of the chromatographic method, thus proving to be a reliable tool for the analysis of these secondary metabolites in hop extracts. Graphical abstract Graphical abstract related to the extraction and analytical methods applied in this work for the analysis of bioactive compounds in Humulus lupulus L. (hop) cones.

Quantitative determinations of levofloxacin and rifampicin in pharmaceutical and urine samples using nuclear magnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

Salem, A. A.; Mossa, H. A.; Barsoum, B. N.

2005-11-01

Rapid, specific and simple methods for determining levofloxacin and rifampicin antibiotic drugs in pharmaceutical and human urine samples were developed. The methods are based on 1H NMR spectroscopy using maleic acid as an internal standard and DMSO-d6 as NMR solvent. Integration of NMR signals at 8.9 and 8.2 ppm were, respectively, used for calculating the concentration of levofloxacin and rifampicin drugs per unit dose. Maleic acid signal at 6.2 ppm was used as the reference signal. Recoveries of (97.0-99.4) ± 0.5 and (98.3-99.7) ± 1.08% were obtained for pure levofloxacin and rifampicin, respectively. Corresponding recoveries of 98.5-100.3 and 96.8-100.0 were, respectively, obtained in pharmaceutical capsules and urine samples. Relative standard deviations (R.S.D.) values ≤2.7 were obtained for analyzed drugs in pure, pharmaceutical and urine samples. Statistical Student's t-test gave t-values ≤2.87 indicating insignificant difference between the real and the experimental values at the 95% confidence level. F-test revealed insignificant difference in precisions between the developed NMR methods and each of fluorimetric and HPLC methods for analyzing levofloxacin and rifampicin.

Quantitative determination and validation of octreotide acetate using 1 H-NMR spectroscopy with internal standard method.

PubMed

Yu, Chen; Zhang, Qian; Xu, Peng-Yao; Bai, Yin; Shen, Wen-Bin; Di, Bin; Su, Meng-Xiang

2018-01-01

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Protein folding by NMR.

PubMed

Zhuravleva, Anastasia; Korzhnev, Dmitry M

2017-05-01

Protein folding is a highly complex process proceeding through a number of disordered and partially folded nonnative states with various degrees of structural organization. These transiently and sparsely populated species on the protein folding energy landscape play crucial roles in driving folding toward the native conformation, yet some of these nonnative states may also serve as precursors for protein misfolding and aggregation associated with a range of devastating diseases, including neuro-degeneration, diabetes and cancer. Therefore, in vivo protein folding is often reshaped co- and post-translationally through interactions with the ribosome, molecular chaperones and/or other cellular components. Owing to developments in instrumentation and methodology, solution NMR spectroscopy has emerged as the central experimental approach for the detailed characterization of the complex protein folding processes in vitro and in vivo. NMR relaxation dispersion and saturation transfer methods provide the means for a detailed characterization of protein folding kinetics and thermodynamics under native-like conditions, as well as modeling high-resolution structures of weakly populated short-lived conformational states on the protein folding energy landscape. Continuing development of isotope labeling strategies and NMR methods to probe high molecular weight protein assemblies, along with advances of in-cell NMR, have recently allowed protein folding to be studied in the context of ribosome-nascent chain complexes and molecular chaperones, and even inside living cells. Here we review solution NMR approaches to investigate the protein folding energy landscape, and discuss selected applications of NMR methodology to studying protein folding in vitro and in vivo. Together, these examples highlight a vast potential of solution NMR in providing atomistic insights into molecular mechanisms of protein folding and homeostasis in health and disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Solution NMR Refinement of a Metal Ion Bound Protein Using Metal Ion Inclusive Restrained Molecular Dynamics Methods

PubMed Central

Chakravorty, Dhruva K.; Wang, Bing; Lee, Chul Won; Guerra, Alfredo J.; Giedroc, David P.; Merz, Kenneth M.

2013-01-01

Correctly calculating the structure of metal coordination sites in a protein during the process of nuclear magnetic resonance (NMR) structure determination and refinement continues to be a challenging task. In this study, we present an accurate and convenient means by which to include metal ions in the NMR structure determination process using molecular dynamics (MD) constrained by NMR-derived data to obtain a realistic and physically viable description of the metal binding site(s). This method provides the framework to accurately portray the metal ions and its binding residues in a pseudo-bond or dummy-cation like approach, and is validated by quantum mechanical/molecular mechanical (QM/MM) MD calculations constrained by NMR-derived data. To illustrate this approach, we refine the zinc coordination complex structure of the zinc sensing transcriptional repressor protein Staphylococcus aureus CzrA, generating over 130 ns of MD and QM/MM MD NMR-data compliant sampling. In addition to refining the first coordination shell structure of the Zn(II) ion, this protocol benefits from being performed in a periodically replicated solvation environment including long-range electrostatics. We determine that unrestrained (not based on NMR data) MD simulations correlated to the NMR data in a time-averaged ensemble. The accurate solution structure ensemble of the metal-bound protein accurately describes the role of conformational dynamics in allosteric regulation of DNA binding by zinc and serves to validate our previous unrestrained MD simulations of CzrA. This methodology has potentially broad applicability in the structure determination of metal ion bound proteins, protein folding and metal template protein-design studies. PMID:23609042

Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria.

PubMed

Magnitsky, Sergey; Dudli, Stefan; Tang, Xinyan; Kaur, Jaskanwaljeet; Diaz, Joycelyn; Miller, Steve; Lotz, Jeffrey C

2018-06-01

Research. The goal of this study was to investigate whether Propionibacteria acnes infection of the intervertebral disc can be detected noninvasively by nuclear magnetic resonance (NMR) spectroscopy. Microbiological studies of surgical samples suggest that a significant subpopulation of back pain patients may have occult disc infection with P. acnes bacteria. This hypothesis is further supported by a double-blind clinical trial showing that back pain patients with Modic type 1 changes may respond to antibiotic treatment. Because significant side effects are associated with antibiotic treatment, there is a need for a noninvasive method to detect whether specific discs in back pain patients are infected with P acnes bacteria. P. acnes bacteria were obtained from human patients. NMR detection of a propionic acid (PA) in the bacteria extracts was conducted on 500 MHz high-resolution spectrometer, whereas in vivo NMR spectroscopy of an isolated bovine disk tissue infected with P. acnes was conducted on 7 T magnetic resonance imaging scanner. NMR spectra of P. acnes metabolites revealed a distinct NMR signal with identical chemical shits (1.05 and 2.18 ppm) as PA (a primary P. acne metabolite). The 1.05 ppm signal does not overlap with other bacteria metabolites, and its intensity increases linearly with P. acnes concentration. Bovine disks injected with P. acnes bacteria revealed a very distinct NMR signal at 1.05 ppm, which linearly increased with P. acnes concentration. The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of discs. This signal does not overlap with other disc metabolites and linearly depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a noninvasive method to detect disc infection in the clinical setting. N/A.

Ab initio/GIAO-CCSD(T) study of structures, energies, and 13C NMR chemical shifts of C4H7(+) and C5H9(+) ions: relative stability and dynamic aspects of the cyclopropylcarbinyl vs bicyclobutonium ions.

PubMed

Olah, George A; Surya Prakash, G K; Rasul, Golam

2008-07-16

The structures and energies of the carbocations C 4H 7 (+) and C 5H 9 (+) were calculated using the ab initio method. The (13)C NMR chemical shifts of the carbocations were calculated using the GIAO-CCSD(T) method. The pisigma-delocalized bisected cyclopropylcarbinyl cation, 1 and nonclassical bicyclobutonium ion, 2 were found to be the minima for C 4H 7 (+) at the MP2/cc-pVTZ level. At the MP4(SDTQ)/cc-pVTZ//MP2/cc-pVTZ + ZPE level the structure 2 is 0.4 kcal/mol more stable than the structure 1. The (13)C NMR chemical shifts of 1 and 2 were calculated by the GIAO-CCSD(T) method. Based on relative energies and (13)C NMR chemical shift calculations, an equilibrium involving the 1 and 2 in superacid solutions is most likely responsible for the experimentally observed (13)C NMR chemical shifts, with the latter as the predominant equilibrating species. The alpha-methylcyclopropylcarbinyl cation, 4, and nonclassical bicyclobutonium ion, 5, were found to be the minima for C 5H 9 (+) at the MP2/cc-pVTZ level. At the MP4(SDTQ)/cc-pVTZ//MP2/cc-pVTZ + ZPE level ion 5 is 5.9 kcal/mol more stable than the structure 4. The calculated (13)C NMR chemical shifts of 5 agree rather well with the experimental values of C 5H 9 (+).

RASSP Benchmark 4 Technical Description.

DTIC Science & Technology

1998-01-09

be carried out. Based on results of the study, an implementation of all, or part, of the system described in this benchmark technical description...validate interface and timing constraints. The ISA level of modeling defines the limit of detail expected in the VHDL virtual prototype. It does not...develop a set of candidate architectures and perform an architecture trade-off study. Candidate proces- sor implementations must then be examined for

JPRS Report, China.

DTIC Science & Technology

1991-10-11

leadership repeatedly begged for leniency, tion policies were not established by legislative proce- saying things, such as "Since we are a state-owned...accountants. Finance and tax departments should join C. We should complete our tax legislation . We should together to examine and approve the...qualifications of sum up and revise as quickly as possible our well- enterprise accountants, who should be allowed to work considered legislation , such as

Report on the Armed Services Technical Information Agency

DTIC Science & Technology

1957-06-30

insert controlling DoD office). • DISTRIBUTION STATEMENT E . Distribution authorized to DoD Components only (fill in reason) (date of determination...Forecast of ASTIA Activity E Proposed DOD Directive re: Cataloging and Abstracting of Reports by Originators F Statistics on ASTIA...for resources, and ( e ) systems and proce- dures. External considerations of user requirements and user satis- faction were beyond the scope of

Resiliency in Future Cyber Combat

DTIC Science & Technology

2016-04-04

including the Internet , telecommunications networks, computer systems, and embed- ded processors and controllers.”6 One important point emerging from the...definition is that while the Internet is part of cyberspace, it is not all of cyberspace. Any computer processor capable of communicating with a...central proces- sor on a modern car are all part of cyberspace, although only some of them are routinely connected to the Internet . Most modern

NMR-invisible ATP in heart: fact or fiction?

PubMed

Bak, M I; Ingwall, J S

1992-06-01

31P-nuclear magnetic resonance (31P-NMR) spectroscopy is widely used to monitor sequential changes in the nucleoside triphosphate (NTP) pool in intact tissues. Recently, the validity of this technique to quantitate incremental changes in ATP in heart has been challenged. Accordingly, we compared NTP measured by 31P-NMR and by chemical techniques in isolated isovolumic rat hearts at 16 and 56 min of oxygenated perfusion and in hearts subjected to 28 min of hypoxia, with or without 28 min of reoxygenation, and 12 or 28 min of ischemia, with or without 28 min of reperfusion. NTP content was calculated from 31P-NMR spectra using an external standard. At the end of each protocol the heart was freeze-clamped, and NTP and ATP contents were determined by chemical assay. After 16 min of normoxic perfusion the values for NTP and ATP contents measured by both methods in the same hearts were indistinguishable. Results from all seven experimental conditions show no significant difference between methods (P = 0.262). Thus both methods detect the same incremental change in NTP and ATP.

Simple 1H NMR spectroscopic method for assay of salts of the contrast agent diatrizoate in commercial solutions.

PubMed

Hanna, G M; Lau-Cam, C A

1996-01-01

A simple, accurate, and specific 1H NMR spectroscopic method was developed for the assay of diatrizoate meglumine or the combination diatrizoate meglumine and diatrizoate sodium in commercial solutions for injection. A mixture of injectable solution and sodium acetate, the internal standard, was diluted with D2O and the 1H NMR spectrum of the solution was obtained. Two approaches were used to calculate the drug content, based on the integral values for the -N-CO-CH3 protons of diatrizoic acid at 2.23 ppm, and -N-CH3 protons of meglumine at 2.73 ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm. Recoveries (mean +/- standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures of various amounts of these compounds with a fixed amount of internal standard were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively. In addition to providing a direct means of simultaneously assaying diatrizoic acid and meglumine, the proposed NMR method can also be used to identify diatrizoate meglumine and each of its molecular components.

Detergent Optimized Membrane Protein Reconstitution in Liposomes for Solid State NMR

PubMed Central

2015-01-01

For small helical membrane proteins, their structures are highly sensitive to their environment, and solid state NMR is a structural technique that can characterize these membrane proteins in native-like lipid bilayers and proteoliposomes. To date, a systematic method by which to evaluate the effect of the solubilizing detergent on proteoliposome preparations for solid state NMR of membrane proteins has not been presented in the literature. A set of experiments are presented aimed at determining the conditions most amenable to dialysis mediated reconstitution sample preparation. A membrane protein from M. tuberculosis is used to illustrate the method. The results show that a detergent that stabilizes the most protein is not always ideal and sometimes cannot be removed by dialysis. By focusing on the lipid and protein binding properties of the detergent, proteoliposome preparations can be readily produced, which provide double the signal-to-noise ratios for both the oriented sample and magic angle spinning solid state NMR. The method will allow more membrane protein drug targets to be structurally characterized in lipid bilayer environments. PMID:24665863

{sup 19}F NMR measurements of NO production in hypertensive ISIAH and OXYS rats

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

Bobko, Andrey A.; Sergeeva, Svetlana V.; Bagryanskaya, Elena G.

2005-05-06

Recently we demonstrated the principal possibility of application of {sup 19}F NMR spin-trapping technique for in vivo {sup {center_dot}}NO detection [Free Radic. Biol. Med. 36 (2004) 248]. In the present study, we employed this method to elucidate the significance of {sup {center_dot}}NO availability in animal models of hypertension. In vivo {sup {center_dot}}NO-induced conversion of the hydroxylamine of the fluorinated nitronyl nitroxide (HNN) to the hydroxylamine of the iminonitroxide (HIN) in hypertensive ISIAH and OXYS rat strains and normotensive Wistar rat strain was measured. Significantly lower HIN/HNN ratios were measured in the blood of the hypertensive rats. The NMR data weremore » found to positively correlate with the levels of nitrite/nitrate evaluated by Griess method and negatively correlate with the blood pressure. In comparison with other traditionally used methods {sup 19}F NMR spectroscopy allows in vivo evaluation of {sup {center_dot}}NO production and provides the basis for in vivo {sup {center_dot}}NO imaging.« less

NMR analysis of compositional heterogeneity in polysaccharides

USDA-ARS?s Scientific Manuscript database

Many copolysaccharides are compositionally heterogeneous, and the composition determined by the usual analytical or spectroscopic methods provides only an average value. For some polysaccharides, the NMR data contain copolymer sequence information, such as diad, triad, and tetrad sequence intensiti...

Quantitative measurement of regional blood flow with gadolinium diethylenetriaminepentaacetate bolus track NMR imaging in cerebral infarcts in rats: validation with the iodo[14C]antipyrine technique.

PubMed Central

Wittlich, F; Kohno, K; Mies, G; Norris, D G; Hoehn-Berlage, M

1995-01-01

NMR bolus track measurements were correlated with autoradiographically determined regional cerebral blood flow (rCBF). The NMR method is based on bolus infusion of the contrast agent gadolinium diethylenetriaminepentaacetate and high-speed T*2-sensitive NMR imaging. The first pass of the contrast agent through the image plane causes a transient decrease of the signal intensity. This time course of the signal intensity is transformed into relative concentrations of the contrast agent in each pixel. The mean transit time and relative blood flow and volume are calculated from such indicator dilution curves. We investigated whether this NMR technique correctly expresses the relative rCBF. The relative blood flow data, calculated from NMR bolus track experiments, and the absolute values of iodo[14C]antipyrine autoradiography were compared. A linear relationship was observed, indicating the proportionality of the transient NMR signal change with CBF. Excellent interindividual reproducibility of calibration constants is observed (r = 0.963). For a given NMR protocol, bolus track measurements calibrated with autoradiography after the experiment allow determination of absolute values for rCBF and regional blood volume. Images Fig. 2 Fig. 3 PMID:7892189

Relaxation time estimation in surface NMR

DOEpatents

Grunewald, Elliot D.; Walsh, David O.

2017-03-21

NMR relaxation time estimation methods and corresponding apparatus generate two or more alternating current transmit pulses with arbitrary amplitudes, time delays, and relative phases; apply a surface NMR acquisition scheme in which initial preparatory pulses, the properties of which may be fixed across a set of multiple acquisition sequence, are transmitted at the start of each acquisition sequence and are followed by one or more depth sensitive pulses, the pulse moments of which are varied across the set of multiple acquisition sequences; and apply processing techniques in which recorded NMR response data are used to estimate NMR properties and the relaxation times T.sub.1 and T.sub.2* as a function of position as well as one-dimensional and two-dimension distributions of T.sub.1 versus T.sub.2* as a function of subsurface position.

In Vivo potassium-39 NMR spectra by the burg maximum-entropy method

NASA Astrophysics Data System (ADS)

Uchiyama, Takanori; Minamitani, Haruyuki

The Burg maximum-entropy method was applied to estimate 39K NMR spectra of mung bean root tips. The maximum-entropy spectra have as good a linearity between peak areas and potassium concentrations as those obtained by fast Fourier transform and give a better estimation of intracellular potassium concentrations. Therefore potassium uptake and loss processes of mung bean root tips are shown to be more clearly traced by the maximum-entropy method.

Determining the Orientation and Localization of Membrane-Bound Peptides

PubMed Central

Hohlweg, Walter; Kosol, Simone; Zangger, Klaus

2012-01-01

Many naturally occurring bioactive peptides bind to biological membranes. Studying and elucidating the mode of interaction is often an essential step to understand their molecular and biological functions. To obtain the complete orientation and immersion depth of such compounds in the membrane or a membrane-mimetic system, a number of methods are available, which are separated in this review into four main classes: solution NMR, solid-state NMR, EPR and other methods. Solution NMR methods include the Nuclear Overhauser Effect (NOE) between peptide and membrane signals, residual dipolar couplings and the use of paramagnetic probes, either within the membrane-mimetic or in the solvent. The vast array of solid state NMR methods to study membrane-bound peptide orientation and localization includes the anisotropic chemical shift, PISA wheels, dipolar waves, the GALA, MAOS and REDOR methods and again the use of paramagnetic additives on relaxation rates. Paramagnetic additives, with their effect on spectral linewidths, have also been used in EPR spectroscopy. Additionally, the orientation of a peptide within a membrane can be obtained by the anisotropic hyperfine tensor of a rigidly attached nitroxide label. Besides these magnetic resonance techniques a series of other methods to probe the orientation of peptides in membranes has been developed, consisting of fluorescence-, infrared- and oriented circular dichroism spectroscopy, colorimetry, interface-sensitive X-ray and neutron scattering and Quartz crystal microbalance. PMID:22044140

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

Exploring high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for metabonomic analysis of apples.

PubMed

Vermathen, Martina; Marzorati, Mattia; Vermathen, Peter

2012-01-01

Classical liquid-state high-resolution (HR) NMR spectroscopy has proved a powerful tool in the metabonomic analysis of liquid food samples like fruit juices. In this paper the application of (1)H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to apple tissue is presented probing its potential for metabonomic studies. The (1)H HR-MAS NMR spectra are discussed in terms of the chemical composition of apple tissue and compared to liquid-state NMR spectra of apple juice. Differences indicate that specific metabolic changes are induced by juice preparation. The feasibility of HR-MAS NMR-based multivariate analysis is demonstrated by a study distinguishing three different apple cultivars by principal component analysis (PCA). Preliminary results are shown from subsequent studies comparing three different cultivation methods by means of PCA and partial least squares discriminant analysis (PLS-DA) of the HR-MAS NMR data. The compounds responsible for discriminating organically grown apples are discussed. Finally, an outlook of our ongoing work is given including a longitudinal study on apples.

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

NASA Astrophysics Data System (ADS)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

NIST-Traceable NMR Method to Determine Quantitative Weight Percentage Purity of Mustard (HD) Feedstock Samples

DTIC Science & Technology

2018-01-01

ECBC-TR-1506 NIST-TRACEABLE NMR METHOD TO DETERMINE QUANTITATIVE WEIGHT PERCENTAGE PURITY OF MUSTARD (HD) FEEDSTOCK SAMPLES David J...McGarvey RESEARCH AND TECHNOLOGY DIRECTORATE William R. Creasy LEIDOS, INC. Abingdon, MD 21009-1261 Theresa R. Connell EXCET, INC...be construed as an official Department of the Army position unless so designated by other authorizing documents. REPORT DOCUMENTATION PAGE

WaVPeak: picking NMR peaks through wavelet-based smoothing and volume-based filtering.

