Nuclear Magnetic Resonance Pulse Sequences Research Articles

Mixed Frequency-/Time-Domain Coherent Multidimensional Spectroscopy: Research Tool or Potential Analytical Method?

Coherent multidimensional spectroscopy (CMDS) is now the optical analogue of nuclear magnetic resonance (NMR). Just as NMR heteronuclear multiple-quantum coherence (HMQC) methods rely on multiple quantum coherences, achieving widespread application requires that CMDS also excites multiple quantum coherences over a wide range of quantum state energies. This Account focuses on frequency-domain CMDS because these methods tune the excitation frequencies to resonance with the desired quantum states and can form multiple quantum coherences between states with very different energies. CMDS methods use multiple excitation pulses to excite multiple quantum states within their dephasing time, so their quantum mechanical phase is maintained. Coherences formed from pairs of the excited states emit coherent beams of light. The temporal ordering of the excitation pulses defines a sequence of coherences that can result in zero, single, double, or higher order coherences as required for multiple quantum coherence CMDS. Defining the temporal ordering and the excitation frequencies and spectrally resolving the output frequency also defines a particular temporal pathway for the coherences, just as an NMR pulse sequence defines an NMR method. Two dimensional contour plots through this multidimensional parameter space allow visualization of the state energies and dynamics. This Account uses nickel and rhodium chelates as models for understanding mixed frequency-/time-domain CMDS. Mixed frequency-/time-domain methods use excitation pulse widths that are comparable to the dephasing times, so multidimensional spectra are obtained by scanning the excitation frequencies, while the coherence and population dynamics are obtained by scanning the time delays. Changing the time delays changes the peaks in the 2D excitation spectra depending upon whether the pulse sequence excites zero, single, or double quantum coherences. In addition, peaks split as a result of the frequency-domain manifestation of quantum beating. Similarly, changing the excitation and monochromator frequencies changes the dependence on the excitation delay times depending upon whether the frequencies match the resonances involved in the different time-ordered pathways. Contour plots that change a time delay and frequency visualize the temporal changes of specific spectral features. Frequency-domain methods are resonant with specific states, so the sequence of coherences and populations is defined. Coherence transfer, however, can cause output beams at unexpected frequencies. Coherence transfer occurs when the thermal bath induces a coherence between two states (a and g) to evolve to a new coherence (b and g). Since the two coherences have different frequencies and since there are different time orderings for the occurrence of coherence transfer, the delay time dependence develops modulations that depend on the coherences' frequency difference. Higher order coherences can also be generated by raising the excitation intensities. New features appear in the 2D spectra and dynamic Stark splittings occur. These effects will form the basis for the higher order multiple quantum coherence methods and also provide a method for probing molecular potential energy surfaces.

Structural Polymorphism of 441-Residue Tau at Single Residue Resolution

Alzheimer disease is characterized by abnormal protein deposits in the brain, such as extracellular amyloid plaques and intracellular neurofibrillary tangles. The tangles are made of a protein called tau comprising 441 residues in its longest isoform. Tau belongs to the class of natively unfolded proteins, binds to and stabilizes microtubules, and partially folds into an ordered β-structure during aggregation to Alzheimer paired helical filaments (PHFs). Here we show that it is possible to overcome the size limitations that have traditionally hampered detailed nuclear magnetic resonance (NMR) spectroscopy studies of such large nonglobular proteins. This is achieved using optimal NMR pulse sequences and matching of chemical shifts from smaller segments in a divide and conquer strategy. The methodology reveals that 441-residue tau is highly dynamic in solution with a distinct domain character and an intricate network of transient long-range contacts important for pathogenic aggregation. Moreover, the single-residue view provided by the NMR analysis reveals unique insights into the interaction of tau with microtubules. Our results establish that NMR spectroscopy can provide detailed insight into the structural polymorphism of very large nonglobular proteins.

