Nuclear Magnetic Resonance Pulse Sequences Research Articles

Analysis of complex mixtures with benchtop nuclear magnetic resonance: Solvent suppression with T2 and diffusion filters.

Benchtop nuclear magnetic resonance (NMR) spectrometers are being employed in a wide variety of applications from undergraduate teaching and research in academia to quality control and process monitoring in industrial settings. Incorporating benchtop NMR in some of these applications presents opportunities for new practical uses of the technology and challenges that truly test the capabilities of compact NMR spectrometers. For instance, the use of protonated solvents in manufacturing or process monitoring requires separating and quantitating the analyte signals of interest from the strong (overwhelming) response from the solvents. Furthermore, due to the lower field strength available with permanent magnet spectrometers, the NMR spectra of complex mixtures can be more difficult to analyze due to partial or complete signal overlap. To address some of these challenges and to extend the range of applications of benchtop NMR, we investigate NMR techniques that enable quantitative analysis of different components in mixtures. These pulse sequences can be used to suppress one or multiple solvent peaks, to filter out signals by spin-spin relaxation time (T2), or to separate signal components by a molecule's diffusion coefficient (NMR diffusometry). In this paper, we discuss quantitative analysis of excipients in buffers for therapeutic proteins to highlight the usefulness of these NMR pulse sequences in the analysis of complex samples with benchtop NMR spectrometers.

Sensitivity-Enhanced Spin Echo Nuclear Magnetic Resonance Pulse Sequence for Quantitative Polymer Characterizations with a Nuclear Magnetic Resonance Cryoprobe

Sensitivity-Enhanced Spin Echo Nuclear Magnetic Resonance Pulse Sequence for Quantitative Polymer Characterizations with a Nuclear Magnetic Resonance Cryoprobe

Experimental and numerical simulation research on counter-current imbibition distance in tight oil reservoirs

Counter-current imbibition behavior is an important mechanism for exploiting oil recovery during shut-in periods after hydraulic fracturing in tight oil reservoirs. However, most researches mainly focused on imbibition recovery and its influencing factors in tight oil reservoirs, while experimental investigations to quantitatively characterize the imbibition distance is still inadequate. In this work, counter-current imbibition experiments under one end open (OEO) boundary condition were conducted, and the dynamic imbibition process in porous media were monitored in real-time by nuclear magnetic resonance (NMR) pulse sequences and NMR imaging to quantify the range of counter-current imbibition and the reduction of oil saturation in-situ. In addition, a one-dimensional (1D) imbibition numerical model with OEO boundary condition at core scale was developed, and the influencing factors on oil production was further discussed in detail. The experimental results illustrated that the overall oil recoveries of nanofluid and deionized (DI) water were 25.37 % and 5.19 %, respectively. Moreover, the advancing distance of nanofluid was 4.44 cm, while DI water advanced only 2.38 cm along the core sample. Nanofluid considerably reduced residual oil saturation and increased movable fluid saturation, making the crude oil to be highly mobilized in micro- and mesopores. The simulated results well verified the counter-current imbibition experimental data, and indicated that the influences of core permeability and fluid viscosity on imbibition performances were more significant than that of core length. The purpose of this work is to provide a new method to determine the extent of counter-current imbibition.

Characterising water in Lunar and Martian regolith materials using nuclear magnetic resonance

Water is critical in the future of space exploration and development of planetary bodies. Benchtop nuclear magnetic resonance (NMR) is a geophysical measurement technique with the potential to be used for identification and characterisation of water resources on planetary bodies, such as the Moon and Mars. In this work, we explore the potential of NMR for space exploration by conducting measurements on Lunar and Martian regolith simulants using two main NMR pulse sequences. The first sequence is a decay due to internal fields (DDIF) pulse sequence which probes the pore size of the porous structure created by the regolith simulants. We then use a simple pore-to-particle size model to estimate the particle size distribution of the simulants and validate this against laser particle size analysis (LPSA) data. The DDIF type sequence can also be used to resolve the material surface relaxivity: which is useful in understanding the concentration of paramagnetic species as well as for correlating the length scales of various water volumes. The second pulse sequence utilised is a multi-echo sequence used to quantify fluid volumes as well as total moisture content within the porous media. The fluid volumes observed include adsorbed or hydrated water bound to clay minerals, as well as interparticle water between the regolith simulant grains. The NMR measured moisture content showed reasonably good agreement to corresponding gravimetric measurements used for validation. Finally, we discuss the implications of the current measurements and provide suggested focal points for potential future developments of NMR systems for space exploration.

