Hartmann-Hahn Match Research Articles

Windowed cross polarization at 55 kHz magic-angle spinning

Cross polarization (CP) transfers via Hartmann-Hahn matching conditions are one of the cornerstones of solid-state magic-angle spinning NMR experiments. Here we investigate a windowed sequence for cross polarization (wCP) at 55 kHz magic-angle spinning, placing one window (and one pulse) per rotor period on one or both rf channels. The wCP sequence is known to have additional matching conditions. We observe a striking similarity between wCP and CP transfer conditions when considering the flip angle of the pulse rather than the rf-field strength applied during the pulse. Using fictitious spin-1/2 formalism and average Hamiltonian theory, we derive an analytical approximation that matches these observed transfer conditions. We recorded data at spectrometers with different external magnetic fields up to 1200 MHz, for strong and weak heteronuclear dipolar couplings. These transfers, and even the selectivity of CP were again found to relate to flip angle (average nutation).

Broadband adiabatic inversion cross-polarization to integer-spin nuclei with application to deuterium NMR.

Solid-state NMR (SSNMR) spectroscopy of integer-spin quadrupolar nuclei is important for the molecular-level characterization of a variety of materials and biological solids; of the integer spins, 2 H (S = 1) is by far the most widely studied, due to its usefulness in probing dynamical motions. SSNMR spectra of integer-spin nuclei often feature very broad powder patterns that arise largely from the effects of the first-order quadrupolar interaction; as such, the acquisition of high-quality spectra continues to remain a challenge. The broadband adiabatic inversion cross-polarization (BRAIN-CP) pulse sequence, which is capable of cross-polarization (CP) enhancement over large bandwidths, has found success for the acquisition of SSNMR spectra of integer-spin nuclei, including 14 N (S = 1), especially when coupled with Carr-Purcell/Meiboom-Gill pulse sequences featuring frequency-swept WURST pulses (WURST-CPMG) for T2 -based signal enhancement. However, to date, there has not been a systematic investigation of the spin dynamics underlying BRAIN-CP, nor any concrete theoretical models to aid in its parameterization for applications to integer-spin nuclei. In addition, the BRAIN-CP/WURST-CPMG scheme has not been demonstrated for generalized application to wideline or ultra-wideline (UW) 2 H SSNMR. Herein, we provide a theoretical description of the BRAIN-CP pulse sequence for spin-1/2 → spin-1 CP under static conditions, featuring a set of analytical equations describing Hartmann-Hahn matching conditions and numerical simulations that elucidate a CP mechanism involving polarization transfer, coherence exchange, and adiabatic inversion. Several experimental examples are presented for comparison with theoretical models and previously developed integer-spin CP methods, demonstrating rapid acquisition of 2 H NMR spectra from efficient broadband CP.

Suppressing 1H Spin Diffusion in Fast MAS Proton Detected Heteronuclear Correlation Solid-State NMR Experiments

Fast magic angle spinning (MAS) and indirect detection by high gyromagnetic ratio (γ) nuclei such as proton or fluorine are increasingly utilized to obtain 2D heteronuclear correlation (HETCOR) solid-state NMR spectra of spin-1/2 nuclei by using cross polarization (CP) for coherence transfer. However, one major drawback of CP HETCOR pulse sequences is that 1H spin diffusion during the back X→1H CP transfer step may result in relayed correlations. This problem is particularly pronounced for the indirect detection of very low-γ nuclei such as 89Y, 103Rh, 109Ag and 183W where long contact times on the order of 10–30 ms are necessary for optimal CP transfer. Here we propose two methods that eliminate relayed correlations and allow more reliable distance information to be obtained from 2D HETCOR NMR spectra. The first method uses Lee-Goldburg (LG) CP during the X→1H back-transfer step to suppress 1H spin diffusion. We determine LG conditions compatible with fast MAS frequencies (νrot) of 40–95 kHz and show that 1H spin diffusion can be efficiently suppressed at low effective radiofrequency (RF) fields (ν1,eff ≪ 0.5νrot) and also at high effective RF fields (ν1,eff ≫ 2νrot). We describe modified Hartmann-Hahn LG-CP match conditions compatible with fast MAS and suitable for indirect detection of moderate-γ nuclei such as 13C, and low-γ nuclei such as 89Y. The second method uses D-RINEPT (dipolar refocused insensitive nuclei enhanced by polarization transfer) during the X→1H back-transfer step of the HETCOR pulse sequence. The effectiveness of these methods for acquiring HETCOR spectra with reduced relayed signal intensities is demonstrated with 1H{13C} HETCOR NMR experiments on l-histidine⋅HCl⋅H2O and 1H{89Y} HETCOR NMR experiments on an organometallic yttrium complex.

