Random phase detection in multidimensional NMR.

PubMed

Maciejewski, Mark W; Fenwick, Matthew; Schuyler, Adam D; Stern, Alan S; Gorbatyuk, Vitaliy; Hoch, Jeffrey C

2011-10-04

Despite advances in resolution accompanying the development of high-field superconducting magnets, biomolecular applications of NMR require multiple dimensions in order to resolve individual resonances, and the achievable resolution is typically limited by practical constraints on measuring time. In addition to the need for measuring long evolution times to obtain high resolution, the need to distinguish the sign of the frequency constrains the ability to shorten measuring times. Sign discrimination is typically accomplished by sampling the signal with two different receiver phases or by selecting a reference frequency outside the range of frequencies spanned by the signal and then sampling at a higher rate. In the parametrically sampled (indirect) time dimensions of multidimensional NMR experiments, either method imposes an additional factor of 2 sampling burden for each dimension. We demonstrate that by using a single detector phase at each time sample point, but randomly altering the phase for different points, the sign ambiguity that attends fixed single-phase detection is resolved. Random phase detection enables a reduction in experiment time by a factor of 2 for each indirect dimension, amounting to a factor of 8 for a four-dimensional experiment, albeit at the cost of introducing sampling artifacts. Alternatively, for fixed measuring time, random phase detection can be used to double resolution in each indirect dimension. Random phase detection is complementary to nonuniform sampling methods, and their combination offers the potential for additional benefits. In addition to applications in biomolecular NMR, random phase detection could be useful in magnetic resonance imaging and other signal processing contexts.

Proton-Based Ultrafast Magic Angle Spinning Solid-State NMR Spectroscopy.

PubMed

Zhang, Rongchun; Mroue, Kamal H; Ramamoorthy, Ayyalusamy

2017-04-18

Protons are vastly abundant in a wide range of exciting macromolecules and thus can be a powerful probe to investigate the structure and dynamics at atomic resolution using solid-state NMR (ssNMR) spectroscopy. Unfortunately, the high signal sensitivity, afforded by the high natural-abundance and high gyromagnetic ratio of protons, is greatly compromised by severe line broadening due to the very strong 1 H- 1 H dipolar couplings. As a result, protons are rarely used, in spite of the desperate need for enhancing the sensitivity of ssNMR to study a variety of systems that are not amenable for high resolution investigation using other techniques including X-ray crystallography, cryo-electron microscopy, and solution NMR spectroscopy. Thanks to the remarkable improvement in proton spectral resolution afforded by the significant advances in magic-angle-spinning (MAS) probe technology, 1 H ssNMR spectroscopy has recently attracted considerable attention in the structural and dynamics studies of various molecular systems. However, it still remains a challenge to obtain narrow 1 H spectral lines, especially from proteins, without resorting to deuteration. In this Account, we review recent proton-based ssNMR strategies that have been developed in our laboratory to further improve proton spectral resolution without resorting to chemical deuteration for the purposes of gaining atomistic-level insights into molecular structures of various crystalline solid systems, using small molecules and peptides as illustrative examples. The proton spectral resolution enhancement afforded by the ultrafast MAS frequencies up to 120 kHz is initially discussed, followed by a description of an ensemble of multidimensional NMR pulse sequences, all based on proton detection, that have been developed to obtain in-depth information from dipolar couplings and chemical shift anisotropy (CSA). Simple single channel multidimensional proton NMR experiments could be performed to probe the proximity of protons for structure determination using 1 H- 1 H dipolar couplings and to evaluate the changes in chemical environments as well as the relative orientation to the external magnetic field using proton CSA. Due to the boost in signal sensitivity enabled by proton detection under ultrafast MAS, by virtue of high proton natural abundance and gyromagnetic ratio, proton-detected multidimensional experiments involving low-γ nuclei can now be accomplished within a reasonable time, while the higher dimension also offers additional resolution enhancement. In addition, the application of proton-based ssNMR spectroscopy under ultrafast MAS in various challenging and crystalline systems is also presented. Finally, we briefly discuss the limitations and challenges pertaining to proton-based ssNMR spectroscopy under ultrafast MAS conditions, such as the presence of high-order dipolar couplings, friction-induced sample heating, and limited sample volume. Although there are still a number of challenges that must be circumvented by further developments in radio frequency pulse sequences, MAS probe technology and approaches to prepare NMR-friendly samples, proton-based ssNMR has already gained much popularity in various research domains, especially in proteins where uniform or site-selective deuteration can be relatively easily achieved. In addition, implementation of the recently developed fast data acquisition approaches would also enable further developments in the design and applications of proton-based ultrafast MAS multidimensional ssNMR techniques.

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.

Quick, sensitive serial NMR experiments with Radon transform.

PubMed

Dass, Rupashree; Kasprzak, Paweł; Kazimierczuk, Krzysztof

2017-09-01

The Radon transform is a potentially powerful tool for processing the data from serial spectroscopic experiments. It makes it possible to decode the rate at which frequencies of spectral peaks shift under the effect of changing conditions, such as temperature, pH, or solvent. In this paper we show how it also improves speed and sensitivity, especially in multidimensional experiments. This is particularly important in the case of low-sensitivity techniques, such as NMR spectroscopy. As an example, we demonstrate how Radon transform processing allows serial measurements of 15 N-HSQC spectra of unlabelled peptides that would otherwise be infeasible. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Nonuniform sampling and non-Fourier signal processing methods in multidimensional NMR.

PubMed

Mobli, Mehdi; Hoch, Jeffrey C

2014-11-01

Beginning with the introduction of Fourier Transform NMR by Ernst and Anderson in 1966, time domain measurement of the impulse response (the free induction decay, FID) consisted of sampling the signal at a series of discrete intervals. For compatibility with the discrete Fourier transform (DFT), the intervals are kept uniform, and the Nyquist theorem dictates the largest value of the interval sufficient to avoid aliasing. With the proposal by Jeener of parametric sampling along an indirect time dimension, extension to multidimensional experiments employed the same sampling techniques used in one dimension, similarly subject to the Nyquist condition and suitable for processing via the discrete Fourier transform. The challenges of obtaining high-resolution spectral estimates from short data records using the DFT were already well understood, however. Despite techniques such as linear prediction extrapolation, the achievable resolution in the indirect dimensions is limited by practical constraints on measuring time. The advent of non-Fourier methods of spectrum analysis capable of processing nonuniformly sampled data has led to an explosion in the development of novel sampling strategies that avoid the limits on resolution and measurement time imposed by uniform sampling. The first part of this review discusses the many approaches to data sampling in multidimensional NMR, the second part highlights commonly used methods for signal processing of such data, and the review concludes with a discussion of other approaches to speeding up data acquisition in NMR. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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).

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.

Selective excitation enables assignment of proton resonances and (1)H-(1)H distance measurement in ultrafast magic angle spinning solid state NMR spectroscopy.

PubMed

Zhang, Rongchun; Ramamoorthy, Ayyalusamy

2015-07-21

Remarkable developments in ultrafast magic angle spinning (MAS) solid-state NMR spectroscopy enabled proton-based high-resolution multidimensional experiments on solids. To fully utilize the benefits rendered by proton-based ultrafast MAS experiments, assignment of (1)H resonances becomes absolutely necessary. Herein, we propose an approach to identify different proton peaks by using dipolar-coupled heteronuclei such as (13)C or (15)N. In this method, after the initial preparation of proton magnetization and cross-polarization to (13)C nuclei, transverse magnetization of desired (13)C nuclei is selectively prepared by using DANTE (Delays Alternating with Nutations for Tailored Excitation) sequence and then, it is transferred to bonded protons with a short-contact-time cross polarization. Our experimental results demonstrate that protons bonded to specific (13)C atoms can be identified and overlapping proton peaks can also be assigned. In contrast to the regular 2D HETCOR experiment, only a few 1D experiments are required for the complete assignment of peaks in the proton spectrum. Furthermore, the finite-pulse radio frequency driven recoupling sequence could be incorporated right after the selection of specific proton signals to monitor the intensity buildup for other proton signals. This enables the extraction of (1)H-(1)H distances between different pairs of protons. Therefore, we believe that the proposed method will greatly aid in fast assignment of peaks in proton spectra and will be useful in the development of proton-based multi-dimensional solid-state NMR experiments to study atomic-level resolution structure and dynamics of solids.

Fast multi-dimensional NMR by minimal sampling

NASA Astrophysics Data System (ADS)

Kupče, Ēriks; Freeman, Ray

2008-03-01

A new scheme is proposed for very fast acquisition of three-dimensional NMR spectra based on minimal sampling, instead of the customary step-wise exploration of all of evolution space. The method relies on prior experiments to determine accurate values for the evolving frequencies and intensities from the two-dimensional 'first planes' recorded by setting t1 = 0 or t2 = 0. With this prior knowledge, the entire three-dimensional spectrum can be reconstructed by an additional measurement of the response at a single location (t1∗,t2∗) where t1∗ and t2∗ are fixed values of the evolution times. A key feature is the ability to resolve problems of overlap in the acquisition dimension. Applied to a small protein, agitoxin, the three-dimensional HNCO spectrum is obtained 35 times faster than systematic Cartesian sampling of the evolution domain. The extension to multi-dimensional spectroscopy is outlined.

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.

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.

Non-uniform sampling: post-Fourier era of NMR data collection and processing.

PubMed

Kazimierczuk, Krzysztof; Orekhov, Vladislav

2015-11-01

The invention of multidimensional techniques in the 1970s revolutionized NMR, making it the general tool of structural analysis of molecules and materials. In the most straightforward approach, the signal sampling in the indirect dimensions of a multidimensional experiment is performed in the same manner as in the direct dimension, i.e. with a grid of equally spaced points. This results in lengthy experiments with a resolution often far from optimum. To circumvent this problem, numerous sparse-sampling techniques have been developed in the last three decades, including two traditionally distinct approaches: the radial sampling and non-uniform sampling. This mini review discusses the sparse signal sampling and reconstruction techniques from the point of view of an underdetermined linear algebra problem that arises when a full, equally spaced set of sampled points is replaced with sparse sampling. Additional assumptions that are introduced to solve the problem, as well as the shape of the undersampled Fourier transform operator (visualized as so-called point spread function), are shown to be the main differences between various sparse-sampling methods. Copyright © 2015 John Wiley & Sons, Ltd.

Selective Data Acquisition in NMR. The Quantification of Anti-phase Scalar Couplings

NASA Astrophysics Data System (ADS)

Hodgkinson, P.; Holmes, K. J.; Hore, P. J.

Almost all time-domain NMR experiments employ "linear sampling," in which the NMR response is digitized at equally spaced times, with uniform signal averaging. Here, the possibilities of nonlinear sampling are explored using anti-phase doublets in the indirectly detected dimensions of multidimensional COSY-type experiments as an example. The Cramér-Rao lower bounds are used to evaluate and optimize experiments in which the sampling points, or the extent of signal averaging at each point, or both, are varied. The optimal nonlinear sampling for the estimation of the coupling constant J, by model fitting, turns out to involve just a few key time points, for example, at the first node ( t= 1/ J) of the sin(π Jt) modulation. Such sparse sampling patterns can be used to derive more practical strategies, in which the sampling or the signal averaging is distributed around the most significant time points. The improvements in the quantification of NMR parameters can be quite substantial especially when, as is often the case for indirectly detected dimensions, the total number of samples is limited by the time available.

Speeding up NMR by in Situ Photo-Induced Reversible Acceleration of T1 -Relaxation (PIRAT).

PubMed

Stadler, Eduard; Dommaschk, Marcel; Frühwirt, Philipp; Herges, Rainer; Gescheidt, Georg

2018-03-05

Increasing the signal-to-noise ratio is one of the major goals in the field of NMR spectroscopy. In this proof of concept, we accelerate relaxation during an NMR pulse sequence using photo-generated paramagnetic states of an inert sensitizer. For the follow-up acquisition period, the system is converted to a diamagnetic state. The reversibility of the photo-induced switching allows extensive repetition required for multidimensional NMR. We thus eliminate the obstacle of line-broadening by the presence of paramagnetic species. In this contribution, we show how cycling of synchronized light/pulse sequences leads to an enhanced efficiency in multidimensional NMR. Our approach utilizes a molecular spin switch reversibly altering between a paramagnetic and diamagnetic state. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective excitation enables assignment of proton resonances and {sup 1}H-{sup 1}H distance measurement in ultrafast magic angle spinning solid state NMR spectroscopy

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

Zhang, Rongchun; Ramamoorthy, Ayyalusamy, E-mail: ramamoor@umich.edu

2015-07-21

Remarkable developments in ultrafast magic angle spinning (MAS) solid-state NMR spectroscopy enabled proton-based high-resolution multidimensional experiments on solids. To fully utilize the benefits rendered by proton-based ultrafast MAS experiments, assignment of {sup 1}H resonances becomes absolutely necessary. Herein, we propose an approach to identify different proton peaks by using dipolar-coupled heteronuclei such as {sup 13}C or {sup 15}N. In this method, after the initial preparation of proton magnetization and cross-polarization to {sup 13}C nuclei, transverse magnetization of desired {sup 13}C nuclei is selectively prepared by using DANTE (Delays Alternating with Nutations for Tailored Excitation) sequence and then, it is transferredmore » to bonded protons with a short-contact-time cross polarization. Our experimental results demonstrate that protons bonded to specific {sup 13}C atoms can be identified and overlapping proton peaks can also be assigned. In contrast to the regular 2D HETCOR experiment, only a few 1D experiments are required for the complete assignment of peaks in the proton spectrum. Furthermore, the finite-pulse radio frequency driven recoupling sequence could be incorporated right after the selection of specific proton signals to monitor the intensity buildup for other proton signals. This enables the extraction of {sup 1}H-{sup 1}H distances between different pairs of protons. Therefore, we believe that the proposed method will greatly aid in fast assignment of peaks in proton spectra and will be useful in the development of proton-based multi-dimensional solid-state NMR experiments to study atomic-level resolution structure and dynamics of solids.« less

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.

NMR of lignins

Treesearch

John Ralph; Larry L. Landucci

2010-01-01

This chapter will consider the basic aspects and findings of several forms of NMR spectroscopy, including separate discussions of proton, carbon, heteronuclear, and multidimensional NMR. Enhanced focus will be on 13C NMR, because of its qualitative and quantitative importance, followed by NMR’s contributions to our understanding of lignin...

High resolution 4-D spectroscopy with sparse concentric shell sampling and FFT-CLEAN.

PubMed

Coggins, Brian E; Zhou, Pei

2008-12-01

Recent efforts to reduce the measurement time for multidimensional NMR experiments have fostered the development of a variety of new procedures for sampling and data processing. We recently described concentric ring sampling for 3-D NMR experiments, which is superior to radial sampling as input for processing by a multidimensional discrete Fourier transform. Here, we report the extension of this approach to 4-D spectroscopy as Randomized Concentric Shell Sampling (RCSS), where sampling points for the indirect dimensions are positioned on concentric shells, and where random rotations in the angular space are used to avoid coherent artifacts. With simulations, we show that RCSS produces a very low level of artifacts, even with a very limited number of sampling points. The RCSS sampling patterns can be adapted to fine rectangular grids to permit use of the Fast Fourier Transform in data processing, without an apparent increase in the artifact level. These artifacts can be further reduced to the noise level using the iterative CLEAN algorithm developed in radioastronomy. We demonstrate these methods on the high resolution 4-D HCCH-TOCSY spectrum of protein G's B1 domain, using only 1.2% of the sampling that would be needed conventionally for this resolution. The use of a multidimensional FFT instead of the slow DFT for initial data processing and for subsequent CLEAN significantly reduces the calculation time, yielding an artifact level that is on par with the level of the true spectral noise.

High Resolution 4-D Spectroscopy with Sparse Concentric Shell Sampling and FFT-CLEAN

PubMed Central

Coggins, Brian E.; Zhou, Pei

2009-01-01

SUMMARY Recent efforts to reduce the measurement time for multidimensional NMR experiments have fostered the development of a variety of new procedures for sampling and data processing. We recently described concentric ring sampling for 3-D NMR experiments, which is superior to radial sampling as input for processing by a multidimensional discrete Fourier transform. Here, we report the extension of this approach to 4-D spectroscopy as Randomized Concentric Shell Sampling (RCSS), where sampling points for the indirect dimensions are positioned on concentric shells, and where random rotations in the angular space are used to avoid coherent artifacts. With simulations, we show that RCSS produces a very low level of artifacts, even with a very limited number of sampling points. The RCSS sampling patterns can be adapted to fine rectangular grids to permit use of the Fast Fourier Transform in data processing, without an apparent increase in the artifact level. These artifacts can be further reduced to the noise level using the iterative CLEAN algorithm developed in radioastronomy. We demonstrate these methods on the high resolution 4-D HCCH-TOCSY spectrum of protein G's B1 domain, using only 1.2% of the sampling that would be needed conventionally for this resolution. The use of a multidimensional FFT instead of the slow DFT for initial data processing and for subsequent CLEAN significantly reduces the calculation time, yielding an artifact level that is on par with the level of the true spectral noise. PMID:18853260

Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA

NASA Astrophysics Data System (ADS)

Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

2014-07-01

Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans.

Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA.

PubMed

Mroue, Kamal H; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H; Morris, Michael D; Ramamoorthy, Ayyalusamy

2014-07-01

Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA=Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the (1)H T1 values were calculated from data collected by (1)H spin-inversion recovery method detected in natural-abundance (13)C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the (1)H T1 values can be successfully reduced by a factor of 3.5 using as low as 10mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the (13)C CPMAS spectra. These results obtained from (13)C-detected CPMAS experiments were further confirmed using (1)H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans. Copyright © 2014 Elsevier Inc. All rights reserved.

Knowledge-based nonuniform sampling in multidimensional NMR.

PubMed

Schuyler, Adam D; Maciejewski, Mark W; Arthanari, Haribabu; Hoch, Jeffrey C

2011-07-01

The full resolution afforded by high-field magnets is rarely realized in the indirect dimensions of multidimensional NMR experiments because of the time cost of uniformly sampling to long evolution times. Emerging methods utilizing nonuniform sampling (NUS) enable high resolution along indirect dimensions by sampling long evolution times without sampling at every multiple of the Nyquist sampling interval. While the earliest NUS approaches matched the decay of sampling density to the decay of the signal envelope, recent approaches based on coupled evolution times attempt to optimize sampling by choosing projection angles that increase the likelihood of resolving closely-spaced resonances. These approaches employ knowledge about chemical shifts to predict optimal projection angles, whereas prior applications of tailored sampling employed only knowledge of the decay rate. In this work we adapt the matched filter approach as a general strategy for knowledge-based nonuniform sampling that can exploit prior knowledge about chemical shifts and is not restricted to sampling projections. Based on several measures of performance, we find that exponentially weighted random sampling (envelope matched sampling) performs better than shift-based sampling (beat matched sampling). While shift-based sampling can yield small advantages in sensitivity, the gains are generally outweighed by diminished robustness. Our observation that more robust sampling schemes are only slightly less sensitive than schemes highly optimized using prior knowledge about chemical shifts has broad implications for any multidimensional NMR study employing NUS. The results derived from simulated data are demonstrated with a sample application to PfPMT, the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum.

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

Simultaneous acquisition of 2D and 3D solid-state NMR experiments for sequential assignment of oriented membrane protein samples.

PubMed

Gopinath, T; Mote, Kaustubh R; Veglia, Gianluigi

2015-05-01

We present a new method called DAISY (Dual Acquisition orIented ssNMR spectroScopY) for the simultaneous acquisition of 2D and 3D oriented solid-state NMR experiments for membrane proteins reconstituted in mechanically or magnetically aligned lipid bilayers. DAISY utilizes dual acquisition of sine and cosine dipolar or chemical shift coherences and long living (15)N longitudinal polarization to obtain two multi-dimensional spectra, simultaneously. In these new experiments, the first acquisition gives the polarization inversion spin exchange at the magic angle (PISEMA) or heteronuclear correlation (HETCOR) spectra, the second acquisition gives PISEMA-mixing or HETCOR-mixing spectra, where the mixing element enables inter-residue correlations through (15)N-(15)N homonuclear polarization transfer. The analysis of the two 2D spectra (first and second acquisitions) enables one to distinguish (15)N-(15)N inter-residue correlations for sequential assignment of membrane proteins. DAISY can be implemented in 3D experiments that include the polarization inversion spin exchange at magic angle via I spin coherence (PISEMAI) sequence, as we show for the simultaneous acquisition of 3D PISEMAI-HETCOR and 3D PISEMAI-HETCOR-mixing experiments.

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.

Monitoring mechanistic details in the synthesis of pyrimidines via real-time, ultrafast multidimensional NMR spectroscopy

PubMed Central

Pardo, Zulay D.; Olsen, Greg; Fernández-Valle, María Encarnación; Frydman, Lucio; Martínez-Álvarez, Roberto; Herrera, Antonio

2016-01-01

Recent years have witnessed unprecedented advances in the development of fast multidimensional NMR acquisition techniques. This progress could open valuable new opportunities for the elucidation of chemical and biochemical processes. This study demonstrates one such capability, with the first real-time 2D dynamic analysis of a complex organic reaction relying on unlabeled substrates. Implementing such measurements required the development of new ultrafast 2D methods, capable of monitoring multiple spectral regions of interest as the reaction progressed. The alternate application of these acquisitions in an interleaved, excitation-optimized fashion, allowed us to extract new structural and dynamic insight concerning the reaction between aliphatic ketones and triflic anhydride in the presence of nitriles to yield alkylpyrimidines. Up to 2500 2D NMR data sets were thus collected over the course of this nearly 100 min long reaction, in an approach resembling that used in functional magnetic resonance imaging. With the aid of these new frequency-selective low-gradient-strength experiments, supplemented by chemical shift calculations of the spectral coordinates observed in the 2D heteronuclear correlations, previously postulated intermediates involved in the alkylpyrimidine formation process could be confirmed, and hitherto undetected ones were revealed. The potential and limitations of the resulting methods are discussed. PMID:22283498

A dynamic nuclear polarization strategy for multi-dimensional Earth's field NMR spectroscopy.

PubMed

Halse, Meghan E; Callaghan, Paul T

2008-12-01

Dynamic nuclear polarization (DNP) is introduced as a powerful tool for polarization enhancement in multi-dimensional Earth's field NMR spectroscopy. Maximum polarization enhancements, relative to thermal equilibrium in the Earth's magnetic field, are calculated theoretically and compared to the more traditional prepolarization approach for NMR sensitivity enhancement at ultra-low fields. Signal enhancement factors on the order of 3000 are demonstrated experimentally using DNP with a nitroxide free radical, TEMPO, which contains an unpaired electron which is strongly coupled to a neighboring (14)N nucleus via the hyperfine interaction. A high-quality 2D (19)F-(1)H COSY spectrum acquired in the Earth's magnetic field with DNP enhancement is presented and compared to simulation.

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.

Single-scan 2D NMR: An Emerging Tool in Analytical Spectroscopy

PubMed Central

Giraudeau, Patrick; Frydman, Lucio

2016-01-01

Two-dimensional Nuclear Magnetic Resonance (2D NMR) spectroscopy is widely used in chemical and biochemical analyses. Multidimensional NMR is also witnessing an increased use in quantitative and metabolic screening applications. Conventional 2D NMR experiments, however, are affected by inherently long acquisition durations, arising from their need to sample the frequencies involved along their indirect domains in an incremented, scan-by-scan nature. A decade ago a so-called “ultrafast” (UF) approach was proposed, capable to deliver arbitrary 2D NMR spectra involving any kind of homo- or hetero-nuclear correlations, in a single scan. During the intervening years the performance of this sub-second 2D NMR methodology has been greatly improved, and UF 2D NMR is rapidly becoming a powerful analytical tool witnessing an expanded scope of applications. The present reviews summarizes the principles and the main developments which have contributed to the success of this approach, and focuses on applications which have been recently demonstrated in various areas of analytical chemistry –from the real time monitoring of chemical and biochemical processes, to extensions in hyphenated techniques and in quantitative applications. PMID:25014342

Quantitative, equal carbon response HSQC experiment, QEC-HSQC

NASA Astrophysics Data System (ADS)

Mäkelä, Valtteri; Helminen, Jussi; Kilpeläinen, Ilkka; Heikkinen, Sami

2016-10-01

Quantitative NMR has become increasingly useful and popular in recent years, with many new and emerging applications in metabolomics, quality control, reaction monitoring and other types of mixture analysis. While sensitive and simple to acquire, the low resolving power of 1D 1H NMR spectra can be a limiting factor when analyzing complex mixtures. This drawback can be solved by observing a different type of nuclei offering improved resolution or with multidimensional experiments, such as HSQC. In this paper, we present a novel Quantitative, Equal Carbon HSQC (QEC-HSQC) experiment providing an equal response across different type of carbons regardless of the number of attached protons, in addition to an uniform response over a wide range of 1JCH couplings. This enables rapid quantification and integration over multiple signals without the need for complete resonance assignments and simplifies the integration of overlapping signals.

Major Variations in HIV-1 Capsid Assembly Morphologies Involve Minor Variations in Molecular Structures of Structurally Ordered Protein Segments*

PubMed Central

Lu, Jun-Xia; Bayro, Marvin J.; Tycko, Robert

2016-01-01

We present the results of solid state nuclear magnetic resonance (NMR) experiments on HIV-1 capsid protein (CA) assemblies with three different morphologies, namely wild-type CA (WT-CA) tubes with 35–60 nm diameters, planar sheets formed by the Arg18-Leu mutant (R18L-CA), and R18L-CA spheres with 20–100 nm diameters. The experiments are intended to elucidate molecular structural variations that underlie these variations in CA assembly morphology. We find that multidimensional solid state NMR spectra of 15N,13C-labeled CA assemblies are remarkably similar for the three morphologies, with only small differences in 15N and 13C chemical shifts, no significant differences in NMR line widths, and few differences in the number of detectable NMR cross-peaks. Thus, the pronounced differences in morphology do not involve major differences in the conformations and identities of structurally ordered protein segments. Instead, morphological variations are attributable to variations in conformational distributions within disordered segments, which do not contribute to the solid state NMR spectra. Variations in solid state NMR signals from certain amino acid side chains are also observed, suggesting differences in the intermolecular dimerization interface between curved and planar CA lattices, as well as possible differences in intramolecular helix-helix packing. PMID:27129282

Sensitivity Gains, Linearity, and Spectral Reproducibility in Nonuniformly Sampled Multidimensional MAS NMR Spectra of High Dynamic Range.

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

Suiter, Christopher L.; Paramasivam, Sivakumar; Hou, Guangjin

Recently, we have demonstrated that considerable inherent sensitivity gains are attained in MAS NMR spectra acquired by nonuniform sampling (NUS) and introduced maximum entropy interpolation (MINT) processing that assures the linearity of transformation between the time and frequency domains. In this report, we examine the utility of the NUS/MINT approach in multidimensional datasets possessing high dynamic range, such as homonuclear 13C–13C correlation spectra. We demonstrate on model compounds and on 1–73-(U-13C,15N)/74–108-(U-15N) E. coli thioredoxin reassembly, that with appropriately constructed 50 % NUS schedules inherent sensitivity gains of 1.7–2.1-fold are readily reached in such datasets. We show that both linearity andmore » line width are retained under these experimental conditions throughout the entire dynamic range of the signals. Furthermore, we demonstrate that the reproducibility of the peak intensities is excellent in the NUS/MINT approach when experiments are repeated multiple times and identical experimental and processing conditions are employed. Finally, we discuss the principles for design and implementation of random exponentially biased NUS sampling schedules for homonuclear 13C–13C MAS correlation experiments that yield high quality artifact-free datasets.« less

Sensitivity gains, linearity, and spectral reproducibility in nonuniformly sampled multidimensional MAS NMR spectra of high dynamic range

PubMed Central

Suiter, Christopher L.; Paramasivam, Sivakumar; Hou, Guangjin; Sun, Shangjin; Rice, David; Hoch, Jeffrey C.; Rovnyak, David

2014-01-01

Recently, we have demonstrated that considerable inherent sensitivity gains are attained in MAS NMR spectra acquired by nonuniform sampling (NUS) and introduced maximum entropy interpolation (MINT) processing that assures the linearity of transformation between the time and frequency domains. In this report, we examine the utility of the NUS/MINT approach in multidimensional datasets possessing high dynamic range, such as homonuclear 13C–13C correlation spectra. We demonstrate on model compounds and on 1–73-(U-13C, 15N)/74–108-(U-15N) E. coli thioredoxin reassembly, that with appropriately constructed 50 % NUS schedules inherent sensitivity gains of 1.7–2.1-fold are readily reached in such datasets. We show that both linearity and line width are retained under these experimental conditions throughout the entire dynamic range of the signals. Furthermore, we demonstrate that the reproducibility of the peak intensities is excellent in the NUS/MINT approach when experiments are repeated multiple times and identical experimental and processing conditions are employed. Finally, we discuss the principles for design and implementation of random exponentially biased NUS sampling schedules for homonuclear 13C–13C MAS correlation experiments that yield high-quality artifact-free datasets. PMID:24752819

Signal enhancement in protein NMR using the spin-noise tuning optimum

PubMed Central

Nausner, Martin; Goger, Michael; Bendet-Taicher, Eli; Schlagnitweit, Judith

2010-01-01

We have assessed the potential of an alternative probe tuning strategy based on the spin-noise response for application in common high-resolution multi-dimensional biomolecular NMR experiments with water signal suppression on aqueous and salty samples. The method requires the adjustment of the optimal tuning condition, which may be offset by several 100 kHz from the conventional tuning settings using the noise response of the water protons as an indicator. Although the radio frequency-pulse durations are typically longer under such conditions, signal-to-noise gains of up to 22% were achieved. At salt concentrations up to 100 mM a substantial sensitivity gain was observed. PMID:20924647

Practical aspects of NMR signal assignment in larger and challenging proteins

PubMed Central

Frueh, Dominique P.

2014-01-01

NMR has matured into a technique routinely employed for studying proteins in near physiological conditions. However, applications to larger proteins are impeded by the complexity of the various correlation maps necessary to assign NMR signals. This article reviews the data analysis techniques traditionally employed for resonance assignment and describes alternative protocols necessary for overcoming challenges in large protein spectra. In particular, simultaneous analysis of multiple spectra may help overcome ambiguities or may reveal correlations in an indirect manner. Similarly, visualization of orthogonal planes in a multidimensional spectrum can provide alternative assignment procedures. We describe examples of such strategies for assignment of backbone, methyl, and nOe resonances. We describe experimental aspects of data acquisition for the related experiments and provide guidelines for preliminary studies. Focus is placed on large folded monomeric proteins and examples are provided for 37, 48, 53, and 81 kDa proteins. PMID:24534088

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

Ultrafast NMR diffusion measurements exploiting chirp spin echoes.

PubMed

Ahola, Susanna; Mankinen, Otto; Telkki, Ville-Veikko

2017-04-01

Standard diffusion NMR measurements require the repetition of the experiment multiple times with varying gradient strength or diffusion delay. This makes the experiment time-consuming and restricts the use of hyperpolarized substances to boost sensitivity. We propose a novel single-scan diffusion experiment, which is based on spatial encoding of two-dimensional data, employing the spin-echoes created by two successive adiabatic frequency-swept chirp π pulses. The experiment is called ultrafast pulsed-field-gradient spin-echo (UF-PGSE). We present a rigorous derivation of the echo amplitude in the UF-PGSE experiment, justifying the theoretical basis of the method. The theory reveals also that the standard analysis of experimental data leads to a diffusion coefficient value overestimated by a few per cent. Although the overestimation is of the order of experimental error and thus insignificant in many practical applications, we propose that it can be compensated by a bipolar gradient version of the experiment, UF-BP-PGSE, or by corresponding stimulated-echo experiment, UF-BP-pulsed-field-gradient stimulated-echo. The latter also removes the effect of uniform background gradients. The experiments offer significant prospects for monitoring fast processes in real time as well as for increasing the sensitivity of experiments by several orders of magnitude by nuclear spin hyperpolarization. Furthermore, they can be applied as basic blocks in various ultrafast multidimensional Laplace NMR experiments. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

Optimized co-solute paramagnetic relaxation enhancement for the rapid NMR analysis of a highly fibrillogenic peptide.

PubMed

Oktaviani, Nur Alia; Risør, Michael W; Lee, Young-Ho; Megens, Rik P; de Jong, Djurre H; Otten, Renee; Scheek, Ruud M; Enghild, Jan J; Nielsen, Niels Chr; Ikegami, Takahisa; Mulder, Frans A A

2015-06-01

Co-solute paramagnetic relaxation enhancement (PRE) is an attractive way to speed up data acquisition in NMR spectroscopy by shortening the T 1 relaxation time of the nucleus of interest and thus the necessary recycle delay. Here, we present the rationale to utilize high-spin iron(III) as the optimal transition metal for this purpose and characterize the properties of its neutral chelate form Fe(DO3A) as a suitable PRE agent. Fe(DO3A) effectively reduces the T 1 values across the entire sequence of the intrinsically disordered protein α-synuclein with negligible impact on line width. The agent is better suited than currently used alternatives, shows no specific interaction with the polypeptide chain and, due to its high relaxivity, is effective at low concentrations and in 'proton-less' NMR experiments. By using Fe(DO3A) we were able to complete the backbone resonance assignment of a highly fibrillogenic peptide from α1-antitrypsin by acquiring the necessary suite of multidimensional NMR datasets in 3 h.

Deterministic multidimensional nonuniform gap sampling.

PubMed

Worley, Bradley; Powers, Robert

2015-12-01

Born from empirical observations in nonuniformly sampled multidimensional NMR data relating to gaps between sampled points, the Poisson-gap sampling method has enjoyed widespread use in biomolecular NMR. While the majority of nonuniform sampling schemes are fully randomly drawn from probability densities that vary over a Nyquist grid, the Poisson-gap scheme employs constrained random deviates to minimize the gaps between sampled grid points. We describe a deterministic gap sampling method, based on the average behavior of Poisson-gap sampling, which performs comparably to its random counterpart with the additional benefit of completely deterministic behavior. We also introduce a general algorithm for multidimensional nonuniform sampling based on a gap equation, and apply it to yield a deterministic sampling scheme that combines burst-mode sampling features with those of Poisson-gap schemes. Finally, we derive a relationship between stochastic gap equations and the expectation value of their sampling probability densities. Copyright © 2015 Elsevier Inc. All rights reserved.

Structure and Membrane Interactions of the Antibiotic Peptide Dermadistinctin K by Multidimensional Solution and Oriented 15N and 31P Solid-State NMR Spectroscopy

PubMed Central

Verly, Rodrigo M.; Moraes, Cléria Mendonça de; Resende, Jarbas M.; Aisenbrey, Christopher; Bemquerer, Marcelo Porto; Piló-Veloso, Dorila; Valente, Ana Paula; Almeida, Fábio C.L.; Bechinger, Burkhard

2009-01-01

DD K, a peptide first isolated from the skin secretion of the Phyllomedusa distincta frog, has been prepared by solid-phase chemical peptide synthesis and its conformation was studied in trifluoroethanol/water as well as in the presence of sodium dodecyl sulfate and dodecylphosphocholine micelles or small unilamellar vesicles. Multidimensional solution NMR spectroscopy indicates an α-helical conformation in membrane environments starting at residue 7 and extending to the C-terminal carboxyamide. Furthermore, DD K has been labeled with 15N at a single alanine position that is located within the helical core region of the sequence. When reconstituted into oriented phosphatidylcholine membranes the resulting 15N solid-state NMR spectrum shows a well-defined helix alignment parallel to the membrane surface in excellent agreement with the amphipathic character of DD K. Proton-decoupled 31P solid-state NMR spectroscopy indicates that the peptide creates a high level of disorder at the level of the phospholipid headgroup suggesting that DD K partitions into the bilayer where it severely disrupts membrane packing. PMID:19289046

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.

Effective rotational correlation times of proteins from NMR relaxation interference

NASA Astrophysics Data System (ADS)

Lee, Donghan; Hilty, Christian; Wider, Gerhard; Wüthrich, Kurt

2006-01-01

Knowledge of the effective rotational correlation times, τc, for the modulation of anisotropic spin-spin interactions in macromolecules subject to Brownian motion in solution is of key interest for the practice of NMR spectroscopy in structural biology. The value of τc enables an estimate of the NMR spin relaxation rates, and indicates possible aggregation of the macromolecular species. This paper reports a novel NMR pulse scheme, [ 15N, 1H]-TRACT, which is based on transverse relaxation-optimized spectroscopy and permits to determine τc for 15N- 1H bonds without interference from dipole-dipole coupling of the amide proton with remote protons. [ 15N, 1H]-TRACT is highly efficient since only a series of one-dimensional NMR spectra need to be recorded. Its use is suggested for a quick estimate of the rotational correlation time, to monitor sample quality and to determine optimal parameters for complex multidimensional NMR experiments. Practical applications are illustrated with the 110 kDa 7,8-dihydroneopterin aldolase from Staphylococcus aureus, the uniformly 15N-labeled Escherichia coli outer membrane protein X (OmpX) in 60 kDa mixed OmpX/DHPC micelles with approximately 90 molecules of unlabeled 1,2-dihexanoyl- sn-glycero-3-phosphocholine (DHPC), and the 16 kDa pheromone-binding protein from Bombyx mori, which cover a wide range of correlation times.

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.

A discrete Fourier-encoded, diagonal-free experiment to simplify homonuclear 2D NMR correlations.

PubMed

Huang, Zebin; Guan, Quanshuai; Chen, Zhong; Frydman, Lucio; Lin, Yulan

2017-07-21

Nuclear magnetic resonance (NMR) spectroscopy has long served as an irreplaceable, versatile tool in physics, chemistry, biology, and materials sciences, owing to its ability to study molecular structure and dynamics in detail. In particular, the connectivity of chemical sites within molecules, and thereby molecular structure, becomes visible by multi-dimensional NMR. Homonuclear correlation experiments are a powerful tool for identifying coupled spins. Generally, diagonal peaks in these correlation spectra display the strongest intensities and do not offer any new information beyond the standard one-dimensional spectrum, whereas weaker, symmetrically placed cross peaks contain most of the coupling information. The cross peaks near the diagonal are often affected by the tails of strong diagonal peaks or even obscured entirely by the diagonal. In this paper, we demonstrate a homonuclear encoding approach based on imparting a discrete phase modulation of the targeted cross peaks and combine it with a site-selective sculpting scheme, capable of simplifying the patterns arising in these 2D correlation spectra. The theoretical principles of the new methods are laid out, and experimental observations are rationalized on the basis of theoretical analyses. The ensuing techniques provide a new way to retrieve 2D coupling information within homonuclear spin systems, with enhanced sensitivity, speed, and clarity.

A discrete Fourier-encoded, diagonal-free experiment to simplify homonuclear 2D NMR correlations

NASA Astrophysics Data System (ADS)

Huang, Zebin; Guan, Quanshuai; Chen, Zhong; Frydman, Lucio; Lin, Yulan

2017-07-01

Nuclear magnetic resonance (NMR) spectroscopy has long served as an irreplaceable, versatile tool in physics, chemistry, biology, and materials sciences, owing to its ability to study molecular structure and dynamics in detail. In particular, the connectivity of chemical sites within molecules, and thereby molecular structure, becomes visible by multi-dimensional NMR. Homonuclear correlation experiments are a powerful tool for identifying coupled spins. Generally, diagonal peaks in these correlation spectra display the strongest intensities and do not offer any new information beyond the standard one-dimensional spectrum, whereas weaker, symmetrically placed cross peaks contain most of the coupling information. The cross peaks near the diagonal are often affected by the tails of strong diagonal peaks or even obscured entirely by the diagonal. In this paper, we demonstrate a homonuclear encoding approach based on imparting a discrete phase modulation of the targeted cross peaks and combine it with a site-selective sculpting scheme, capable of simplifying the patterns arising in these 2D correlation spectra. The theoretical principles of the new methods are laid out, and experimental observations are rationalized on the basis of theoretical analyses. The ensuing techniques provide a new way to retrieve 2D coupling information within homonuclear spin systems, with enhanced sensitivity, speed, and clarity.

Molecular understanding of Abeta peptide interaction with isoflurane, propofol, and thiopental: NMR spectroscopic study.

PubMed

Mandal, Pravat K; Williams, John P; Mandal, Ratna

2007-01-23

Abeta peptide is the major component of senile plaques (SP), which accumulate in the brain of a patient with Alzheimer's disease (AD). A recent report indicated that isoflurane enhanced Abeta oligomerization (micro-aggregation) and subsequent cytotoxicity of the Abeta peptide. A separate study showed that a clinically relevant concentration of isoflurane induces apoptosis and increases Abeta production in a human neuroglioma cell line. In vitro studies have indicated that halothane interacts specifically with Abeta peptide to induce oligomerization and that Abeta42 oligomerizes faster than Abeta40. The specific interactions of isoflurane, propofol, and thiopental with uniformly 15N labeled Abeta40 and Abeta42 peptide were investigated using multidimensional nuclear magnetic resonance (NMR) experiments. We found that isoflurane and propofol (at higher concentration) interact with Abeta40 peptides and induce Abeta oligomerization. Thiopental does not interact with specific residues (G29, A30, and I31) of Abeta40; hence, the peptide remains in the monomeric form. On the basis of our NMR study, thiopental does not oligomerize Abeta40 even at higher concentrations.

Peak picking NMR spectral data using non-negative matrix factorization.

PubMed

Tikole, Suhas; Jaravine, Victor; Rogov, Vladimir; Dötsch, Volker; Güntert, Peter

2014-02-11

Simple peak-picking algorithms, such as those based on lineshape fitting, perform well when peaks are completely resolved in multidimensional NMR spectra, but often produce wrong intensities and frequencies for overlapping peak clusters. For example, NOESY-type spectra have considerable overlaps leading to significant peak-picking intensity errors, which can result in erroneous structural restraints. Precise frequencies are critical for unambiguous resonance assignments. To alleviate this problem, a more sophisticated peaks decomposition algorithm, based on non-negative matrix factorization (NMF), was developed. We produce peak shapes from Fourier-transformed NMR spectra. Apart from its main goal of deriving components from spectra and producing peak lists automatically, the NMF approach can also be applied if the positions of some peaks are known a priori, e.g. from consistently referenced spectral dimensions of other experiments. Application of the NMF algorithm to a three-dimensional peak list of the 23 kDa bi-domain section of the RcsD protein (RcsD-ABL-HPt, residues 688-890) as well as to synthetic HSQC data shows that peaks can be picked accurately also in spectral regions with strong overlap.

Solution structure of the DNA-binding domain of the heat shock transcription factor determined by multidimensional heteronuclear magnetic resonance spectroscopy.

PubMed Central

Damberger, F. F.; Pelton, J. G.; Harrison, C. J.; Nelson, H. C.; Wemmer, D. E.

1994-01-01

The solution structure of the 92-residue DNA-binding domain of the heat shock transcription factor from Kluyveromyces lactis has been determined using multidimensional NMR methods. Three-dimensional (3D) triple resonance, 1H-13C-13C-1H total correlation spectroscopy, and 15N-separated total correlation spectroscopy-heteronuclear multiple quantum correlation experiments were used along with various 2D spectra to make nearly complete assignments for the backbone and side-chain 1H, 15N, and 13C resonances. Five-hundred eighty-three NOE constraints identified in 3D 13C- and 15N-separated NOE spectroscopy (NOESY)-heteronuclear multiple quantum correlation spectra and a 4-dimensional 13C/13C-edited NOESY spectrum, along with 35 phi, 9 chi 1, and 30 hydrogen bond constraints, were used to calculate 30 structures by hybrid distance geometry/stimulated annealing protocol, of which 24 were used for structural comparison. The calculations revealed that a 3-helix bundle packs against a small 4-stranded antiparallel beta-sheet. The backbone RMS deviation (RMSD) for the family of structures was 1.03 +/- 0.19 A with respect to the average structure. The topology is analogous to that of the C-terminal domain of the catabolite gene activator protein and appears to be in the helix-turn-helix family of DNA-binding proteins. The overall fold determined by the NMR data is consistent with recent crystallographic work on this domain (Harrison CJ, Bohm AA, Nelson HCM, 1994, Science 263:224) as evidenced by RMSD between backbone atoms in the NMR and X-ray structures of 1.77 +/- 0.20 A. Several differences were identified some of which may be due to protein-protein interactions in the crystal. PMID:7849597

Artifacts in time-resolved NUS: A case study of NOE build-up curves from 2D NOESY.

PubMed

Dass, Rupashree; Kasprzak, Paweł; Koźmiński, Wiktor; Kazimierczuk, Krzysztof

2016-04-01

Multidimensional NMR spectroscopy requires time-consuming sampling of indirect dimensions and so is usually used to study stable samples. However, dynamically changing compounds or their mixtures commonly occur in problems of natural science. Monitoring them requires the use multidimensional NMR in a time-resolved manner - in other words, a series of quick spectra must be acquired at different points in time. Among the many solutions that have been proposed to achieve this goal, time-resolved non-uniform sampling (TR-NUS) is one of the simplest. In a TR-NUS experiment, the signal is sampled using a shuffled random schedule and then divided into overlapping subsets. These subsets are then processed using one of the NUS reconstruction methods, for example compressed sensing (CS). The resulting stack of spectra forms a temporal "pseudo-dimension" that shows the changes caused by the process occurring in the sample. CS enables the use of small subsets of data, which minimizes the averaging of the effects studied. Yet, even within these limited timeframes, the sample undergoes certain changes. In this paper we discuss the effect of varying signal amplitude in a TR-NUS experiment. Our theoretical calculations show that the variations within the subsets lead to t1-noise, which is dependent on the rate of change of the signal amplitude. We verify these predictions experimentally. As a model case we choose a novel 2D TR-NOESY experiment in which mixing time is varied in parallel with shuffled NUS in the indirect dimension. The experiment, performed on a sample of strychnine, provides a near-continuous NOE build-up curve, whose shape closely reflects the t1-noise level. 2D TR-NOESY reduces the measurement time compared to the conventional approach and makes it possible to verify the theoretical predictions about signal variations during TR-NUS. Copyright © 2016 Elsevier Inc. All rights reserved.

Discrete decoding based ultrafast multidimensional nuclear magnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

Wei, Zhiliang; Lin, Liangjie; Ye, Qimiao; Li, Jing; Cai, Shuhui; Chen, Zhong

2015-07-01

The three-dimensional (3D) nuclear magnetic resonance (NMR) spectroscopy constitutes an important and powerful tool in analyzing chemical and biological systems. However, the abundant 3D information arrives at the expense of long acquisition times lasting hours or even days. Therefore, there has been a continuous interest in developing techniques to accelerate recordings of 3D NMR spectra, among which the ultrafast spatiotemporal encoding technique supplies impressive acquisition speed by compressing a multidimensional spectrum in a single scan. However, it tends to suffer from tradeoffs among spectral widths in different dimensions, which deteriorates in cases of NMR spectroscopy with more dimensions. In this study, the discrete decoding is proposed to liberate the ultrafast technique from tradeoffs among spectral widths in different dimensions by focusing decoding on signal-bearing sites. For verifying its feasibility and effectiveness, we utilized the method to generate two different types of 3D spectra. The proposed method is also applicable to cases with more than three dimensions, which, based on the experimental results, may widen applications of the ultrafast technique.

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

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

Challenges and perspectives in quantitative NMR.

PubMed

Giraudeau, Patrick

2017-01-01

This perspective article summarizes, from the author's point of view at the beginning of 2016, the major challenges and perspectives in the field of quantitative NMR. The key concepts in quantitative NMR are first summarized; then, the most recent evolutions in terms of resolution and sensitivity are discussed, as well as some potential future research directions in this field. A particular focus is made on methodologies capable of boosting the resolution and sensitivity of quantitative NMR, which could open application perspectives in fields where the sample complexity and the analyte concentrations are particularly challenging. These include multi-dimensional quantitative NMR and hyperpolarization techniques such as para-hydrogen-induced polarization or dynamic nuclear polarization. Because quantitative NMR cannot be dissociated from the key concepts of analytical chemistry, i.e. trueness and precision, the methodological developments are systematically described together with their level of analytical performance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Peak picking NMR spectral data using non-negative matrix factorization

PubMed Central

2014-01-01

Background Simple peak-picking algorithms, such as those based on lineshape fitting, perform well when peaks are completely resolved in multidimensional NMR spectra, but often produce wrong intensities and frequencies for overlapping peak clusters. For example, NOESY-type spectra have considerable overlaps leading to significant peak-picking intensity errors, which can result in erroneous structural restraints. Precise frequencies are critical for unambiguous resonance assignments. Results To alleviate this problem, a more sophisticated peaks decomposition algorithm, based on non-negative matrix factorization (NMF), was developed. We produce peak shapes from Fourier-transformed NMR spectra. Apart from its main goal of deriving components from spectra and producing peak lists automatically, the NMF approach can also be applied if the positions of some peaks are known a priori, e.g. from consistently referenced spectral dimensions of other experiments. Conclusions Application of the NMF algorithm to a three-dimensional peak list of the 23 kDa bi-domain section of the RcsD protein (RcsD-ABL-HPt, residues 688-890) as well as to synthetic HSQC data shows that peaks can be picked accurately also in spectral regions with strong overlap. PMID:24511909

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.

Solid-state 27Al MRI and NMR thermometry for catalytic applications with conventional (liquids) MRI instrumentation and techniques.

PubMed

Koptyug, Igor V; Sagdeev, Dmitry R; Gerkema, Edo; Van As, Henk; Sagdeev, Renad Z

2005-07-01

Multidimensional images of Al2O3 pellets, cordierite monolith, glass tube, polycrystalline V2O5 and other materials have been detected by 27Al, 51V, and 23Na NMR imaging using techniques and instrumentation conventionally employed for imaging of liquids. These results demonstrate that, contrary to the widely accepted opinion, imaging of "rigid" solids does not necessarily require utilization of solid state NMR imaging approaches, pulse sequences and hardware even for quadrupolar nuclei which exhibit line widths in excess of 100 kHz, such as 51V in polycrystalline V2O5. It is further demonstrated that both 27Al NMR signal intensity and spin-lattice relaxation time decrease with increasing temperature and thus can potentially serve as temperature sensitive parameters for spatially resolved NMR thermometry.

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

Reconstruction of full high-resolution HSQC using signal split in aliased spectra.

PubMed

Foroozandeh, Mohammadali; Jeannerat, Damien

2015-11-01

Resolution enhancement is a long-sought goal in NMR spectroscopy. In conventional multidimensional NMR experiments, such as the (1) H-(13) C HSQC, the resolution in the indirect dimensions is typically 100 times lower as in 1D spectra because it is limited by the experimental time. Reducing the spectral window can significantly increase the resolution but at the cost of ambiguities in frequencies as a result of spectral aliasing. Fortunately, this information is not completely lost and can be retrieved using methods in which chemical shifts are encoded in the aliased spectra and decoded after processing to reconstruct high-resolution (1) H-(13) C HSQC spectrum with full spectral width and a resolution similar to that of 1D spectra. We applied a new reconstruction method, RHUMBA (reconstruction of high-resolution using multiplet built on aliased spectra), to spectra obtained from the differential evolution for non-ambiguous aliasing-HSQC and the new AMNA (additional modulation for non-ambiguous aliasing)-HSQC experiments. The reconstructed spectra significantly facilitate both manual and automated spectral analyses and structure elucidation based on heteronuclear 2D experiments. The resolution is enhanced by two orders of magnitudes without the usual complications due to spectral aliasing. Copyright © 2015 John Wiley & Sons, Ltd.

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

Constant-time 2D and 3D through-bond correlation NMR spectroscopy of solids under 60 kHz MAS

PubMed Central

Zhang, Rongchun; Ramamoorthy, Ayyalusamy

2016-01-01

Establishing connectivity and proximity of nuclei is an important step in elucidating the structure and dynamics of molecules in solids using magic angle spinning (MAS) NMR spectroscopy. Although recent studies have successfully demonstrated the feasibility of proton-detected multidimensional solid-state NMR experiments under ultrafast-MAS frequencies and obtaining high-resolution spectral lines of protons, assignment of proton resonances is a major challenge. In this study, we first re-visit and demonstrate the feasibility of 2D constant-time uniform-sign cross-peak correlation (CTUC-COSY) NMR experiment on rigid solids under ultrafast-MAS conditions, where the sensitivity of the experiment is enhanced by the reduced spin-spin relaxation rate and the use of low radio-frequency power for heteronuclear decoupling during the evolution intervals of the pulse sequence. In addition, we experimentally demonstrate the performance of a proton-detected pulse sequence to obtain a 3D 1H/13C/1H chemical shift correlation spectrum by incorporating an additional cross-polarization period in the CTUC-COSY pulse sequence to enable proton chemical shift evolution and proton detection in the incrementable t1 and t3 periods, respectively. In addition to through-space and through-bond 13C/1H and 13C/13C chemical shift correlations, the 3D 1H/13C/1H experiment also provides a COSY-type 1H/1H chemical shift correlation spectrum, where only the chemical shifts of those protons, which are bonded to two neighboring carbons, are correlated. By extracting 2D F1/F3 slices (1H/1H chemical shift correlation spectrum) at different 13C chemical shift frequencies from the 3D 1H/13C/1H spectrum, resonances of proton atoms located close to a specific carbon atom can be identified. Overall, the through-bond and through-space homonuclear/heteronuclear proximities determined from the 3D 1H/13C/1H experiment would be useful to study the structure and dynamics of a variety of chemical and biological solids. PMID:26801026

Characterization of Silicon Nanocrystal Surfaces by Multidimensional Solid-State NMR Spectroscopy

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

Hanrahan, Michael P.; Fought, Ellie L.; Windus, Theresa L.

The chemical and photophysical properties of silicon nanocrystals (Si NCs) are strongly dependent on the chemical composition and structure of their surfaces. Here we use fast magic angle spinning (MAS) and proton detection to enable the rapid acquisition of dipolar and scalar 2D 1H– 29Si heteronuclear correlation (HETCOR) solid-state NMR spectra and reveal a molecular picture of hydride-terminated and alkyl-functionalized surfaces of Si NCs produced in a nonthermal plasma. 2D 1H– 29Si HETCOR and dipolar 2D 1H– 1H multiple-quantum correlation spectra illustrate that resonances from surface mono-, di-, and trihydride groups cannot be resolved, contrary to previous literature assignments. Insteadmore » the 2D NMR spectra illustrate that there is large distribution of 1H and 29Si chemical shifts for the surface hydride species in both the as-synthesized and functionalized Si NCs. However, proton-detected 1H– 29Si refocused INEPT experiments can be used to unambiguously differentiate NMR signals from the different surface hydrides. Varying the 29Si evolution time in refocused INEPT experiments and fitting the oscillation of the NMR signals allows for the relative populations of the different surface hydrides to be estimated. This analysis confirms that monohydride species are the predominant surface species on the as-synthesized Si NCs. A reduction in the populations of the di- and trihydrides is observed upon functionalization with alkyl groups, consistent with our previous hypothesis that the trihydride, or silyl (*SiH 3), group is primarily responsible for initiating surface functionalization reactions. Density functional theory (DFT) calculations were used to obtain quantum chemical structural models of the Si NC surface and reproduce the observed 1H and 29Si chemical shifts. Furthermore, the approaches outlined here will be useful to obtain a more detailed picture of surface structures for Si NCs and other hydride-passivated nanomaterials.« less

Characterization of Silicon Nanocrystal Surfaces by Multidimensional Solid-State NMR Spectroscopy

DOE PAGES

Hanrahan, Michael P.; Fought, Ellie L.; Windus, Theresa L.; ...