Unique Backbone-Water Interaction Detected in Sphingomyelin Bilayers with 1H/ 31P and 1H/ 13C HETCOR MAS NMR Spectroscopy

Two-dimensional 1H/ 31P dipolar heteronuclear correlation (HETCOR) magic-angle spinning nuclear magnetic resonance (NMR) is used to investigate the correlation of the lipid headgroup with various intra- and intermolecular proton environments. Cross-polarization NMR techniques involving 31P have not been previously pursued to a great extent in lipid bilayers due to the long 1H- 31P distances and high degree of headgroup mobility that averages the dipolar coupling in the liquid crystalline phase. The results presented herein show that this approach is very promising and yields information not readily available with other experimental methods. Of particular interest is the detection of a unique lipid backbone-water intermolecular interaction in egg sphingomyelin (SM) that is not observed in lipids with glycerol backbones like phosphatidylcholines. This backbone-water interaction in SM is probed when a mixing period allowing magnetization exchange between different 1H environments via the nuclear Overhauser effect (NOE) is included in the NMR pulse sequence. The molecular information provided by these 1H/ 31P dipolar HETCOR experiments with NOE mixing differ from those previously obtained by conventional NOE spectroscopy and heteronuclear NOE spectroscopy NMR experiments. In addition, two-dimensional 1H/ 13C INEPT HETCOR experiments with NOE mixing support the 1H/ 31P dipolar HETCOR results and confirm the presence of a H 2O environment that has nonvanishing dipolar interactions with the SM backbone.

Optimization of NMR analysis of biological fluids for quantitative accuracy

With the rising interest in the use of nuclear magnetic resonance (NMR) for the study of biological fluids such as urine and serum for metabonomic or diagnostic purposes, new challenges have arisen concerning the efficacy of NMR data acquisition and analysis. In particular the quantification of sample constituents such as metabolites is of great importance. This study compares five one-dimensional proton NMR pulse sequences using synthetic urine samples to determine appropriate acquisition parameters for reasonable sample throughput and accuracy. Each pulse sequence has its own advantages and limitations with respect to solvent suppression, stable baseline, exchangeable protons, and quantization of resonances near the residual water peak. Hardware issues such as low-pass filters, unique to each spectrometer, also impact quantitation accuracy. Metabolite concentrations were determined using integration referenced to an added internal standard, and using the Chenomx NMR Suite software package. Since nuclei in different metabolites and the internal standard all have different longitudinal relaxation rates (T 1) we included a mathematical correction factor for quantitation.

Symbolic NMR product operator calculations

AbstractSymbolic nuclear magnetic resonance (NMR) product operator calculations provide an analytic, intuitive, yet precise description of the time evolution of the density operator during an NMR experiment. NMR experiments are implemented as pulse sequences consisting of short radiofrequency pulses separated by delay periods during which the spin system evolves under the influence of the static external magnetic field and spin–spin interactions. The quantum mechanical calculations to follow the time evolution of the density operator can be decomposed into the repeated application of a set of simple rules, known as the product operator formalism, that naturally lend themselves to symbolic computation. This article describes a complete implementation of the NMR Product Operator formalism in MAthematica (POMA), which has greatly simplified the development of many NMR pulse sequences, and provided insight into their functioning. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Nuclear magnetic resonance proton dipolar order relaxation in thermotropic liquid crystals: A quantum theoretical approach