On the theory of the spin I = 1/2 double quantum NMR: Effects of spins spatial displacements between RF pulses.

Spatial displacements of spins between radio frequency pulses in a Double-Quantum (DQ) nuclear magnetic resonance pulse sequence generate additional terms in the effective DQ Hamiltonian. We derive a simple expression that allows the estimation and control of these contributions to the initial rise of the DQ build up function by variation of experimental parameters in systems performing anomalous diffusion. The application of polymers is discussed.

Quantitative analysis of diffusion regimes in iron ore with low field NMR

SUMMARY The use of nuclear magnetic resonance (NMR) techniques allows in situ characterization of geophysical properties such as moisture content, permeability and wettability. However, the accuracy and applicability of such measurements is limited by internal magnetic field gradients which are a consequence of magnetic susceptibility differences at solid–fluid interfaces. Such effects are particularly prominent in iron ore rock samples which contain ferrimagnetic and ferromagnetic mineralogy leading to high magnetic susceptibility. Multiple echo time Carr–Purcell–Meiboom–Gill (CPMG) NMR pulse sequences are commonly used to capture the influence of internal gradients, with the intention of deconvoluting diffusion in effective internal gradients (geff) from true transver relaxation (T2). The interpretation of such measurements is complicated by the presence of multiple diffusive regimes: the short-time (ST), motionally averaged and localization regimes respectively. We introduce a new model for diffusive NMR signal attenuation, called the multiregime model which is intended to better capture diffusive behaviour across the three regimes. The multiregime model is compared against previous methods for quantifying diffusive decay (the ST only and generalized inversion models). Multi-echo measurements of iron ore samples are fit with each model in order to quantify 2-D T2–geff distributions. The resulting distributions demonstrate how the multiregime model can provide insight into the relative influence of the different diffusive regimes in a given sample. This assists in understanding the influence of diffusive decay on measurement accuracy, for example the increased measurement error with increasing prevalence of the localization regime. The multiregime model provides a key step in accurately segregating surface relaxation and diffusive relaxation, which is crucial for accurately estimating pore size distributions, permeability and wettability in high magnetic susceptibility samples using NMR.

Review of Recent Developments in NMR Core Analysis

The last 10 years have witnessed numerous new developments and advancements in nuclear magnetic resonance (NMR) rock core analysis both in conventional and unconventional reservoirs. On the hardware side, NMR instruments are now capable of handling hundreds of thousands of radio frequency (RF) pulses, and the pulses can be more closely spaced than ever. This allows measuring samples with very fast relaxation times, which was not possible before. Higher field NMR spectrometers operating at frequencies of ~12 MHz and ~20 MHz (in addition to the standard low-field ~2 MHz instruments) were introduced, which drastically improved the signal-to-noise ratio (SNR) and even allowed two-dimensional (2D) and three-dimensional (3D) NMR imaging to be performed on the samples to complement traditional relaxation measurements. Another consequence of using higher field instruments is that even samples with a very low amount of NMR signal can now provide useful data in a reasonable amount of time. Additional hardware improvements include the development of NMR-compatible high-temperature and high-pressure vessels and faster and more robust electronics and computers, which allow faster data acquisition, processing, and a more user-friendly environment for new NMR pulse sequence design and implementation. Following the hardware improvements, new applications were developed for rock core analysis, including modified Carl-Purcell-Meiboom-Gill (CPMG) pulse sequences for minimizing sample heating. NMR-based wettability, relative permeability, capillary pressure, cuttings, and long core measurements have also been successful. In unconventionals, NMR-based gas isotherm measurements and fluid-typing measurements are now common practices. This review paper sets out to summarize the recent NMR developments in the industry as well as provide references where more details can be found on each topic.