2017-11-22

The chemical and photophysical properties of silicon nanocrystals (Si NCs) are strongly dependent on the chemical composition and structure of their surfaces. Here we use fast magic angle spinning (MAS) and proton detection to enable the rapid acquisition of dipolar and scalar 2D 1H– 29Si heteronuclear correlation (HETCOR) solid-state NMR spectra and reveal a molecular picture of hydride-terminated and alkyl-functionalized surfaces of Si NCs produced in a nonthermal plasma. 2D 1H– 29Si HETCOR and dipolar 2D 1H– 1H multiple-quantum correlation spectra illustrate that resonances from surface mono-, di-, and trihydride groups cannot be resolved, contrary to previous literature assignments. Insteadmore » the 2D NMR spectra illustrate that there is large distribution of 1H and 29Si chemical shifts for the surface hydride species in both the as-synthesized and functionalized Si NCs. However, proton-detected 1H– 29Si refocused INEPT experiments can be used to unambiguously differentiate NMR signals from the different surface hydrides. Varying the 29Si evolution time in refocused INEPT experiments and fitting the oscillation of the NMR signals allows for the relative populations of the different surface hydrides to be estimated. This analysis confirms that monohydride species are the predominant surface species on the as-synthesized Si NCs. A reduction in the populations of the di- and trihydrides is observed upon functionalization with alkyl groups, consistent with our previous hypothesis that the trihydride, or silyl (*SiH 3), group is primarily responsible for initiating surface functionalization reactions. Density functional theory (DFT) calculations were used to obtain quantum chemical structural models of the Si NC surface and reproduce the observed 1H and 29Si chemical shifts. Furthermore, the approaches outlined here will be useful to obtain a more detailed picture of surface structures for Si NCs and other hydride-passivated nanomaterials.« less

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.

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.

Multidimensional oriented solid-state NMR experiments enable the sequential assignment of uniformly 15N labeled integral membrane proteins in magnetically aligned lipid bilayers.

PubMed

Mote, Kaustubh R; Gopinath, T; Traaseth, Nathaniel J; Kitchen, Jason; Gor'kov, Peter L; Brey, William W; Veglia, Gianluigi

2011-11-01

Oriented solid-state NMR is the most direct methodology to obtain the orientation of membrane proteins with respect to the lipid bilayer. The method consists of measuring (1)H-(15)N dipolar couplings (DC) and (15)N anisotropic chemical shifts (CSA) for membrane proteins that are uniformly aligned with respect to the membrane bilayer. A significant advantage of this approach is that tilt and azimuthal (rotational) angles of the protein domains can be directly derived from analytical expression of DC and CSA values, or, alternatively, obtained by refining protein structures using these values as harmonic restraints in simulated annealing calculations. The Achilles' heel of this approach is the lack of suitable experiments for sequential assignment of the amide resonances. In this Article, we present a new pulse sequence that integrates proton driven spin diffusion (PDSD) with sensitivity-enhanced PISEMA in a 3D experiment ([(1)H,(15)N]-SE-PISEMA-PDSD). The incorporation of 2D (15)N/(15)N spin diffusion experiments into this new 3D experiment leads to the complete and unambiguous assignment of the (15)N resonances. The feasibility of this approach is demonstrated for the membrane protein sarcolipin reconstituted in magnetically aligned lipid bicelles. Taken with low electric field probe technology, this approach will propel the determination of sequential assignment as well as structure and topology of larger integral membrane proteins in aligned lipid bilayers. © Springer Science+Business Media B.V. 2011

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.

High-resolution NMR spectroscopy of encapsulated proteins dissolved in low-viscosity fluids

PubMed Central

Nucci, Nathaniel V.; Valentine, Kathleen G.; Wand, A. Joshua

2014-01-01

High-resolution multi-dimensional solution NMR is unique as a biophysical and biochemical tool in its ability to examine both the structure and dynamics of macromolecules at atomic resolution. Conventional solution NMR approaches, however, are largely limited to examinations of relatively small (< 25 kDa) molecules, mostly due to the spectroscopic consequences of slow rotational diffusion. Encapsulation of macromolecules within the protective nanoscale aqueous interior of reverse micelles dissolved in low viscosity fluids has been developed as a means through which the ‘slow tumbling problem’ can be overcome. This approach has been successfully applied to diverse proteins and nucleic acids ranging up to 100 kDa, considerably widening the range of biological macromolecules to which conventional solution NMR methodologies may be applied. Recent advances in methodology have significantly broadened the utility of this approach in structural biology and molecular biophysics. PMID:24656086

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.

Constant-time 2D and 3D through-bond correlation NMR spectroscopy of solids under 60 kHz MAS

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

Zhang, Rongchun; Ramamoorthy, Ayyalusamy, E-mail: ramamoor@umich.edu

2016-01-21

Establishing connectivity and proximity of nuclei is an important step in elucidating the structure and dynamics of molecules in solids using magic angle spinning (MAS) NMR spectroscopy. Although recent studies have successfully demonstrated the feasibility of proton-detected multidimensional solid-state NMR experiments under ultrafast-MAS frequencies and obtaining high-resolution spectral lines of protons, assignment of proton resonances is a major challenge. In this study, we first re-visit and demonstrate the feasibility of 2D constant-time uniform-sign cross-peak correlation (CTUC-COSY) NMR experiment on rigid solids under ultrafast-MAS conditions, where the sensitivity of the experiment is enhanced by the reduced spin-spin relaxation rate and themore » use of low radio-frequency power for heteronuclear decoupling during the evolution intervals of the pulse sequence. In addition, we experimentally demonstrate the performance of a proton-detected pulse sequence to obtain a 3D {sup 1}H/{sup 13}C/{sup 1}H chemical shift correlation spectrum by incorporating an additional cross-polarization period in the CTUC-COSY pulse sequence to enable proton chemical shift evolution and proton detection in the incrementable t{sub 1} and t{sub 3} periods, respectively. In addition to through-space and through-bond {sup 13}C/{sup 1}H and {sup 13}C/{sup 13}C chemical shift correlations, the 3D {sup 1}H/{sup 13}C/{sup 1}H experiment also provides a COSY-type {sup 1}H/{sup 1}H chemical shift correlation spectrum, where only the chemical shifts of those protons, which are bonded to two neighboring carbons, are correlated. By extracting 2D F1/F3 slices ({sup 1}H/{sup 1}H chemical shift correlation spectrum) at different {sup 13}C chemical shift frequencies from the 3D {sup 1}H/{sup 13}C/{sup 1}H spectrum, resonances of proton atoms located close to a specific carbon atom can be identified. Overall, the through-bond and through-space homonuclear/heteronuclear proximities determined from the 3D {sup 1}H/{sup 13}C/{sup 1}H experiment would be useful to study the structure and dynamics of a variety of chemical and biological solids.« less

Structure of a Double Transmembrane Fragment of a G-Protein-Coupled Receptor in Micelles

PubMed Central

Neumoin, Alexey; Cohen, Leah S.; Arshava, Boris; Tantry, Subramanyam; Becker, Jeffrey M.; Zerbe, Oliver; Naider, Fred

2009-01-01

Abstract The structure and dynamic properties of an 80-residue fragment of Ste2p, the G-protein-coupled receptor for α-factor of Saccharomyces cerevisiae, was studied in LPPG micelles with the use of solution NMR spectroscopy. The fragment Ste2p(G31-T110) (TM1-TM2) consisted of 19 residues from the N-terminal domain, the first TM helix (TM1), the first cytoplasmic loop, the second TM helix (TM2), and seven residues from the first extracellular loop. Multidimensional NMR experiments on [15N], [15N, 13C], [15N, 13C, 2H]-labeled TM1-TM2 and on protein fragments selectively labeled at specific amino acid residues or protonated at selected methyl groups resulted in >95% assignment of backbone and side-chain nuclei. The NMR investigation revealed the secondary structure of specific residues of TM1-TM2. TALOS constraints and NOE connectivities were used to calculate a structure for TM1-TM2 that was highlighted by the presence of three α-helices encompassing residues 39–47, 49–72, and 80–103, with higher flexibility around the internal Arg58 site of TM1. RMSD values of individually superimposed helical segments 39–47, 49–72, and 80–103 were 0.25 ± 0.10 Å, 0.40 ± 0.13 Å, and 0.57 ± 0.19 Å, respectively. Several long-range interhelical connectivities supported the folding of TM1-TM2 into a tertiary structure typified by a crossed helix that splays apart toward the extracellular regions and contains considerable flexibility in the G56VRSG60 region. 15N-relaxation and hydrogen-deuterium exchange data support a stable fold for the TM parts of TM1-TM2, whereas the solvent-exposed segments are more flexible. The NMR structure is consistent with the results of biochemical experiments that identified the ligand-binding site within this region of the receptor. PMID:19383463

Structural Changes and Proapoptotic Peroxidase Activity of Cardiolipin-Bound Mitochondrial Cytochrome c

PubMed Central

Mandal, Abhishek; Hoop, Cody L.; DeLucia, Maria; Kodali, Ravindra; Kagan, Valerian E.; Ahn, Jinwoo; van der Wel, Patrick C.A.

2015-01-01

The cellular process of intrinsic apoptosis relies on the peroxidation of mitochondrial lipids as a critical molecular signal. Lipid peroxidation is connected to increases in mitochondrial reactive oxygen species, but there is also a required role for mitochondrial cytochrome c (cyt-c). In apoptotic mitochondria, cyt-c gains a new function as a lipid peroxidase that catalyzes the reactive oxygen species-mediated chemical modification of the mitochondrial lipid cardiolipin (CL). This peroxidase activity is caused by a conformational change in the protein, resulting from interactions between cyt-c and CL. The nature of the conformational change and how it causes this gain-of-function remain uncertain. Via a combination of functional, structural, and biophysical experiments we investigate the structure and peroxidase activity of cyt-c in its membrane-bound state. We reconstituted cyt-c with CL-containing lipid vesicles, and determined the increase in peroxidase activity resulting from membrane binding. We combined these assays of CL-induced proapoptotic activity with structural and dynamic studies of the membrane-bound protein via solid-state NMR and optical spectroscopy. Multidimensional magic angle spinning (MAS) solid-state NMR of uniformly 13C,15N-labeled protein was used to detect site-specific conformational changes in oxidized and reduced horse heart cyt-c bound to CL-containing lipid bilayers. MAS NMR and Fourier transform infrared measurements show that the peripherally membrane-bound cyt-c experiences significant dynamics, but also retains most or all of its secondary structure. Moreover, in two-dimensional and three-dimensional MAS NMR spectra the CL-bound cyt-c displays a spectral resolution, and thus structural homogeneity, that is inconsistent with extensive membrane-induced unfolding. Cyt-c is found to interact primarily with the membrane interface, without significantly disrupting the lipid bilayer. Thus, membrane binding results in cyt-c gaining the increased peroxidase activity that represents its pivotal proapoptotic function, but we do not observe evidence for large-scale unfolding or penetration into the membrane core. PMID:26536264

Structural characterization by NMR of the natively unfolded extracellular domain of beta-dystroglycan: toward the identification of the binding epitope for alpha-dystroglycan.

PubMed

Bozzi, Manuela; Bianchi, Marzia; Sciandra, Francesca; Paci, Maurizio; Giardina, Bruno; Brancaccio, Andrea; Cicero, Daniel O

2003-11-25

Dystroglycan (DG) is an adhesion molecule playing a crucial role for tissue stability during both early embriogenesis and adulthood and is composed by two tightly interacting subunits: alpha-DG, membrane-associated and highly glycosylated, and the transmembrane beta-DG. Recently, by solid-phase binding assays and NMR experiments, we have shown that the C-terminal domain of alpha-DG interacts with a recombinant extracellular fragment of beta-DG (positions 654-750) independently from glycosylation and that the linear binding epitope is located between residues 550 and 565 of alpha-DG. In order to elucidate which moieties of beta-DG are specifically involved in the complex with alpha-DG, the ectodomain has been recombinantly expressed and purified in a labeled ((13)C,(15)N) form and studied by multidimensional NMR. Although it represents a natively unfolded protein domain, we obtained an almost complete backbone assignment. Chemical shift index, (1)H-(15)N heteronuclear single-quantum coherence and nuclear Overhauser effect (HSQC-NOESY) spectra and (3)J(HN,H)(alpha) coupling constant values confirm that this protein is highly disordered, but (1)H-(15)N steady-state NOE experiments indicate that the protein presents two regions of different mobility. The first one, between residues 659 and 722, is characterized by a limited degree of mobility, whereas the C-terminal portion, containing about 30 amino acids, is highly flexible. The binding of beta-DG(654-750) to the C-terminal region of the alpha subunit, alpha-DG(485-620), has been investigated, showing that the region of beta-DG(654-750) between residues 691 and 719 is involved in the interaction.

Multidimensional NMR analysis reveals truncated lignin structures in wood decayed by the brown rot basidiomycete Postia placenta

Treesearch

Daniel J. Yelle; Dongsheng Wei; John Ralph; Kenneth E. Hammel

2011-01-01

Lignocellulose biodegradation, an essential step in terrestrial carbon cycling, generally involves removal of the recalcitrant lignin barrier that otherwise prevents infiltration by microbial polysaccharide hydrolases. However, fungi that cause brown rot of wood, a major route for biomass recycling in coniferous forests, utilize wood polysaccharides efficiently while...

Use of X-Ray Diffraction, Molecular Simulations, and Spectroscopy to Determine the Molecular Packing in a Polymer-Fullerene Bimolecular Crystal

DTIC Science & Technology

2012-09-05

Richter , M. F. Toney , M. Heeney , I. McCulloch , ACS Nano 2009 , 3 , 780 . [ 19 ] H. W. Spiess , Macromolecules 43 , 5479 . [ 20 ] K...Schmidt-Rohr , H. W. Spiess , Multidimensional Solid-State NMR and Polymers , Academic Press , London 1994 . [ 21 ] C. Yang , J. G. Hu

Spatial reorientation experiments for NMR of solids and partially oriented liquids.

PubMed

Martin, Rachel W; Kelly, John E; Collier, Kelsey A

2015-11-01

Motional reorientation experiments are extensions of Magic Angle Spinning (MAS) where the rotor axis is changed in order to average out, reintroduce, or scale anisotropic interactions (e.g. dipolar couplings, quadrupolar interactions or chemical shift anisotropies). This review focuses on Variable Angle Spinning (VAS), Switched Angle Spinning (SAS), and Dynamic Angle Spinning (DAS), all of which involve spinning at two or more different angles sequentially, either in successive experiments or during a multidimensional experiment. In all of these experiments, anisotropic terms in the Hamiltonian are scaled by changing the orientation of the spinning sample relative to the static magnetic field. These experiments vary in experimental complexity and instrumentation requirements. In VAS, many one-dimensional spectra are collected as a function of spinning angle. In SAS, dipolar couplings and/or chemical shift anisotropies are reintroduced by switching the sample between two different angles, often 0° or 90° and the magic angle, yielding a two-dimensional isotropic-anisotropic correlation spectrum. Dynamic Angle Spinning (DAS) is a related experiment that is used to simultaneously average out the first- and second-order quadrupolar interactions, which cannot be accomplished by spinning at any unique rotor angle in physical space. Although motional reorientation experiments generally require specialized instrumentation and data analysis schemes, some are accessible with only minor modification of standard MAS probes. In this review, the mechanics of each type of experiment are described, with representative examples. Current and historical probe and coil designs are discussed from the standpoint of how each one accomplishes the particular objectives of the experiment(s) it was designed to perform. Finally, applications to inorganic materials and liquid crystals, which present very different experimental challenges, are discussed. The review concludes with perspectives on how motional reorientation experiments can be applied to current problems in chemistry, molecular biology, and materials science, given the many advances in high-field NMR magnets, fast spinning, and sample preparation realized in recent years. Copyright © 2015 Elsevier B.V. All rights reserved.

Dynamical network of residue–residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation

PubMed Central

Doshi, Urmi; Holliday, Michael J.; Eisenmesser, Elan Z.; Hamelberg, Donald

2016-01-01

Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue–residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general. PMID:27071107

SABRE hyperpolarization enables high-sensitivity 1H and 13C benchtop NMR spectroscopy.

PubMed

Richardson, Peter M; Parrott, Andrew J; Semenova, Olga; Nordon, Alison; Duckett, Simon B; Halse, Meghan E

2018-06-19

Benchtop NMR spectrometers operating with low magnetic fields of 1-2 T at sub-ppm resolution show great promise as analytical platforms that can be used outside the traditional laboratory environment for industrial process monitoring. One current limitation that reduces the uptake of benchtop NMR is associated with the detection fields' reduced sensitivity. Here we demonstrate how para-hydrogen (p-H2) based signal amplification by reversible exchange (SABRE), a simple to achieve hyperpolarization technique, enhances agent detectability within the environment of a benchtop (1 T) NMR spectrometer so that informative 1H and 13C NMR spectra can be readily recorded for low-concentration analytes. SABRE-derived 1H NMR signal enhancements of up to 17 000-fold, corresponding to 1H polarization levels of P = 5.9%, were achieved for 26 mM pyridine in d4-methanol in a matter of seconds. Comparable enhancement levels can be achieved in both deuterated and protio solvents but now the SABRE-enhanced analyte signals dominate due to the comparatively weak thermally-polarized solvent response. The SABRE approach also enables the acquisition of 13C NMR spectra of analytes at natural isotopic abundance in a single scan as evidenced by hyperpolarized 13C NMR spectra of tens of millimolar concentrations of 4-methylpyridine. Now the associated signal enhancement factors are up to 45 500 fold (P = 4.0%) and achieved in just 15 s. Integration of an automated SABRE polarization system with the benchtop NMR spectrometer framework produces renewable and reproducible NMR signal enhancements that can be exploited for the collection of multi-dimensional NMR spectra, exemplified here by a SABRE-enhanced 2D COSY NMR spectrum.

Solution structure of the antitermination protein NusB of Escherichia coli: a novel all-helical fold for an RNA-binding protein.

PubMed Central

Huenges, M; Rölz, C; Gschwind, R; Peteranderl, R; Berglechner, F; Richter, G; Bacher, A; Kessler, H; Gemmecker, G

1998-01-01

The NusB protein of Escherichia coli is involved in the regulation of rRNA biosynthesis by transcriptional antitermination. In cooperation with several other proteins, it binds to a dodecamer motif designated rrn boxA on the nascent rRNA. The antitermination proteins of E.coli are recruited in the replication cycle of bacteriophage lambda, where they play an important role in switching from the lysogenic to the lytic cycle. Multidimensional heteronuclear NMR experiments were performed with recombinant NusB protein labelled with 13C, 15N and 2H. The three-dimensional structure of the protein was solved from 1926 NMR-derived distances and 80 torsion angle restraints. The protein folds into an alpha/alpha-helical topology consisting of six helices; the arginine-rich N-terminus appears to be disordered. Complexation of the protein with an RNA dodecamer equivalent to the rrn boxA site results in chemical shift changes of numerous amide signals. The overall packing of the protein appears to be conserved, but the flexible N-terminus adopts a more rigid structure upon RNA binding, indicating that the N-terminus functions as an arginine-rich RNA-binding motif (ARM). PMID:9670024

Structural and dynamic characterization of eukaryotic gene regulatory protein domains in solution

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

Lee, Andrew Loyd

Solution NMR was primarily used to characterize structure and dynamics in two different eukaryotic protein systems: the δ-Al-ε activation domain from c-jun and the Drosophila RNA-binding protein Sex-lethal. The second system is the Drosophila Sex-lethal (Sxl) protein, an RNA-binding protein which is the ``master switch`` in sex determination. Sxl contains two adjacent RNA-binding domains (RBDs) of the RNP consensus-type. The NMR spectrum of the second RBD (Sxl-RBD2) was assigned using multidimensional heteronuclear NMR, and an intermediate-resolution family of structures was calculated from primarily NOE distance restraints. The overall fold was determined to be similar to other RBDs: a βαβ-βαβ patternmore » of secondary structure, with the two helices packed against a 4-stranded anti-parallel β-sheet. In addition 15N T 1, T 2, and 15N/ 1H NOE relaxation measurements were carried out to characterize the backbone dynamics of Sxl-RBD2 in solution. RNA corresponding to the polypyrimidine tract of transformer pre-mRNA was generated and titrated into 3 different Sxl-RBD protein constructs. Combining Sxl-RBD1+2 (bht RBDs) with this RNA formed a specific, high affinity protein/RNA complex that is amenable to further NMR characterization. The backbone 1H, 13C, and 15N resonances of Sxl-RBD1+2 were assigned using a triple-resonance approach, and 15N relaxation experiments were carried out to characterize the backbone dynamics of this complex. The changes in chemical shift in Sxl-RBD1+2 upon binding RNA are observed using Sxl-RBD2 as a substitute for unbound Sxl-RBD1+2. This allowed the binding interface to be qualitatively mapped for the second domain.« less

Automated peak picking and peak integration in macromolecular NMR spectra using AUTOPSY.

PubMed

Koradi, R; Billeter, M; Engeli, M; Güntert, P; Wüthrich, K

1998-12-01

A new approach for automated peak picking of multidimensional protein NMR spectra with strong overlap is introduced, which makes use of the program AUTOPSY (automated peak picking for NMR spectroscopy). The main elements of this program are a novel function for local noise level calculation, the use of symmetry considerations, and the use of lineshapes extracted from well-separated peaks for resolving groups of strongly overlapping peaks. The algorithm generates peak lists with precise chemical shift and integral intensities, and a reliability measure for the recognition of each peak. The results of automated peak picking of NOESY spectra with AUTOPSY were tested in combination with the combined automated NOESY cross peak assignment and structure calculation routine NOAH implemented in the program DYANA. The quality of the resulting structures was found to be comparable with those from corresponding data obtained with manual peak picking. Copyright 1998 Academic Press.

Rapid 3D NMR using the filter diagonalization method: application to oligosaccharides derivatized with 13C-labeled acetyl groups

NASA Astrophysics Data System (ADS)

Armstrong, Geoffrey S.; Cano, Kristin E.; Mandelshtam, Vladimir A.; Shaka, A. J.; Bendiak, Brad

2004-09-01

Rapid 3D NMR spectroscopy of oligosaccharides having isotopically labeled acetyl "isotags" was made possible with high resolution in the indirect dimensions using the filter diagonalization method (FDM). A pulse sequence was designed for the optimal correlation of acetyl methyl protons, methyl carbons, and carbonyl carbons. The multi-dimensional nature of the FDM, coupled with the advantages of constant-time evolution periods, resulted in marked improvements over Fourier transform (FT) and mirror-image linear prediction (MI-LP) processing methods. The three methods were directly compared using identical data sets. A highly resolved 3D spectrum was achieved with the FDM using a very short experimental time (28 min).

Rapid 3D NMR using the filter diagonalization method: application to oligosaccharides derivatized with 13C-labeled acetyl groups.

PubMed

Armstrong, Geoffrey S; Cano, Kristin E; Mandelshtam, Vladimir A; Shaka, A J; Bendiak, Brad

2004-09-01

Rapid 3D NMR spectroscopy of oligosaccharides having isotopically labeled acetyl "isotags" was made possible with high resolution in the indirect dimensions using the filter diagonalization method (FDM). A pulse sequence was designed for the optimal correlation of acetyl methyl protons, methyl carbons, and carbonyl carbons. The multi-dimensional nature of the FDM, coupled with the advantages of constant-time evolution periods, resulted in marked improvements over Fourier transform (FT) and mirror-image linear prediction (MI-LP) processing methods. The three methods were directly compared using identical data sets. A highly resolved 3D spectrum was achieved with the FDM using a very short experimental time (28 min).

HIFI-C: a robust and fast method for determining NMR couplings from adaptive 3D to 2D projections.

PubMed

Cornilescu, Gabriel; Bahrami, Arash; Tonelli, Marco; Markley, John L; Eghbalnia, Hamid R

2007-08-01

We describe a novel method for the robust, rapid, and reliable determination of J couplings in multi-dimensional NMR coupling data, including small couplings from larger proteins. The method, "High-resolution Iterative Frequency Identification of Couplings" (HIFI-C) is an extension of the adaptive and intelligent data collection approach introduced earlier in HIFI-NMR. HIFI-C collects one or more optimally tilted two-dimensional (2D) planes of a 3D experiment, identifies peaks, and determines couplings with high resolution and precision. The HIFI-C approach, demonstrated here for the 3D quantitative J method, offers vital features that advance the goal of rapid and robust collection of NMR coupling data. (1) Tilted plane residual dipolar couplings (RDC) data are collected adaptively in order to offer an intelligent trade off between data collection time and accuracy. (2) Data from independent planes can provide a statistical measure of reliability for each measured coupling. (3) Fast data collection enables measurements in cases where sample stability is a limiting factor (for example in the presence of an orienting medium required for residual dipolar coupling measurements). (4) For samples that are stable, or in experiments involving relatively stronger couplings, robust data collection enables more reliable determinations of couplings in shorter time, particularly for larger biomolecules. As a proof of principle, we have applied the HIFI-C approach to the 3D quantitative J experiment to determine N-C' RDC values for three proteins ranging from 56 to 159 residues (including a homodimer with 111 residues in each subunit). A number of factors influence the robustness and speed of data collection. These factors include the size of the protein, the experimental set up, and the coupling being measured, among others. To exhibit a lower bound on robustness and the potential for time saving, the measurement of dipolar couplings for the N-C' vector represents a realistic "worst case analysis". These couplings are among the smallest currently measured, and their determination in both isotropic and anisotropic media demands the highest measurement precision. The new approach yielded excellent quantitative agreement with values determined independently by the conventional 3D quantitative J NMR method (in cases where sample stability in oriented media permitted these measurements) but with a factor of 2-5 in time savings. The statistical measure of reliability, measuring the quality of each RDC value, offers valuable adjunct information even in cases where modest time savings may be realized.

MetaboID: a graphical user interface package for assignment of 1H NMR spectra of bodyfluids and tissues.

PubMed

MacKinnon, Neil; Somashekar, Bagganahalli S; Tripathi, Pratima; Ge, Wencheng; Rajendiran, Thekkelnaycke M; Chinnaiyan, Arul M; Ramamoorthy, Ayyalusamy

2013-01-01

Nuclear magnetic resonance based measurements of small molecule mixtures continues to be confronted with the challenge of spectral assignment. While multi-dimensional experiments are capable of addressing this challenge, the imposed time constraint becomes prohibitive, particularly with the large sample sets commonly encountered in metabolomic studies. Thus, one-dimensional spectral assignment is routinely performed, guided by two-dimensional experiments on a selected sample subset; however, a publicly available graphical interface for aiding in this process is currently unavailable. We have collected spectral information for 360 unique compounds from publicly available databases including chemical shift lists and authentic full resolution spectra, supplemented with spectral information for 25 compounds collected in-house at a proton NMR frequency of 900 MHz. This library serves as the basis for MetaboID, a Matlab-based user interface designed to aid in the one-dimensional spectral assignment process. The tools of MetaboID were built to guide resonance assignment in order of increasing confidence, starting from cursory compound searches based on chemical shift positions to analysis of authentic spike experiments. Together, these tools streamline the often repetitive task of spectral assignment. The overarching goal of the integrated toolbox of MetaboID is to centralize the one dimensional spectral assignment process, from providing access to large chemical shift libraries to providing a straightforward, intuitive means of spectral comparison. Such a toolbox is expected to be attractive to both experienced and new metabolomic researchers as well as general complex mixture analysts. Copyright © 2012 Elsevier Inc. All rights reserved.

Design and characterization of a W-band system for modulated DNP experiments.

PubMed

Guy, Mallory L; Zhu, Lihuang; Ramanathan, Chandrasekhar

2015-12-01

Magnetic-field and microwave-frequency modulated DNP experiments have been shown to yield improved enhancements over conventional DNP techniques, and even to shorten polarization build-up times. The resulting increase in signal-to-noise ratios can lead to significantly shorter acquisition times in signal-limited multi-dimensional NMR experiments and pave the way to the study of even smaller sample volumes. In this paper we describe the design and performance of a broadband system for microwave frequency- and amplitude-modulated DNP that has been engineered to minimize both microwave and thermal losses during operation at liquid helium temperatures. The system incorporates a flexible source that can generate arbitrary waveforms at 94GHz with a bandwidth greater than 1GHz, as well as a probe that efficiently transmits the millimeter waves from room temperature outside the magnet to a cryogenic environment inside the magnet. Using a thin-walled brass tube as an overmoded waveguide to transmit a hybrid HE11 mode, it is possible to limit the losses to 1dB across a 2GHz bandwidth. The loss is dominated by the presence of a quartz window used to isolate the waveguide pipe. This performance is comparable to systems with corrugated waveguide or quasi-optical components. The overall excitation bandwidth of the probe is seen to be primarily determined by the final antenna or resonator used to excite the sample and its coupling to the NMR RF coil. Understanding the instrumental limitations imposed on any modulation scheme is key to understanding the observed DNP results and potentially identifying the underlying mechanisms. We demonstrate the utility of our design with a set of triangular frequency-modulated DNP experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

250 GHz CW Gyrotron Oscillator for Dynamic Nuclear Polarization in Biological Solid State NMR

PubMed Central

Bajaj, Vikram S.; Hornstein, Melissa K.; Kreischer, Kenneth E.; Sirigiri, Jagadishwar R.; Woskov, Paul P.; Mak-Jurkauskas, Melody L.; Herzfeld, Judith; Temkin, Richard J.; Griffin, Robert G.

2009-01-01

In this paper, we describe a 250 GHz gyrotron oscillator, a critical component of an integrated system for magic angle spinning (MAS) dynamic nuclear polarization (DNP) experiments at 9T, corresponding to 380 MHz 1H frequency. The 250 GHz gyrotron is the first gyro-device designed with the goal of seamless integration with an NMR spectrometer for routine DNP-enhanced NMR spectroscopy and has operated under computer control for periods of up to 21 days with a 100% duty cycle. Following a brief historical review of the field, we present studies of the membrane protein bacteriorhodopsin (bR) using DNP-enhanced multidimensional NMR. These results include assignment of active site resonances in [U-13C,15N]-bR and demonstrate the utility of DNP for studies of membrane proteins. Next, we review the theory of gyro-devices from quantum mechanical and classical viewpoints and discuss the unique considerations that apply to gyrotron oscillators designed for DNP experiments. We then characterize the operation of the 250 GHz gyrotron in detail, including its long-term stability and controllability. We have measured the spectral purity of the gyrotron emission using both homodyne and heterodyne techniques. Radiation intensity patterns from the corrugated waveguide that delivers power to the NMR probe were measured using two new techniques to confirm pure mode content: a thermometric approach based on the temperature-dependent color of liquid crystalline media applied to a substrate and imaging with a pyroelectric camera. We next present a detailed study of the mode excitation characteristics of the gyrotron. Exploration of the operating characteristics of several fundamental modes reveals broadband continuous frequency tuning of up to 1.8 GHz as a function of the magnetic field alone, a feature that may be exploited in future tunable gyrotron designs. Oscillation of the 250 GHz gyrotron at the second harmonic of cyclotron resonance begins at extremely low beam currents (as low 12 mA) at frequencies between 320–365 GHz, suggesting an efficient route for the generation of even higher frequency radiation. The low starting currents were attributed to an elevated cavity Q, which is confirmed by cavity thermal load measurements. We conclude with an appendix containing a detailed description of the control system that safely automates all aspects of the gyrotron operation. PMID:17942352

"Ersatz" and "hybrid" NMR spectral estimates using the filter diagonalization method.

PubMed

Ridge, Clark D; Shaka, A J

2009-03-12

The filter diagonalization method (FDM) is an efficient and elegant way to make a spectral estimate purely in terms of Lorentzian peaks. As NMR spectral peaks of liquids conform quite well to this model, the FDM spectral estimate can be accurate with far fewer time domain points than conventional discrete Fourier transform (DFT) processing. However, noise is not efficiently characterized by a finite number of Lorentzian peaks, or by any other analytical form, for that matter. As a result, noise can affect the FDM spectrum in different ways than it does the DFT spectrum, and the effect depends on the dimensionality of the spectrum. Regularization to suppress (or control) the influence of noise to give an "ersatz", or EFDM, spectrum is shown to sometimes miss weak features, prompting a more conservative implementation of filter diagonalization. The spectra obtained, called "hybrid" or HFDM spectra, are acquired by using regularized FDM to obtain an "infinite time" spectral estimate and then adding to it the difference between the DFT of the data and the finite time FDM estimate, over the same time interval. HFDM has a number of advantages compared to the EFDM spectra, where all features must be Lorentzian. They also show better resolution than DFT spectra. The HFDM spectrum is a reliable and robust way to try to extract more information from noisy, truncated data records and is less sensitive to the choice of regularization parameter. In multidimensional NMR of liquids, HFDM is a conservative way to handle the problems of noise, truncation, and spectral peaks that depart significantly from the model of a multidimensional Lorentzian peak.

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

NASA Astrophysics Data System (ADS)

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

2008-08-01

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

Establishing a molecular relationship between chondritic and cometary organic solids

PubMed Central

Cody, George D.; Heying, Emily; Alexander, Conel M. O.; Nittler, Larry R.; Kilcoyne, A. L. David; Sandford, Scott A.

2011-01-01

Multidimensional solid-state NMR spectroscopy is used to refine the identification and abundance determination of functional groups in insoluble organic matter (IOM) isolated from a carbonaceous chondrite (Murchison, CM2). It is shown that IOM is composed primarily of highly substituted single ring aromatics, substituted furan/pyran moieties, highly branched oxygenated aliphatics, and carbonyl groups. A pathway for producing an IOM-like molecular structure through formaldehyde polymerization is proposed and tested experimentally. Solid-state 13C NMR analysis of aqueously altered formaldehyde polymer reveals considerable similarity with chondritic IOM. Carbon X-ray absorption near edge structure spectroscopy of formaldehyde polymer reveals the presence of similar functional groups across certain Comet 81P/Wild 2 organic solids, interplanetary dust particles, and primitive IOM. Variation in functional group concentration amongst these extraterrestrial materials is understood to be a result of various degrees of processing in the parent bodies, in space, during atmospheric entry, etc. These results support the hypothesis that chondritic IOM and cometary refractory organic solids are related chemically and likely were derived from formaldehyde polymer. The fine-scale morphology of formaldehyde polymer produced in the experiment reveals abundant nanospherules that are similar in size and shape to organic nanoglobules that are ubiquitous in primitive chondrites. PMID:21464292

Peak picking multidimensional NMR spectra with the contour geometry based algorithm CYPICK.

PubMed

Würz, Julia M; Güntert, Peter

2017-01-01

The automated identification of signals in multidimensional NMR spectra is a challenging task, complicated by signal overlap, noise, and spectral artifacts, for which no universally accepted method is available. Here, we present a new peak picking algorithm, CYPICK, that follows, as far as possible, the manual approach taken by a spectroscopist who analyzes peak patterns in contour plots of the spectrum, but is fully automated. Human visual inspection is replaced by the evaluation of geometric criteria applied to contour lines, such as local extremality, approximate circularity (after appropriate scaling of the spectrum axes), and convexity. The performance of CYPICK was evaluated for a variety of spectra from different proteins by systematic comparison with peak lists obtained by other, manual or automated, peak picking methods, as well as by analyzing the results of automated chemical shift assignment and structure calculation based on input peak lists from CYPICK. The results show that CYPICK yielded peak lists that compare in most cases favorably to those obtained by other automated peak pickers with respect to the criteria of finding a maximal number of real signals, a minimal number of artifact peaks, and maximal correctness of the chemical shift assignments and the three-dimensional structure obtained by fully automated assignment and structure calculation.

Computer vision-based automated peak picking applied to protein NMR spectra.

PubMed

Klukowski, Piotr; Walczak, Michal J; Gonczarek, Adam; Boudet, Julien; Wider, Gerhard

2015-09-15

A detailed analysis of multidimensional NMR spectra of macromolecules requires the identification of individual resonances (peaks). This task can be tedious and time-consuming and often requires support by experienced users. Automated peak picking algorithms were introduced more than 25 years ago, but there are still major deficiencies/flaws that often prevent complete and error free peak picking of biological macromolecule spectra. The major challenges of automated peak picking algorithms is both the distinction of artifacts from real peaks particularly from those with irregular shapes and also picking peaks in spectral regions with overlapping resonances which are very hard to resolve by existing computer algorithms. In both of these cases a visual inspection approach could be more effective than a 'blind' algorithm. We present a novel approach using computer vision (CV) methodology which could be better adapted to the problem of peak recognition. After suitable 'training' we successfully applied the CV algorithm to spectra of medium-sized soluble proteins up to molecular weights of 26 kDa and to a 130 kDa complex of a tetrameric membrane protein in detergent micelles. Our CV approach outperforms commonly used programs. With suitable training datasets the application of the presented method can be extended to automated peak picking in multidimensional spectra of nucleic acids or carbohydrates and adapted to solid-state NMR spectra. CV-Peak Picker is available upon request from the authors. gsw@mol.biol.ethz.ch; michal.walczak@mol.biol.ethz.ch; adam.gonczarek@pwr.edu.pl Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Revisiting the NMR structure of the ultrafast downhill folding protein gpW from bacteriophage λ.

PubMed

Sborgi, Lorenzo; Verma, Abhinav; Muñoz, Victor; de Alba, Eva

2011-01-01

GpW is a 68-residue protein from bacteriophage λ that participates in virus head morphogenesis. Previous NMR studies revealed a novel α+β fold for this protein. Recent experiments have shown that gpW folds in microseconds by crossing a marginal free energy barrier (i.e., downhill folding). These features make gpW a highly desirable target for further experimental and computational folding studies. As a step in that direction, we have re-determined the high-resolution structure of gpW by multidimensional NMR on a construct that eliminates the purification tags and unstructured C-terminal tail present in the prior study. In contrast to the previous work, we have obtained a full manual assignment and calculated the structure using only unambiguous distance restraints. This new structure confirms the α+β topology, but reveals important differences in tertiary packing. Namely, the two α-helices are rotated along their main axis to form a leucine zipper. The β-hairpin is orthogonal to the helical interface rather than parallel, displaying most tertiary contacts through strand 1. There also are differences in secondary structure: longer and less curved helices and a hairpin that now shows the typical right-hand twist. Molecular dynamics simulations starting from both gpW structures, and calculations with CS-Rosetta, all converge to our gpW structure. This confirms that the original structure has strange tertiary packing and strained secondary structure. A comparison of NMR datasets suggests that the problems were mainly caused by incomplete chemical shift assignments, mistakes in NOE assignment and the inclusion of ambiguous distance restraints during the automated procedure used in the original study. The new gpW corrects these problems, providing the appropriate structural reference for future work. Furthermore, our results are a cautionary tale against the inclusion of ambiguous experimental information in the determination of protein structures.

A new algorithm for reliable and general NMR resonance assignment.

PubMed

Schmidt, Elena; Güntert, Peter

2012-08-01

The new FLYA automated resonance assignment algorithm determines NMR chemical shift assignments on the basis of peak lists from any combination of multidimensional through-bond or through-space NMR experiments for proteins. Backbone and side-chain assignments can be determined. All experimental data are used simultaneously, thereby exploiting optimally the redundancy present in the input peak lists and circumventing potential pitfalls of assignment strategies in which results obtained in a given step remain fixed input data for subsequent steps. Instead of prescribing a specific assignment strategy, the FLYA resonance assignment algorithm requires only experimental peak lists and the primary structure of the protein, from which the peaks expected in a given spectrum can be generated by applying a set of rules, defined in a straightforward way by specifying through-bond or through-space magnetization transfer pathways. The algorithm determines the resonance assignment by finding an optimal mapping between the set of expected peaks that are assigned by definition but have unknown positions and the set of measured peaks in the input peak lists that are initially unassigned but have a known position in the spectrum. Using peak lists obtained by purely automated peak picking from the experimental spectra of three proteins, FLYA assigned correctly 96-99% of the backbone and 90-91% of all resonances that could be assigned manually. Systematic studies quantified the impact of various factors on the assignment accuracy, namely the extent of missing real peaks and the amount of additional artifact peaks in the input peak lists, as well as the accuracy of the peak positions. Comparing the resonance assignments from FLYA with those obtained from two other existing algorithms showed that using identical experimental input data these other algorithms yielded significantly (40-142%) more erroneous assignments than FLYA. The FLYA resonance assignment algorithm thus has the reliability and flexibility to replace most manual and semi-automatic assignment procedures for NMR studies of proteins.

Probing surface hydrogen bonding and dynamics by natural abundance, multidimensional, 17O DNP-NMR spectroscopy

DOE PAGES

Perras, Frederic A.; Chaudhary, Umesh; Slowing, Igor I.; ...

2016-05-06

Dynamic nuclear polarization (DNP)-enhanced solid-state nuclear magnetic resonance (SSNMR) spectroscopy is increasingly being used as a tool for the atomic-level characterization of surface sites. DNP surface-enhanced SSNMR spectroscopy of materials has, however, been limited to studying relatively receptive nuclei, and the particularly rare 17O nuclide, which is of great interest for materials science, has not been utilized. We demonstrate that advanced 17O SSNMR experiments can be performed on surface species at natural isotopic abundance using DNP. We use 17O DNP surface-enhanced 2D SSNMR to measure 17O{ 1H} HETCOR spectra as well as dipolar oscillations on a series of thermally treatedmore » mesoporous silica nanoparticle samples having different pore diameters. These experiments allow for a nonintrusive and unambiguous characterization of hydrogen bonding and dynamics at the surface of the material; no other single experiment can give such details about the interactions at the surface. Lastly, our data show that, upon drying, strongly hydrogen-bonded surface silanols, whose motions are greatly restricted by the interaction when compared to lone silanols, are selectively dehydroxylated.« less

NMRNet: A deep learning approach to automated peak picking of protein NMR spectra.

PubMed

Klukowski, Piotr; Augoff, Michal; Zieba, Maciej; Drwal, Maciej; Gonczarek, Adam; Walczak, Michal J

2018-03-14

Automated selection of signals in protein NMR spectra, known as peak picking, has been studied for over 20 years, nevertheless existing peak picking methods are still largely deficient. Accurate and precise automated peak picking would accelerate the structure calculation, and analysis of dynamics and interactions of macromolecules. Recent advancement in handling big data, together with an outburst of machine learning techniques, offer an opportunity to tackle the peak picking problem substantially faster than manual picking and on par with human accuracy. In particular, deep learning has proven to systematically achieve human-level performance in various recognition tasks, and thus emerges as an ideal tool to address automated identification of NMR signals. We have applied a convolutional neural network for visual analysis of multidimensional NMR spectra. A comprehensive test on 31 manually-annotated spectra has demonstrated top-tier average precision (AP) of 0.9596, 0.9058 and 0.8271 for backbone, side-chain and NOESY spectra, respectively. Furthermore, a combination of extracted peak lists with automated assignment routine, FLYA, outperformed other methods, including the manual one, and led to correct resonance assignment at the levels of 90.40%, 89.90% and 90.20% for three benchmark proteins. The proposed model is a part of a Dumpling software (platform for protein NMR data analysis), and is available at https://dumpling.bio/. michaljerzywalczak@gmail.compiotr.klukowski@pwr.edu.pl. Supplementary data are available at Bioinformatics online.

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

ERIC Educational Resources Information Center

Chesick, John P.

1989-01-01

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

Triple-resonance multidimensional NMR study of calmodulin complexed with the binding domain of skeletal muscle myosin light-chain kinase: Indication of a conformational change in the central helix

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

Ikura, Mitsuhiko; Kay, L.E.; Bax, A.

Heteronuclear 3D and 4D NMR experiments have been used to obtain {sup 1}H, {sup 13}C, and {sup 15}N backbone chemical shift assignments in Ca{sup 2+}-loaded clamodulin complexed with a 26-residue synthetic peptide (M13) corresponding to the calmodulin-bionding domain (residues 577-602) of rabbit skeletal muscle muosin light-chain kinase. Comparison of the chemical shift values with those observed in peptide-free calmodulin shows that binding of M13 peptide induces substantial chemical shift changes that are not localized in one particular region of the protein. The largest changes are found in the first helix of the Ca{sup 2+}-binding site 1 (E11-E14), the N-terminal portionmore » of the central helix (M72-D78), and the second helix of the Ca{sup 2+}-binding site 4 (F141-M145). Analysis of backbone NOE connectivities indicates a change from {alpha}-helical to an extended conformation for residues 75-77 upon complexation with M13. Upon complexation with M13, a significant decrease in the amide exchange rate is observed for residues T110, L112, G113, and E114 at the end of the second helix of site 3.« less

Chemoselective detection and discrimination of carbonyl-containing compounds in metabolite mixtures by 1H-detected 15N NMR

PubMed Central

Lane, Andrew N.; Arumugam, Sengodagounder; Lorkiewicz, Pawel K.; Higashi, Richard M.; Laulhé, Sébastien; Nantz, Michael H.; Moseley, Hunter N.B.; Fan, Teresa W.-M.

2015-01-01

NMR spectra of mixtures of metabolites extracted from cells or tissues are extremely complex, reflecting the large number of compounds that are present over a wide range of concentrations. Although multidimensional NMR can greatly improve resolution as well as improve reliability of compound assignments, lower abundance metabolites often remain hidden. We have developed a carbonyl selective aminooxy probe that specifically reacts with free keto and aldehyde functions, but not carboxylates. By incorporating 15N in the aminooxy functional group, 15N-edited NMR was used to select exclusively those metabolites that contain a free carbonyl function while all other metabolites are rejected. Here we demonstrate that the chemical shifts of the aminooxy adducts of ketones and aldehydes are very different, which can be used to discriminate between aldoses and ketoses for example. Utilizing the 2 or 3 bond 15N-1H couplings, the 15N-edited NMR analysis was optimized first with authentic standards and then applied to an extract of the lung adenocarcinoma cell line A549. More than 30 carbonyl containing compounds at NMR detectable levels, 6 of which we have assigned by reference to our database. As the aminooxy probe contains a permanently charged quaternary ammonium group, the adducts are also optimized for detection by mass spectrometry. Thus, this sample preparation technique provides a better link between the two structural determination tools, thereby paving the way to faster and more reliable identification of both known and unknown metabolites directly in crude biological extracts. PMID:25616249

A model of the complex between human {beta}-microseminoprotein and CRISP-3 based on NMR data

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

Ghasriani, Houman; Fernlund, Per; Udby, Lene

2009-01-09

{beta}-Microseminoprotein (MSP), a 10 kDa seminal plasma protein, forms a tight complex with cysteine-rich secretory protein 3 (CRISP-3) from granulocytes. The 3D structure of human MSP has been determined but there is as yet no 3D structure for CRISP-3. We have now studied the complex between human MSP and CRISP-3 with multidimensional NMR. {sup 15}N-HSQC spectra show substantial differences between free and complexed hMSP. Using several 3D-NMR spectra of triply labeled hMSP in complex with a recombinant N-terminal domain of CRISP-3, most of the backbone of hMSP could be assigned. The data show that only one side of hMSP, comprisingmore » {beta}-strands 1, 4, 5, and 8 are affected by the complex formation, indicating that {beta}-strands 1 and 8 form the main binding surface. Based on this we present a tentative structure for the hMSP-CRISP-3 complex using the known crystal structure of triflin as a model of CRISP-3.« less

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)

NASA Astrophysics Data System (ADS)

Snyder, David A.; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase.

NMR Studies of Dynamic Biomolecular Conformational Ensembles

PubMed Central

Torchia, Dennis A.

2015-01-01

Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on timescales ranging from ps to ms, both in solution and in the solid state. However, due to the complexity of biomolecules, it is not possible to extract a unique atomic-resolution description of biomolecular motions even from extensive NMR data when many conformations are sampled on multiple timescales. For this reason, powerful computational approaches are increasingly applied to large NMR data sets to elucidate conformational ensembles sampled by biomolecules. In the past decade, considerable attention has been directed at an important class of biomolecules that function by binding to a wide variety of target molecules. Questions of current interest are: “Does the free biomolecule sample a conformational ensemble that encompasses the conformations found when it binds to various targets; and if so, on what time scale is the ensemble sampled?” This article reviews recent efforts to answer these questions, with a focus on comparing ensembles obtained for the same biomolecules by different investigators. A detailed comparison of results obtained is provided for three biomolecules: ubiquitin, calmodulin and the HIV-1 trans-activation response RNA. PMID:25669739

Multidimensional Screening as a Pharmacology Laboratory Experience.

ERIC Educational Resources Information Center

Malone, Marvin H.; And Others

1979-01-01

A multidimensional pharmacodynamic screening experiment that addresses drug interaction is included in the pharmacology-toxicology laboratory experience of pharmacy students at the University of the Pacific. The student handout with directions for the procedure is reproduced, drug compounds tested are listed, and laboratory evaluation results are…

Accessible NMR Experiments Studying the Hydrodynamics of [subscript 15]N-Enriched Ubiquitin at Low Fields

ERIC Educational Resources Information Center

Thompson, Laura E.; Rovnyak, David

2007-01-01

We have recently developed and implemented two experiments in biomolecular NMR for an undergraduate-level biophysical chemistry laboratory with commercially available [subscript 15]N-enriched human ubiquitin. These experiments take advantage of [subscript 15]N direct detection of the NMR signal. The first experiment develops skills in acquiring…

Accessible NMR Experiments Studying the Hydrodynamics of [superscript 15]N-Enriched Ubiquitin at Low Fields

ERIC Educational Resources Information Center

Thompson, Laura E.; Rovnyak, David

2007-01-01

We have recently developed and implemented two experiments in biomolecular NMR for an undergraduate-level biophysical chemistry laboratory with commercially available [superscript 15]N-enriched human ubiquitin. These experiments take advantage of [superscript 15]N direct detection of the NMR signal. The first experiment develops skills in…

Preliminary Development of a Multidimensional Semantic Patient Experience Measurement Questionnaire.

PubMed

Kleiss, James A

2016-10-01

The purpose of this research was to assess the utility and reliability of a multidimensional patient experience measurement questionnaire in a clinical setting. Patient experience has emerged as an important metric for quality of healthcare. A number of separate concepts have been used to measure patient experience, but psychological research suggests that subjective experience is actually a composite of several independent concepts including: (a) evaluation/valence, (b) potency/control, (c) activity/arousal, and (d) novelty. The present research evaluates the reliability of a multidimensional patient experience measurement questionnaire in a clinical setting. A multidimensional semantic differential questionnaire was developed to measure the four underlying semantic dimensions of patient experience mentioned above. A group of 60 patients used the questionnaire to assess prescan expectations and postscan experience of a magnetic resonance scan. Data for one patient were deleted because their scan was interrupted. Results revealed more positive evaluation/valence, higher potency/control, and lower activity/arousal for postscan ratings compared to prescan expectations. Ratings of novelty were neutral in both the prescan and the postscan conditions. Subsequent analysis suggested that internal consistency for some concepts could be improved by replacing several specific rating scales. Present results provide evidence of the utility and reliability of a multidimensional semantic questionnaire for measuring patient experience in an actual clinical setting. Recommendations to improve internal consistency for the concepts potency/control, activity/arousal, and novelty were also provided. © The Author(s) 2016.

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.

An Inversion Recovery NMR Kinetics Experiment

ERIC Educational Resources Information Center

Williams, Travis J.; Kershaw, Allan D.; Li, Vincent; Wu, Xinping

2011-01-01

A convenient laboratory experiment is described in which NMR magnetization transfer by inversion recovery is used to measure the kinetics and thermochemistry of amide bond rotation. The experiment utilizes Varian spectrometers with the VNMRJ 2.3 software, but can be easily adapted to any NMR platform. The procedures and sample data sets in this…

Conformation and dynamics of the ligand shell of a water-soluble Au102 nanoparticle.

PubMed

Salorinne, Kirsi; Malola, Sami; Wong, O Andrea; Rithner, Christopher D; Chen, Xi; Ackerson, Christopher J; Häkkinen, Hannu

2016-01-21

Inorganic nanoparticles, stabilized by a passivating layer of organic molecules, form a versatile class of nanostructured materials with potential applications in material chemistry, nanoscale physics, nanomedicine and structural biology. While the structure of the nanoparticle core is often known to atomic precision, gaining precise structural and dynamical information on the organic layer poses a major challenge. Here we report a full assignment of (1)H and (13)C NMR shifts to all ligands of a water-soluble, atomically precise, 102-atom gold nanoparticle stabilized by 44 para-mercaptobenzoic acid ligands in solution, by using a combination of multidimensional NMR methods, density functional theory calculations and molecular dynamics simulations. Molecular dynamics simulations augment the data by giving information about the ligand disorder and visualization of possible distinct ligand conformations of the most dynamic ligands. The method demonstrated here opens a way to controllable strategies for functionalization of ligated nanoparticles for applications.

Conformation and dynamics of the ligand shell of a water-soluble Au102 nanoparticle

PubMed Central

Salorinne, Kirsi; Malola, Sami; Wong, O. Andrea; Rithner, Christopher D.; Chen, Xi; Ackerson, Christopher J.; Häkkinen, Hannu

2016-01-01

Inorganic nanoparticles, stabilized by a passivating layer of organic molecules, form a versatile class of nanostructured materials with potential applications in material chemistry, nanoscale physics, nanomedicine and structural biology. While the structure of the nanoparticle core is often known to atomic precision, gaining precise structural and dynamical information on the organic layer poses a major challenge. Here we report a full assignment of 1H and 13C NMR shifts to all ligands of a water-soluble, atomically precise, 102-atom gold nanoparticle stabilized by 44 para-mercaptobenzoic acid ligands in solution, by using a combination of multidimensional NMR methods, density functional theory calculations and molecular dynamics simulations. Molecular dynamics simulations augment the data by giving information about the ligand disorder and visualization of possible distinct ligand conformations of the most dynamic ligands. The method demonstrated here opens a way to controllable strategies for functionalization of ligated nanoparticles for applications. PMID:26791253

Solid-state NMR studies of proteins immobilized on inorganic surfaces

DOE PAGES

Shaw, Wendy J.