PubMed

Liu, Zhi; Abbas, Ahmed; Jing, Bing-Yi; Gao, Xin

2012-04-01

Nuclear magnetic resonance (NMR) has been widely used as a powerful tool to determine the 3D structures of proteins in vivo. However, the post-spectra processing stage of NMR structure determination usually involves a tremendous amount of time and expert knowledge, which includes peak picking, chemical shift assignment and structure calculation steps. Detecting accurate peaks from the NMR spectra is a prerequisite for all following steps, and thus remains a key problem in automatic NMR structure determination. We introduce WaVPeak, a fully automatic peak detection method. WaVPeak first smoothes the given NMR spectrum by wavelets. The peaks are then identified as the local maxima. The false positive peaks are filtered out efficiently by considering the volume of the peaks. WaVPeak has two major advantages over the state-of-the-art peak-picking methods. First, through wavelet-based smoothing, WaVPeak does not eliminate any data point in the spectra. Therefore, WaVPeak is able to detect weak peaks that are embedded in the noise level. NMR spectroscopists need the most help isolating these weak peaks. Second, WaVPeak estimates the volume of the peaks to filter the false positives. This is more reliable than intensity-based filters that are widely used in existing methods. We evaluate the performance of WaVPeak on the benchmark set proposed by PICKY (Alipanahi et al., 2009), one of the most accurate methods in the literature. The dataset comprises 32 2D and 3D spectra from eight different proteins. Experimental results demonstrate that WaVPeak achieves an average of 96%, 91%, 88%, 76% and 85% recall on (15)N-HSQC, HNCO, HNCA, HNCACB and CBCA(CO)NH, respectively. When the same number of peaks are considered, WaVPeak significantly outperforms PICKY. WaVPeak is an open source program. The source code and two test spectra of WaVPeak are available at http://faculty.kaust.edu.sa/sites/xingao/Pages/Publications.aspx. The online server is under construction. statliuzhi@xmu.edu.cn; ahmed.abbas@kaust.edu.sa; majing@ust.hk; xin.gao@kaust.edu.sa.

WaVPeak: picking NMR peaks through wavelet-based smoothing and volume-based filtering

PubMed Central

Liu, Zhi; Abbas, Ahmed; Jing, Bing-Yi; Gao, Xin

2012-01-01

Motivation: Nuclear magnetic resonance (NMR) has been widely used as a powerful tool to determine the 3D structures of proteins in vivo. However, the post-spectra processing stage of NMR structure determination usually involves a tremendous amount of time and expert knowledge, which includes peak picking, chemical shift assignment and structure calculation steps. Detecting accurate peaks from the NMR spectra is a prerequisite for all following steps, and thus remains a key problem in automatic NMR structure determination. Results: We introduce WaVPeak, a fully automatic peak detection method. WaVPeak first smoothes the given NMR spectrum by wavelets. The peaks are then identified as the local maxima. The false positive peaks are filtered out efficiently by considering the volume of the peaks. WaVPeak has two major advantages over the state-of-the-art peak-picking methods. First, through wavelet-based smoothing, WaVPeak does not eliminate any data point in the spectra. Therefore, WaVPeak is able to detect weak peaks that are embedded in the noise level. NMR spectroscopists need the most help isolating these weak peaks. Second, WaVPeak estimates the volume of the peaks to filter the false positives. This is more reliable than intensity-based filters that are widely used in existing methods. We evaluate the performance of WaVPeak on the benchmark set proposed by PICKY (Alipanahi et al., 2009), one of the most accurate methods in the literature. The dataset comprises 32 2D and 3D spectra from eight different proteins. Experimental results demonstrate that WaVPeak achieves an average of 96%, 91%, 88%, 76% and 85% recall on 15N-HSQC, HNCO, HNCA, HNCACB and CBCA(CO)NH, respectively. When the same number of peaks are considered, WaVPeak significantly outperforms PICKY. Availability: WaVPeak is an open source program. The source code and two test spectra of WaVPeak are available at http://faculty.kaust.edu.sa/sites/xingao/Pages/Publications.aspx. The online server is under construction. Contact: statliuzhi@xmu.edu.cn; ahmed.abbas@kaust.edu.sa; majing@ust.hk; xin.gao@kaust.edu.sa PMID:22328784

High-pressure nuclear magnetic resonance studies of fuel cell membranes

NASA Astrophysics Data System (ADS)

Mananga, Eugene Stephane

This thesis focuses on the use of high pressure NMR to study transport properties in electrolyte membranes used for fuel cells. The main concern is in studying the self-diffusion coefficients of ions and molecules in membranes and solutions, which can be used to characterize electrolytes in fuel cells. For this purpose, a high-pressure fringe field NMR method to study transport properties in material systems useful for fuel cell and battery electrolytes, was designed, developed, and implemented. In this investigation, pressure is the thermodynamic variable to obtain additional information about the ionic transport process, which could yield the crucial parameter, activation volume. Most of the work involves proton NMR, with additional investigations of others nuclei, such as fluorine, phosphorus and lithium. Using the FFG method, two fuel cell membrane types (NAFION-117, SPTES), and different dilutions of phosphoric acid were investigated, as was LiTf salt in Diglyme solution, which is used as a lithium battery electrolyte. In addition to high-pressure NMR diffusion measurements carried out in the fringe field gradient for the investigation of SPTES, pulse field gradient spin echo NMR was also used to characterize the water diffusion, in addition to measuring diffusion rates as a function of temperature. This second method allows us to measure distinct diffusion coefficients in cases where the different nuclear (proton) environments can be resolved in the NMR spectrum. Polymer electrolyte systems, in which the mobility of both cations and anions is probed by NMR self-diffusion measurements using standard pulsed field gradient methods and static gradient measurements as a function of applied hydrostatic pressure, were also investigated. The material investigated is the low molecular weight liquid diglyme/LiCF3SO3 (LiTf) complexes which can be used as electrolytes in lithium batteries. Finally, high-pressure diffusion coefficient measurements of phosphoric acid in water at different concentrations: proton (1H) and phosphorus (31P) nuclei have been performed using the static field gradient spin-echo nuclear magnetic resonance. This study is expected to be helpful in improving the understanding of phosphoric acid fuel cell technology.

Unraveling the meaning of chemical shifts in protein NMR.

PubMed

Berjanskii, Mark V; Wishart, David S

2017-11-01

Chemical shifts are among the most informative parameters in protein NMR. They provide wealth of information about protein secondary and tertiary structure, protein flexibility, and protein-ligand binding. In this report, we review the progress in interpreting and utilizing protein chemical shifts that has occurred over the past 25years, with a particular focus on the large body of work arising from our group and other Canadian NMR laboratories. More specifically, this review focuses on describing, assessing, and providing some historical context for various chemical shift-based methods to: (1) determine protein secondary and super-secondary structure; (2) derive protein torsion angles; (3) assess protein flexibility; (4) predict residue accessible surface area; (5) refine 3D protein structures; (6) determine 3D protein structures and (7) characterize intrinsically disordered proteins. This review also briefly covers some of the methods that we previously developed to predict chemical shifts from 3D protein structures and/or protein sequence data. It is hoped that this review will help to increase awareness of the considerable utility of NMR chemical shifts in structural biology and facilitate more widespread adoption of chemical-shift based methods by the NMR spectroscopists, structural biologists, protein biophysicists, and biochemists worldwide. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

PICKY: a novel SVD-based NMR spectra peak picking method.

PubMed

Alipanahi, Babak; Gao, Xin; Karakoc, Emre; Donaldson, Logan; Li, Ming

2009-06-15

Picking peaks from experimental NMR spectra is a key unsolved problem for automated NMR protein structure determination. Such a process is a prerequisite for resonance assignment, nuclear overhauser enhancement (NOE) distance restraint assignment, and structure calculation tasks. Manual or semi-automatic peak picking, which is currently the prominent way used in NMR labs, is tedious, time consuming and costly. We introduce new ideas, including noise-level estimation, component forming and sub-division, singular value decomposition (SVD)-based peak picking and peak pruning and refinement. PICKY is developed as an automated peak picking method. Different from the previous research on peak picking, we provide a systematic study of the proposed method. PICKY is tested on 32 real 2D and 3D spectra of eight target proteins, and achieves an average of 88% recall and 74% precision. PICKY is efficient. It takes PICKY on average 15.7 s to process an NMR spectrum. More important than these numbers, PICKY actually works in practice. We feed peak lists generated by PICKY to IPASS for resonance assignment, feed IPASS assignment to SPARTA for fragments generation, and feed SPARTA fragments to FALCON for structure calculation. This results in high-resolution structures of several proteins, for example, TM1112, at 1.25 A. PICKY is available upon request. The peak lists of PICKY can be easily loaded by SPARKY to enable a better interactive strategy for rapid peak picking.

Symmetry based frequency domain processing to remove harmonic noise from surface nuclear magnetic resonance measurements

NASA Astrophysics Data System (ADS)

Hein, Annette; Larsen, Jakob Juul; Parsekian, Andrew D.

2017-02-01

Surface nuclear magnetic resonance (NMR) is a unique geophysical method due to its direct sensitivity to water. A key limitation to overcome is the difficulty of making surface NMR measurements in environments with anthropogenic electromagnetic noise, particularly constant frequency sources such as powerlines. Here we present a method of removing harmonic noise by utilizing frequency domain symmetry of surface NMR signals to reconstruct portions of the spectrum corrupted by frequency-domain noise peaks. This method supplements the existing NMR processing workflow and is applicable after despiking, coherent noise cancellation, and stacking. The symmetry based correction is simple, grounded in mathematical theory describing NMR signals, does not introduce errors into the data set, and requires no prior knowledge about the harmonics. Modelling and field examples show that symmetry based noise removal reduces the effects of harmonics. In one modelling example, symmetry based noise removal improved signal-to-noise ratio in the data by 10 per cent. This improvement had noticeable effects on inversion parameters including water content and the decay constant T2*. Within water content profiles, aquifer boundaries and water content are more accurate after harmonics are removed. Fewer spurious water content spikes appear within aquifers, which is especially useful for resolving multilayered structures. Within T2* profiles, estimates are more accurate after harmonics are removed, especially in the lower half of profiles.

Exploiting periodic first-principles calculations in NMR spectroscopy of disordered solids.

PubMed

Ashbrook, Sharon E; Dawson, Daniel M

2013-09-17

Much of the information contained within solid-state nuclear magnetic resonance (NMR) spectra remains unexploited because of the challenges in obtaining high-resolution spectra and the difficulty in assigning those spectra. Recent advances that enable researchers to accurately and efficiently determine NMR parameters in periodic systems have revolutionized the application of density functional theory (DFT) calculations in solid-state NMR spectroscopy. These advances are particularly useful for experimentalists. The use of first-principles calculations aids in both the interpretation and assignment of the complex spectral line shapes observed for solids. Furthermore, calculations provide a method for evaluating potential structural models against experimental data for materials with poorly characterized structures. Determining the structure of well-ordered, periodic crystalline solids can be straightforward using methods that exploit Bragg diffraction. However, the deviations from periodicity, such as compositional, positional, or temporal disorder, often produce the physical properties (such as ferroelectricity or ionic conductivity) that may be of commercial interest. With its sensitivity to the atomic-scale environment, NMR provides a potentially useful tool for studying disordered materials, and the combination of experiment with first-principles calculations offers a particularly attractive approach. In this Account, we discuss some of the issues associated with the practical implementation of first-principles calculations of NMR parameters in solids. We then use two key examples to illustrate the structural insights that researchers can obtain when applying such calculations to disordered inorganic materials. First, we describe an investigation of cation disorder in Y2Ti(2-x)Sn(x)O7 pyrochlore ceramics using (89)Y and (119)Sn NMR. Researchers have proposed that these materials could serve as host phases for the encapsulation of lanthanide- and actinide-bearing radioactive waste. In a second example, we discuss how (17)O NMR can be used to probe the dynamic disorder of H in hydroxyl-humite minerals (nMg2SiO4·Mg(OH)2), and how (19)F NMR can be used to understand F substitution in these systems. The combination of first-principles calculations and multinuclear NMR spectroscopy facilitates the investigation of local structure, disorder, and dynamics in solids. We expect that applications will undoubtedly become more widespread with further advances in computational and experimental methods. Insight into the atomic-scale environment is a crucial first step in understanding the structure-property relationships in solids, and it enables the efficient design of future materials for a range of end uses.

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.

Detection of platinum dihydride bisphosphine complexes and studies of their reactivity through para-hydrogen-enhanced NMR methods.

PubMed

Godard, Cyril; López-Serrano, Joaquín; Gálvez-López, María-Dolores; Roselló-Merino, Marta; Duckett, Simon B; Khazal, Iman; Lledós, Agustí; Whitwood, Adrian C

2008-01-01

In-situ NMR studies on the reactions of Pt{CH2 = CHSi(Me)2}2O)(PCy3) with phosphines, HSiEt3 and--hydrogen or Pt(L)(L')(Me)(2) alone enable the detection of cis-Pt(L)(L')(H)2 [L = PCy3 and L' = PCy2H, PPh3 or PCy3] which then undergo hydride site interchange and H2 reductive elimination on the NMR timescale.

Emerging new strategies for successful metabolite identification in metabolomics

PubMed Central

Bingol, Kerem; Bruschweiler-Li, Lei; Li, Dawei; Zhang, Bo; Xie, Mouzhe; Brüschweiler, Rafael

2016-01-01

This review discusses strategies for the identification of metabolites in complex biological mixtures, as encountered in metabolomics, which have emerged in the recent past. These include NMR database-assisted approaches for the identification of commonly known metabolites as well as novel combinations of NMR and MS analysis methods for the identification of unknown metabolites. The use of certain chemical additives to the NMR tube can permit identification of metabolites with specific physical chemical properties. PMID:26915807

Extracting protein dynamics information from overlapped NMR signals using relaxation dispersion difference NMR spectroscopy.

PubMed

Konuma, Tsuyoshi; Harada, Erisa; Sugase, Kenji

2015-12-01

Protein dynamics plays important roles in many biological events, such as ligand binding and enzyme reactions. NMR is mostly used for investigating such protein dynamics in a site-specific manner. Recently, NMR has been actively applied to large proteins and intrinsically disordered proteins, which are attractive research targets. However, signal overlap, which is often observed for such proteins, hampers accurate analysis of NMR data. In this study, we have developed a new methodology called relaxation dispersion difference that can extract conformational exchange parameters from overlapped NMR signals measured using relaxation dispersion spectroscopy. In relaxation dispersion measurements, the signal intensities of fluctuating residues vary according to the Carr-Purcell-Meiboon-Gill pulsing interval, whereas those of non-fluctuating residues are constant. Therefore, subtraction of each relaxation dispersion spectrum from that with the highest signal intensities, measured at the shortest pulsing interval, leaves only the signals of the fluctuating residues. This is the principle of the relaxation dispersion difference method. This new method enabled us to extract exchange parameters from overlapped signals of heme oxygenase-1, which is a relatively large protein. The results indicate that the structural flexibility of a kink in the heme-binding site is important for efficient heme binding. Relaxation dispersion difference requires neither selectively labeled samples nor modification of pulse programs; thus it will have wide applications in protein dynamics analysis.

Extended internal standard method for quantitative 1H NMR assisted by chromatography (EIC) for analyte overlapping impurity on 1H NMR spectra.

PubMed

Saito, Naoki; Kitamaki, Yuko; Otsuka, Satoko; Yamanaka, Noriko; Nishizaki, Yuzo; Sugimoto, Naoki; Imura, Hisanori; Ihara, Toshihide

2018-07-01

We devised a novel extended internal standard method of quantitative 1 H NMR (qNMR) assisted by chromatography (EIC) that accurately quantifies 1 H signal areas of analytes, even when the chemical shifts of the impurity and analyte signals overlap completely. When impurity and analyte signals overlap in the 1 H NMR spectrum but can be separated in a chromatogram, the response ratio of the impurity and an internal standard (IS) can be obtained from the chromatogram. If the response ratio can be converted into the 1 H signal area ratio of the impurity and the IS, the 1 H signal area of the analyte can be evaluated accurately by mathematically correcting the contributions of the 1 H signal area of the impurity overlapping the analyte in the 1 H NMR spectrum. In this study, gas chromatography and liquid chromatography were used. We used 2-chlorophenol and 4-chlorophenol containing phenol as an impurity as examples in which impurity and analyte signals overlap to validate and demonstrate the EIC, respectively. Because the 1 H signals of 2-chlorophenol and phenol can be separated in specific alkaline solutions, 2-chlorophenol is suitable to validate the EIC by comparing analytical value obtained by the EIC with that by only qNMR under the alkaline condition. By the EIC, the purity of 2-chlorophenol was obtained with a relative expanded uncertainty (k = 2) of 0.24%. The purity matched that obtained under the alkaline condition. Furthermore, the EIC was also validated by evaluating the phenol content with the absolute calibration curve method by gas chromatography. Finally, we demonstrated that the EIC was possible to evaluate the purity of 4-chlorophenol, with a relative expanded uncertainty (k = 2) of 0.22%, which was not able to be separated from the 1 H signal of phenol under any condition. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Deuterium and lithium-6 MAS NMR studies of manganese oxide electrode materials

NASA Astrophysics Data System (ADS)

Paik, Younkee

Electrolytic manganese dioxide (EMD) is used world wide as the cathode materials in both lithium and alkaline primary (non-rechargeable) batteries. We have developed deuterium and lithium MAS NMR techniques to study EMD and related manganese oxides and hydroxides, where diffraction techniques are of limited value due to a highly defective nature of the structures. Deuterons in EMD, manganite, groutite, and deuterium-intercalated pyrolusite and ramsdellite were detected by NMR, for the first time, and their locations and motions in the structures were analyzed by applying variable temperature NMR techniques. Discharge mechanisms of EMD in alkaline (aqueous) electrolytes were studied, in conjunction with step potential electrochemical spectroscopic (SPECS) method, and five distinctive discharge processes were proposed. EMD is usually heat-treated at about 300--400°C to remove water to be used in lithium batteries. Details of the effects of heat-treatment, such as structural and compositional changes as a function of heat-treatment temperature, were studied by a combination of MAS NMR, XRD, and thermogravimetric analysis. Lithium local environments in heat-treated EMD (HEMD) that were discharged in lithium cells, were described in terms of related environments found in model compounds pyrolusite and ramsdellite where specific Li + sites were detected by MAS NMR and the hyperfine shift scale method of Grey et al. Acid-leaching of Li2MnO3 represents an approach for synthesizing new or modified manganese oxide electrode materials for lithium rechargeable batteries. Progressive removal of lithium from specific crystallographic sites, followed by a gradual change of the crystal structure, was monitored by a combination of NMR and XRD techniques.

Profiling Redox and Energy Coenzymes in Whole Blood, Tissue and Cells Using NMR Spectroscopy.

PubMed

Gowda, G A Nagana

2018-05-14

Coenzymes of cellular redox reactions and cellular energy, as well as antioxidants mediate biochemical reactions fundamental to the functioning of all living cells. Conventional analysis methods lack the opportunity to evaluate these important redox and energy coenzymes and antioxidants in a single step. Major coenzymes include redox coenzymes: NAD⁺ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), NADP⁺ (oxidized nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate); energy coenzymes: ATP (adenosine triphosphate), ADP (adenosine diphosphate) and AMP (adenosine monophosphate); and antioxidants: GSSG (oxidized glutathione) and GSH (reduced glutathione). We show here that a simple ¹H NMR experiment can measure these coenzymes and antioxidants in tissue and whole blood apart from a vast pool of other metabolites. In addition, focused on the goal of identification of coenzymes in subcellular fractions, we demonstrate analysis of coenzymes in the cytoplasm using breast cancer cells. Owing to their unstable nature, or low concentrations, most of the coenzymes either evade detection or lose their integrity when established sample preparation and analysis methods are used. To overcome this challenge, here we describe the development of new methods to detect these molecules without affecting the integrity of other metabolites. We used an array of 1D and 2D NMR methods, chemical shift databases, pH measurements and spiking with authentic compounds to establish the identity of peaks for the coenzymes and antioxidants in NMR spectra. Interestingly, while none of the coenzymes and antioxidants were detected in plasma, they were abundant in whole blood. Considering that the coenzymes and antioxidants represent a sensitive measure of human health and risk for numerous diseases, the presented NMR methods to measure them in one step potentially open new opportunities in the metabolomics field.

Computational approach to integrate 3D X-ray microtomography and NMR data

NASA Astrophysics Data System (ADS)

Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Trevizan, Willian A.; Fortulan, Carlos A.; Bonagamba, Tito J.