Use of magic sandwich echo and fast field cycling NMR relaxometry on honey adulteration with corn syrup

Adulteration is defined as the intentional addition of a material that is not a part of the nature. In this study, a non-conventional time domain nuclear magnetic resonance (TD-NMR) pulse sequence: magic sandwich echo (MSE) was used to detect the adulteration of honey by glucose syrup (GS) and high fructose corn syrup (HFCS) accompanied with T1 and T2 relaxation times. Also, fast field cycling NMR (FFC-NMR) relaxometry and multivariate analysis were performed to investigate the adulteration. Higher maltose in GS and changing glucose to water ratio of HFCS gave high correlation with the crystal content values. In HFCS adulteration, two separate populations of protons having different T2 values were detected and T1 times were also used to determine GS adulteration. Addition of GS increased T1 while addition of HFCS increased T2 , significantly. The results showed that it is possible to differentiate the unadulterated and adulterated honey samples by using TD-NMR relaxation times and crystal content values obtained by the MSE sequence. By FFC-NMR relaxometry, not only GS addition but also the amount of GS was examined. The multivariate analysis technique of principal component analysis was able to distinguish the types of adulterants. © 2021 Society of Chemical Industry.

Explicit phenomenological solutions for magnetization exposed to an arbitrary NMR diffusion steady state pulse sequence.

Explicit phenomenological solutions to recurrence relations for the bulk transverse and longitudinal magnetization found using the Torrey-Bloch equations with relaxation effects are used to investigate nuclear magnetic resonance (NMR) diffusion measurements. Of particular interest are steady state NMR (self-)diffusion measurements that reduce experimental time that can extend the techniques to quickly reacting systems. The solutions for bulk transverse and longitudinal magnetization presented here are used to investigate the average behavior of the transverse and longitudinal magnetization in forming a steady state and are used to derive new expressions for the steady state longitudinal magnetization. These solutions can be applied to a noninteracting spin 1/2 ensemble undergoing free diffusion exposed to an arbitrary NMR pulse sequence containing arbitrary magnetic field gradient waveforms. The closed algebraic form method presented here has an advantage over iterative procedures for calculating transverse and longitudinal magnetization for the analysis and development of steady state pulse sequences. Previous theoretical results for steady state diffusion measurements are also reproduced. The Mathematica code for these solutions is provided in the supplementary material.

Neopetrothiazide: An Intriguing Pentacyclic Thiazide Alkaloid from the Sponge Neopetrosia sp.

Neopetrothiazide (1), a pentacyclic isoquinoline quinone, was isolated from a Neopetrosia sp. sponge. The structure elucidation was facilitated by utilizing long-range heteronuclear single quantum multiple bond correlation (LR-HSQMBC) and heteronuclear multiple bond correlation (HMBC) nuclear magnetic resonance (NMR) pulse sequences optimized to detect four- and five-bond 1H-13C heteronuclear correlations. These NMR experiments can help assign proton-deficient structural motifs like neopetrothiazide (1), which has 14 contiguous nonprotonated centers (C, N, and S). Neopetrothiazide (1), with an unprecedented thiazide-fused structural scaffold, is the first natural product containing a thiazide moiety.

Singlet to triplet conversion in molecular hydrogen and its role in parahydrogen induced polarization.

Detailed experimental and comprehensive theoretical analysis of singlet-triplet conversion in molecular hydrogen dissolved in a solution together with organometallic complexes used in experiments with parahydrogen (the H2 molecule in its nuclear singlet spin state) is reported. We demonstrate that this conversion, which gives rise to formation of orthohydrogen (the H2 molecule in its nuclear triplet spin state), is a remarkably efficient process that strongly reduces the resulting NMR (nuclear magnetic resonance) signal enhancement, here of 15N nuclei polarized at high fields using suitable NMR pulse sequences. We make use of a simple improvement of traditional pulse sequences, utilizing a single pulse on the proton channel that gives rise to an additional strong increase of the signal. Furthermore, analysis of the enhancement as a function of the pulse length allows one to estimate the actual population of the spin states of H2. We are also able to demonstrate that the spin conversion process in H2 is strongly affected by the concentration of 15N nuclei. This observation allows us to explain the dependence of the 15N signal enhancement on the abundance of 15N isotopes.