2014-10-29

Solid state NMR is the primary tool for studying the quantitative, site-specific structure, orientation, and dynamics of biomineralization proteins under biologically relevant conditions. Two calcium phosphate proteins, statherin and leucine rich amelogenin protein (LRAP), have been studied in depth and have different features, challenging our ability to extract design principles. More recent studies of the significantly larger full-length amelogenin represent a challenging but necessary step to ultimately investigate the full diversity of biomineralization proteins. Interactions of amino acids and silaffin peptide with silica are also being studied, along with qualitative studies of proteins interacting with calcium carbonate. Dipolar recoupling techniquesmore » have formed the core of the quantitative studies, yet, the need for isolated spin pairs makes this approach costly and time intensive. The use of multi-dimensional techniques is advancing, methodology which, despite its challenges with these difficult-to-study proteins, will continue to drive future advancements in this area.« less

On the problem of resonance assignments in solid state NMR of uniformly 15N, 13C-labeled proteins

NASA Astrophysics Data System (ADS)

Tycko, Robert

2015-04-01

Determination of accurate resonance assignments from multidimensional chemical shift correlation spectra is one of the major problems in biomolecular solid state NMR, particularly for relative large proteins with less-than-ideal NMR linewidths. This article investigates the difficulty of resonance assignment, using a computational Monte Carlo/simulated annealing (MCSA) algorithm to search for assignments from artificial three-dimensional spectra that are constructed from the reported isotropic 15N and 13C chemical shifts of two proteins whose structures have been determined by solution NMR methods. The results demonstrate how assignment simulations can provide new insights into factors that affect the assignment process, which can then help guide the design of experimental strategies. Specifically, simulations are performed for the catalytic domain of SrtC (147 residues, primarily β-sheet secondary structure) and the N-terminal domain of MLKL (166 residues, primarily α-helical secondary structure). Assuming unambiguous residue-type assignments and four ideal three-dimensional data sets (NCACX, NCOCX, CONCA, and CANCA), uncertainties in chemical shifts must be less than 0.4 ppm for assignments for SrtC to be unique, and less than 0.2 ppm for MLKL. Eliminating CANCA data has no significant effect, but additionally eliminating CONCA data leads to more stringent requirements for chemical shift precision. Introducing moderate ambiguities in residue-type assignments does not have a significant effect.

Synthesis and Resolution of the Atropisomeric 1,1'-Bi-2-Naphthol: An Experiment in Organic Synthesis and 2-D NMR Spectroscopy

ERIC Educational Resources Information Center

Mak, Kendrew K. W.

2004-01-01

NMR spectroscopy is presented. It is seen that the experiment regarding the synthesis and resolution of 1,1'-Bi-2-naphtol presents a good experiment for teaching organic synthesis and NMR spectroscopy and provides a strategy for obtaining enantiopure compounds from achiral starting materials.

Enhancing the resolution of 1H and 13C solid-state NMR spectra by reduction of anisotropic bulk magnetic susceptibility broadening.

PubMed

Hanrahan, Michael P; Venkatesh, Amrit; Carnahan, Scott L; Calahan, Julie L; Lubach, Joseph W; Munson, Eric J; Rossini, Aaron J

2017-10-25

We demonstrate that natural isotopic abundance 2D heteronuclear correlation (HETCOR) solid-state NMR spectra can be used to significantly reduce or eliminate the broadening of 1 H and 13 C solid-state NMR spectra of organic solids due to anisotropic bulk magnetic susceptibility (ABMS). ABMS often manifests in solids with aromatic groups, such as active pharmaceutical ingredients (APIs), and inhomogeneously broadens the NMR peaks of all nuclei in the sample. Inhomogeneous peaks with full widths at half maximum (FWHM) of ∼1 ppm typically result from ABMS broadening and the low spectral resolution impedes the analysis of solid-state NMR spectra. ABMS broadening of solid-state NMR spectra has previously been eliminated using 2D multiple-quantum correlation experiments, or by performing NMR experiments on diluted materials or single crystals. However, these experiments are often infeasible due to their poor sensitivity and/or provide limited gains in resolution. 2D 1 H- 13 C HETCOR experiments have previously been applied to reduce susceptibility broadening in paramagnetic solids and we show that this strategy can significantly reduce ABMS broadening in diamagnetic organic solids. Comparisons of 1D solid-state NMR spectra and 1 H and 13 C solid-state NMR spectra obtained from 2D 1 H- 13 C HETCOR NMR spectra show that the HETCOR spectrum directly increases resolution by a factor of 1.5 to 8. The direct gain in resolution is determined by the ratio of the inhomogeneous 13 C/ 1 H linewidth to the homogeneous 1 H linewidth, with the former depending on the magnitude of the ABMS broadening and the strength of the applied field and the latter on the efficiency of homonuclear decoupling. The direct gains in resolution obtained using the 2D HETCOR experiments are better than that obtained by dilution. For solids with long proton longitudinal relaxation times, dynamic nuclear polarization (DNP) was applied to enhance sensitivity and enable the acquisition of 2D 1 H- 13 C HETCOR NMR spectra. 2D 1 H- 13 C HETCOR experiments were applied to resolve and partially assign the NMR signals of the form I and form II polymorphs of aspirin in a sample containing both forms. These findings have important implications for ultra-high field NMR experiments, optimization of decoupling schemes and assessment of the fundamental limits on the resolution of solid-state NMR spectra.

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP).

PubMed

Snyder, David A; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase. Copyright © 2015 Elsevier Inc. All rights reserved.

A short recollection on the paper entitled "A common sense approach to peak picking in two-, three-, and four-dimensional spectra using automatic computer analysis of contour diagrams" by D.S. Garrett, R. Powers, A.M. Gronenborn, and G.M. Clore [J. Magn. Reson. 95 (1991) 214-220].

PubMed

Garrett, Daniel S; Gronenborn, Angela M; Clore, G Marius

2011-12-01

The Contour Approach to Peak Picking was developed to aid in the analysis and interpretation and of multidimensional NMR spectra of large biomolecules. In essence, it comprises an interactive graphics software tool to computationally select resonance positions in heteronuclear, 3- and 4D spectra. Copyright © 2011. Published by Elsevier Inc.

A Solid-State NMR Experiment: Analysis of Local Structural Environments in Phosphate Glasses

ERIC Educational Resources Information Center

Anderson, Stanley E.; Saiki, David; Eckert, Hellmut; Meise-Gresch, Karin

2004-01-01

An experiment that can be used to directly study the local chemical environments of phosphorus in solid amorphous materials is demonstrated. The experiment aims at familiarizing the students of chemistry with the principles of solid-state NMR, by having them synthesize a simple phosphate glass, and making them observe the (super 31)P NMR spectrum,…

U.S. EPA High-Field NMR Facility with Remote Accessibility

EPA Science Inventory

EPA’s High-Field Nuclear Magnetic Resonance Research Facility housed in Athens, GA has two Varian 600 MHz NMR spectrometers used for conducting sophisticated experiments in environmental science. Off-site users can ship their samples and perform their NMR experiments remotely fr...

Novel dimeric metabolites from Alternaria tagetica.

PubMed

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

2000-08-01

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

Interaction of lafutidine in binding to human serum albumin in gastric ulcer therapy: STD-NMR, WaterLOGSY-NMR, NMR relaxation times, Tr-NOESY, molecule docking, and spectroscopic studies.

PubMed

Yang, Hongqin; Huang, Yanmei; He, Jiawei; Li, Shanshan; Tang, Bin; Li, Hui

2016-09-15

In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, (1)H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic Tuning Matching Cycler (ATMC) in situ NMR spectroscopy as a novel approach for real-time investigations of Li- and Na-ion batteries

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

Pecher, Oliver; Bayley, Paul M.; Liu, Hao

We have developed and explored the use of a new Automatic Tuning Matching Cycler (ATMC) in situ NMR probe system to track the formation of intermediate phases and investigate electrolyte decomposition during electrochemical cycling of Li- and Na-ion batteries (LIBs and NIBs). The new approach addresses many of the issues arising during in situ NMR, e.g., significantly different shifts of the multi-component samples, changing sample conditions (such as the magnetic susceptibility and conductivity) during cycling, signal broadening due to paramagnetism as well as interferences between the NMR and external cycler circuit that might impair the experiments. We provide practical insightmore » into how to conduct ATMC in situ NMR experiments and discuss applications of the methodology to LiFePO4 (LFP) and Na3V2(PO4)2F3 cathodes as well as Na metal anodes. Automatic frequency sweep 7Li in situ NMR reveals significant changes of the strongly paramagnetic broadened LFP line shape in agreement with the structural changes due to delithiation. Additionally, 31P in situ NMR shows a full separation of the electrolyte and cathode NMR signals and is a key feature for a deeper understanding of the processes occurring during charge/discharge on the local atomic scale of NMR. 31P in situ NMR with “on-the-fly” re-calibrated, varying carrier frequencies on Na3V2(PO4)2F3 as a cathode in a NIB enabled the detection of different P signals within a huge frequency range of 4000 ppm. The experiments show a significant shift and changes in the number as well as intensities of 31P signals during desodiation/sodiation of the cathode. The in situ experiments reveal changes of local P environments that in part have not been seen in ex situ NMR investigations. Furthermore, we applied ATMC 23Na in situ NMR on symmetrical Na–Na cells during galvanostatic plating. An automatic adjustment of the NMR carrier frequency during the in situ experiment ensured on-resonance conditions for the Na metal and electrolyte peak, respectively. Thus, interleaved measurements with different optimal NMR set-ups for the metal and electrolyte, respectively, became possible. This allowed the formation of different Na metal species as well as a quantification of electrolyte consumption during the electrochemical experiment to be monitored. The new approach is likely to benefit a further understanding of Na-ion battery chemistries.« less

Automatic Tuning Matching Cycler (ATMC) in situ NMR spectroscopy as a novel approach for real-time investigations of Li- and Na-ion batteries

NASA Astrophysics Data System (ADS)

Pecher, Oliver; Bayley, Paul M.; Liu, Hao; Liu, Zigeng; Trease, Nicole M.; Grey, Clare P.

2016-04-01

We have developed and explored the use of a new Automatic Tuning Matching Cycler (ATMC) in situ NMR probe system to track the formation of intermediate phases and investigate electrolyte decomposition during electrochemical cycling of Li- and Na-ion batteries (LIBs and NIBs). The new approach addresses many of the issues arising during in situ NMR, e.g., significantly different shifts of the multi-component samples, changing sample conditions (such as the magnetic susceptibility and conductivity) during cycling, signal broadening due to paramagnetism as well as interferences between the NMR and external cycler circuit that might impair the experiments. We provide practical insight into how to conduct ATMC in situ NMR experiments and discuss applications of the methodology to LiFePO4 (LFP) and Na3V2(PO4)2F3 cathodes as well as Na metal anodes. Automatic frequency sweep 7Li in situ NMR reveals significant changes of the strongly paramagnetic broadened LFP line shape in agreement with the structural changes due to delithiation. Additionally, 31P in situ NMR shows a full separation of the electrolyte and cathode NMR signals and is a key feature for a deeper understanding of the processes occurring during charge/discharge on the local atomic scale of NMR. 31P in situ NMR with "on-the-fly" re-calibrated, varying carrier frequencies on Na3V2(PO4)2F3 as a cathode in a NIB enabled the detection of different P signals within a huge frequency range of 4000 ppm. The experiments show a significant shift and changes in the number as well as intensities of 31P signals during desodiation/sodiation of the cathode. The in situ experiments reveal changes of local P environments that in part have not been seen in ex situ NMR investigations. Furthermore, we applied ATMC 23Na in situ NMR on symmetrical Na-Na cells during galvanostatic plating. An automatic adjustment of the NMR carrier frequency during the in situ experiment ensured on-resonance conditions for the Na metal and electrolyte peak, respectively. Thus, interleaved measurements with different optimal NMR set-ups for the metal and electrolyte, respectively, became possible. This allowed the formation of different Na metal species as well as a quantification of electrolyte consumption during the electrochemical experiment to be monitored. The new approach is likely to benefit a further understanding of Na-ion battery chemistries.

Nuclear magnetic resonance studies of quadrupolar nuclei and dipolar field effects

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

Urban, Jeffry Todd

Experimental and theoretical research conducted in two areas in the field of nuclear magnetic resonance (NMR) spectroscopy is presented: (1) studies of the coherent quantum-mechanical control of the angular momentum dynamics of quadrupolar (spin I > 1/2) nuclei and its application to the determination of molecular structure; and (2) applications of the long-range nuclear dipolar field to novel NMR detection methodologies.The dissertation is organized into six chapters. The first two chapters and associated appendices are intended to be pedagogical and include an introduction to the quantum mechanical theory of pulsed NMR spectroscopy and the time dependent theory of quantum mechanics.more » The third chapter describes investigations of the solid-state multiple-quantum magic angle spinning (MQMAS) NMR experiment applied to I = 5/2 quadrupolar nuclei. This work reports the use of rotary resonance-matched radiofrequency irradiation for sensitivity enhancement of the I = 5/2 MQMAS experiment. These experiments exhibited certain selective line narrowing effects which were investigated theoretically.The fourth chapter extends the discussion of multiple quantum spectroscopy of quadrupolar nuclei to a mostly theoretical study of the feasibility of enhancing the resolution of nitrogen-14 NMR of large biomolecules in solution via double-quantum spectroscopy. The fifth chapter continues to extend the principles of multiple quantum NMR spectroscopy of quadrupolar nuclei to make analogies between experiments in NMR/nuclear quadrupolar resonance (NQR) and experiments in atomic/molecular optics (AMO). These analogies are made through the Hamiltonian and density operator formalism of angular momentum dynamics in the presence of electric and magnetic fields.The sixth chapter investigates the use of the macroscopic nuclear dipolar field to encode the NMR spectrum of an analyte nucleus indirectly in the magnetization of a sensor nucleus. This technique could potentially serve as an encoding module for the recently developed NMR remote detection experiment. The feasibility of using hyperpolarized xenon-129 gas as a sensor is discussed. This work also reports the use of an optical atomic magnetometer to detect the nuclear magnetization of Xe-129 gas, which has potential applicability as a detection module for NMR remote detection experiments.« less

Two-dimensional NMR spectrometry

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

Farrar, T.C.

1987-06-01

This article is the second in a two-part series. In part one (ANALYTICAL CHEMISTRY, May 15) the authors discussed one-dimensional nuclear magnetic resonance (NMR) spectra and some relatively advanced nuclear spin gymnastics experiments that provide a capability for selective sensitivity enhancements. In this article and overview and some applications of two-dimensional NMR experiments are presented. These powerful experiments are important complements to the one-dimensional experiments. As in the more sophisticated one-dimensional experiments, the two-dimensional experiments involve three distinct time periods: a preparation period, t/sub 0/; an evolution period, t/sub 1/; and a detection period, t/sub 2/.

Water absorption of freeze-dried meat at different water activities: a multianalytical approach using sorption isotherm, differential scanning calorimetry, and nuclear magnetic resonance.

PubMed

Venturi, Luca; Rocculi, Pietro; Cavani, Claudio; Placucci, Giuseppe; Dalla Rosa, Marco; Cremonini, Mauro A

2007-12-26

Hydration of freeze-dried chicken breast meat was followed in the water activity range of aw=0.12-0.99 by a multianalytical approach comprising of sorption isotherm, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The amount of frozen water and the shape of the T2-relaxogram were evaluated at each water content by DSC and NMR, respectively. Data revealed an agreement between sorption isotherm and DSC experiments about the onset of bulk water (aw=0.83-0.86), and NMR detected mobile water starting at aw=0.75. The origin of the short-transverse relaxation time part of the meat NMR signal was also reinvestigated through deuteration experiments and proposed to arise from protons belonging to plasticized matrix structures. It is proved both by D2O experiments and by gravimetry that the extra protons not contributing to the water content in the NMR experiments are about 6.4% of the total proton NMR CPMG signal of meat.

Isolation, folding and structural investigations of the amino acid transporter OEP16

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

Ni, Da Qun; Zook, James; Klewer, Douglas A.

2011-12-01

Membrane proteins compose more than 30% of all proteins in the living cell. However, many membrane proteins have low abundance in the cell and cannot be isolated from natural sources in concentrations suitable for structure analysis. The overexpression, reconstitution, and stabilization of membrane proteins are complex and remain a formidable challenge in membrane protein characterization. Here we describe a novel, in vitro folding procedure for a cation-selective channel protein, the outer envelope membrane protein 16 (OEP16) of pea chloroplast, overexpressed in Escherichia coli in the form of inclusion bodies. The protein is purified and then folded with detergent on amore » Ni-NTA affinity column. Final concentrations of reconstituted OEP16 of up to 24 mg/ml have been achieved, which provides samples that are sufficient for structural studies by NMR and crystallography. Reconstitution of OEP16 in detergent micelles was monitored by circular dichroism, fluorescence, and NMR spectroscopy. Tryptophan fluorescence spectra of heterologous expressed OEP16 in micelles are similar to spectra of functionally active OEP16 in liposomes, which indicates folding of the membrane protein in detergent micelles. CD spectroscopy studies demonstrate a folded protein consisting primarily of a-helices. 15N-HSQC NMR spectra also provide evidence for a folded protein. We present here a convenient, effective and quantitative method to screen large numbers of conditions for optimal protein stability by using microdialysis chambers in combination with fluorescence spectroscopy. Recent collection of multidimensional NMR data at 500, 600 and 800 MHz demonstrated that the protein is suitable for structure determination by NMR and stable for weeks during data collection.« less

A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data

PubMed Central

Vehtari, Aki; Mäkinen, Ville-Petteri; Soininen, Pasi; Ingman, Petri; Mäkelä, Sanna M; Savolainen, Markku J; Hannuksela, Minna L; Kaski, Kimmo; Ala-Korpela, Mika

2007-01-01

Background A key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by 1H NMR spectroscopy of serum. Results A Bayesian methodology, with a biochemical motivation, is presented for a real 1H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC) and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG), 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively). The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the 1H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the 1H NMR spectra. Conclusion The systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics. PMID:17493257

Isolation, folding and structural investigations of the amino acid transporter OEP16.

PubMed

Ni, Da Qun; Zook, James; Klewer, Douglas A; Nieman, Ronald A; Soll, J; Fromme, Petra

2011-12-01

Membrane proteins compose more than 30% of all proteins in the living cell. However, many membrane proteins have low abundance in the cell and cannot be isolated from natural sources in concentrations suitable for structure analysis. The overexpression, reconstitution, and stabilization of membrane proteins are complex and remain a formidable challenge in membrane protein characterization. Here we describe a novel, in vitro folding procedure for a cation-selective channel protein, the outer envelope membrane protein 16 (OEP16) of pea chloroplast, overexpressed in Escherichia coli in the form of inclusion bodies. The protein is purified and then folded with detergent on a Ni-NTA affinity column. Final concentrations of reconstituted OEP16 of up to 24 mg/ml have been achieved, which provides samples that are sufficient for structural studies by NMR and crystallography. Reconstitution of OEP16 in detergent micelles was monitored by circular dichroism, fluorescence, and NMR spectroscopy. Tryptophan fluorescence spectra of heterologous expressed OEP16 in micelles are similar to spectra of functionally active OEP16 in liposomes, which indicates folding of the membrane protein in detergent micelles. CD spectroscopy studies demonstrate a folded protein consisting primarily of α-helices. ¹⁵N-HSQC NMR spectra also provide evidence for a folded protein. We present here a convenient, effective and quantitative method to screen large numbers of conditions for optimal protein stability by using microdialysis chambers in combination with fluorescence spectroscopy. Recent collection of multidimensional NMR data at 500, 600 and 800 MHz demonstrated that the protein is suitable for structure determination by NMR and stable for weeks during data collection. Copyright © 2011. Published by Elsevier Inc.

A Comprehensive Approach to the Patient at End of Life: Assessment of Multidimensional Suffering

PubMed Central

Wachholtz, Amy B.; Fitch, Christina E.; Makowski, Suzana; Tjia, Jennifer

2016-01-01

Pain is a multidimensional, complex experience. There are many challenges in identifying and meeting the needs of patients experiencing pain. Evaluation of pain from a bio-psycho-social-spiritual framework is particularly germane for patients approaching the end of life. This review explores the relation between the psychospiritual dimensions of suffering and the experience of physical pain, and how to assess and treat pain in a multidimensional framework. A review of empirical data on the relation between pain and suffering as well as interdisciplinary evidence-based approaches to alleviate suffering are provided. PMID:27043799

Dipeptide Structural Analysis Using Two-Dimensional NMR for the Undergraduate Advanced Laboratory

ERIC Educational Resources Information Center

Gonzalez, Elizabeth; Dolino, Drew; Schwartzenburg, Danielle; Steiger, Michelle A.

2015-01-01

A laboratory experiment was developed to introduce students in either an organic chemistry or biochemistry lab course to two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy using simple biomolecules. The goal of this experiment is for students to understand and interpret the information provided by a 2D NMR spectrum. Students are…

Structure of the Complex between a Heparan Sulfate Octasaccharide and Mycobacterial Heparin-Binding Hemagglutinin.

PubMed

Huang, Teng-Yi; Irene, Deli; Zulueta, Medel Manuel L; Tai, Tzu-Jui; Lain, Shih-Han; Cheng, Cheng-Po; Tsai, Ping-Xi; Lin, Shu-Yi; Chen, Zhi-Geng; Ku, Chiao-Chu; Hsiao, Chwan-Deng; Chyan, Chia-Lin; Hung, Shang-Cheng

2017-04-03

Heparin-binding hemagglutinin (HBHA) is a 199 amino acid virulence factor at the envelope of Mycobacterium tuberculosis that contributes to latent tuberculosis. The binding of HBHA to respiratory epithelial cells, which leads to extrapulmonary dissemination of the pathogen, is mediated by cell-surface heparan sulfate (HS). We report the structural characterization of the HBHA/HS complex by NMR spectroscopy. To develop a model for the molecular recognition, the first chemically synthesized uniformly 13 C- and 15 N-labeled HS octasaccharide and a uniformly 13 C- and 15 N-labeled form of HBHA were prepared. Residues 180-195 at the C-terminal region of HBHA show large chemical shift perturbation upon association with the octasaccharide. Molecular dynamics simulations conforming to the multidimensional NMR data revealed key electrostatic and even hydrophobic interactions between the binding partners that may aid in the development of agents targeting the binding event. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Titration of Alanine Monitored by NMR Spectroscopy: A Biochemistry Laboratory Experiment

ERIC Educational Resources Information Center

Waller, Francis J.; And Others

1977-01-01

The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

NMR and MALDI-TOF MS based characterization of exopolysaccharides in anaerobic microbial aggregates from full-scale reactors

PubMed Central

Gonzalez-Gil, Graciela; Thomas, Ludivine; Emwas, Abdul-Hamid; Lens, Piet N. L.; Saikaly, Pascal E.

2015-01-01

Anaerobic granular sludge is composed of multispecies microbial aggregates embedded in a matrix of extracellular polymeric substances (EPS). Here we characterized the chemical fingerprint of the polysaccharide fraction of EPS in anaerobic granules obtained from full-scale reactors treating different types of wastewater. Nuclear magnetic resonance (NMR) signals of the polysaccharide region from the granules were very complex, likely as a result of the diverse microbial population in the granules. Using nonmetric multidimensional scaling (NMDS), the 1H NMR signals of reference polysaccharides (gellan, xanthan, alginate) and those of the anaerobic granules revealed that there were similarities between the polysaccharides extracted from granules and the reference polysaccharide alginate. Further analysis of the exopolysaccharides from anaerobic granules, and reference polysaccharides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that exopolysaccharides from two of the anaerobic granular sludges studied exhibited spectra similar to that of alginate. The presence of sequences related to the synthesis of alginate was confirmed in the metagenomes of the granules. Collectively these results suggest that alginate-like exopolysaccharides are constituents of the EPS matrix in anaerobic granular sludge treating different industrial wastewater. This finding expands the engineered environments where alginate has been found as EPS constituent of microbial aggregates. PMID:26391984

Solid-state NMR investigations of cellulose structure and interactions with matrix polysaccharides in plant primary cell walls.

PubMed

Wang, Tuo; Hong, Mei

2016-01-01

Until recently, the 3D architecture of plant cell walls was poorly understood due to the lack of high-resolution techniques for characterizing the molecular structure, dynamics, and intermolecular interactions of the wall polysaccharides in these insoluble biomolecular mixtures. We introduced multidimensional solid-state NMR (SSNMR) spectroscopy, coupled with (13)C labelling of whole plants, to determine the spatial arrangements of macromolecules in near-native plant cell walls. Here we review key evidence from 2D and 3D correlation NMR spectra that show relatively few cellulose-hemicellulose cross peaks but many cellulose-pectin cross peaks, indicating that cellulose microfibrils are not extensively coated by hemicellulose and all three major polysaccharides exist in a single network rather than two separate networks as previously proposed. The number of glucan chains in the primary-wall cellulose microfibrils has been under active debate recently. We show detailed analysis of quantitative (13)C SSNMR spectra of cellulose in various wild-type (WT) and mutant Arabidopsis and Brachypodium primary cell walls, which consistently indicate that primary-wall cellulose microfibrils contain at least 24 glucan chains. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

NMR and MALDI-TOF MS based characterization of exopolysaccharides in anaerobic microbial aggregates from full-scale reactors.

PubMed

Gonzalez-Gil, Graciela; Thomas, Ludivine; Emwas, Abdul-Hamid; Lens, Piet N L; Saikaly, Pascal E

2015-09-22

Anaerobic granular sludge is composed of multispecies microbial aggregates embedded in a matrix of extracellular polymeric substances (EPS). Here we characterized the chemical fingerprint of the polysaccharide fraction of EPS in anaerobic granules obtained from full-scale reactors treating different types of wastewater. Nuclear magnetic resonance (NMR) signals of the polysaccharide region from the granules were very complex, likely as a result of the diverse microbial population in the granules. Using nonmetric multidimensional scaling (NMDS), the (1)H NMR signals of reference polysaccharides (gellan, xanthan, alginate) and those of the anaerobic granules revealed that there were similarities between the polysaccharides extracted from granules and the reference polysaccharide alginate. Further analysis of the exopolysaccharides from anaerobic granules, and reference polysaccharides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that exopolysaccharides from two of the anaerobic granular sludges studied exhibited spectra similar to that of alginate. The presence of sequences related to the synthesis of alginate was confirmed in the metagenomes of the granules. Collectively these results suggest that alginate-like exopolysaccharides are constituents of the EPS matrix in anaerobic granular sludge treating different industrial wastewater. This finding expands the engineered environments where alginate has been found as EPS constituent of microbial aggregates.

Anvil cell gasket design for high pressure nuclear magnetic resonance experiments beyond 30 GPa

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

Meier, Thomas; Haase, Jürgen

2015-12-15

Nuclear magnetic resonance (NMR) experiments are reported at up to 30.5 GPa of pressure using radiofrequency (RF) micro-coils with anvil cell designs. These are the highest pressures ever reported with NMR, and are made possible through an improved gasket design based on nano-crystalline powders embedded in epoxy resin. Cubic boron-nitride (c-BN), corundum (α-Al{sub 2}O{sub 3}), or diamond based composites have been tested, also in NMR experiments. These composite gaskets lose about 1/2 of their initial height up to 30.5 GPa, allowing for larger sample quantities and preventing damages to the RF micro-coils compared to precipitation hardened CuBe gaskets. It ismore » shown that NMR shift and resolution are less affected by the composite gaskets as compared to the more magnetic CuBe. The sensitivity can be as high as at normal pressure. The new, inexpensive, and simple to engineer gaskets are thus superior for NMR experiments at high pressures.« less

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

PubMed

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

2018-01-02

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

Sensitivity of nonuniform sampling NMR.

PubMed

Palmer, Melissa R; Suiter, Christopher L; Henry, Geneive E; Rovnyak, James; Hoch, Jeffrey C; Polenova, Tatyana; Rovnyak, David

2015-06-04

Many information-rich multidimensional experiments in nuclear magnetic resonance spectroscopy can benefit from a signal-to-noise ratio (SNR) enhancement of up to about 2-fold if a decaying signal in an indirect dimension is sampled with nonconsecutive increments, termed nonuniform sampling (NUS). This work provides formal theoretical results and applications to resolve major questions about the scope of the NUS enhancement. First, we introduce the NUS Sensitivity Theorem in which any decreasing sampling density applied to any exponentially decaying signal always results in higher sensitivity (SNR per square root of measurement time) than uniform sampling (US). Several cases will illustrate this theorem and show that even conservative applications of NUS improve sensitivity by useful amounts. Next, we turn to a serious limitation of uniform sampling: the SNR by US decreases for extending evolution times, and thus total experimental times, beyond 1.26T2 (T2 = signal decay constant). Thus, SNR and resolution cannot be simultaneously improved by extending US beyond 1.26T2. We find that NUS can eliminate this constraint, and we introduce the matched NUS SNR Theorem: an exponential sampling density matched to the signal decay always improves the SNR with additional evolution time. Though proved for a specific case, broader classes of NUS densities also improve SNR with evolution time. Applications of these theoretical results are given for a soluble plant natural product and a solid tripeptide (u-(13)C,(15)N-MLF). These formal results clearly demonstrate the inadequacies of applying US to decaying signals in indirect nD-NMR dimensions, supporting a broader adoption of NUS.

Hydrolysis Studies and Quantitative Determination of Aluminum Ions Using [superscript 27]Al NMR: An Undergraduate Analytical Chemistry Experiment

ERIC Educational Resources Information Center

Curtin, Maria A.; Ingalls, Laura R.; Campbell, Andrew; James-Pederson, Magdalena

2008-01-01

This article describes a novel experiment focused on metal ion hydrolysis and the equilibria related to metal ions in aqueous systems. Using [superscript 27]Al NMR, the students become familiar with NMR spectroscopy as a quantitative analytical tool for the determination of aluminum by preparing a standard calibration curve using standard aluminum…

Experimental Determination of pK[subscript a] Values by Use of NMR Chemical Shifts, Revisited

ERIC Educational Resources Information Center

Gift, Alan D.; Stewart, Sarah M.; Bokashanga, Patrick Kwete

2012-01-01

This laboratory experiment, using proton NMR spectroscopy to determine the dissociation constant for heterocyclic bases, has been modified from a previously described experiment. A solution of a substituted pyridine is prepared using deuterium oxide (D[subscript 2]O) as the solvent. The pH of the solution is adjusted and proton NMR spectra are…

Multidimensional scaling analysis of financial time series based on modified cross-sample entropy methods

NASA Astrophysics Data System (ADS)

He, Jiayi; Shang, Pengjian; Xiong, Hui

2018-06-01

Stocks, as the concrete manifestation of financial time series with plenty of potential information, are often used in the study of financial time series. In this paper, we utilize the stock data to recognize their patterns through out the dissimilarity matrix based on modified cross-sample entropy, then three-dimensional perceptual maps of the results are provided through multidimensional scaling method. Two modified multidimensional scaling methods are proposed in this paper, that is, multidimensional scaling based on Kronecker-delta cross-sample entropy (MDS-KCSE) and multidimensional scaling based on permutation cross-sample entropy (MDS-PCSE). These two methods use Kronecker-delta based cross-sample entropy and permutation based cross-sample entropy to replace the distance or dissimilarity measurement in classical multidimensional scaling (MDS). Multidimensional scaling based on Chebyshev distance (MDSC) is employed to provide a reference for comparisons. Our analysis reveals a clear clustering both in synthetic data and 18 indices from diverse stock markets. It implies that time series generated by the same model are easier to have similar irregularity than others, and the difference in the stock index, which is caused by the country or region and the different financial policies, can reflect the irregularity in the data. In the synthetic data experiments, not only the time series generated by different models can be distinguished, the one generated under different parameters of the same model can also be detected. In the financial data experiment, the stock indices are clearly divided into five groups. Through analysis, we find that they correspond to five regions, respectively, that is, Europe, North America, South America, Asian-Pacific (with the exception of mainland China), mainland China and Russia. The results also demonstrate that MDS-KCSE and MDS-PCSE provide more effective divisions in experiments than MDSC.

Citrus Quality Control: An NMR/MRI Problem-Based Experiment

ERIC Educational Resources Information Center

Erhart, Sarah E.; McCarrick, Robert M.; Lorigan, Gary A.; Yezierski, Ellen J.

2016-01-01

An experiment seated in an industrial context can provide an engaging framework and unique learning opportunity for an upper-division physical chemistry laboratory. An experiment that teaches NMR/MRI through a problem-based quality control of citrus products was developed. In this experiment, using a problem-based learning (PBL) approach, students…

Phase-sensitive spectral estimation by the hybrid filter diagonalization method.

PubMed

Celik, Hasan; Ridge, Clark D; Shaka, A J

2012-01-01

A more robust way to obtain a high-resolution multidimensional NMR spectrum from limited data sets is described. The Filter Diagonalization Method (FDM) is used to analyze phase-modulated data and cast the spectrum in terms of phase-sensitive Lorentzian "phase-twist" peaks. These spectra are then used to obtain absorption-mode phase-sensitive spectra. In contrast to earlier implementations of multidimensional FDM, the absolute phase of the data need not be known beforehand, and linear phase corrections in each frequency dimension are possible, if they are required. Regularization is employed to improve the conditioning of the linear algebra problems that must be solved to obtain the spectral estimate. While regularization smoothes away noise and small peaks, a hybrid method allows the true noise floor to be correctly represented in the final result. Line shape transformation to a Gaussian-like shape improves the clarity of the spectra, and is achieved by a conventional Lorentzian-to-Gaussian transformation in the time-domain, after inverse Fourier transformation of the FDM spectra. The results obtained highlight the danger of not using proper phase-sensitive line shapes in the spectral estimate. The advantages of the new method for the spectral estimate are the following: (i) the spectrum can be phased by conventional means after it is obtained; (ii) there is a true and accurate noise floor; and (iii) there is some indication of the quality of fit in each local region of the spectrum. The method is illustrated with 2D NMR data for the first time, but is applicable to n-dimensional data without any restriction on the number of time/frequency dimensions. Copyright © 2011. Published by Elsevier Inc.

Indirectly detected chemical shift correlation NMR spectroscopy in solids under fast magic angle spinning

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

Mao, Kanmi

The development of fast magic angle spinning (MAS) opened up an opportunity for the indirect detection of insensitive low-γ nuclei (e.g., 13C and 15N) via the sensitive high-{gamma} nuclei (e.g., 1H and 19F) in solid-state NMR, with advanced sensitivity and resolution. In this thesis, new methodology utilizing fast MAS is presented, including through-bond indirectly detected heteronuclear correlation (HETCOR) spectroscopy, which is assisted by multiple RF pulse sequences for 1H- 1H homonuclear decoupling. Also presented is a simple new strategy for optimization of 1H- 1H homonuclear decoupling. As applications, various classes of materials, such as catalytic nanoscale materials, biomolecules, and organic complexes, are studied by combining indirect detection and other one-dimensional (1D) and two-dimensional (2D) NMR techniques. Indirectly detected through-bond HETCOR spectroscopy utilizing refocused INEPT (INEPTR) mixing was developed under fast MAS (Chapter 2). The time performance of this approach in 1H detected 2D 1H{l_brace} 13C{r_brace} spectra was significantly improved, by a factor of almost 10, compared to the traditional 13C detected experiments, as demonstrated by measuring naturally abundant organic-inorganic mesoporous hybrid materials. The through-bond scheme was demonstrated as a new analytical tool, which provides complementary structural information in solid-state systems in addition to through-space correlation. To further benefit the sensitivity of the INEPT transfer in rigid solids, the combined rotation and multiple-pulse spectroscopy (CRAMPS) was implemented for homonuclear 1H decoupling under fast MAS (Chapter 3). Several decoupling schemes (PMLG5 m more » $$\\bar{x}$$, PMLG5 mm $$\\bar{x}$$x and SAM3) were analyzed to maximize the performance of through-bond transfer based on decoupling efficiency as well as scaling factors. Indirect detection with assistance of PMLG m $$\\bar{x}$$ during INEPTR transfer proved to offer the highest sensitivity gains of 3-10. In addition, the CRAMPS sequence was applied under fast MAS to increase the 1H resolution during t 1 evolution in the traditional, 13C detected HETCOR scheme. Two naturally abundant solids, tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLF-OH) and brown coal, with well ordered and highly disordered structures, respectively, are studied to confirm the capabilities of these techniques. Concomitantly, a simple optimization of 1H homonuclear dipolar decoupling at MAS rates exceeding 10 kHz was developed (Chapter 4). The fine-tuned decoupling efficiency can be obtained by minimizing the signal loss due to transverse relaxation in a simple spin-echo experiment, using directly the sample of interest. The excellent agreement between observed decoupling pattern and earlier theoretical predictions confirmed the utility of this strategy. The properties of naturally abundant surface-bound fluorocarbon groups in mesoporous silica nanoparticles (MSNs) were investigated by the above-mentioned multidimensional solid-state NMR experiments and theoretical modeling (Chapter 5). Two conformations of (pentafluorophenyl)propyl groups (abbreviated as PFP) were determined as PFP-prone and PFP-upright, whose aromatic rings are located above the siloxane bridges and in roughly upright position, respectively. Several 1D and 2D NMR techniques were implemented in the characterizations, including indirectly detected 1H{l_brace} 13C{r_brace} and 19F{l_brace} 13C{r_brace} 2D HETCOR, Carr-Purcell-Meiboom-Gill (CPMG) assisted 29Si direct polarization and 29Si 19F 2D experiments, 2D double-quantum (DQ) 19F MAS NMR spectra and spin-echo measurements. Furthermore, conformational details of two types of PFP were confirmed by theoretical calculation, operated by Dr. Takeshi Kobayashi. Finally, the arrangement of two surfactants, cetyltrimetylammoium bromide (CTAB) and cetylpyridinium bromide (CPB), mixed inside the MSN pores, was studied by solid-state NMR (Chapter 6). By analyzing the 1H- 1H DQMAS and NOESY correlation spectra, the CTAB and CPB molecules were shown to co-exist inside the pores without forming significant monocomponent domains. A 'folded-over' conformation of CPB headgroups was proposed according to the results from 1H- 29Si 2D HETCOR.« less

A Review of Multidimensional, Multifluid Intermediate-scale Experiments: Flow Behavior, Saturation Imaging, and Tracer Detection and Quantification

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

Oostrom, Mart; Dane, J. H.; Wietsma, Thomas W.

2007-08-01

A review is presented of original multidimensional, intermediate-scale experiments involving non-aqueous phase liquid (NAPL) flow behavior, imaging, and detection/quantification with solute tracers. In a companion paper (Oostrom, M., J.H. Dane, and T.W. Wietsma. 2006. A review of multidimensional, multifluid intermediate-scale experiments: Nonaqueous phase dissolution and enhanced remediation. Vadose Zone Journal 5:570-598) experiments related to aqueous dissolution and enhanced remediation were discussed. The experiments investigating flow behavior include infiltration and redistribution experiments with both light and dense NAPLs in homogeneous and heterogeneous porous medium systems. The techniques used for NAPL saturation mapping for intermediate-scale experiments include photon-attenuation methods such as gammamore » and X-ray techniques, and photographic methods such as the light reflection, light transmission, and multispectral image analysis techniques. Solute tracer methods used for detection and quantification of NAPL in the subsurface are primarily limited to variations of techniques comparing the behavior of conservative and partitioning tracers. Besides a discussion of the experimental efforts, recommendations for future research at this laboratory scale are provided.« less

NMR spectroscopy of single sub-nL ova with inductive ultra-compact single-chip probes

PubMed Central

Grisi, Marco; Vincent, Franck; Volpe, Beatrice; Guidetti, Roberto; Harris, Nicola; Beck, Armin; Boero, Giovanni

2017-01-01

Nuclear magnetic resonance (NMR) spectroscopy enables non-invasive chemical studies of intact living matter. However, the use of NMR at the volume scale typical of microorganisms is hindered by sensitivity limitations, and experiments on single intact organisms have so far been limited to entities having volumes larger than 5 nL. Here we show NMR spectroscopy experiments conducted on single intact ova of 0.1 and 0.5 nL (i.e. 10 to 50 times smaller than previously achieved), thereby reaching the relevant volume scale where life development begins for a broad variety of organisms, humans included. Performing experiments with inductive ultra-compact (1 mm2) single-chip NMR probes, consisting of a low noise transceiver and a multilayer 150 μm planar microcoil, we demonstrate that the achieved limit of detection (about 5 pmol of 1H nuclei) is sufficient to detect endogenous compounds. Our findings suggest that single-chip probes are promising candidates to enable NMR-based study and selection of microscopic entities at biologically relevant volume scales. PMID:28317887

Enhanced efficiency of solid-state NMR investigations of energy materials using an external automatic tuning/matching (eATM) robot.

PubMed

Pecher, Oliver; Halat, David M; Lee, Jeongjae; Liu, Zigeng; Griffith, Kent J; Braun, Marco; Grey, Clare P

2017-02-01

We have developed and explored an external automatic tuning/matching (eATM) robot that can be attached to commercial and/or home-built magic angle spinning (MAS) or static nuclear magnetic resonance (NMR) probeheads. Complete synchronization and automation with Bruker and Tecmag spectrometers is ensured via transistor-transistor-logic (TTL) signals. The eATM robot enables an automated "on-the-fly" re-calibration of the radio frequency (rf) carrier frequency, which is beneficial whenever tuning/matching of the resonance circuit is required, e.g. variable temperature (VT) NMR, spin-echo mapping (variable offset cumulative spectroscopy, VOCS) and/or in situ NMR experiments of batteries. This allows a significant increase in efficiency for NMR experiments outside regular working hours (e.g. overnight) and, furthermore, enables measurements of quadrupolar nuclei which would not be possible in reasonable timeframes due to excessively large spectral widths. Additionally, different tuning/matching capacitor (and/or coil) settings for desired frequencies (e.g. 7 Li and 31 P at 117 and 122MHz, respectively, at 7.05 T) can be saved and made directly accessible before automatic tuning/matching, thus enabling automated measurements of multiple nuclei for one sample with no manual adjustment required by the user. We have applied this new eATM approach in static and MAS spin-echo mapping NMR experiments in different magnetic fields on four energy storage materials, namely: (1) paramagnetic 7 Li and 31 P MAS NMR (without manual recalibration) of the Li-ion battery cathode material LiFePO 4 ; (2) paramagnetic 17 O VT-NMR of the solid oxide fuel cell cathode material La 2 NiO 4+δ ; (3) broadband 93 Nb static NMR of the Li-ion battery material BNb 2 O 5 ; and (4) broadband static 127 I NMR of a potential Li-air battery product LiIO 3 . In each case, insight into local atomic structure and dynamics arises primarily from the highly broadened (1-25MHz) NMR lineshapes that the eATM robot is uniquely suited to collect. These new developments in automation of NMR experiments are likely to advance the application of in and ex situ NMR investigations to an ever-increasing range of energy storage materials and systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Enhanced efficiency of solid-state NMR investigations of energy materials using an external automatic tuning/matching (eATM) robot

NASA Astrophysics Data System (ADS)

Pecher, Oliver; Halat, David M.; Lee, Jeongjae; Liu, Zigeng; Griffith, Kent J.; Braun, Marco; Grey, Clare P.

2017-02-01

We have developed and explored an external automatic tuning/matching (eATM) robot that can be attached to commercial and/or home-built magic angle spinning (MAS) or static nuclear magnetic resonance (NMR) probeheads. Complete synchronization and automation with Bruker and Tecmag spectrometers is ensured via transistor-transistor-logic (TTL) signals. The eATM robot enables an automated "on-the-fly" re-calibration of the radio frequency (rf) carrier frequency, which is beneficial whenever tuning/matching of the resonance circuit is required, e.g. variable temperature (VT) NMR, spin-echo mapping (variable offset cumulative spectroscopy, VOCS) and/or in situ NMR experiments of batteries. This allows a significant increase in efficiency for NMR experiments outside regular working hours (e.g. overnight) and, furthermore, enables measurements of quadrupolar nuclei which would not be possible in reasonable timeframes due to excessively large spectral widths. Additionally, different tuning/matching capacitor (and/or coil) settings for desired frequencies (e.g.7Li and 31P at 117 and 122 MHz, respectively, at 7.05 T) can be saved and made directly accessible before automatic tuning/matching, thus enabling automated measurements of multiple nuclei for one sample with no manual adjustment required by the user. We have applied this new eATM approach in static and MAS spin-echo mapping NMR experiments in different magnetic fields on four energy storage materials, namely: (1) paramagnetic 7Li and 31P MAS NMR (without manual recalibration) of the Li-ion battery cathode material LiFePO4; (2) paramagnetic 17O VT-NMR of the solid oxide fuel cell cathode material La2NiO4+δ; (3) broadband 93Nb static NMR of the Li-ion battery material BNb2O5; and (4) broadband static 127I NMR of a potential Li-air battery product LiIO3. In each case, insight into local atomic structure and dynamics arises primarily from the highly broadened (1-25 MHz) NMR lineshapes that the eATM robot is uniquely suited to collect. These new developments in automation of NMR experiments are likely to advance the application of in and ex situ NMR investigations to an ever-increasing range of energy storage materials and systems.

Superoxygenated Water as an Experimental Sample for NMR Relaxometry

ERIC Educational Resources Information Center

Nestle, Nikolaus; Dakkouri, Marwan; Rauscher, Hubert

2004-01-01

The increase in NMR relaxation rates as a result of dissolved paramagnetic species on the sample of superoxygenated drinking water is demonstrated. It is concluded that oxygen content in NMR samples is an important issue and can give rise to various problems in the interpretation of both spectroscopic and NMR imaging or relaxation experiments.

Numerical simulation of NQR/NMR: Applications in quantum computing.

PubMed

Possa, Denimar; Gaudio, Anderson C; Freitas, Jair C C

2011-04-01

A numerical simulation program able to simulate nuclear quadrupole resonance (NQR) as well as nuclear magnetic resonance (NMR) experiments is presented, written using the Mathematica package, aiming especially applications in quantum computing. The program makes use of the interaction picture to compute the effect of the relevant nuclear spin interactions, without any assumption about the relative size of each interaction. This makes the program flexible and versatile, being useful in a wide range of experimental situations, going from NQR (at zero or under small applied magnetic field) to high-field NMR experiments. Some conditions specifically required for quantum computing applications are implemented in the program, such as the possibility of use of elliptically polarized radiofrequency and the inclusion of first- and second-order terms in the average Hamiltonian expansion. A number of examples dealing with simple NQR and quadrupole-perturbed NMR experiments are presented, along with the proposal of experiments to create quantum pseudopure states and logic gates using NQR. The program and the various application examples are freely available through the link http://www.profanderson.net/files/nmr_nqr.php. Copyright © 2011 Elsevier Inc. All rights reserved.

High-sensitivity NMR beyond 200,000 atmospheres of pressure

NASA Astrophysics Data System (ADS)

Meier, T.; Reichardt, S.; Haase, J.

2015-08-01

Pressure-induced changes in the chemical or electronic structure of solids require pressures well into the Giga-Pascal (GPa) range due to the strong bonding. Anvil cell designs can reach such pressures, but their small and mostly inaccessible sample chamber has severely hampered NMR experiments in the past. With a new cell design that has a radio frequency (RF) micro-coil in the high pressure chamber, NMR experiments beyond 20 Giga-Pascal are reported for the first time. 1 H NMR of water shows sensitivity and resolution obtained with the cells, and 63 Cu NMR on a cuprate superconductor (YBa2Cu3O7-δ) demonstrates that single-crystals can be investigated, as well. 115 In NMR of the ternary chalcogenide AgInTe2 discovers an insulator-metal transition with shift and relaxation measurements. The pressure cells can be mounted easily on standard NMR probes that fit commercial wide-bore magnets with regular cryostats for field- and temperature-dependent measurements ready for many applications in physics and chemistry.

Alternating current circuit theory and pulsed NMR (Nuclear Magnetic Resonance)

NASA Astrophysics Data System (ADS)

Gerstein, B. C.

1987-06-01

Pulsed NMR, by definition, deals with time varying excitations. These excitations, supplied by resonant circuits which provide a pulse of radiofrequency (frequencies in the megahertz region) power to a resonant circuit containing, among other things, a coil of wire, or inductor, in which a sample under investigation is placed for purposes of the nuclear magnetic resonance experiment. There are therefore two features of the pulse NMR experiment. First is the fact that we have available a source of continuous wave (CW) alternating current at some angular frequency, omega, measured in radians per second. This source is generally supplied by an ultrastable device called a frequency synthesizer. The second feature of the pulsed NMR experiment is that the sample is not continuously irradiated, but a pulse of radiofrequency oscillation is applied to the sample. This report discusses alternating current theory, resonant circuits and the equipment used in this experiment.

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

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.

Use of NMR and NMR Prediction Software to Identify Components in Red Bull Energy Drinks

ERIC Educational Resources Information Center

Simpson, Andre J.; Shirzadi, Azadeh; Burrow, Timothy E.; Dicks, Andrew P.; Lefebvre, Brent; Corrin, Tricia

2009-01-01

A laboratory experiment designed as part of an upper-level undergraduate analytical chemistry course is described. Students investigate two popular soft drinks (Red Bull Energy Drink and sugar-free Red Bull Energy Drink) by NMR spectroscopy. With assistance of modern NMR prediction software they identify and quantify major components in each…

Trajectories of Change in University Students' General Views of Group Work Following One Single Group Assignment: Significance of Instructional Context and Multidimensional Aspects of Experience

ERIC Educational Resources Information Center

Wosnitza, Marold; Volet, Simone

2014-01-01

This paper examines how distinct trajectories of change in students' general views of group work over the duration of one single group assignment could be explained by multidimensional aspects of their experience and the overall instructional context. Science (336) and Education (377) students involved in a semester-long group assignment…

Selective observation of charge storing ions in supercapacitor electrode materials.

PubMed

Forse, Alexander C; Griffin, John M; Grey, Clare P

2018-02-01

Nuclear magnetic resonance (NMR) spectroscopy has emerged as a useful technique for probing the structure and dynamics of the electrode-electrolyte interface in supercapacitors, as ions inside the pores of the carbon electrodes can be studied separately from bulk electrolyte. However, in some cases spectral resolution can limit the information that can be obtained. In this study we address this issue by showing how cross polarisation (CP) NMR experiments can be used to selectively observe the in-pore ions in supercapacitor electrode materials. We do this by transferring magnetisation from 13 C nuclei in porous carbons to nearby nuclei in the cations ( 1 H) or anions ( 19 F) of an ionic liquid. Two-dimensional NMR experiments and CP kinetics measurements confirm that in-pore ions are located within Ångströms of sp 2 -hybridised carbon surfaces. Multinuclear NMR experiments hold promise for future NMR studies of supercapacitor systems where spectral resolution is limited. Copyright © 2017 University of Cambridge. Published by Elsevier Inc. All rights reserved.

An advanced NMR protocol for the structural characterization of aluminophosphate glasses.

PubMed

van Wüllen, Leo; Tricot, Grégory; Wegner, Sebastian

2007-10-01

In this work a combination of complementary advanced solid-state nuclear magnetic resonance (NMR) strategies is employed to analyse the network organization in aluminophosphate glasses to an unprecedented level of detailed insight. The combined results from MAS, MQMAS and (31)P-{(27)Al}-CP-heteronuclear correlation spectroscopy (HETCOR) NMR experiments allow for a detailed speciation of the different phosphate and aluminate species present in the glass. The interconnection of these local building units to an extended three-dimensional network is explored employing heteronuclear dipolar and scalar NMR approaches to quantify P-O-Al connectivity by (31)P{(27)Al}-heteronuclear multiple quantum coherence (HMQC), -rotational echo adiabatic passage double resonance (REAPDOR) and -HETCOR NMR as well as (27)Al{(31)P}-rotational echo double resonance (REDOR) NMR experiments, complemented by (31)P-2D-J-RESolved MAS NMR experiments to probe P-O-P connectivity utilizing the through bond scalar J-coupling. The combination of the results from the various NMR approaches enables us to not only quantify the phosphate units present in the glass but also to identify their respective structural environments within the three-dimensional network on a medium length scale employing a modified Q notation, Q(n)(m),(AlO)(x), where n denotes the number of connected tetrahedral phosphate, m gives the number of aluminate species connected to a central phosphate unit and x specifies the nature of the bonded aluminate species (i.e. 4, 5 or 6 coordinate aluminium).

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.

Assigning the NMR Spectrum of Glycidol: An Advanced Organic Chemistry Exercise

ERIC Educational Resources Information Center

Helms, Eric; Arpaia, Nicholas; Widener, Melissa

2007-01-01

Various one- and two-dimensional NMR experiments have been found to be extremely useful for assigning the proton and carbon NMR spectra of glycidol. The technique provides extremely valuable information aiding in the complete assignment of the peaks.

Quartz Crystal Temperature Sensor for MAS NMR

NASA Astrophysics Data System (ADS)

Simon, Gerald

1997-10-01

Quartz crystal temperature sensors (QCTS) were tested for the first time as wireless thermometers in NMR MAS rotors utilizing the NMR RF technique itself for exiting and receiving electro-mechanical quartz resonances. This new tool in MAS NMR has a high sensitivity, linearity, and precision. When compared to the frequently used calibration of the variable temperature in the NMR system by a solid state NMR chemical shift thermometer (CST), such as lead nitrate, QCTS shows a number of advantages. It is an inert thermometer in close contact with solid samples operating parallel to the NMR experiment. QCTS can be manufactured for any frequency to be near a NMR frequency of interest (typically 1 to 2 MHz below or above). Due to the strong response of the crystal, signal detection is possible without changing the tuning of the MAS probe. The NMR signal is not influenced due to the relative sharp crystal resonance, restricted excitation by finite pulses, high probeQvalues, and commonly used audio filters. The quadratic dependence of the temperature increase on spinning speed is the same for the QCTS and for the CST lead nitrate and is discussed in terms of frictional heat in accordance with the literature about lead nitrate and with the results of a simple rotor speed jump experiment with differently radial located lead nitrate in the rotor.

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

EASY: a simple tool for simultaneously removing background, deadtime and acoustic ringing in quantitative NMR spectroscopy--part I: basic principle and applications.