By means of the Jeener-Broekaert nuclear magnetic resonance pulse sequence, the proton spin system of a liquid crystal can be prepared in quasiequilibrium states of high dipolar order, which relax to thermal equilibrium with the molecular environment with a characteristic time (T1D). Previous studies of the Larmor frequency and temperature dependence of T1D in thermotropic liquid crystals, that included field cycling and conventional high-field experiments, showed that the slow hydrodynamic modes dominate the behavior of T1D, even at high Larmor frequencies. This noticeable predominance of the cooperative fluctuations (known as order fluctuations of the director, OFD) could not be explained by standard models based on the spin-lattice relaxation theory in the limit of high temperature (weak order). This fact points out the necessity of investigating the role of the quantum terms neglected in the usual high temperature theory of dipolar order relaxation. In this work, we present a generalization of the proton dipolar order relaxation theory for highly correlated systems, which considers all the spins belonging to correlated domains as an open quantum system interacting with quantum bath. As starting point, we deduce a formulation of the Markovian master equation of relaxation for the statistical spin operator, valid for all temperatures, which is suitable for introducing a dipolar spin temperature in the quantum regime, without further assumptions about the form of the spin-lattice Hamiltonian. In order to reflect the slow dynamics occurring in correlated systems, we lift the usual short-correlation-time assumption by including the average over the motion of the dipolar Hamiltonian together with the Zeeman Hamiltonian into the time evolution operator. In this way, we calculate the time dependence of the spin operators in the interaction picture in a closed form, valid for high magnetic fields, bringing into play the spin-spin interactions within the microscopic time scale. Then, by adopting the spin-temperature density operator to represent the collective state of the spin system, and removing the traditional hypothesis of high temperature, we deduce an expression for the first order quantum contribution to T1D (-1), in terms of spectral densities, with coefficients in form of spin traces. The properties that distinguish our result from the high-temperature T1D (-1) are as follows. (a) It is exclusively associated to cooperative fluctuations. (b) Because of its quantum character, it relies on both considering the lattice degrees of freedom quantum mechanically and including the spin-spin interactions in the microscopic time scale. With regard to the average dipolar Hamiltonian, only the nonsecular part plays a relevant role. (c) Associated with the structure of the spin operator involved in the quantum contribution, a term arises which is proportional to the number of spins in the correlated molecular domains, showing that the quantum contribution may be of macroscopic size in highly correlated systems. When applied to nematic liquid crystals, the new term exhibits the typical nu(-1/2) Larmor frequency dependence through the spectral density of the OFD, in consistence with the experimental results.

WISE NMR characterization of nanoscale heterogeneity and mobility in supercontracted Nephila clavipes spider dragline silk.

The addition of water to spider dragline silk results in fiber contraction to 50% its initial length and significant changes to the mechanical properties of the silk. This event has been termed supercontraction. A decrease in strength and increase in elasticity have been reported when the silk is in contact with water. Two-dimensional wide-line separation (WISE) nuclear magnetic resonance (NMR) is implemented to correlate (13)C chemical shifts with mobility by observing the corresponding (1)H line widths and line shapes in water-saturated spider dragline silk. The WISE NMR spectrum of the native silk exhibits (1)H line widths that are approximately 40 kHz for all carbon environments characteristic of a rigid organic system. In contrast, the water-saturated case displays a component of the (1)H line that is narrowed to approximately 5 kHz for the glycine C(alpha) and a newly resolved alanine helical environment while the alanine C(beta) corresponding to the beta-sheet conformation remains broad. These results indicate that water permeates the amorphous, glycine-rich matrix and not the crystalline, polyalanine beta-sheets. A delay time is added to the WISE NMR pulse sequence to monitor spin diffusion between the amorphous, mobile region and the crystalline domains. The time required for spin diffusion to reach spatial equilibrium is related to the length scale of the polyalanine crystallites. This technique is employed to measure crystalline domain sizes on the nanometer length scale in water-solvated spider dragline silk. These results provide further insight into the structure of spider silk and mechanism of supercontraction.

Fast emulsion droplet sizing using NMR self-diffusion measurements

Emulsion droplet sizing using pulsed field gradient (PFG) nuclear magnetic resonance (NMR) is a well-established technique. Traditionally these measurements require total acquisition times of typically 5–20 min per sample, which severely limits our ability to use this method to study dynamic processes. Here we present the application and verification of an NMR pulse sequence, Difftrain, which enables emulsion droplet size distributions to be measured in 3–10 s. We have previously introduced applications of Difftrain (C. Buckley, K.G. Hollingsworth, A.J. Sederman, D.J. Holland, M.L. Johns, L.F. Gladden, J. Magn. Reson. 161 (2003) 112–117), including the droplet sizing of a single unimodal emulsion sample. In this paper, several model emulsions containing different oils are measured and the results compared directly with sizing provided by laser scattering. In this manner, the Difftrain method is verified and its possibilities and limitations are explored. Guidelines are proposed for the range of droplet sizes for which accurate results can be produced. The Difftrain technique opens up the possibility of studying non-equilibrium emulsions; a study of the in situ emulsification of a 21% v/v water-in-silicone oil emulsion is presented.