A cross-polarization based rotating-frame separated-local-field NMR experiment under ultrafast MAS conditions

Rotating-frame separated-local-field solid-state NMR experiments measure highly resolved heteronuclear dipolar couplings which, in turn, provide valuable interatomic distances for structural and dynamic studies of molecules in the solid-state. Though many different rotating-frame SLF sequences have been put forth, recent advances in ultrafast MAS technology have considerably simplified pulse sequence requirements due to the suppression of proton–proton dipolar interactions. In this study we revisit a simple two-dimensional 1H–13C dipolar coupling/chemical shift correlation experiment using 13C detected cross-polarization with a variable contact time (CPVC) and systematically study the conditions for its optimal performance at 60kHz MAS. In addition, we demonstrate the feasibility of a proton-detected version of the CPVC experiment. The theoretical analysis of the CPVC pulse sequence under different Hartmann–Hahn matching conditions confirms that it performs optimally under the ZQ (w1H−w1C=±wr) condition for polarization transfer. The limits of the cross polarization process are explored and precisely defined as a function of offset and Hartmann–Hahn mismatch via spin dynamics simulation and experiments on a powder sample of uniformly 13C-labeled L-isoleucine. Our results show that the performance of the CPVC sequence and subsequent determination of 1H–13C dipolar couplings are insensitive to 1H/13C frequency offset frequency when high RF fields are used on both RF channels. Conversely, the CPVC sequence is quite sensitive to the Hartmann–Hahn mismatch, particularly for systems with weak heteronuclear dipolar couplings. We demonstrate the use of the CPVC based SLF experiment as a tool to identify different carbon groups, and hope to motivate the exploration of more sophisticated 1H detected avenues for ultrafast MAS.

Hartmann-Hahn 2D-map to optimize the RAMP-CPMAS NMR experiment for pharmaceutical materials

Cross polarization-magic angle spinning (CPMAS) is the most used experiment for solid-state NMR measurements in the pharmaceutical industry, with the well-known variant RAMP-CPMAS its dominant implementation. The experimental work presented in this contribution focuses on the entangled effects of the main parameters of such an experiment. The shape of the RAMP-CP pulse has been considered as well as the contact time duration, and a particular attention also has been devoted to the radio-frequency (RF) field inhomogeneity. (13)C CPMAS NMR spectra have been recorded with a systematic variation of (13)C and (1)H constant radiofrequency field pair values and represented as a Hartmann-Hahn matching two-dimensional map. Such a map yields a rational overview of the intricate optimal conditions necessary to achieve an efficient CP magnetization transfer. The map also highlights the effects of sweeping the RF by the RAMP-CP pulse on the number of Hartmann-Hahn matches crossed and how RF field inhomogeneity helps in increasing the CP efficiency by using a larger fraction of the sample. In the light of the results, strategies for optimal RAMP-CPMAS measurements are suggested, which lead to a much higher efficiency than constant amplitude CP experiment.

ChemInform Abstract: Solid State CPMAS 13C and 15N NMR Spectroscopy in Organic Geochemistry and How Spin Dynamics Can Either Aggravate or Improve Spectra Interpretation

AbstractReview: 128 refs.