PubMed

Jaeger, Christian; Hemmann, Felix

2014-01-01

Elimination of Artifacts in NMR SpectroscopY (EASY) is a simple but very effective tool to remove simultaneously any real NMR probe background signal, any spectral distortions due to deadtime ringdown effects and -specifically- severe acoustic ringing artifacts in NMR spectra of low-gamma nuclei. EASY enables and maintains quantitative NMR (qNMR) as only a single pulse (preferably 90°) is used for data acquisition. After the acquisition of the first scan (it contains the wanted NMR signal and the background/deadtime/ringing artifacts) the same experiment is repeated immediately afterwards before the T1 waiting delay. This second scan contains only the background/deadtime/ringing parts. Hence, the simple difference of both yields clean NMR line shapes free of artefacts. In this Part I various examples for complete (1)H, (11)B, (13)C, (19)F probe background removal due to construction parts of the NMR probes are presented. Furthermore, (25)Mg EASY of Mg(OH)2 is presented and this example shows how extremely strong acoustic ringing can be suppressed (more than a factor of 200) such that phase and baseline correction for spectra acquired with a single pulse is no longer a problem. EASY is also a step towards deadtime-free data acquisition as these effects are also canceled completely. EASY can be combined with any other NMR experiment, including 2D NMR, if baseline distortions are a big problem. © 2013 Published by Elsevier Inc.

"Cooking the sample": radiofrequency induced heating during solid-state NMR experiments.

PubMed

d'Espinose de Lacaillerie, Jean-Baptiste; Jarry, Benjamin; Pascui, Ovidiu; Reichert, Detlef

2005-09-01

Dissipation of radiofrequency (RF) energy as heat during continuous wave decoupling in solid-state NMR experiment was examined outside the conventional realm of such phenomena. A significant temperature increase could occur while performing dynamic NMR measurements provided the sample contains polar molecules and the sequence calls for relatively long applications of RF power. It was shown that the methyl flip motion in dimethylsulfone (DMS) is activated by the decoupling RF energy conversion to heat during a CODEX pulse sequence. This introduced a significant bias in the correlation time-temperature dependency measurement used to obtain the activation energy of the motion. By investigating the dependency of the temperature increase in hydrated lead nitrate on experimental parameters during high-power decoupling one-pulse experiments, the mechanisms for the RF energy deposition was identified. The samples were heated due to dissipation of the energy absorbed by dielectric losses, a phenomenon commonly known as "microwave" heating. It was thus established that during solid-state NMR experiments at moderate B0 fields, RF heating could lead to the heating of samples containing polar molecules such as hydrated polymers and inorganic solids. In particular, this could result in systematic errors for slow dynamics measurements by solid-state NMR.

A theoretical case study of type I and type II beta-turns.

PubMed

Czinki, Eszter; Császár, Attila G; Perczel, András

2003-03-03

NMR chemical shielding anisotropy tensors have been computed by employing a medium size basis set and the GIAO-DFT(B3LYP) formalism of electronic structure theory for all of the atoms of type I and type II beta-turn models. The models contain all possible combinations of the amino acid residues Gly, Ala, Val, and Ser, with all possible side-chain orientations where applicable in a dipeptide. The several hundred structures investigated contain either constrained or optimized phi, psi, and chi dihedral angles. A statistical analysis of the resulting large database was performed and multidimensional (2D and 3D) chemical-shift/chemical-shift plots were generated. The (1)H(alpha-13)C(alpha), (13)C(alpha-1)H(alpha-13)C(beta), and (13)C(alpha-1)H(alpha-13)C' 2D and 3D plots have the notable feature that the conformers clearly cluster in distinct regions. This allows straightforward identification of the backbone and side-chain conformations of the residues forming beta-turns. Chemical shift calculations on larger For-(L-Ala)(n)-NH(2) (n=4, 6, 8) models, containing a single type I or type II beta-turn, prove that the simple models employed are adequate. A limited number of chemical shift calculations performed at the highly correlated CCSD(T) level prove the adequacy of the computational method chosen. For all nuclei, statistically averaged theoretical and experimental shifts taken from the BioMagnetic Resonance Bank (BMRB) exhibit good correlation. These results confirm and extend our previous findings that chemical shift information from selected multiple-pulse NMR experiments could be employed directly to extract folding information for polypeptides and proteins.

NMR analysis of a kinetically trapped intermediate of a disulfide-deficient mutant of the starch-binding domain of glucoamylase.

PubMed

Sugimoto, Hayuki; Noda, Yasuo; Segawa, Shin-ichi

2011-09-16

A thermally unfolded disulfide-deficient mutant of the starch-binding domain of glucoamylase refolds into a kinetically trapped metastable intermediate when subjected to a rapid lowering of temperature. We attempted to characterise this intermediate using multidimensional NMR spectroscopy. The (1)H-(15)N heteronuclear single quantum coherence spectrum after a rapid temperature decrease (the spectrum of the intermediate) showed good chemical shift dispersion but was significantly different from that of the native state, suggesting that the intermediate adopts a nonnative but well-structured conformation. Large chemical shift changes for the backbone amide protons between the native and the intermediate states were observed for residues in the β-sheet consisting of strands 2, 3, 5, 6, and 7 as well as in the C-terminal region. These residues were found to be in close proximity to aromatic residues, suggesting that the chemical shift changes are mainly due to ring current shifts caused by the aromatic residues. The two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy experiments showed that the intermediate contained substantial, native-like NOE connectivities, although there were fewer cross peaks in the spectrum of the intermediate compared with that of the native state. It was also shown that there were native-like interresidue NOEs for residues buried in the protein, whereas many of the NOE cross peaks were lost for the residues involved in a surface-exposed aromatic cluster. These results suggest that, in the intermediate, the aromatic cluster at the surface is structurally less organised, whereas the interior of the protein has relatively rigid, native-like side-chain packing. Copyright © 2011 Elsevier Ltd. All rights reserved.

A new window towards multidimensional sensing of transition metal cations through dual mode sensing ability of N-benzyl-(3-hydoxy-2-naphthalene): Emission enhancement coupled remarkable spectral shift

NASA Astrophysics Data System (ADS)

Paul, Bijan Kumar; Mahanta, Subrata; Singh, Rupashree Balia; Guchhait, Nikhil

2011-06-01

A structurally simple Schiff base N-benzyl-(3-hydroxy-2-naphthalene) (NBHN32) has been synthesized and characterized by 1H NMR, 13C NMR, and DEPT spectroscopy. The photophysical behaviour of NBHN32 in response to the presence of various transition metal cations has been explored by means of steady-state absorption, emission and time-resolved emission spectroscopy techniques. Efficient through space intramolecular photoinduced electron transfer (PET) between the naphthalene fluorophore and the imine group has been argued for extremely low fluorescence yield of NBHN32 compared to the parent molecule 3-hydroxy-2-naphthaldehyde (HN32) containing the same fluorophore but lacking the receptor moiety. Transition metal ion-induced emission enhancement is thus addressed on the lexicon of perturbation of the PET by the metal ions. Apart from fluorescence enhancement, transition metal ion imparts remarkable shift of the emission maxima of NBHN32, which is another unique aspect on the proposed ability of NBHN32 to function as a fluorescence chemosensor.

High-sensitivity NMR beyond 200,000 atmospheres of pressure.

PubMed

Meier, T; Reichardt, S; Haase, J

2015-08-01

Pressure-induced changes in the chemical or electronic structure of solids require pressures well into the Giga-Pascal (GPa) range due to the strong bonding. Anvil cell designs can reach such pressures, but their small and mostly inaccessible sample chamber has severely hampered NMR experiments in the past. With a new cell design that has a radio frequency (RF) micro-coil in the high pressure chamber, NMR experiments beyond 20 Giga-Pascal are reported for the first time. (1)H NMR of water shows sensitivity and resolution obtained with the cells, and (63)Cu NMR on a cuprate superconductor (YBa2Cu3O7-δ) demonstrates that single-crystals can be investigated, as well. (115)In NMR of the ternary chalcogenide AgInTe2 discovers an insulator-metal transition with shift and relaxation measurements. The pressure cells can be mounted easily on standard NMR probes that fit commercial wide-bore magnets with regular cryostats for field- and temperature-dependent measurements ready for many applications in physics and chemistry. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of Solution Viscosity via Diffusion-Ordered NMR Spectroscopy (DOSY)

ERIC Educational Resources Information Center

Li, Weibin; Kagan, Gerald; Hopson, Russell; Williard, Paul G.

2011-01-01

Increasingly, the undergraduate chemistry curriculum includes nuclear magnetic resonance (NMR) spectroscopy. Advanced NMR techniques are often taught including two-dimensional gradient-based experiments. An investigation of intermolecular forces including viscosity, by a variety of methods, is often integrated in the undergraduate physical and…

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.

Imidazole as a pH Probe: An NMR Experiment for the General Chemistry Laboratory

ERIC Educational Resources Information Center

Hagan, William J., Jr.; Edie, Dennis L.; Cooley, Linda B.

2007-01-01

The analysis describes an NMR experiment for the general chemistry laboratory, which employs an unknown imidazole solution to measure the pH values. The described mechanism can also be used for measuring the acidity within the isolated cells.

Cation Hydration Constants by Proton NMR: A Physical Chemistry Experiment.

ERIC Educational Resources Information Center

Smith, Robert L.; And Others

1988-01-01

Studies the polarization effect on water by cations and anions. Describes an experiment to illustrate the polarization effect of sodium, lithium, calcium, and strontium ions on the water molecule in the hydration spheres of the ions. Analysis is performed by proton NMR. (MVL)

ODIN-object-oriented development interface for NMR.

PubMed

Jochimsen, Thies H; von Mengershausen, Michael

2004-09-01

A cross-platform development environment for nuclear magnetic resonance (NMR) experiments is presented. It allows rapid prototyping of new pulse sequences and provides a common programming interface for different system types. With this object-oriented interface implemented in C++, the programmer is capable of writing applications to control an experiment that can be executed on different measurement devices, even from different manufacturers, without the need to modify the source code. Due to the clear design of the software, new pulse sequences can be created, tested, and executed within a short time. To post-process the acquired data, an interface to well-known numerical libraries is part of the framework. This allows a transparent integration of the data processing instructions into the measurement module. The software focuses mainly on NMR imaging, but can also be used with limitations for spectroscopic experiments. To demonstrate the capabilities of the framework, results of the same experiment, carried out on two NMR imaging systems from different manufacturers are shown and compared with the results of a simulation.

Conformationally selective multidimensional chemical shift ranges in proteins from a PACSY database purged using intrinsic quality criteria

PubMed Central

Hong, Mei

2016-01-01

We have determined refined multidimensional chemical shift ranges for intra-residue correlations (13C–13C, 15N–13C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 13C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited “hand-picked” data sets, we show that ~94 % of the 13C NMR data and almost all 15N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6 % of the 13C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. −2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra-residue cross peaks by inspection or by using a provided command-line Python script (PLUQin), which should be useful in protein structure determination. The refined chemical shift distributions are utilized in a simple quality test (SQAT) that should be applied to new protein NMR data before deposition in a databank, and they could benefit many other chemical-shift based tools. PMID:26787537

Bringing NMR and IR Spectroscopy to High Schools

ERIC Educational Resources Information Center

Bonjour, Jessica L.; Hass, Alisa L.; Pollock, David W.; Huebner, Aaron; Frost, John A.

2017-01-01

Development of benchtop, portable Fourier transform nuclear magnetic resonance (NMR) and infrared (IR) spectrometers has opened up opportunities for creating university-high school partnerships that provide high school students with hands-on experience with NMR and IR instruments. With recent changes to the international baccalaureate chemistry…

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

NASA Astrophysics Data System (ADS)

Prasad, M.; Livo, K.

2017-12-01

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

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

Effects of radiation damping for biomolecular NMR experiments in solution: a hemisphere concept for water suppression

PubMed Central

Ishima, Rieko

2016-01-01

Abundant solvent nuclear spins, such as water protons in aqueous solution, cause radiation damping in NMR experiments. It is important to know how the effect of radiation damping appears in high-resolution protein NMR because macromolecular studies always require very high magnetic field strengths with a highly sensitive NMR probe that can easily cause radiation damping. Here, we show the behavior of water magnetization after a pulsed-field gradient (PFG) using nutation experiments at 900 MHz with a cryogenic probe: when water magnetization is located in the upper hemisphere (having +Z component, parallel to the external magnetic field), dephasing of the magnetization by a PFG effectively suppresses residual water magnetization in the transverse plane. In contrast, when magnetization is located in the lower hemisphere (having −Z component), the small residual transverse component remaining after a PFG is still sufficient to induce radiation damping. Based on this observation, we designed 1H-15N HSQC experiments in which water magnetization is maintained in the upper hemisphere, but not necessarily along Z, and compared them with the conventional experiments, in which water magnetization is inverted during the t1 period. The result demonstrates moderate gain of signal-to-noise ratio, 0–28%. Designing the experiments such that water magnetization is maintained in the upper hemisphere allows shorter pulses to be used compared to the complete water flip-back and, thereby, is useful as a building block of protein NMR pulse programs in solution. PMID:27524944

A NMR experiment for simultaneous correlations of valine and leucine/isoleucine methyls with carbonyl chemical shifts in proteins.

PubMed

Tugarinov, Vitali; Venditti, Vincenzo; Marius Clore, G

2014-01-01

A methyl-detected 'out-and-back' NMR experiment for obtaining simultaneous correlations of methyl resonances of valine and isoleucine/leucine residues with backbone carbonyl chemical shifts, SIM-HMCM(CGCBCA)CO, is described. The developed pulse-scheme serves the purpose of convenience in recording a single data set for all Ile(δ1), Leu(δ) and Val(γ) (ILV) methyl positions instead of acquiring two separate spectra selective for valine or leucine/isoleucine residues. The SIM-HMCM(CGCBCA)CO experiment can be used for ILV methyl assignments in moderately sized protein systems (up to ~100 kDa) where the backbone chemical shifts of (13)C(α), (13)Cβ and (13)CO are known from prior NMR studies and where some losses in sensitivity can be tolerated for the sake of an overall reduction in NMR acquisition time.

The Impact of Learner Characteristics on the Multi-Dimensional Construct of Social Presence

ERIC Educational Resources Information Center

Mykota, David

2017-01-01

This study explored the impact of learner characteristics on the multi-dimensional construct of social presence as measured by the computer-mediated communication questionnaire. Using Multiple Analysis of Variance findings reveal that the number of online courses taken and computer-mediated communication experience significantly affect the…

The Effects of Verbal Pretraining on the Multidimensional Generalization Behavior of Children

ERIC Educational Resources Information Center

Spiker, Charles C.; And Others

1972-01-01

Predictions for multidimensional generalization were derived from Hull-Spence learning theory, and an experiment is reported that was designed to test this aspect of the theory. Alternative to this analysis is presented in PS 502 062; authors respond in PS 502 063. (Authors/MB)

Monitoring an Induced Permafrost Warming Experiment Using ERT, Temperature, and NMR in Fairbanks, Alaska

NASA Astrophysics Data System (ADS)

Ulrich, C.; Ajo Franklin, J. B.; Ekblaw, I.; Lindsey, N.; Wagner, A. M.; Saari, S.; Daley, T. M.; Freifeld, B. M.

2016-12-01

As global temperatures continue to rise, permafrost landscapes will experience more rapid changes than other global climate zones. Permafrost thaw is a result of increased temperatures in arctic settings resulting in surface deformation and subsurface hydrology changes. From an engineering perspective, surface deformation poses a threat to the stability of existing infrastructure such as roads, utility piping, and building structures. Preemptively detecting or monitoring subsurface thaw dynamics presents a difficult challenge due to the long time scales as deformation occurs. Increased subsurface moisture content results from permafrost thaw of which electrical resistivity tomography (ERT), soil temperature, and nuclear magnetic resonance (NMR) are directly sensitive. In this experiment we evaluate spatial and temporal changes in subsurface permafrost conditions (moisture content and temperature) at a experimental heating plot in Fairbanks, AK. This study focuses on monitoring thaw signatures using multiple collocated electrical resistivity (ERT), borehole temperature, and borehole nuclear magnetic resonance (NMR) measurements. Timelapse ERT (sensitive to changes in moisture content) was inverted using collocated temperature and NMR to constrain ERT inversions. Subsurface thermal state was monitored with timelapse thermistors, sensitive to soil ice content. NMR was collected in multiple boreholes and is sensitive to changes in moisture content and pore scale distribution. As permafrost thaws more hydrogen, in the form of water, is available resulting in a changing NMR response. NMR requires the availability of liquid water in order to induce spin of the hydrogen molecule, hence, if frozen water molecules will be undetectable. In this study, the permafrost is poised close to 0oC and is mainly silt with small pore dimensions; this combination makes NMR particularly useful due to the possibility of sub-zero thaw conditions within the soil column. Overall this experiment presents a complementary suite of methods that provides feedback on subsurface permafrost state even in cases where soil texture might control unfrozen water content.

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 NMR to Expand Chemistry Research and Educational Experiences at North Carolina Central University, an Historically Black University

DTIC Science & Technology

analytical chemistry . Most students do not get hands-on training with an NMR within their classroom or laboratory courses. The NMR will provide...unique opportunities to our students as they train to become the next generation of scientists, doctors, and engineers .

An Integrated Laboratory Project in NMR Spectroscopy.

ERIC Educational Resources Information Center

Hudson, Reggie L.; Pendley, Bradford D.

1988-01-01

Describes an advanced NMR project that can be done with a 60-MHz continuous-wave proton spectrometer. Points out the main purposes are to give students experience in second-order NMR analysis, the simplification of spectra by raising the frequency, and the effect of non-hydrogen nuclei on proton resonances. (MVL)

On the use of ultracentrifugal devices for routine sample preparation in biomolecular magic-angle-spinning NMR

PubMed Central

Mandal, Abhishek; Boatz, Jennifer C.; Wheeler, Travis; van der Wel, Patrick C. A.

2017-01-01

A number of recent advances in the field of magic-angle-spinning (MAS) solid-state NMR have enabled its application to a range of biological systems of ever increasing complexity. To retain biological relevance, these samples are increasingly studied in a hydrated state. At the same time, experimental feasibility requires the sample preparation process to attain a high sample concentration within the final MAS rotor. We discuss these considerations, and how they have led to a number of different approaches to MAS NMR sample preparation. We describe our experience of how custom-made (or commercially available) ultracentrifugal devices can facilitate a simple, fast and reliable sample preparation process. A number of groups have since adopted such tools, in some cases to prepare samples for sedimentation-style MAS NMR experiments. Here we argue for a more widespread adoption of their use for routine MAS NMR sample preparation. PMID:28229262

Trispyrazolylborate Complexes: An Advanced Synthesis Experiment Using Paramagnetic NMR, Variable-Temperature NMR, and EPR Spectroscopies

ERIC Educational Resources Information Center

Abell, Timothy N.; McCarrick, Robert M.; Bretz, Stacey Lowery; Tierney, David L.

2017-01-01

A structured inquiry experiment for inorganic synthesis has been developed to introduce undergraduate students to advanced spectroscopic techniques including paramagnetic nuclear magnetic resonance and electron paramagnetic resonance. Students synthesize multiple complexes with unknown first row transition metals and identify the unknown metals by…

Lost in space: design of experiments and scientific exploration in a Hogarth Universe.

PubMed

Lendrem, Dennis W; Lendrem, B Clare; Woods, David; Rowland-Jones, Ruth; Burke, Matthew; Chatfield, Marion; Isaacs, John D; Owen, Martin R

2015-11-01

A Hogarth, or 'wicked', universe is an irregular environment generating data to support erroneous beliefs. Here, we argue that development scientists often work in such a universe. We demonstrate that exploring these multidimensional spaces using small experiments guided by scientific intuition alone, gives rise to an illusion of validity and a misplaced confidence in that scientific intuition. By contrast, design of experiments (DOE) permits the efficient mapping of such complex, multidimensional spaces. We describe simulation tools that enable research scientists to explore these spaces in relative safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

A complete 1H and 13C NMR data assignment for the diterpene methyl (-)-zanzibarate by 2D spectroscopy and NOE experiments.

PubMed

Imamura, P M; Miranda, P C M L; Giacomini, R A

2004-06-01

The 1H and 13C NMR spectra of methyl (-)-zanzibarate (1), an ent-labdanic diterpene isolated from the epicarp of Hymenaea courbaril var. altissima (Leguminosaea, Cesalpinoideae, Detariae), was fully assigned by COSY experiments, 13C/1H shift correlation diagrams and NOE experiments. Copyright 2004 John Wiley & Sons, Ltd.

Diels-Alder Cycloadditions: A MORE Experiment in the Organic Laboratory Including a Diene Identification Exercise Involving NMR Spectroscopy and Molecular Modeling

ERIC Educational Resources Information Center

Shaw, Roosevelt; Severin, Ashika; Balfour, Miguel; Nettles, Columbus

2005-01-01

Two Diels-Alder reactions are described that are suitable for a MORE (microwave-induced organic reaction enhanced) experiment in the organic chemistry laboratory course. A second experiment in which the splitting patterns of the vinyl protons in the nuclear magnetic resonance (NMR) spectra of two MORE adducts are used in conjunction with molecular…

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17). part 1: development and content validity.

PubMed

Morris, S; Li, Y; Smith, J A M; Dube', S; Burbridge, C; Symonds, T

2017-05-16

Fibromyalgia (FM), a disorder characterized by chronic widespread pain and tenderness, affects greater than five million individuals in the United States alone. Patients experience multiple symptoms in addition to pain, and among them, fatigue is one of the most bothersome and disabling. There is a growing body of literature suggesting that fatigue is a multidimensional concept. Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO) measure of FM-related fatigue meets Food and Drug Administration (FDA) requirements to support a product label claim. Therefore, the objective of this research was to evaluate qualitative and quantitative data previously gathered to inform the development of a comprehensive, multidimensional, PRO measure to assess FM-related fatigue in FM clinical trials. Existing qualitative and quantitative data from three previously conducted studies in patients with FM were reviewed to inform the initial development of a multidimensional PRO measure of FM-related fatigue: 1) a concept elicitation study involving in-depth, open-ended interviews with patients with FM in the United States (US) (N = 20), Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a methodology study that explored initial psychometrics of the item pool (N = 145 US patients with FM). Five domains were identified that intend to capture the broad experience of FM-related fatigue reported in the qualitative research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Seventeen of the original pool of 23 items were selected to best capture these five dimensions. These 17 items formed the basis of a newly developed multidimensional PRO measure to assess FM-related fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 (MDF-Fibro-17). Qualitative analysis, and preliminary quantitative item level data, confirmed that FM-related fatigue is multidimensional and provided strong support for the content validity of the MDF-Fibro-17. The next stage was to quantitatively evaluate the measure to confirm the factor structure, psychometric properties, sensitivity to change, and meaningful change. This has been conducted and is being reported separately.

NMR properties of 3He-A in biaxially anisotropic aerogel

NASA Astrophysics Data System (ADS)

Dmitriev, V. V.; Krasnikhin, D. A.; Senin, A. A.; Yudin, A. N.

2012-12-01

Theoretical model of G.E. Volovik for A-like phase of 3He in aerogel suggests formation of Larkin-Imry-Ma state of Anderson-Brinkmann-Morel order parameter. Most of results of NMR studies of A-like phase are in a good agreement with this model in assumption of uniaxial anisotropy, except for some of experiments in weakly anisotropic aerogel samples. We demonstrate that these results can be described in frames of the same model in assumption of biaxial anisotropy. Parameters of anisotropy in these experiments can be determined from the NMR data.

A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers

PubMed Central

Dubroca, Thierry; Smith, Adam N.; Pike, Kevin J.; Froud, Stuart; Wylde, Richard; Trociewitz, Bianca; McKay, Johannes; Mentink-Vigier, Frederic; van Tol, Johan; Wi, Sungsool; Brey, William; Long, Joanna R.; Frydman, Lucio; Hill, Stephen

2018-01-01

Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110 K, while a 31P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results have been produced with large sample volumes (~100 μL, i.e. 3 mm diameter NMR tubes). PMID:29459343

A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers

NASA Astrophysics Data System (ADS)

Dubroca, Thierry; Smith, Adam N.; Pike, Kevin J.; Froud, Stuart; Wylde, Richard; Trociewitz, Bianca; McKay, Johannes; Mentink-Vigier, Frederic; van Tol, Johan; Wi, Sungsool; Brey, William; Long, Joanna R.; Frydman, Lucio; Hill, Stephen

2018-04-01

Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110 K, while a 31P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results have been produced with large sample volumes (∼100 μL, i.e. 3 mm diameter NMR tubes).

A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers.

PubMed

Dubroca, Thierry; Smith, Adam N; Pike, Kevin J; Froud, Stuart; Wylde, Richard; Trociewitz, Bianca; McKay, Johannes; Mentink-Vigier, Frederic; van Tol, Johan; Wi, Sungsool; Brey, William; Long, Joanna R; Frydman, Lucio; Hill, Stephen

2018-04-01

Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T ( 1 H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13 C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110 K, while a 31 P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T ( 1 H 600 MHz). Moreover these results have been produced with large sample volumes (∼100 µL, i.e. 3 mm diameter NMR tubes). Copyright © 2018 Elsevier Inc. All rights reserved.

Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis.

PubMed

de Luca, Katie; Parkinson, Lynne; Downie, Aron; Blyth, Fiona; Byles, Julie

2017-03-01

The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio-demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis.

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…

An NMR Experiment Based on Off-the-Shelf Digital Data-Acquisition Equipment

ERIC Educational Resources Information Center

Hilty, Christian; Bowen, Sean

2010-01-01

Nuclear magnetic resonance (NMR) poses significant challenges for teaching in the context of an undergraduate laboratory, foremost because of high equipment cost. Current off-the-shelf data-acquisition hardware, however, is sufficiently powerful to constitute the core of a fully digital NMR spectrometer operating at the earth's field. We present…

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

PubMed

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

2012-09-07

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

A Multidimensional Approach to Examine Student Interdisciplinary Learning in Science and Engineering in Higher Education

ERIC Educational Resources Information Center

Spelt, Elisabeth Jacoba Hendrika; Luning, Pieternelleke Arianne; van Boekel, Martinus A. J. S.; Mulder, Martin

2017-01-01

Preparing science and engineering students to work in interdisciplinary teams necessitates research on teaching and learning of interdisciplinary thinking. A multidimensional approach was taken to examine student interdisciplinary learning in a master course on food quality management. The collected 615 student experiences were analysed for the…

Pain and symptom management in palliative care and at end of life.

PubMed

Wilkie, Diana J; Ezenwa, Miriam O

2012-01-01

The purpose of this review is to provide a literature update of the research published since 2004 on pain and symptom management in palliative care and at end of life. Findings suggest that pain and symptoms are inadequately assessed and managed, even at the end of life. Although not pervasive, there is evidence of racial/ethnic disparities in symptom management in palliative care and at end of life. There is a need for a broader conceptualization and measurement of pain and symptom management as multidimensional experiences. There is insufficient evidence about mechanisms underlying pain at end of life. Although there are advances in the knowledge of pain as a multidimensional experience and the many symptoms that occur sometimes with pain, gaps remain. One approach to addressing the gaps will involve assessment and management of pain and symptoms as multidimensional experiences in people receiving palliative care and at end of life. Copyright © 2012 Elsevier Inc. All rights reserved.

A ferromagnetic shim insert for NMR magnets - Towards an integrated gyrotron for DNP-NMR spectroscopy.

PubMed

Ryan, Herbert; van Bentum, Jan; Maly, Thorsten

2017-04-01

In recent years high-field Dynamic Nuclear Polarization (DNP) enhanced NMR spectroscopy has gained significant interest. In high-field DNP-NMR experiments (⩾400MHz 1 H NMR, ⩾9.4T) often a stand-alone gyrotron is used to generate high microwave/THz power to produce sufficiently high microwave induced B 1e fields at the position of the NMR sample. These devices typically require a second, stand-alone superconducting magnet to operate. Here we present the design and realization of a ferroshim insert, to create two iso-centers inside a commercially available wide-bore NMR magnet. This work is part of a larger project to integrate a gyrotron into NMR magnets, effectively eliminating the need for a second, stand-alone superconducting magnet. Copyright © 2017 Elsevier Inc. All rights reserved.

An NMR Study of Isotope Effect on Keto-Enol Tautomerization: A Physical Organic Chemistry Experiment

ERIC Educational Resources Information Center

Atkinson, D.; Chechik, V.

2004-01-01

Isotope substitution often affects the rate of an organic reaction and can be used to reveal the underlying mechanism. A series of experiments that use (super 1)H NMR to determine primary and secondary isotope effects, activation parameters, and the regioselectivity of butanone enolization are described.

NMR Determination of Hydrogen Bond Thermodynamics in a Simple Diamide: A Physical Chemistry Experiment

ERIC Educational Resources Information Center

Morton, Janine G.; Joe, Candice L.; Stolla, Massiel C.; Koshland, Sophia R.; Londergan, Casey H.; Schofield, Mark H.

2015-01-01

Variable temperature NMR spectroscopy is used to determine the ?H° and ?S° of hydrogen bond formation in a simple diamide. In this two- or three-day experiment, students synthesize N,N'-dimethylmalonamide, dimethylsuccinamide, dimethylglutaramide, or dimethyladipamide from methylamine and the corresponding diester (typically in 50% recrystallized…

The Complexation of the Na(super +) by 18-Crown-6 Studied via Nuclear Magnetic Resonance

ERIC Educational Resources Information Center

Peters, Steven J.; Stevenson, Cheryl D.

2004-01-01

A student friendly experiment that teaches several important concepts of modern nuclear magnetic resonance (NMR), like multinuclear capabilities, the NMR time scale, and time-averaged signals, is described along with some important concepts of thermo chemical equilibria. The mentioned experiment involves safe and inexpensive compounds, such as…

Using Nuclear Magnetic Resonance Spectroscopy for Measuring Ternary Phase Diagrams

ERIC Educational Resources Information Center

Woodworth, Jennifer K.; Terrance, Jacob C.; Hoffmann, Markus M.

2006-01-01

A laboratory experiment is presented for the upper-level undergraduate physical chemistry curriculum in which the ternary phase diagram of water, 1-propanol and n-heptane is measured using proton nuclear magnetic resonance (NMR) spectroscopy. The experiment builds upon basic concepts of NMR spectral analysis, typically taught in the undergraduate…

A complete vibrational study on a potential environmental toxicant agent, the 3,3',4,4'-tetrachloroazobenzene combining the FTIR, FTRaman, UV-Visible and NMR spectroscopies with DFT calculations.

PubMed

Castillo, María V; Pergomet, Jorgelina L; Carnavale, Gustavo A; Davies, Lilian; Zinczuk, Juan; Brandán, Silvia A

2015-01-05

In this study 3,3',4,4'-tetrachloroazobenzene (TCAB) was prepared and then characterized by infrared, Raman, multidimensional nuclear magnetic resonance (NMR) and ultraviolet-visible spectroscopies. The density functional theory (DFT) together with the 6-31G(*) and 6-311++G(**) basis sets were used to study the structures and vibrational properties of the two cis and trans isomers of TCAB. The harmonic vibrational wavenumbers for the optimized geometries were calculated at the same theory levels. A complete assignment of all the observed bands in the vibrational spectra of TCAB was performed combining the DFT calculations with the scaled quantum mechanical force field (SQMFF) methodology. The molecular electrostatic potentials, atomic charges, bond orders and frontier orbitals for the two isomers of TCAB were compared and analyzed. The comparison of the theoretical ultraviolet-visible spectrum with the corresponding experimental demonstrates a good concordance while the calculated (1)H and (13)C chemicals shifts are in good conformity with the corresponding experimental NMR spectra of TCAB in solution. The npp(*) transitions for both forms were studied by natural bond orbital (NBO) while the topological properties were calculated by employing Bader's Atoms in the Molecules (AIM) theory. This study shows that the cis and trans isomers exhibit different structural and vibrational properties and absorption bands. Copyright © 2014. Published by Elsevier B.V.

Recent progress in heteronuclear long-range NMR of complex carbohydrates: 3D H2BC and clean HMBC.

PubMed

Meier, Sebastian; Petersen, Bent O; Duus, Jens Ø; Sørensen, Ole W

2009-11-02

The new NMR experiments 3D H2BC and clean HMBC are explored for challenging applications to a complex carbohydrate at natural abundance of (13)C. The 3D H2BC experiment is crucial for sequential assignment as it yields heteronuclear one- and two-bond together with COSY correlations for the (1)H spins, all in a single spectrum with good resolution and non-informative diagonal-type peaks suppressed. Clean HMBC is a remedy for the ubiquitous problem of strong coupling induced one-bond correlation artifacts in HMBC spectra of carbohydrates. Both experiments work well for one of the largest carbohydrates whose structure has been determined by NMR, not least due to the enhanced resolution offered by the third dimension in 3D H2BC and the improved spectral quality due to artifact suppression in clean HMBC. Hence these new experiments set the scene to take advantage of the sensitivity boost achieved by the latest generation of cold probes for NMR structure determination of even larger and more complex carbohydrates in solution.

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.

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.

Determination of Solvent Effects on Keto-Enol Equilibria of 1,3-Dicarbonyl Compounds Using NMR: Revisiting a Classic Physical Chemistry Experiment

ERIC Educational Resources Information Center

Cook, A. Gilbert; Feltman, Paul M.

2007-01-01

The use of proton NMR to determine the equilibrium position of tautomeric 1,3-dicarbonyl compounds in various solvents has been a classic physical chemistry experiment. We are presenting an expansion of the excellent description of this experiment by Garland, Shoemaker, and Nibler. Often the assumption is made that the keto tautomer is always the…

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.

Evaluation of protein adsorption and preferred binding regions in multimodal chromatography using NMR

PubMed Central

Chung, Wai Keen; Freed, Alexander S.; Holstein, Melissa A.; McCallum, Scott A.; Cramer, Steven M.

2010-01-01

NMR titration experiments with labeled human ubiquitin were employed in concert with chromatographic data obtained with a library of ubiquitin mutants to study the nature of protein adsorption in multimodal (MM) chromatography. The elution order of the mutants on the MM resin was significantly different from that obtained by ion-exchange chromatography. Further, the chromatographic results with the protein library indicated that mutations in a defined region induced greater changes in protein affinity to the solid support. Chemical shift mapping and determination of dissociation constants from NMR titration experiments with the MM ligand and isotopically enriched ubiquitin were used to determine and rank the relative binding affinities of interaction sites on the protein surface. The results with NMR confirmed that the protein possessed a distinct preferred binding region for the MM ligand in agreement with the chromatographic results. Finally, coarse-grained ligand docking simulations were employed to study the modes of interaction between the MM ligand and ubiquitin. The use of NMR titration experiments in concert with chromatographic data obtained with protein libraries represents a previously undescribed approach for elucidating the structural basis of protein binding affinity in MM chromatographic systems. PMID:20837551

Observation of NMR noise from solid samples.

PubMed

Schlagnitweit, Judith; Dumez, Jean-Nicolas; Nausner, Martin; Jerschow, Alexej; Elena-Herrmann, Bénédicte; Müller, Norbert

2010-11-01

We demonstrate that proton NMR noise signals, i.e. NMR spectra without excitation by radio frequency, can be obtained from solid samples. Experimental results are shown for static and magic-angle spinning conditions. In addition, a tuning procedure based on the probes' NMR noise characteristics and similar to the one described previously for liquids probes can also be used to optimize signal-to-noise ratios in ¹H-MAS experiments. Copyright © 2010 Elsevier Inc. All rights reserved.

Mechanistic insight into formation and changes of nanoparticles in MgF2 sols evidenced by liquid and solid state NMR.

PubMed

Karg, M; Scholz, G; König, R; Kemnitz, E

2012-02-28

The fluorolytic sol-gel reaction of magnesium methoxide with HF in methanol was studied by (19)F, (1)H and (13)C liquid and solid state NMR. In (19)F NMR five different species were identified, three of which belong to magnesium fluoride nanoparticles, i.e. NMR gave access to local structures of solid particles in suspensions. The long-term evolution of (19)F signals was followed and along with (19)F MAS NMR experiments of sols rotating at 13 kHz mechanistic insights into the ageing processes were obtained.

Identification and MS-assisted interpretation of genetically influenced NMR signals in human plasma

PubMed Central

2013-01-01

Nuclear magnetic resonance spectroscopy (NMR) provides robust readouts of many metabolic parameters in one experiment. However, identification of clinically relevant markers in 1H NMR spectra is a major challenge. Association of NMR-derived quantities with genetic variants can uncover biologically relevant metabolic traits. Using NMR data of plasma samples from 1,757 individuals from the KORA study together with 655,658 genetic variants, we show that ratios between NMR intensities at two chemical shift positions can provide informative and robust biomarkers. We report seven loci of genetic association with NMR-derived traits (APOA1, CETP, CPS1, GCKR, FADS1, LIPC, PYROXD2) and characterize these traits biochemically using mass spectrometry. These ratios may now be used in clinical studies. PMID:23414815

Characterizing slow chemical exchange in nucleic acids by carbon CEST and low spin-lock field R(1ρ) NMR spectroscopy.

PubMed

Zhao, Bo; Hansen, Alexandar L; Zhang, Qi

2014-01-08

Quantitative characterization of dynamic exchange between various conformational states provides essential insights into the molecular basis of many regulatory RNA functions. Here, we present an application of nucleic-acid-optimized carbon chemical exchange saturation transfer (CEST) and low spin-lock field R(1ρ) relaxation dispersion (RD) NMR experiments in characterizing slow chemical exchange in nucleic acids that is otherwise difficult if not impossible to be quantified by the ZZ-exchange NMR experiment. We demonstrated the application on a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and R(1ρ) RD profiles of base and sugar carbons revealed slow exchange dynamics involving a sparsely populated (p ~ 10%) and shortly lived (τ ~ 10 ms) NMR "invisible" state. The utility of CEST and low spin-lock field R(1ρ) RD experiments in studying slow exchange was further validated in characterizing an exchange as slow as ~60 s(-1).

Characterizing Slow Chemical Exchange in Nucleic Acids by Carbon CEST and Low Spin-Lock Field R1ρ NMR Spectroscopy

PubMed Central

Zhao, Bo; Hansen, Alexandar L.; Zhang, Qi

2016-01-01

Quantitative characterization of dynamic exchange between various conformational states provides essential insights into the molecular basis of many regulatory RNA functions. Here, we present an application of nucleic-acid-optimized carbon chemical exchange saturation transfer (CEST) and low spin-lock field R1ρ relaxation dispersion (RD) NMR experiments in characterizing slow chemical exchange in nucleic acids that is otherwise difficult if not impossible to be quantified by the ZZ-exchange NMR experiment. We demonstrated the application on a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and R1ρ RD profiles of base and sugar carbons revealed slow exchange dynamics involving a sparsely populated (p ~ 10%) and shortly lived (τ ~ 10 ms) NMR “invisible” state. The utility of CEST and low spin-lock field R1ρ RD experiments in studying slow exchange was further validated in characterizing an exchange as slow as ~60 s−1. PMID:24299272

Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

PubMed Central

Ling, C. R.; Foster, M. A.; Mallard, J. R.

1979-01-01

In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered. PMID:526431

Dynamic Nuclear Polarization-Enhanced Biomolecular NMR Spectroscopy at High Magnetic Field with Fast Magic-Angle Spinning.

PubMed

Jaudzems, Kristaps; Bertarello, Andrea; Chaudhari, Sachin R; Pica, Andrea; Cala-De Paepe, Diane; Barbet-Massin, Emeline; Pell, Andrew J; Akopjana, Inara; Kotelovica, Svetlana; Gajan, David; Ouari, Olivier; Tars, Kaspars; Pintacuda, Guido; Lesage, Anne

2018-06-18

Dynamic nuclear polarization (DNP) is a powerful way to overcome the sensitivity limitation of magic-angle-spinning (MAS) NMR experiments. However, the resolution of the DNP NMR spectra of proteins is compromised by severe line broadening associated with the necessity to perform experiments at cryogenic temperatures and in the presence of paramagnetic radicals. High-quality DNP-enhanced NMR spectra of the Acinetobacter phage 205 (AP205) nucleocapsid can be obtained by combining high magnetic field (800 MHz) and fast MAS (40 kHz). These conditions yield enhanced resolution and long coherence lifetimes allowing the acquisition of resolved 2D correlation spectra and of previously unfeasible scalar-based experiments. This enables the assignment of aromatic resonances of the AP205 coat protein and its packaged RNA, as well as the detection of long-range contacts, which are not observed at room temperature, opening new possibilities for structure determination. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

ERIC Educational Resources Information Center

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

2017-01-01

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

Analysis of Bromination of Ethylbenzene Using a 45 MHz NMR Spectrometer: An Undergraduate Organic Chemistry Laboratory Experiment

ERIC Educational Resources Information Center

Isaac-Lam, Meden F.

2014-01-01

A 45 MHz benchtop NMR spectrometer is used to identify the structures and determine the amount of 1-bromoethylbenzene and 1,1-dibromoethylbenzene produced from free-radical bromination of ethylbenzene. The experiment is designed for nonchemistry majors, specifically B.S. Biology students, in a predominantly undergraduate institution with…

Five Evils: Multidimensional Poverty and Race in America

ERIC Educational Resources Information Center

Reeves, Richard; Rodrigue, Edward; Kneebone, Elizabeth

2016-01-01

Poverty is about a lack of money, but it's not only about that. As a lived experience, poverty is also characterized by ill health, insecurity, discomfort, isolation, and more. To put it another way: Poverty is multidimensional, and its dimensions often cluster together to intensify the negative effects of being poor. In this first of a two-part…

Friendship Group Identification, Multidimensional Self-Concept, and Experience of Developmental Tasks in Adolescence

ERIC Educational Resources Information Center

Tarrant, Mark; MacKenzie, Liam; Hewitt, Lisa A.

2006-01-01

This study applied a social identity perspective to the study of adolescent self-concept and social development. British adolescents aged 14-15 years (N=114) completed a questionnaire which asked them to: (i) rate their degree of identification with a school-based friendship group; (ii) complete a measure of multi-dimensional self-concept; and…

The Multidimensionality of Calling: Conceptualization, Measurement and a Bicultural Perspective

ERIC Educational Resources Information Center

Hagmaier, Tamara; Abele, Andrea E.

2012-01-01

The experience of a calling may be seen as the ultimate form of subjective career success that has many positive consequences for individuals and organizations. We are here concerned with the conceptualization of a new multidimensional measure of calling, the MCM. In the first two studies we employed a qualitative approach and came up with five…

Double cross-polarization MAS NMR in the assignment of abundant-spin resonances: ¹⁹F-{²⁹Si}-¹⁹F FBCP/MAS NMR of fluoride ions incorporated in calcium silicate hydrate (C-S-H) phases.

PubMed

Tran, Thuan T; Bildsøe, Henrik; Jakobsen, Hans J; Skibsted, Jørgen

2012-08-01

A new version of the double cross-polarization MAS NMR experiment, which transfers polarization Forth and Back (FBCP) between high- and low-γ spin nuclei, is presented. The pulse sequence is demonstrated by ¹⁹F-{²⁹Si}-¹⁹F and ¹⁹F-{¹³C}-¹⁹F FBCP NMR spectra of a mixture of cuspidine (Ca₄Si₂O₇F₂) and Teflon (-CF₂-)(n). The experiment is useful for assignment of the high-γ spin resonances, as demonstrated by ¹⁹F-{²⁹Si}-¹⁹F FBCP NMR of a fluoride-containing calcium-silicate-hydrate (C-S-H) phase, where the ¹⁹F resonance from fluoride ions incorporated in the interlayer structure of the C-S-H phase is identified. Copyright © 2012 Elsevier Inc. All rights reserved.

NMR reaction monitoring in flow synthesis

PubMed Central

Gomez, M Victoria

2017-01-01

Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is reviewed. Some recent selected applications have been collected, including synthetic applications, the determination of the kinetic and thermodynamic parameters and reaction optimization, even in single experiments and on the μL scale. Finally, software that allows automatic reaction monitoring and optimization is discussed. PMID:28326137

NMR reaction monitoring in flow synthesis.

PubMed

Gomez, M Victoria; de la Hoz, Antonio

2017-01-01

Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is reviewed. Some recent selected applications have been collected, including synthetic applications, the determination of the kinetic and thermodynamic parameters and reaction optimization, even in single experiments and on the μL scale. Finally, software that allows automatic reaction monitoring and optimization is discussed.

A new window towards multidimensional sensing of transition metal cations through dual mode sensing ability of N-benzyl-(3-hydoxy-2-naphthalene): emission enhancement coupled remarkable spectral shift.

PubMed

Paul, Bijan Kumar; Mahanta, Subrata; Singh, Rupashree Balia; Guchhait, Nikhil

2011-06-01

A structurally simple Schiff base N-benzyl-(3-hydroxy-2-naphthalene) (NBHN32) has been synthesized and characterized by (1)H NMR, (13)C NMR, and DEPT spectroscopy. The photophysical behaviour of NBHN32 in response to the presence of various transition metal cations has been explored by means of steady-state absorption, emission and time-resolved emission spectroscopy techniques. Efficient through space intramolecular photoinduced electron transfer (PET) between the naphthalene fluorophore and the imine group has been argued for extremely low fluorescence yield of NBHN32 compared to the parent molecule 3-hydroxy-2-naphthaldehyde (HN32) containing the same fluorophore but lacking the receptor moiety. Transition metal ion-induced emission enhancement is thus addressed on the lexicon of perturbation of the PET by the metal ions. Apart from fluorescence enhancement, transition metal ion imparts remarkable shift of the emission maxima of NBHN32, which is another unique aspect on the proposed ability of NBHN32 to function as a fluorescence chemosensor. Copyright © 2011 Elsevier B.V. All rights reserved.

Contributed Review: Nuclear magnetic resonance core analysis at 0.3 T

NASA Astrophysics Data System (ADS)

Mitchell, Jonathan; Fordham, Edmund J.

2014-11-01

Nuclear magnetic resonance (NMR) provides a powerful toolbox for petrophysical characterization of reservoir core plugs and fluids in the laboratory. Previously, there has been considerable focus on low field magnet technology for well log calibration. Now there is renewed interest in the study of reservoir samples using stronger magnets to complement these standard NMR measurements. Here, the capabilities of an imaging magnet with a field strength of 0.3 T (corresponding to 12.9 MHz for proton) are reviewed in the context of reservoir core analysis. Quantitative estimates of porosity (saturation) and pore size distributions are obtained under favorable conditions (e.g., in carbonates), with the added advantage of multidimensional imaging, detection of lower gyromagnetic ratio nuclei, and short probe recovery times that make the system suitable for shale studies. Intermediate field instruments provide quantitative porosity maps of rock plugs that cannot be obtained using high field medical scanners due to the field-dependent susceptibility contrast in the porous medium. Example data are presented that highlight the potential applications of an intermediate field imaging instrument as a complement to low field instruments in core analysis and for materials science studies in general.

NMR 1H,13C, 15N backbone and 13C side chain resonance assignment of the G12C mutant of human K-Ras bound to GDP.

PubMed

Sharma, Alok K; Lee, Seung-Joo; Rigby, Alan C; Townson, Sharon A

2018-05-02

K-Ras is a key driver of oncogenesis, accounting for approximately 80% of Ras-driven human cancers. The small GTPase cycles between an inactive, GDP-bound and an active, GTP-bound state, regulated by guanine nucleotide exchange factors and GTPase activating proteins, respectively. Activated K-Ras regulates cell proliferation, differentiation and survival by signaling through several effector pathways, including Raf-MAPK. Oncogenic mutations that impair the GTPase activity of K-Ras result in a hyperactivated state, leading to uncontrolled cellular proliferation and tumorogenesis. A cysteine mutation at glycine 12 is commonly found in K-Ras associated cancers, and has become a recent focus for therapeutic intervention. We report here 1 H N, 15 N, and 13 C resonance assignments for the 19.3 kDa (aa 1-169) human K-Ras protein harboring an oncogenic G12C mutation in the GDP-bound form (K-RAS G12C-GDP ), using heteronuclear, multidimensional NMR spectroscopy. Backbone 1 H- 15 N correlations have been assigned for all non-proline residues, except for the first methionine residue.

The Potential Exploitation of the Mediterranean Invasive Alga Caulerpa cylindracea: Can the Invasion Be Transformed into a Gain?

PubMed Central

Stabili, Loredana; Fraschetti, Simonetta; Acquaviva, Maria Immacolata; Cavallo, Rosa Anna; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Gerardi, Carmela; Narracci, Marcella; Rizzo, Lucia

2016-01-01

Recently, there is a growing interest towards the development of strategies for invasive seaweed control and exploitation as source of secondary metabolites. Here, we investigated the potential of exploitation in biotechnology and recycling options in eradication programs of the lipidic extract of the Mediterranean invasive seaweed Caulerpa cylindracea (Chlorophyta). The chemical characterization was carried out by means of multinuclear and multidimensional NMR spectroscopy. The fatty acid profile of C. cylindracea assessed the presence of several types of molecules known for antioxidant activity such as carotenoids, chlorophylls, pheophytins, and sterols. The NMR spectroscopy showed also the characteristic signals of saturated, unsaturated, and free fatty acids as well as other metabolites including the biopolymer polyhydroxybutyrate. The lipidic extract exerted an antioxidant activity corresponding to 552.14 ± 69.13 mmol Trolox equivalent/g (ORAC) and to 70.3 ± 2.67 mmol Trolox equivalent/g (TEAC). The extract showed an antibacterial activity against several Vibrio species, suggesting its potential use in the control of diseases in mariculture. Our results show that C. cylindracea, representing a critical hazard in coastal areas, could be transformed into a gain supporting specific management actions to reduce the effects of human pressures. PMID:27854274

Characterization of Pharmaceutical Cocrystals and Salts by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy

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

Zhao, Li; Hanrahan, Michael P.; Chakravarty, Paroma

Multicomponent solids such as cocrystals have emerged as a way to control and engineer the stability, solubility and manufacturability of solid active pharmaceutical ingredients (APIs). Cocrystals are typically formed by solution- or solid-phase reactions of APIs with suitable cocrystal coformers, which are often weak acids. One key structural question about a given multicomponent solid is whether it should be classified as a salt, where the basic API is protonated by the acid, or as a cocrystal, where the API and coformer remain neutral and engage in hydrogen bonding interactions. It has previously been demonstrated that solid-state NMR spectroscopy is amore » powerful probe of structure in cocrystals and salts of APIs, however, the poor sensitivity of solid-state NMR spectroscopy usually restricts the types of experiments that can be performed. Here relayed dynamic nuclear polarization (DNP) was applied to reduce solid-state NMR experiments by one to two orders of magnitude for salts and cocrystals of a complex API. The large sensitivity gains from DNP facilitates rapid acquisition of natural isotopic abundance 13C and 15N solid-state NMR spectra. Critically, DNP enables double resonance 1H-15N solid-state NMR experiments such as 2D 1H-15N HETCOR, 1H-15N CP-build up, 15N{1H} J-resolved/attached proton tests, 1H-15N DIPSHIFT and 1H-15N PRESTO. The latter two experiments allow 1H-15N dipolar coupling constants and H-N bond lengths to be accurately measured, providing an unambiguous assignment of nitrogen protonation state and definitive classification of the multi-component solids as cocrystals or salts. In conclusion, these types of measurements should also be extremely useful in the context of polymorph discrimination, NMR crystallography structure determination and for probing hydrogen bonding in a variety of organic materials.« less

Characterization of Pharmaceutical Cocrystals and Salts by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy

DOE PAGES

Zhao, Li; Hanrahan, Michael P.; Chakravarty, Paroma; ...

2018-02-15

Multicomponent solids such as cocrystals have emerged as a way to control and engineer the stability, solubility and manufacturability of solid active pharmaceutical ingredients (APIs). Cocrystals are typically formed by solution- or solid-phase reactions of APIs with suitable cocrystal coformers, which are often weak acids. One key structural question about a given multicomponent solid is whether it should be classified as a salt, where the basic API is protonated by the acid, or as a cocrystal, where the API and coformer remain neutral and engage in hydrogen bonding interactions. It has previously been demonstrated that solid-state NMR spectroscopy is amore » powerful probe of structure in cocrystals and salts of APIs, however, the poor sensitivity of solid-state NMR spectroscopy usually restricts the types of experiments that can be performed. Here relayed dynamic nuclear polarization (DNP) was applied to reduce solid-state NMR experiments by one to two orders of magnitude for salts and cocrystals of a complex API. The large sensitivity gains from DNP facilitates rapid acquisition of natural isotopic abundance 13C and 15N solid-state NMR spectra. Critically, DNP enables double resonance 1H-15N solid-state NMR experiments such as 2D 1H-15N HETCOR, 1H-15N CP-build up, 15N{1H} J-resolved/attached proton tests, 1H-15N DIPSHIFT and 1H-15N PRESTO. The latter two experiments allow 1H-15N dipolar coupling constants and H-N bond lengths to be accurately measured, providing an unambiguous assignment of nitrogen protonation state and definitive classification of the multi-component solids as cocrystals or salts. In conclusion, these types of measurements should also be extremely useful in the context of polymorph discrimination, NMR crystallography structure determination and for probing hydrogen bonding in a variety of organic materials.« less

Motions and entropies in proteins as seen in NMR relaxation experiments and molecular dynamics simulations.

PubMed

Allnér, Olof; Foloppe, Nicolas; Nilsson, Lennart

2015-01-22

Molecular dynamics simulations of E. coli glutaredoxin1 in water have been performed to relate the dynamical parameters and entropy obtained in NMR relaxation experiments, with results extracted from simulated trajectory data. NMR relaxation is the most widely used experimental method to obtain data on dynamics of proteins, but it is limited to relatively short timescales and to motions of backbone amides or in some cases (13)C-H vectors. By relating the experimental data to the all-atom picture obtained in molecular dynamics simulations, valuable insights on the interpretation of the experiment can be gained. We have estimated the internal dynamics and their timescales by calculating the generalized order parameters (O) for different time windows. We then calculate the quasiharmonic entropy (S) and compare it to the entropy calculated from the NMR-derived generalized order parameter of the amide vectors. Special emphasis is put on characterizing dynamics that are not expressed through the motions of the amide group. The NMR and MD methods suffer from complementary limitations, with NMR being restricted to local vectors and dynamics on a timescale determined by the rotational diffusion of the solute, while in simulations, it may be difficult to obtain sufficient sampling to ensure convergence of the results. We also evaluate the amount of sampling obtained with molecular dynamics simulations and how it is affected by the length of individual simulations, by clustering of the sampled conformations. We find that two structural turns act as hinges, allowing the α helix between them to undergo large, long timescale motions that cannot be detected in the time window of the NMR dipolar relaxation experiments. We also show that the entropy obtained from the amide vector does not account for correlated motions of adjacent residues. Finally, we show that the sampling in a total of 100 ns molecular dynamics simulation can be increased by around 50%, by dividing the trajectory into 10 replicas with different starting velocities.

Characterization of active phosphorus surface sites at synthetic carbonate-free fluorapatite using single-pulse 1H, 31P, and 31P CP MAS NMR.