Measurement of dilute 29Si species in solution using a large volume coil and DEFT NMR

A large-sample-volume nuclear magnetic resonance (NMR) spectroscopy probehead has been developed for the detection and characterization of low concentrations of 29Si species in aqueous solution. The approach described entails the use of a large-diameter radio frequency solenoid coil that permits substantially larger sample volumes to be investigated at moderate magnetic field strengths, compared with conventional NMR probehead configurations. In addition, difficulties presented by long 29Si T1 relaxation times have been circumvented by using the DEFT NMR pulse sequence, which permits more rapid signal averaging. Through a combination of these hardware and methodological improvements, high-resolution 29Si NMR spectra have been obtained at 4.2 T (29Si resonance frequency = 36.8 MHz) for an 800 microM solution of 96% 29Si-enriched silicic acid, H4SiO4 (pH approximately 8), with a signal-to-noise ratio of 16 and a line width of 31 Hz after 3 h of total measurement time.

Fast mixing device inside a nuclear magnetic resonance magnet: A tool for observing early steps in protein folding

We describe a device designed to perform a fast mixing of two solutions inside the magnet of a nuclear magnetic resonance (NMR) spectrometer. The apparatus is totally nonmagnetic; it operates via a system of pneumatic valves, which drives a syringe to inject the first solution into the NMR tube that already contains the other solution. An important point is that before and after the injection, the solution in the NMR tube is free of any perturbing injecting device. The injection is controlled by the spectrometer software in the NMR pulse sequence. Simple experiments have been performed to assess the viability of the device, and evaluate the dead time after injection, as well as the loss of homogeneity and the mixing capabilities. The device described can mix up to 200 μl of solution with the solution already present in the NMR tube in less than 50 ms, with a negligible loss of homogeneity during injection. The device was specifically designed for protein folding studies but can find a general purpose for chemical reactions involving small amounts of compounds.

The relationship between ensemble quantum computing logical gates and NMR pulse sequence engineering exemplified by the SWAP operation

This paper describes how to derive nuclear magnetic resonance (NMR) pulse sequences suitable as ensemble quantum computing logical gates by known systematic tools for design of pulse sequences in NMR spectroscopy. This is in contrast to the current trend of developing NMR pulse sequences for ensemble quantum computing independent of established NMR spectroscopic technology, although many of the pertinent spin manipulations are already known in NMR spectroscopy. The SWAP operation is discussed in detail and one version is only (2J)−1long, which compares favorably with 3(2J)−1 in a recent implementation (Linden N, Barjat H, Kupce E, Freeman R. Chem Phys Lett 1999; 307:198–204). Alternatively, the number of π pulses can be reduced in that sequence. © 2000 John Wiley & Sons, Inc. Concepts Magn Reson 12: 389–395, 2000

Generalized methods for the development of quantum logic gates for an NMR quantum information processor

Logic gates such as the controlled-NOT (c-NOT) and Toffoli gates play a key role in quantum information processing (QIP) and quantum computing. A natural extension of such gates would necessarily operate on one quantum bit (qubit) conditional on the state of the remaining qubits in the system. We show that such selective gates, termed $(\mathrm{controlled}{)}^{n}\ensuremath{-}\mathrm{NOT}$ gates, or ${\mathrm{c}}^{n}\ensuremath{-}\mathrm{NOT}$ gates, are convenient in nuclear magnetic resonance (NMR) implementations of QIP and are straightforward to implement. NMR pulse sequences for these gates can be built using classical methods as well as insights from geometric algebra. These methods yield equivalent NMR pulse sequences for the generation of ${\mathrm{c}}^{n}\ensuremath{-}\mathrm{NOT}$ gates for any number of control spins. In this work, a catalog of ${\mathrm{c}}^{n}\ensuremath{-}\mathrm{NOT}$ gates for systems of as many as 16 spins is provided along with an experimental implementation of a ${\mathrm{c}}^{3}\ensuremath{-}\mathrm{N}\mathrm{O}\mathrm{T}$ gate on a four spin system, ${}^{13}\mathrm{C}$ alanine.