Solid state CPMAS 13C and 15N NMR spectroscopy in organic geochemistry and how spin dynamics can either aggravate or improve spectra interpretation

Because the ongoing discussion about the reliability of solid state cross polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) spectroscopy still leaves uncertainty with respect to its usefulness in organic geochemistry, the present work provides a brief introduction into the basic principles of this technique and gives some explanation about the potential source of non-quantitative results. In addition, relaxation data are supplied which are necessary for the correct adjustment of NMR acquisition parameters. High contents of paramagnetics or moisture indeed affect the CP dynamics, complicating quantification of solid state NMR data obtained with a standard protocol. Whereas the latter can be avoided by carefully drying the sample, the first is often circumvented by demineralization with hydrofluoric acid (HF). Although this can yield considerable organic matter loss, the given examples demonstrate that differences in the intensity distribution of the spectra before and after HF treatment are most likely due to a selective alteration of the relaxation kinetics of protons closely interacting with paramagnetics. It is further shown that single pulse excitation does not necessarily provide quantitative data, since some geopolymers (e.g. cellulose) relax extremely slowly. At high magnetic fields and low spinning speeds, spinning side bands can overlap with relevant signals and obscure the intensity distribution. At spinning speeds >6 kHz, the range of the correct Hartmann–Hahn match is reduced, resulting in a preferential intensity loss of weakly coupling carbons which can be avoided by the application of special pulse sequences. In principal, the acquisition of quantitative CPMAS NMR data from geochemical samples is possible, although this often requires an in depth analysis of the relaxation parameters. Further, the latter also represents a powerful tool for the identification of geochemical compounds by providing additional information about their physical status and their spatial relationships to each other.

Effect of ramp size and sample spinning speed on CPMAS 13C NMR spectra of soil organic matter

Cross polarization (CP) magic angle spinning (MAS) 13C NMR spectroscopy is a solid state NMR technique widely applied to study the chemical composition of natural organic matter. In high magnetic fields (>7 T), fast sample spinning is required in order to reduce the influence of spinning sidebands underlying other chemical shift regions. As the spinning speed increases, the Hartmann–Hahn matching profiles break down into a series of narrow matching bands. In order to account for this instability variable amplitude cross polarization techniques (e.g. VACP, ramp-CP) have been developed. In the present study, we experimentally verified the stability of the Hartmann–Hahn condition under two MAS speeds for different samples with known structure and two different humic acids. For a complete restoration of flat matching profiles, large ramp sizes were needed. The matching profiles of the humic acids showed that both samples needed different ramp sizes to restore flat profiles. A set up based on the matching profiles of the commonly used glycine would have led to an insufficient ramp size for one of the humic acids. For the characterization of natural organic matter, we hence recommend to roughly set the matching conditions with a standard and subsequently optimize the matching conditions on a more complex, preferably representative, sample such as a humic acid. We would suggest to either run an array of different ramp sizes until maximum signal intensity is reached for all chemical shift regions or, in the case of unavailable measurement time, to use a ramp size twice the spinning speed.

A practical guide for the setup of a 1H– 31P– 13C double cross-polarization (DCP) experiment

O-phospho- l-threonine is a convenient sample to setup a 1H– 31P– 13C double cross-polarization (DCP) Hartmann–Hahn match. The 1H– 31P– 13C technique is extremely sensitive to the rate of the sample spinning. Both zero-quantum (ZQ) and double-quantum (DQ) cross-polarization operate at an average spinning rate (6–7 kHz). At higher spinning rates (10 kHz), the DQCP mechanism dominates and leads to a reduction of signal intensity, in particular for lower 31P RF field strength. The application of two shape pulses during the second cross-polarization greatly improves the signal to noise ratio allowing the recording of better quality spectra. 31P– 13C spectrally induced filtering in combination with cross-polarization (SPECIFIC-CP) experiments can be carried out under ZQCP and DQCP conditions if careful attention is paid to the choice of RF field amplitudes and carriers Ω. Application of 1D and 2D 1H– 31P– 13C experiments is demonstrated on model samples; disodium ATP hydrate and O-phospho- l-tyrosine.

2 n -SEMA -a robust solid state nuclear magnetic resonance experiment for measuring heteronuclear dipolar couplings in static oriented systems using effective transverse spin-lock