PubMed

Jarlbring, Mathias; Sandström, Dan E; Antzutkin, Oleg N; Forsling, Willis

2006-05-09

The chemically active phosphorus surface sites defined as PO(x), PO(x)H, and PO(x)H2, where x = 1, 2, or 3, and the bulk phosphorus groups of PO4(3-) at synthetic carbonate-free fluorapatite (Ca5(PO4)3F) have been studied by means of single-pulse 1H,31P, and 31P CP MAS NMR. The changes in composition and relative amounts of each surface species are evaluated as a function of pH. By combining spectra from single-pulse 1H and 31P MAS NMR and data from 31P CP MAS NMR experiments at varying contact times in the range 0.2-3.0 ms, it has been possible to distinguish between resonance lines in the NMR spectra originating from active surface sites and bulk phosphorus groups and also to assign the peaks in the NMR spectra to the specific phosphorus species. In the 31P CP MAS NMR experiments, the spinning frequency was set to 4.2 kHz; in the single-pulse 1H MAS NMR experiments, the spinning frequency was 10 kHz. The 31P CP MAS NMR spectrum of fluorapatite at pH 5.9 showed one dominating resonance line at 2.9 ppm assigned to originate from PO4(3-) groups and two weaker shoulder peaks at 5.4 and 0.8 ppm which were assigned to the unprotonated PO(x) (PO, PO2-, and PO3(2-)) and protonated PO(x)H (PO2H and PO3H-) surface sites. At pH 12.7, the intensity of the peak representing unprotonated PO(x) surface sites has increased 1.7% relative to the bulk peak, while the intensity of the peaks of the protonated species PO(x)H have decreased 1.4% relative to the bulk peak. At pH 3.5, a resonance peak at -4.5 ppm has appeared in the 31P CP MAS NMR spectrum assigned to the surface species PO(x)H2 (PO3H2). The results from the 1H MAS and 31P CP MAS NMR measurements indicated that H+, OH-, and physisorbed H2O at the surface were released during the drying process at 200 degrees C.

[superscript 31]P NMR of the Pyruvate Kinase Reaction: An Undergraduate Experiment in Enzyme Kinetics

ERIC Educational Resources Information Center

Werner, R. Marshall; Johnson, Austin

2017-01-01

Understanding how to perform an enzyme assay is a critical learning skill in the undergraduate biochemistry curriculum. Students in biochemistry typically have been exposed to the use of NMR spectroscopy as a tool to determine chemical structure, but rarely are they exposed to the utility of NMR to evaluate enzyme kinetics. Furthermore, coverage…

Determination of Molecular Self-Diffusion Coefficients Using Pulsed-Field-Gradient NMR: An Experiment for Undergraduate Physical Chemistry Laboratory

ERIC Educational Resources Information Center

Harmon, Jennifer; Coffman, Cierra; Villarrial, Spring; Chabolla, Steven; Heisel, Kurt A.; Krishnan, Viswanathan V.

2012-01-01

NMR spectroscopy has become one of the primary tools that chemists utilize to characterize a range of chemical species in the solution phase, from small organic molecules to medium-sized proteins. A discussion of NMR spectroscopy is an essential component of physical and biophysical chemistry lecture courses, and a number of instructional…

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…

Dynamic NMR of Intramolecular Exchange Processes in EDTA Complexes of Sc[superscript 3+], Y[superscript 3+], and La[superscript 3+

ERIC Educational Resources Information Center

Ba, Yong; Han, Steven; Ni, Lily; Su, Tony; Garcia, Andres

2006-01-01

Dynamic NMR makes use of the effect of chemical exchanges on NMR spectra to study kinetics and thermodynamics. An advanced physical chemistry lab experiment was developed to study the intramolecular exchange processes of EDTA (the disodium salt of ethylenediaminetetraacetic acid) metal complexes. EDTA is an important chelating agent, used in…

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.

1H-detected MAS solid-state NMR experiments enable the simultaneous mapping of rigid and dynamic domains of membrane proteins

NASA Astrophysics Data System (ADS)

Gopinath, T.; Nelson, Sarah E. D.; Veglia, Gianluigi

2017-12-01

Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is emerging as a unique method for the atomic resolution structure determination of native membrane proteins in lipid bilayers. Although 13C-detected ssNMR experiments continue to play a major role, recent technological developments have made it possible to carry out 1H-detected experiments, boosting both sensitivity and resolution. Here, we describe a new set of 1H-detected hybrid pulse sequences that combine through-bond and through-space correlation elements into single experiments, enabling the simultaneous detection of rigid and dynamic domains of membrane proteins. As proof-of-principle, we applied these new pulse sequences to the membrane protein phospholamban (PLN) reconstituted in lipid bilayers under moderate MAS conditions. The cross-polarization (CP) based elements enabled the detection of the relatively immobile residues of PLN in the transmembrane domain using through-space correlations; whereas the most dynamic region, which is in equilibrium between folded and unfolded states, was mapped by through-bond INEPT-based elements. These new 1H-detected experiments will enable one to detect not only the most populated (ground) states of biomacromolecules, but also sparsely populated high-energy (excited) states for a complete characterization of protein free energy landscapes.

The pursuit of happiness measurement: a psychometric model based on psychophysiological correlates.

PubMed

Pietro, Cipresso; Silvia, Serino; Giuseppe, Riva

2014-01-01

Everyone is interested in the pursuit of happiness, but the real problem for the researchers is how to measure it. Our aim was to deeply investigate happiness measurement through biomedical signals, using psychophysiological methods to objectify the happiness experiences measurements. The classic valence-arousal model of affective states to study happiness has been extensively used in psychophysiology. However, really few studies considered a real combination of these two dimensions and no study further investigated multidimensional models. More, most studies focused mainly on self-report to measure happiness and a deeper psychophysiological investigation on the dimensions of such an experience is still missing. A multidimensional model of happiness is presented and both the dimensions and the measures extracted within each dimension are comprehensively explained. This multidimensional model aims at being a milestone for future systematic study on psychophysiology of happiness and affective states.

The Multidimensional Loss Scale: validating a cross-cultural instrument for measuring loss.

PubMed

Vromans, Lyn; Schweitzer, Robert D; Brough, Mark

2012-04-01

The Multidimensional Loss Scale (MLS) represents the first instrument designed specifically to index Experience of Loss Events and Loss Distress across multiple domains (cultural, social, material, and intrapersonal) relevant to refugee settlement. Recently settled Burmese adult refugees (N = 70) completed a questionnaire battery, including MLS items. Analyses explored MLS internal consistency, convergent and divergent validity, and factor structure. Cronbach alphas indicated satisfactory internal consistency for Experience of Loss Events (0.85) and Loss Distress (0.92), reflecting a unitary construct of multidimensional loss. Loss Distress did not correlate with depression or anxiety symptoms and correlated moderately with interpersonal grief and trauma symptoms, supporting divergent and convergent validity. Factor analysis provided preliminary support for a five-factor model: Loss of Symbolic Self, Loss of Interdependence, Loss of Home, Interpersonal Loss, and Loss of Intrapersonal Integrity. Received well by participants, the new scale shows promise for application in future research and practice.

Moissanite anvil cell design for Giga-Pascal nuclear magnetic resonance.

PubMed

Meier, Thomas; Herzig, Tobias; Haase, Jürgen

2014-04-01

A new design of a non-magnetic high-pressure anvil cell for nuclear magnetic resonance (NMR) experiments at Giga-Pascal pressures is presented, which uses a micro-coil inside the pressurized region for high-sensitivity NMR. The comparably small cell has a length of 22 mm and a diameter of 18 mm, so it can be used with most NMR magnets. The performance of the cell is demonstrated with external-force vs. internal-pressure experiments, and the cell is shown to perform well at pressures up to 23.5 GPa using 800 μm 6H-SiC large cone Boehler-type anvils. (1)H, (23)Na, (27)Al, (69)Ga, and (71)Ga NMR test measurements are presented, which show a resolution of better than 4.5 ppm, and an almost maximum possible signal-to-noise ratio.

Protein-nucleotide contacts in motor proteins detected by DNP-enhanced solid-state NMR.

PubMed

Wiegand, Thomas; Liao, Wei-Chih; Ong, Ta Chung; Däpp, Alexander; Cadalbert, Riccardo; Copéret, Christophe; Böckmann, Anja; Meier, Beat H

2017-11-01

DNP (dynamic nuclear polarization)-enhanced solid-state NMR is employed to directly detect protein-DNA and protein-ATP interactions and identify the residue type establishing the intermolecular contacts. While conventional solid-state NMR can detect protein-DNA interactions in large oligomeric protein assemblies in favorable cases, it typically suffers from low signal-to-noise ratios. We show here, for the oligomeric DnaB helicase from Helicobacter pylori complexed with ADP and single-stranded DNA, that this limitation can be overcome by using DNP-enhanced spectroscopy. Interactions are established by DNP-enhanced 31 P- 13 C polarization-transfer experiments followed by the recording of a 2D 13 C- 13 C correlation experiment. The NMR spectra were obtained in less than 2 days and allowed the identification of residues of the motor protein involved in nucleotide binding.

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.

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

PubMed

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

2018-05-10

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

An Enzyme Kinetics Experiment for the Undergraduate Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Olsen, Robert J.; Olsen, Julie A.; Giles, Greta A.

2010-01-01

An experiment using [superscript 1]H NMR spectroscopy to observe the kinetics of the acylase 1-catalyzed hydrolysis of "N"-acetyl-DL-methionine has been developed for the organic laboratory. The L-enantiomer of the reactant is hydrolyzed completely in less than 2 h, and [superscript 1]H NMR spectroscopic data from a single sample can be worked up…

Scaffolding Students' Skill Development by First Introducing Advanced Techniques through the Synthesis and [superscript 15]N NMR Analysis of Cinnamamides

ERIC Educational Resources Information Center

Shuldburg, Sara; Carroll, Jennifer

2017-01-01

An advanced undergraduate experiment involving the synthesis and characterization of a series of six unique cinnamamides is described. This experiment allows for a progressive mastery of skills students need to tackle more complex NMR structure elucidation problems. Characterization of the products involves IR spectroscopy, GCMS, and proton,…

Extraction and [superscript 1]H NMR Analysis of Fats from Convenience Foods: A Laboratory Experiment for Organic Chemistry

ERIC Educational Resources Information Center

Hartel, Aaron M.; Moore, Amy C.

2014-01-01

The extraction and analysis of fats from convenience foods (crackers, cookies, chips, candies) has been developed as an experiment for a second-year undergraduate organic chemistry laboratory course. Students gravimetrically determine the fat content per serving and then perform a [superscript 1]H NMR analysis of the recovered fat to determine the…

Computer simulation of FT-NMR multiple pulse experiment

NASA Astrophysics Data System (ADS)

Allouche, A.; Pouzard, G.

1989-04-01

Using the product operator formalism in its real form, SIMULDENS expands the density matrix of a scalar coupled nuclear spin system and simulates analytically a large variety of FT-NMR multiple pulse experiments. The observable transverse magnetizations are stored and can be combined to represent signal accumulation. The programming language is VAX PASCAL, but a MacIntosh Turbo Pascal Version is also available.

Genetic algorithm optimized triply compensated pulses in NMR spectroscopy

NASA Astrophysics Data System (ADS)

Manu, V. S.; Veglia, Gianluigi

2015-11-01

Sensitivity and resolution in NMR experiments are affected by magnetic field inhomogeneities (of both external and RF), errors in pulse calibration, and offset effects due to finite length of RF pulses. To remedy these problems, built-in compensation mechanisms for these experimental imperfections are often necessary. Here, we propose a new family of phase-modulated constant-amplitude broadband pulses with high compensation for RF inhomogeneity and heteronuclear coupling evolution. These pulses were optimized using a genetic algorithm (GA), which consists in a global optimization method inspired by Nature's evolutionary processes. The newly designed π and π / 2 pulses belong to the 'type A' (or general rotors) symmetric composite pulses. These GA-optimized pulses are relatively short compared to other general rotors and can be used for excitation and inversion, as well as refocusing pulses in spin-echo experiments. The performance of the GA-optimized pulses was assessed in Magic Angle Spinning (MAS) solid-state NMR experiments using a crystalline U-13C, 15N NAVL peptide as well as U-13C, 15N microcrystalline ubiquitin. GA optimization of NMR pulse sequences opens a window for improving current experiments and designing new robust pulse sequences.

Contact replacement for NMR resonance assignment.

PubMed

Xiong, Fei; Pandurangan, Gopal; Bailey-Kellogg, Chris

2008-07-01

Complementing its traditional role in structural studies of proteins, nuclear magnetic resonance (NMR) spectroscopy is playing an increasingly important role in functional studies. NMR dynamics experiments characterize motions involved in target recognition, ligand binding, etc., while NMR chemical shift perturbation experiments identify and localize protein-protein and protein-ligand interactions. The key bottleneck in these studies is to determine the backbone resonance assignment, which allows spectral peaks to be mapped to specific atoms. This article develops a novel approach to address that bottleneck, exploiting an available X-ray structure or homology model to assign the entire backbone from a set of relatively fast and cheap NMR experiments. We formulate contact replacement for resonance assignment as the problem of computing correspondences between a contact graph representing the structure and an NMR graph representing the data; the NMR graph is a significantly corrupted, ambiguous version of the contact graph. We first show that by combining connectivity and amino acid type information, and exploiting the random structure of the noise, one can provably determine unique correspondences in polynomial time with high probability, even in the presence of significant noise (a constant number of noisy edges per vertex). We then detail an efficient randomized algorithm and show that, over a variety of experimental and synthetic datasets, it is robust to typical levels of structural variation (1-2 AA), noise (250-600%) and missings (10-40%). Our algorithm achieves very good overall assignment accuracy, above 80% in alpha-helices, 70% in beta-sheets and 60% in loop regions. Our contact replacement algorithm is implemented in platform-independent Python code. The software can be freely obtained for academic use by request from the authors.

Nuclear magnetic resonance relaxation and diffusion measurements as a proxy for soil properties

NASA Astrophysics Data System (ADS)

Duschl, Markus; Pohlmeier, Andreas; Galvosas, Petrik; Vereecken, Harry

2013-04-01

Nuclear Magnetic Resonance (NMR) relaxation and NMR diffusion measurements are two of a series of fast and non-invasive NMR applications widely used e.g. as well logging tools in petroleum exploration [1]. For experiments with water, NMR relaxation measures the relaxation behaviour of former excited water molecules, and NMR diffusion evaluates the self-diffusion of water. Applied in porous media, both relaxation and diffusion measurements depend on intrinsic properties of the media like pore size distribution, connectivity and tortuosity of the pores, and water saturation [2, 3]. Thus, NMR can be used to characterise the pore space of porous media not only in consolidated sediments but also in soil. The physical principle behind is the relaxation of water molecules in an external magnetic field after excitation. In porous media water molecules in a surface layer of the pores relax faster than the molecules in bulk water because of interactions with the pore wall. Thus, the relaxation in smaller pores is generally faster than in bigger pores resulting in a relaxation time distribution for porous media with a range of pore sizes like soil [4]. In NMR diffusion experiments, there is an additional encoding of water molecules by application of a magnetic field gradient. Subsequent storage of the magnetization and decoding enables the determination of the mean square displacement and therefore of the self-diffusion of the water molecules [5]. Employing various relaxation and diffusion experiments, we get a measure of the surface to volume ratio of the pores and the tortuosity of the media. In this work, we show the characterisation of a set of sand and soil samples covering a wide range of textural classes by NMR methods. Relaxation times were monitored by the Carr-Purcell-Meiboom-Gill sequence and analysed using inverse Laplace transformation. Apparent self-diffusion constants were detected by a 13-intervall pulse sequence and variation of the storage time. We correlated the results with various soil properties like texture, water retention parameters, and hydraulic conductivity. This way we show that we can predict soil properties by NMR measurements and that we are able use results of NMR measurements as a proxy without the need of direct measurements. [1] Song, Y.-Q., Vadose Zone Journal, 9 (2010) [2] Stingaciu, L. R., et al., Water Resources Research, 46 (2010) [3] Vogt, C., et al., Journal of Applied Geophysics, 50 (2002) [4] Barrie, P. J., Annual Reports on NMR Spectroscopy, 41 (2000) [5] Stallmach, F., Galvosas, P., Annual Reports on NMR Spectroscopy, 61 (2007)

Structural analysis of geochemical samples by solid-state nuclear magnetic resonance spectrometry. Role of paramagnetic material

USGS Publications Warehouse

Vassallo, A.M.; Wilson, M.A.; Collin, P.J.; Oades, J.M.; Waters, A.G.; Malcolm, R.L.

1987-01-01

An examination of coals, coal tars, a fulvic acid, and soil fractions by solid-state 13C NMR spectrometry has demonstrated widely differing behavior regarding quantitative representation in the spectrum. Spin counting experiments on coal tars and the fulvic acid show that almost all the sample carbon is observed in both solution and solid-state NMR spectra. Similar experiments on two coals (a lignite and a bituminous coal) show that most (70-97%) of the carbon is observed; however, when the lignite is ion exchanged with 3% (w/w) Fe3+, the fraction of carbon observed drops to below 10%. In additional experiments signal intensity from soil samples is enhanced by a simple dithionite treatment. This is illustrated by 13C, 27Al, and 29Si solid-state NMR experiments on soil fractions. ?? 1987 American Chemical Society.

Historical Development of Learning Style Inventories from Dichotomous Cognitive Concepts of Field Dependence and Field Independence to Multi-Dimensional Assessment.

ERIC Educational Resources Information Center

Tamaoka, Katsuo

The historical development of learning style inventories is examined from the dichotomous concepts of cognitive styles to multidimensional assessment. Based on a series of experiments on vertical perception, H. A. Witkin formed the concepts of field-dependent and field-independent cognitive styles. Using the term "learning styles"…

Psychometric Evaluation of the Multidimensional Assessment of Fatigue Scale for Use with Pregnant and Postpartum Women

ERIC Educational Resources Information Center

Fairbrother, Nichole; Hutton, Eileen K.; Stoll, Kathrin; Hall, Wendy; Kluka, Sandy

2008-01-01

Although fatigue is a common experience for pregnant women and new mothers, few measures of fatigue have been validated for use with this population. To address this gap, the authors assessed psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale, which was used in 2 independent samples of pregnant women. Results…

Multidimensional Latent Markov Models in a Developmental Study of Inhibitory Control and Attentional Flexibility in Early Childhood

ERIC Educational Resources Information Center

Bartolucci, Francesco; Solis-Trapala, Ivonne L.

2010-01-01

We demonstrate the use of a multidimensional extension of the latent Markov model to analyse data from studies with repeated binary responses in developmental psychology. In particular, we consider an experiment based on a battery of tests which was administered to pre-school children, at three time periods, in order to measure their inhibitory…

An investigation into the effects of pore connectivity on T2 NMR relaxation

NASA Astrophysics Data System (ADS)

Ghomeshi, Shahin; Kryuchkov, Sergey; Kantzas, Apostolos

2018-04-01

Nuclear Magnetic Resonance (NMR) is a powerful technique used to characterize fluids and flow in porous media. The NMR relaxation curves are closely related to pore geometry, and the inversion of the NMR relaxometry data is known to give useful information with regards to pore size distribution (PSD) through the relative amplitudes of the fluids stored in the small and large pores. While this information is crucial, the main challenge for the successful use of the NMR measurements is the proper interpretation of the measured signals. Natural porous media patterns consist of complex pore structures with many interconnected or "coupled" regions, as well as isolated pores. This connectivity along the throats changes the relaxation distribution and in order to properly interpret this data, a thorough understanding of the effects of pore connectivity on the NMR relaxation distribution is warranted. In this paper we address two main points. The first pertains to the fact that there is a discrepancy between the relaxation distribution obtained from experiments, and the ones obtained from solving the mathematical models of diffusion process in the digitized images of the pore space. There are several reasons that may attribute to this such as the lack of a proper incorporation of surface roughness into the model. However, here we are more interested in the effects of pore connectivity and to understand why the typical NMR relaxation distribution obtained from experiments are wider, while the numerical simulations predict that a wider NMR relaxation distribution may indicate poor connectivity. Secondly, by not taking into account the pore coupling effects, from our experience in interpreting the data, we tend to underestimate the pore volume of small pores and overestimate the amplitudes in the large pores. The role of pore coupling becomes even more prominent in rocks with small pore sizes such as for example in shales, clay in sandstones, and in the microstructures of carbonates.

NMR crystallography to probe the breathing effect of the MIL-53(Al) metal-organic framework using solid-state NMR measurements of 13C-27Al distances.

PubMed

Giovine, Raynald; Volkringer, Christophe; Trébosc, Julien; Amoureux, Jean Paul; Loiseau, Thierry; Lafon, Olivier; Pourpoint, Frédérique

2017-03-01

The metal-organic framework MIL-53(Al) (aluminium terephthalate) exhibits a structural transition between two porous structures with large pore (lp) or narrow pore (np) configurations. This transition, called the breathing effect, is observed upon changes in temperature or external pressure, as well as with the adsorption of guest molecules, such as H 2 O, within the pores. We show here how these different pore openings can be detected by observing the dephasing of 13 C magnetization under 13 C- 27 Al dipolar couplings using Rotational-Echo Saturation-Pulse Double-Resonance (RESPDOR) solid-state NMR experiments with Simultaneous Frequency and Amplitude Modulation (SFAM) recoupling. These double-resonance NMR experiments between 13 C and 27 Al nuclei, which have close Larmor frequencies, are feasible thanks to the use of a frequency splitter. The experimental SFAM-RESPDOR signal fractions agree well with those simulated from the MIL-53(Al)-lp and -np crystal structures obtained from powder X-ray diffraction analysis. Hence, these 13 C- 27 Al solid-state NMR experiments validate these structures and confirm their rigidity. A similar agreement is reported for the framework ligands in the as-synthesized (as) MIL-53(Al), in which the pores contain free ligands. Furthermore, in this case, 13 C-{ 27 Al} SFAM-RESPDOR experiments allow an estimation of the average distance between the free ligands and the 27 Al nuclei of the framework.

Improving Multidimensional Wireless Sensor Network Lifetime Using Pearson Correlation and Fractal Clustering

PubMed Central

Almeida, Fernando R.; Brayner, Angelo; Rodrigues, Joel J. P. C.; Maia, Jose E. Bessa

2017-01-01

An efficient strategy for reducing message transmission in a wireless sensor network (WSN) is to group sensors by means of an abstraction denoted cluster. The key idea behind the cluster formation process is to identify a set of sensors whose sensed values present some data correlation. Nowadays, sensors are able to simultaneously sense multiple different physical phenomena, yielding in this way multidimensional data. This paper presents three methods for clustering sensors in WSNs whose sensors collect multidimensional data. The proposed approaches implement the concept of multidimensional behavioral clustering. To show the benefits introduced by the proposed methods, a prototype has been implemented and experiments have been carried out on real data. The results prove that the proposed methods decrease the amount of data flowing in the network and present low root-mean-square error (RMSE). PMID:28590450

Improving Multidimensional Wireless Sensor Network Lifetime Using Pearson Correlation and Fractal Clustering.

PubMed

Almeida, Fernando R; Brayner, Angelo; Rodrigues, Joel J P C; Maia, Jose E Bessa

2017-06-07

An efficient strategy for reducing message transmission in a wireless sensor network (WSN) is to group sensors by means of an abstraction denoted cluster. The key idea behind the cluster formation process is to identify a set of sensors whose sensed values present some data correlation. Nowadays, sensors are able to simultaneously sense multiple different physical phenomena, yielding in this way multidimensional data. This paper presents three methods for clustering sensors in WSNs whose sensors collect multidimensional data. The proposed approaches implement the concept of multidimensional behavioral clustering . To show the benefits introduced by the proposed methods, a prototype has been implemented and experiments have been carried out on real data. The results prove that the proposed methods decrease the amount of data flowing in the network and present low root-mean-square error (RMSE).

Optical pumping and xenon NMR

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

Raftery, M. Daniel

1991-11-01

Nuclear Magnetic Resonance (NMR) spectroscopy of xenon has become an important tool for investigating a wide variety of materials, especially those with high surface area. The sensitivity of its chemical shift to environment, and its chemical inertness and adsorption properties make xenon a particularly useful NMR probe. This work discusses the application of optical pumping to enhance the sensitivity of xenon NMR experiments, thereby allowing them to be used in the study of systems with lower surface area. A novel method of optically-pumping 129Xe in low magnetic field below an NMR spectrometer and subsequent transfer of the gas to highmore » magnetic field is described. NMR studies of the highly polarized gas adsorbed onto powdered samples with low to moderate surface areas are now possible. For instance, NMR studies of optically-pumped xenon adsorbed onto polyacrylic acid show that xenon has a large interaction with the surface. By modeling the low temperature data in terms of a sticking probability and the gas phase xenon-xenon interaction, the diffusion coefficient for xenon at the surface of the polymer is determined. The sensitivity enhancement afforded by optical pumping also allows the NMR observation of xenon thin films frozen onto the inner surfaces of different sample cells. The geometry of the thin films results in interesting line shapes that are due to the bulk magnetic susceptibility of xenon. Experiments are also described that combine optical pumping with optical detection for high sensitivity in low magnetic field to observe the quadrupoler evolution of 131 Xe spins at the surface of the pumping cells. In cells with macroscopic asymmetry, a residual quadrupolar interaction causes a splitting in the 131Xe NMR frequencies in bare Pyrex glass cells and cells with added hydrogen.« less

Optical pumping and xenon NMR

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

Raftery, M.D.

1991-11-01

Nuclear Magnetic Resonance (NMR) spectroscopy of xenon has become an important tool for investigating a wide variety of materials, especially those with high surface area. The sensitivity of its chemical shift to environment, and its chemical inertness and adsorption properties make xenon a particularly useful NMR probe. This work discusses the application of optical pumping to enhance the sensitivity of xenon NMR experiments, thereby allowing them to be used in the study of systems with lower surface area. A novel method of optically-pumping [sup 129]Xe in low magnetic field below an NMR spectrometer and subsequent transfer of the gas tomore » high magnetic field is described. NMR studies of the highly polarized gas adsorbed onto powdered samples with low to moderate surface areas are now possible. For instance, NMR studies of optically-pumped xenon adsorbed onto polyacrylic acid show that xenon has a large interaction with the surface. By modeling the low temperature data in terms of a sticking probability and the gas phase xenon-xenon interaction, the diffusion coefficient for xenon at the surface of the polymer is determined. The sensitivity enhancement afforded by optical pumping also allows the NMR observation of xenon thin films frozen onto the inner surfaces of different sample cells. The geometry of the thin films results in interesting line shapes that are due to the bulk magnetic susceptibility of xenon. Experiments are also described that combine optical pumping with optical detection for high sensitivity in low magnetic field to observe the quadrupoler evolution of 131 Xe spins at the surface of the pumping cells. In cells with macroscopic asymmetry, a residual quadrupolar interaction causes a splitting in the [sup 131]Xe NMR frequencies in bare Pyrex glass cells and cells with added hydrogen.« less

A Discovery-Based Experiment Involving Rearrangement in the Conversion of Alcohols to Alkyl Halides: Permanent Magnet [to the thirteenth power]C NMR in the First-Semester Organic Chemistry Lab

ERIC Educational Resources Information Center

Kjonaas, Richard A.; Tucker, Ryand J. F.

2008-01-01

The use of permanent magnet [to the thirteenth power]C NMR in large-section first-semester organic chemistry lab courses is limited by the availability of experiments that not only hinge on first-semester lecture topics, but which also produce at least 0.5 mL of neat liquid sample. This article reports a discovery-based experiment that meets both…

Enzymatic Resolution of 1-Phenylethanol and Formation of a Diastereomer: An Undergraduate [superscript 1]H NMR Experiment to Introduce Chiral Chemistry

ERIC Educational Resources Information Center

Faraldos, Juan A.; Giner, Jos-Luis; Smith, David H.; Wilson, Mark; Ronhovde, Kyla; Wilson, Erin; Clevette, David; Holmes, Andrea E.; Rouhier, Kerry

2011-01-01

This organic laboratory experiment introduces students to stereoselective enzyme reactions, resolution of enantiomers, and NMR analysis of diastereomers. The reaction between racemic 1-phenylethanol and vinyl acetate in hexane to form an ester is catalyzed by acylase I. The unreacted alcohol is then treated with a chiral acid and the resulting…

Polymer-Supported Reagents and [to the first power]H-[to the nineteenth power]F NMR Couplings: The Synthesis of 2-Fluoroacetophenone

ERIC Educational Resources Information Center

Pohl, Nicola; Schwarz, Kimberly

2008-01-01

We describe an experiment for the undergraduate organic laboratory curriculum in which 2-bromoacetophenone is converted to 2-fluoroacetophenone using a solid-phase nucleophilic fluorine source. The experiment introduces students to the utility of solid-phase reagents in organic synthesis, to NMR-active nuclei other than [to the first power]H…

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.

Supramolecular Amino Acid Based Hydrogels: Probing the Contribution of Additive Molecules using NMR Spectroscopy

PubMed Central

Ramalhete, Susana M.; Nartowski, Karol P.; Sarathchandra, Nichola; Foster, Jamie S.; Round, Andrew N.; Angulo, Jesús

2017-01-01

Abstract Supramolecular hydrogels are composed of self‐assembled solid networks that restrict the flow of water. l‐Phenylalanine is the smallest molecule reported to date to form gel networks in water, and it is of particular interest due to its crystalline gel state. Single and multi‐component hydrogels of l‐phenylalanine are used herein as model materials to develop an NMR‐based analytical approach to gain insight into the mechanisms of supramolecular gelation. Structure and composition of the gel fibres were probed using PXRD, solid‐state NMR experiments and microscopic techniques. Solution‐state NMR studies probed the properties of free gelator molecules in an equilibrium with bound molecules. The dynamics of exchange at the gel/solution interfaces was investigated further using high‐resolution magic angle spinning (HR‐MAS) and saturation transfer difference (STD) NMR experiments. This approach allowed the identification of which additive molecules contributed in modifying the material properties. PMID:28401991

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.

Moissanite anvil cell design for giga-pascal nuclear magnetic resonance

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

Meier, Thomas; Herzig, Tobias; Haase, Jürgen

2014-04-15

A new design of a non-magnetic high-pressure anvil cell for nuclear magnetic resonance (NMR) experiments at Giga-Pascal pressures is presented, which uses a micro-coil inside the pressurized region for high-sensitivity NMR. The comparably small cell has a length of 22 mm and a diameter of 18 mm, so it can be used with most NMR magnets. The performance of the cell is demonstrated with external-force vs. internal-pressure experiments, and the cell is shown to perform well at pressures up to 23.5 GPa using 800 μm 6H-SiC large cone Boehler-type anvils. {sup 1}H, {sup 23}Na, {sup 27}Al, {sup 69}Ga, and {supmore » 71}Ga NMR test measurements are presented, which show a resolution of better than 4.5 ppm, and an almost maximum possible signal-to-noise ratio.« less

Note: Commercial SQUID magnetometer-compatible NMR probe and its application for studying a quantum magnet.

PubMed

Vennemann, T; Jeong, M; Yoon, D; Magrez, A; Berger, H; Yang, L; Živković, I; Babkevich, P; Rønnow, H M

2018-04-01

We present a compact nuclear magnetic resonance (NMR) probe which is compatible with a magnet of a commercial superconducting quantum interference device magnetometer and demonstrate its application to the study of a quantum magnet. We employ trimmer chip capacitors to construct an NMR tank circuit for low temperature measurements. Using a magnetic insulator MoOPO 4 with S = 1/2 (Mo 5+ ) as an example, we show that the T-dependence of the circuit is weak enough to allow the ligand-ion NMR study of magnetic systems. Our 31 P NMR results are compatible with previous bulk susceptibility and neutron scattering experiments and furthermore reveal unconventional spin dynamics.

Note: Commercial SQUID magnetometer-compatible NMR probe and its application for studying a quantum magnet

NASA Astrophysics Data System (ADS)

Vennemann, T.; Jeong, M.; Yoon, D.; Magrez, A.; Berger, H.; Yang, L.; Živković, I.; Babkevich, P.; Rønnow, H. M.

2018-04-01

We present a compact nuclear magnetic resonance (NMR) probe which is compatible with a magnet of a commercial superconducting quantum interference device magnetometer and demonstrate its application to the study of a quantum magnet. We employ trimmer chip capacitors to construct an NMR tank circuit for low temperature measurements. Using a magnetic insulator MoOPO4 with S = 1/2 (Mo5+) as an example, we show that the T-dependence of the circuit is weak enough to allow the ligand-ion NMR study of magnetic systems. Our 31P NMR results are compatible with previous bulk susceptibility and neutron scattering experiments and furthermore reveal unconventional spin dynamics.

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

PubMed

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

2007-01-24

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

3D TOCSY-HSQC NMR for metabolic flux analysis using non-uniform sampling

DOE PAGES

Reardon, Patrick N.; Marean-Reardon, Carrie L.; Bukovec, Melanie A.; ...

2016-02-05

13C-Metabolic Flux Analysis ( 13C-MFA) is rapidly being recognized as the authoritative method for determining fluxes through metabolic networks. Site-specific 13C enrichment information obtained using NMR spectroscopy is a valuable input for 13C-MFA experiments. Chemical shift overlaps in the 1D or 2D NMR experiments typically used for 13C-MFA frequently hinder assignment and quantitation of site-specific 13C enrichment. Here we propose the use of a 3D TOCSY-HSQC experiment for 13C-MFA. We employ Non-Uniform Sampling (NUS) to reduce the acquisition time of the experiment to a few hours, making it practical for use in 13C-MFA experiments. Our data show that the NUSmore » experiment is linear and quantitative. Identification of metabolites in complex mixtures, such as a biomass hydrolysate, is simplified by virtue of the 13C chemical shift obtained in the experiment. In addition, the experiment reports 13C-labeling information that reveals the position specific labeling of subsets of isotopomers. As a result, the information provided by this technique will enable more accurate estimation of metabolic fluxes in larger metabolic networks.« less

Shimming of a Magnet for Calibration of NMR Probes for the Muon g-2 Experiment

NASA Astrophysics Data System (ADS)

Bielajew, Rachel

2013-10-01

The Muon g-2 Experiment at Fermilab aims to measure the anomalous magnetic moment aμ ≡ (g-2)/2 of the muon to the precision of 0.14 parts per million. This experimental value of aμ can then be compared to the similarly precise theoretical predictions of the Standard Model in order to test the completeness of the model. The value of aμ is extracted from muons precessing in a magnetic field. The magnetic field will be measured with a set of 400 Nuclear Magnetic Resonance (NMR) probes, which have the ability to measure the field to a precision of tens of parts per billion. Before the Muon g-2 Experiment can take place, new NMR probes must be designed, built, and tested using a 1.45 Tesla test magnet at the University of Washington Center for Experimental Nuclear Physics and Astrophysics (CENPA). In order to achieve a significant signal from NMR probes, the magnetic field in which the probes are immersed must be extremely uniform. The existing magnet at CENPA has an approximately linear gradient in magnetic field of about 1 Gauss per centimeter in the smoothest direction. A pair of adjacent square Helmholtz coils was designed and built to create a linear gradient in order to cancel the existing gradient. The length of the NMR signals improved with the implementation of the coils. The results of the addition of the coils to the magnet on the signals from the NMR probes will be presented.

Determination of Multiple φ-Torsion Angles in Proteins by Selective and Extensive 13C Labeling and Two-Dimensional Solid-State NMR

NASA Astrophysics Data System (ADS)

Hong, Mei

1999-08-01

We describe an approach to efficiently determine the backbone conformation of solid proteins that utilizes selective and extensive 13C labeling in conjunction with two-dimensional magic-angle-spinning NMR. The selective 13C labeling approach aims to reduce line broadening and other multispin complications encountered in solid-state NMR of uniformly labeled proteins while still enhancing the sensitivity of NMR spectra. It is achieved by using specifically labeled glucose or glycerol as the sole carbon source in the protein expression medium. For amino acids synthesized in the linear part of the biosynthetic pathways, [1-13C]glucose preferentially labels the ends of the side chains, while [2-13C]glycerol labels the Cα of these residues. Amino acids produced from the citric-acid cycle are labeled in a more complex manner. Information on the secondary structure of such a labeled protein was obtained by measuring multiple backbone torsion angles φ simultaneously, using an isotropic-anisotropic 2D correlation technique, the HNCH experiment. Initial experiments for resonance assignment of a selectively 13C labeled protein were performed using 15N-13C 2D correlation spectroscopy. From the time dependence of the 15N-13C dipolar coherence transfer, both intraresidue and interresidue connectivities can be observed, thus yielding partial sequential assignment. We demonstrate the selective 13C labeling and these 2D NMR experiments on a 8.5-kDa model protein, ubiquitin. This isotope-edited NMR approach is expected to facilitate the structure determination of proteins in the solid state.

Experimental Determination of pK[subscript a] Values and Metal Binding for Biomolecular Compounds Using [superscript 31]P NMR Spectroscopy

ERIC Educational Resources Information Center

Swartz, Mason A.; Tubergen, Philip J.; Tatko, Chad D.; Baker, Rachael A.

2018-01-01

This lab experiment uses [superscript 31]P NMR spectroscopy of biomolecules to determine pK[subscript a] values and the binding energies of metal/biomolecule complexes. Solutions of adenosine nucleotides are prepared, and a series of [superscript 31]P NMR spectra are collected as a function of pH and in the absence and presence of magnesium or…

Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles.

PubMed

Bendahan, David; Chatel, Benjamin; Jue, Thomas

2017-12-01

Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O 2 Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O 2 requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb. In contrast, 1 H NMR has only detected the Mb signal in contracting muscle, and comparative NIRS and NMR experiments indicate a predominant Mb contribution. The present study has examined the question of the NIRS signal origin by measuring simultaneously the 1 H NMR, 31 P NMR, and NIRS signals in finger flexor muscles during the transition from rest to contraction, recovery, ischemia, and reperfusion. The experiment results confirm a predominant Mb contribution to the NIRS signal from muscle. Given the NMR and NIRS corroborated changes in the intracellular O 2 , the analysis shows that at the onset of muscle contraction, O 2 declines immediately and reaches new steady states as contraction intensity rises. Moreover, lactate formation increases even under quite aerobic condition. Copyright © 2017 the American Physiological Society.

Novel NMR tools to study structure and dynamics of biomembranes.

PubMed

Gawrisch, Klaus; Eldho, Nadukkudy V; Polozov, Ivan V

2002-06-01

Nuclear magnetic resonance (NMR) studies on biomembranes have benefited greatly from introduction of magic angle spinning (MAS) NMR techniques. Improvements in MAS probe technology, combined with the higher magnetic field strength of modern instruments, enables almost liquid-like resolution of lipid resonances. The cross-relaxation rates measured by nuclear Overhauser enhancement spectroscopy (NOESY) provide new insights into conformation and dynamics of lipids with atomic-scale resolution. The data reflect the tremendous motional disorder in the lipid matrix. Transfer of magnetization by spin diffusion along the proton network of lipids is of secondary relevance, even at a long NOESY mixing time of 300 ms. MAS experiments with re-coupling of anisotropic interactions, like the 13C-(1)H dipolar couplings, benefit from the excellent resolution of 13C shifts that enables assignment of the couplings to specific carbon atoms. The traditional 2H NMR experiments on deuterated lipids have higher sensitivity when conducted on oriented samples at higher magnetic field strength. A very large number of NMR parameters from lipid bilayers is now accessible, providing information about conformation and dynamics for every lipid segment. The NMR methods have the sensitivity and resolution to study lipid-protein interaction, lateral lipid organization, and the location of solvents and drugs in the lipid matrix.

Development of a micro nuclear magnetic resonance system

NASA Astrophysics Data System (ADS)

Goloshevsky, Artem

Application of Nuclear Magnetic Resonance (NMR) to on-line/in-line control of industrial processes is currently limited by equipment costs and requirements for installation. A superconducting magnet generating strong fields is the most expensive part of a typical NMR instrument. In industrial environments, fringe magnetic fields make accommodation of NMR instruments difficult. However, a portable, low-cost and low-field magnetic resonance system can be used in virtually any environment. Development of a number of hardware components for a portable, low-cost NMR instrument is reported in this dissertation. Chapter one provides a discussion on a miniaturized Helmholtz spiral radio-frequency (RF) coil (average diameter equal to 3.5 mm) and an NMR probe built around a capillary (outer diameter = 1.59 mm and inner diameter = 1.02 mm) for flow imaging. Experiments of NMR spectroscopy, static and dynamic (flow) imaging, conducted with the use of the miniaturized coil, are described. Chapter two presents a microfabricated package of two biaxial gradient coils and a Helmholtz RF coil. Planar configuration of discrete wires was used to create magnetic field gradients. Performance of the microfabricated gradient coils while imaging water flow compared well with a commercial gradient set of much larger size. Chapter three reports on flow imaging experiments with power law fluids (aqueous solutions of sodium salt of carboxymethyl cellulose (CMC)) of different viscosities, carried out in the NMR probe with the miniaturized RF coil and capillary. Viscosities of the CMC solutions were determined based on the curve fits of the velocity profiles and simultaneous measurements of the flow rates. The curve fits were carried out according to the power law model equations. The NMR viscosity measurements compared well with measurements of the same CMC samples, performed on a conventional rotational rheometer. A portable, home-built transceiver, designed for NMR applications utilizing a miniaturized RF coil, is described in chapter four. The maximum RF power, occurring in the transceiver, was 21.5 dBm. Two transistor-transistor logic (TTL) switches functioned as an active duplexer. A quadrature detection scheme was used. The transceiver, combined with a filter/amplifier module, data acquisition (DAQ and RF generating PC boards, was successfully tested in NMR spectroscopy experiments at low magnetic field. It was demonstrated that, starting with the RF probe, a typical, large size NMR instrument can be miniaturized without impairment to the quality of the data. Such an instrument will be readily used in many industrial process control applications (e.g. for analysis of material properties and identification of chemicals).

The (HMI9293) acquisition of a 200 MHz nuclear magnetic resonance spectrometer

NASA Astrophysics Data System (ADS)

Hageman, James H.

1994-09-01

With the funds awarded from DOD-AFOSR and matching funds from New Mexico State a new Varian Gemini 200 MHz nmr was purchased and installed in the spring of 1994. This instrument is capable of 1H and 130 nmr, is very sensitive, and can also do Hetcor experiments to facilitate proton assignments. It is very easy to use and has proven thus far to be extremely reliable. The change in the research output in the department has been significant. Whereas previously students had to sometimes wait days to run routine nmr spectra because our high field instrument was otherwise occupied with longer experiments, now they can run spectra immediately (or with minimal wait). This speeds up structure assignments, and gives students instant gratification when experiments succeed and rapid feedback when they are not successful.

The application of absolute quantitative (1)H NMR spectroscopy in drug discovery and development.

PubMed

Singh, Suruchi; Roy, Raja

2016-07-01

The identification of a drug candidate and its structural determination is the most important step in the process of the drug discovery and for this, nuclear magnetic resonance (NMR) is one of the most selective analytical techniques. The present review illustrates the various perspectives of absolute quantitative (1)H NMR spectroscopy in drug discovery and development. It deals with the fundamentals of quantitative NMR (qNMR), the physiochemical properties affecting qNMR, and the latest referencing techniques used for quantification. The precise application of qNMR during various stages of drug discovery and development, namely natural product research, drug quantitation in dosage forms, drug metabolism studies, impurity profiling and solubility measurements is elaborated. To achieve this, the authors explore the literature of NMR in drug discovery and development between 1963 and 2015. It also takes into account several other reviews on the subject. qNMR experiments are used for drug discovery and development processes as it is a non-destructive, versatile and robust technique with high intra and interpersonal variability. However, there are several limitations also. qNMR of complex biological samples is incorporated with peak overlap and a low limit of quantification and this can be overcome by using hyphenated chromatographic techniques in addition to NMR.

119Sn-NMR investigations on superconducting Ca 3Ir 4Sn 13: Evidence for multigap superconductivity

DOE PAGES

Sarkar, R.; Petrovic, C.; Bruckner, F.; ...

2015-09-25

In this study, we report bulk superconductivity (SC) in Ca 3Ir 4Sn 13 by means of 119Sn nuclear magnetic resonance (NMR) experiments. Two classical signatures of BCS superconductivity in spin-lattice relaxation rate (1/T 1), namely the Hebel–Slichter coherence peak just below the T c, and the exponential decay in the superconducting phase, are evident. The noticeable decrease of 119Sn Knight shift below T c indicates spin-singlet superconductivity. The temperature dependence of the spin-lattice relaxation rate 119(1/T 1) is convincingly described by the multigap isotropic superconducting gap. NMR experiments do not witness any sign of enhanced spin fluctuations.

What Is the True Color of Fresh Meat? A Biophysical Undergraduate Laboratory Experiment Investigating the Effects of Ligand Binding on Myoglobin Using Optical, EPR, and NMR Spectroscopy

ERIC Educational Resources Information Center

Linenberger, Kimberly; Bretz, Stacey Lowery; Crowder, Michael W.; McCarrick, Robert; Lorigan, Gary A.; Tierney, David L.

2011-01-01

With an increased focus on integrated upper-level laboratories, we present an experiment integrating concepts from inorganic, biological, and physical chemistry content areas. Students investigate the effects of ligand strength on the spectroscopic properties of the heme center in myoglobin using UV-vis, [superscript 1]H NMR, and EPR…

(1)H-(13)C Hetero-nuclear dipole-dipole couplings of methyl groups in stationary and magic angle spinning solid-state NMR experiments of peptides and proteins.

PubMed

Wu, Chin H; Das, Bibhuti B; Opella, Stanley J

2010-02-01

(13)C NMR of isotopically labeled methyl groups has the potential to combine spectroscopic simplicity with ease of labeling for protein NMR studies. However, in most high resolution separated local field experiments, such as polarization inversion spin exchange at the magic angle (PISEMA), that are used to measure (1)H-(13)C hetero-nuclear dipolar couplings, the four-spin system of the methyl group presents complications. In this study, the properties of the (1)H-(13)C hetero-nuclear dipolar interactions of (13)C-labeled methyl groups are revealed through solid-state NMR experiments on a range of samples, including single crystals, stationary powders, and magic angle spinning of powders, of (13)C(3) labeled alanine alone and incorporated into a protein. The spectral simplifications resulting from proton detected local field (PDLF) experiments are shown to enhance resolution and simplify the interpretation of results on single crystals, magnetically aligned samples, and powders. The complementarity of stationary sample and magic angle spinning (MAS) measurements of dipolar couplings is demonstrated by applying polarization inversion spin exchange at the magic angle and magic angle spinning (PISEMAMAS) to unoriented samples. Copyright 2009 Elsevier Inc. All rights reserved.

Optimization of identity operation in NMR spectroscopy via genetic algorithm: Application to the TEDOR experiment

NASA Astrophysics Data System (ADS)

Manu, V. S.; Veglia, Gianluigi

2016-12-01

Identity operation in the form of π pulses is widely used in NMR spectroscopy. For an isolated single spin system, a sequence of even number of π pulses performs an identity operation, leaving the spin state essentially unaltered. For multi-spin systems, trains of π pulses with appropriate phases and time delays modulate the spin Hamiltonian to perform operations such as decoupling and recoupling. However, experimental imperfections often jeopardize the outcome, leading to severe losses in sensitivity. Here, we demonstrate that a newly designed Genetic Algorithm (GA) is able to optimize a train of π pulses, resulting in a robust identity operation. As proof-of-concept, we optimized the recoupling sequence in the transferred-echo double-resonance (TEDOR) pulse sequence, a key experiment in biological magic angle spinning (MAS) solid-state NMR for measuring multiple carbon-nitrogen distances. The GA modified TEDOR (GMO-TEDOR) experiment with improved recoupling efficiency results in a net gain of sensitivity up to 28% as tested on a uniformly 13C, 15N labeled microcrystalline ubiquitin sample. The robust identity operation achieved via GA paves the way for the optimization of several other pulse sequences used for both solid- and liquid-state NMR used for decoupling, recoupling, and relaxation experiments.

High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification

NASA Astrophysics Data System (ADS)

Kotler, Samuel A.; Brender, Jeffrey R.; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M. Banaszak; Marsh, E. Neil. G.; Ramamoorthy, Ayyalusamy

2015-07-01

Alzheimer’s disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling 1H-1H NMR experiments to overcome many of these limitations. Using 1H-1H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time 1H-1H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils.

High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification

PubMed Central

Kotler, Samuel A.; Brender, Jeffrey R.; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M. Banaszak; Marsh, E. Neil. G.; Ramamoorthy, Ayyalusamy

2015-01-01

Alzheimer’s disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling 1H-1H NMR experiments to overcome many of these limitations. Using 1H-1H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time 1H-1H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5–15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils. PMID:26138908

High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification.

PubMed

Kotler, Samuel A; Brender, Jeffrey R; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M Banaszak; Marsh, E Neil G; Ramamoorthy, Ayyalusamy

2015-07-03

Alzheimer's disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling (1)H-(1)H NMR experiments to overcome many of these limitations. Using (1)H-(1)H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time (1)H-(1)H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils.

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

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.

SIMPSON: A General Simulation Program for Solid-State NMR Spectroscopy

NASA Astrophysics Data System (ADS)

Bak, Mads; Rasmussen, Jimmy T.; Nielsen, Niels Chr.

2000-12-01

A computer program for fast and accurate numerical simulation of solid-state NMR experiments is described. The program is designed to emulate a NMR spectrometer by letting the user specify high-level NMR concepts such as spin systems, nuclear spin interactions, RF irradiation, free precession, phase cycling, coherence-order filtering, and implicit/explicit acquisition. These elements are implemented using the Tcl scripting language to ensure a minimum of programming overhead and direct interpretation without the need for compilation, while maintaining the flexibility of a full-featured programming language. Basicly, there are no intrinsic limitations to the number of spins, types of interactions, sample conditions (static or spinning, powders, uniaxially oriented molecules, single crystals, or solutions), and the complexity or number of spectral dimensions for the pulse sequence. The applicability ranges from simple 1D experiments to advanced multiple-pulse and multiple-dimensional experiments, series of simulations, parameter scans, complex data manipulation/visualization, and iterative fitting of simulated to experimental spectra. A major effort has been devoted to optimizing the computation speed using state-of-the-art algorithms for the time-consuming parts of the calculations implemented in the core of the program using the C programming language. Modification and maintenance of the program are facilitated by releasing the program as open source software (General Public License) currently at http://nmr.imsb.au.dk. The general features of the program are demonstrated by numerical simulations of various aspects for REDOR, rotational resonance, DRAMA, DRAWS, HORROR, C7, TEDOR, POST-C7, CW decoupling, TPPM, F-SLG, SLF, SEMA-CP, PISEMA, RFDR, QCPMG-MAS, and MQ-MAS experiments.

SIMPSON: A general simulation program for solid-state NMR spectroscopy

NASA Astrophysics Data System (ADS)

Bak, Mads; Rasmussen, Jimmy T.; Nielsen, Niels Chr.

2011-12-01

A computer program for fast and accurate numerical simulation of solid-state NMR experiments is described. The program is designed to emulate a NMR spectrometer by letting the user specify high-level NMR concepts such as spin systems, nuclear spin interactions, RF irradiation, free precession, phase cycling, coherence-order filtering, and implicit/explicit acquisition. These elements are implemented using the Tel scripting language to ensure a minimum of programming overhead and direct interpretation without the need for compilation, while maintaining the flexibility of a full-featured programming language. Basicly, there are no intrinsic limitations to the number of spins, types of interactions, sample conditions (static or spinning, powders, uniaxially oriented molecules, single crystals, or solutions), and the complexity or number of spectral dimensions for the pulse sequence. The applicability ranges from simple ID experiments to advanced multiple-pulse and multiple-dimensional experiments, series of simulations, parameter scans, complex data manipulation/visualization, and iterative fitting of simulated to experimental spectra. A major effort has been devoted to optimizing the computation speed using state-of-the-art algorithms for the time-consuming parts of the calculations implemented in the core of the program using the C programming language. Modification and maintenance of the program are facilitated by releasing the program as open source software (General Public License) currently at http://nmr.imsb.au.dk. The general features of the program are demonstrated by numerical simulations of various aspects for REDOR, rotational resonance, DRAMA, DRAWS, HORROR, C7, TEDOR, POST-C7, CW decoupling, TPPM, F-SLG, SLF, SEMA-CP, PISEMA, RFDR, QCPMG-MAS, and MQ-MAS experiments.

Double proton transfer in the complex of acetic acid with methanol: Theory versus experiment

NASA Astrophysics Data System (ADS)

Fernández-Ramos, Antonio; Smedarchina, Zorka; Rodríguez-Otero, Jesús

2001-01-01

To test the approximate instanton approach to intermolecular proton-transfer dynamics, we report multidimensional ab initio bimolecular rate constants of HH, HD, and DD exchange in the complex of acetic acid with methanol in tetrahydrofuran-d8, and compare them with the NMR (nuclear magnetic resonance) experiments of Gerritzen and Limbach. The bimolecular rate constants are evaluated as products of the exchange rates and the equilibrium rate constants of complex formation in solution. The two molecules form hydrogen-bond bridges and the exchange occurs via concerted transfer of two protons. The dynamics of this transfer is evaluated in the complete space of 36 vibrational degrees of freedom. The geometries of the two isolated molecules, the complex, and the transition states corresponding to double proton transfer are fully optimized at QCISD (quadratic configuration interaction including single and double substitutions) level of theory, and the normal-mode frequencies are calculated at MP2 (Møller-Plesset perturbation theory of second order) level with the 6-31G (d,p) basis set. The presence of the solvent is taken into account via single-point calculations over the gas phase geometries with the PCM (polarized continuum model). The proton exchange rate constants, calculated with the instanton method, show the effect of the structure and strength of the hydrogen bonds, reflected in the coupling between the tunneling motion and the other vibrations of the complex. Comparison with experiment, which shows substantial kinetic isotopic effects (KIE), indicates that tunneling prevails over classic exchange for the whole temperature range of observation. The unusual behavior of the experimental KIE upon single and double deuterium substitution is well reproduced and is related to the synchronicity of two-atom tunneling.