Coherence-transfer table: A convenient method for deriving coherence-transfer pathways of an NMR pulse sequence. I. Coherence-transfer table inIx, Iy, andIz system

A method for deriving coherence-transfer pathways of a nuclear magnetic resonance (NMR) pulse sequence in a table format, called a coherence-transfer table, has been developed. This method provides a convenient and easy-to-understand means to describe coherence transfers. In a coherence-transfer table, coherence at any time point, all the coherence-transfer pathways, and their NMR signals can be easily found. The coherence-transfer table method helps in understanding the effects of phase cycling. It is very useful in analyzing various multidimensional NMR pulse sequences. ©1999 John Wiley & Sons, Inc. Concepts Magn Reson 11: 393–408, 1999

Quantum Logic Gates and Nuclear Magnetic Resonance Pulse Sequences

There has recently been considerable interest in the use of nuclear magnetic resonance (NMR) as a technology for the implementation of small quantum computers. These computers operate by the laws of quantum mechanics, rather than classical mechanics and can be used to implement new quantum algorithms. Here we describe how NMR in principle can be used to implement all the elements required to build quantum computers, and draw comparisons between the pulse sequences involved and those of more conventional NMR experiments.

Vibrational echoes: A new approach to condensed-matter vibrational spectroscopy

This review describes the first ultrafast infrared vibrational echo experiments, which are used to examine liquids, glasses and proteins. Like the nuclear magnetic resonance (NMR) spin echo and other NMR pulse sequences, the vibrational echo can extract dynamical and spectroscopic information that cannot be obtained from a vibrational absorption spectrum. The vibrational echo measures the homogeneous vibrationallinewidtheven if the absorption line is massively inhomogeneously broadened. When combined with pump-probe (transient absorption) experiments, the homogeneous pure dephasing (energy level fluctuations) is obtained. Conducting these experiments as a function of temperature provides information on dynamics and intermolecular interactions. The nature of the method and the experimental procedures are outlined. Experimental results are presented for the metal carbonyl solutes, W(CO) and Rh(CO) acac, in several glassy and liquid solvents. The dynamics of the CO ligand bound at the active site of the protein myoglobin are examined and compared with those in several myoglobin mutants. The results provide insights into protein dynamics and how protein structural fluctuations are communicated to a ligand bound at the active site. In addition,two new vibrational echo methods are reviewed. One method involves using multilevel vibrational coherences, which gives rise to vibrational echo beats, to measure vibrational anharmonicities and excited-state dephasing. The other method, in which a vibrational echo spectrum is taken, is demonstrated to be capable of the suppression of unwanted background that dominates the normal vibrational absorption spectrum.

Evaluation of 3D NMR Experiments for the Characterization of Polymer Structure

A series of three-dimensional (3D) nuclear magnetic resonance (NMR) pulse sequences, utilizing pulsed-field gradient (PFG) techniques, were developed or adapted from biological experiments for applications in the characterization of polymer structure. These experiments form the foundation of a suite of experiments which can be used to characterize the structure of polymers and other heteroatom-containing organic materials, in much the same way that the data from multiple 3D NMR experiments have been used in biological structure determination. Several variations of an1H/X/Y chemical shift correlation (HXY) experiment are exhibited, and the HCX sequence (where Y =13C) is combined with13C homonuclear isotropic mixing to generate new pulse sequences which provide additional structural information. In this paper, the spectra of poly(α,β-13C2-styrene) (PS) prepared by diphenylphosphinyl radical (DPPR) initiated polymerization of α,β-13C2-styrene are used to illustrate the application of these techniques for characterization of polymer chain end structures. Comments on the relative advantages of the pulse sequence are provided. Although polymers are used to illustrate the applications of these pulse sequences, the sequences can just as easily be used to study other organic structures containing an NMR-active X nucleus. Organometallic chemistry is especially suited for applications of these NMR experiments.