2018-07-01

Nowadays, most of the efforts in NMR applied to porous media are dedicated to studying the molecular fluid dynamics within and among the pores. These analyses have a higher complexity due to morphology and chemical composition of rocks, besides dynamic effects as restricted diffusion, diffusional coupling, and exchange processes. Since the translational nuclear spin diffusion in a confined geometry (e.g. pores and fractures) requires specific boundary conditions, the theoretical solutions are restricted to some special problems and, in many cases, computational methods are required. The Random Walk Method is a classic way to simulate self-diffusion along a Digital Porous Medium. Bergman model considers the magnetic relaxation process of the fluid molecules by including a probability rate of magnetization survival under surface interactions. Here we propose a statistical approach to correlate surface magnetic relaxivity with the computational method applied to the NMR relaxation in order to elucidate the relationship between simulated relaxation time and pore size of the Digital Porous Medium. The proposed computational method simulates one- and two-dimensional NMR techniques reproducing, for example, longitudinal and transverse relaxation times (T1 and T2, respectively), diffusion coefficients (D), as well as their correlations. For a good approximation between the numerical and experimental results, it is necessary to preserve the complexity of translational diffusion through the microstructures in the digital rocks. Therefore, we use Digital Porous Media obtained by 3D X-ray microtomography. To validate the method, relaxation times of ideal spherical pores were obtained and compared with the previous determinations by the Brownstein-Tarr model, as well as the computational approach proposed by Bergman. Furthermore, simulated and experimental results of synthetic porous media are compared. These results make evident the potential of computational physics in the analysis of the NMR data for complex porous materials.

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.

Simulations of molecular diffusion in lattices of cells: insights for NMR of red blood cells.

PubMed Central

Regan, David G; Kuchel, Philip W

2002-01-01

The pulsed field-gradient spin-echo (PGSE) nuclear magnetic resonance (NMR) experiment, conducted on a suspension of red blood cells (RBC) in a strong magnetic field yields a q-space plot consisting of a series of maxima and minima. This is mathematically analogous to a classical optical diffraction pattern. The method provides a noninvasive and novel means of characterizing cell suspensions that is sensitive to changes in cell shape and packing density. The positions of the features in a q-space plot characterize the rate of exchange across the membrane, cell dimensions, and packing density. A diffusion tensor, containing information regarding the diffusion anisotropy of the system, can also be derived from the PGSE NMR data. In this study, we carried out Monte Carlo simulations of diffusion in suspensions of "virtual" cells that had either biconcave disc (as in RBC) or oblate spheroid geometry. The simulations were performed in a PGSE NMR context thus enabling predictions of q-space and diffusion tensor data. The simulated data were compared with those from real PGSE NMR diffusion experiments on RBC suspensions that had a range of hematocrit values. Methods that facilitate the processing of q-space data were also developed. PMID:12080109

Re-polarization of nuclear spins using selective SABRE-INEPT.

PubMed

Knecht, Stephan; Kiryutin, Alexey S; Yurkovskaya, Alexandra V; Ivanov, Konstantin L

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH 2 , the H 2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε. For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε≈260 for 15 N nuclei, whereas SABRE-INEPT with re-polarization yields ε>2000. We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques. Copyright © 2017 Elsevier Inc. All rights reserved.

Re-polarization of nuclear spins using selective SABRE-INEPT

NASA Astrophysics Data System (ADS)

Knecht, Stephan; Kiryutin, Alexey S.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L.

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε . For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε ≈ 260 for 15N nuclei, whereas SABRE-INEPT with re-polarization yields ε > 2000 . We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques.

Combined NMR and EPR Spectroscopy to Determine Structures of Viral Fusion Domains in Membranes

PubMed Central

Tamm, Lukas K.; Lai, Alex L.; Li, Yinling

2008-01-01

Methods are described to determine the structures of viral membrane fusion domains in detergent micelles by NMR and in lipid bilayers by site-directed spin labeling and EPR spectroscopy. Since in favorable cases, the lower-resolution spin label data obtained in lipid bilayers fully support the higher-resolution structures obtained by solution NMR, it is possible to graft the NMR structural coordinates into membranes using the EPR-derived distance restraints to the lipid bilayer. Electron paramagnetic dynamics and distance measurements in bilayers support conclusions drawn from NMR in detergent micelles. When these methods are applied to a structure determination of the influenza virus fusion domain and four point mutations with different functional phenotypes, it is evident that a fixed-angle boomerang structure with a glycine edge on the outside of the N-terminal arm is both necessary and sufficient to support membrane fusion. The human immunodeficiency virus fusion domain forms a straight helix with a flexible C-terminus. While EPR data for this fusion domain are not yet available, it is tentatively speculated that, because of its higher hydrophobicity, a critically tilted insertion may occur even in the absence of a kinked boomerang structure in this case. PMID:17963720

Conformational analysis of capsaicin using 13C, 15N MAS NMR, GIAO DFT and GA calculations

NASA Astrophysics Data System (ADS)

Siudem, Paweł; Paradowska, Katarzyna; Bukowicki, Jarosław

2017-10-01

Capsaicin produced by plants from genus Capsicum exerts multiple pharmacological effects and has found applications in food and pharmaceutical industry. The alkaloid was studied by a combined approach: solid-state NMR, GA conformational search and GIAO DFT methods. The 13C CPMAS NMR spectra were recorded using variable contact time and dipolar dephasing experiments. The results of cross-polarization (CP) kinetics, such as TCP values and long T1ρH (100-200 ms), indicated that the capsaicin molecule is fairly mobile, especially at the end of the aliphatic chain. The15N MAS NMR spectrum showed one narrow signal at -255 ppm. Genetic algorithm (GA) search with multi modal optimization was used to find low-energy conformations of capsaicin. Theoretical GIAO DFT calculations were performed using different basis sets to characterize five selected conformations. 13C CPMAS NMR was used as a validation method and the experimental chemical shifts were compared with those calculated for selected stable conformers. Conformational analysis suggests that the side chain can be bent or extended. A comparison of the experimental and the calculated chemical shifts indicates that solid capsaicin does not have the same structure as those established by PWXRD.

Simulations of molecular diffusion in lattices of cells: insights for NMR of red blood cells.

PubMed

Regan, David G; Kuchel, Philip W

2002-07-01

The pulsed field-gradient spin-echo (PGSE) nuclear magnetic resonance (NMR) experiment, conducted on a suspension of red blood cells (RBC) in a strong magnetic field yields a q-space plot consisting of a series of maxima and minima. This is mathematically analogous to a classical optical diffraction pattern. The method provides a noninvasive and novel means of characterizing cell suspensions that is sensitive to changes in cell shape and packing density. The positions of the features in a q-space plot characterize the rate of exchange across the membrane, cell dimensions, and packing density. A diffusion tensor, containing information regarding the diffusion anisotropy of the system, can also be derived from the PGSE NMR data. In this study, we carried out Monte Carlo simulations of diffusion in suspensions of "virtual" cells that had either biconcave disc (as in RBC) or oblate spheroid geometry. The simulations were performed in a PGSE NMR context thus enabling predictions of q-space and diffusion tensor data. The simulated data were compared with those from real PGSE NMR diffusion experiments on RBC suspensions that had a range of hematocrit values. Methods that facilitate the processing of q-space data were also developed.

Fully automatic assignment of small molecules' NMR spectra without relying on chemical shift predictions.

PubMed

Castillo, Andrés M; Bernal, Andrés; Patiny, Luc; Wist, Julien

2015-08-01

We present a method for the automatic assignment of small molecules' NMR spectra. The method includes an automatic and novel self-consistent peak-picking routine that validates NMR peaks in each spectrum against peaks in the same or other spectra that are due to the same resonances. The auto-assignment routine used is based on branch-and-bound optimization and relies predominantly on integration and correlation data; chemical shift information may be included when available to fasten the search and shorten the list of viable assignments, but in most cases tested, it is not required in order to find the correct assignment. This automatic assignment method is implemented as a web-based tool that runs without any user input other than the acquired spectra. Copyright © 2015 John Wiley & Sons, Ltd.

Is biomedical nuclear magnetic resonance limited by a revisitable paradigm in physics?

PubMed

de Certaines, J D

2005-12-14

The history of nuclear magnetic resonance (NMR) can be divided generally into two phases: before the Second World War, molecular beam methods made it possible to detect the whole set of spins. However, these methods were destructive for the sample and had a very low precision. The publications of F. Bloch and E. Purcell in 1946 opened up a second phase for NMR with the study of condensed matter, but at the expense of an enormous loss in theoretical sensitivity. During more than half a century, the method of Bloch and Purcell, based on inductive detection of the NMR signal, has allowed many developments in biomedicine. But, curiously, this severely constraining limitation on sensitivity has not been called into question during this half-century, as if the pioneers of the pre-war period had been forgotten.

Elucidating structural characteristics of biomass using solution-state 2 D NMR with a mixture of deuterated dimethylsulfoxide and hexamethylphosphoramide

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

Pu, Yunqiao; Ragauskas, Arthur J.; Yoo, Chang Geun

In recent developments of NMR methods for characterization of lignocellulosic biomass allow improved understanding of plant cell-wall structures with minimal deconstruction and modification of biomass. This study introduces a new NMR solvent system composed of dimethylsulfoxide (DMSO- d 6) and hexamethylphosphoramide (HMPA- d 18). HMPA as a co-solvent enhanced swelling and mobility of the biomass samples; thereby it allowed enhancing signals of NMR spectra. Moreover, the structural information of biomass was successfully analyzed by the proposed NMR solvent system (DMSO- d 6/HMPA-d 18; 4:1, v/v) with different biomass. The proposed bi-solvent system does not require derivatization or isolation of biomass,more » facilitating a facile sample preparation and involving with no signals overlapping with biomass peaks. Furthermore, it also allows analyzing biomass with a room-temperature NMR probe instead of cryo-probes, which are traditionally used for enhancing signal intensities.« less

Elucidating structural characteristics of biomass using solution-state 2 D NMR with a mixture of deuterated dimethylsulfoxide and hexamethylphosphoramide

DOE PAGES

Pu, Yunqiao; Ragauskas, Arthur J.; Yoo, Chang Geun; ...

2016-04-26

In recent developments of NMR methods for characterization of lignocellulosic biomass allow improved understanding of plant cell-wall structures with minimal deconstruction and modification of biomass. This study introduces a new NMR solvent system composed of dimethylsulfoxide (DMSO- d 6) and hexamethylphosphoramide (HMPA- d 18). HMPA as a co-solvent enhanced swelling and mobility of the biomass samples; thereby it allowed enhancing signals of NMR spectra. Moreover, the structural information of biomass was successfully analyzed by the proposed NMR solvent system (DMSO- d 6/HMPA-d 18; 4:1, v/v) with different biomass. The proposed bi-solvent system does not require derivatization or isolation of biomass,more » facilitating a facile sample preparation and involving with no signals overlapping with biomass peaks. Furthermore, it also allows analyzing biomass with a room-temperature NMR probe instead of cryo-probes, which are traditionally used for enhancing signal intensities.« less

Developments in μSR and β NMR: Beyond a Muon Lifetime

NASA Astrophysics Data System (ADS)

Kiefl, Robert F.

Advances in the use of μSR and β-NMR are driven by technical developments. New methods were developed which allowed us to learn surprising things about muonium in semiconductors, its electronic structure, its relationship to hydrogen, its ability to diffuse via quantum tunneling, and its metastability. Similarly in the area of high Tc superconductors new capabilities in spectrometer design led to new information on the properties of superconducting vortices and how they interact. The development of low energy β-NMR at TRIUMF and LE-μSR at PSI has made it possible to study electronic and magnetic properties of thin films and interfaces where conventional NMR lacks the required sensitivity. Low energy β-NMR is almost identical to μSR in principle, but the longer lifetime of 8Li allows one to probe the system on a very different time scale. In this sense β-NMR can be viewed as a complement or extension of μSR.

Natural abundance (25)Mg solid-state NMR of mg oxyanion systems: a combined experimental and computational study.

PubMed

Cahill, Lindsay S; Hanna, John V; Wong, Alan; Freitas, Jair C C; Yates, Jonathan R; Harris, Robin K; Smith, Mark E

2009-09-28

Solid-state (25)Mg magic angle spinning nuclear magnetic resonance (MAS NMR) data are reported from a range of organic and inorganic magnesium-oxyanion compounds at natural abundance. To constrain the determination of the NMR interaction parameters (delta(iso), chi(Q), eta(Q)) data have been collected at three external magnetic fields (11.7, 14.1 and 18.8 T). Corresponding NMR parameters have also been calculated by using density functional theory (DFT) methods using the GIPAW approach, with good correlations being established between experimental and calculated values of both chi(Q) and delta(iso). These correlations demonstrate that the (25)Mg NMR parameters are very sensitive to the structure, with small changes in the local Mg(2+) environment and the overall hydration state profoundly affecting the observed spectra. The observations suggest that (25)Mg NMR spectroscopy is a potentially potent probe for addressing some key problems in inorganic materials and of metal centres in biologically relevant molecules.

Shear rheology and 1H TD-NMR combined to low-field RheoNMR: Set-up and application to quiescent and flow-induced crystallization of polymers

NASA Astrophysics Data System (ADS)

Räntzsch, Volker; Özen, Mürüvvet Begüm; Ratzsch, Karl-Friedrich; Guthausen, Gisela; Wilhelm, Manfred

2017-05-01

Rheology provides access to the flow properties of soft matter, while 1H TD-NMR is a useful technique for the characterization of molecular dynamics. To achieve greater insight into the interplay of these domains, especially under flow, it is desirable to combine these two methods in one set-up. We present a low-field RheoNMR set-up based on a portable 30 MHz 1H NMR unit that was integrated into a commercial strain-controlled shear rheometer. This unique combination can simultaneously conduct a full rheological characterization (G', G", |η*|, FT-Rheology: I3/1, Q0) while monitoring molecular dynamics in-situ via 1H TD-NMR for temperatures from -15 to +210 °C. Possible applications include the quantitative measurement of the composition in multiphase systems (fats, polymers, etc.) and soft matter during the application of flow, e.g. measurements on the flow-induced crystallization of polymers.

Elucidating Structural Characteristics of Biomass using Solution-State 2 D NMR with a Mixture of Deuterated Dimethylsulfoxide and Hexamethylphosphoramide.

PubMed

Yoo, Chang Geun; Pu, Yunqiao; Li, Mi; Ragauskas, Arthur J

2016-05-23

Recent developments of NMR methods for characterization of lignocellulosic biomass allow improved understanding of plant cell-wall structures with minimal deconstruction and modification of biomass. This study introduces a new NMR solvent system composed of dimethylsulfoxide (DMSO-d6 ) and hexamethylphosphoramide (HMPA-d18 ). HMPA as a co-solvent enhanced swelling and mobility of the biomass samples; thereby it allowed enhancing signals of NMR spectra. The structural information of biomass was successfully analyzed by the proposed NMR solvent system (DMSO-d6 /HMPA-d18 ; 4:1, v/v) with different biomass. The proposed bi-solvent system does not require derivatization or isolation of biomass, facilitating a facile sample preparation and involving with no signals overlapping with biomass peaks. It also allows analyzing biomass with a room-temperature NMR probe instead of cryo-probes, which are traditionally used for enhancing signal intensities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Integrated NMR Core and Log Investigations With Respect to ODP LEG 204

NASA Astrophysics Data System (ADS)

Arnold, J.; Pechnig, R.; Clauser, C.; Anferova, S.; Blümich, B.

2005-12-01

NMR techniques are widely used in the oil industry and are one of the most suitable methods to evaluate in-situ formation porosity and permeability. Recently, efforts are directed towards adapting NMR methods also to the Ocean Drilling Program (ODP) and the upcoming Integrated Ocean Drilling Program (IODP). We apply a newly developed light-weight, mobile NMR core scanner as a non-destructive instrument to determine routinely rock porosity and to estimate the pore size distribution. The NMR core scanner is used for transverse relaxation measurements on water-saturated core sections using a CPMG sequence with a short echo time. A regularized Laplace-transform analysis yields the distribution of transverse relaxation times T2. In homogeneous magnetic fields, T2 is proportional to the pore diameter of rocks. Hence, the T2 signal maps the pore-size distribution of the studied rock samples. For fully saturated samples the integral of the distribution curve and the CPMG echo amplitude extrapolated to zero echo time are proportional to porosity. Preliminary results show that the NMR core scanner is a suitable tool to determine rock porosity and to estimate pore size distribution of limestones and sandstones. Presently our investigations focus on Leg 204, where NMR Logging-While-Drilling (LWD) was performed for the first time in ODP. Leg 204 was drilled into Hydrate Ridge on the Cascadia accretionary margin, offshore Oregon. All drilling and logging operations were highly successful, providing excellent core, wireline, and LWD data from adjacent boreholes. Cores recovered during Leg 204 consist mainly of clay and claystone. As the NMR core scanner operates at frequencies higher than that of the well-logging sensor it has a shorter dead time. This advantage makes the NMR core scanner sensitive to signals with T2 values down to 0.1 ms as compared to 3 ms in NMR logging. Hence, we can study even rocks with small pores, such as the mudcores recovered during Leg 204. We present a comparison of data from core scanning and NMR logging. Future integration of conventional wireline data and electrical borehole wall images (RAB/FMS) will provide a detailed characterization of the sediments in terms of lithology, petrophysics and, fluid flow properties.

Unambiguous metabolite identification in high-throughput metabolomics by hybrid 1D 1 H NMR/ESI MS 1 approach: Hybrid 1D 1 H NMR/ESI MS 1 metabolomics method

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

Walker, Lawrence R.; Hoyt, David W.; Walker, S. Michael

We present a novel approach to improve accuracy of metabolite identification by combining direct infusion ESI MS1 with 1D 1H NMR spectroscopy. The new approach first applies standard 1D 1H NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in metabolomics library. This generates a list of candidate metabolites. The list contains false positive and ambiguous identifications. Next, we constrained the list with the chemical formulas derived from high-resolution direct infusion ESI MS1 spectrum of the same sample. Detection of the signals of a metabolitemore » both in NMR and MS significantly improves the confidence of identification and eliminates false positive identification. 1D 1H NMR and direct infusion ESI MS1 spectra of a sample can be acquired in parallel in several minutes. This is highly beneficial for rapid and accurate screening of hundreds of samples in high-throughput metabolomics studies. In order to make this approach practical, we developed a software tool, which is integrated to Chenomx NMR Suite. The approach is demonstrated on a model mixture, tomato and Arabidopsis thaliana metabolite extracts, and human urine.« less

Application of pulsed field gradient NMR techniques for investigating binding of flavor compounds to macromolecules.

PubMed

Jung, Da-Mi; De Ropp, Jeffrey S; Ebeler, Susan E

2002-07-17

Two diffusion-based NMR techniques are presented and used to investigate the binding of selected flavor compounds to macromolecules. A pulsed field gradient NMR (PFG-NMR) method was applied to measure the apparent diffusion coefficients of four alkanone compounds as they associated with bovine serum albumin (BSA). The change in the apparent diffusion coefficient as a function of the BSA/alkanone ratio was fitted to yield binding constants (K(a)()) and binding stoichiometry (n) for each alkanone. The results showed that the apparent diffusion coefficients of alkanones increased with a decrease in the BSA/alkanone ratios, and the measured values of K(a)() and n were comparable with those obtained with other methods and depended on the alkanone structure. A diffusion-based nuclear Overhauser effect (called diffusion NOE pumping) method was also applied to screen mixtures of flavor compounds and identify those that have a binding affinity to complex macromolecules. Using this technique benzaldehyde and vanillin were observed to bind with bovine serum albumin, whereas 2-phenylethanol was identified as a nonbinding or weakly binding ligand with BSA. The diffusion NOE pumping method was also applied to a hydro alcoholic solution of cacao bean tannin extracts to which a mixture of ethylbenzoate, benzaldehyde, and 2-phenylethanol was added. The diffusion NOE pumping technique clearly indicated that ethylbenzoate had a stronger binding affinity to the polymeric (-)-epicatechin units of the cacao bean tannin extracts than the other two flavor compounds. The results successfully demonstrate the potential applications of diffusion-based NMR techniques for studying flavors and nonvolatile food matrix interactions.

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.

Comparison of soil organic carbon speciation using C NEXAFS and CPMAS 13C NMR spectroscopy.

PubMed

Prietzel, Jörg; Müller, Svenja; Kögel-Knabner, Ingrid; Thieme, Jürgen; Jaye, Cherno; Fischer, Daniel

2018-07-01

We compared synchrotron-based C near-edge X-ray absorption fine structure (NEXAFS) and CPMAS 13 C nuclear magnetic resonance (NMR) spectroscopy with respect to their precision and accuracy to quantify different organic carbon (OC) species in defined mixtures of soil organic matter source compounds. We also used both methods to quantify different OC species in organic surface horizons of a Histic Leptosol as well as in mineral topsoil and subsoil horizons of two soils with different parent material, stage of pedogenesis, and OC content (Cambisol: 15-30 OC mgg -1 , Podzol: 0.9-7 OC mgg -1 ). CPMAS 13 C NMR spectroscopy was more accurate and precise (mean recovery of different C functional groups 96-103%) than C NEXAFS spectroscopy (mean recovery 92-113%). For organic surface and topsoil samples, NMR spectroscopy consistently yielded larger O-alkyl C percentages and smaller alkyl C percentages than C NEXAFS spectroscopy. For the Cambisol subsoil samples both methods performed well and showed similar C speciation results. NEXAFS spectroscopy yielded excellent spectra with a high signal-to-noise ratio also for OC-poor Podzol subsoil samples, whereas this was not the case for CPMAS 13 C NMR spectroscopy even after sample treatment with HF. Our results confirm the analytical power of CPMAS 13 C NMR spectroscopy for a reliable quantitative OC speciation in soils with >10mgOCg -1 . Moreover, they highlight the potential of synchrotron-based C NEXAFS spectroscopy as fast, non-invasive method to semi-quantify different C functional groups in soils with low C content (0.9-10mgg -1 ). Copyright © 2018 Elsevier B.V. All rights reserved.