A Markov Random Field Framework for Protein Side-Chain Resonance Assignment

NASA Astrophysics Data System (ADS)

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

Nuclear magnetic resonance (NMR) spectroscopy plays a critical role in structural genomics, and serves as a primary tool for determining protein structures, dynamics and interactions in physiologically-relevant solution conditions. The current speed of protein structure determination via NMR is limited by the lengthy time required in resonance assignment, which maps spectral peaks to specific atoms and residues in the primary sequence. Although numerous algorithms have been developed to address the backbone resonance assignment problem [68,2,10,37,14,64,1,31,60], little work has been done to automate side-chain resonance assignment [43, 48, 5]. Most previous attempts in assigning side-chain resonances depend on a set of NMR experiments that record through-bond interactions with side-chain protons for each residue. Unfortunately, these NMR experiments have low sensitivity and limited performance on large proteins, which makes it difficult to obtain enough side-chain resonance assignments. On the other hand, it is essential to obtain almost all of the side-chain resonance assignments as a prerequisite for high-resolution structure determination. To overcome this deficiency, we present a novel side-chain resonance assignment algorithm based on alternative NMR experiments measuring through-space interactions between protons in the protein, which also provide crucial distance restraints and are normally required in high-resolution structure determination. We cast the side-chain resonance assignment problem into a Markov Random Field (MRF) framework, and extend and apply combinatorial protein design algorithms to compute the optimal solution that best interprets the NMR data. Our MRF framework captures the contact map information of the protein derived from NMR spectra, and exploits the structural information available from the backbone conformations determined by orientational restraints and a set of discretized side-chain conformations (i.e., rotamers). A Hausdorff-based computation is employed in the scoring function to evaluate the probability of side-chain resonance assignments to generate the observed NMR spectra. The complexity of the assignment problem is first reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is used to find a set of optimal side-chain resonance assignments that best fit the NMR data. We have tested our algorithm on NMR data for five proteins, including the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), human ubiquitin, the ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta (pol η UBZ), and the human Set2-Rpb1 interacting domain (hSRI). Our algorithm assigns resonances for more than 90% of the protons in the proteins, and achieves about 80% correct side-chain resonance assignments. The final structures computed using distance restraints resulting from the set of assigned side-chain resonances have backbone RMSD 0.5 - 1.4 Å and all-heavy-atom RMSD 1.0 - 2.2 Å from the reference structures that were determined by X-ray crystallography or traditional NMR approaches. These results demonstrate that our algorithm can be successfully applied to automate side-chain resonance assignment and high-quality protein structure determination. Since our algorithm does not require any specific NMR experiments for measuring the through-bond interactions with side-chain protons, it can save a significant amount of both experimental cost and spectrometer time, and hence accelerate the NMR structure determination process.

Measurement and Quantification of Heterogeneity, Flow, and Mass Transfer in Porous Media Using NMR Low-Field Techiques

NASA Astrophysics Data System (ADS)

Paciok, E.; Olaru, A. M.; Haber, A.; van Landeghem, M.; Haber-Pohlmeier, S.; Sucre, O. E.; Perlo, J.; Casanova, F.; Blümich, B.; RWTH Aachen Mobile Low-Field NMR

2011-12-01

Nuclear magnetic resonance (NMR) is renowned for its unique potential to both reveal and correlate spectroscopic, relaxometric, spatial and dynamic properties in a large variety of organic and inorganic systems. NMR has no restrictions regarding sample opacity and is an entirely non-invasive method, which makes it the ideal tool for the investigation of porous media. However, for years NMR research of soils was limited by the use of high-field NMR devices, which necessitated elaborate NMR experiments and were not applicable to bulky samples or on-site field measurements. The evolution of low-field NMR devices during the past 20 years has brought forth portable, small-scale NMR systems with open and closed magnet arrangements specialized to specific NMR applications. In combination with recent advances in 2D-NMR Laplace methodology [1], low-field NMR has opened up the possibility to study real-life microporous systems ranging from granular media to natural soils and oil well boreholes. Thus, information becomes available, which before has not been accessible with high-field NMR. In this work, we present our recent progress in mobile low-field NMR probe design for field measurements of natural soils: a slim-line logging tool, which can be rammed into the soil of interest on-site. The performance of the device is demonstrated in measurements of moisture profiles of model soils [2] and field measurements of relaxometric properties and moisture profiles of natural soils [3]. Moreover, an improved concept of the slim-line logging tool is shown, with a higher excitation volume and a better signal-to-noise due to an improved coil design. Furthermore, we present our recent results in 2D exchange relaxometry and simulation. These include relaxation-relaxation experiments on natural soils with varying degree of moisture saturation, where we could draw a connection between the relaxometric properties of the soil to its pore size-related diffusivity and to its clay content. Also models, simulations and possibilities are discussed to derive from the so obtained information a "characteristic pore shape" that can be used to characterize and to fingerprint natural soils. [1] L. Venkataramanan et al., IEEE Trans. Signal Process. 2002, 50, 1017-26. [2] O. Sucre et al., Open Magn. Reson. J. 2010, 3, 63-68. [3] B. Blümich et al., New J. Phys. 2011, 13, 015003.

Interfaces in polymer nanocomposites – An NMR study

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

Böhme, Ute; Scheler, Ulrich, E-mail: scheler@ipfdd.de

Nuclear Magnetic Resonance (NMR) is applied for the investigation of polymer nanocomposites. Solid-state NMR is applied to study the modification steps to compatibilize layered double hydroxides with non-polar polymers. {sup 1}H relaxation NMR gives insight on the polymer dynamics over a wide range of correlation times. For the polymer chain dynamics the transverse relaxation time T{sub 2} is most suited. In this presentation we report on two applications of T{sub 2} measurements under external mechanical stress. In a low-field system relaxation NMR studies are performed in-situ under uniaxial stress. High-temperature experiments in a Couette cell permit the investigation of themore » polymer dynamics in the melt under shear flow.« less

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.

1H and 13C NMR spectra of C-6 and C-9 substituted 3-azabicyclco[3.3.1]nonanes.

PubMed

Goodall, Kirsten; Brimble, Margaret; Barker, David

2008-01-01

The 1H and 13C NMR data for 3-azabicyclo[3.3.1]nonanes with OH and OMe substituents at C-6 and C-9 were measured using 1D (DEPT) and 2D (COSY, HSQC, HMBC, NOESY) experiments. Comparison of this NMR data illustrates the effects of stereochemistry and substitution at these positions. Copyright (c) 2007 John Wiley & Sons, Ltd.

Active elimination of radio frequency interference for improved signal-to-noise ratio for in-situ NMR experiments in strong magnetic field gradients

NASA Astrophysics Data System (ADS)

Ibrahim, M.; Pardi, C. I.; Brown, T. W. C.; McDonald, P. J.

2018-02-01

Improvement in the signal-to-noise ratio of Nuclear Magnetic Resonance (NMR) systems may be achieved either by increasing the signal amplitude or by decreasing the noise. The noise has multiple origins - not all of which are strictly "noise": incoherent thermal noise originating in the probe and pre-amplifiers, probe ring down or acoustic noise and coherent externally broadcast radio frequency transmissions. The last cannot always be shielded in open access experiments. In this paper, we show that pulsed, low radio-frequency data communications are a significant source of broadcast interference. We explore two signal processing methods of de-noising short T2∗ NMR experiments corrupted by these communications: Linear Predictive Coding (LPC) and the Discrete Wavelet Transform (DWT). Results are shown for numerical simulations and experiments conducted under controlled conditions with pseudo radio frequency interference. We show that both the LPC and DWT methods have merit.

NMR Stratagems for the Study of Multiple Kinetic Hydrogen/Deuterium Isotope Effectsof Proton Exchange. Example: Di-p-fluorophenylformamidine/THF

NASA Astrophysics Data System (ADS)

Limbach, Hans-Heinrich; Meschede, Ludger; Scherer, Gerd

1989-05-01

Stratagems are presented for the determination of kinetic isotope effects of proton exchange reactions by dynamic NMR spectroscopy. In such experiments, lineshape analyses and/or polarization transfer experiments are performed on the exchanging protons or deuterons as well as on remote spins, as a function of the deuterium fraction in the mobile proton sites. These methods are NMR analogs of previous proton inventory techniques involving classical kinetic methods. A theory is developed in order to derive the kinetic isotope effects as well as the number of transferred protons from the experimental NMR spectra. The technique is then applied to the problem of proton exchange in the system 15N,15N'-di-p-fluorophenylibrmamidine, a nitrogen analog of formic acid, dissolved in tetrahydrofuran-d8 (THF). DFFA forms two conformers in THF to which s-trans and s-cis structures have been assigned. Only the s-trans conformer is able to dimerize and exchange protons. Lineshape simulations and magnetization transfer experiments were carried out at 189,2 K, at a concentration of 0.02 mol l-1, as a function of the deuterium fraction D in the 1H-15N sites. Using 1H NMR spectroscopy, a linear dependence of the inverse proton lifetimes on D was observed. From this it was concluded that two protons are transported in the rate limiting step of the proton exchange. This result is expected for a double proton transfer in an s-trans dimer with a cyclic structure. The full kinetic HH/HD/DD isotope effects of 233:11:1 at 189 K were determined through 19F NMR experiments on the same samples. The deviation from the rule of geometric mean, although substantial, is much smaller than found in previous studies of intramolecular HH transfer reactions. Possible causes of this effect are discussed.

Streamlining workflow and automation to accelerate laboratory scale protein production.

PubMed

Konczal, Jennifer; Gray, Christopher H

2017-05-01

Protein production facilities are often required to produce diverse arrays of proteins for demanding methodologies including crystallography, NMR, ITC and other reagent intensive techniques. It is common for these teams to find themselves a bottleneck in the pipeline of ambitious projects. This pressure to deliver has resulted in the evolution of many novel methods to increase capacity and throughput at all stages in the pipeline for generation of recombinant proteins. This review aims to describe current and emerging options to accelerate the success of protein production in Escherichia coli. We emphasize technologies that have been evaluated and implemented in our laboratory, including innovative molecular biology and expression vectors, small-scale expression screening strategies and the automation of parallel and multidimensional chromatography. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Insight into hydrogen bonding of uranyl hydroxide layers and capsules by use of 1H magic-angle spinning NMR spectroscopy [Insight into the hydrogen bonding for uranyl hydroxides using 1H MAS NMR spectroscopy

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

Alam, Todd M.; Liao, Zuolei; Nyman, May

Solid-state 1H magic-angle spinning (MAS) NMR was used to investigate local proton environments in anhydrous [UO 2(OH) 2] (α-UOH) and hydrated uranyl hydroxide [(UO 2) 4O(OH) 6·5H 2O (metaschoepite). For the metaschoepite material, proton resonances of the μ 2-OH hydroxyl and interlayer waters were resolved, with two-dimensional (2D) double-quantum (DQ) 1H– 1H NMR correlation experiments revealing strong dipolar interactions between these different proton species. The experimental NMR results were combined with first-principles CASTEP GIPAW (gauge including projector-augmented wave) chemical shift calculations to develop correlations between hydrogen-bond strength and observed 1H NMR chemical shifts. Furthermore, these NMR correlations allowed characterization ofmore » local hydrogen-bond environments in uranyl U 24 capsules and of changes in hydrogen bonding that occurred during thermal dehydration of metaschoepite.« less

NMR at pressures up to 90 GPa

NASA Astrophysics Data System (ADS)

Meier, Thomas; Khandarkhaeva, Saiana; Petitgirard, Sylvain; Körber, Thomas; Lauerer, Alexander; Rössler, Ernst; Dubrovinsky, Leonid

2018-07-01

The past 15 years have seen an astonishing increase in Nuclear Magnetic Resonance (NMR) sensitivity and accessible pressure range in high-pressure NMR experiments, owing to a series of new developments of NMR spectroscopy applied to the diamond anvil cell (DAC). Recently, with the application of electro-magnetic lenses, so-called Lenz lenses, in toroidal diamond indenter cells, pressures of up to 72 GPa with NMR spin sensitivities of about 1012 spin/Hz1/2 has been achieved. Here, we describe the implementation of a refined NMR resonator structure using a pair of double stage Lenz lenses driven by a Helmholtz coil within a standard DAC, allowing to measure sample volumes as small as 100 pl prior to compression. With this set-up, pressures close to 100 GPa could be realised repeatedly, with enhanced spin sensitivities of about 5 × 1011 spin/Hz1/2. The manufacturing and handling of these new NMR-DACs is relatively easy and straightforward, which will allow for further applications in physics, chemistry, or biochemistry.

Insight into hydrogen bonding of uranyl hydroxide layers and capsules by use of 1H magic-angle spinning NMR spectroscopy [Insight into the hydrogen bonding for uranyl hydroxides using 1H MAS NMR spectroscopy

DOE PAGES

Alam, Todd M.; Liao, Zuolei; Nyman, May; ...

2016-04-27

Solid-state 1H magic-angle spinning (MAS) NMR was used to investigate local proton environments in anhydrous [UO 2(OH) 2] (α-UOH) and hydrated uranyl hydroxide [(UO 2) 4O(OH) 6·5H 2O (metaschoepite). For the metaschoepite material, proton resonances of the μ 2-OH hydroxyl and interlayer waters were resolved, with two-dimensional (2D) double-quantum (DQ) 1H– 1H NMR correlation experiments revealing strong dipolar interactions between these different proton species. The experimental NMR results were combined with first-principles CASTEP GIPAW (gauge including projector-augmented wave) chemical shift calculations to develop correlations between hydrogen-bond strength and observed 1H NMR chemical shifts. Furthermore, these NMR correlations allowed characterization ofmore » local hydrogen-bond environments in uranyl U 24 capsules and of changes in hydrogen bonding that occurred during thermal dehydration of metaschoepite.« less

Sensitivity-enhanced detection of non-labile proton and carbon NMR spectra on water resonances.

PubMed

Novakovic, Mihajlo; Martinho, Ricardo P; Olsen, Gregory L; Lustig, Michael S; Frydman, Lucio

2017-12-20

Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals of labile protons by continuously transferring these protons' saturation to an abundant solvent pool like water. The present study expands these principles by fusing into these experiments homonuclear isotropic mixing sequences, enabling the water-enhanced detection of non-exchangeable species. Further opportunities are opened by the addition of coupling-mediated heteronuclear polarization transfers, which then impose on the water resonance a saturation stemming from non-labile heteronuclear species like 13 C. To multiplex the ensuing experiments, these relayed approaches are combined with time-domain schemes involving multiple Ramsey-labeling experiments imparting the frequencies of the non-labile sites on the water resonance, via chemical exchange. 13 C and 1 H NMR spectra were detected in this fashion with about two-fold SNR amplification vis-à-vis conventionally detected spectroscopies. When combined with non-uniform sampling principles, this methodology thus becomes a sensitive alternative to detect non-exchangeable species in biomolecules. Still, multiple parameters including the scalar couplings and solvent exchange rates, will affect the efficiency and consequently the practicality of the overall experiment.

Modeling Quantum Dynamics in Multidimensional Systems

NASA Astrophysics Data System (ADS)

Liss, Kyle; Weinacht, Thomas; Pearson, Brett

2017-04-01

Coupling between different degrees-of-freedom is an inherent aspect of dynamics in multidimensional quantum systems. As experiments and theory begin to tackle larger molecular structures and environments, models that account for vibrational and/or electronic couplings are essential for interpretation. Relevant processes include intramolecular vibrational relaxation, conical intersections, and system-bath coupling. We describe a set of simulations designed to model coupling processes in multidimensional molecular systems, focusing on models that provide insight and allow visualization of the dynamics. Undergraduates carried out much of the work as part of a senior research project. In addition to the pedagogical value, the simulations allow for comparison between both explicit and implicit treatments of a system's many degrees-of-freedom.

Utilizing Multidimensional Measures of Race in Education Research: The Case of Teacher Perceptions

PubMed Central

Irizarry, Yasmiyn

2015-01-01

Education scholarship on race using quantitative data analysis consists largely of studies on the black-white dichotomy, and more recently, on the experiences of student within conventional racial/ethnic categories (white, Hispanic/Latina/o, Asian, black). Despite substantial shifts in the racial and ethnic composition of American children, studies continue to overlook the diverse racialized experiences for students of Asian and Latina/o descent, the racialization of immigration status, and the educational experiences of Native American students. This study provides one possible strategy for developing multidimensional measures of race using large-scale datasets and demonstrates the utility of multidimensional measures for examining educational inequality, using teacher perceptions of student behavior as a case in point. With data from the first grade wave of the Early Childhood Longitudinal Study, Kindergarten Cohort of 1998–1999, I examine differences in teacher ratings of Externalizing Problem Behaviors and Approaches to Learning across fourteen racialized subgroups at the intersections of race, ethnicity, and immigrant status. Results show substantial subgroup variation in teacher perceptions of problem and learning behaviors, while also highlighting key points of divergence and convergence within conventional racial/ethnic categories. PMID:26413559

Utilizing Multidimensional Measures of Race in Education Research: The Case of Teacher Perceptions.

PubMed

Irizarry, Yasmiyn

2015-10-01

Education scholarship on race using quantitative data analysis consists largely of studies on the black-white dichotomy, and more recently, on the experiences of student within conventional racial/ethnic categories (white, Hispanic/Latina/o, Asian, black). Despite substantial shifts in the racial and ethnic composition of American children, studies continue to overlook the diverse racialized experiences for students of Asian and Latina/o descent, the racialization of immigration status, and the educational experiences of Native American students. This study provides one possible strategy for developing multidimensional measures of race using large-scale datasets and demonstrates the utility of multidimensional measures for examining educational inequality, using teacher perceptions of student behavior as a case in point. With data from the first grade wave of the Early Childhood Longitudinal Study, Kindergarten Cohort of 1998-1999, I examine differences in teacher ratings of Externalizing Problem Behaviors and Approaches to Learning across fourteen racialized subgroups at the intersections of race, ethnicity, and immigrant status. Results show substantial subgroup variation in teacher perceptions of problem and learning behaviors, while also highlighting key points of divergence and convergence within conventional racial/ethnic categories.

Application of spin-exchange relaxation-free magnetometry to the Cosmic Axion Spin Precession Experiment

NASA Astrophysics Data System (ADS)

Wang, Tao; Kimball, Derek F. Jackson; Sushkov, Alexander O.; Aybas, Deniz; Blanchard, John W.; Centers, Gary; Kelley, Sean R. O.'; Wickenbrock, Arne; Fang, Jiancheng; Budker, Dmitry

2018-03-01

The Cosmic Axion Spin Precession Experiment (CASPEr) seeks to measure oscillating torques on nuclear spins caused by axion or axion-like-particle (ALP) dark matter via nuclear magnetic resonance (NMR) techniques. A sample spin-polarized along a leading magnetic field experiences a resonance when the Larmor frequency matches the axion/ALP Compton frequency, generating precessing transverse nuclear magnetization. Here we demonstrate a Spin-Exchange Relaxation-Free (SERF) magnetometer with sensitivity ≈ 1 fT /√{ Hz } and an effective sensing volume of 0.1 cm3 that may be useful for NMR detection in CASPEr. A potential drawback of SERF-magnetometer-based NMR detection is the SERF's limited dynamic range. Use of a magnetic flux transformer to suppress the leading magnetic field is considered as a potential method to expand the SERF's dynamic range in order to probe higher axion/ALP Compton frequencies.

Successful Sampling Strategy Advances Laboratory Studies of NMR Logging in Unconsolidated Aquifers

NASA Astrophysics Data System (ADS)

Behroozmand, Ahmad A.; Knight, Rosemary; Müller-Petke, Mike; Auken, Esben; Barfod, Adrian A. S.; Ferré, Ty P. A.; Vilhelmsen, Troels N.; Johnson, Carole D.; Christiansen, Anders V.

2017-11-01

The nuclear magnetic resonance (NMR) technique has become popular in groundwater studies because it responds directly to the presence and mobility of water in a porous medium. There is a need to conduct laboratory experiments to aid in the development of NMR hydraulic conductivity models, as is typically done in the petroleum industry. However, the challenge has been obtaining high-quality laboratory samples from unconsolidated aquifers. At a study site in Denmark, we employed sonic drilling, which minimizes the disturbance of the surrounding material, and extracted twelve 7.6 cm diameter samples for laboratory measurements. We present a detailed comparison of the acquired laboratory and logging NMR data. The agreement observed between the laboratory and logging data suggests that the methodologies proposed in this study provide good conditions for studying NMR measurements of unconsolidated near-surface aquifers. Finally, we show how laboratory sample size and condition impact the NMR measurements.

Studies of organic paint binders by NMR spectroscopy

NASA Astrophysics Data System (ADS)

Spyros, A.; Anglos, D.

2006-06-01

Nuclear magnetic resonance spectroscopy is applied to the study of aged binding media used in paintings, namely linseed oil, egg tempera and an acrylic medium. High resolution 1D and 2D NMR experiments establish the state of hydrolysis and oxidation of the linseed and egg tempera binders after five years of aging, by determining several markers sensitive to the hydrolytic and oxidative processes of the binder lipid fraction. The composition of the acrylic binder co-polymer is determined by 2D NMR spectroscopy, while the identification of a surfactant, poly(ethylene glycol), found in greater amounts in aged acrylic medium, is reported. The non-destructive nature of the proposed analytical NMR methodology, and minimization of the amount of binder material needed through the use of sophisticated cryoprobes and hyphenated LC-NMR techniques, make NMR attractive for the arts analyst, in view of its rapid nature and experimental simplicity.

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).

“Invisible” Conformers of an Antifungal Disulfide Protein Revealed by Constrained Cold and Heat Unfolding, CEST-NMR Experiments, and Molecular Dynamics Calculations

PubMed Central

Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

2015-01-01

Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20–40 % at 298 K in a disulfide-rich protein. In addition, sensitive 15N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR “dark matter”. Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. PMID:25676351

High-Resolution NMR Reveals Secondary Structure and Folding of Amino Acid Transporter from Outer Chloroplast Membrane

PubMed Central

Zook, James D.; Molugu, Trivikram R.; Jacobsen, Neil E.; Lin, Guangxin; Soll, Jürgen; Cherry, Brian R.; Brown, Michael F.; Fromme, Petra

2013-01-01

Solving high-resolution structures for membrane proteins continues to be a daunting challenge in the structural biology community. In this study we report our high-resolution NMR results for a transmembrane protein, outer envelope protein of molar mass 16 kDa (OEP16), an amino acid transporter from the outer membrane of chloroplasts. Three-dimensional, high-resolution NMR experiments on the 13C, 15N, 2H-triply-labeled protein were used to assign protein backbone resonances and to obtain secondary structure information. The results yield over 95% assignment of N, HN, CO, Cα, and Cβ chemical shifts, which is essential for obtaining a high resolution structure from NMR data. Chemical shift analysis from the assignment data reveals experimental evidence for the first time on the location of the secondary structure elements on a per residue basis. In addition T 1Z and T2 relaxation experiments were performed in order to better understand the protein dynamics. Arginine titration experiments yield an insight into the amino acid residues responsible for protein transporter function. The results provide the necessary basis for high-resolution structural determination of this important plant membrane protein. PMID:24205117

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

An ultra-low cost NMR device with arbitrary pulse programming

NASA Astrophysics Data System (ADS)

Chen, Hsueh-Ying; Kim, Yaewon; Nath, Pulak; Hilty, Christian

2015-06-01

Ultra-low cost, general purpose electronics boards featuring microprocessors or field programmable gate arrays (FPGA) are reaching capabilities sufficient for direct implementation of NMR spectrometers. We demonstrate a spectrometer based on such a board, implemented with a minimal need for the addition of custom electronics and external components. This feature allows such a spectrometer to be readily implemented using typical knowledge present in an NMR laboratory. With FPGA technology, digital tasks are performed with precise timing, without the limitation of predetermined hardware function. In this case, the FPGA is used for programming of arbitrarily timed pulse sequence events, and to digitally generate required frequencies. Data acquired from a 0.53 T permanent magnet serves as a demonstration of the flexibility of pulse programming for diverse experiments. Pulse sequences applied include a spin-lattice relaxation measurement using a pulse train with small-flip angle pulses, and a Carr-Purcell-Meiboom-Gill experiment with phase cycle. Mixing of NMR signals with a digitally generated, 4-step phase-cycled reference frequency is further implemented to achieve sequential quadrature detection. The flexibility in hardware implementation permits tailoring this type of spectrometer for applications such as relaxometry, polarimetry, diffusometry or NMR based magnetometry.

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.

A Solid-State NMR Study of Selenium Substitution into Nanocrystalline Hydroxyapatite

PubMed Central

Kolmas, Joanna; Kuras, Marzena; Oledzka, Ewa; Sobczak, Marcin

2015-01-01

The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300-1.2SeO4) or selenite (HA300-1.2SeO3) substituted hydroxyapatites were synthesized using the standard wet method and heated at 300 °C to remove loosely bonded water. PXRD data showed that all samples are single-phase, nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions affected the lattice constants. In selenium-containing samples the concentration of Se was very similar and amounted to 9.55% and 9.64%, for HA300-1.2SeO4 and HA300-1.2SeO3, respectively. PXRD and ssNMR data showed that the selenite doping significantly decreases the crystallite size and crystallinity degree. 31P and 1H NMR experiments demonstrated the developed surface hydrated layer in all samples, especially in HA300-1.2SeO3. 1H NMR studies showed the dehydroxylation of HA during the selenium oxyanions substitution and the existence of hydrogen bonding in structural hydroxyl group channels. 1H→77Se cross polarization NMR experiments indicated that selenites and selenates are located in the crystal lattice and on the crystal surface. PMID:25997001

A highly versatile automatized setup for quantitative measurements of PHIP enhancements

NASA Astrophysics Data System (ADS)

Kiryutin, Alexey S.; Sauer, Grit; Hadjiali, Sara; Yurkovskaya, Alexandra V.; Breitzke, Hergen; Buntkowsky, Gerd

2017-12-01

The design and application of a versatile and inexpensive experimental extension to NMR spectrometers is described that allows to carry out highly reproducible PHIP experiments directly in the NMR sample tube, i.e. under PASADENA condition, followed by the detection of the NMR spectra of hyperpolarized products with high spectral resolution. Employing this high resolution it is feasible to study kinetic processes in the solution with high accuracy. As a practical example the dissolution of hydrogen gas in the liquid and the PHIP kinetics during the hydrogenation reaction of Fmoc-O-propargyl-L-tyrosine in acetone-d6 are monitored. The timing of the setup is fully controlled by the pulse-programmer of the NMR spectrometer. By flushing with an inert gas it is possible to efficiently quench the hydrogenation reaction in a controlled fashion and to detect the relaxation of hyperpolarization without a background reaction. The proposed design makes it possible to carry out PHIP experiments in an automatic mode and reliably determine the enhancement of polarized signals.

Crossover from Commensurate to Incommensurate Antiferromagnetism in Stoichiometric NaFeAs Revealed by Single-Crystal 23Na,75As-NMR Experiments

NASA Astrophysics Data System (ADS)

Kitagawa, Kentaro; Mezaki, Yuji; Matsubayashi, Kazuyuki; Uwatoko, Yoshiya; Takigawa, Masashi

2011-03-01

We report the results of 23Na and 75As nuclear magnetic resonance (NMR) experiments on a self-flux grown high-quality single crystal of stoichiometric NaFeAs. The NMR spectra reveal a tetragonal to twinned-orthorhombic structural phase transition at TO = 57 K and an antiferromagnetic (AF) transition at TAF = 45 K. The divergent behavior of nuclear relaxation rate near TAF shows significant anisotropy, indicating that the critical slowing down of stripe-type AF fluctuations are strongly anisotropic in spin space. The NMR spectra at sufficiently low temperatures consist of sharp peaks showing a commensurate stripe AF order with a small moment of ˜0.3 μB. However, the spectra just below TAF exhibit a highly asymmetric broadening pointing to an incommensurate modulation. The commensurate-incommensurate crossover in NaFeAs shows a certain similarity to the behavior of SrFe2As2 under high pressure.

Calcium environment in silicate and aluminosilicate glasses probed by ⁴³Ca MQMAS NMR experiments and MD-GIPAW calculations.

PubMed

Gambuzzi, Elisa; Pedone, Alfonso; Menziani, Maria Cristina; Angeli, Frédéric; Florian, Pierre; Charpentier, Thibault

2015-01-01

⁴³Ca MQMAS NMR spectra of three silica-based glasses in which Ca²⁺ ions play different structural roles have been collected and processed in order to extract the underlying NMR parameter distributions. The NMR parameters have been interpreted with the help of molecular dynamics simulations and DFT-GIPAW calculations. This synergetic experimental-computational approach has allowed us to investigate the Ca environment, to estimate Ca coordination numbers from MD-derived models, and to push further the discussion about ⁴³Ca NMR sensitivity to the first and second coordination spheres: ⁴³Ca δiso and Ca-O distance can be successfully correlated as a function of Ca coordination number. Copyright © 2015 Elsevier Inc. All rights reserved.

Modification and intercalation of layered zirconium phosphates: a solid-state NMR monitoring.

PubMed

Bakhmutov, Vladimir I; Kan, Yuwei; Sheikh, Javeed Ahmad; González-Villegas, Julissa; Colón, Jorge L; Clearfield, Abraham

2017-07-01

Several layered zirconium phosphates treated with Zr(IV) ions, modified by monomethoxy-polyethyleneglycol-monophosphate and intercalated with doxorubicin hydrochloride have been studied by solid-state MAS NMR techniques. The organic components of the phosphates have been characterized by the 13 C{ 1 H} CP MAS NMR spectra compared with those of initial compounds. The multinuclear NMR monitoring has provided to establish structure and covalent attachment of organic/inorganic moieties to the surface and interlayer spaces of the phosphates. The MAS NMR experiments including kinetics of proton-phosphorus cross polarization have resulted in an unusual structure of zirconium phosphate 6 combining decoration of the phosphate surface by polymer units and their partial intercalation into the interlayer space. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Scientific Visualization Tools for Enhancement of Undergraduate Research

NASA Astrophysics Data System (ADS)

Rodriguez, W. J.; Chaudhury, S. R.

2001-05-01

Undergraduate research projects that utilize remote sensing satellite instrument data to investigate atmospheric phenomena pose many challenges. A significant challenge is processing large amounts of multi-dimensional data. Remote sensing data initially requires mining; filtering of undesirable spectral, instrumental, or environmental features; and subsequently sorting and reformatting to files for easy and quick access. The data must then be transformed according to the needs of the investigation(s) and displayed for interpretation. These multidimensional datasets require views that can range from two-dimensional plots to multivariable-multidimensional scientific visualizations with animations. Science undergraduate students generally find these data processing tasks daunting. Generally, researchers are required to fully understand the intricacies of the dataset and write computer programs or rely on commercially available software, which may not be trivial to use. In the time that undergraduate researchers have available for their research projects, learning the data formats, programming languages, and/or visualization packages is impractical. When dealing with large multi-dimensional data sets appropriate Scientific Visualization tools are imperative in allowing students to have a meaningful and pleasant research experience, while producing valuable scientific research results. The BEST Lab at Norfolk State University has been creating tools for multivariable-multidimensional analysis of Earth Science data. EzSAGE and SAGE4D have been developed to sort, analyze and visualize SAGE II (Stratospheric Aerosol and Gas Experiment) data with ease. Three- and four-dimensional visualizations in interactive environments can be produced. EzSAGE provides atmospheric slices in three-dimensions where the researcher can change the scales in the three-dimensions, color tables and degree of smoothing interactively to focus on particular phenomena. SAGE4D provides a navigable four-dimensional interactive environment. These tools allow students to make higher order decisions based on large multidimensional sets of data while diminishing the level of frustration that results from dealing with the details of processing large data sets.

SIMPSON: a general simulation program for solid-state NMR spectroscopy.

PubMed

Bak, M; Rasmussen, J T; Nielsen, N C

2000-12-01

A computer program for fast and accurate numerical simulation of solid-state NMR experiments is described. The program is designed to emulate a NMR spectrometer by letting the user specify high-level NMR concepts such as spin systems, nuclear spin interactions, RF irradiation, free precession, phase cycling, coherence-order filtering, and implicit/explicit acquisition. These elements are implemented using the Tcl scripting language to ensure a minimum of programming overhead and direct interpretation without the need for compilation, while maintaining the flexibility of a full-featured programming language. Basically, there are no intrinsic limitations to the number of spins, types of interactions, sample conditions (static or spinning, powders, uniaxially oriented molecules, single crystals, or solutions), and the complexity or number of spectral dimensions for the pulse sequence. The applicability ranges from simple 1D experiments to advanced multiple-pulse and multiple-dimensional experiments, series of simulations, parameter scans, complex data manipulation/visualization, and iterative fitting of simulated to experimental spectra. A major effort has been devoted to optimizing the computation speed using state-of-the-art algorithms for the time-consuming parts of the calculations implemented in the core of the program using the C programming language. Modification and maintenance of the program are facilitated by releasing the program as open source software (General Public License) currently at http://nmr.imsb.au.dk. The general features of the program are demonstrated by numerical simulations of various aspects for REDOR, rotational resonance, DRAMA, DRAWS, HORROR, C7, TEDOR, POST-C7, CW decoupling, TPPM, F-SLG, SLF, SEMA-CP, PISEMA, RFDR, QCPMG-MAS, and MQ-MAS experiments. Copyright 2000 Academic Press.

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

PubMed Central

2011-01-01

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

Automatic differential analysis of NMR experiments in complex samples.

PubMed

Margueritte, Laure; Markov, Petar; Chiron, Lionel; Starck, Jean-Philippe; Vonthron-Sénécheau, Catherine; Bourjot, Mélanie; Delsuc, Marc-André

2018-06-01

Liquid state nuclear magnetic resonance (NMR) is a powerful tool for the analysis of complex mixtures of unknown molecules. This capacity has been used in many analytical approaches: metabolomics, identification of active compounds in natural extracts, and characterization of species, and such studies require the acquisition of many diverse NMR measurements on series of samples. Although acquisition can easily be performed automatically, the number of NMR experiments involved in these studies increases very rapidly, and this data avalanche requires to resort to automatic processing and analysis. We present here a program that allows the autonomous, unsupervised processing of a large corpus of 1D, 2D, and diffusion-ordered spectroscopy experiments from a series of samples acquired in different conditions. The program provides all the signal processing steps, as well as peak-picking and bucketing of 1D and 2D spectra, the program and its components are fully available. In an experiment mimicking the search of a bioactive species in a natural extract, we use it for the automatic detection of small amounts of artemisinin added to a series of plant extracts and for the generation of the spectral fingerprint of this molecule. This program called Plasmodesma is a novel tool that should be useful to decipher complex mixtures, particularly in the discovery of biologically active natural products from plants extracts but can also in drug discovery or metabolomics studies. Copyright © 2017 John Wiley & Sons, Ltd.

A multidimensional approach to examine student interdisciplinary learning in science and engineering in higher education

NASA Astrophysics Data System (ADS)

Spelt, Elisabeth Jacoba Hendrika; Luning, Pieternelleke Arianne; van Boekel, Martinus A. J. S.; Mulder, Martin

2017-11-01

Preparing science and engineering students to work in interdisciplinary teams necessitates research on teaching and learning of interdisciplinary thinking. A multidimensional approach was taken to examine student interdisciplinary learning in a master course on food quality management. The collected 615 student experiences were analysed for the cognitive, emotional, and social learning dimensions using the learning theory of Illeris. Of these 615 experiences, the analysis showed that students reported 214, 194, and 207 times on, respectively, the emotional, the cognitive, and the social dimension. Per learning dimension, key learning experiences featuring interdisciplinary learning were identified such as 'frustrations in selecting and matching disciplinary knowledge to complex problems' (emotional), 'understanding how to apply theoretical models or concepts to real-world situations' (cognitive), and 'socially engaging with peers to recognise similarities in perceptions and experiences' (social). Furthermore, the results showed that students appreciated the cognitive dimension relatively more than the emotional and social dimensions.

New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads to novel discoveries in Moorella thermoaceticum metabolic profiles

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

Xue, Junfeng; Isern, Nancy G.; Ewing, R James

An in-situ nuclear magnetic resonance (NMR) bioreactor was developed and employed to monitor microbial metabolism under batch-growth conditions in real time. We selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic, acetogenic, gram-positive bacterium with potential for industrial production of chemicals. The metabolic profiles of M. thermoacetica were characterized during growth in batch mode on xylose (a component of lignocellulosic biomass) using the new generation NMR bioreactor in combination with high-resolution, high sensitivity NMR (HR-NMR) spectroscopy. In-situ NMR measurements were performed using water-suppressed H-1 NMR spectroscopy at an NMR frequencymore » of 500 MHz, and aliquots of the bioreactor contents were taken for 600 MHz HR-NMR spectroscopy at specific intervals to confirm metabolite identifications and expand metabolite coverage. M. thermoacetica demonstrated the metabolic potential to produce formate, ethanol and methanol from xylose, in addition to its known capability of producing acetic acid. Real-time monitoring of bioreactor conditions showed a temporary pH decrease, with a concomitant increase in formic acid during exponential growth. Fermentation experiments performed outside of the magnet showed that the strong magnetic field employed for NMR detection did not significantly affect cell metabolism. Use of the in-situ NMR bioreactor facilitated monitoring of the fermentation process in real time, enabling identification of intermediate and end-point metabolites and their correlation with pH and biomass produced during culture growth. Real-time monitoring of culture metabolism using the NMR bioreactor in combination with the HR-NMR spectroscopy will allow optimization of the metabolism of microorganisms producing valuable bioproducts.« less

Complete NMR assignment of a bisecting hybrid-type oligosaccharide transferred by Mucor hiemalis endo-β-N-acetylglucosaminidase.

PubMed

Yamanoi, Takashi; Oda, Yoshiki; Katsuraya, Kaname; Inazu, Toshiyuki; Yamamoto, Kenji

2016-06-02

This study describes the complete nuclear magnetic resonance (NMR) spectral assignment of a bisecting hybrid-type oligosaccharide 1, transferred by Mucor hiemalis endo-β-N-acetylglucosaminidase (Endo-M). Through (1)H- and (13)C-NMR, DQF-COSY, HSQC, HMBC, TOCSY, and NOESY experiments, we determine the structure of the glycoside linkage formed by the Endo-M transglycosylation, i.e., the connection between GlcNAc and GlcNAc in oligosaccharide 1. Copyright © 2016 Elsevier Ltd. All rights reserved.

NMR studies of field induced magnetism in CeCoIn5

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

Graf, Matthias; Curro, Nicholas J; Young, Ben - Li

2009-01-01

Recent Nuclear Magnetic Resonance and elastic neutron scattering experiments have revealed conclusively the presence of static incommensurate magnetism in the field-induced B phase of CeCoIns, We analyze the NMR data assuming the hyperfine coupling to the 1n(2) nuclei is anisotropic and simulate the spectra for several different magnetic structures, The NMR data are consistent with ordered Ce moments along the [001] direction, but are relatively insensitive to the direction of the incommensurate wavevector.

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.

Automated Microflow NMR: Routine Analysis of Five-Microliter Samples

PubMed Central

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

2006-01-01

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

In situ {sup 13}C MAS NMR study of n-hexane conversion on Pt and Pd supported on basic materials

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

Ivanova, I.I.; Pasau-Claerbout, A.; Seivert, M.

n-Hexane conversion was studied in situ on Pt and Pd supported on aluminum-stabilized magnesium oxide and Pt on Zeolite KL catalysts (Pt/Mg(Al)O, Pd/Mg(Al)O and Pt/KL) by means of {sup 13}C MAS NMR spectroscopy. n-Hexane 1-{sup 13}C was used as a labelled reactant. Forty NMR lines corresponding to 14 different products were resolved and identified. The NMR line assignments were confirmed by adsorption of model compounds. The NMR results were further quantified and compared with continuous flow microreactor tests. Four parallel reaction pathways were identified under flow conditions: isomerization, cracking, dehydrocyclization, and dehydrogenation. Aromatization occurs via two reaction routes: (1) n-hexanemore » dehydrogenation towards hexadienes and hexatrienes, followed by dehydrogenation of a cyclic intermediate. The former reaction pathway is prevented under NMR batch conditions. High pressures induced in the NMR cells at high reaction temperatures (573, 653 K) shift the reaction equilibrium towards hydrogenation. NMR experiments showed that on Pt catalysts aromatization occurs via a cyclohexane intermediate, whereas on Pd it takes place via methylcyclopentane ring enlargement. 54 refs., 15 figs., 3 tabs.« less

6D Visualization of Multidimensional Data by Means of Cognitive Technology

NASA Astrophysics Data System (ADS)

Vitkovskiy, V.; Gorohov, V.; Komarinskiy, S.

2010-12-01

On the basis of the cognitive graphics concept, we worked out the SW-system for visualization and analysis. It allows to train and to aggravate intuition of researcher, to raise his interest and motivation to the creative, scientific cognition, to realize process of dialogue with the very problems simultaneously. The Space Hedgehog system is the next step in the cognitive means of the multidimensional data analyze. The technique and technology cognitive 6D visualization of the multidimensional data is developed on the basis of the cognitive visualization research and technology development. The Space Hedgehog system allows direct dynamic visualization of 6D objects. It is developed with use of experience of the program Space Walker creation and its applications.

ComVisMD - compact visualization of multidimensional data: experimenting with cricket players data

NASA Astrophysics Data System (ADS)

Dandin, Shridhar B.; Ducassé, Mireille

2018-03-01

Database information is multidimensional and often displayed in tabular format (row/column display). Presented in aggregated form, multidimensional data can be used to analyze the records or objects. Online Analytical database Processing (OLAP) proposes mechanisms to display multidimensional data in aggregated forms. A choropleth map is a thematic map in which areas are colored in proportion to the measurement of a statistical variable being displayed, such as population density. They are used mostly for compact graphical representation of geographical information. We propose a system, ComVisMD inspired by choropleth map and the OLAP cube to visualize multidimensional data in a compact way. ComVisMD displays multidimensional data like OLAP Cube, where we are mapping an attribute a (first dimension, e.g. year started playing cricket) in vertical direction, object coloring based on b (second dimension, e.g. batting average), mapping varying-size circles based on attribute c (third dimension, e.g. highest score), mapping numbers based on attribute d (fourth dimension, e.g. matches played). We illustrate our approach on cricket players data, namely on two tables Country and Player. They have a large number of rows and columns: 246 rows and 17 columns for players of one country. ComVisMD’s visualization reduces the size of the tabular display by a factor of about 4, allowing users to grasp more information at a time than the bare table display.

Fast experiments for structure elucidation of small molecules: Hadamard NMR with multiple receivers.

PubMed

Gierth, Peter; Codina, Anna; Schumann, Frank; Kovacs, Helena; Kupče, Ēriks

2015-11-01

We propose several significant improvements to the PANSY (Parallel NMR SpectroscopY) experiments-PANSY COSY and PANSY-TOCSY. The improved versions of these experiments provide sufficient spectral information for structure elucidation of small organic molecules from just two 2D experiments. The PANSY-TOCSY-Q experiment has been modified to allow for simultaneous acquisition of three different types of NMR spectra-1D C-13 of non-protonated carbon sites, 2D TOCSY and multiplicity edited 2D HETCOR. In addition the J-filtered 2D PANSY-gCOSY experiment records a 2D HH gCOSY spectrum in parallel with a (1) J-filtered HC long-range HETCOR spectrum as well as offers a simplified data processing. In addition to parallel acquisition, further time savings are feasible because of significantly smaller F1 spectral windows as compared to the indirect detection experiments. Use of cryoprobes and multiple receivers can significantly alleviate the sensitivity issues that are usually associated with the so called direct detection experiments. In cases where experiments are sampling limited rather than sensitivity limited further reduction of experiment time is achieved by using Hadamard encoding. In favorable cases the total recording time for the two PANSY experiments can be reduced to just 40 s. The proposed PANSY experiments provide sufficient information to allow the CMCse software package (Bruker) to solve structures of small organic molecules. Copyright © 2015 John Wiley & Sons, Ltd.

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.

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.

NMR at pressures up to 90 GPa.

PubMed

Meier, Thomas; Khandarkhaeva, Saiana; Petitgirard, Sylvain; Körber, Thomas; Lauerer, Alexander; Rössler, Ernst; Dubrovinsky, Leonid

2018-05-14

The past 15 years have seen an astonishing increase in Nuclear Magnetic Resonance (NMR) sensitivity and accessible pressure range in high-pressure NMR experiments, owing to a series of new developments of NMR spectroscopy applied to the diamond anvil cell (DAC). Recently, with the application of electro-magnetic lenses, so-called Lenz lenses, in toroidal diamond indenter cells, pressures of up to 72 GPa with NMR spin sensitivities of about 10 12  spin/Hz 1/2 has been achieved. Here, we describe the implementation of a refined NMR resonator structure using a pair of double stage Lenz lenses driven by a Helmholtz coil within a standard DAC, allowing to measure sample volumes as small as 100 pl prior to compression. With this set-up, pressures close to 100 GPa could be realised repeatedly, with enhanced spin sensitivities of about 5 × 10 11 spin/Hz 1/2 . The manufacturing and handling of these new NMR-DACs is relatively easy and straightforward, which will allow for further applications in physics, chemistry, or biochemistry. Copyright © 2018 Elsevier Inc. All rights reserved.

Self-Association of N-Methylacetamide Examined by Infrared and NMR Spectroscopies

ERIC Educational Resources Information Center

Schenck, Heather L.; Hui, KaWai

2011-01-01

These spectroscopic experiments investigate polarity and concentration effects on self-association behavior in N-methylacetamide. Inquiry can be limited to the concentration dependence of hydrogen bonding and estimation of dimerization constant (NMR studies) or to the effect of solvent polarity on extent of hydrogen bonding (IR studies). The…

An NMR Protonation Study of Metal Diethylenetriaminepentaacetic Acid Complexes.

ERIC Educational Resources Information Center

Letkeman, Peter

1979-01-01

This experiment is suitable for an integrated laboratory course for senior chemistry majors. It introduces the student to a study of the relative basicity of different proton accepting sites. It serves as an opportunity to learn about nmr techniques and could extend to infrared, as well. (BB)

Synthetic Methods for Ester Bond Formation and Conformational Analysis of Ester-Containing Carbohydrates

NASA Astrophysics Data System (ADS)

Hackbusch, Sven

This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general. Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity dependent on the presence or absence of an achiral amine catalyst. In particular, this work establishes a structure-activity relationship with regard to the trans-2-substituent and its role as a chiral auxiliary in the reversal of diastereoselectivity. In the second part, the synthesis of various ester-linked carbohydrate derivatives, and their conformational analysis is presented. Using multidimensional NMR experiments and computational methods, the compounds' solution-phase structures were established and the effect of the ester functional group on the molecules' flexibility and three-dimensional (3D) structure was investigated and compared to ether or glycosidic linkages. To aid in this, a novel Karplus equation for the C(sp2)OCH angle in ester-linked carbohydrates was developed on the basis of a model ester-linked carbohydrate. This equation describes the sinusoidal relationship between the C(sp2)OCH dihedral angle and the corresponding 3JCH coupling constant that can be determined from a J-HMBC NMR experiment. The insights from this research will be useful in describing the 3D structure of naturally occurring and lab-made ester-linked derivatives of carbohydrates, as well as guiding the de novo-design of carbohydrate based compounds with specific shape constraints for its use as enzyme inhibitors or similar targets. In addition, the above project led to the development of a methodology for the synthesis of symmetrical ester molecules from primary alcohols using a mild oxidative esterification reaction, which proceeds in hydrous solvents using a nitrosyl radical catalyst. The reaction could be performed with a variety of alcohols and the resulting compounds are of interest in the fragrance and flavor industries.

Application of the Allan Variance to Time Series Analysis in Astrometry and Geodesy: A Review.

PubMed

Malkin, Zinovy

2016-04-01

The Allan variance (AVAR) was introduced 50 years ago as a statistical tool for assessing the frequency standards deviations. For the past decades, AVAR has increasingly been used in geodesy and astrometry to assess the noise characteristics in geodetic and astrometric time series. A specific feature of astrometric and geodetic measurements, as compared with clock measurements, is that they are generally associated with uncertainties; thus, an appropriate weighting should be applied during data analysis. In addition, some physically connected scalar time series naturally form series of multidimensional vectors. For example, three station coordinates time series X, Y, and Z can be combined to analyze 3-D station position variations. The classical AVAR is not intended for processing unevenly weighted and/or multidimensional data. Therefore, AVAR modifications, namely weighted AVAR (WAVAR), multidimensional AVAR (MAVAR), and weighted multidimensional AVAR (WMAVAR), were introduced to overcome these deficiencies. In this paper, a brief review is given of the experience of using AVAR and its modifications in processing astrogeodetic time series.

Dynamics in supercooled polyalcohols: Primary and secondary relaxation

NASA Astrophysics Data System (ADS)

Döß, A.; Paluch, M.; Sillescu, H.; Hinze, G.

2002-10-01

We have studied details of the molecular dynamics in a series of pure polyalcohols by means of dielectric spectroscopy and 2H nuclear magnetic resonance (NMR). From glycerol to threitol, xylitol and sorbitol a systematic change in the dynamics of the primary and secondary relaxation is found. With increasing molecular weight and fragility an increase in the width of the α-peak is observed. Details of the molecular reorientation process responsible for the α-relaxation were exploited by two-dimensional NMR experiments. It is found that in the same sequence of polyalcohols the appearance of the secondary relaxation changes gradually from a wing type scenario to a pronounced β-peak. From NMR experiments using selectively deuterated samples the molecular origin of the secondary relaxation could be elucidated in more detail.

Speeding up nuclear magnetic resonance spectroscopy by the use of SMAll Recovery Times - SMART NMR

NASA Astrophysics Data System (ADS)

Vitorge, Bruno; Bodenhausen, Geoffrey; Pelupessy, Philippe

2010-11-01

A drastic reduction of the time required for two-dimensional NMR experiments can be achieved by reducing or skipping the recovery delay between successive experiments. Novel SMAll Recovery Times (SMART) methods use orthogonal pulsed field gradients in three spatial directions to select the desired pathways and suppress interference effects. Two-dimensional spectra of dilute amino acids with concentrations as low as 2 mM can be recorded in about 0.1 s per increment in the indirect domain.

Measurement of Ligand–Target Residence Times by 1H Relaxation Dispersion NMR Spectroscopy

PubMed Central

2016-01-01

A ligand-observed 1H NMR relaxation experiment is introduced for measuring the binding kinetics of low-molecular-weight compounds to their biomolecular targets. We show that this approach, which does not require any isotope labeling, is applicable to ligand–target systems involving proteins and nucleic acids of variable molecular size. The experiment is particularly useful for the systematic investigation of low affinity molecules with residence times in the micro- to millisecond time regime. PMID:27933946

Static and dynamic stereochemistry of the conformational atropisomers of tetra(o-tolyl)benzene.

PubMed

Lunazzi, Lodovico; Mazzanti, Andrea; Minzoni, Mirko

2005-11-25

[graph: see text] Whereas only one atropisomer of 1,2,4,5-tetra(o-tolyl)benzene was observed by X-ray diffraction in the solid, five conformational atropisomers were detected by low-temperature NMR in solution. Their structures were assigned by a combination of NOE experiments, solvent effect, and ab initio calculations. Variable temperature dynamic NMR and bidimensional EXSY experiments allowed the barrier for the interconversion of these atropisomers to be determined (deltaG(double dagger) = 15.3 kcal mol(-1)).

Tracing bacterial metabolism using multi-nuclear (1H, 2H, and 13C) Solid State NMR: Realizing an Idea Initiated by James Scott

NASA Astrophysics Data System (ADS)

Cody, G.; Fogel, M. L.; Jin, K.; Griffen, P.; Steele, A.; Wang, Y.

2011-12-01

Approximately 6 years ago, while at the Geophysical Laboratory, James Scott became interested in the application of Solid State Nuclear Magnetic Resonance Spectroscopy to study bacterial metabolism. As often happens, other experiments intervened and the NMR experiments were not pursued. We have revisited Jame's question and find that using a multi-nuclear approach (1H, 2H, and 13C Solid State NMR) on laboratory cell culture has some distinct advantages. Our experiments involved batch cultures of E. coli (MG1655) harvested at stationary phase. In all experiments the growth medium consisted of MOPS medium for enterobacteria, where the substrate is glucose. In one set of experiments, 10 % of the water was D2O; in another 10 % of the glucose was per-deuterated. The control experiment used both water and glucose at natural isotopic abundance. A kill control of dead E. coli immersed in pure D2O for an extended period exhibited no deuterium incorporation. In both deuterium enriched experiments, considerable incorporation of deuterium into E. coli's biomolecular constituents was detected via 2H Solid State NMR. In the case of the D2O enriched experiment, 58 % of the incorporated deuterium is observed in a sharp peak at a frequency of 0.31 ppm, consistent with D incorporation in the cell membrane lipids, the remainder is observed in a broad peak at a higher frequency (centered at 5.4 ppm, but spanning out to beyond 10 ppm) that is consistent with D incorporation into predominantly DNA and RNA. In the case of the D-glucose experiments, 61 % of the deuterium is observed in a sharp resonance peak at 0.34 ppm, also consistent with D incorporation into membrane lipids, the remainder of the D is observed at a broad resonance peak centered at 4.3 ppm, consistent with D enrichment in glycogen. Deuterium abundance in the E. coli cells grown in 10 % D2O is nearly 2X greater than that grown with 10 % D-glucose. Very subtle differences are observed in both the 1H and 13C solid-state NMR experiments, most notably in the spectral region corresponding to glycogen H and C, respectively. Interestingly, whereas in both experiments the predominant site of incorporation was in the membrane lipids, the line width of the aliphatic-D resonance in the D2O enriched experiment is 67 % wider than that observed in the D-glucose enriched experiment. This difference could be due to greater residual 1H-2H dipolar coupling in membrane lipids synthesized with 10 % D2O due to D being incorporated during NADP(D) reduction of the fatty acid precursor during synthesis and the H-glucose being the source of carbon and hydrogen starting with acetyl-CoA. In the case of the D-glucose experiment, the narrower absorption line may be consistent with individual FA's being more homogeneously deuterated. Analysis of the membrane lipids is currently being performed via GCMS in order to gain potentially more insight to guide interpretation of the 2H solid state NMR spectra.

Non-Uniform Sampling and J-UNIO Automation for Efficient Protein NMR Structure Determination.

PubMed

Didenko, Tatiana; Proudfoot, Andrew; Dutta, Samit Kumar; Serrano, Pedro; Wüthrich, Kurt

2015-08-24

High-resolution structure determination of small proteins in solution is one of the big assets of NMR spectroscopy in structural biology. Improvements in the efficiency of NMR structure determination by advances in NMR experiments and automation of data handling therefore attracts continued interest. Here, non-uniform sampling (NUS) of 3D heteronuclear-resolved [(1)H,(1)H]-NOESY data yielded two- to three-fold savings of instrument time for structure determinations of soluble proteins. With the 152-residue protein NP_372339.1 from Staphylococcus aureus and the 71-residue protein NP_346341.1 from Streptococcus pneumonia we show that high-quality structures can be obtained with NUS NMR data, which are equally well amenable to robust automated analysis as the corresponding uniformly sampled data. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Vivo Use of 1D and 2D 1H NMR to Examine the Glycosylation of Scopoletin in Duboisia myoporoides Cell Suspensions.