Separated local field (SLF) spectroscopy is a powerful technique to measure heteronuclear dipolar couplings. The method provides site-specific dipolar couplings for oriented samples such as membrane proteins oriented in lipid bilayers and liquid crystals. A majority of the SLF techniques utilize the well-known Polarization Inversion Spin Exchange at Magic Angle (PISEMA) pulse scheme which employs spin exchange at the magic angle under Hartmann-Hahn match. Though PISEMA provides a relatively large scaling factor for the heteronuclear dipolar coupling and a better resolution along the dipolar dimension, it has a few shortcomings. One of the major problems with PISEMA is that the sequence is very much sensitive to proton carrier offset and the measured dipolar coupling changes dramatically with the change in the carrier frequency. The study presented here focuses on modified PISEMA sequences which are relatively insensitive to proton offsets over a large range. In the proposed sequences, the proton magnetization is cycled through two quadrants while the effective field is cycled through either two or four quadrants. The modified sequences have been named as 2(n)-SEMA where n represents the number of quadrants the effective field is cycled through. Experiments carried out on a liquid crystal and a single crystal of a model peptide demonstrate the usefulness of the modified sequences. A systematic study under various offsets and Hartmann-Hahn mismatch conditions has been carried out and the performance is compared with PISEMA under similar conditions.

Intermediate motions and dipolar couplings as studied by Lee–Goldburg cross-polarization NMR: Hartmann–Hahn matching profiles

In this article, we evaluate the use of simple Lee-Goldburg cross-polarization (LG-CP) NMR experiments for obtaining quantitative information of molecular motion in the intermediate regime. In particular, we introduce the measurement of Hartmann-Hahn matching profiles for the assessment of heteronuclear dipolar couplings as well as dynamics as a reliable and robust alternative to the more common analysis of build-up curves. We have carried out dynamic spin dynamics simulations in order to test the method's sensitivity to intermediate motion and address its limitations concerning possible experimental imperfections. We further demonstrate the successful use of simple theoretical concepts, most prominently Anderson-Weiss (AW) theory, to analyze the data. We further propose an alternative way to estimate activation energies of molecular motions, based upon the acquisition of only two LG-CP spectra per temperature at different temperatures. As experimental tests, molecular jumps in imidazole methyl sulfonate, trimethylsulfoxonium iodide, and bisphenol A polycarbonate were investigated with the new method.

Efficient cross-polarization using a composite 0° pulse for NMR studies on static solids

In most solid-state NMR experiments, cross-polarization is an essential step to detect low-γ nuclei such as 13C and 15N. In this study, we present a new cross-polarization scheme using spin-locks composed of composite 0° pulses in the RF channels of high-γ and low-γ nuclei to establish the Hartmann–Hahn match. The composite 0° pulses with no net nutation-angle{(2 π) X − (2 π) − X − (2 π) Y − (2 π) − Y −} n applied simultaneously to both high-γ ( I) and low-γ ( S) nuclei create an effective heteronuclear dipolar Hamiltonian H d ( 0 ) = d 2 ( 2 I Z S Z + I X S X + I Y S Y ) , which is capable of transferring the Z-component of the I spin magnetization to the Z-component of the S spin magnetization. It also retains a homonuclear dipolar coupling Hamiltonian that enables the flip–flop transfer among abundant spins. While our experimental results indicate that the new pulse sequence, called composite zero cross- polarization (COMPOZER-CP) performs well on adamantane, it is expected to be more valuable to study semi-solids like liquid crystalline materials and model lipid membranes. Theoretical analysis of COMPOZER-CP is presented along with experimental results. Our experimental results demonstrate that COMPOZER-CP overcomes the RF field inhomogeneity and Hartmann–Hahn mismatch for static solids. Experimental results comparing the performance of COMPOZER-CP with that of the traditional constant-amplitude CP and rampCP sequences are also presented in this paper.

The utility of phase alternated pulses for the measurement of dipolar couplings in 2D-SLF experiments

The measurement of hetero-nuclear dipolar coupling using two-dimensional separated local field (SLF-2D) NMR experiments is a powerful technique for the determination of the structure and dynamics of molecules in the solid state and in liquid crystals. However, the experiment is sensitive to a number of factors such as the Hartmann–Hahn match condition, proton frequency off-set and rf heating. It is shown here that by the use of phase alternated pulses during spin-exchange the effect of rf mismatch on the dipolar coupling measurement can be compensated over a wide range of off-sets. Phase alternation together with time and amplitude modulation has also been considered and incorporated into a pulse scheme that combines spin exchange with homonuclear spin decoupling based on magic sandwich sequence and named as SAMPI4. Such time and amplitude averaged nutation experiments use relatively low rf power and generate less sample heating. One of these schemes has been applied on liquid crystal samples and is observed to perform well and yield spectra with high resolution.