Multiple acquisition of magic angle spinning solid-state NMR experiments using one receiver: Application to microcrystalline and membrane protein preparations

NASA Astrophysics Data System (ADS)

Gopinath, T.; Veglia, Gianluigi

2015-04-01

Solid-state NMR spectroscopy of proteins is a notoriously low-throughput technique. Relatively low-sensitivity and poor resolution of protein samples require long acquisition times for multidimensional NMR experiments. To speed up data acquisition, we developed a family of experiments called Polarization Optimized Experiments (POE), in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. POE allow the concatenation of multiple 2D or 3D pulse sequences into a single experiment, thus potentially combining all of the aforementioned advances, boosting the capability of ssNMR spectrometers at least two-fold without the addition of any hardware. In this perspective, we describe the first generation of POE, such as dual acquisition MAS (or DUMAS) methods, and then illustrate the evolution of these experiments into MEIOSIS, a method that enables the simultaneous acquisition of multiple 2D and 3D spectra. Using these new pulse schemes for the solid-state NMR investigation of biopolymers makes it possible to obtain sequential resonance assignments, as well as distance restraints, in about half the experimental time. While designed for acquisition of heteronuclei, these new experiments can be easily implemented for proton detection and coupled with other recent advancements, such as dynamic nuclear polarization (DNP), to improve signal to noise. Finally, we illustrate the application of these methods to microcrystalline protein preparations as well as single and multi-span membrane proteins reconstituted in lipid membranes.

NMR investigation and theoretical calculations of the solvent effect on the conformation of valsartan

NASA Astrophysics Data System (ADS)

Chashmniam, Saeed; Tafazzoli, Mohsen

2017-11-01

Structure and conformational properties of valsartan were studied by advanced NMR techniques and quantum calculation methods. Potential energy scanning using B3LYP/6-311++g** and B3LYP-D3/6-311++g** methods were performed and four conformers (V1-V4) at minimum points of PES diagram were observed. According to the NMR spectra in acetone-d6, there are two conformers (M and m) with m/M = 0.52 ratio simultaneously and energy barriers of the two conformers were predicted from chemical shifts and multiplicities. While, intramolecular hydrogen bond at tetrazole ring and carboxylic groups prevent the free rotation on N6sbnd C11 bond in M-conformer, this bond rotates freely in m-conformer. On the other hand, intramolecular hydrogen bond at carbonyl and carboxylic acid can be observed at m-conformer. So, different intramolecular hydrogen bond is the reason for the stability of both M and m structures. Quite interestingly, 1H NMR spectra in CDCl3 show two distinct conformers (N and n) with unequal ratio which are differ from M-m conformers. Also, intramolecular hydrogen bond seven-member ring involving five-membered tetrazole ring and carboxylic acid group observed in both N and n-conformers Solvent effect, by using a set of polar and non-polar solvents including DMSO-d6, methanol-d4, benzene-d6, THF-d8, nitromethane-d3, methylene chloride-d2 and acetonitrile-d3 were investigated. NMR parameters include chemical shifts and spin-spin coupling constants were obtained from a set of 2D NMR spectra (H-H COSY, HMQC and HMBC). For this purpose, several DFT functionals from LDA, GGA and hybrid categories were used which the hybrid method showed better agreement with experiment values.

Multiple acquisition of magic angle spinning solid-state NMR experiments using one receiver: application to microcrystalline and membrane protein preparations.

PubMed

Gopinath, T; Veglia, Gianluigi

2015-04-01

Solid-state NMR spectroscopy of proteins is a notoriously low-throughput technique. Relatively low-sensitivity and poor resolution of protein samples require long acquisition times for multidimensional NMR experiments. To speed up data acquisition, we developed a family of experiments called Polarization Optimized Experiments (POE), in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. POE allow the concatenation of multiple 2D or 3D pulse sequences into a single experiment, thus potentially combining all of the aforementioned advances, boosting the capability of ssNMR spectrometers at least two-fold without the addition of any hardware. In this perspective, we describe the first generation of POE, such as dual acquisition MAS (or DUMAS) methods, and then illustrate the evolution of these experiments into MEIOSIS, a method that enables the simultaneous acquisition of multiple 2D and 3D spectra. Using these new pulse schemes for the solid-state NMR investigation of biopolymers makes it possible to obtain sequential resonance assignments, as well as distance restraints, in about half the experimental time. While designed for acquisition of heteronuclei, these new experiments can be easily implemented for proton detection and coupled with other recent advancements, such as dynamic nuclear polarization (DNP), to improve signal to noise. Finally, we illustrate the application of these methods to microcrystalline protein preparations as well as single and multi-span membrane proteins reconstituted in lipid membranes. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiple Acquisition of Magic Angle Spinning Solid-State NMR Experiments Using One Receiver: Application to Microcrystalline and Membrane Protein Preparations

PubMed Central

Gopinath, T.; Veglia, Gianluigi

2015-01-01

Solid-State NMR spectroscopy of proteins is a notoriously low-throughput technique. Relatively low-sensitivity and poor resolution of protein samples require long acquisition times for multidimensional NMR experiments. To speed up data acquisition, we developed a family of experiments called Polarization Optimized Experiments (POE), in which we utilized the orphan spin operators that are discarded in classical multidimensional NMR experiments, recovering them to allow simultaneous acquisition of multiple 2D and 3D experiments, all while using conventional probes with spectrometers equipped with one receiver. POEs allow the concatenation of multiple 2D or 3D pulse sequences into a single experiment, thus potentially combining all of the aforementioned advances, boosting the capability of ssNMR spectrometers at least two-fold without the addition of any hardware. In this Perspective, we describe the first generation of POEs, such as dual acquisition MAS (or DUMAS) methods, and then illustrate the evolution of these experiments into MEIOSIS, a method that enables the simultaneous acquisition of multiple 2D and 3D spectra. Using these new pulse schemes for the solid-state NMR investigation of biopolymers makes it possible to obtain sequential resonance assignments, as well as distance restraints, in about half the experimental time. While designed for acquisition of heteronuclei, these new experiments can be easily implemented for proton detection and coupled with other recent advancements, such as dynamic polarization, to improve signal to noise. Finally, we illustrate the application of these methods to microcrystalline protein preparations as well as single and multi-span membrane proteins reconstituted in lipid membranes. PMID:25797011

Very Large Scale Integrated Circuits for Military Systems.

DTIC Science & Technology

1981-01-01

ABBREVIATIONS A/D Analog-to-digital C AGC Automatic Gain Control A A/J Anti-jam ASP Advanced Signal Processor AU Arithmetic Units C.AD Computer-Aided...ESM) equipments (Ref. 23); in lieu of an adequate automatic proces- sing capability, the function is now performed manually (Ref. 24), which involves...a human operator, displays, etc., and a sacrifice in performance (acquisition speed, saturation signal density). Various automatic processing

Using Parallel Processing for Problem Solving.

DTIC Science & Technology

1979-12-01

are the basic parallel proces- sing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities...Language primitives are provided for manipulating running activities. Viewpoints are a generalization of context FOM -(over "*’ DD I FON 1473 ’EDITION OF I...arc the basic parallel processing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities. Language

Reconfiguration in Robust Distributed Real-Time Systems Based on Global Checkpoints

DTIC Science & Technology

1991-12-01

achieved by utilizing distributed systems in which a single application program executes on multiple processors, connected to a network. The distributed...single application program executes on multiple proces- sors, connected to a network. The distributed nature of such systems make it possible to ...resident at every node. How - ever, the responsibility for execution of a particular function is assigned to only one node in this framework. This function

Food Program: Army Troop Issue Subsistence Activity Operating Policies

DTIC Science & Technology

1993-01-04

through 10). (2) Table, food preparation, stainless steel , 48 by 30 by 36, 3 each (tables should be numbered 1 through 3). d. Detailed instructions...installation Directorate of Contracting (DOC) in CONUS normally acquires subsistence authorized for local purchase on a free on-board (FOB) destination...blanket purchase agreement ( BPA ) and other local purchase contracts established at the installation. The proce- dures for such authorization are in the

Avionic Radome Materials

DTIC Science & Technology

1974-10-01

polyester chains. Cross-linking, normally known as the curing process, is brought about by free radicals supplied by a catalyst, usually an organic...peroxide. Cure is normally carried out at room temperature, but a higher tenmerature may be used, depending on the reactivity of the catalyst. In the...selection of an elevated cure temperature permits wide versatility and a large measure of control over the proces-ing of these resins. Since the direct

A Multi-Sensor Aerogeophysical Study of Afghanistan

DTIC Science & Technology

2007-01-01

magnetometer coupled with an Applied Physics 539 3-axis fluxgate mag- netometer for compensation of the aircraft field; • an Applanix DSS 301 digital...survey. DATA COlleCTION AND PROCeSSINg Photogrammetry More than 65,000 high-resolution photogram- metric images were collected using an Applanix Digital...HSI L-Band Polarimetric Imaging Radar KGPS Dual Gravity Meters Common Sensor Bomb-bay Pallet Applanix DSS Camera Sensor Suite • Magnetometer • Gravity

Technology Against Terrorism: The Federal Effort

DTIC Science & Technology

1991-07-01

control appli - control and airport security plans. Some difficulties cations, irises of those seeking entry would be have arisen: now that specific...Washington International Air- tion. Among more advanced technologies are four of port as a test-bed. Sandia is applying to airport interest: voice...and 300 by 1999. criteria as well as evaluation standards and proce- In further tests carried out at JFK Airport in New dures for future EDS devices

Innovative Bioreactor Development for Methanotrophic Biodegradation of Trichloroethylene

DTIC Science & Technology

1994-01-01

biodegradation ot TCE for system optimization and process scaleup; 4. To determine the advantage of pulsed flow over steady-state operation through computer...TCE to nonhazardous products. The process is co-metabolic, i.e., the microorganisms do not derive any energetic advantage from degradation of the TCE...proces-. aleup; 4. To determine the advantage of pulsed flow over steady-state operation through computer process simulation using the empirical Alvarez

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.

Theoretical Modeling of (99)Tc NMR Chemical Shifts.

PubMed

Hall, Gabriel B; Andersen, Amity; Washton, Nancy M; Chatterjee, Sayandev; Levitskaia, Tatiana G

2016-09-06

Technetium-99 (Tc) displays a rich chemistry due to its wide range of accessible oxidation states (from -I to +VII) and ability to form coordination compounds. Determination of Tc speciation in complex mixtures is a major challenge, and (99)Tc nuclear magnetic resonance (NMR) spectroscopy is widely used to probe chemical environments of Tc in odd oxidation states. However, interpretation of (99)Tc NMR data is hindered by the lack of reference compounds. Density functional theory (DFT) calculations can help to fill this gap, but to date few computational studies have focused on (99)Tc NMR of compounds and complexes. This work evaluates the effectiveness of both pure generalized gradient approximation and their corresponding hybrid functionals, both with and without the inclusion of scalar relativistic effects, to model the (99)Tc NMR spectra of Tc(I) carbonyl compounds. With the exception of BLYP, which performed exceptionally well overall, hybrid functionals with inclusion of scalar relativistic effects are found to be necessary to accurately calculate (99)Tc NMR spectra. The computational method developed was used to tentatively assign an experimentally observed (99)Tc NMR peak at -1204 ppm to fac-Tc(CO)3(OH)3(2-). This study examines the effectiveness of DFT computations for interpretation of the (99)Tc NMR spectra of Tc(I) coordination compounds in high salt alkaline solutions.

Exploring Mass Transfer in Mesoporous Zeolites by NMR Diffusometry

PubMed Central

Mehlhorn, Dirk; Valiullin, Rustem; Kärger, Jörg; Cho, Kanghee; Ryoo, Ryong

2012-01-01

With the advent of mesoporous zeolites, the exploration of their transport properties has become a task of primary importance for the auspicious application of such materials in separation technology and heterogeneous catalysis. After reviewing the potential of the pulsed field gradient method of NMR (PFG NMR) for this purpose in general, in a case study using a specially prepared mesoporous zeolite NaCaA as a host system and propane as a guest molecule, examples of the attainable information are provided. PMID:28817004

NMR Relaxometry to Characterize the Drug Structural Phase in a Porous Construct.

PubMed

Thrane, Linn W; Berglund, Emily A; Wilking, James N; Vodak, David; Seymour, Joseph D

2018-06-14

Nuclear magnetic resonance (NMR) frequency spectra and T 2 relaxation time measurements, using a high-power radio frequency probe, are shown to characterize the presence of an amorphous drug in a porous silica construct. The results indicate the ability of non-solid-state NMR methods to characterize crystalline and amorphous solid structural phases in drugs. Two-dimensional T 1 - T 2 magnetic relaxation time correlation experiments are shown to monitor the impact of relative humidity on the drug in a porous silica tablet.

Nuclear Magnetic Resonance Spectroscopy

DTIC Science & Technology

1992-04-23

prototypical materials. NMR spectros- 3 copy has proven itself to be exceptionally adaptable to new Av I t 1 ab I 1 ty Godea SENiS 13 problem areas. A good ...8217 SENIS 4 as a scholarly enterprise is clearly in good health. Ironically, 3 the number of NMR articles published in this journal is down SENis 14...s tailed assessment of this method (JI) which also serves as a SEN0 o good overview of the relevant literature. Olah has published sRN12s NMR studies

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

A Step-by-Step Picture of Pulsed (Time-Domain) NMR.

ERIC Educational Resources Information Center

Schwartz, Leslie J.

1988-01-01

Discusses a method for teaching time pulsed NMR principals that are as simple and pictorial as possible. Uses xyz coordinate figures and presents theoretical explanations using a Fourier transformation spectrum. Assumes no previous knowledge of quantum mechanics for students. Usable for undergraduates. (MVL)

Rapid Identification of Synthetic Cannabinoids in Herbal Incenses with DART-MS and NMR.

PubMed

Marino, Michael A; Voyer, Brandy; Cody, Robert B; Dane, A John; Veltri, Mercurio; Huang, Ling

2016-01-01

The usage of herbal incenses containing synthetic cannabinoids has caused an increase in medical incidents and triggered legislations to ban these products throughout the world. Law enforcement agencies are experiencing sample backlogs due to the variety of the products and the addition of new and still-legal compounds. In our study, proton nuclear magnetic resonance (NMR) spectroscopy was employed to promptly screen the synthetic cannabinoids after their rapid, direct detection on the herbs and in the powders by direct analysis in real time mass spectrometry (DART-MS). A simple sample preparation protocol was employed on 50 mg of herbal sample matrices for quick NMR detection. Ten synthetic cannabinoids were discovered in fifteen herbal incenses. The combined DART-MS and NMR methods can be used to quickly screen synthetic cannabinoids in powder and herbal samples, serving as a complementary approach to conventional GC-MS or LC-MS methods. © 2015 American Academy of Forensic Sciences.

Solid-state NMR studies of theophylline co-crystals with dicarboxylic acids.

PubMed

Pindelska, Edyta; Sokal, Agnieszka; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Kolodziejski, Waclaw

2014-11-01

In this work, three polycrystalline materials containing co-crystals of theophylline with malonic, maleic, and glutaric acids were studied using (13)C, (15)N and (1)H solid-state NMR and FT-IR spectroscopy. The NMR assignments were supported by gauge including projector augmented waves (GIPAW) calculations of chemical shielding, performed using X-ray determined geometry. The experimental (13)C cross polarization/magic angle spinning (CP/MAS) NMR results and the calculated isotropic chemical shifts were in excellent agreement. A rapid and convenient method for theophylline co-crystals crystal structure analysis has been proposed for co-crystals, which are potentially new APIs. Copyright © 2014 Elsevier B.V. All rights reserved.

Dipolar induced para-hydrogen-induced polarization.

PubMed

Buntkowsky, Gerd; Gutmann, Torsten; Petrova, Marina V; Ivanov, Konstantin L; Bommerich, Ute; Plaumann, Markus; Bernarding, Johannes

2014-01-01

Analytical expressions for the signal enhancement in solid-state PHIP NMR spectroscopy mediated by homonuclear dipolar interactions and single pulse or spin-echo excitation are developed and simulated numerically. It is shown that an efficient enhancement of the proton NMR signal in solid-state NMR studies of chemisorbed hydrogen on surfaces is possible. Employing typical reaction efficacy, enhancement-factors of ca. 30-40 can be expected both under ALTADENA and under PASADENA conditions. This result has important consequences for the practical application of the method, since it potentially allows the design of an in-situ flow setup, where the para-hydrogen is adsorbed and desorbed from catalyst surfaces inside the NMR magnet. Copyright © 2014 Elsevier Inc. All rights reserved.

Multidimensional NMR inversion without Kronecker products: Multilinear inversion

NASA Astrophysics Data System (ADS)

Medellín, David; Ravi, Vivek R.; Torres-Verdín, Carlos

2016-08-01

Multidimensional NMR inversion using Kronecker products poses several challenges. First, kernel compression is only possible when the kernel matrices are separable, and in recent years, there has been an increasing interest in NMR sequences with non-separable kernels. Second, in three or more dimensions, the singular value decomposition is not unique; therefore kernel compression is not well-defined for higher dimensions. Without kernel compression, the Kronecker product yields matrices that require large amounts of memory, making the inversion intractable for personal computers. Finally, incorporating arbitrary regularization terms is not possible using the Lawson-Hanson (LH) or the Butler-Reeds-Dawson (BRD) algorithms. We develop a minimization-based inversion method that circumvents the above problems by using multilinear forms to perform multidimensional NMR inversion without using kernel compression or Kronecker products. The new method is memory efficient, requiring less than 0.1% of the memory required by the LH or BRD methods. It can also be extended to arbitrary dimensions and adapted to include non-separable kernels, linear constraints, and arbitrary regularization terms. Additionally, it is easy to implement because only a cost function and its first derivative are required to perform the inversion.

Challenges in NMR-based structural genomics

NASA Astrophysics Data System (ADS)

Sue, Shih-Che; Chang, Chi-Fon; Huang, Yao-Te; Chou, Ching-Yu; Huang, Tai-huang

2005-05-01

Understanding the functions of the vast number of proteins encoded in many genomes that have been completely sequenced recently is the main challenge for biologists in the post-genomics era. Since the function of a protein is determined by its exact three-dimensional structure it is paramount to determine the 3D structures of all proteins. This need has driven structural biologists to undertake the structural genomics project aimed at determining the structures of all known proteins. Several centers for structural genomics studies have been established throughout the world. Nuclear magnetic resonance (NMR) spectroscopy has played a major role in determining protein structures in atomic details and in a physiologically relevant solution state. Since the number of new genes being discovered daily far exceeds the number of structures determined by both NMR and X-ray crystallography, a high-throughput method for speeding up the process of protein structure determination is essential for the success of the structural genomics effort. In this article we will describe NMR methods currently being employed for protein structure determination. We will also describe methods under development which may drastically increase the throughput, as well as point out areas where opportunities exist for biophysicists to make significant contribution in this important field.

Quantitative solid-state 13C nuclear magnetic resonance spectrometric analyses of wood xylen: effect of increasing carbohydrate content

USGS Publications Warehouse

Bates, A.L.; Hatcher, P.G.

1992-01-01

Isolated lignin with a low carbohydrate content was spiked with increasing amounts of alpha-cellulose, and then analysed by solid-state 13C nuclear magnetic resonance (NMR) using cross-polarization with magic angle spinning (CPMAS) and dipolar dephasing methods in order to assess the quantitative reliability of CPMAS measurement of carbohydrate content and to determine how increasingly intense resonances for carbohydrate carbons affect calculations of the degree of lignin's aromatic ring substitution and methoxyl carbon content. Comparisons were made of the carbohydrate content calculated by NMR with carbohydrate concentrations obtained by phenol-sulfuric acid assay and by the calculation from the known amounts of cellulose added. The NMR methods used in this study yield overestimates for carbohydrate carbons due to resonance area overlap from the aliphatic side chain carbons of lignin. When corrections are made for these overlapping resonance areas, the NMR results agree very well with results obtained by other methods. Neither the calculated methoxyl carbon content nor the degree of aromatic ring substitution in lignin, both calculated from dipolar dephasing spectra, change with cellulose content. Likewise, lignin methoxyl content does not correlate with cellulose abundance when measured by integration of CPMAS spectra. ?? 1992.