PubMed

Fliniaux, Ophélie; Roscher, Albrecht; Cailleu, Dominique; Mesnard, François

2018-06-14

Cell suspensions initiated from Duboisia myoporoides -a shrub belonging to the Solanaceae family and being a rich source of tropane alkaloids-previously showed their ability to glycosylate scopoletin into scopolin, which represent coumarins showing health benefits. To investigate the time course of this glycosylation reaction, an in vivo NMR approach was developed using a perfusion system in an 8-mm NMR tube and 1 H NMR with 1D and 2D (TOCSY and NOESY) experiments. The time course of metabolic changes could therefore be followed without any labeling. Georg Thieme Verlag KG Stuttgart · New York.

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

Koeller, E.; Dobmann, G.; Kuhn, W.

Initial results are presented on the application of NMR techniques to prepregs in order to characterize the crosslink state under exposure to room and elevated (50 C) temperature. The experiments were conducted with a MSL-400 Bruker NMR spectrometer and microimaging system which works at 400 MHz. Aside from the sensitive measurement of the cross-link density there is also the potential to separate the influence of moisture content as a further parameter contributing to the aging process. It is shown that these experimental results correlate with results of destructive tests and document the potential of NMR as a NDT tool. Anmore » NMR-image of the moisture distribution in a glassfiber reinforced expoxy resin sample is shown. 17 refs.« less

Quantitative two-dimensional HSQC experiment for high magnetic field NMR spectrometers

NASA Astrophysics Data System (ADS)

Koskela, Harri; Heikkilä, Outi; Kilpeläinen, Ilkka; Heikkinen, Sami

2010-01-01

The finite RF power available on carbon channel in proton-carbon correlation experiments leads to non-uniform cross peak intensity response across carbon chemical shift range. Several classes of broadband pulses are available that alleviate this problem. Adiabatic pulses provide an excellent magnetization inversion over a large bandwidth, and very recently, novel phase-modulated pulses have been proposed that perform 90° and 180° magnetization rotations with good offset tolerance. Here, we present a study how these broadband pulses (adiabatic and phase-modulated) can improve quantitative application of the heteronuclear single quantum coherence (HSQC) experiment on high magnetic field strength NMR spectrometers. Theoretical and experimental examinations of the quantitative, offset-compensated, CPMG-adjusted HSQC (Q-OCCAHSQC) experiment are presented. The proposed experiment offers a formidable improvement to the offset performance; 13C offset-dependent standard deviation of the peak intensity was below 6% in range of ±20 kHz. This covers the carbon chemical shift range of 150 ppm, which contains the protonated carbons excluding the aldehydes, for 22.3 T NMR magnets. A demonstration of the quantitative analysis of a fasting blood plasma sample obtained from a healthy volunteer is given.

Dipolar recoupling in solid state NMR by phase alternating pulse sequences

PubMed Central

Lin, J.; Bayro, M.; Griffin, R. G.; Khaneja, N.

2009-01-01

We describe some new developments in the methodology of making heteronuclear and homonuclear recoupling experiments in solid state NMR insensitive to rf-inhomogeneity by phase alternating the irradiation on the spin system every rotor period. By incorporating delays of half rotor periods in the pulse sequences, these phase alternating experiments can be made γ encoded. The proposed methodology is conceptually different from the standard methods of making recoupling experiments robust by the use of ramps and adiabatic pulses in the recoupling periods. We show how the concept of phase alternation can be incorporated in the design of homonuclear recoupling experiments that are both insensitive to chemical-shift dispersion and rf-inhomogeneity. PMID:19157931

A closer look at the nitrogen next door: 1H-15N NMR methods for glycosaminoglycan structural characterization

NASA Astrophysics Data System (ADS)

Langeslay, Derek J.; Beni, Szabolcs; Larive, Cynthia K.

2012-03-01

Recently, experimental conditions were presented for the detection of the N-sulfoglucosamine (GlcNS) NHSO3- or sulfamate 1H and 15N NMR resonances of the pharmaceutically and biologically important glycosaminoglycan (GAG) heparin in aqueous solution. In the present work, we explore further the applicability of nitrogen-bound proton detection to provide structural information for GAGs. Compared to the detection of 15N chemical shifts of aminosugars through long-range couplings using the IMPACT-HNMBC pulse sequence, the more sensitive two-dimensional 1H-15N HSQC-TOCSY experiments provided additional structural data. The IMPACT-HNMBC experiment remains a powerful tool as demonstrated by the spectrum measured for the unsubstituted amine of 3-O-sulfoglucosamine (GlcN(3S)), which cannot be observed with the 1H-15N HSQC-TOCSY experiment due to the fast exchange of the amino group protons with solvent. The 1H-15N HSQC-TOCSY NMR spectrum reported for the mixture of model compounds GlcNS and N-acetylglucosamine (GlcNAc) demonstrate the broad utility of this approach. Measurements for the synthetic pentasaccharide drug Arixtra® (Fondaparinux sodium) in aqueous solution illustrate the power of this NMR pulse sequence for structural characterization of highly similar N-sulfoglucosamine residues in GAG-derived oligosaccharides.

2H and 27Al solid-state NMR study of the local environments in Al-doped 2-line ferrihydrite, goethite, and lepidocrocite

DOE PAGES

Kim, Jongsik; Ilott, Andrew J.; Middlemiss, Derek S.; ...

2015-05-13

Although substitution of aluminum into iron oxides and oxyhydroxides has been extensively studied, it is difficult to obtain accurate incorporation levels. Assessing the distribution of dopants within these materials has proven especially challenging because bulk analytical techniques cannot typically determine whether dopants are substituted directly into the bulk iron oxide or oxyhydroxide phase or if they form separate, minor phase impurities. These differences have important implications for the chemistry of these iron-containing materials, which are ubiquitous in the environment. In this work, 27Al and 2H NMR experiments are performed on series of Al-substituted goethite, lepidocrocite, and 2-line ferrihydrite in ordermore » to develop an NMR method to track Al substitution. The extent of Al substitution into the structural frameworks of each compound is quantified by comparing quantitative 27Al MAS NMR results with those from elemental analysis. Magnetic measurements are performed for the goethite series to compare with NMR measurements. Static 27Al spin–echo mapping experiments are used to probe the local environments around the Al substituents, providing clear evidence that they are incorporated into the bulk iron phases. As a result, predictions of the 2H and 27Al NMR hyperfine contact shifts in Al-doped goethite and lepidocrocite, obtained from a combined first-principles and empirical magnetic scaling approach, give further insight into the distribution of the dopants within these phases.« less

Detecting diffusion-diffraction patterns in size distribution phantoms using double-pulsed field gradient NMR: Theory and experiments.

PubMed

Shemesh, Noam; Ozarslan, Evren; Basser, Peter J; Cohen, Yoram

2010-01-21

NMR observable nuclei undergoing restricted diffusion within confining pores are important reporters for microstructural features of porous media including, inter-alia, biological tissues, emulsions and rocks. Diffusion NMR, and especially the single-pulsed field gradient (s-PFG) methodology, is one of the most important noninvasive tools for studying such opaque samples, enabling extraction of important microstructural information from diffusion-diffraction phenomena. However, when the pores are not monodisperse and are characterized by a size distribution, the diffusion-diffraction patterns disappear from the signal decay, and the relevant microstructural information is mostly lost. A recent theoretical study predicted that the diffusion-diffraction patterns in double-PFG (d-PFG) experiments have unique characteristics, such as zero-crossings, that make them more robust with respect to size distributions. In this study, we theoretically compared the signal decay arising from diffusion in isolated cylindrical pores characterized by lognormal size distributions in both s-PFG and d-PFG methodologies using a recently presented general framework for treating diffusion in NMR experiments. We showed the gradual loss of diffusion-diffraction patterns in broadening size distributions in s-PFG and the robustness of the zero-crossings in d-PFG even for very large standard deviations of the size distribution. We then performed s-PFG and d-PFG experiments on well-controlled size distribution phantoms in which the ground-truth is well-known a priori. We showed that the microstructural information, as manifested in the diffusion-diffraction patterns, is lost in the s-PFG experiments, whereas in d-PFG experiments the zero-crossings of the signal persist from which relevant microstructural information can be extracted. This study provides a proof of concept that d-PFG may be useful in obtaining important microstructural features in samples characterized by size distributions.

Solution structure of the His12 --> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium.

PubMed Central

Cai, M.; Huang, Y.; Caffrey, M.; Zheng, R.; Craigie, R.; Clore, G. M.; Gronenborn, A. M.

1998-01-01

The solution structure of His12 --> Cys mutant of the N-terminal zinc binding domain (residues 1-55; IN(1-55)) of HIV-1 integrase complexed to cadmium has been solved by multidimensional heteronuclear NMR spectroscopy. The overall structure is very similar to that of the wild-type N-terminal domain complexed to zinc. In contrast to the wild-type domain, however, which exists in two interconverting conformational states arising from different modes of coordination of the two histidine side chains to the metal, the cadmium complex of the His12 --> Cys mutant exists in only a single form at low pH. The conformation of the polypeptide chain encompassing residues 10-18 is intermediate between the two forms of the wild-type complex. PMID:9865962

Flexibility, Diversity, and Cooperativity: Pillars of Enzyme Catalysis

PubMed Central

Hammes, Gordon G.; Benkovic, Stephen J.; Hammes-Schiffer, Sharon

2011-01-01

This brief review discusses our current understanding of the molecular basis of enzyme catalysis. A historical development is presented, beginning with steady state kinetics and progressing through modern fast reaction methods, NMR, and single molecule fluorescence techniques. Experimental results are summarized for ribonuclease, aspartate aminotransferase, and especially dihydrofolate reductase (DHFR). Multiple intermediates, multiple conformations, and cooperative conformational changes are shown to be an essential part of virtually all enzyme mechanisms. In the case of DHFR, theoretical investigations have provided detailed information about the movement of atoms within the enzyme-substrate complex as the reaction proceeds along the collective reaction coordinate for hydride transfer. A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface. Protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model. PMID:22029278

Decoupling Principle Analysis and Development of a Parallel Three-Dimensional Force Sensor

PubMed Central

Zhao, Yanzhi; Jiao, Leihao; Weng, Dacheng; Zhang, Dan; Zheng, Rencheng

2016-01-01

In the development of the multi-dimensional force sensor, dimension coupling is the ubiquitous factor restricting the improvement of the measurement accuracy. To effectively reduce the influence of dimension coupling on the parallel multi-dimensional force sensor, a novel parallel three-dimensional force sensor is proposed using a mechanical decoupling principle, and the influence of the friction on dimension coupling is effectively reduced by making the friction rolling instead of sliding friction. In this paper, the mathematical model is established by combining with the structure model of the parallel three-dimensional force sensor, and the modeling and analysis of mechanical decoupling are carried out. The coupling degree (ε) of the designed sensor is defined and calculated, and the calculation results show that the mechanical decoupling parallel structure of the sensor possesses good decoupling performance. A prototype of the parallel three-dimensional force sensor was developed, and FEM analysis was carried out. The load calibration and data acquisition experiment system are built, and then calibration experiments were done. According to the calibration experiments, the measurement accuracy is less than 2.86% and the coupling accuracy is less than 3.02%. The experimental results show that the sensor system possesses high measuring accuracy, which provides a basis for the applied research of the parallel multi-dimensional force sensor. PMID:27649194

The Pursuit of Happiness Measurement: A Psychometric Model Based on Psychophysiological Correlates

PubMed Central

Pietro, Cipresso; Silvia, Serino; Giuseppe, Riva

2014-01-01

Everyone is interested in the pursuit of happiness, but the real problem for the researchers is how to measure it. Our aim was to deeply investigate happiness measurement through biomedical signals, using psychophysiological methods to objectify the happiness experiences measurements. The classic valence-arousal model of affective states to study happiness has been extensively used in psychophysiology. However, really few studies considered a real combination of these two dimensions and no study further investigated multidimensional models. More, most studies focused mainly on self-report to measure happiness and a deeper psychophysiological investigation on the dimensions of such an experience is still missing. A multidimensional model of happiness is presented and both the dimensions and the measures extracted within each dimension are comprehensively explained. This multidimensional model aims at being a milestone for future systematic study on psychophysiology of happiness and affective states. It seems everyone has a view on happiness. Joan Collins, theDalai Lama and over 100 others have released new titles on the subject since the beginning of 2001 Richard Tooth “The Psychology of Happiness (2nd Edition)”Michael Argyle, Routledge PMID:24955383

Imaging a multidimensional multichannel potential energy surface: Photodetachment of H(-)(NH3) and NH4 (.).

PubMed

Hu, Qichi; Song, Hongwei; Johnson, Christopher J; Li, Jun; Guo, Hua; Continetti, Robert E

2016-06-28

Probes of the Born-Oppenheimer potential energy surfaces governing polyatomic molecules often rely on spectroscopy for the bound regions or collision experiments in the continuum. A combined spectroscopic and half-collision approach to image nuclear dynamics in a multidimensional and multichannel system is reported here. The Rydberg radical NH4 and the double Rydberg anion NH4 (-) represent a polyatomic system for benchmarking electronic structure and nine-dimensional quantum dynamics calculations. Photodetachment of the H(-)(NH3) ion-dipole complex and the NH4 (-) DRA probes different regions on the neutral NH4 PES. Photoelectron energy and angular distributions at photon energies of 1.17, 1.60, and 2.33 eV compare well with quantum dynamics. Photoelectron-photofragment coincidence experiments indicate dissociation of the nascent NH4 Rydberg radical occurs to H + NH3 with a peak kinetic energy of 0.13 eV, showing the ground state of NH4 to be unstable, decaying by tunneling-induced dissociation on a time scale beyond the present scope of multidimensional quantum dynamics.

Manipulating femtosecond spin-orbit torques with laser pulse sequences to control magnetic memory states and ringing

NASA Astrophysics Data System (ADS)

Lingos, P. C.; Wang, J.; Perakis, I. E.

2015-05-01

Femtosecond (fs) coherent control of collective order parameters is important for nonequilibrium phase dynamics in correlated materials. Here, we propose such control of ferromagnetic order based on using nonadiabatic optical manipulation of electron-hole (e -h ) photoexcitations to create fs carrier-spin pulses with controllable direction and time profile. These spin pulses are generated due to the time-reversal symmetry breaking arising from nonperturbative spin-orbit and magnetic exchange couplings of coherent photocarriers. By tuning the nonthermal populations of exchange-split, spin-orbit-coupled semiconductor band states, we can excite fs spin-orbit torques that control complex magnetization pathways between multiple magnetic memory states. We calculate the laser-induced fs magnetic anisotropy in the time domain by using density matrix equations of motion rather than the quasiequilibrium free energy. By comparing to pump-probe experiments, we identify a "sudden" out-of-plane magnetization canting displaying fs magnetic hysteresis, which agrees with switchings measured by the static Hall magnetoresistivity. This fs transverse spin-canting switches direction with magnetic state and laser frequency, which distinguishes it from the longitudinal nonlinear optical and demagnetization effects. We propose that sequences of clockwise or counterclockwise fs spin-orbit torques, photoexcited by shaping two-color laser-pulse sequences analogous to multidimensional nuclear magnetic resonance (NMR) spectroscopy, can be used to timely suppress or enhance magnetic ringing and switching rotation in magnetic memories.

Fast 2D NMR Spectroscopy for In vivo Monitoring of Bacterial Metabolism in Complex Mixtures.

PubMed

Dass, Rupashree; Grudzia Ż, Katarzyna; Ishikawa, Takao; Nowakowski, Michał; Dȩbowska, Renata; Kazimierczuk, Krzysztof

2017-01-01

The biological toolbox is full of techniques developed originally for analytical chemistry. Among them, spectroscopic experiments are very important source of atomic-level structural information. Nuclear magnetic resonance (NMR) spectroscopy, although very advanced in chemical and biophysical applications, has been used in microbiology only in a limited manner. So far, mostly one-dimensional 1 H experiments have been reported in studies of bacterial metabolism monitored in situ . However, low spectral resolution and limited information on molecular topology limits the usability of these methods. These problems are particularly evident in the case of complex mixtures, where spectral peaks originating from many compounds overlap and make the interpretation of changes in a spectrum difficult or even impossible. Often a suite of two-dimensional (2D) NMR experiments is used to improve resolution and extract structural information from internuclear correlations. However, for dynamically changing sample, like bacterial culture, the time-consuming sampling of so-called indirect time dimensions in 2D experiments is inefficient. Here, we propose the technique known from analytical chemistry and structural biology of proteins, i.e., time-resolved non-uniform sampling. The method allows application of 2D (and multi-D) experiments in the case of quickly varying samples. The indirect dimension here is sparsely sampled resulting in significant reduction of experimental time. Compared to conventional approach based on a series of 1D measurements, this method provides extraordinary resolution and is a real-time approach to process monitoring. In this study, we demonstrate the usability of the method on a sample of Escherichia coli culture affected by ampicillin and on a sample of Propionibacterium acnes , an acne causing bacterium, mixed with a dose of face tonic, which is a complicated, multi-component mixture providing complex NMR spectrum. Through our experiments we determine the exact concentration and time at which the anti-bacterial agents affect the bacterial metabolism. We show, that it is worth to extend the NMR toolbox for microbiology by including techniques of 2D z-TOCSY, for total "fingerprinting" of a sample and 2D 13 C-edited HSQC to monitor changes in concentration of metabolites in selected metabolic pathways.

Multinuclear Solid-State Magnetic Resonance as a Sensitive Probe of Structural Changes upon the Occurrence of Halogen Bonding in Co-crystals.

PubMed

Widdifield, Cory M; Cavallo, Gabriella; Facey, Glenn A; Pilati, Tullio; Lin, Jingxiang; Metrangolo, Pierangelo; Resnati, Giuseppe; Bryce, David L

2013-09-02

Although the understanding of intermolecular interactions, such as hydrogen bonding, is relatively well-developed, many additional weak interactions work both in tandem and competitively to stabilize a given crystal structure. Due to a wide array of potential applications, a substantial effort has been invested in understanding the halogen bond. Here, we explore the utility of multinuclear ((13)C, (14/15)N, (19)F, and (127)I) solid-state magnetic resonance experiments in characterizing the electronic and structural changes which take place upon the formation of five halogen-bonded co-crystalline product materials. Single-crystal X-ray diffraction (XRD) structures of three novel co-crystals which exhibit a 1:1 stoichiometry between decamethonium diiodide (i.e., [(CH3)3N(+)(CH2)10N(+)(CH3)3][2 I(-)]) and different para-dihalogen-substituted benzene moieties (i.e., p-C6X2Y4, X=Br, I; Y=H, F) are presented. (13)C and (15)N NMR experiments carried out on these and related systems validate sample purity, but also serve as indirect probes of the formation of a halogen bond in the co-crystal complexes in the solid state. Long-range changes in the electronic environment, which manifest through changes in the electric field gradient (EFG) tensor, are quantitatively measured using (14)N NMR spectroscopy, with a systematic decrease in the (14)N quadrupolar coupling constant (CQ) observed upon halogen bond formation. Attempts at (127)I solid-state NMR spectroscopy experiments are presented and variable-temperature (19)F NMR experiments are used to distinguish between dynamic and static disorder in selected product materials, which could not be conclusively established using solely XRD. Quantum chemical calculations using the gauge-including projector augmented-wave (GIPAW) or relativistic zeroth-order regular approximation (ZORA) density functional theory (DFT) approaches complement the experimental NMR measurements and provide theoretical corroboration for the changes in NMR parameters observed upon the formation of a halogen bond. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectroscopy 101: A Practical Introduction to Spectroscopy and Analysis for Undergraduate Organic Chemistry Laboratories

ERIC Educational Resources Information Center

Morrill, Lucas A.; Kammeyer, Jacquelin K.; Garg, Neil K.

2017-01-01

An undergraduate organic chemistry laboratory that provides an introduction to various spectroscopic techniques is reported. Whereas organic spectroscopy is most often learned and practiced in the context of reaction analyses, this laboratory experiment allows students to become comfortable with [superscript 1]H NMR, [superscript 13]C NMR, and IR…

BetaNMR Experiments on Liquid Samples

NASA Astrophysics Data System (ADS)

Gottberg, A.; Stachura, M.; Hemmingsen, L.; Macfarlane, W. A.; Bio-Beta-Nmr Collaboration; Collaps Collaboration

2016-09-01

In 2012 betaNMR spectroscopy was successfully applied on liquid samples; an achievement which opens new opportunities in the fields of chemistry and biochemistry. This project was motivated by the need for finding a new experimental approach to directly study biologically highly relevant metal ions, such as Mg(II), Cu(I), Ca(II), and Zn(II), which are silent in most spectroscopic techniques. The resonance spectrum recorded for Mg-31 implanted into an ionic liquid sample showed two resonances which originate from Mg ions occupying two different coordination geometries, illustrating that this technique can discriminate between different structures. This proof-of-principle result lays the foundation for studies of these metal ions at low concentrations and in environments of biological relevance where other methods are silent. The prototype chamber for bio-betaNMR allows for experiments not only on different samples such as: liquids, gels and solids, but also operates at different vacuum environments. In order to exploit the potential of betaNMR on liquid samples, tests with polarized beams of Mg-29 and Mg-31 have recently been performed at the ISAC facility at TRIUMF.

Genotype evaluation of cowpea seeds (Vigna unguiculata) using 1H qNMR combined with exploratory tools and solid-state NMR.

PubMed

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

2017-01-01

The ultimate aim of this study was to apply a non-targeted chemometric analysis (principal component analysis and hierarchical clustering analysis using the heat map approach) of NMR data to investigate the variability of organic compounds in nine genotype cowpea seeds, without any complex pre-treatment. In general, both exploratory tools show that Tvu 233, CE-584, and Setentão genotypes presented higher amount mainly of raffinose and Tvu 382 presented the highest content of choline and least content of raffinose. The evaluation of the aromatic region showed the Setentão genotype with highest content of niacin/vitamin B3 whereas Tvu 382 with lowest amount. To investigate rigid and mobile components in the seeds cotyledon, 13 C CP and SP/MAS solid-state NMR experiments were performed. The cotyledon of the cowpea comprised a rigid part consisting of starch as well as a soft portion made of starch, fatty acids, and protein. The variable contact time experiment suggests the presence of lipid-amylose complexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental optimization and shielding for NMR experiments and imaging in the earth's magnetic field.

PubMed

Favre, B; Bonche, J P; Meheir, H; Peyrin, J O

1990-02-01

For many years, a number of laboratories have been working on the applications of very low field NMR. In 1985, our laboratory presented the first NMR images using the earth's magnetic field. However, the use of this technique was limited by the weakness of the signal and the disturbing effects of the environment on the signal-to-noise ratio and on the homogeneity of the static magnetic field. Therefore experiments has to be performed in places with low environmental disturbances, such as open country or large parks. In 1986, we installed a new station in Lyon, in the town's hostile environment. Good NMR signals can now be obtained (with a signal-to-noise ratio better than 200 and a time constant T2 better than 3s for 200-mnl water samples and at a temperature of about 40 degrees C). We report the terrace roof of our faculty building. Gradient coils were used to correct the local inhomogeneities of the earth's magnetic field. We show FIDs and MR images of water-filled tubes made with or without these improvements.

Multinuclear nanoliter one-dimensional and two-dimensional NMR spectroscopy with a single non-resonant microcoil

NASA Astrophysics Data System (ADS)

Fratila, Raluca M.; Gomez, M. Victoria; Sýkora, Stanislav; Velders, Aldrik H.

2014-01-01

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique, but its low sensitivity and highly sophisticated, costly, equipment severely constrain more widespread applications. Here we show that a non-resonant planar transceiver microcoil integrated in a microfluidic chip (detection volume 25 nl) can detect different nuclides in the full broad-band range of Larmor frequencies (at 9.4 T from 61 to 400 MHz). Routine one-dimensional (1D) and two-dimensional (2D), homo- and heteronuclear experiments can be carried out using the broad-band coil set-up. Noteworthy, heteronuclear 2D experiments can be performed in a straightforward manner on virtually any combination of nuclides (from classical 1H-13C to more exotic combinations like 19F-31P) both in coupled and decoupled mode. Importantly, the concept of a non-resonant system provides magnetic field-independent NMR probes; moreover, the small-volume alleviates problems related to field inhomogeneity, making the broad-band coil an attractive option for, for example, portable and table-top NMR systems.

Triple Resonance Solid State NMR Experiments with Reduced Dimensionality Evolution Periods

NASA Astrophysics Data System (ADS)

Astrof, Nathan S.; Lyon, Charles E.; Griffin, Robert G.

2001-10-01

Two solid state NMR triple resonance experiments which utilize the simultaneous incrementation of two chemical shift evolution periods to obtain a spectrum with reduced dimensionality are described. The CON CA experiment establishes the correlation of 13Ci-1 to 13Cαi and 15Ni by simultaneously encoding the 13COi-1 and 15Ni chemical shifts. The CAN COCA experiment establishes the correlation 13Cai and 15COi to 13Cαi-1 and 15Ni-1 within a single experiment by simultaneous encoding of the 13Cαi and 15Ni chemical shifts. This experiment establishes sequential amino acid correlations in close analogy to the solution state HNCA experiment. Reduced dimensionality 2D experiments are a practical alternative to recording multiple 3D data sets for the purpose of obtaining sequence-specific resonance assignments of peptides and proteins in the solid state.

Advanced solid-state NMR spectroscopy of natural organic matter.

PubMed

Mao, Jingdong; Cao, Xiaoyan; Olk, Dan C; Chu, Wenying; Schmidt-Rohr, Klaus

2017-05-01

Solid-state NMR is essential for the characterization of natural organic matter (NOM) and is gaining importance in geosciences and environmental sciences. This review is intended to highlight advanced solid-state NMR techniques, especially a systematic approach to NOM characterization, and their applications to the study of NOM. We discuss some basics of how to acquire high-quality and quantitative solid-state 13 C NMR spectra, and address some common technical mistakes that lead to unreliable spectra of NOM. The identification of specific functional groups in NOM, primarily based on 13 C spectral-editing techniques, is described and the theoretical background of some recently-developed spectral-editing techniques is provided. Applications of solid-state NMR to investigating nitrogen (N) in NOM are described, focusing on limitations of the widely used 15 N CP/MAS experiment and the potential of improved advanced NMR techniques for characterizing N forms in NOM. Then techniques used for identifying proximities, heterogeneities and domains are reviewed, and some examples provided. In addition, NMR techniques for studying segmental dynamics in NOM are reviewed. We also briefly discuss applications of solid-state NMR to NOM from various sources, including soil organic matter, aquatic organic matter, organic matter in atmospheric particulate matter, carbonaceous meteoritic organic matter, and fossil fuels. Finally, examples of NMR-based structural models and an outlook are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

Pressure-resisting cell for high-pressure, high-resolution nuclear magnetic resonance measurements at very high magnetic fields

NASA Astrophysics Data System (ADS)

Yamada, H.; Nishikawa, K.; Honda, M.; Shimura, T.; Akasaka, K.; Tabayashi, K.

2001-02-01

A pressure-resisting cell system has been developed for high-pressure high-resolution nuclear magnetic resonance (NMR) measurements up to a maximum pressure of 600 MPa. This cell system is capable of performing high-pressure experiments with any standard spectrometer, including modern high field NMR machines. A full description of the high-pressure NMR assembly mounted on a 750 MHz spectrometer is presented along with a detailed explanation of the procedure for preparing the pressure-resisting quartz and glass cells.

Ultralow field NMR spectrometer with an atomic magnetometer near room temperature

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

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

PubMed

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

2015-06-23

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

In vivo observation of tree drought response with low-field NMR and neutron imaging

DOE PAGES

Malone, Michael W.; Yoder, Jacob; Hunter, James F.; ...

2016-05-06

Using a simple low-field NMR system, we monitored water content in a living tree in a greenhouse over 2 months. By continuously running the system, we observed changes in tree water content on a scale of half an hour. The data showed a diurnal change in water content consistent both with previous NMR and biological observations. Neutron imaging experiments show that our NMR signal is primarily due to water being rapidly transported through the plant, and not to other sources of hydrogen, such as water in cytoplasm, or water in cell walls. After accounting for the role of temperature inmore » the observed NMR signal, we demonstrate a change in the diurnal signal behavior due to simulated drought conditions for the tree. Lastly, these results illustrate the utility of our system to perform noninvasive measurements of tree water content outside of a temperature controlled environment.« less

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 spectroscopy of Group 13 metal ions: biologically relevant aspects.

PubMed

André, J P; Mäcke, H R

2003-12-01

In spite of the fact that Group 13 metal ions (Al(3+), Ga(3+), In(3+) and Tl(+/3+)) show no main biological role, they are NMR-active nuclides which can be used in magnetic resonance spectroscopy of biologically relevant systems. The fact that these metal ions are quadrupolar (with the exception of thallium) means that they are particularly sensitive to ligand type and coordination geometry. The line width of the NMR signals of their complexes shows a strong dependence on the symmetry of coordination, which constitutes an effective tool in the elucidation of structures. Here we report published NMR studies of this family of elements, applied to systems of biological importance. Special emphasis is given to binding studies of these cations to biological molecules, such as proteins, and to chelating agents of radiopharmaceutical interest. The possibility of in vivo NMR studies is also stressed, with extension to (27)Al-based MRI (magnetic resonance imaging) experiments.

In vivo observation of tree drought response with low-field NMR and neutron imaging

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

Malone, Michael W.; Yoder, Jacob; Hunter, James F.

Using a simple low-field NMR system, we monitored water content in a living tree in a greenhouse over 2 months. By continuously running the system, we observed changes in tree water content on a scale of half an hour. The data showed a diurnal change in water content consistent both with previous NMR and biological observations. Neutron imaging experiments show that our NMR signal is primarily due to water being rapidly transported through the plant, and not to other sources of hydrogen, such as water in cytoplasm, or water in cell walls. After accounting for the role of temperature inmore » the observed NMR signal, we demonstrate a change in the diurnal signal behavior due to simulated drought conditions for the tree. Lastly, these results illustrate the utility of our system to perform noninvasive measurements of tree water content outside of a temperature controlled environment.« less

NMR Studies of Low-Gamma Nuclei in Solids

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

Wasylishen, Roderick E.; Forgeron, Michelle A.; Siegel, Renee

2006-07-24

Over the past five years we have devoted considerable time to solid-state NMR investigaitons of nuclei, which are traditionally known as "difficult" because of their small magnetic moments. These include quadrupolar nuclei such as 35Cl, 53 Cr, 91Zr, 95Mo, 99Ru, 131 Xe, as well as spin-1/2 nuclei such as 109Ag. While NMR studies of such isotopes remain challenging, the use of moderate to high magnetic field strengths together with a variety of enhancement techniques is leading to many interesting applications. In this talk some of our successes in studying these isotopes will be presented. For example, we will present preliminarymore » results of 131Xe NMR studies of solid sodium perxenate, as well as 109Ag NMR studies of silver dialkylphosphites. Our experience using population enhancement techniques that utilize hyperbolic secant pulses will also be discussed.« less

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.

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.

Continuous-wave Submillimeter-wave Gyrotrons

PubMed Central

Han, Seong-Tae; Griffin, Robert G.; Hu, Kan-Nian; Joo, Chan-Gyu; Joye, Colin D.; Mastovsky, Ivan; Shapiro, Michael A.; Sirigiri, Jagadishwar R.; Temkin, Richard J.; Torrezan, Antonio C.; Woskov, Paul P.

2007-01-01

Recently, dynamic nuclear polarization enhanced nuclear magnetic resonance (DNP/NMR) has emerged as a powerful technique to obtain significant enhancements in spin spectra from biological samples. For DNP in modern NMR systems, a high power continuous-wave source in the submillimeter wavelength range is necessary. Gyrotrons can deliver tens of watts of CW power at submillimeter wavelengths and are well suited for use in DNP/NMR spectrometers. To date, 140 GHz and 250 GHz gyrotrons are being employed in DNP spectrometer experiments at 200 MHz and 380 MHz at MIT. A 460 GHz gyrotron, which has operated with 8 W of CW output power, will soon be installed in a 700 MHz NMR spectrometer. High power radiation with good spectral and spatial resolution from these gyrotrons should provide NMR spectrometers with high signal enhancement through DNP. Also, these tubes operating at submillimeter wavelengths should have important applications in research in physics, chemistry, biology, materials science and medicine. PMID:17404605

Confirmatory Factor Analysis of Scores on the Clinical Experience Rubric: A Measure of Dispositions for Preservice Teachers

ERIC Educational Resources Information Center

Flowers, Claudia

2006-01-01

This study examines the underlying structure of the Clinical Experience Rubric (CER), which is designed to assess preservice teachers' dispositions during the clinical experiences. Dispositions were conceptualized as being a multidimensional construct with three related factors: (a) professionalism, (b) teaching quality, and (c) relationship with…

NMR Microscopy - Micron-Level Resolution.

NASA Astrophysics Data System (ADS)

Kwok, Wing-Chi Edmund

1990-01-01

Nuclear Magnetic Resonance Imaging (MRI) has been developed into a powerful and widely used diagnostic tool since the invention of techniques using linear magnetic field gradients in 1973. The variety of imaging contrasts obtainable in MRI, such as spin density, relaxation times and flow rate, gives MRI a significant advantage over other imaging techniques. For common diagnostic applications, image resolutions have been in the order of millimeters with slice thicknesses in centimeters. For many research applications, however, resolutions in the order of tens of microns or smaller are needed. NMR Imaging in these high resolution disciplines is known as NMR microscopy. Compared with conventional microscopy, NMR microscopy has the advantage of being non-invasive and non-destructive. The major obstacles of NMR microscopy are low signal-to-noise ratio and effects due to spin diffusion. To overcome these difficulties, more sensitive RF probes and very high magnetic field gradients have to be used. The most effective way to increase sensitivity is to build smaller probes. Microscope probes of different designs have been built and evaluated. Magnetic field gradient coils that can produce linear field gradients up to 450 Gauss/cm were also assembled. In addition, since microscope probes often employ remote capacitors for RF tuning, the associated signal loss in the transmission line was studied. Imaging experiments have been carried out in a 2.1 Tesla small bore superconducting magnet using the typical two-dimensional spin warp imaging technique. Images have been acquired for both biological and non-biological samples. The highest resolution was obtained in an image of a nerve bundle from the spinal cord of a racoon and has an in-plane resolution of 4 microns. These experiments have demonstrated the potential application of NMR microscopy to pathological research, nervous system study and non -destructive testings of materials. One way to further improve NMR microscopy is to implement a higher static magnetic field which will increase signal strength. In the future, NMR microscopy should prove to be useful in the studies of cell linings, T1 & T2 relaxation mechanisms and NMR contrast agents.

Natural abundance high-resolution solid state 2 H NMR spectroscopy

NASA Astrophysics Data System (ADS)

Aliev, Abil E.; Harris, Kenneth D. M.; Apperley, David C.

1994-08-01

We report for the first time an approach for natural abundance solid state 2 H NMR spectroscopy involving magic angle sample spinning (MAS), high-power 1 H decoupling (HPPD) and 1 H- 2 H cross polarization (CP). Taking tetrakis(trimethylsilyl)silane (TTMSS), adamantane, 1-chloroadamantane, hexamethylbenzene (HMB), 2,2-dimethyl-1,3-propanediol (DMPD) and 2-hydroxymethyl-2-methyl-1,3-propanediol (HMPD) as examples, it has been shown that the combination of HPPD and MAS can be applied readily to study rotator phase solids, allowing isotropic peaks arising from chemically inequivalent 2 H nuclei to be resolved. For natural abundance samples of TTMSS and chloroadamantane, it has been shown that 2 H CP/HPPD/MAS NMR experiments, involving polarization transfer from 1 H to 2 H, may provide considerable sensitivity enhancement in comparison with single pulse experiments.

Natural abundance high-resolution solid state 2 H NMR spectroscopy

NASA Astrophysics Data System (ADS)

Aliev, Abil E.; Harris, Kenneth D. M.; Apperley, David C.

1994-08-01

We report for the first time an approach for natural abundance solid state 2H NMR spectroscopy involving magic angle sample spinning (MAS), high-power 1H decoupling (HPPD) and 1H- 2H cross polarization (CP). Taking tetrakis(trimethylsilyl)silane (TTMSS), adamantane, 1-chloroadamantane, hexamethylbenzene (HMB), 2,2-dimethyl-1,3-propanediol (DMPD) and 2-hydroxymethyl-2-methyl-1,3-propanediol (HMPD) as examples, it has been shown that the combination of HPPD and MAS can be applied readily to study rotator phase solids, allowing isotropic peaks arising from chemically inequivalent 2H nuclei to be resolved. For natural abundance samples of TTMSS and chloroadamantane, it has been shown that 2H CP/HPPD/MAS NMR experiments, involving polarization transfer from 1H to 2H, may provide considerable sensitivity enhancement in comparison with single pulse experiments.

NMR-based diffusion lattice imaging

NASA Astrophysics Data System (ADS)

Laun, Frederik Bernd; Müller, Lars; Kuder, Tristan Anselm

2016-03-01

Nuclear magnetic resonance (NMR) diffusion experiments are widely employed as they yield information about structures hindering the diffusion process, e.g., about cell membranes. While it has been shown in recent articles that these experiments can be used to determine the shape of closed pores averaged over a volume of interest, it is still an open question how much information can be gained in open well-connected systems. In this theoretical work, it is shown that the full structure information of connected periodic systems is accessible. To this end, the so-called "SEquential Rephasing by Pulsed field-gradient Encoding N Time intervals" (SERPENT) sequence is used, which employs several diffusion encoding gradient pulses with different amplitudes. Two two-dimensional solid matrices that are surrounded by an NMR-visible medium are considered: a hexagonal lattice of cylinders and a rectangular lattice of isosceles triangles.

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.

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.

Using liquid and solid state NMR and photoluminescence to study the synthesis and solubility properties of amine capped silicon nanoparticles.

PubMed

Giuliani, J R; Harley, S J; Carter, R S; Power, P P; Augustine, M P

2007-08-01

Water soluble silicon nanoparticles were prepared by the reaction of bromine terminated silicon nanoparticles with 3-(dimethylamino)propyl lithium and characterized with liquid and solid state nuclear magnetic resonance (NMR) and photoluminescence (PL) spectroscopies. The surface site dependent 29Si chemical shifts and the nuclear spin relaxation rates from an assortment of 1H-29Si heteronuclear solid state NMR experiments for the amine coated reaction product are consistent with both the 1H and 13C liquid state NMR results and routine transmission electron microscopy, ultra-violet/visible, and Fourier transform infrared measurements. PL was used to demonstrate the pH dependent solubility properties of the amine passivated silicon nanoparticles.

Multinuclear solid film state NMR studies of metal oxide catalysts and minerals

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

Maxwell, R.S.; Stec, D.F.; Ellis, P.D.

1996-10-01

Several of our investigations of heterogeneous process by novel NMR experiments and analyses are reviewed and the utility and limitations of NMR spectroscopy for these areas discussed. Out studies have included the following: dynamics and arrangements of proton-containing adsorbates, primarily Bronsted acid sites and water, on the surface of zirconia and alumina catalysts; hydrogen dynamics and coordinates in synthetic aluminum oxyhydroxides; phase separation and crystallinity of synthetic minerals. In combination with the complementary results obtained in our laboratory via infrared spectroscopy, thermal analysis (primarily TGA and DSC), and catalytic activity measurements, these NMR data provide unique and valuable information onmore » atomic and molecular dynamics, identities, and structures without requiring pristine, single crystal specimens.« less

Detailed Multidimensional Simulations of the Structure and Dynamics of Flames

NASA Technical Reports Server (NTRS)

Patnaik, G.; Kailasanath, K.

1999-01-01

Numerical simulations in which the various physical and chemical processes can be independently controlled can significantly advance our understanding of the structure, stability, dynamics and extinction of flames. Therefore, our approach has been to use detailed time-dependent, multidimensional, multispecies numerical models to perform carefully designed computational experiments of flames on Earth and in microgravity environments. Some of these computational experiments are complementary to physical experiments performed under the Microgravity Program while others provide a fundamental understanding that cannot be obtained from physical experiments alone. In this report, we provide a brief summary of our recent research highlighting the contributions since the previous microgravity combustion workshop. There are a number of mechanisms that can cause flame instabilities and result in the formation of dynamic multidimensional structures. In the past, we have used numerical simulations to show that it is the thermo-diffusive instability rather than an instability due to preferential diffusion that is the dominant mechanism for the formation of cellular flames in lean hydrogen-air mixtures. Other studies have explored the role of gravity on flame dynamics and extinguishment, multi-step kinetics and radiative losses on flame instabilities in rich hydrogen-air flames, and heat losses on burner-stabilized flames in microgravity. The recent emphasis of our work has been on exploring flame-vortex interactions and further investigating the structure and dynamics of lean hydrogen-air flames in microgravity. These topics are briefly discussed after a brief discussion of our computational approach for solving these problems.

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.

Synthetic Approaches to (smif)2Ti (smif = 1,3-di-(2-pyridyl)-2-azaallyl) Reveal Redox Non-Innocence and C-C Bond-Formation

PubMed Central

Frazier, Brenda A.; Wolczanski, Peter T.; Keresztes, Ivan; DeBeer, Serena; Lobkovsky, Emil B.; Pierpont, Aaron W.; Cundari, Thomas R.

2012-01-01

Attempted syntheses of (smif)2Ti (smif = 1,3-di-(2-pyridyl)-2-azaallyl) based on metatheses of TiClnLm (n = 2–4) with M(smif) (M = Li, Na), in the presence of a reducing agent (Na/Hg) when necessary, failed, but several apparent Ti(II) species were identified by X-ray crystallography and multidimensional NMR spectroscopy: (smif){Li(smif-smif)}Ti (1, X-ray), [(smif)Ti]2(μ-κ3,κ3-N,N(py)2-smif,smif) (2), (smif)Ti(κ3-N,N(py)2-smif,(smif)H) (3), and (smif)Ti(dpma) (4). NMR spectroscopy and K-edge XAS showed that each compound possesses ligands that are redox non-innnocent, such that d1 Ti(III) centers AF-couple to ligand radicals: (smif){Li(smif-smif)2−}TiIII (1), [(smif2−)TiIII]2(μ-κ3,κ3-N,N(py)2-smif,smif) (2), [(smif2−)TiIII](κ3-N,N(py)2-smif,(smif)H) (3), and (smif2−)TiIII(dpma) (4). The instability of the (smif)2Ti relative to its C-C coupled dimer, 2, is rationalized via the complementary nature of the amide and smif radical anion ligands, which are also common to 3 and 4. Calculations support this contention. PMID:22830452

Friendship group identification, multidimensional self-concept, and experience of developmental tasks in adolescence.

PubMed

Tarrant, Mark; MacKenzie, Liam; Hewitt, Lisa A

2006-08-01

This study applied a social identity perspective to the study of adolescent self-concept and social development. British adolescents aged 14-15 years (N=114) completed a questionnaire which asked them to: (i) rate their degree of identification with a school-based friendship group; (ii) complete a measure of multi-dimensional self-concept; and (iii) report their experiences of a variety of personal, relational and socio-institutional (e.g., achieving economic independence) developmental tasks. Compared to low identifiers, participants who were highly identified with a friendship group reported highest levels of self-esteem; and these differences were most marked in non-academic domains of self. High identifiers also displayed higher levels of general self-esteem and reported more positive experiences of personal and relational developmental tasks. The discussion focuses on the potential benefits to understanding of social developmental processes that can be derived from a consideration of adolescents' subjective appraisals of their peer relations.

Measuring diffusion-relaxation correlation maps using non-uniform field gradients of single-sided NMR devices.

PubMed

Nogueira d'Eurydice, Marcel; Galvosas, Petrik

2014-11-01

Single-sided NMR systems are becoming a relevant tool in industry and laboratory environments due to their low cost, low maintenance and capacity to evaluate quantity and quality of hydrogen based materials. The performance of such devices has improved significantly over the last decade, providing increased field homogeneity, field strength and even controlled static field gradients. For a class of these devices, the configuration of the permanent magnets provides a linear variation of the magnetic field and can be used in diffusion measurements. However, magnet design depends directly on its application and, according to the purpose, the field homogeneity may significantly be compromised. This may prevent the determination of diffusion properties of fluids based on the natural inhomogeneity of the field using known techniques. This work introduces a new approach that extends the applicability of diffusion-editing CPMG experiments to NMR devices with highly inhomogeneous magnetic fields, which do not vary linearly in space. Herein, we propose a method to determine a custom diffusion kernel based on the gradient distribution, which can be seen as a signature of each NMR device. This new diffusion kernel is then utilised in the 2D inverse Laplace transform (2D ILT) in order to determine diffusion-relaxation correlation maps of homogeneous multi-phasic fluids. The experiments were performed using NMR MObile Lateral Explore (MOLE), which is a single-sided NMR device designed to maximise the volume at the sweet spot with enhanced depth penetration. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Changes to the Student Loan Experience: Psychological Predictors and Outcomes

ERIC Educational Resources Information Center

Mueller, Thomas

2014-01-01

This study builds on the work of scholars who have explored psychological perceptions of the student loan experience. Survey analysis ("N" = 175) revealed a multidimensional model was developed through factor analysis and testing, which revealed four latent variables: "Duress," "Mandatory," "Financial," and…

Conceptual-level workflow modeling of scientific experiments using NMR as a case study

PubMed Central

Verdi, Kacy K; Ellis, Heidi JC; Gryk, Michael R

2007-01-01

Background Scientific workflows improve the process of scientific experiments by making computations explicit, underscoring data flow, and emphasizing the participation of humans in the process when intuition and human reasoning are required. Workflows for experiments also highlight transitions among experimental phases, allowing intermediate results to be verified and supporting the proper handling of semantic mismatches and different file formats among the various tools used in the scientific process. Thus, scientific workflows are important for the modeling and subsequent capture of bioinformatics-related data. While much research has been conducted on the implementation of scientific workflows, the initial process of actually designing and generating the workflow at the conceptual level has received little consideration. Results We propose a structured process to capture scientific workflows at the conceptual level that allows workflows to be documented efficiently, results in concise models of the workflow and more-correct workflow implementations, and provides insight into the scientific process itself. The approach uses three modeling techniques to model the structural, data flow, and control flow aspects of the workflow. The domain of biomolecular structure determination using Nuclear Magnetic Resonance spectroscopy is used to demonstrate the process. Specifically, we show the application of the approach to capture the workflow for the process of conducting biomolecular analysis using Nuclear Magnetic Resonance (NMR) spectroscopy. Conclusion Using the approach, we were able to accurately document, in a short amount of time, numerous steps in the process of conducting an experiment using NMR spectroscopy. The resulting models are correct and precise, as outside validation of the models identified only minor omissions in the models. In addition, the models provide an accurate visual description of the control flow for conducting biomolecular analysis using NMR spectroscopy experiment. PMID:17263870

Conceptual-level workflow modeling of scientific experiments using NMR as a case study.

PubMed

Verdi, Kacy K; Ellis, Heidi Jc; Gryk, Michael R

2007-01-30

Scientific workflows improve the process of scientific experiments by making computations explicit, underscoring data flow, and emphasizing the participation of humans in the process when intuition and human reasoning are required. Workflows for experiments also highlight transitions among experimental phases, allowing intermediate results to be verified and supporting the proper handling of semantic mismatches and different file formats among the various tools used in the scientific process. Thus, scientific workflows are important for the modeling and subsequent capture of bioinformatics-related data. While much research has been conducted on the implementation of scientific workflows, the initial process of actually designing and generating the workflow at the conceptual level has received little consideration. We propose a structured process to capture scientific workflows at the conceptual level that allows workflows to be documented efficiently, results in concise models of the workflow and more-correct workflow implementations, and provides insight into the scientific process itself. The approach uses three modeling techniques to model the structural, data flow, and control flow aspects of the workflow. The domain of biomolecular structure determination using Nuclear Magnetic Resonance spectroscopy is used to demonstrate the process. Specifically, we show the application of the approach to capture the workflow for the process of conducting biomolecular analysis using Nuclear Magnetic Resonance (NMR) spectroscopy. Using the approach, we were able to accurately document, in a short amount of time, numerous steps in the process of conducting an experiment using NMR spectroscopy. The resulting models are correct and precise, as outside validation of the models identified only minor omissions in the models. In addition, the models provide an accurate visual description of the control flow for conducting biomolecular analysis using NMR spectroscopy experiment.

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

ERIC Educational Resources Information Center

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

2015-01-01

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

Self-Assembly, Guest Capture, and NMR Spectroscopy of a Metal-Organic Cage in Water

ERIC Educational Resources Information Center

Go, Eun Bin; Srisuknimit, Veerasak; Cheng, Stephanie L.; Vosburg, David A.

2016-01-01

A green organic-inorganic laboratory experiment has been developed in which students prepare a self-assembling iron cage in D[subscript 2]O at room temperature. The tetrahedral cage captures a small, neutral molecule such as cyclohexane or tetrahydrofuran. [Superscript 1]H NMR analysis distinguishes captured and free guests through diagnostic…

Structure Determination of Unknown Organic Liquids Using NMR and IR Spectroscopy: A General Chemistry Laboratory

ERIC Educational Resources Information Center

Pavel, John T.; Hyde, Erin C.; Bruch, Martha D.

2012-01-01

This experiment introduced general chemistry students to the basic concepts of organic structures and to the power of spectroscopic methods for structure determination. Students employed a combination of IR and NMR spectroscopy to perform de novo structure determination of unknown alcohols, without being provided with a list of possible…

Introducing High School Students to NMR Spectroscopy through Percent Composition Determination Using Low-Field Spectrometers

ERIC Educational Resources Information Center

Bonjour, Jessica L.; Pitzer, Joy M.; Frost, John A.

2015-01-01

Mole to gram conversions, density, and percent composition are fundamental concepts in first year chemistry at the high school or undergraduate level; however, students often find it difficult to engage with these concepts. We present a simple laboratory experiment utilizing portable nuclear magnetic resonance spectroscopy (NMR) to determine the…

Probing hydrogen bonding in cocrystals and amorphous dispersions using (14)N-(1)H HMQC solid-state NMR.

PubMed

Tatton, Andrew S; Pham, Tran N; Vogt, Frederick G; Iuga, Dinu; Edwards, Andrew J; Brown, Steven P

2013-03-04

Cocrystals and amorphous solid dispersions have generated interest in the pharmaceutical industry as an alternative to more established solid delivery forms. The identification of intermolecular hydrogen bonding interactions in a nicotinamide palmitic acid cocrystal and a 50% w/w acetaminophen-polyvinylpyrrolidone solid dispersion are reported using advanced solid-state magic-angle spinning (MAS) NMR methods. The application of a novel (14)N-(1)H HMQC experiment, where coherence transfer is achieved via through-space couplings, is shown to identify specific hydrogen bonding motifs. Additionally, (1)H isotropic chemical shifts and (14)N electric field gradient (EFG) parameters, both accessible from (14)N-(1)H HMQC experiments, are shown to be sensitive to changes in hydrogen bonding geometry. Numerous indicators of molecular association are accessible from this experiment, including NH cross-peaks occurring from intermolecular hydrogen bonds and changes in proton chemical shifts or electric field gradient parameters. First-principles calculations using the GIPAW approach that yield accurate estimates of isotropic chemical shifts, and EFG parameters were used to assist in assignment. It is envisaged that (14)N-(1)H HMQC solid state NMR experiments could become a valuable screening technique of solid delivery forms in the pharmaceutical industry.

"Invisible" conformers of an antifungal disulfide protein revealed by constrained cold and heat unfolding, CEST-NMR experiments, and molecular dynamics calculations.

PubMed

Fizil, Ádám; Gáspári, Zoltán; Barna, Terézia; Marx, Florentine; Batta, Gyula

2015-03-23

Transition between conformational states in proteins is being recognized as a possible key factor of function. In support of this, hidden dynamic NMR structures were detected in several cases up to populations of a few percent. Here, we show by two- and three-state analysis of thermal unfolding, that the population of hidden states may weight 20-40 % at 298 K in a disulfide-rich protein. In addition, sensitive (15) N-CEST NMR experiments identified a low populated (0.15 %) state that was in slow exchange with the folded PAF protein. Remarkably, other techniques failed to identify the rest of the NMR "dark matter". Comparison of the temperature dependence of chemical shifts from experiments and molecular dynamics calculations suggests that hidden conformers of PAF differ in the loop and terminal regions and are most similar in the evolutionary conserved core. Our observations point to the existence of a complex conformational landscape with multiple conformational states in dynamic equilibrium, with diverse exchange rates presumably responsible for the completely hidden nature of a considerable fraction. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

High resolution NMR study of T{sub 1} magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

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

Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L., E-mail: ivanov@tomo.nsc.ru

2014-10-21

Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I–III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T{sub 1}-relaxation timesmore » at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.« less

Computer-intensive simulation of solid-state NMR experiments using SIMPSON.

PubMed

Tošner, Zdeněk; Andersen, Rasmus; Stevensson, Baltzar; Edén, Mattias; Nielsen, Niels Chr; Vosegaard, Thomas

2014-09-01

Conducting large-scale solid-state NMR simulations requires fast computer software potentially in combination with efficient computational resources to complete within a reasonable time frame. Such simulations may involve large spin systems, multiple-parameter fitting of experimental spectra, or multiple-pulse experiment design using parameter scan, non-linear optimization, or optimal control procedures. To efficiently accommodate such simulations, we here present an improved version of the widely distributed open-source SIMPSON NMR simulation software package adapted to contemporary high performance hardware setups. The software is optimized for fast performance on standard stand-alone computers, multi-core processors, and large clusters of identical nodes. We describe the novel features for fast computation including internal matrix manipulations, propagator setups and acquisition strategies. For efficient calculation of powder averages, we implemented interpolation method of Alderman, Solum, and Grant, as well as recently introduced fast Wigner transform interpolation technique. The potential of the optimal control toolbox is greatly enhanced by higher precision gradients in combination with the efficient optimization algorithm known as limited memory Broyden-Fletcher-Goldfarb-Shanno. In addition, advanced parallelization can be used in all types of calculations, providing significant time reductions. SIMPSON is thus reflecting current knowledge in the field of numerical simulations of solid-state NMR experiments. The efficiency and novel features are demonstrated on the representative simulations. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

Chen, H.C.