Spatial molecular-dynamically ordered NMR spectroscopy of intact bodies and heterogeneous systems

Noninvasive evaluation of the spatial distribution of chemical composition and diffusion behavior of materials is becoming possible by advanced nuclear magnetic resonance (NMR) pulse sequence editing. However, there is room for improvement in the spectral resolution and analytical method for application to heterogeneous samples. Here, we develop applications for comprehensively evaluating compounds and their dynamics in intact bodies and heterogeneous systems from NMR data, including spatial z-position, chemical shift, and diffusion or relaxation. This experiment is collectively named spatial molecular-dynamically ordered spectroscopy (SMOOSY). Pseudo-three-dimensional (3D) SMOOSY spectra of an intact shrimp and two heterogeneous systems are recorded to evaluate this methodology. Information about dynamics is mapped onto two-dimensional (2D) chemical shift imaging spectra using a pseudo-spectral imaging method with a processing tool named SMOOSY processor. Pseudo-2D SMOOSY spectral images can non-invasively assess the different dynamics of the compounds at each spatial z-position of the shrimp’s body and two heterogeneous systems.

Pore-fluid characterizations and microscopic mechanisms of sedimentary rocks with three-dimensional NMR: Tight sandstone as an example

Pore-fluid is directly related to the reservoir quality. Three-dimensional (3D) nuclear magnetic resonance (NMR) can be used for charactering pore-fluid due to its sensitivity to fluid components saturated in sedimentary rocks. In this paper, taken a tight sandstone as an example, investigating pore-fluid characterizations and microscopic mechanisms through 3D NMR. Firstly, a commonly used 3D NMR pulse sequence, tri-window pulse sequence, in actual oilfield was presented and its data processing workflow was exhibited briefly. Then, random-walk method was modified to simulate the pulse sequence measurements at different pore-fluid cases in tight sandstone, such as pure water case, oil-water case, and gas-water case. Finally, pore-fluid 3D NMR responses were exhibited and their microscopic mechanisms were explored. The results show that 3D NMR can identify different fluid components saturated in sedimentary rocks; wetting fluid saturation directly affect wetting fluid relaxation time, but the non-wetting fluid relaxation information is independent of fluid saturation; wetting fluid has an obvious restricted diffusion as a lower saturation; an obvious difference between gas signal and water or oil signal in two-dimensional relaxation spectra due to high longitudinal to transverse relaxation time ratio of pore gas. These simulations provide a theoretical basis for interpreting 3D NMR macroscopic responses, which should be helpful for pore-fluid identifying in tight oil and gas reservoirs.

T1-Noise eliminated dipolar heteronuclear multiple-quantum coherence solid-state NMR spectroscopy.

Heteronuclear correlation (HETCOR) spectroscopy is one of the key tools in the arsenal of the solid-state NMR spectroscopist to probe chemical and spatial proximities between two different nuclei and enhance spectral resolution. Dipolar heteronuclear multiple-quantum coherence (D-HMQC) is a powerful technique that can be potentially utilized to obtain 1H detected 2D HETCOR solid-state NMR spectra of any NMR active nucleus. A long-standing problem in 1H detected D-HMQC solid-state NMR experiments is the presence of t1-noise which reduces sensitivity and impedes spectral interpretation. In this contribution, we describe novel pulse sequences, termed t1-noise eliminated (TONE) D-HMQC, that minimize t1-noise and can provide higher sensitivity and resolution than conventional D-HMQC. Monte-Carlo and numerical simulations confirm that t1-noise in conventional D-HMQC primarily occurs because random MAS frequency fluctuations cause variations in the NMR signal amplitude from scan to scan, leading to imperfect cancellation of uncorrelated signals by phase cycling. The TONE D-HMQC sequence uses 1H π-pulses to refocus the evolution of 1H CSA across each SR421 recoupling block, improving the stability of the pulse sequence to random MAS frequency fluctuations. The 1H refocusing pulses also restore the orthogonality of in-phase and anti-phase magnetization for all crystallite orientations at the end of each recoupling block, enabling the use of 90° flip-back or LG spin-lock trim pulses to reduce the intensity of uncorrelated signals. We demonstrate the application of these methods to acquire 1H detected 2D 1H{35Cl} and 1H{13C} HETCOR spectra of histidine·HCl·H2O with reduced t1-noise. To show generality, we also apply these methods to obtain 2D 1H{17O} spectra of 20%-17O fmoc-alanine and for the first time at natural abundance, 2D 1H{25Mg} HETCOR spectra of magnesium hydroxide. The TONE D-HMQC sequences are also used to probe 1H-25Mg and 1H-27Al proximities in Mg-Al layered double hydroxides and confirm the even mixing of Mg and Al in these materials.