Solution and solid-state effects on NMR chemical shifts in sesquiterpene lactones: NMR, X-ray, and theoretical methods.

PubMed

Dračínský, Martin; Buděšínský, Miloš; Warżajtis, Beata; Rychlewska, Urszula

2012-01-12

Selected guaianolide type sesquiterpene lactones were studied combining solution and solid-state NMR spectroscopy with theoretical calculations of the chemical shifts in both environments and with the X-ray data. The experimental (1)H and (13)C chemical shifts in solution were successfully reproduced by theoretical calculations (with the GIAO method and DFT B3LYP 6-31++G**) after geometry optimization (DFT B3LYP 6-31 G**) in vacuum. The GIPAW method was used for calculations of solid-state (13)C chemical shifts. The studied cases involved two polymorphs of helenalin, two pseudopolymorphs of 6α-hydroxydihydro-aromaticin and two cases of multiple asymmetric units in crystals: one in which the symmetry-independent molecules were connected by a series of hydrogen bonds (geigerinin) and the other in which the symmetry-independent molecules, deprived of any specific intermolecular interactions, differed in the conformation of the side chain (badkhysin). Geometrically different molecules present in the crystal lattices could be easily distinguished in the solid-state NMR spectra. Moreover, the experimental differences in the (13)C chemical shifts corresponding to nuclei in different polymorphs or in geometrically different molecules were nicely reproduced with the GIPAW calculations.

Chemical tagging of chlorinated phenols for their facile detection and analysis by NMR spectroscopy

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

Valdez, Carlos A.; Leif, Roald N.

2015-03-22

A derivatization method that employs diethyl (bromodifluoromethyl) phosphonate (DBDFP) to efficiently tag the endocrine disruptor pentachlorophenol (PCP) and other chlorinated phenols (CPs) along with their reliable detection and analysis by NMR is presented. The method accomplishes the efficient alkylation of the hydroxyl group in CPs with the difluoromethyl (CF 2H) moiety in extremely rapid fashion (5 min), at room temperature and in an environmentally benign manner. The approach proved successful in difluoromethylating a panel of 18 chlorinated phenols, yielding derivatives that displayed unique 1H, 19F NMR spectra allowing for the clear discrimination between isomerically related CPs. Due to its biphasicmore » nature, the derivatization can be applied to both aqueous and organic mixtures where the analysis of CPs is required. Furthermore, the methodology demonstrates that PCP along with other CPs can be selectively derivatized in the presence of other various aliphatic alcohols, underscoring the superiority of the approach over other general derivatization methods that indiscriminately modify all analytes in a given sample. The present work demonstrates the first application of NMR on the qualitative analysis of these highly toxic and environmentally persistent species.« less

Development of Selective Excitation Methods in Nuclear Magnetic Resonance: Investigation of Hemoglobin Oxygenation in Erythrocytes Using Proton and Phosphorus -31 Nuclear Magnetic Resonance

NASA Astrophysics Data System (ADS)

Fetler, Bayard Keith

1993-01-01

Nuclear magnetic resonance (NMR) offers a potential method for making measurements of the percent oxygenation of hemoglobin (Hb) in living tissue non-invasively. As a demonstration of the feasibility of such measurements, we measured the percent oxygenation of Hb in red blood cells (erythrocytes) using resonances in the proton-NMR (^1H-NMR) spectrum which are characteristic of oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb), and are due to the unique magnetic properties of these molecules. To perform these measurements, we developed a new NMR method of selectively exciting signals in a region of interest with uniform phase and amplitude, while suppressing the signal of the water resonance. With this method, we are able to make exact calculations distinguishing between uniform phase excitation produced at large flip-angles using the non-linear properties of the Bloch equations, and uniform phase excitation produced at small flip-angles using asymmetric pulse excitation functions. We measured the percent oxygenation of three characteristic ^1H-NMR resonances of Hb: two from deoxy-Hb, originating from the N_delta H protons of histidine residue F8, which occur at different frequencies for the alpha and beta chains of Hb; and one from oxy-Hb, originating from the gamma_2 -CH_3 protons of valine residue E11. We performed experiments both on fresh erythrocytes and on erythrocytes depleted of 2,3-diphosphoglycerate (2,3-DPG), and found that oxygen is more tightly bound to Hb in the former case. In both fresh and 2,3-DPG-depleted samples, we found that: (i) from the deoxy-Hb marker resonances, there is a small but significant difference in the oxygen saturation between the alpha and beta chains; (ii) the decrease in the areas of the deoxy-Hb marker resonances correlates well with the increase in the percent oxygenation of Hb as measured optically; (iii) the area of the oxy-Hb marker resonance may be up to ~15% less than the optically measured Hb saturation. We are thus able to demonstrate the feasibility and validity of using this method to measure the oxygen saturation of Hb using ^1H-NMR.

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.

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

Wemmer, D.E.; Kumar, N.V.; Metrione, R.M.

Toxin II from Radianthus paumotensis (Rp/sub II/) has been investigated by high-resolution NMR and chemical sequencing methods. Resonance assignments have been obtained for this protein by the sequential approach. NMR assignments could not be made consistent with the previously reported primary sequence for this protein, and chemical methods have been used to determine a sequence with which the NMR data are consistent. Analysis of the 2D NOE spectra shows that the protein secondary structure is comprised of two sequences of ..beta..-sheet, probably joined into a distorted continuous sheet, connected by turns and extended loops, without any regular ..cap alpha..-helical segments.more » The residues previously implicated in activity in this class of proteins, D8 and R13, occur in a loop region.« less

Two Phase Flow Measurements by Nuclear Magnetic Resonance (NMR)

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

Altobelli, Stephen A; Fukushima, Eiichi

In concentrated suspensions, there is a tendency for the solid phase to migrate from regions of high shear rate to regions of low shear (Leighton & Acrivos, 1987). In the early years that our effort was funded by the DOE Division of Basic Energy Science, quantitative measurement of this process in neutrally buoyant suspensions was a major focus (Abbott, et al., 1991; Altobelli, et al., 1991). Much of this work was used to improve multi-phase numerical models at Sandia National Laboratories. Later, our collaborators at Sandia and the University of New Mexico incorporated body forces into their numerical models ofmore » suspension flow (Rao, Mondy, Sun, et al., 2002). We developed experiments that allow us to study flows driven by buoyancy, to characterize these flows in well-known and useful engineering terms (Altobelli and Mondy, 2002) and to begin to explore the less well-understood area of flows with multiple solid phases (Beyea, Altobelli, et al., 2003). We also studied flows that combine the effects of shear and buoyancy, and flows of suspensions made from non-Newtonian liquids (Rao, Mondy, Baer, et al, 2002). We were able to demonstrate the usefulness of proton NMR imaging of liquid phase concentration and velocity and produced quantitative data not obtainable by other methods. Fluids flowing through porous solids are important in geophysics and in chemical processing. NMR techniques have been widely used to study liquid flow in porous media. We pioneered the extension of these studies to gas flows (Koptyug, et al, 2000, 2000, 2001, 2002). This extension allows us to investigate a wider range of Peclet numbers, and to gather data on problems of interest in catalysis. We devised two kinds of NMR experiments for three-phase systems. Both experiments employ two NMR visible phases and one phase that gives no NMR signal. The earlier method depends on the two visible phases differing in a NMR relaxation property. The second method (Beyea, Altobelli, et al., 2003) uses two different nuclei, protons and 19F. It also uses two different types of NMR image formation, a conventional spin-echo and a single-point method. The single-point method is notable for being useful for imaging materials which are much more rigid than can usually be studied by NMR imaging. We use it to image “low density” polyethylene (LDPE) plastic in this application. We have reduced the imaging time for this three-phase imaging method to less than 10 s per pair of profiles by using new hardware. Directly measuring the solid LDPE signal was a novel feature for multi-phase flow studies. We also used thermally polarized gas NMR (as opposed to hyper-polarized gas) which produces low signal to noise ratios because gas densities are on the order of 1000 times smaller than liquid densities. However since we used multi-atom molecules that have short T1's and operated at elevated pressures we could overcome some of the losses. Thermally polarized gases have advantages over hyperpolarized gases in the ease of preparation, and in maintaining a well-defined polarization. In these studies (Codd and Altobelli, 2003), we used stimulated echo sequences to successfully obtain propagators of gas in bead packs out to observation times of 300 ms. Zarraga, et al. (2000) used laser-sheet profilometry to investigate normal stress differences in concentrated suspensions. Recently we developed an NMR imaging analog for comparison with numerical work that is being performed by Rekha Rao at Sandia National Laboratories (Rao, Mondy, Sun, et al, 2002). A neutrally buoyant suspension of 100 mm PMMA spheres in a Newtonian liquid was sheared in a vertical Couette apparatus inside the magnet. The outer cylinder rotates and the inner cylinder is fixed. At these low rotation rates, the free-surface of the Newtonian liquid shows no measurable deformation, but the suspension clearly shows its non-Newtonian character.« less

Systematic Evaluation of Non-Uniform Sampling Parameters in the Targeted Analysis of Urine Metabolites by 1H,1H 2D NMR Spectroscopy.

PubMed

Schlippenbach, Trixi von; Oefner, Peter J; Gronwald, Wolfram

2018-03-09

Non-uniform sampling (NUS) allows the accelerated acquisition of multidimensional NMR spectra. The aim of this contribution was the systematic evaluation of the impact of various quantitative NUS parameters on the accuracy and precision of 2D NMR measurements of urinary metabolites. Urine aliquots spiked with varying concentrations (15.6-500.0 µM) of tryptophan, tyrosine, glutamine, glutamic acid, lactic acid, and threonine, which can only be resolved fully by 2D NMR, were used to assess the influence of the sampling scheme, reconstruction algorithm, amount of omitted data points, and seed value on the quantitative performance of NUS in 1 H, 1 H-TOCSY and 1 H, 1 H-COSY45 NMR spectroscopy. Sinusoidal Poisson-gap sampling and a compressed sensing approach employing the iterative re-weighted least squares method for spectral reconstruction allowed a 50% reduction in measurement time while maintaining sufficient quantitative accuracy and precision for both types of homonuclear 2D NMR spectroscopy. Together with other advances in instrument design, such as state-of-the-art cryogenic probes, use of 2D NMR spectroscopy in large biomedical cohort studies seems feasible.

An Introduction to Biological NMR Spectroscopy*

PubMed Central

Marion, Dominique

2013-01-01

NMR spectroscopy is a powerful tool for biologists interested in the structure, dynamics, and interactions of biological macromolecules. This review aims at presenting in an accessible manner the requirements and limitations of this technique. As an introduction, the history of NMR will highlight how the method evolved from physics to chemistry and finally to biology over several decades. We then introduce the NMR spectral parameters used in structural biology, namely the chemical shift, the J-coupling, nuclear Overhauser effects, and residual dipolar couplings. Resonance assignment, the required step for any further NMR study, bears a resemblance to jigsaw puzzle strategy. The NMR spectral parameters are then converted into angle and distances and used as input using restrained molecular dynamics to compute a bundle of structures. When interpreting a NMR-derived structure, the biologist has to judge its quality on the basis of the statistics provided. When the 3D structure is a priori known by other means, the molecular interaction with a partner can be mapped by NMR: information on the binding interface as well as on kinetic and thermodynamic constants can be gathered. NMR is suitable to monitor, over a wide range of frequencies, protein fluctuations that play a crucial role in their biological function. In the last section of this review, intrinsically disordered proteins, which have escaped the attention of classical structural biology, are discussed in the perspective of NMR, one of the rare available techniques able to describe structural ensembles. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 16 MCP). PMID:23831612

PICKY: a novel SVD-based NMR spectra peak picking method

PubMed Central

Alipanahi, Babak; Gao, Xin; Karakoc, Emre; Donaldson, Logan; Li, Ming

2009-01-01

Motivation: Picking peaks from experimental NMR spectra is a key unsolved problem for automated NMR protein structure determination. Such a process is a prerequisite for resonance assignment, nuclear overhauser enhancement (NOE) distance restraint assignment, and structure calculation tasks. Manual or semi-automatic peak picking, which is currently the prominent way used in NMR labs, is tedious, time consuming and costly. Results: We introduce new ideas, including noise-level estimation, component forming and sub-division, singular value decomposition (SVD)-based peak picking and peak pruning and refinement. PICKY is developed as an automated peak picking method. Different from the previous research on peak picking, we provide a systematic study of the proposed method. PICKY is tested on 32 real 2D and 3D spectra of eight target proteins, and achieves an average of 88% recall and 74% precision. PICKY is efficient. It takes PICKY on average 15.7 s to process an NMR spectrum. More important than these numbers, PICKY actually works in practice. We feed peak lists generated by PICKY to IPASS for resonance assignment, feed IPASS assignment to SPARTA for fragments generation, and feed SPARTA fragments to FALCON for structure calculation. This results in high-resolution structures of several proteins, for example, TM1112, at 1.25 Å. Availability: PICKY is available upon request. The peak lists of PICKY can be easily loaded by SPARKY to enable a better interactive strategy for rapid peak picking. Contact: mli@uwaterloo.ca PMID:19477998

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.

Position-Specific Hydrogen and Carbon Isotope Fractionations of Light Hydrocarbons by Quantitative NMR

NASA Astrophysics Data System (ADS)

Liu, C.; Mcgovern, G. P.; Horita, J.

2015-12-01

Traditional isotope ratio mass spectrometry methods to measure 2H/1H and 13C/12C ratios of organic molecules only provide average isotopic values of whole molecules. During the measurement process, valuable information of position-specific isotope fractionations (PSIF) between non-equivalent H and C positions is lost, which can provide additional very useful information about the origins and history of organic molecules. Quantitative nuclear magnetic resonance (NMR) spectrometry can measure 2H and 13C PSIF of organic molecules without destruction. The 2H and 13C signals from different positions of a given molecule show up as distinctive peaks in an NMR spectrum, and their peak areas are proportional to the 2H and 13C populations at each position. Moreover, quantitative NMR can be applied to a wide variety of organic molecules. We have been developing quantitative NMR methods to determine 2H and 13C PSIF of light hydrocarbons (propane, butane and pentane), using J-Young and custom-made high-pressure NMR cells. With careful conditioning of the NMR spectrometer (e.g. tuning, shimming) and effective 1H -13C decoupling, precision of ± <10‰ (2H) and ± <1‰ (13C) can be readily attainable after several hours of acquisition. Measurement time depends on the relaxation time of interested nucleus and the total number of scans needed for high signal-to-noise ratios. Our data for commercial, pure hydrocarbon samples showed that 2H PSIF in the hydrocarbons can be larger than 60‰ and that 13C PSIF can be as large as 15‰. Comparison with theoretical calculations indicates that the PSIF patterns of some hydrocarbon samples reflect non-equilibrium processes in their productions.

Probing the stereo-electronic properties of cationic rhodium complexes bearing chiral diphosphine ligands by 103Rh NMR.

PubMed

Fabrello, Amandine; Dinoi, Chiara; Perrin, Lionel; Kalck, Philippe; Maron, Laurent; Urrutigoity, Martine; Dechy-Cabaret, Odile

2010-11-01

(103)Rh NMR represents a powerful tool to assess the global electronic and steric contribution of diphosphine ligands on [Rh(COD)(diphosphine)](+) complexes. In the case of DIOP, BINAP and MeDUPHOS, this approach proved to be more informative than classical CO-stretching frequency measurements. After validation, this method has been extended to a set of seven diphosphines. (103)Rh NMR measurements on [Rh(COD)(diphosphine)]PF(6) lead to the following order of donor properties: dppe > MeBPE > MeDUPHOS > dppb > DIOP > BINAP > Tol-BINAP. This trend has been validated by DFT in the case of DIOP, BINAP and MeDUPHOS. In conjunction, (31)P NMR chemical shift has been shown to reflect the ring constraints of the Rh-diphosphine scaffold. This contribution is a step towards a mechanistic investigation of the catalytic hydrogenation of unsaturated substrates by (103)Rh NMR and DFT. 2010 John Wiley & Sons, Ltd.

Recent Advances in Targeted and Untargeted Metabolomics by NMR and MS/NMR Methods

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

Bingol, Kerem

Metabolomics has made significant progress in multiple fronts in the last 18 months. This minireview aimed to give an overview of these advancements in the light of their contribution to targeted and untargeted metabolomics. New computational approaches have emerged to overcome manual absolute quantitation step of metabolites in 1D 1H NMR spectra. This provides more consistency between inter-laboratory comparisons. Integration of 2D NMR metabolomics databases under a unified web server allowed very accurate identification of the metabolites that have been catalogued in these databases. For the remaining uncatalogued and unknown metabolites, new cheminformatics approaches have been developed by combining NMRmore » and mass spectrometry. These hybrid NMR/MS approaches accelerated the identification of unknowns in untargeted studies, and now they are allowing to profile ever larger number of metabolites in application studies.« less

Quantum memory enhanced nuclear magnetic resonance of nanometer-scale samples with a single spin in diamond

NASA Astrophysics Data System (ADS)

Aslam, Nabeel; Pfender, Matthias; Zaiser, Sebastian; Favaro de Oliveira, Felipe; Momenzadeh, S. Ali; Denisenko, Andrej; Isoya, Junichi; Neumann, Philipp; Wrachtrup, Joerg

Recently nuclear magnetic resonance (NMR) of nanoscale samples at ambient conditions has been achieved with nitrogen-vacancy (NV) centers in diamond. So far the spectral resolution in the NV NMR experiments was limited by the sensor's coherence time, which in turn prohibited revealing the chemical composition and dynamics of the system under investigation. By entangling the NV electron spin sensor with a long-lived memory spin qubit we increase the spectral resolution of NMR measurement sequences for the detection of external nuclear spins. Applying the latter sensor-memory-couple it is particularly easy to track diffusion processes, to identify the molecules under study and to deduce the actual NV center depth inside the diamond. We performed nanoscale NMR on several liquid and solid samples exhibiting unique NMR response. Our method paves the way for nanoscale identification of molecule and protein structures and dynamics of conformational changes.

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.

Parahydrogen-enhanced zero-field nuclear magnetic resonance

NASA Astrophysics Data System (ADS)

Theis, T.; Ganssle, P.; Kervern, G.; Knappe, S.; Kitching, J.; Ledbetter, M. P.; Budker, D.; Pines, A.

2011-07-01

Nuclear magnetic resonance, conventionally detected in magnetic fields of several tesla, is a powerful analytical tool for the determination of molecular identity, structure and function. With the advent of prepolarization methods and detection schemes using atomic magnetometers or superconducting quantum interference devices, interest in NMR in fields comparable to the Earth's magnetic field and below (down to zero field) has been revived. Despite the use of superconducting quantum interference devices or atomic magnetometers, low-field NMR typically suffers from low sensitivity compared with conventional high-field NMR. Here we demonstrate direct detection of zero-field NMR signals generated through parahydrogen-induced polarization, enabling high-resolution NMR without the use of any magnets. The sensitivity is sufficient to observe spectra exhibiting 13C-1H scalar nuclear spin-spin couplings (known as J couplings) in compounds with 13C in natural abundance, without the need for signal averaging. The resulting spectra show distinct features that aid chemical fingerprinting.

TINS, target immobilized NMR screening: an efficient and sensitive method for ligand discovery.

PubMed

Vanwetswinkel, Sophie; Heetebrij, Robert J; van Duynhoven, John; Hollander, Johan G; Filippov, Dmitri V; Hajduk, Philip J; Siegal, Gregg

2005-02-01

We propose a ligand screening method, called TINS (target immobilized NMR screening), which reduces the amount of target required for the fragment-based approach to drug discovery. Binding is detected by comparing 1D NMR spectra of compound mixtures in the presence of a target immobilized on a solid support to a control sample. The method has been validated by the detection of a variety of ligands for protein and nucleic acid targets (K(D) from 60 to 5000 muM). The ligand binding capacity of a protein was undiminished after 2000 different compounds had been applied, indicating the potential to apply the assay for screening typical fragment libraries. TINS can be used in competition mode, allowing rapid characterization of the ligand binding site. TINS may allow screening of targets that are difficult to produce or that are insoluble, such as membrane proteins.

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.

Automated structure determination of proteins with the SAIL-FLYA NMR method.

PubMed

Takeda, Mitsuhiro; Ikeya, Teppei; Güntert, Peter; Kainosho, Masatsune

2007-01-01

The labeling of proteins with stable isotopes enhances the NMR method for the determination of 3D protein structures in solution. Stereo-array isotope labeling (SAIL) provides an optimal stereospecific and regiospecific pattern of stable isotopes that yields sharpened lines, spectral simplification without loss of information, and the ability to collect rapidly and evaluate fully automatically the structural restraints required to solve a high-quality solution structure for proteins up to twice as large as those that can be analyzed using conventional methods. Here, we describe a protocol for the preparation of SAIL proteins by cell-free methods, including the preparation of S30 extract and their automated structure analysis using the FLYA algorithm and the program CYANA. Once efficient cell-free expression of the unlabeled or uniformly labeled target protein has been achieved, the NMR sample preparation of a SAIL protein can be accomplished in 3 d. A fully automated FLYA structure calculation can be completed in 1 d on a powerful computer system.