Selective polarization transfer using a single rf field

NMR is a popular and mature technique used in fields as diverse as chemistry, biology, or material science. One reason for this versatility lies in its ability to correlate the nuclei that are present in one molecule to another. This provides the researcher with correlation maps allowing for studies of the molecules at an atomic level. Selective experiments allow isolation of one such correlation to focus on spins of interest. This leads to a savings in precious experimental time by reducing the dimension of the experiment, which in turn may enable one to record more elaborate experiments that would otherwise not be amenable within reasonable acquisition times. Here, we present an alternative method to selectively transfer magnetization using a single rf field. This technique, which we call single field polarization transfer, allows to obtain longitudinal two-spin order of two scalar-coupled spins when only one of them is irradiated. The method is easy to implement and does not depend on stringent conditions, such as Hartmann-Hahn matching for selective cross-polarization transfers or very long inversion pulses and identification of coupling satellites in selective population inversion experiments.

Cross polarization from spins I=1∕2 to spins S=1 in nuclear magnetic resonance with magic angle sample spinning

Spin locking of the nuclear magnetization of a spin with S=1 such as deuterium in the presence of a radio-frequency field under magic angle spinning (MAS) is described in terms of adiabatic modulations of the energy levels. In a brief initial period, part of the initial density operator nutates about the Hamiltonian and is dephased. The remaining spin-locked state undergoes persistent oscillatory transfer processes between various coherences with a periodicity given by the rotation of the sample. While all crystallites in the powder undergo such periodic transfer processes, the phases of the oscillations depend on the angle gamma of the crystallites. The angle gamma is the azimuthal angle defining the orientation of the unique axis of the quadrupolar interaction tensor in a rotor-fixed frame. The theory is extended to describe cross-polarization between spins S=1 and I=12 under MAS. There are four distinct Hartmann-Hahn matching conditions that correspond to four zero-quantum matching conditions, all of which are shifted and broadened compared to their spin S=12 counterparts. These matching conditions are further split into a family of sideband conditions separated by the spinning frequency. The theory allows the calculation of both shifts and broadening factors of the matching conditions, as verified by simulations and experiments.

Remarkable reduction of rf power by ATANSEMA and DATANSEMA separated local field in solid-state NMR spectroscopy

We propose a novel approach to markedly reduce rf power for both 1H and observed nuclei during spin exchange for separated local field experiments. The rf power to satisfy the Hartmann–Hahn matching conditions during spin exchange for observed nuclei was arbitrarily reduced by alternating the directions of effective fields for 1H nuclei with unequal duration times and amplitudes. The proposed techniques were compared experimentally with those developed previously by the authors. The rf power for observed nuclei and average 1H were reduced by factors of 9 and 2, respectively, for 13C NMR signals of liquid crystalline 5CB.

Selective homonuclear Hartmann–Hahn transfer method for in vivo spectral editing in the human brain

A novel selective homonuclear Hartmann-Hahn transfer method for in vivo spectral editing is proposed and applied to measurements of gamma-aminobutyric acid (GABA) in the human brain at 3 T. The proposed method utilizes a new concept for in vivo spectral editing, the spectral selectivity of which is not based on a conventional editing pulse but based on the stringent requirement of the doubly selective Hartmann-Hahn match. The sensitivity and spectral selectivity of GABA detection achieved by this doubly selective Hartmann-Hahn match scheme was superior to that achievable by conventional in vivo spectral editing techniques providing both sensitivity enhancement and excellent suppression of overlapping resonances in a single shot. Since double-quantum filtering gradients were not employed, singlets such as the NAA methyl group at 2.02 ppm and the creatine methylene group at 3.92 ppm were detected simultaneously. These singlets may serve as navigators for the spectral phase of GABA and for frequency shifts during measurements. The estimated concentration of GABA in the frontoparietal region of the human brain in vivo was 0.7 +/- 0.2 mumol/g (mean +/- SD, n = 12).