Coherence transfer delay optimisation in PSYCOSY experiments.

PSYCOSY is an f1 broadband homonuclear decoupled version of the COSY nuclear magnetic resonance pulse sequence. Here, we investigate by a combination of experimental measurements, spatially distributed spin dynamics simulations, and analytical predictions the coherence evolution delay necessary in PSYCOSY experiments to ensure intensity discrimination in favour of the correlations typically arising from short range (n J, n ≤ 3) 1 H-1 H couplings and show that, in general, a coherence evolution delay of around 35 ms is optimum.

Resolution enhancement and proton proximity probed by 3D TQ/DQ/SQ proton NMR spectroscopy under ultrafast magic-angle-spinning beyond 70 kHz.

Proton nuclear magnetic resonance (NMR) in solid state has gained significant attention in recent years due to the remarkable resolution and sensitivity enhancement afforded by ultrafast magic-angle-spinning (MAS). In spite of the substantial suppression of 1H-1H dipolar couplings, the proton spectral resolution is still poor compared to that of 13C or 15N NMR, rendering it challenging for the structural and conformational analysis of complex chemicals or biological solids. Herein, by utilizing the benefits of double-quantum (DQ) and triple-quantum (TQ) coherences, we propose a 3D single-channel pulse sequence that correlates proton triple-quantum/double-quantum/single-quantum (TQ/DQ/SQ) chemical shifts. In addition to the two-spin proximity information, this 3D TQ/DQ/SQ pulse sequence enables more reliable extraction of three-spin proximity information compared to the regular 2D TQ/SQ correlation experiment, which could aid in revealing the proton network in solids. Furthermore, the TQ/DQ slice taken at a specific SQ chemical shift only reveals the local correlations to the corresponding SQ chemical shift, and thus it enables accurate assignments of the proton peaks along the TQ and DQ dimensions and simplifies the interpretation of proton spectra especially for dense proton networks. The high performance of this 3D pulse sequence is well demonstrated on small compounds, L-alanine and a tripeptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (MLF). We expect that this new methodology can inspire the development of multidimensional solid-state NMR pulse sequences using the merits of TQ and DQ coherences and enable high-throughput investigations of complex solids using abundant protons.

Excitation of singlet-triplet coherences in pairs of nearly-equivalent spins.

We present approaches for an efficient excitation of singlet-triplet coherences in pairs of nearly-equivalent spins. Standard Nuclear Magnetic Resonance (NMR) pulse sequences do not excite these coherences at all or with very low efficiency. The single quantum singlet-triplet coherences, here termed the outer singlet-triplet coherences, correspond to lines of low intensity in the NMR spectrum of a strongly-coupled spin pair (they are sometimes referred to as "forbidden transitions"), whereas the zero-quantum coherences, here termed the inner singlet-triplet coherences, do not have a direct spectral manifestation. In the present study, we investigated singlet-triplet coherences in a pair of nearly-equivalent carbon spins of the 13C-isotopomer of a specially designed naphthalene derivative with optimized relaxation properties. We propose and compare several techniques to drive the singlet-triplet coherence in strongly coupled spin pairs. First, we study different methods for efficient excitation of the outer singlet-triplet coherences. The achieved conversion efficiency of magnetization to the coherences of interest is close to the theoretically allowed maximum. Second, we propose methods to convert the outer coherences into the inner singlet-triplet coherence. The inner singlet-triplet coherence is insensitive to field inhomogeneity and can be long-lived. By probing this coherence, we perform a very precise measurement of the spin-spin J-couplings. A remarkable property of this coherence is that it can be preserved even in absence of a spin-locking radiofrequency field. Consequently, it is possible to shuttle the sample between different magnetic fields preserving the coherence. This allows one to study the field dependence of the relaxation time, TIST, of the inner singlet-triplet coherence by performing field-cycling experiments. We observed dramatic changes of the ratio TIST/T1 from about 1 (in strong fields) up to 2.4 (in weak fields), which is the evidence of a significant influence of the chemical shift anisotropy on relaxation. We have detected a remarkably long lifetime of the inner singlet-triplet coherence of about 200 s at the magnetic field of 5 mT.