5570019 Method for magnetic resonance spectroscopic imaging with multiple spin-echoes

A nuclear magnetic resonance pulse sequence to provide spectral encoding so that the resulting series of spin-echoes each include both spatial and spectral information for spectroscopic imaging. Atoms within the object are excited and may then be spatially encoded, as by a phase encoding gradient. A series of refocusing pulses is then applied, inducing a respective series of spin-echoes. Spectral information is directly encoded in the spin-echo signals. The multiple spin-echoes may be used for sampling different points of k-space, and/or for increasing the signal-to-noise ratio by averaging. In an alternative embodiment, the present invention produces compound weighted spectroscopic images by selecting the period between refocussing pulses according to the coupling constant of a group contained in the compound; thereby, the signal of the selected compounds modulate with a known frequency different for compounds with different coupling constants.

5596274 Determining bound and unbound fluid volumes using nuclear magnetic resonance pulse sequences

A borehole logging tool comprises a Nuclear Magnetic Resonance (NMR) tool and is pulsed according to a selected sequence. An interpretation is performed which involves a singular value decomposition and compression of data obtained by the tool. The compressed data is then subjected to a nonegative, linear least square fit to obtain a distribution function. The distribution function is used in determining bound fluid volume, unbound fluid volume, total porosity, spin-lattice relaxation time, spin-spin relaxation time, and mean relaxation time using only the pulse NMR tool.

High temperature hydrogen diffusion in Zr0.33Ni0.67[sbnd]Hx amorphous alloys

The proton content in Zr0.33Ni0.67Hx amorphous alloy was monitored by changes in electrical resistivity and with the extraplated spin echo amplitude measured by the Carr-Purcell-Meiboom-Gill (CPMG) nuclear magnetic resonance pulse sequence in the temperature interval 300 to 450 K. Both methods show that the hydrogen desorption processes can be approximately divided into two ranges. The first is a fast process which is at present not interpretable. In the second stage, the process is thermally activated, and the activation energy calcualted from the resistivity changes is equal to 0.32 ± 0.04 eV. The CPMG spin echo measurements also give the spin-spin relaxation time of diffusing protons and the activation energy of this process, 0.34 ± 0.02 eV, is exactly the same as extracted from the resistivity measurements.

Investigation of Coronary Vessels in Microscopic Dimensions by Two- and Three-dimensional NMR Microscopic Imaging in the Isolated Rat Heart

Nuclear magnetic resonance (NMR) imaging of macroscopic coronary vessels is rapidly advancing, whereas little attention has focused on development of NMR techniques for investigation of coronary microvessels. Such techniques would be of particular importance, since conventional methods to visualize coronary microvessels have specific limitations. The aim of our study was to develop two- and three-dimensional (2D and 3D) high-resolution imaging of coronary microvessels. Quantitative analysis of vessel size was performed in tomograms and applied to evaluate the vasoconstrictor effect of endothelin 1. Angiographic imaging was performed on an 11.75-T magnet by 2D and 3D gradient-echo pulse sequences. In tomograms, the validity of this method in providing correct vessel size was tested by phantom experiments. Experiments were carried out in the isolated constant-pressure-perfused rat heart with continuous registration of coronary flow and left ventricular pressure. NMR pulse sequences were pressure-triggered in mid diastole. Four groups of hearts were studied. In group 1 (n = 20), 2D imaging perpendicular and parallel to the long axis of the heart was performed. Cross sections of vessels with diameter > 140 microns were clearly detectable. In group 2 (control, n = 5) and group 3 (n = 13), tomograms perpendicular to the long axis were obtained before and after administration of vehicle (group 2) and 200 pmol endothelin 1 bolus (group 3). Vehicle had no effect on vessel cross section. Endothelin 1, which decreased global coronary flow by 47%, reduced vessel cross section by 38 +/- 19%. A weak but, on average, significant inverse correlation between area of cross section and vessel size was found. In group 4 (n = 10), 3D imaging was performed in 7 normal hearts and 3 hearts with anterior myocardial infarction. A 3D image of the entire coronary artery tree was obtained, revealing excellent agreement with anatomic studies. In infarcted rat hearts, occlusion of the left coronary artery was demonstrated. Visualization and quantification of coronary microvessels are feasible by NMR microscopy. NMR microscopy bears the potential of becoming a powerful tool for the investigation of the coronary microcirculation.