1988-01-01

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

Experimental research of gas shale electrical properties by NMR and the combination of imbibition and drainage

NASA Astrophysics Data System (ADS)

Dong, Xu; Sun, Jianmeng; Li, Jun; Gao, Hui; Liu, Xuefeng; Wang, Jinjie

2015-08-01

Gas shale has shown considerable force in gas production worldwide, but little attention has been paid to its electrical properties, which are essential for reservoir evaluation and differentiating absorbed gas and free gas. In this study, experiments are designed to research water saturation establishment methods and electrical properties of gas shale. Nuclear magnetic resonance (NMR) with short echo space (TE) is used to identify water saturation and distribution of saturated pores which contribute to the conductivity. The experimental results indicate that NMR with shorter TE can estimate porosity and fluid distribution better than NMR with longer TE. A full range of water saturation is established by the combination of new-type spontaneous imbibition and semi-permeable plate drainage techniques. Spontaneous imbibition gains water saturation from 0% to near irreducible water saturation, and, semi-permeable plate drainage desaturates from 100% to irreducible water saturation. The RI-Sw curve shows a nonlinear relationship, and can be divided into three parts with different behaviors. The comparative analysis of transverse relaxation time (T2) distribution and RI-Sw curves, indicates that free water, and water trapped by capillarity in the non-clay matrix, differ in terms of electrical conductivity from water absorbed in clay. The new experiments prove the applicability of imbibition, drainage and NMR in investigating electrical properties of gas shale and differentiating fluid distribution which makes contribution to conductivity.

In situ NMR spectroscopy of supercapacitors: insight into the charge storage mechanism.

PubMed

Wang, Hao; Forse, Alexander C; Griffin, John M; Trease, Nicole M; Trognko, Lorie; Taberna, Pierre-Louis; Simon, Patrice; Grey, Clare P

2013-12-18

Electrochemical capacitors, commonly known as supercapacitors, are important energy storage devices with high power capabilities and long cycle lives. Here we report the development and application of in situ nuclear magnetic resonance (NMR) methodologies to study changes at the electrode-electrolyte interface in working devices as they charge and discharge. For a supercapacitor comprising activated carbon electrodes and an organic electrolyte, NMR experiments carried out at different charge states allow quantification of the number of charge storing species and show that there are at least two distinct charge storage regimes. At cell voltages below 0.75 V, electrolyte anions are increasingly desorbed from the carbon micropores at the negative electrode, while at the positive electrode there is little change in the number of anions that are adsorbed as the voltage is increased. However, above a cell voltage of 0.75 V, dramatic increases in the amount of adsorbed anions in the positive electrode are observed while anions continue to be desorbed at the negative electrode. NMR experiments with simultaneous cyclic voltammetry show that supercapacitor charging causes marked changes to the local environments of charge storing species, with periodic changes of their chemical shift observed. NMR calculations on a model carbon fragment show that the addition and removal of electrons from a delocalized system should lead to considerable increases in the nucleus-independent chemical shift of nearby species, in agreement with our experimental observations.

In Situ NMR Spectroscopy of Supercapacitors: Insight into the Charge Storage Mechanism

PubMed Central

2013-01-01

Electrochemical capacitors, commonly known as supercapacitors, are important energy storage devices with high power capabilities and long cycle lives. Here we report the development and application of in situ nuclear magnetic resonance (NMR) methodologies to study changes at the electrode–electrolyte interface in working devices as they charge and discharge. For a supercapacitor comprising activated carbon electrodes and an organic electrolyte, NMR experiments carried out at different charge states allow quantification of the number of charge storing species and show that there are at least two distinct charge storage regimes. At cell voltages below 0.75 V, electrolyte anions are increasingly desorbed from the carbon micropores at the negative electrode, while at the positive electrode there is little change in the number of anions that are adsorbed as the voltage is increased. However, above a cell voltage of 0.75 V, dramatic increases in the amount of adsorbed anions in the positive electrode are observed while anions continue to be desorbed at the negative electrode. NMR experiments with simultaneous cyclic voltammetry show that supercapacitor charging causes marked changes to the local environments of charge storing species, with periodic changes of their chemical shift observed. NMR calculations on a model carbon fragment show that the addition and removal of electrons from a delocalized system should lead to considerable increases in the nucleus-independent chemical shift of nearby species, in agreement with our experimental observations. PMID:24274637

Compressed sensing and the reconstruction of ultrafast 2D NMR data: Principles and biomolecular applications.

PubMed

Shrot, Yoav; Frydman, Lucio

2011-04-01

A topic of active investigation in 2D NMR relates to the minimum number of scans required for acquiring this kind of spectra, particularly when these are dictated by sampling rather than by sensitivity considerations. Reductions in this minimum number of scans have been achieved by departing from the regular sampling used to monitor the indirect domain, and relying instead on non-uniform sampling and iterative reconstruction algorithms. Alternatively, so-called "ultrafast" methods can compress the minimum number of scans involved in 2D NMR all the way to a minimum number of one, by spatially encoding the indirect domain information and subsequently recovering it via oscillating field gradients. Given ultrafast NMR's simultaneous recording of the indirect- and direct-domain data, this experiment couples the spectral constraints of these orthogonal domains - often calling for the use of strong acquisition gradients and large filter widths to fulfill the desired bandwidth and resolution demands along all spectral dimensions. This study discusses a way to alleviate these demands, and thereby enhance the method's performance and applicability, by combining spatial encoding with iterative reconstruction approaches. Examples of these new principles are given based on the compressed-sensed reconstruction of biomolecular 2D HSQC ultrafast NMR data, an approach that we show enables a decrease of the gradient strengths demanded in this type of experiments by up to 80%. Copyright © 2011 Elsevier Inc. All rights reserved.

Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study.

PubMed

Ferro, Monica; Castiglione, Franca; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco; Mele, Andrea

2016-08-15

The chemical cross-linking of β-cyclodextrin (β-CD) with ethylenediaminetetraacetic dianhydride (EDTA) led to branched polymers referred to as cyclodextrin nanosponges (CDNSEDTA). Two different preparations are described with 1:4 and 1:8 CD-EDTA molar ratios. The corresponding cross-linked polymers were contacted with 0.27 M aqueous solution of ibuprofen sodium salt (IP) leading to homogeneous, colorless, drug loaded hydrogels. The systems were characterized by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Pulsed field gradient spin echo (PGSE) NMR spectroscopy was used to determine the mean square displacement (MSD) of IP inside the polymeric gel at different observation times td. The data were further processed in order to study the time dependence of MSD: MSD = f(td). The proposed methodology is useful to characterize the different diffusion regimes that, in principle, the solute may experience inside the hydrogel, namely normal or anomalous diffusion. The full protocols including the polymer preparation and purification, the obtainment of drug-loaded hydrogels, the NMR sample preparation, the measurement of MSD by HR-MAS NMR spectroscopy and the final data processing to achieve the time dependence of MSD are here reported and discussed. The presented experiments represent a paradigmatic case and the data are discussed in terms of innovative approach to the characterization of the transport properties of an encapsulated guest within a polymeric host of potential application for drug delivery.

Determining pH at elevated pressure and temperature using in situ ¹³C NMR.

PubMed

Surface, J Andrew; Wang, Fei; Zhu, Yanzhe; Hayes, Sophia E; Giammar, Daniel E; Conradi, Mark S

2015-02-03

We have developed an approach for determining pH at elevated pressures and temperatures by using (13)C NMR measurements of inorganic carbon species together with a geochemical equilibrium model. The approach can determine in situ pH with precision better than 0.1 pH units at pressures, temperatures, and ionic strengths typical of geologic carbon sequestration systems. A custom-built high pressure NMR probe was used to collect (13)C NMR spectra of (13)C-labeled CO2 reactions with NaOH solutions and Mg(OH)2 suspensions at pressures up to 107 bar and temperatures of 80 °C. The quantitative nature of NMR spectroscopy allows the concentration ratio [CO2]/[HCO3(-)] to be experimentally determined. This ratio is then used with equilibrium constants calculated for the specific pressure and temperature conditions and appropriate activity coefficients for the solutes to calculate the in situ pH. The experimentally determined [CO2]/[HCO3(-)] ratios agree well with the predicted values for experiments performed with three different concentrations of NaOH and equilibration with multiple pressures of CO2. The approach was then applied to experiments with Mg(OH)2 slurries in which the change in pH could track the dissolution of CO2 into solution, rapid initial Mg(OH)2 dissolution, and onset of magnesium carbonate precipitation.

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.

Theoretical Modeling of 99 Tc NMR Chemical Shifts

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

Hall, Gabriel B.; Andersen, Amity; Washton, Nancy M.

Technetium (Tc) displays a rich chemistry due to the wide range of oxidation states (from -I to +VII) and ability to form coordination compounds. Determination of Tc speciation in complex mixtures is a major challenge, and 99Tc NMR spec-troscopy is widely used to probe chemical environments of Tc in odd oxidation states. However interpretation of the 99Tc NMR data is hindered by the lack of reference compounds. DFT computations can help fill this gap, but to date few com-putational studies have focused on 99Tc NMR of compounds and complexes. This work systematically evaluates the inclu-sion small percentages of Hartree-Fock exchangemore » correlation and relativistic effects in DFT computations to support in-terpretation of the 99Tc NMR spectra. Hybrid functionals are found to perform better than their pure GGA counterparts, and non-relativistic calculations have been found to generally show a lower mean absolute deviation from experiment. Overall non-relativistic PBE0 and B3PW91 calculations are found to most accurately predict 99Tc NMR chemical shifts.« less

Investigating the Hydrolysis Reactions of a Chemical Warfare Agent Surrogate. A Systematic Study using 1H, 13C, 17O, 19F, 31P, and 35Cl NMR Spectroscopy

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

Alam, Todd M.; Wilson, Brendan W.

2015-07-24

During the summer of 2015, I participated in the DHS HS-STEM fellowship at Sandia National Laboratories (SNL, NM) under the supervision of Dr. Todd M. Alam in his Nuclear Magnetic Resonance (NMR) Spectroscopy research group. While with the group, my main project involved pursing various hydrolysis reactions with Diethyl Chlorophosphate (DECP), a surrogate for the agent Sarin (GB). Specifically, I performed different hydrolysis reactions, monitored and tracked the different phosphorous containing species using phosphorous ( 31P) NMR spectroscopy. With the data collected, I performed kinetics studies mapping the rates of DECP hydrolysis. I also used the NMR of different nucleimore » such as 1H, 13C, 17O, and 35Cl to help understand the complexity of the reactions that take place. Finally, my last task at SNL was to work with Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) NMR Spectroscopy optimizing conditions for 19F- 31P filtering NMR experiments.« less

Modeling an in-register, parallel "iowa" aβ fibril structure using solid-state NMR data from labeled samples with rosetta.

PubMed

Sgourakis, Nikolaos G; Yau, Wai-Ming; Qiang, Wei

2015-01-06

Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For β-amyloid (Aβ) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of Aβ using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper" core interactions are determined using a number of solid-state NMR techniques on sparsely (13)C-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa" mutant (D23N) at high resolution (1.2Å backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Heterogeneous Coordination Environments in Lithium-Neutralized Ionomers Identified Using 1H and 7Li MAS NMR

PubMed Central

Alam, Todd M.; Jenkins, Janelle E.; Bolintineanu, Dan S.; Stevens, Mark J.; Frischknecht, Amalie L.; Buitrago, C. Francisco; Winey, Karen I.; Opper, Kathleen L.; Wagener, Kenneth B.

2012-01-01

The carboxylic acid proton and the lithium coordination environments for precise and random Li-neutralized polyethylene acrylic acid P(E-AA) ionomers were explored using high speed solid-state 1H and 7Li MAS NMR. While the 7Li NMR revealed only a single Li coordination environment, the chemical shift temperature variation was dependent on the precise or random nature of the P(E-AA) ionomer. The 1H MAS NMR revealed two different carboxylic acid proton environments in these materials. By utilizing 1H-7Li rotational echo double resonance (REDOR) MAS NMR experiments, it was demonstrated that the proton environments correspond to different average 1H-7Li distances, with the majority of the protonated carboxylic acids having a close through space contact with the Li. Molecular dynamics simulations suggest that the shortest 1H-7Li distance corresponds to un-neutralized carboxylic acids directly involved in the coordination environment of Li clusters. These solid-state NMR results show that heterogeneous structural motifs need to be included when developing descriptions of these ionomer materials.

Solid-state NMR spectroscopy of 18.5 kDa myelin basic protein reconstituted with lipid vesicles: spectroscopic characterisation and spectral assignments of solvent-exposed protein fragments.

PubMed

Zhong, Ligang; Bamm, Vladimir V; Ahmed, Mumdooh A M; Harauz, George; Ladizhansky, Vladimir

2007-12-01

Myelin basic protein (MBP, 18.5 kDa isoform) is a peripheral membrane protein that is essential for maintaining the structural integrity of the multilamellar myelin sheath of the central nervous system. Reconstitution of the most abundant 18.5 kDa MBP isoform with lipid vesicles yields an aggregated assembly mimicking the protein's natural environment, but which is not amenable to standard solution NMR spectroscopy. On the other hand, the mobility of MBP in such a system is variable, depends on the local strength of the protein-lipid interaction, and in general is of such a time scale that the dipolar interactions are averaged out. Here, we used a combination of solution and solid-state NMR (ssNMR) approaches: J-coupling-driven polarization transfers were combined with magic angle spinning and high-power decoupling to yield high-resolution spectra of the mobile fragments of 18.5 kDa murine MBP in membrane-associated form. To partially circumvent the problem of short transverse relaxation, we implemented three-dimensional constant-time correlation experiments (NCOCX, NCACX, CONCACX, and CAN(CO)CX) that were able to provide interresidue and intraresidue backbone correlations. These experiments resulted in partial spectral assignments for mobile fragments of the protein. Additional nuclear Overhauser effect spectroscopy (NOESY)-based experiments revealed that the mobile fragments were exposed to solvent and were likely located outside the lipid bilayer, or in its hydrophilic portion. Chemical shift index analysis showed that the fragments were largely disordered under these conditions. These combined approaches are applicable to ssNMR investigations of other peripheral membrane proteins reconstituted with lipids.

Multinuclear NMR studies of single lipid bilayers supported in cylindrical aluminum oxide nanopores.

PubMed

Gaede, Holly C; Luckett, Keith M; Polozov, Ivan V; Gawrisch, Klaus

2004-08-31

Lipid bilayers were deposited inside the 0.2 microm pores of anodic aluminum oxide (AAO) filters by extrusion of multilamellar liposomes and their properties studied by 2H, 31P, and 1H solid-state NMR. Only the first bilayer adhered strongly to the inner surface of the pores. Additional layers were washed out easily by a flow of water as demonstrated by 1H magic angle spinning NMR experiments with addition of Pr3+ ions to shift accessible lipid headgroup resonances. A 13 mm diameter Anopore filter of 60 microm thickness oriented approximately 2.5 x 10(-7) mol of lipid as a single bilayer, corresponding to a total membrane area of about 500 cm2. The 2H NMR spectra of chain deuterated POPC are consistent with adsorption of wavy, tubular bilayers to the inner pore surface. By NMR diffusion experiments, we determined the average length of those lipid tubules to be approximately 0.4 microm. There is evidence for a thick water layer between lipid tubules and the pore surface. The ends of tubules are well sealed against the pore such that Pr3+ ions cannot penetrate into the water underneath the bilayers. We successfully trapped poly(ethylene glycol) (PEG) with a molecular weight of 8000 in this water layer. From the quantity of trapped PEG, we calculated an average water layer thickness of 3 nm. Lipid order parameters and motional properties are unperturbed by the solid support, in agreement with existence of a water layer. Such unperturbed, solid supported membranes are ideal for incorporation of membrane-spanning proteins with large intra- and extracellular domains. The experiments suggest the promise of such porous filters as membrane support in biosensors.

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.

RF-SABRE: A Way to Continuous Spin Hyperpolarization at High Magnetic Fields.

PubMed

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

2015-10-29

A new technique is developed that allows one to carry out the signal amplification by reversible exchange (SABRE) experiments at high magnetic field. SABRE is a hyperpolarization method, which utilizes transfer of spin order from para-hydrogen to the spins of a substrate in transient iridium complexes. Previously, it has been thought that such a transfer of spin order is only efficient at low magnetic fields, notably, at level anti-crossing (LAC) regions. Here it is demonstrated that LAC conditions can also be fulfilled at high fields under the action of a RF field. The high-field RF-SABRE experiment can be implemented using commercially available nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) machines and does not require technically demanding field-cycling. The achievable NMR enhancements are around 100 for several substrates as compared to their NMR signals at thermal equilibrium conditions at 4.7 T. The frequency dependence of RF-SABRE is comprised of well pronounced peaks and dips, whose position and amplitude are conditioned solely by the magnetic resonance parameters such as chemical shifts and scalar coupling of the spin system involved in the polarization transfer and by the amplitude of the RF field. Thus, the proposed method can serve as a new sensitive tool for probing transient complexes. Simulations of the dependence of magnetization transfer (i.e., NMR signal amplifications) on the frequency and amplitude of the RF field are in good agreement with the developed theoretical approach. Furthermore, the method enables continuous re-hyperpolarization of the SABRE substrate over a long period of time, giving a straightforward way to repetitive NMR experiments.

Detection and characterization of serine and threonine hydroxyl protons in Bacillus circulans xylanase by NMR spectroscopy.

PubMed

Brockerman, Jacob A; Okon, Mark; McIntosh, Lawrence P

2014-01-01

Hydroxyl protons on serine and threonine residues are not well characterized in protein structures determined by both NMR spectroscopy and X-ray crystallography. In the case of NMR spectroscopy, this is in large part because hydroxyl proton signals are usually hidden under crowded regions of (1)H-NMR spectra and remain undetected by conventional heteronuclear correlation approaches that rely on strong one-bond (1)H-(15)N or (1)H-(13)C couplings. However, by filtering against protons directly bonded to (13)C or (15)N nuclei, signals from slowly-exchanging hydroxyls can be observed in the (1)H-NMR spectrum of a uniformly (13)C/(15)N-labeled protein. Here we demonstrate the use of a simple selective labeling scheme in combination with long-range heteronuclear scalar correlation experiments as an easy and relatively inexpensive way to detect and assign these hydroxyl proton signals. Using auxtrophic Escherichia coli strains, we produced Bacillus circulans xylanase (BcX) labeled with (13)C/(15)N-serine or (13)C/(15)N-threonine. Signals from two serine and three threonine hydroxyls in these protein samples were readily observed via (3)JC-OH couplings in long-range (13)C-HSQC spectra. These scalar couplings (~5-7 Hz) were measured in a sample of uniformly (13)C/(15)N-labeled BcX using a quantitative (13)C/(15)N-filtered spin-echo difference experiment. In a similar approach, the threonine and serine hydroxyl hydrogen exchange kinetics were measured using a (13)C/(15)N-filtered CLEANEX-PM pulse sequence. Collectively, these experiments provide insights into the structural and dynamic properties of several serine and threonine hydroxyls within this model protein.

A Multidisciplinary Approach to High Throughput Nuclear Magnetic Resonance Spectroscopy

PubMed Central

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

2016-01-01

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

Development of a Measure of the Experience of Being Bullied in Youth

ERIC Educational Resources Information Center

Hunt, Caroline; Peters, Lorna; Rapee, Ronald M.

2012-01-01

The Personal Experiences Checklist (PECK) was developed to provide a multidimensional assessment of a young person's personal experience of being bullied that covered the full range of bullying behaviors, including covert relational forms of bullying and cyber bullying. A sample of 647 school children were used to develop the scale, and a 2nd…

Characterization and analysis of structural isomers of dimethyl methoxypyrazines in cork stoppers and ladybugs (Harmonia axyridis and Coccinella septempunctata).

PubMed

Slabizki, Petra; Legrum, Charlotte; Meusinger, Reinhard; Schmarr, Hans-Georg

2014-10-01

The three constitutional isomers of dimethyl-substituted methoxypyrazines: 3,5-dimethyl-2-methoxypyrazine 1; 2,5-dimethyl-3-methoxypyrazine 2; and 2,3-dimethyl-5-methoxypyrazine 3 are potent flavor compounds with similar mass spectrometric, gas chromatographic, and nuclear magnetic resonance spectroscopic behavior. Therefore, unambiguous analytical determination is critical, particularly in complex matrices. The unequivocal identification of 1-3 could be achieved by homo- and heteronuclear NMR correlation experiments. The observed mass fragmentation for 1-3 is proposed and discussed, benefitting from synthesized partially deuterated 1 and 2. On common polar and apolar stationary phases used in gas chromatography (GC) 1 and 2 show similar behavior whereas 3 can be separated. In our focus on off-flavor analysis with respect to wine aroma, 1 has been described as a "moldy" off-flavor compound in cork and 2 as a constituent in Harmonia axyridis contributing to the so-called "ladybug taint," whereas 3 has not yet been described as a constituent of wine aroma. A successful separation of 1 and 2 could be achieved on octakis-(2,3-di-O-pentyl-6-O-methyl)-γ-cyclodextrin as stationary phase in GC. Applying heart-cut multidimensional GC analysis with tandem mass spectrometric detection we could confirm the presence of 1 as a "moldy" off-flavor compound in cork. However, in the case of Harmonia axyridis, a previous identification of 2 has to be reconsidered. In our experiments we identified the constitutional isomer 1, which was also found in Coccinella septempunctata, another species discussed with respect to the "ladybug taint." The analysis of such structurally related compounds is a demonstrative example for the importance of a chromatographic separation, as mass spectrometric data by itself could not guarantee the unequivocal identification.

Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation

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

Thurman, Ryan D.; Kathir, Karuppanan Muthusamy; Rajalingam, Dakshinamurthy

Highlights: Black-Right-Pointing-Pointer The structural basis of the Kallmann syndrome is elucidated. Black-Right-Pointing-Pointer Kallmann syndrome mutation (A168S) induces a subtle conformational change(s). Black-Right-Pointing-Pointer Structural interactions mediated by beta-sheet G are most perturbed. Black-Right-Pointing-Pointer Ligand (FGF)-receptor interaction(s) is completely abolished by Kallmann mutation. Black-Right-Pointing-Pointer Kallmann mutation directly affects the FGF signaling process. -- Abstract: Kallmann syndrome (KS) is a developmental disease that expresses in patients as hypogonadotropic hypogonadism and anosmia. KS is commonly associated with mutations in the extracellular D2 domain of the fibroblast growth factor receptor (FGFR). In this study, for the first time, the molecular basis for the FGFR associatedmore » KS mutation (A168S) is elucidated using a variety of biophysical experiments, including multidimensional NMR spectroscopy. Secondary and tertiary structural analysis using far UV circular dichroism, fluorescence and limited trypsin digestion assays suggest that the KS mutation induces subtle tertiary structure change in the D2 domain of FGFR. Results of isothermal titration calorimetry experiments show the KS mutation causes a 10-fold decrease in heparin binding affinity and also a complete loss in ligand (FGF-1) binding. {sup 1}H-{sup 15}N chemical perturbation data suggest that complete loss in the ligand (FGF) binding affinity is triggered by a subtle conformational change that disrupts crucial structural interactions in both the heparin and the FGF binding sites in the D2 domain of FGFR. The novel findings reported in this study are expected to provide valuable clues toward a complete understanding of the other genetic diseases linked to mutations in the FGFR.« less

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).

Mathematical Modeling and Data Analysis of NMR Experiments using Hyperpolarized 13C Metabolites

PubMed Central

Pagès, Guilhem; Kuchel, Philip W.

2013-01-01

Rapid-dissolution dynamic nuclear polarization (DNP) has made significant impact in the characterization and understanding of metabolism that occurs on the sub-minute timescale in several diseases. While significant efforts have been made in developing applications, and in designing rapid-imaging radiofrequency (RF) and magnetic field gradient pulse sequences, very few groups have worked on implementing realistic mathematical/kinetic/relaxation models to fit the emergent data. The critical aspects to consider when modeling DNP experiments depend on both nuclear magnetic resonance (NMR) and (bio)chemical kinetics. The former constraints are due to the relaxation of the NMR signal and the application of ‘read’ RF pulses, while the kinetic constraints include the total amount of each molecular species present. We describe the model-design strategy we have used to fit and interpret our DNP results. To our knowledge, this is the first report on a systematic analysis of DNP data. PMID:25114541

Novel detection schemes of nuclear magnetic resonance and magnetic resonance imaging: applications from analytical chemistry to molecular sensors.

PubMed

Harel, Elad; Schröder, Leif; Xu, Shoujun

2008-01-01

Nuclear magnetic resonance (NMR) is a well-established analytical technique in chemistry. The ability to precisely control the nuclear spin interactions that give rise to the NMR phenomenon has led to revolutionary advances in fields as diverse as protein structure determination and medical diagnosis. Here, we discuss methods for increasing the sensitivity of magnetic resonance experiments, moving away from the paradigm of traditional NMR by separating the encoding and detection steps of the experiment. This added flexibility allows for diverse applications ranging from lab-on-a-chip flow imaging and biological sensors to optical detection of magnetic resonance imaging at low magnetic fields. We aim to compare and discuss various approaches for a host of problems in material science, biology, and physics that differ from the high-field methods routinely used in analytical chemistry and medical imaging.

Defining the interaction of human soluble lectin ZG16p and mycobacterial phosphatidylinositol mannosides

PubMed Central

Ikeda, Akemi; Kojima-Aikawa, Kyoko; Taniguchi, Naoyuki; Varón Silva, Daniel; Feizi, Ten; Seeberger, Peter H.; Yamaguchi, Yoshiki

2018-01-01

ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analyses of the interactions of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs), using glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation Transfer Difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interacts with ZG16p using the mannose residues. Binding site of PIMs is identified by chemical shift perturbation experiments using uniformly 15N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan, which would help to consider the physiological role of ZG16p. PMID:25919894

Structural investigation of Titan tholins by solution-state 1H, 13C, and 15N NMR: one-dimensional and decoupling experiments.

PubMed

He, Chao; Lin, Guangxin; Upton, Kathleen T; Imanaka, Hiroshi; Smith, Mark A

2012-05-17

Titan, the largest moon of Saturn, is enveloped in a reddish brown organic haze. Titan haze is presumed to be formed from methane and nitrogen (CH(4) and N(2)) in Titan's upper atmosphere through energetic photochemistry and particle bombardment. Though Titan haze has been directly investigated using methods including the Cassini mission, its formation mechanism and the contributing chemical structures and prebiotic potential are still not well developed. We report here the structural investigation of the (13)C and (15)N labeled, simulated Titan haze aerosol (tholin) by solution-state NMR. The one-dimensional (1)H, (13)C, and (15)N NMR spectra and decoupling experiments indicate that the tholin sample contains amine, nitrile, imine, and N-heteroaromatic compounds of tremendous import in understanding complex organic chemistry in anaerobic, extraterrestrial environments.

H2BC: a new technique for NMR analysis of complex carbohydrates.

PubMed

Petersen, Bent O; Vinogradov, Evguenii; Kay, William; Würtz, Peter; Nyberg, Nils T; Duus, Jens Ø; Sørensen, Ole W

2006-03-20

It is demonstrated that the H2BC NMR pulse sequence (J. Am. Chem. Soc.2005, 127, 6154, Magn. Reson. Chem.2005, 43, 971-974) offers unambiguous assignments and significant simplification of NMR spectra of large and complex carbohydrates compared to other techniques for the establishment of correlations over more than one bond. H2BC almost exclusively correlates protons and proton-bearing carbon spins separated by two covalent bonds and is independent of occasionally vanishing (2)J(CH) coupling constants, which alleviates the problem of missing two-bond correlations in HMBC spectra. H2BC also solves the problem of distinguishing two- and three-bond correlations in HSQC-TOCSY or HMBC. It is a further asset of H2BC that the experiment is significantly shorter than HMBC and HSQC-TOCSY, and hence less sensitive to transverse relaxation. The H2BC experiment is demonstrated on an approximately 30-residue oligosaccharide from Francisella victoria.

Long-range 1H-1H NMR correlation: extending connectivities to remote bonds via an intermediate heterospin.

PubMed

Parella, Teodor; Espinosa, Juan Félix

2008-05-01

An out-and-stay 2D proton-proton NMR correlation experiment is proposed to detect long-range proton-proton connectivities up to six and seven bonds away. The magnetization flow pathway is based on a consecutive, dual-step J(CH)-transfer mechanism and it allows one to trace out (1)H-(1)H connectivities between protons belonging to different spin systems. This novel experimental scheme will be particularly useful in cases when carbon resonances overlap, providing connectivity information that could not be obtained in a HMBC experiment. The success of the experiment is demonstrated in the structural studies of a wide variety of chemical compounds. 2008 John Wiley & Sons, Ltd.

A nonlocal electron conduction model for multidimensional radiation hydrodynamics codes

NASA Astrophysics Data System (ADS)

Schurtz, G. P.; Nicolaï, Ph. D.; Busquet, M.

2000-10-01

Numerical simulation of laser driven Inertial Confinement Fusion (ICF) related experiments require the use of large multidimensional hydro codes. Though these codes include detailed physics for numerous phenomena, they deal poorly with electron conduction, which is the leading energy transport mechanism of these systems. Electron heat flow is known, since the work of Luciani, Mora, and Virmont (LMV) [Phys. Rev. Lett. 51, 1664 (1983)], to be a nonlocal process, which the local Spitzer-Harm theory, even flux limited, is unable to account for. The present work aims at extending the original formula of LMV to two or three dimensions of space. This multidimensional extension leads to an equivalent transport equation suitable for easy implementation in a two-dimensional radiation-hydrodynamic code. Simulations are presented and compared to Fokker-Planck simulations in one and two dimensions of space.

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

NASA Astrophysics Data System (ADS)

Geppi, Marco; Forte, Claudia

1999-03-01

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

In situ observations of water production and distribution in an operating H2/O2 PEM fuel cell assembly using 1H NMR microscopy.

PubMed

Feindel, Kirk W; LaRocque, Logan P-A; Starke, Dieter; Bergens, Steven H; Wasylishen, Roderick E

2004-09-22

Proton NMR imaging was used to investigate in situ the distribution of water in a polymer electrolyte membrane fuel cell operating on H2 and O2. In a single experiment, water was monitored in the gas flow channels, the membrane electrode assembly, and in the membrane surrounding the catalysts. Radial gradient diffusion removes water from the catalysts into the surrounding membrane. This research demonstrates the strength of 1H NMR microscopy as an aid for designing fuel cells to optimize water management.

Enhanced detection of aldehydes in Extra-Virgin Olive Oil by means of band selective NMR spectroscopy

NASA Astrophysics Data System (ADS)

Dugo, Giacomo; Rotondo, Archimede; Mallamace, Domenico; Cicero, Nicola; Salvo, Andrea; Rotondo, Enrico; Corsaro, Carmelo

2015-02-01

High resolution Nuclear Magnetic Resonance (NMR) spectroscopy is a very powerful tool for comprehensive food analyses and especially for Extra-Virgin Olive Oils (EVOOs). We use the NMR technique to study the spectral region of aldehydes (8-10 ppm) for EVOOs coming from the south part of Italy. We perform novel experiments by using mono and bidimensional band selective spin-echo pulse sequences and identify four structural classes of aldehydes in EVOOs. For the first time such species are identified in EVOOs without any chemical treatment; only dilution with CDCl3 is employed. This would allow the discrimination of different EVOOs for the aldehydes content increasing the potentiality of the NMR technique in the screening of metabolites for geographical characterization of EVOOs.

Continuous hyperpolarization with parahydrogen in a membrane reactor

NASA Astrophysics Data System (ADS)

Lehmkuhl, Sören; Wiese, Martin; Schubert, Lukas; Held, Mathias; Küppers, Markus; Wessling, Matthias; Blümich, Bernhard

2018-06-01

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the "Signal Amplification by Reversible Exchange" (SABRE) approach uses para-enriched hydrogen, p-H2, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H2, supply and consecutive detection in a 1 T NMR spectrometer. Two SABRE substrates pyridine and nicotinamide were hyperpolarized, and more than 1000-fold signal enhancement was found. Our strategy combines low-field NMR spectrometry and a membrane flow reactor. This enables precise control of the experimental conditions such as liquid and gas pressures, and volume flow for ensuring repeatable maximum polarization.

Hydrogen bonds determine the signal arrangement in 13C NMR spectra of nicotinate

NASA Astrophysics Data System (ADS)

Gamov, G. A.; Kuranova, N. N.; Pogonin, A. E.; Aleksandriiskii, V. V.; Sharnin, V. A.

2018-02-01

Present work reports on studies of sodium nicotinate solutions in water and aqueous ethanol by means of 1H, 13C, 15N NMR spectroscopy. The H(2) nucleus was observed to be the least shielded among pyridine ring protons whilst C(6) signal placed in the lowest field in relation to the other pyridine carbons. The hydrogen bonds formation between nicotinate and water molecules was shown to be probable reason of signal arrangement in 13C NMR spectra of nicotinate. The heteronitrogen of nicotinate is less prone to the hydrogen bonding with water molecules than that of nicotinamide. The data on the change in the Gibbs energy of the nicotinate transfer and the results of the 13C NMR experiment are compared.

First principles NMR calculations of phenylphosphinic acid C 6H 5HPO(OH): Assignments, orientation of tensors by local field experiments and effect of molecular motion

NASA Astrophysics Data System (ADS)

Gervais, C.; Coelho, C.; Azaı¨s, T.; Maquet, J.; Laurent, G.; Pourpoint, F.; Bonhomme, C.; Florian, P.; Alonso, B.; Guerrero, G.; Mutin, P. H.; Mauri, F.

2007-07-01

The complete set of NMR parameters for 17O enriched phenylphosphinic acid C 6H 5HP ∗O( ∗OH) is calculated from first principles by using the Gauge Including Projected Augmented Wave (GIPAW) approach [C.J. Pickard, F. Mauri, All-electron magnetic response with pseudopotentials: NMR chemical shifts, Phys. Rev. B 63 (2001) 245101/1-245101/13]. The analysis goes beyond the successful assignment of the spectra for all nuclei ( 1H, 13C, 17O, 31P), as: (i) the 1H CSA (chemical shift anisotropy) tensors (magnitude and orientation) have been interpreted in terms of H bonding and internuclear distances. (ii) CSA/dipolar local field correlation experiments have allowed the orientation of the direct P-H bond direction in the 31P CSA tensor to be determined. Experimental and calculated data were compared. (iii) The overestimation of the calculated 31P CSA has been explained by local molecular reorientation and confirmed by low temperature static 1H → 31P CP experiments.

NMR-based diffusion pore imaging.

PubMed

Laun, Frederik Bernd; Kuder, Tristan Anselm; Wetscherek, Andreas; Stieltjes, Bram; Semmler, Wolfhard

2012-08-01

Nuclear magnetic resonance (NMR) diffusion experiments offer a unique opportunity to study boundaries restricting the diffusion process. In a recent Letter [Phys. Rev. Lett. 107, 048102 (2011)], we introduced the idea and concept that such diffusion experiments can be interpreted as NMR imaging experiments. Consequently, images of closed pores, in which the spins diffuse, can be acquired. In the work presented here, an in-depth description of the diffusion pore imaging technique is provided. Image artifacts due to gradient profiles of finite duration, field inhomogeneities, and surface relaxation are considered. Gradients of finite duration lead to image blurring and edge enhancement artifacts. Field inhomogeneities have benign effects on diffusion pore images, and surface relaxation can lead to a shrinkage and shift of the pore image. The relation between boundary structure and the imaginary part of the diffusion weighted signal is analyzed, and it is shown that information on pore coherence can be obtained without the need to measure the phase of the diffusion weighted signal. Moreover, it is shown that quite arbitrary gradient profiles can be used for diffusion pore imaging. The matrices required for numerical calculations are stated and provided as supplemental material.

Increasing verbal knowledge mediates development of multidimensional emotion representations

PubMed Central

Nook, Erik C.; Sasse, Stephanie F.; Lambert, Hilary K.; McLaughlin, Katie A.; Somerville, Leah H.

2017-01-01

How do people represent their own and others’ emotional experiences? Contemporary emotion theories and growing evidence suggest that the conceptual representation of emotion plays a central role in how people understand the emotions both they and other people feel.1–6 Although decades of research indicate that adults typically represent emotion concepts as multidimensional, with valence (positive—negative) and arousal (activating—deactivating) as two primary dimensions,7–10 little is known about how this bidimensional (or circumplex) representation arises.11 Here we show that emotion representations develop from a monodimensional focus on valence to a bidimensional focus on both valence and arousal from age 6 to age 25. We investigated potential mechanisms underlying this effect and found that increasing verbal knowledge mediated emotion representation development over and above three other potential mediators: (i) fluid reasoning, (ii) the general ability to represent non-emotional stimuli bidimensionally, and (iii) task-related behaviors (e.g., using extreme ends of rating scales). These results suggest that verbal development facilitates the expansion of emotion concept representations (and potentially emotional experiences) from a “positive or negative” dichotomy in childhood to a multidimensional organization in adulthood. PMID:29399639

Imaging a multidimensional multichannel potential energy surface: Photodetachment of H{sup −}(NH{sub 3}) and NH{sub 4}{sup −}

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

Hu, Qichi; Johnson, Christopher J.; Continetti, Robert E., E-mail: hguo@umn.edu, E-mail: rcontinetti@ucsd.edu

2016-06-28

Probes of the Born-Oppenheimer potential energy surfaces governing polyatomic molecules often rely on spectroscopy for the bound regions or collision experiments in the continuum. A combined spectroscopic and half-collision approach to image nuclear dynamics in a multidimensional and multichannel system is reported here. The Rydberg radical NH{sub 4} and the double Rydberg anion NH{sub 4}{sup −} represent a polyatomic system for benchmarking electronic structure and nine-dimensional quantum dynamics calculations. Photodetachment of the H{sup −}(NH{sub 3}) ion-dipole complex and the NH{sub 4}{sup −} DRA probes different regions on the neutral NH{sub 4} PES. Photoelectron energy and angular distributions at photon energiesmore » of 1.17, 1.60, and 2.33 eV compare well with quantum dynamics. Photoelectron-photofragment coincidence experiments indicate dissociation of the nascent NH{sub 4} Rydberg radical occurs to H + NH{sub 3} with a peak kinetic energy of 0.13 eV, showing the ground state of NH{sub 4} to be unstable, decaying by tunneling-induced dissociation on a time scale beyond the present scope of multidimensional quantum dynamics.« less

A Qualitative-Quantitative H-NMR Experiment for the Instrumental Analysis Laboratory.

ERIC Educational Resources Information Center

Phillips, John S.; Leary, James J.

1986-01-01

Describes an experiment combining qualitative and quantitative information from hydrogen nuclear magnetic resonance spectra. Reviews theory, discusses the experimental approach, and provides sample results. (JM)

A non-uniformly sampled 4D HCC(CO)NH-TOCSY experiment processed using maximum entropy for rapid protein sidechain assignment

PubMed Central

Mobli, Mehdi; Stern, Alan S.; Bermel, Wolfgang; King, Glenn F.; Hoch, Jeffrey C.

2010-01-01

One of the stiffest challenges in structural studies of proteins using NMR is the assignment of sidechain resonances. Typically, a panel of lengthy 3D experiments are acquired in order to establish connectivities and resolve ambiguities due to overlap. We demonstrate that these experiments can be replaced by a single 4D experiment that is time-efficient, yields excellent resolution, and captures unique carbon-proton connectivity information. The approach is made practical by the use of non-uniform sampling in the three indirect time dimensions and maximum entropy reconstruction of the corresponding 3D frequency spectrum. This 4D method will facilitate automated resonance assignment procedures and it should be particularly beneficial for increasing throughput in NMR-based structural genomics initiatives. PMID:20299257

Synthesis of Polystyrene and Molecular Weight Determination by [superscript 1]H NMR End-Group Analysis

ERIC Educational Resources Information Center

Wackerly, Jay Wm.; Dunne, James F.

2017-01-01

A procedure for the solution polymerization of styrene using di-"tert"-butyl peroxide (DTBP) as the initiator is described. The use of DTBP allows for end-group analysis by [superscript 1]H NMR spectroscopy and calculation of the number-average molecular weight of the polymer. This experiment was designed as a laboratory introduction to…

Isobutylene Dimerization: A Discovery-Based Exploration of Mechanism and Regioselectivity by NMR Spectroscopy and Molecular Modeling

ERIC Educational Resources Information Center

Schuster, Mariah L.; Peterson, Karl P.; Stoffregen, Stacey A.

2018-01-01

This two-period undergraduate laboratory experiment involves the synthesis of a mixture of isomeric unknowns, isolation of the mixture by means of distillation, and characterization of the two products primarily by NMR spectroscopy (1D and 2D) supported with IR spectroscopy and GC-MS techniques. Subsequent calculation and examination of the…

An Introduction to Drug Discovery by Probing Protein-Substrate Interactions Using Saturation Transfer Difference-Nuclear Magnetic Resonance (STD-NMR)

ERIC Educational Resources Information Center

Guegan, Jean-Paul; Daniellou, Richard

2012-01-01

NMR spectroscopy is a powerful tool for characterizing and identifying molecules and nowadays is even used to characterize complex systems in biology. In the experiment presented here, students learned how to apply this modern technique to probe interactions between small molecules and proteins. With the use of simple organic synthesis, students…

Thermal convection currents in NMR: flow profiles and implications for coherence pathway selection

PubMed

Jerschow

2000-07-01

Rayleigh-Benard convection currents are visualized in a vertical cylindrical tube by means of magnetic resonance imaging. Axially antisymmetric flow, multiple vertical rolls, and twisted node planes are observed. The flow can also be induced by strong RF irradiation. Its effects on the coherence pathways in NMR experiments employing field gradients are discussed. Copyright 2000 Academic Press.

Synthesis, high-resolution NMR spectroscopic analysis, and single-crystal X-ray diffraction of isoxazoline tetracycles.

PubMed

Fascio, Mirta L; Alvarez-Larena, Angel; D'Accorso, Norma B

2002-11-29

Three isoxazoline tetracycles were obtained enantiomerically pure by intramolecular 1,3-dipolar cycloaddition. The characterization of the new compounds was performed by high-resolution 1H and 13C NMR spectroscopy. The relative configuration of the new chiral centers was determined by NOESY experiments and confirmed by single-crystal X-ray structural analysis.

Can enzyme engineering benefit from the modulation of protein motions? Lessons learned from NMR relaxation dispersion experiments.

PubMed

Doucet, Nicolas

2011-04-01

Despite impressive progress in protein engineering and design, our ability to create new and efficient enzyme activities remains a laborious and time-consuming endeavor. In the past few years, intricate combinations of rational mutagenesis, directed evolution and computational methods have paved the way to exciting engineering examples and are now offering a new perspective on the structural requirements of enzyme activity. However, these structure-function analyses are usually guided by the time-averaged static models offered by enzyme crystal structures, which often fail to describe the functionally relevant 'invisible states' adopted by proteins in space and time. To alleviate such limitations, NMR relaxation dispersion experiments coupled to mutagenesis studies have recently been applied to the study of enzyme catalysis, effectively complementing 'structure-function' analyses with 'flexibility-function' investigations. In addition to offering quantitative, site-specific information to help characterize residue motion, these NMR methods are now being applied to enzyme engineering purposes, providing a powerful tool to help characterize the effects of controlling long-range networks of flexible residues affecting enzyme function. Recent advancements in this emerging field are presented here, with particular attention to mutagenesis reports highlighting the relevance of NMR relaxation dispersion tools in enzyme engineering.

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

Rheo-NMR Measurements of Cocoa Butter Crystallized Under

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

Mudge, E.; Mazzanti, G

2009-01-01

Modifications of a benchtop NMR instrument were made to apply temperature control to a shearing NMR cell. This has enabled the determination in situ of the solid fat content (SFC) of cocoa butter under shearing conditions. The cocoa butter was cooled at 3 C/min to three final temperatures of 17.5, 20.0, and 22.5 C with applied shear rates between 45 and 720 s-1. Polymorphic transitions of the cocoa butter were determined using synchrotron X-ray diffraction with an identical shearing system constructed of Lexan. Sheared samples were shown to have accelerated phase transitions compared to static experiments. In experiments where formmore » V was confirmed to be the dominant polymorph, the final SFC averaged around 50%. However, when other polymorphic forms were formed, a lower SFC was measured because the final temperature was within the melting range of that polymorph and only partial crystallization happened. A shear rate of 720 s-1 delayed phase transitions, likely due to viscous heating of the sample. Pulsed NMR is an invaluable tool for determining the crystalline fraction in hydrogen containing materials, yet its use for fundamental and industrial research on fat or alkanes crystallization under shear has only recently been developed.« less

Improved Spin-Echo-Edited NMR Diffusion Measurements

NASA Astrophysics Data System (ADS)

Otto, William H.; Larive, Cynthia K.

2001-12-01

The need for simple and robust schemes for the analysis of ligand-protein binding has resulted in the development of diffusion-based NMR techniques that can be used to assay binding in protein solutions containing a mixture of several ligands. As a means of gaining spectral selectivity in NMR diffusion measurements, a simple experiment, the gradient modified spin-echo (GOSE), has been developed to reject the resonances of coupled spins and detect only the singlets in the 1H NMR spectrum. This is accomplished by first using a spin echo to null the resonances of the coupled spins. Following the spin echo, the singlet magnetization is flipped out of the transverse plane and a dephasing gradient is applied to reduce the spectral artifacts resulting from incomplete cancellation of the J-coupled resonances. The resulting modular sequence is combined here with the BPPSTE pulse sequence; however, it could be easily incorporated into any pulse sequence where additional spectral selectivity is desired. Results obtained with the GOSE-BPPSTE pulse sequence are compared with those obtained with the BPPSTE and CPMG-BPPSTE experiments for a mixture containing the ligands resorcinol and tryptophan in a solution of human serum albumin.

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.

A Multidimensional Assessment of Children in Conflictual Contexts: The Case of Kenya

ERIC Educational Resources Information Center

Okech, Jane E. Atieno

2012-01-01

Children in Kenya's Kisumu District Primary Schools (N = 430) completed three measures of trauma. Respondents completed the "My Worst Experience Scale" (MWES; Hyman and Snook 2002) and its supplement, the "School Alienation and Trauma Survey" (SATS; Hyman and Snook 2002), sharing their worst experiences overall and specifically…

Sealed rotors for in situ high temperature high pressure MAS NMR

DOE PAGES

Hu, Jian Z.; Hu, Mary Y.; Zhao, Zhenchao; ...

2015-07-06

Magic angle spinning (MAS) nuclear magnetic resonance (NMR) investigations on heterogeneous samples containing solids, semi-solids, liquid and gases or a mixture of them under non-conventional conditions of a combined high pressure and high temperature, or cold temperature suffer from the unavailability of a perfectly sealed rotor. Here, we report the design of reusable and perfectly-sealed all-zircornia MAS rotors. The rotors are easy to use and are suitable for operation temperatures from below 0 to 250 °C and pressures up to 100 bar. As an example of potential applications we performed in situ MAS NMR investigations of AlPO₄-5 molecular sieve crystallization,more » a kinetic study of the cyclohexanol dehydration reaction using 13C MAS NMR, and an investigation of the metabolomics of intact biological tissue at low temperature using 1H HR-MAS NMR spectroscopy. The in situ MAS NMR experiments performed using the reported rotors allowed reproduction of the results from traditional batch reactions, while offering more detailed quantitative information at the molecular level, as demonstrated for the molecular sieve synthesis and activation energy measurements for cyclohexanol dehydration. The perfectly sealed rotor also shows promising application for metabolomics studies using 1H HR-MAS NMR.« less

Sealed rotors for in situ high temperature high pressure MAS NMR

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

Hu, Jian Z.; Hu, Mary Y.; Zhao, Zhenchao

Magic angle spinning (MAS) nuclear magnetic resonance (NMR) investigations on heterogeneous samples containing solids, semi-solids, liquid and gases or a mixture of them under non-conventional conditions of a combined high pressure and high temperature, or cold temperature suffer from the unavailability of a perfectly sealed rotor. Here, we report the design of reusable and perfectly-sealed all-zircornia MAS rotors. The rotors are easy to use and are suitable for operation temperatures from below 0 to 250 °C and pressures up to 100 bar. As an example of potential applications we performed in situ MAS NMR investigations of AlPO₄-5 molecular sieve crystallization,more » a kinetic study of the cyclohexanol dehydration reaction using 13C MAS NMR, and an investigation of the metabolomics of intact biological tissue at low temperature using 1H HR-MAS NMR spectroscopy. The in situ MAS NMR experiments performed using the reported rotors allowed reproduction of the results from traditional batch reactions, while offering more detailed quantitative information at the molecular level, as demonstrated for the molecular sieve synthesis and activation energy measurements for cyclohexanol dehydration. The perfectly sealed rotor also shows promising application for metabolomics studies using 1H HR-MAS NMR.« less

Magnetic Field Gradient Calibration as an Experiment to Illustrate Magnetic Resonance Imaging

ERIC Educational Resources Information Center

Seedhouse, Steven J.; Hoffmann, Markus M.

2008-01-01

A nuclear magnetic resonance (NMR) spectroscopy experiment for the undergraduate physical chemistry laboratory is described that encompasses both qualitative and quantitative pedagogical goals. Qualitatively, the experiment illustrates how images are obtained in magnetic resonance imaging (MRI). Quantitatively, students experience the…

Interfacial Ca2+ environments in nanocrystalline apatites revealed by dynamic nuclear polarization enhanced 43Ca NMR spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Daniel; Leroy, César; Crevant, Charlène; Bonhomme-Coury, Laure; Babonneau, Florence; Laurencin, Danielle; Bonhomme, Christian; de Paëpe, Gaël

2017-01-01

The interfaces within bones, teeth and other hybrid biomaterials are of paramount importance but remain particularly difficult to characterize at the molecular level because both sensitive and selective techniques are mandatory. Here, it is demonstrated that unprecedented insights into calcium environments, for example the differentiation of surface and core species of hydroxyapatite nanoparticles, can be obtained using solid-state NMR, when combined with dynamic nuclear polarization. Although calcium represents an ideal NMR target here (and de facto for a large variety of calcium-derived materials), its stable NMR-active isotope, calcium-43, is a highly unreceptive probe. Using the sensitivity gains from dynamic nuclear polarization, not only could calcium-43 NMR spectra be obtained easily, but natural isotopic abundance 2D correlation experiments could be recorded for calcium-43 in short experimental time. This opens perspectives for the detailed study of interfaces in nanostructured materials of the highest biological interest as well as calcium-based nanosystems in general.

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

Spatially resolved NMR spectra for the Swiss cheese model in heavy fermion PuCoGa5 superconductor

NASA Astrophysics Data System (ADS)

Das, Tanmoy; Zhu, Jian-Xin; Balatsky, A. V.; Graf, M. J.

2011-03-01

Spatially resolved NMR experiments, which probe the local electronic excitations, play a vital role for studying the pairing symmetry of unconventional superconductors. Here we calculate the spatial modulation of the NMR spin-lattice relaxation rate (1/T1) for the Swiss cheese model as a function of impurity concentration in PuCoGa5 superconductor. The local suppression of the superconducting order parameter due to impurities is related to the number of holes in the Swiss cheese model. Our results indicate that Friedel-like oscillations,as seen in the local-density of states near an impurity, are also present in the behavior of 1/T1 as one moves away from the impurity site. We demonstrate that the gap nodes, which are filled by disorder, can be probed by NMR through the local information encoded in the spectra. The advantage of spatially resolved NMR compared to STM measurements is that the former probe is not sensitive to surface states. Work is supported by US DOE.

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.

Fast and Efficient Fragment-Based Lead Generation by Fully Automated Processing and Analysis of Ligand-Observed NMR Binding Data.

PubMed

Peng, Chen; Frommlet, Alexandra; Perez, Manuel; Cobas, Carlos; Blechschmidt, Anke; Dominguez, Santiago; Lingel, Andreas

2016-04-14

NMR binding assays are routinely applied in hit finding and validation during early stages of drug discovery, particularly for fragment-based lead generation. To this end, compound libraries are screened by ligand-observed NMR experiments such as STD, T1ρ, and CPMG to identify molecules interacting with a target. The analysis of a high number of complex spectra is performed largely manually and therefore represents a limiting step in hit generation campaigns. Here we report a novel integrated computational procedure that processes and analyzes ligand-observed proton and fluorine NMR binding data in a fully automated fashion. A performance evaluation comparing automated and manual analysis results on (19)F- and (1)H-detected data sets shows that the program delivers robust, high-confidence hit lists in a fraction of the time needed for manual analysis and greatly facilitates visual inspection of the associated NMR spectra. These features enable considerably higher throughput, the assessment of larger libraries, and shorter turn-around times.

Refocused linewidths less than 10 Hz in 1H solid-state NMR.

PubMed

Paruzzo, Federico M; Stevanato, Gabriele; Halse, Meghan E; Schlagnitweit, Judith; Mammoli, Daniele; Lesage, Anne; Emsley, Lyndon

2018-06-02

Coherence lifetimes in homonuclear dipolar decoupled 1 H solid-state NMR experiments are usually on the order of a few ms. We discover an oscillation that limits the lifetime of the coherences by recording spin-echo dephasing curves. We find that this oscillation can be removed by the application of a double spin-echo experiment, leading to coherence lifetimes of more than 45 ms in adamantane and more that 22 ms in β-AspAla, corresponding to refocused linewidths of less than 7 and 14 Hz respectively. Copyright © 2018 Elsevier Inc. All rights reserved.

Ultra-slow dynamics in low density amorphous ice revealed by deuteron NMR: indication of a glass transition.

PubMed

Löw, Florian; Amann-Winkel, Katrin; Loerting, Thomas; Fujara, Franz; Geil, Burkhard

2013-06-21

The postulated glass-liquid transition of low density amorphous ice (LDA) is investigated with deuteron NMR stimulated echo experiments. Such experiments give access to ultra-slow reorientations of water molecules on time scales expected for structural relaxation of glass formers close to the glass-liquid transition temperature. An involved data analysis is necessary to account for signal contributions originating from a gradual crystallization to cubic ice. Even if some ambiguities remain, our findings support the view that pressure amorphized LDA ices are of glassy nature and undergo a glass-liquid transition before crystallization.

A Method for Generating Reduced-Order Linear Models of Multidimensional Supersonic Inlets

NASA Technical Reports Server (NTRS)

Chicatelli, Amy; Hartley, Tom T.

1998-01-01

Simulation of high speed propulsion systems may be divided into two categories, nonlinear and linear. The nonlinear simulations are usually based on multidimensional computational fluid dynamics (CFD) methodologies and tend to provide high resolution results that show the fine detail of the flow. Consequently, these simulations are large, numerically intensive, and run much slower than real-time. ne linear simulations are usually based on large lumping techniques that are linearized about a steady-state operating condition. These simplistic models often run at or near real-time but do not always capture the detailed dynamics of the plant. Under a grant sponsored by the NASA Lewis Research Center, Cleveland, Ohio, a new method has been developed that can be used to generate improved linear models for control design from multidimensional steady-state CFD results. This CFD-based linear modeling technique provides a small perturbation model that can be used for control applications and real-time simulations. It is important to note the utility of the modeling procedure; all that is needed to obtain a linear model of the propulsion system is the geometry and steady-state operating conditions from a multidimensional CFD simulation or experiment. This research represents a beginning step in establishing a bridge between the controls discipline and the CFD discipline so that the control engineer is able to effectively use multidimensional CFD results in control system design and analysis.