Capillary-tube package devices for the quantitative performance evaluation of nuclear magnetic resonance spectrometers and pulse sequences.

With the increased sensitivity of modern nuclear magnetic resonance (NMR) spectrometers, the minimum amount needed for chemical-shift referencing of NMR spectra has decreased to a point where a few microliters can be sufficient to observe a reference signal. The reduction in the amount of required reference material is the basis for the NMR Capillary-tube Package (CapPack) platform that utilizes capillary tubes with inner diameters smaller than 150 µm as NMR-tube inserts for external reference standards. It is shown how commercially available electrophoresis capillary tubes with outer diameters of 360 µm are filled with reference liquids or solutions and then permanently sealed by the arc discharge plasma of a commercially available fusion splicer normally employed for joining optical fibers. The permanently sealed capillaries can be used as external references for chemical-shift, signal-to-noise, resolution, and concentration calibration. Combining a number of permanently sealed capillaries to form CapPack devices leads to additional applications such as performance evaluation of NMR spectrometers and NMR pulse sequences. A 10-capillary-tube side-by-side Gradient CapPack device is used in combination with one or two constant gradients, produced by room-temperature shim coils, to monitor the excitation profiles of shaped pulses. One example illustrates the performance of hyperbolic secant (sech) pulses in the EXponentially Converging Eradication Pulse Train (EXCEPT) solvent suppression sequence. The excitation profile of the pulse sequence is obtained in a single gradient NMR experiment. A clustered T 1 CapPack device is introduced consisting of a coaxial NMR-tube insert that holds seven capillary tubes filled with aqueous solutions of different concentrations of the paramagnetic relaxation agent copper(ii) sulfate (CuSO4). The different CuSO4 concentrations lead to spin-lattice relaxation times in the seven capillary tubes that cover a range which extends to more than an order of magnitude. Clustered T 1 CapPack devices are best suited to quantify the effects that relaxation has on magnetizations and coherences during the execution of NMR experiments, which is demonstrated for the order-of-magnitude T 1 insensitivity of signal suppression with EXCEPT.

Quantitative 1H-1H Distances in Protonated Solids by Frequency-Selective Recoupling at Fast Magic Angle Spinning NMR.

Nuclear magnetic resonance (NMR) spectroscopy of protons in protonated solids is challenging. Fast magic angle spinning (MAS) and homonuclear decoupling schemes, in conjunction, with high magnetic fields have improved the proton resolution. However, experiments to quantitatively measure 1H-1H distances still remain elusive due to the dense proton-proton dipolar coupling network. A novel MAS solid-state NMR pulse sequence is proposed to selectively recouple and measure interproton distances in protonated samples. The phase-modulated sequence combined with a judicious choice of transmitter frequency is used to measure quantitative 1H-1H distances on the order of 3 Å in l-histidine·HCl·H2O, despite the presence of other strongly coupled protons. This method provides a major boost to NMR crystallography approaches for structural determination of pharmaceutical molecules by directly measuring 1H-1H distances. The band-selective nature of the sequence also enables observation of selective 1H-1H correlations (e.g., HN-HN/HN-Hα/ΗΝ-ΗMethyl) in peptides and proteins, which should serve as useful restraints in structure determination.

Coherent control of solid state nuclear spin nano-ensembles

Detecting and controlling nuclear spin nano-ensembles is crucial for the further development of nuclear magnetic resonance (NMR) spectroscopy and for the emerging solid state quantum technology. Here we present the fabrication of a ≈1 nanometre thick diamond layer consisting of 13C nuclear spins doped with nitrogen-vacancy centres (NV) embedded in a spin-free 12C crystal matrix. A single NV in the vicinity of the layer is used for polarization of the 13C spins and the readout of their magnetization. We demonstrate a method for coherent control of few tens of nuclear spins by using radio frequency pulses, and show the basic coherent control experiments, Rabi oscillations and Ramsey spectroscopy, though any NMR pulse sequence can be implemented. The results shown here present an important step towards the realization of a nuclear spin based quantum simulator.