Crystallographic structure refinement with quadrupolar nuclei: a combined solid-state NMR and GIPAW DFT example using MgBr(2).

PubMed

Widdifield, Cory M; Bryce, David L

2009-09-07

Solid-state NMR spectroscopy and GIPAW DFT calculations reveal the pronounced sensitivity of (79/81)Br and (25)Mg quadrupolar coupling constants to subtle aspects of solid state structure which were not previously detected by pXRD methods.

A novel cardanol-based antioxidant and its application in vegetable oils and biodiesel

USDA-ARS?s Scientific Manuscript database

A novel antioxidant, epoxidized cardanol (ECD), derived from cardanol has been synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD in vegetable oils and biodiesel was evaluated by the pressurized differential scanning calorimetry and Rancimat methods, respectively....

Synthesis of epoxidized cardanol and its antioxidative properties for vegetable oils and biodiesel

USDA-ARS?s Scientific Manuscript database

A novel antioxidant epoxidized cardanol (ECD), derived from cardanol, was synthesized and characterized by FT-IR, 1H-NMR and 13C-NMR. Oxidative stability of ECD used in vegetable oils and biodiesel was evaluated by pressurized differential scanning calorimetry (PDSC) and the Rancimat method, respect...

Flow-through lipid nanotube arrays for structure-function studies of membrane proteins by solid-state NMR spectroscopy.

PubMed

Chekmenev, Eduard Y; Gor'kov, Peter L; Cross, Timothy A; Alaouie, Ali M; Smirnov, Alex I

2006-10-15

A novel method for studying membrane proteins in a native lipid bilayer environment by solid-state NMR spectroscopy is described and tested. Anodic aluminum oxide (AAO) substrates with flow-through 175 nm wide and 60-mum-long nanopores were employed to form macroscopically aligned peptide-containing lipid bilayers that are fluid and highly hydrated. We demonstrate that the surfaces of both leaflets of such bilayers are fully accessible to aqueous solutes. Thus, high hydration levels as well as pH and desirable ion and/or drug concentrations could be easily maintained and modified as desired in a series of experiments with the same sample. The method allows for membrane protein NMR experiments in a broad pH range that could be extended to as low as 1 and as high as 12 units for a period of up to a few hours and temperatures as high as 70 degrees C without losing the lipid alignment or bilayers from the nanopores. We demonstrate the utility of this method by a solid-state 19.6 T (17)O NMR study of reversible binding effects of mono- and divalent ions on the chemical shift properties of the Leu(10) carbonyl oxygen of transmembrane pore-forming peptide gramicidin A (gA). We further compare the (17)O shifts induced by binding metal ions to the binding of protons in the pH range from 1 to 12 and find a significant difference. This unexpected result points to a difference in mechanisms for ion and proton conduction by the gA pore. We believe that a large number of solid-state NMR-based studies, including structure-function, drug screening, proton exchange, pH, and other titration experiments, will benefit significantly from the method described here.

Numerical simulation of multi-dimensional NMR response in tight sandstone

NASA Astrophysics Data System (ADS)

Guo, Jiangfeng; Xie, Ranhong; Zou, Youlong; Ding, Yejiao

2016-06-01

Conventional logging methods have limitations in the evaluation of tight sandstone reservoirs. The multi-dimensional nuclear magnetic resonance (NMR) logging method has the advantage that it can simultaneously measure transverse relaxation time (T 2), longitudinal relaxation time (T 1) and diffusion coefficient (D). In this paper, we simulate NMR measurements of tight sandstone with different wettability and saturations by the random walk method and obtain the magnetization decays of Carr-Purcell-Meiboom-Gill pulse sequences with different wait times (TW) and echo spacings (TE) under a magnetic field gradient, resulting in D-T 2-T 1 maps by the multiple echo trains joint inversion method. We also study the effects of wettability, saturation, signal-to-noise ratio (SNR) of data and restricted diffusion on the D-T 2-T 1 maps in tight sandstone. The results show that with decreasing wetting fluid saturation, the surface relaxation rate of the wetting fluid gradually increases and the restricted diffusion phenomenon becomes more and more obvious, which leads to the wetting fluid signal moving along the direction of short relaxation and the direction of the diffusion coefficient decreasing in D-T 2-T 1 maps. Meanwhile, the non-wetting fluid position in D-T 2-T 1 maps does not change with saturation variation. With decreasing SNR, the ability to identify water and oil signals based on NMR maps gradually decreases. The wetting fluid D-T 1 and D-T 2 correlations in NMR diffusion-relaxation maps of tight sandstone are obtained through expanding the wetting fluid restricted diffusion models, and are further applied to recognize the wetting fluid in simulated D-T 2 maps and D-T 1 maps.

Disposal of Chemical Agent Identification Sets at Rocky Mountain Arsenal, Colorado. Volume 2. Appendices A-D

DTIC Science & Technology

1983-08-01

N ENTER UNIT NURSER YOU ARE USING FOR THE DATA TAPE 11 FIGURE A-20 A-15 PMOMR TO P"IN? PROCES: DATA SHEET - DECOMED PIC CONTRL INSERT DATA TAPE IN...EXCHANGE/COOLER 70 CONTROL PANEL1 ACTUATORPFEELER 71 TV MONITOR 2 MOTOR 72 CART TOP3 PUMP 73 CIRCUIT BREAKER 4 VALVE 74 5 BELT 75 LIGHT6 SEAL 76 MIRAN 807

Fiches pratiques: L'imagier; Jeu de mecano; Le Proces de la tour; Homo ludens (Practical Ideas: The Print-Maker; Erector Set Game; The Trial of the Tower; Man the Gameplayer).

ERIC Educational Resources Information Center

Boiron, Michel; And Others

1989-01-01

Four activities for the French classroom are described, including vocabulary development games using pictures of animals and a puzzle of the Eiffel Tower, simulation of the conflict over the Eiffel Tower's construction, and a reading comprehension exercise using Spanish, French, nonsense Spanish and French, and cloze versions of a text. (MSE)

Building and Verifying a Predictive Model of Interruption Resumption

DTIC Science & Technology

2012-03-01

field, the vocal module speaks, the motor module moves the body, and the con- figural and manipulative modules perform spatial proces- sing [14]–[16...person cannot remember themselves. As described earlier, the model depends critically upon the basic properties of declarative memories. When a...success because the model’s ability to re- trieve an episodic code depends critically on the amount of time spent on the interruption. Also recall that

Interactive Activation Model of Speech Perception.

DTIC Science & Technology

1984-11-01

contract. 0 Elar, .l... & .McC’lelland .1.1. Speech perception a, a cognitive proces,: The interactive act ia- %e., tion model of speech perception. In...attempts to provide a machine solution to the problem of speech perception. A second kind of model, growing out of Cognitive Psychology, attempts to...architectures to cognitive and perceptual problems. We also owe a debt to what we might call the computational connectionists -- those who have applied highly

Deburring: an annotated bibliography. Volume VI

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

Gillespie, L.K.

1980-07-01

An annotated summary of 138 articles and publications on burrs, burr prevention and deburring is presented. Thirty-seven deburring processes are listed. Entries cited include English, Russian, French, Japanese, and German language articles. Entries are indexed by deburring processes, author, and language. Indexes also indicate which references discuss equipment and tooling, how to use a proces economics, burr properties, and how to design to minimize burr problems. Research studies are identified as are the materials deburred.

NMR Shielding in Metals Using the Augmented Plane Wave Method

PubMed Central

2015-01-01

We present calculations of solid state NMR magnetic shielding in metals, which includes both the orbital and the complete spin response of the system in a consistent way. The latter contains an induced spin-polarization of the core states and needs an all-electron self-consistent treatment. In particular, for transition metals, the spin hyperfine field originates not only from the polarization of the valence s-electrons, but the induced magnetic moment of the d-electrons polarizes the core s-states in opposite direction. The method is based on DFT and the augmented plane wave approach as implemented in the WIEN2k code. A comparison between calculated and measured NMR shifts indicates that first-principle calculations can obtain converged results and are more reliable than initially concluded based on previous publications. Nevertheless large k-meshes (up to 2 000 000 k-points in the full Brillouin-zone) and some Fermi-broadening are necessary. Our results show that, in general, both spin and orbital components of the NMR shielding must be evaluated in order to reproduce experimental shifts, because the orbital part cancels the shift of the usually highly ionic reference compound only for simple sp-elements but not for transition metals. This development paves the way for routine NMR calculations of metallic systems. PMID:26322148

Partitioning of nitroxides in dispersed systems investigated by ultrafiltration, EPR and NMR spectroscopy.

PubMed

Krudopp, Heimke; Sönnichsen, Frank D; Steffen-Heins, Anja

2015-08-15

The partitioning behavior of paramagnetic nitroxides in dispersed systems can be determined by deconvolution of electron paramagnetic resonance (EPR) spectra giving equivalent results with the validated methods of ultrafiltration techniques (UF) and pulsed-field gradient nuclear magnetic resonance spectroscopy (PFG-NMR). The partitioning behavior of nitroxides with increasing lipophilicity was investigated in anionic, cationic and nonionic micellar systems and 10 wt% o/w emulsions. Apart from EPR spectra deconvolution, the PFG-NMR was used in micellar solutions as a non-destructive approach, while UF based on separation of very small volume of the aqueous phase. As a function of their substituent and lipophilicity, the proportions of nitroxides that were solubilized in the micellar or emulsion interface increased with increasing nitroxide lipophilicity for all emulsifier used. Comparing the different approaches, EPR deconvolution and UF revealed comparable nitroxide proportions that were solubilized in the interfaces. Those proportions were higher than found with PFG-NMR. For PFG-NMR self-diffusion experiments the reduced nitroxides were used revealing a high dynamic of hydroxylamines and emulsifiers. Deconvolution of EPR spectra turned out to be the preferred method for measuring the partitioning behavior of paramagnetic molecules as it enables distinguishing between several populations at their individual solubilization sites. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

Untangle soil-water-mucilage interactions: 1H NMR Relaxometry is lifting the veil

NASA Astrophysics Data System (ADS)

Brax, Mathilde; Buchmann, Christian; Schaumann, Gabriele Ellen

2017-04-01

Mucilage is mainly produced at the root tips and has a high water holding capacity derived from highly hydrophilic gel-forming substances. The objective of the MUCILAGE project is to understand the mechanistic role of mucilage for the regulation of water supply for plants. Our subproject investigates the chemical and physical properties of mucilage as pure gel and mixed with soil. 1H-NMR Relaxometry and PFG NMR represent non-intrusive powerful methods for soil scientific research by allowing quantification of the water distribution as well as monitoring of the water mobility in soil pores and gel phases.Relaxation of gel water differs from the one of pure water due to additional interactions with the gel matrix. Mucilage in soil leads to a hierarchical pore structure, consisting of the polymeric biohydrogel network surrounded by the surface of soil particles. The two types of relaxation rates 1/T1 and 1/T2 measured with 1H-NMR relaxometry refer to different relaxation mechanisms of water, while PFG-NMR measures the water self-diffusion coefficient. The objective of our study is to distinguish in situ water in gel from pore water in a simplified soil system, and to determine how the "gel effect" affects both relaxation rates and the water self-diffusion coefficient in porous systems. We demonstrate how the mucilage concentration and the soil solution alter the properties of water in the respective gel phases and pore systems in model soils. To distinguish gel-inherent processes from classical processes, we investigated the variations of the water mobility in pure chia mucilage under different conditions by using 1H-NMR relaxometry and PFG NMR. Using model soils, the signals coming from pore water and gel water were differentiated. We combined the equations describing 1H-NMR relaxation in porous systems and our experimental results, to explain how the presence of gel in soil affects 1H-NMR relaxation. Out of this knowledge we propose a method, which determines in situ the presence of mucilage in soil and characterizes several gel-specific parameters of the mucilage. Based on these findings, we discussed the potential and limitations of 1H-NMR relaxometry for following natural swelling and shrinking processes of a natural biopolymer in soil.

The Development and Use of Internal Amplification Controls (IACs) with DNA Profiling Kits for Forensic DNA Analysis.

PubMed

Zahra, Nathalie; Goodwin, William

2016-01-01

Biological samples recovered for forensic investigations are often degraded and/or have low amounts of DNA; in addition, in some instances the samples may be contaminated with chemicals that can act as PCR inhibitors. As a consequence this can make interpretation of the results challenging with the possibility of having partial profiles and false negative results. Because of the impact of DNA analysis on forensic investigations, it is important to monitor the process of DNA profiling, in particular the amplification reaction. In this chapter we describe a method for the in-house generation and use of internal amplification controls (IACs) with DNA profiling kits to monitor the success of the PCR proces. In the example we show the use of the SGM Plus® kit. These controls can also be used to aid the interpretation of the DNA profile.

Intermediate couplings: NMR at the solids-liquids interface

NASA Astrophysics Data System (ADS)

Spence, Megan

2006-03-01

Anisotropic interactions like dipolar couplings and chemical shift anisotropy have long offered solid-state NMR spectroscopists valuable structural information. Recently, solution-state NMR structural studies have begun to exploit residual dipolar couplings of biological molecules in weakly anisotropic solutions. These residual couplings are about 0.1% of the coupling magnitudes observed in the solid state, allowing simple, high-resolution NMR spectra to be retained. In this work, we examine the membrane-associated opioid, leucine enkephalin (lenk), in which the ordering is ten times larger than that for residual dipolar coupling experiments, requiring a combination of solution-state and solid-state NMR techniques. We adapted conventional solid-state NMR techniques like adiabatic cross- polarization and REDOR for use with such a system, and measured small amide bond dipolar couplings in order to determine the orientation of the amide bonds (and therefore the peptide) with respect to the membrane surface. However, the couplings measured indicate large structural rearrangements on the surface and contradict the published structures obtained by NOESY constraints, a reminder that such methods are of limited use in the presence of large-scale dynamics.

Mechanisms of amyloid formation revealed by solution NMR

PubMed Central

Karamanos, Theodoros K.; Kalverda, Arnout P.; Thompson, Gary S.; Radford, Sheena E.

2015-01-01

Amyloid fibrils are proteinaceous elongated aggregates involved in more than fifty human diseases. Recent advances in electron microscopy and solid state NMR have allowed the characterization of fibril structures to different extents of refinement. However, structural details about the mechanism of fibril formation remain relatively poorly defined. This is mainly due to the complex, heterogeneous and transient nature of the species responsible for assembly; properties that make them difficult to detect and characterize in structural detail using biophysical techniques. The ability of solution NMR spectroscopy to investigate exchange between multiple protein states, to characterize transient and low-population species, and to study high molecular weight assemblies, render NMR an invaluable technique for studies of amyloid assembly. In this article we review state-of-the-art solution NMR methods for investigations of: (a) protein dynamics that lead to the formation of aggregation-prone species; (b) amyloidogenic intrinsically disordered proteins; and (c) protein–protein interactions on pathway to fibril formation. Together, these topics highlight the power and potential of NMR to provide atomic level information about the molecular mechanisms of one of the most fascinating problems in structural biology. PMID:26282197

Protein 19F-labeling using transglutaminase for the NMR study of intermolecular interactions.

PubMed

Hattori, Yoshikazu; Heidenreich, David; Ono, Yuki; Sugiki, Toshihiko; Yokoyama, Kei-Ichi; Suzuki, Ei-Ichiro; Fujiwara, Toshimichi; Kojima, Chojiro

2017-08-01

The preparation of stable isotope-labeled proteins is important for NMR studies, however, it is often hampered in the case of eukaryotic proteins which are not readily expressed in Escherichia coli. Such proteins are often conveniently investigated following post-expression chemical isotope tagging. Enzymatic 15 N-labeling of glutamine side chains using transglutaminase (TGase) has been applied to several proteins for NMR studies. 19 F-labeling is useful for interaction studies due to its high NMR sensitivity and susceptibility. Here, 19 F-labeling of glutamine side chains using TGase and 2,2,2-trifluoroethylamine hydrochloride was established for use in an NMR study. This enzymatic 19 F-labeling readily provided NMR detection of protein-drug and protein-protein interactions with complexes of about 100 kDa since the surface residues provided a good substrate for TGase. The 19 F-labeling method was 3.5-fold more sensitive than 15 N-labeling, and could be combined with other chemical modification techniques such as lysine 13 C-methylation. 13 C-dimethylated- 19 F-labeled FKBP12 provided more accurate information concerning the FK506 binding site.

Structural changes of starch during baking and staling of rye bread.

PubMed

Mihhalevski, Anna; Heinmaa, Ivo; Traksmaa, Rainer; Pehk, Tõnis; Mere, Arvo; Paalme, Toomas

2012-08-29

Rye sourdough breads go stale more slowly than wheat breads. To understand the peculiarities of bread staling, rye sourdough bread, wheat bread, and a number of starches were studied using wide-angle X-ray diffraction, nuclear magnetic resonance ((13)C CP MAS NMR, (1)H NMR, (31)P NMR), polarized light microscopy, rheological methods, microcalorimetry, and measurement of water activity. The degree of crystallinity of starch in breads decreased with hydration and baking to 3% and increased during 11 days of storage to 21% in rye sourdough bread and to 26% in wheat bread. (13)C NMR spectra show that the chemical structures of rye and wheat amylopectin and amylose contents are very similar; differences were found in the starch phospholipid fraction characterized by (31)P NMR. The (13)C CP MAS NMR spectra demonstrate that starch in rye sourdough breads crystallize in different forms than in wheat bread. It is proposed that different proportions of water incorporation into the crystalline structure of starch during staling and changes in starch fine structure cause the different rates of staling of rye and wheat bread.

Signal Enhancement in HPLC/Micro-Coil NMR Using Automated Column Trapping

PubMed Central

Djukovic, Danijel; Liu, Shuhui; Henry, Ian; Tobias, Brian; Raftery, Daniel

2008-01-01

A new HPLC-NMR system is described that performs analytical separation, pre-concentration, and NMR spectroscopy in rapid succession. The central component of our method is the online pre-concentration sequence that improves the match between post-column analyte peak volume and the micro-coil NMR detection volume. Separated samples are collected on to a C18 guard column with a mobile phase composed of 90% D2O/10% acetonitrile-D3, and back-flashed to the NMR micro-coil probe with 90% acetonitrile-D3/10% D2O. In order to assess the performance of our unit, we separated a standard mixture of 1 mM ibuprofen, naproxen, and phenylbutazone using a commercially available C18 analytical column. The S/N measurements from the NMR acquisitions indicated that we achieved signal enhancement factors up to 10.4 (±1.2)-fold. Furthermore, we observed that pre-concentration factors increased as the injected amount of analyte decreased. The highest concentration enrichment of 14.7 (±2.2)-fold was attained injecting 100 μL solution of 0.2 mM (~4 μg) ibuprofen. PMID:17037915

Demetalation of Fe, Mn, and Cu chelates and complexes: application to the NMR analysis of micronutrient fertilizers.

PubMed

López-Rayo, Sandra; Lucena, Juan J; Laghi, Luca; Cremonini, Mauro A

2011-12-28

The application of nuclear magnetic resonance (NMR) for the quality control of fertilizers based on Fe(3+), Mn(2+), and Cu(2+) chelates and complexes is precluded by the strong paramagnetism of metals. Recently, a method based on the use of ferrocyanide has been described to remove iron from commercial iron chelates based on the o,o-EDDHA [ethylenediamine-N,N'bis(2-hydroxyphenylacetic)acid] chelating agent for their analysis and quantification by NMR. The present work extended that procedure to other paramagnetic ions, manganese and copper, and other chelating, EDTA (ethylenediaminetetraacetic acid), IDHA [N-(1,2-dicarboxyethyl)-d,l-aspartic acid], and complexing agents, gluconate and heptagluconate. Results showed that the removal of the paramagnetic ions was complete, allowing us to obtain (1)H NMR spectra characterized by narrow peaks. The quantification of the ligands by NMR and high-performance liquid chromatography showed that their complete recovery was granted. The NMR analysis enabled detection and quantification of unknown impurities without the need of pure compounds as internal standards.

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

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.

Toroid cavity/coil NMR multi-detector

DOEpatents

Gerald, II, Rex E.; Meadows, Alexander D.; Gregar, Joseph S.; Rathke, Jerome W.

2007-09-18

An analytical device for rapid, non-invasive nuclear magnetic resonance (NMR) spectroscopy of multiple samples using a single spectrometer is provided. A modified toroid cavity/coil detector (TCD), and methods for conducting the simultaneous acquisition of NMR data for multiple samples including a protocol for testing NMR multi-detectors are provided. One embodiment includes a plurality of LC resonant circuits including spatially separated toroid coil inductors, each toroid coil inductor enveloping its corresponding sample volume, and tuned to resonate at a predefined frequency using a variable capacitor. The toroid coil is formed into a loop, where both ends of the toroid coil are brought into coincidence. Another embodiment includes multiple micro Helmholtz coils arranged on a circular perimeter concentric with a central conductor of the toroid cavity.

Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

PubMed

Silva Elipe, Maria Victoria; Milburn, Robert R

2016-06-01

Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Solid-State NMR Spectroscopy of Metal–Organic Framework Compounds (MOFs)

PubMed Central

Hoffmann, Herbert C.; Debowski, Marta; Müller, Philipp; Paasch, Silvia; Senkovska, Irena; Kaskel, Stefan; Brunner, Eike

2012-01-01

Nuclear Magnetic Resonance (NMR) spectroscopy is a well-established method for the investigation of various types of porous materials. During the past decade, metal–organic frameworks have attracted increasing research interest. Solid-state NMR spectroscopy has rapidly evolved into an important tool for the study of the structure, dynamics and flexibility of these materials, as well as for the characterization of host–guest interactions with adsorbed species such as xenon, carbon dioxide, water, and many others. The present review introduces and highlights recent developments in this rapidly growing field.

Rotating-frame gradient fields for magnetic resonance imaging and nuclear magnetic resonance in low fields

DOEpatents

Bouchard, Louis-Serge; Pines, Alexander; Demas, Vasiliki

2014-01-21

A system and method for Fourier encoding a nuclear magnetic resonance (NMR) signal is disclosed. A static magnetic field B.sub.0 is provided along a first direction. An NMR signal from the sample is Fourier encoded by applying a rotating-frame gradient field B.sub.G superimposed on the B.sub.0, where the B.sub.G comprises a vector component rotating in a plane perpendicular to the first direction at an angular frequency .omega.in a laboratory frame. The Fourier-encoded NMR signal is detected.

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.

1H, 13C, 15N NMR analysis of sildenafil base and citrate (Viagra) in solution, solid state and pharmaceutical dosage forms.

PubMed

Wawer, Iwona; Pisklak, Maciej; Chilmonczyk, Zdzisław

2005-08-10

Sildenafil citrate (SC) (Viagra) and sildenafil base in pure form are easily and unequivocally characterized by multinuclear NMR spectroscopy. Analysis of chemical shifts indicates that: (i) N6-H forms intramolecular hydrogen bonds, (ii) N25 is protonated in the salt and (iii) intermolecular OH...N hydrogen bonds involving N2 and N4 are present in the solid sildenafil citrate. 13C CPMAS NMR method has been proposed for the identification and quantitation of Viagra in its pharmaceutical formulations.

Quantitative nuclear magnetic resonance for additives determination in an electrolytic nickel bath.

PubMed

Ostra, Miren; Ubide, Carlos; Vidal, Maider

2011-02-01

The use of proton nuclear magnetic resonance (¹H-NMR) for the quantitation of additives in a commercial electrolytic nickel bath (Supreme Plus Brilliant, Atotech formulation) is reported. A simple and quick method is described that needs only the separation of nickel ions by precipitation with NaOH. The four additives in the bath (A-5(2X), leveler; Supreme Plus Brightener (SPB); SA-1, leveler; NPA, wetting agent; all of them are commercial names from Atotech) can be quantified, whereas no other analytical methods have been found in the literature for SA-1 and NPA. Two calibration methods have been tried: integration of NMR signals with the use of a proper internal standard and partial least squares regression applied to the characteristic NMR peaks. The multivariate method was preferred because of accuracy and precision. Multivariate limits of detection of about 4 mL L⁻¹ A-5(2X), 0.4 mL L⁻¹ SPB, 0.2 mL L⁻¹ SA-1 and 0.6 mL L⁻¹ NPA were found. The dynamic ranges are suitable to follow the concentration of additives in the bath along electrodeposition. ¹H-NMR spectra provide evidence for SPB and SA-1 consumption (A-5(2X) and NPA keep unchanged along the process) and the growth of some products from SA-1 degradation can be followed. The method can, probably, be extended to other electrolytic nickel baths.

Orthogonal Comparison of GC-MS and 1H NMR Spectroscopy for Short Chain Fatty Acid Quantitation.

PubMed

Cai, Jingwei; Zhang, Jingtao; Tian, Yuan; Zhang, Limin; Hatzakis, Emmanuel; Krausz, Kristopher W; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

2017-08-01

Short chain fatty acids (SCFAs) are important regulators of host physiology and metabolism and may contribute to obesity and associated metabolic diseases. Interest in SCFAs has increased in part due to the recognized importance of how production of SCFAs by the microbiota may signal to the host. Therefore, reliable, reproducible, and affordable methods for SCFA profiling are required for accurate identification and quantitation. In the current study, four different methods for SCFA (acetic acid, propionic acid, and butyric acid) extraction and quantitation were compared using two independent platforms including gas chromatography coupled with mass spectrometry (GC-MS) and 1 H nuclear magnetic resonance (NMR) spectroscopy. Sensitivity, recovery, repeatability, matrix effect, and validation using mouse fecal samples were determined across all methods. The GC-MS propyl esterification method exhibited superior sensitivity for acetic acid and butyric acid measurement (LOD < 0.01 μg mL -1 , LOQ < 0.1 μg mL -1 ) and recovery accuracy (99.4%-108.3% recovery rate for 100 μg mL -1 SCFA mixed standard spike in and 97.8%-101.8% recovery rate for 250 μg mL -1 SCFAs mixed standard spike in). NMR methods by either quantitation relative to an internal standard or quantitation using a calibration curve yielded better repeatability and minimal matrix effects compared to GC-MS methods. All methods generated good calibration curve linearity (R 2 > 0.99) and comparable measurement of fecal SCFA concentration. Lastly, these methods were used to quantitate fecal SCFAs obtained from conventionally raised (CONV-R) and germ free (GF) mice. Results from global metabolomic analysis of feces generated by 1 H NMR and bomb calorimetry were used to further validate these approaches.

31P NMR Characterization of Tricin and Its Structurally Similar Flavonoids

DOE PAGES

Li, Mi; Pu, Yunqiao; Tschaplinski, Timothy J.; ...

2017-04-24

Tricin, a flavonoid metabolite, has been recently identified as a component of lignin in select monocot plants. This finding has initiated consideration on updating the lignin biosynthesis pathway. Here, we report a rapid method of determination of tricin in corn stover lignin, based on 31P nuclear magnetic resonance (NMR) spectroscopy by phosphitylating with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane (TMDP). Nine other flavonoids, with similar structure to tricin, have also been examined using the current method. The application of 31P NMR enables rapid identification of tricin-like flavonoids in the heterogeneous lignin polymer. The well resolved spectroscopic peaks from these derivatized flavonoids and lignin functional groupsmore » provide important information for the determination of flavonoids individually or their association with lignin.« less

31P NMR Characterization of Tricin and Its Structurally Similar Flavonoids

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

Li, Mi; Pu, Yunqiao; Tschaplinski, Timothy J.

Tricin, a flavonoid metabolite, has been recently identified as a component of lignin in select monocot plants. This finding has initiated consideration on updating the lignin biosynthesis pathway. Here, we report a rapid method of determination of tricin in corn stover lignin, based on 31P nuclear magnetic resonance (NMR) spectroscopy by phosphitylating with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane (TMDP). Nine other flavonoids, with similar structure to tricin, have also been examined using the current method. The application of 31P NMR enables rapid identification of tricin-like flavonoids in the heterogeneous lignin polymer. The well resolved spectroscopic peaks from these derivatized flavonoids and lignin functional groupsmore » provide important information for the determination of flavonoids individually or their association with lignin.« less

Protein structure estimation from NMR data by matrix completion.

PubMed

Li, Zhicheng; Li, Yang; Lei, Qiang; Zhao, Qing

2017-09-01

Knowledge of protein structures is very important to understand their corresponding physical and chemical properties. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the main methods to measure protein structure. In this paper, we propose a two-stage approach to calculate the structure of a protein from a highly incomplete distance matrix, where most data are obtained from NMR. We first randomly "guess" a small part of unobservable distances by utilizing the triangle inequality, which is crucial for the second stage. Then we use matrix completion to calculate the protein structure from the obtained incomplete distance matrix. We apply the accelerated proximal gradient algorithm to solve the corresponding optimization problem. Furthermore, the recovery error of our method is analyzed, and its efficiency is demonstrated by several practical examples.

Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

PubMed

Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang

2010-06-01

In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization. Copyright 2010 Elsevier Inc. 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/.

Production and NMR signal optimization of hyperpolarized 13C-labeled amino acids

NASA Astrophysics Data System (ADS)

Parish, Christopher; Niedbalski, Peter; Ferguson, Sarah; Kiswandhi, Andhika; Lumata, Lloyd

Amino acids are targeted nutrients for consumption by cancers to sustain their rapid growth and proliferation. 13C-enriched amino acids are important metabolic tracers for cancer diagnostics using nuclear magnetic resonance (NMR) spectroscopy. Despite this diagnostic potential, 13C NMR of amino acids however is hampered by the inherently low NMR sensitivity of the 13C nuclei. In this work, we have employed a physics technique known as dynamic nuclear polarization (DNP) to enhance the NMR signals of 13C-enriched amino acids. DNP works by transferring the high polarization of electrons to the nuclear spins via microwave irradiation at low temperature and high magnetic field. Using a fast dissolution method in which the frozen polarized samples are dissolved rapidly with superheated water, injectable solutions of 13C-amino acids with highly enhanced NMR signals (by at least 5,000-fold) were produced at room temperature. Factors that affect the NMR signal enhancement levels such as the choice of free radical polarizing agents and sample preparation will be discussed along with the thermal mixing physics model of DNP. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

Multidimensional High-Resolution Magic Angle Spinning and Solution-State NMR Characterization of 13C-labeled Plant Metabolites and Lignocellulose

PubMed Central

Mori, Tetsuya; Tsuboi, Yuuri; Ishida, Nobuhiro; Nishikubo, Nobuyuki; Demura, Taku; Kikuchi, Jun

2015-01-01

Lignocellulose, which includes mainly cellulose, hemicellulose, and lignin, is a potential resource for the production of chemicals and for other applications. For effective production of materials derived from biomass, it is important to characterize the metabolites and polymeric components of the biomass. Nuclear magnetic resonance (NMR) spectroscopy has been used to identify biomass components; however, the NMR spectra of metabolites and lignocellulose components are ambiguously assigned in many cases due to overlapping chemical shift peaks. Using our 13C-labeling technique in higher plants such as poplar samples, we demonstrated that overlapping peaks could be resolved by three-dimensional NMR experiments to more accurately assign chemical shifts compared with two-dimensional NMR measurements. Metabolites of the 13C-poplar were measured by high-resolution magic angle spinning NMR spectroscopy, which allows sample analysis without solvent extraction, while lignocellulose components of the 13C-poplar dissolved in dimethylsulfoxide/pyridine solvent were analyzed by solution-state NMR techniques. Using these methods, we were able to unambiguously assign chemical shifts of small and macromolecular components in 13C-poplar samples. Furthermore, using samples of less than 5 mg, we could differentiate between two kinds of genes that were overexpressed in poplar samples, which produced clearly modified plant cell wall components. PMID:26143886

Computational approach to integrate 3D X-ray microtomography and NMR data.

PubMed

Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G; Trevizan, Willian A; Fortulan, Carlos A; Bonagamba, Tito J

2018-05-04

Nowadays, most of the efforts in NMR applied to porous media are dedicated to studying the molecular fluid dynamics within and among the pores. These analyses have a higher complexity due to morphology and chemical composition of rocks, besides dynamic effects as restricted diffusion, diffusional coupling, and exchange processes. Since the translational nuclear spin diffusion in a confined geometry (e.g. pores and fractures) requires specific boundary conditions, the theoretical solutions are restricted to some special problems and, in many cases, computational methods are required. The Random Walk Method is a classic way to simulate self-diffusion along a Digital Porous Medium. Bergman model considers the magnetic relaxation process of the fluid molecules by including a probability rate of magnetization survival under surface interactions. Here we propose a statistical approach to correlate surface magnetic relaxivity with the computational method applied to the NMR relaxation in order to elucidate the relationship between simulated relaxation time and pore size of the Digital Porous Medium. The proposed computational method simulates one- and two-dimensional NMR techniques reproducing, for example, longitudinal and transverse relaxation times (T 1 and T 2 , respectively), diffusion coefficients (D), as well as their correlations. For a good approximation between the numerical and experimental results, it is necessary to preserve the complexity of translational diffusion through the microstructures in the digital rocks. Therefore, we use Digital Porous Media obtained by 3D X-ray microtomography. To validate the method, relaxation times of ideal spherical pores were obtained and compared with the previous determinations by the Brownstein-Tarr model, as well as the computational approach proposed by Bergman. Furthermore, simulated and experimental results of synthetic porous media are compared. These results make evident the potential of computational physics in the analysis of the NMR data for complex porous materials. Copyright © 2018 Elsevier Inc. All rights reserved.

Taraxacin, a new guaianolide from Taraxacum wallichii.

PubMed

Ahmad, V U; Yasmeen, S; Ali, Z; Khan, M A; Choudhary, M I; Akhtar, F; Miana, G A; Zahid, M

2000-07-01

A new guaianolide, taraxacin (1), and a known sesquiterpene ketolactone (2) have been isolated from an ethyl acetate-soluble part of a methanolic extract of Taraxacum wallichii. The structure of 1 was established using NMR, MS, and X-ray crystallographic methods. The (13)C NMR data of 2 is also being reported for the first time.

1H and 13C-NMR studies on phenol-formaldehyde prepolymers for tannin-based adhesives

Treesearch

Gerald W. McGraw; Lawerence L. Lanucci; Seiji Ohara; Richard W. Hemingway

1989-01-01

The number average structure and the molecular weight distribution of phenol-formaldehyde prepolymers for use in synthesis of tannin-based adhesive resins were determined with 1H and 13C-NMR spectroscopy and gel permeation chromatography of acetylated resins. These methods were used to determine differences in phenol-...

Solid-state NMR imaging system

DOEpatents

Gopalsami, Nachappa; Dieckman, Stephen L.; Ellingson, William A.

1992-01-01

An apparatus for use with a solid-state NMR spectrometer includes a special imaging probe with linear, high-field strength gradient fields and high-power broadband RF coils using a back projection method for data acquisition and image reconstruction, and a real-time pulse programmer adaptable for use by a conventional computer for complex high speed pulse sequences.

High-resolution solution-state NMR of unfractionated plant cell walls

Treesearch

John Ralph; Fachuang Lu; Hoon Kim; Dino Ress; Daniel J. Yelle; Kenneth E. Hammel; Sally A. Ralph; Bernadette Nanayakkara; Armin Wagner; Takuya Akiyama; Paul F. Schatz; Shawn D. Mansfield; Noritsugu Terashima; Wout Boerjan; Bjorn Sundberg; Mattias Hedenstrom

2009-01-01

Detailed structural studies on the plant cell wall have traditionally been difficult. NMR is one of the preeminent structural tools, but obtaining high-resolution solution-state spectra has typically required fractionation and isolation of components of interest. With recent methods for dissolution of, admittedly, finely divided plant cell wall material, the wall can...

Surface and interfacial properties of soy-based polysoaps

USDA-ARS?s Scientific Manuscript database

Soybean oil (SO) was polymerized by the reaction of its double bonds in the presence of a catalyst. The resulting polymer (PSO) was positively identified using a combination of FTIR, 1H NMR, 13C NMR, and GPC methods. PSO was hydrolyzed into polysoaps with Na+, K+ or TEA+ (triethanol amine) counter i...

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.

Application of ¹H NMR for the characterisation and authentication of ''Tonda Gentile Trilobata" hazelnuts from Piedmont (Italy).

PubMed

Caligiani, Augusta; Coisson, Jean Daniel; Travaglia, Fabiano; Acquotti, Domenico; Palla, Gerardo; Palla, Luigi; Arlorio, Marco

2014-04-01

The Italian hazelnut (Corylus avellana L.) cultivar "Tonda Gentile Trilobata" (TGT) is covered by protected geographical indication "Nocciola Piemonte" and is well-known as the best-suited hazelnut for the industrial transformation into roasted kernel. The hazelnut cultivar identification is primarily based on morphological characteristics, so there is the need for more objective analytical methods for high quality hazelnut authentication. This study reports the (1)H NMR fingerprinting of raw and roasted hazelnut, with the aim of obtaining hazelnut classification based on their spectroscopic pattern. (1)H NMR analyses were carried out on polar extracts of TGT and other cultivars: the data were analysed with multivariate statistical methods. Results showed that (1)H NMR combined with chemometrics is useful to characterise the hazelnuts as a function of the cultivars, both on raw and roasted form. The classification models allowed identifying molecular markers useful to distinguish TGT from other types, among these trigonelline, amino acids and an unidentified orto-disubstituted aromatic compound. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Experimental (FT-IR, FT-Raman, 1H, 13C NMR) and theoretical study of alkali metal 2-aminobenzoates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Świsłocka, R.; Regulska, E.; Lewandowski, W.

2008-09-01

The influence of lithium, sodium, potassium, rubidium and cesium on the electronic system of the 2-aminobenzoic acid was studied by the methods of molecular spectroscopy. The vibrational (FT-IR, FT-Raman) and NMR ( 1H and 13C) spectra for 2-aminobenzoic acid and its alkali metal salts were recorded. The assignment of vibrational spectra was done on the basis of literature data, theoretical calculations and our previous experience. Characteristic shifts of bands and changes in intensities of bands along the metal series were observed. The changes of chemical shifts of protons ( 1H NMR) and carbons ( 13C NMR) in the series of studied alkali metal 2-aminobenzoates were observed too. Optimized geometrical structures of studied compounds were calculated by B3LYP method using 6-311++G ∗∗ basis set. Geometric aromaticity indices, dipole moments and energies were also calculated. The theoretical wavenumbers and intensities of IR and Raman spectra were obtained. The calculated parameters were compared to experimental characteristic of studied compounds.

Photochemical Degradation of the Anticancer Drug Bortezomib by V-UV/UV (185/254 nm) Investigated by (1)H NMR Fingerprinting: A Way to Follow Aromaticity Evolution.

PubMed

Martignac, Marion; Balayssac, Stéphane; Gilard, Véronique; Benoit-Marquié, Florence

2015-06-18

We have investigated the removal of bortezomib, an anticancer drug prescribed in multiple myeloma, using the photochemical advanced oxidation process of V-UV/UV (185/254 nm). We used two complementary analytical techniques to follow the removal rate of bortezomib. Nuclear magnetic resonance (NMR) is a nonselective method requiring no prior knowledge of the structures of the byproducts and permits us to provide a spectral signature (fingerprinting approach). This untargeted method provides clues to the molecular structure changes and information on the degradation of the parent drug during the irradiation process. This holistic NMR approach could provide information for monitoring aromaticity evolution. We use liquid chromatography, coupled with high-resolution mass spectrometry (LC-MS), to correlate results obtained by (1)H NMR and for accurate identification of the byproducts, in order to understand the mechanistic degradation pathways of bortezomib. The results show that primary byproducts come from photoassisted deboronation of bortezomib at 254 nm. A secondary byproduct of pyrazinecarboxamide was also identified. We obtained a reliable correlation between these two analytical techniques.

Investigation of Local Structures in Cation-ordered Microwave Dielectric A Solid-state NMR and First Principle Calculation Study

NASA Astrophysics Data System (ADS)

Kalfarisi, Rony G.

Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy has proven to be a powerful method to probe the local structure and dynamics of a system. In powdered solids, the nuclear spins experience various anisotropic interactions which depend on the molecular orientation. These anisotropic interactions make ssNMR very useful as they give a specific appearance to the resonance lines of the spectra. The position and shape of these resonance lines can be related to local structure and dynamics of the system under study. My research interest has focused around studying local structures and dynamics of quadrupolar nuclei in materials using ssNMR spectroscopy. 7Li and 93Nb ssNMR magic angle spinning (MAS) spectra, acquired at 17.6 and 7.06 T, have been used to evaluate the structural and dynamical properties of cation-ordered microwave dielectric materials. Microwave dielectric materials are essential in the application of wireless telecommunication, biomedical engineering, and other scientific and industrial implementations that use radio and microwave signals. The study of the local environment with respect to average structure, such as X-ray diffraction study, is essential for the better understanding of the correlations between structures and properties of these materials. The investigation for short and medium range can be performed with the use of ssNMR techniques. Even though XRD results show cationic ordering at the B-site (third coordination sphere), NMR spectra show a presence of disorder materials. This was indicated by the observation of a distribution in NMR parameters derived from experimental . {93}Nb NMR spectraand supported by theoretical calculations.