The effect of Hartmann–Hahn mismatching on polarization inversion spin exchange at the magic angle

The effect of the Hartmann–Hahn mismatch Δ= ω eff− ω 1S during polarization inversion spin exchange at the magic angle (PISEMA) has been investigated, where ω eff and ω 1S represent the amplitudes of the 1H effective spin-locking field at the magic angle and the 15N RF spin-locking field, respectively. During the PISEMA evolution period, the exact Hartmann–Hahn match condition (i.e., Δ=0) yields a maximum dipolar scaling factor of 0.816 for PISEMA experiments, while any mismatch results in two different effective fields for the first and second half of each frequency switched Lee–Goldburg (FSLG) cycle. The mismatch effect on the scaling factor depends strongly on the transition angle from one effective field to the other within each FSLG cycle as well as on the cycle time. At low RF spin-lock amplitudes in which the FSLG cycle time is relatively long, the scaling factor rapidly becomes smaller as ω 1S becomes greater than ω eff. On the other hand, when ω 1S< ω eff, there is relatively little effect on the scaling factor with variation in Δ. As a result, the presence of RF inhomogeneities may significantly broaden the line-width in the dipolar dimension because of the mismatch effect. Higher RF spin-lock amplitudes result in a relatively small variation for the scaling factor. Furthermore, ramped amplitude of the 15N RF spin-lock field in synchronization with the flip-flop of the FSLG sequence minimizes the transition angle between the two effective fields within the FSLG cycle. It is shown experimentally that such a ramped amplitude not only gives rise to the same scaling factor but also results in a narrower dipolar line-width in comparison with the rectangular amplitude.

Theoretical and experimental assessment of single- and multiple-quantum cross-polarization in solid state NMR

Continuous wave cross-polarization (CP) NMR experiments with magic angle spinning (MAS) are reviewed for the case of isolated spin pairs I-S, with spin quantum numbers I = ½ and S ½ (1/2, 3/2, …). For two spin-1/2 nuclei, the Hartmann-Hahn matching conditions are examined at various sample rotation rates νR, especially with regard to off-resonance behaviour. In addition to signal enhancement, the CPMAS experiment can be used for the selective determination of inter-nuclear distances between spin-1/2 nuclei. Theoretical examination of the CP transfers to single-quantum (1Q-CPMAS) and multiple-quantum (MQ-CPMAS) levels of quadrupolar nuclei is presented. Simple analytical formulae describing the Hartmann-Hahn matching under various experimental conditions are verified using computer simulations of the spin density matrix under MAS, and the experimental data. The strategies for the most efficient acquisition of 1Q-CPMAS and MQ-CPMAS spectra are extensively discussed.

Examples of Hartmann–Hahn Match Conditions for CP/MAS between Two Half-Integer Quadrupolar Nuclei

Hartmann–Hahn match conditions for n2 → M2 CP/MAS between two quadrupolar nuclei, spin-lock signal as a function of effective nutation frequency, and the correlation of effective nutation frequency and radiofrequency field strength are reported for three samples: sodium diborate (Na2B4O7), aluminum boride (AlB2), and lithium aluminate (LiAlO2). Radiofrequency field strengths used for CP/MAS are both greater and less than the sample spinning speed of 10 kHz, resulting in the observation of both zero-quantum and double-quantum matches, which have signals of opposite sign. The match conditions for Na2B4O7 are as expected from published theory and CP/MAS experiments on spins 12 and n2 (n = 3 or 5) with quadrupole frequencies (ωQ) large compared to the radiofrequency field strength of the CP contact pulse, consisting mainly of sideband matches at one and two times the sample spinning frequency, and the correlation of effective nutation frequency and radiofrequency field strength supports the conclusion that ωQ is large for both 11B and 23Na. Aluminum-27 in AlB2 may have either small or intermediate ωQ, and 7Li in LiAlO2 is proposed to have intermediate ωQ in relation to the radiofrequency field strength, and both have curves of the spin-lock signal as a function of effective nutation frequency with central minima, differing from those of the nuclei with large ωQ. The sign of the CP/MAS signal for AlB2 and LiAlO2 appears to vary with the CP field strengths for the two nuclei so that positive or negative signals cannot be consistently correlated with zero- or double-quantum matches. However, it is possible to assign at least some of the matches as close to integral multiples of the sample spinning frequency, and some of these are matches at greater than two times the sample spinning frequency.