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

PubMed Central

2012-01-01

Background Red yeast rice (i.e., rice fermented with Monascus spp.), as a food supplement, is claimed to be blood cholesterol-lowering. The red yeast rice constituent monacolin K, also known as lovastatin, is an inhibitor of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase. This article aims to develop a sensitive nuclear magnetic resonance (NMR) method to determine the total statin content of red yeast rice products. Methods The total statin content was determined by a 400 MHz 1H NMR spectroscopic method, based on the integration of the multiplet at δ 5.37-5.32 ppm of a hydrogen at the hexahydronaphthalene moiety in comparison to an external calibration with lovastatin. The activity of HMG-CoA reductase was measured by a commercial spectrophotometric assay kit. Results The NMR detection limit for total statins was 6 mg/L (equivalent to 0.3 mg/capsule, if two capsules are dissolved in 50 mL ethanol). The relative standard deviations were consistently lower than 11%. The total statin concentrations of five red yeast rice supplements were between 1.5 and 25.2 mg per specified daily dose. A dose-dependent inhibition of the HMG-CoA reductase enzyme activity by the red yeast rice products was demonstrated. Conclusion A simple and direct NMR assay was developed to determine the total statin content in red yeast rice. The assay can be applied for the determination of statin content for the regulatory control of red yeast rice products. PMID:22439629

[Derivative spectrophotometric and NMR spectroscopic study in pharmaceutical science].

PubMed

Kitamura, Keisuke

2007-10-01

This review starts with an introduction of derivative spectrophotometry followed by a description on the construction of a personal computer-assisted derivative spectrophotometric (DS) system. An acquisition system for inputting digitalized absorption spectra into personal computers and a BASIC program for calculating derivative spectra were developed. Then, applications of the system to drug analyses that are difficult with traditional absorption methods are described. Following this, studies on the interactions of drugs with biological macromolecules by the DS and NMR methods were discussed. An (1)H NMR study elucidated that the small unilamellar vesicle (SUV) has a single membrane made of a phosphatidylcholine bilayer, and that chlorpromazine interacts with both the outer and inner layers. (13)C NMR revealed a reduction of the dissociation constants of phenothiazine drugs due to their interaction with SUV. The partition coefficients of phenothiazine, benzodiazepine and steroid drugs in an SUV-water system and the effects of cholesterol or amino lipids content on these partition coefficients were examined by the DS method. The binding constants of phenothiazine drugs to bovine serum albumin (BSA) and the influence of Na(+), K(+), Cl(-), Br(-), and I(-) on these binding constants were determined by DS. It was found that I(-), Br(-), Cl(-) reduce the binding constants in this order, and that Na(+) and K(+) have no effect. A (19)F NMR study revealed that triflupromazine binds to BSA and human serum albumin in two regions including Site II with different populations, and that a nonsteroidal anti-inflammatory drug, niflumic acid, binds Sites Ia and Ib.

Photo-CIDNP NMR spectroscopy of amino acids and proteins.

PubMed

Kuhn, Lars T

2013-01-01

Photo-chemically induced dynamic nuclear polarization (CIDNP) is a nuclear magnetic resonance (NMR) phenomenon which, among other things, is exploited to extract information on biomolecular structure via probing solvent-accessibilities of tryptophan (Trp), tyrosine (Tyr), and histidine (His) amino acid side chains both in polypeptides and proteins in solution. The effect, normally triggered by a (laser) light-induced photochemical reaction in situ, yields both positive and/or negative signal enhancements in the resulting NMR spectra which reflect the solvent exposure of these residues both in equilibrium and during structural transformations in "real time". As such, the method can offer - qualitatively and, to a certain extent, quantitatively - residue-specific structural and kinetic information on both the native and, in particular, the non-native states of proteins which, often, is not readily available from more routine NMR techniques. In this review, basic experimental procedures of the photo-CIDNP technique as applied to amino acids and proteins are discussed, recent improvements to the method highlighted, and future perspectives presented. First, the basic principles of the phenomenon based on the theory of the radical pair mechanism (RPM) are outlined. Second, a description of standard photo-CIDNP applications is given and it is shown how the effect can be exploited to extract residue-specific structural information on the conformational space sampled by unfolded or partially folded proteins on their "path" to the natively folded form. Last, recent methodological advances in the field are highlighted, modern applications of photo-CIDNP in the context of biological NMR evaluated, and an outlook into future perspectives of the method is given.

Observation of force-detected nuclear magnetic resonance in a homogeneous field

PubMed Central

Madsen, L. A.; Leskowitz, G. M.; Weitekamp, D. P.

2004-01-01

We report the experimental realization of BOOMERANG (better observation of magnetization, enhanced resolution, and no gradient), a sensitive and general method of magnetic resonance. The prototype millimeter-scale NMR spectrometer shows signal and noise levels in agreement with the design principles. We present 1H and 19F NMR in both solid and liquid samples, including time-domain Fourier transform NMR spectroscopy, multiple-pulse echoes, and heteronuclear J spectroscopy. By measuring a 1H-19F J coupling, this last experiment accomplishes chemically specific spectroscopy with force-detected NMR. In BOOMERANG, an assembly of permanent magnets provides a homogeneous field throughout the sample, while a harmonically suspended part of the assembly, a detector, is mechanically driven by spin-dependent forces. By placing the sample in a homogeneous field, signal dephasing by diffusion in a field gradient is made negligible, enabling application to liquids, in contrast to other force-detection methods. The design appears readily scalable to μm-scale samples where it should have sensitivity advantages over inductive detection with microcoils and where it holds great promise for application of magnetic resonance in biology, chemistry, physics, and surface science. We briefly discuss extensions of the BOOMERANG method to the μm and nm scales. PMID:15326302

Specific RNA-protein interactions detected with saturation transfer difference NMR.

PubMed

Harris, Kimberly A; Shekhtman, Alexander; Agris, Paul F

2013-08-01

RNA, at the forefront of biochemical research due to its central role in biology, is recognized by proteins through various mechanisms. Analysis of the RNA-protein interface provides insight into the recognition determinants and function. As such, there is a demand for developing new methods to characterize RNA-protein interactions. Saturation transfer difference (STD) NMR can identify binding ligands for proteins in a rather short period of time, with data acquisitions of just a few hours. Two RNA-protein systems involved in RNA modification were studied using STD NMR. The N (6)-threonylcarbamoyltransferase, YrdC, with nucleoside-specific recognition, was shown to bind the anticodon stem-loop of tRNA(Lys)UUU. The points of contact on the RNA were assigned and a binding interface was identified. STD NMR was also applied to the interaction of the archaeal ribosomal protein, L7Ae, with the box C/D K-turn RNA. The distinctiveness of the two RNA-protein interfaces was evident. Both RNAs exhibited strong STD signals indicative of direct contact with the respective protein, but reflected the nature of recognition. Characterization of nucleic acid recognition determinants traditionally involves cost and time prohibitive methods. This approach offers significant insight into interaction interfaces fairly rapidly, and complements existing structural methods.

Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods

PubMed Central

Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

2013-01-01

Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L2-norm regularization. However, sparse representation methods via L1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72–88, 2013. PMID:23847452

Laplace Inversion of Low-Resolution NMR Relaxometry Data Using Sparse Representation Methods.

PubMed

Berman, Paula; Levi, Ofer; Parmet, Yisrael; Saunders, Michael; Wiesman, Zeev

2013-05-01

Low-resolution nuclear magnetic resonance (LR-NMR) relaxometry is a powerful tool that can be harnessed for characterizing constituents in complex materials. Conversion of the relaxation signal into a continuous distribution of relaxation components is an ill-posed inverse Laplace transform problem. The most common numerical method implemented today for dealing with this kind of problem is based on L 2 -norm regularization. However, sparse representation methods via L 1 regularization and convex optimization are a relatively new approach for effective analysis and processing of digital images and signals. In this article, a numerical optimization method for analyzing LR-NMR data by including non-negativity constraints and L 1 regularization and by applying a convex optimization solver PDCO, a primal-dual interior method for convex objectives, that allows general linear constraints to be treated as linear operators is presented. The integrated approach includes validation of analyses by simulations, testing repeatability of experiments, and validation of the model and its statistical assumptions. The proposed method provides better resolved and more accurate solutions when compared with those suggested by existing tools. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 72-88, 2013.

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.

Automated NMR structure determination of stereo-array isotope labeled ubiquitin from minimal sets of spectra using the SAIL-FLYA system.

PubMed

Ikeya, Teppei; Takeda, Mitsuhiro; Yoshida, Hitoshi; Terauchi, Tsutomu; Jee, Jun-Goo; Kainosho, Masatsune; Güntert, Peter

2009-08-01

Stereo-array isotope labeling (SAIL) has been combined with the fully automated NMR structure determination algorithm FLYA to determine the three-dimensional structure of the protein ubiquitin from different sets of input NMR spectra. SAIL provides a complete stereo- and regio-specific pattern of stable isotopes that results in sharper resonance lines and reduced signal overlap, without information loss. Here we show that as a result of the superior quality of the SAIL NMR spectra, reliable, fully automated analyses of the NMR spectra and structure calculations are possible using fewer input spectra than with conventional uniformly 13C/15N-labeled proteins. FLYA calculations with SAIL ubiquitin, using a single three-dimensional "through-bond" spectrum (and 2D HSQC spectra) in addition to the 13C-edited and 15N-edited NOESY spectra for conformational restraints, yielded structures with an accuracy of 0.83-1.15 A for the backbone RMSD to the conventionally determined solution structure of SAIL ubiquitin. NMR structures can thus be determined almost exclusively from the NOESY spectra that yield the conformational restraints, without the need to record many spectra only for determining intermediate, auxiliary data of the chemical shift assignments. The FLYA calculations for this report resulted in 252 ubiquitin structure bundles, obtained with different input data but identical structure calculation and refinement methods. These structures cover the entire range from highly accurate structures to seriously, but not trivially, wrong structures, and thus constitute a valuable database for the substantiation of structure validation methods.

Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR

PubMed Central

Fenwick, R. Bryn; van den Bedem, Henry; Fraser, James S.; Wright, Peter E.

2014-01-01

Detailed descriptions of atomic coordinates and motions are required for an understanding of protein dynamics and their relation to molecular recognition, catalytic function, and allostery. Historically, NMR relaxation measurements have played a dominant role in the determination of the amplitudes and timescales (picosecond–nanosecond) of bond vector fluctuations, whereas high-resolution X-ray diffraction experiments can reveal the presence of and provide atomic coordinates for multiple, weakly populated substates in the protein conformational ensemble. Here we report a hybrid NMR and X-ray crystallography analysis that provides a more complete dynamic picture and a more quantitative description of the timescale and amplitude of fluctuations in atomic coordinates than is obtainable from the individual methods alone. Order parameters (S2) were calculated from single-conformer and multiconformer models fitted to room temperature and cryogenic X-ray diffraction data for dihydrofolate reductase. Backbone and side-chain order parameters derived from NMR relaxation experiments are in excellent agreement with those calculated from the room-temperature single-conformer and multiconformer models, showing that the picosecond timescale motions observed in solution occur also in the crystalline state. These motions are quenched in the crystal at cryogenic temperatures. The combination of NMR and X-ray crystallography in iterative refinement promises to provide an atomic resolution description of the alternate conformational substates that are sampled through picosecond to nanosecond timescale fluctuations of the protein structure. The method also provides insights into the structural heterogeneity of nonmethyl side chains, aromatic residues, and ligands, which are less commonly analyzed by NMR relaxation measurements. PMID:24474795

The potential for the indirect crystal structure verification of methyl glycosides based on acetates' parent structures: GIPAW and solid-state NMR approaches

NASA Astrophysics Data System (ADS)

Szeleszczuk, Łukasz; Gubica, Tomasz; Zimniak, Andrzej; Pisklak, Dariusz M.; Dąbrowska, Kinga; Cyrański, Michał K.; Kańska, Marianna

2017-10-01

A convenient method for the indirect crystal structure verification of methyl glycosides was demonstrated. Single-crystal X-ray diffraction structures for methyl glycoside acetates were deacetylated and subsequently subjected to DFT calculations under periodic boundary conditions. Solid-state NMR spectroscopy served as a guide for calculations. A high level of accuracy of the modelled crystal structures of methyl glycosides was confirmed by comparison with published results of neutron diffraction study using RMSD method.

Novel nuclear magnetic resonance techniques for studying biological molecules

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

Laws, David Douglas

2000-06-01

Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. Inmore » this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (Φ/Ψ) dihedral angles by comparing experimentally determined 13C a, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.« less

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 Methods, Applications and Trends for Groundwater Evaluation and Management

NASA Astrophysics Data System (ADS)

Walsh, D. O.; Grunewald, E. D.

2011-12-01

Nuclear magnetic resonance (NMR) measurements have a tremendous potential for improving groundwater characterization, as they provide direct detection and measurement of groundwater and unique information about pore-scale properties. NMR measurements, commonly used in chemistry and medicine, are utilized in geophysical investigations through non-invasive surface NMR (SNMR) or downhole NMR logging measurements. Our recent and ongoing research has focused on improving the performance and interpretation of NMR field measurements for groundwater characterization. Engineering advancements have addressed several key technical challenges associated with SNMR measurements. Susceptibility of SNMR measurements to environmental noise has been dramatically reduced through the development of multi-channel acquisition hardware and noise-cancellation software. Multi-channel instrumentation (up to 12 channels) has also enabled more efficient 2D and 3D imaging. Previous limitations in measuring NMR signals from water in silt, clay and magnetic geology have been addressed by shortening the instrument dead-time from 40 ms to 4 ms, and increasing the power output. Improved pulse sequences have been developed to more accurately estimate NMR relaxation times and their distributions, which are sensitive to pore size distributions. Cumulatively, these advancements have vastly expanded the range of environments in which SNMR measurements can be obtained, enabling detection of groundwater in smaller pores, in magnetic geology, in the unsaturated zone, and nearby to infrastructure (presented here in case studies). NMR logging can provide high-resolution estimates of bound and mobile water content and pore size distributions. While NMR logging has been utilized in oil and gas applications for decades, its use in groundwater investigations has been limited by the large size and high cost of oilfield NMR logging tools and services. Recently, engineering efforts funded by the US Department of Energy have produced an NMR logging tool that is much smaller and less costly than comparable oilfield NMR logging tools. This system is specifically designed for near surface groundwater investigations, incorporates small diameter probes (as small as 1.67 inches diameter) and man-portable surface stations, and provides NMR data and information content on par with oilfield NMR logging tools. A direct-push variant of this logging tool has also been developed. Key challenges associated with small diameter tools include inherently lower SNR and logging speeds, the desire to extend the sensitive zone as far as possible into unconsolidated formations, and simultaneously maintaining high power and signal fidelity. Our ongoing research in groundwater NMR aims to integrating surface and borehole measurements for regional-scale permeability mapping, and to develop in-place NMR sensors for long term monitoring of contaminant and remediation processes. In addition to groundwater resource characterization, promising new applications of NMR include assessing water content in ice and permafrost, management of groundwater in mining operations, and evaluation and management of groundwater in civil engineering applications.

The Law of Federal Employment.

DTIC Science & Technology

1991-08-01

See Ryan v. Federal Deposit Insurance Corp., 565 F.2d 762 (D.C. Cir. 1977). The EEOC regulations in this area are currently codified at 29 C.F.R. SS...attorney’s fee as part of the costs. 10.2 Reculatory Requirements. a. EEOC Implementation of Title VII, 1964 Civil Riqhts Act. EEOC regulations ...complaint proced.res and rights to appeal to EEOC and obtain judicial review are described in the following regulations . 29 C.F.R. S 1613.213

The RAILER System for Maintenance Management of U.S. Army Railroad Networks: RAILER 1 Description and Use

DTIC Science & Technology

1988-09-01

the report. Field Testing Specific aspects of field procedures have been tested at Fort Devens , MA, and at the Consolidated Rail Corporation (Conrail...days of formalized training on the system, both field proce- dures and computer operations, were conducted by USA-CERL at Fort Devens , MA. Attendees...included representatives from TSC, Fort Devens , FORSCOM, and the T.K. Dyer Corp. Initial Track Segmenting and Component Identification The office work

Advances in solid-state NMR of cellulose.

PubMed

Foston, Marcus

2014-06-01

Nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical and enabling technology in biofuel research. Over the past few decades, lignocellulosic biomass and its conversion to supplement or displace non-renewable feedstocks has attracted increasing interest. The application of solid-state NMR spectroscopy has long been seen as an important tool in the study of cellulose and lignocellulose structure, biosynthesis, and deconstruction, especially considering the limited number of effective solvent systems and the significance of plant cell wall three-dimensional microstructure and component interaction to conversion yield and rate profiles. This article reviews common and recent applications of solid-state NMR spectroscopy methods that provide insight into the structural and dynamic processes of cellulose that control bulk properties and biofuel conversion. Copyright © 2014 Elsevier Ltd. All rights reserved.

NMR/MRI with hyperpolarized gas and high Tc SQUID

DOEpatents

Schlenga, Klaus; de Souza, Ricardo E.; Wong-Foy, Annjoe; Clarke, John; Pines, Alexander

2000-01-01

A method and apparatus for the detection of nuclear magnetic resonance (NMR) signals and production of magnetic resonance imaging (MRI) from samples combines the use of hyperpolarized inert gases to enhance the NMR signals from target nuclei in a sample and a high critical temperature (Tc) superconducting quantum interference device (SQUID) to detect the NMR signals. The system operates in static magnetic fields of 3 mT or less (down to 0.1 mT), and at temperatures from liquid nitrogen (77K) to room temperature. Sample size is limited only by the size of the magnetic field coils and not by the detector. The detector is a high Tc SQUID magnetometer designed so that the SQUID detector can be very close to the sample, which can be at room temperature.

The plane-wave DFT investigations into the structure and the 11B solid-state NMR parameters of lithium fluorooxoborates

NASA Astrophysics Data System (ADS)

Czernek, Jiří; Brus, Jiří

2016-12-01

The strategy for an application of the first-principles calculations on crystalline systems to predict the 11B solid-state NMR powder-patterns is described, and its efficacy is demonstrated for two novel lithium-containing fluorooxborates, Li2B3O4F3 and Li2B6O9F2. This strategy involves the plane-wave DFT computations of the NMR parameters, whose values are then scaled and used in the spectral simulations, and are supposed to be directly applicable in the NMR crystallography studies of boron-containing systems. In particular, the GIPAW method and the PBE, PW91, and RPBE functionals are applied. Issues specific to the signal-assignment of the two compounds are also discussed.

Bacterial Expression and Purification of the Amyloidogenic Peptide PAPf39 for Multidimensional NMR Spectroscopy

PubMed Central

Shanmuganathan, Aranganathan; Bishop, Anthony C.; French, Kinsley C.; McCallum, Scott A.; Makhatadze, George I.

2013-01-01

PAPf39 is a 39 residue peptide fragment from human prostatic acidic phosphatase that forms amyloid fibrils in semen. These fibrils have been implicated in facilitating HIV transmission. To enable structural studies of PAPf39 by NMR spectroscopy, efficient methods allowing the production of milligram quantities of isotopically labeled peptide are essential. Here, we report the high-yield expression, as a fusion to ubiquitin at the N-terminus and an intein at the C-terminus, and purification of uniformly labeled 13C- and 15N-labeled PAPf39 peptide. This allows the study of the PAPf39 monomer conformational ensemble by NMR spectroscopy. To this end, we performed the NMR chemical shift assignment of the PAPf39 peptide in the monomeric state at low pH. PMID:23314347

A multi-standard approach for GIAO (13)C NMR calculations.

PubMed

Sarotti, Ariel M; Pellegrinet, Silvina C

2009-10-02

The influence of the reference standard employed in the calculation of (13)C NMR chemical shifts was investigated over a large variety of known organic compounds, using different quantum chemistry methods and basis sets. After detailed analysis of the collected data, we found that methanol and benzene are excellent reference standards for computing NMR shifts of sp(3)- and sp-sp(2)-hybridized carbon atoms, respectively. This multi-standard approach (MSTD) performs better than TMS in terms of accuracy and precision and also displays much lower dependence on the level of theory employed. The use of mPW1PW91/6-31G(d)//mPW1PW91/6-31G(d) level is recommended for accurate (13)C NMR chemical shift prediction at low computational cost.

Metabolic studies of mammalian cells by 31P-NMR using a continuous perfusion technique.

PubMed

Knop, R H; Chen, C W; Mitchell, J B; Russo, A; McPherson, S; Cohen, J S

1984-07-20

Levels of ATP and Pi in metabolically active Chinese hamster lung fibroblasts were monitored noninvasively by 31P-NMR over many hours and under a variety of conditions. The cells were embedded in a matrix of agarose gel in the form of fine threads which were continuously perfused in a standard NMR tube. The small diameter of the thread allows rapid diffusion of metabolites and drugs into the cells. The changes in ATP and Pi levels were followed as a function of time in response to perfusion with a glucose-containing medium, with isotonic saline and with a medium containing 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation. This gel-thread perfusion method should enable routine NMR studies of cellular metabolism, and may have other potential biological applications.