Ultra‐Low‐Field NMR Relaxation and Diffusion Measurements Using an Optical Magnetometer

Nuclear magnetic resonance (NMR) relaxometry and diffusometry are important tools for the characterization of heterogeneous materials and porous media, with applications including medical imaging, food characterization and oil‐well logging. These methods can be extremely effective in applications where high‐resolution NMR is either unnecessary, impractical, or both, as is the case in the emerging field of portable chemical characterization. Here, we present a proof‐of‐concept experiment demonstrating the use of high‐sensitivity optical magnetometers as detectors for ultra‐low‐field NMR relaxation and diffusion measurements.     

Pure In‐Phase Heteronuclear Correlation NMR Experiments

A general NMR approach to provide pure in‐phase (PIP) multiplets in heteronuclear correlation experiments is described. The implementation of a zero‐quantum filter efficiently suppresses any unwanted anti‐phase contributions that usually distort the multiplet pattern of cross‐peaks and can hamper their analysis. The clean pattern obtained in PIP‐HSQMBC experiments is suitable for a direct extraction of coupling constants in resolved signals, for a peak‐fitting process from a reference signal, and for the application of the IPAP technique in non‐resolved multiplets.     

Suppressing One‐Bond Correlations in HMBC Spectra: Improved Performance for the BIRD–HMBC Pulse Sequence

An improved version of the BIRD–HMBC experiment is proposed. In comparison to the original version, the filtering (suppression of ¹ J_CH signals) is accomplished using a double tuned G‐BIRD filter positioned in the middle of the long‐range correlations evolution period. Compensation of offset dependence by replacing the rectangular 180° pulses with the broadband inversion pulses (BIPs), with superior inversion performance and improved tolerance to B₁ field inhomogeneity, significantly improves the sensitivity of the original BIRD–HMBC experiment. For usual one‐bond coupling constants ranges (115–180 Hz), optimal results are easily obtained by adjusting the delays, δ, of the BIRD elements to an average J value. For larger ranges (e.g. 110–260 Hz), the use of a double tuned G‐BIRD filter allows excellent suppression degrees for all types of one‐bond constants present in a molecule, superior to the original scheme and other purging schemes. These attributes make the improved version of the BIRD–HMBC experiment a valuable and robust tool for rapid spectral analysis and rapid checks of molecular skeletons with a minimum spectrometer time. Copyright © 2009 John Wiley & Sons, Ltd.     

Accelerated NMR Spectroscopy with Low‐Rank Reconstruction

Accelerated multi‐dimensional NMR spectroscopy is a prerequisite for high‐throughput applications, studying short‐lived molecular systems and monitoring chemical reactions in real time. Non‐uniform sampling is a common approach to reduce the measurement time. Here, a new method for high‐quality spectra reconstruction from non‐uniformly sampled data is introduced, which is based on recent developments in the field of signal processing theory and uses the so far unexploited general property of the NMR signal, its low rank. Using experimental and simulated data, we demonstrate that the low‐rank reconstruction is a viable alternative to the current state‐of‐the‐art technique compressed sensing. In particular, the low‐rank approach is good in preserving of low‐intensity broad peaks, and thus increases the effective sensitivity in the reconstructed spectra.     

Real‐Time Band‐Selective Homonuclear Proton Decoupling for Improving Sensitivity and Resolution in Phase‐Sensitive J‐Resolved Spectroscopy

Real‐time band‐selective homonuclear ¹H decoupling during data acquisition of z‐filtered J‐resolved spectroscopy produces ¹H‐decoupled ¹H NMR spectra and leads to sensitivity enhancement and improved resolution, and thus aids the measurement of J couplings and residual dipolar couplings in crowded regions of ¹H NMR spectrum. High quality spectra from peptides, organic molecules, and also from enantiomers dissolved in weakly aligned chiral media are reported.     

Clean Absorption‐Mode NMR Data Acquisition

A new acquisition : Based on “phase‐shifted mirrored sampling” (PMS) of indirect evolution periods of multi‐dimensional experiments, new acquisition schemes eliminate, without application of a phase correction, dispersive signal components that exacerbate peak identification and shift peak maxima. The resulting enhanced resolution is of particular value for systems with high chemical shift degeneracy.

     

PSYCHE CPMG–HSQMBC: An NMR Spectroscopic Method for Precise and Simple Measurement of Long‐Range Heteronuclear Coupling Constants

Among the NMR spectroscopic parameters, long‐range heteronuclear coupling constants convey invaluable information on torsion angles relevant to glycosidic linkages of carbohydrates. A broadband homonuclear decoupled PSYCHE CPMG–HSQMBC method for the precise and direct measurement of multiple‐bond heteronuclear couplings is presented. The PSYCHE scheme built into the pulse sequence efficiently eliminates unwanted proton–proton splittings from the heteronuclear multiplets so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between peak maxima of pure antiphase doublets. Moreover, PSYCHE CPMG–HSQMBC can provide significant improvement in sensitivity as compared to an earlier Zangger–Sterk‐based method. Applications of the proposed pulse sequence are demonstrated for the extraction of ⁿJ(¹H,⁷⁷Se) and ⁿJ(¹H,¹³C) values, respectively, in carbohydrates; further extensions can be envisioned in any J‐based structural and conformational studies.     

Next‐Generation Heteronuclear Decoupling for High‐Field Biomolecular NMR Spectroscopy

Ultra‐high‐field NMR spectroscopy requires an increased bandwidth for heteronuclear decoupling, especially in biomolecular NMR applications. Composite pulse decoupling cannot provide sufficient bandwidth at practical power levels, and adiabatic pulse decoupling with sufficient bandwidth is compromised by sideband artifacts. A novel low‐power, broadband heteronuclear decoupling pulse is presented that generates minimal, ultra‐low sidebands. The pulse was derived using optimal control theory and represents a new generation of decoupling pulses free from the constraints of periodic and cyclic sequences. In comparison to currently available state‐of‐the‐art methods this novel pulse provides greatly improved decoupling performance that satisfies the demands of high‐field biomolecular NMR spectroscopy.     

Accelerating Diffusion‐Ordered NMR Spectroscopy by Joint Sparse Sampling of Diffusion and Time Dimensions

Diffusion‐ordered multidimensional NMR spectroscopy is a valuable technique for the analysis of complex chemical mixtures. However, this method is very time‐consuming because of the costly sampling of a multidimensional signal. Various sparse sampling techniques have been proposed to accelerate such measurements, but they have always been limited to frequency dimensions of NMR spectra. It is now revealed how sparse sampling can be extended to diffusion dimensions.     

Non‐Linear Signal Detection Improvement by Radiation Damping in Single‐Pulse NMR Spectra

When NMR lines overlap and at least one of them is affected by radiation damping, the resonance line shapes of all lines are no longer Lorentzian. We report the appearance of narrow signal distortions, which resemble hole‐burnt spectra. This new experimental phenomenon facilitates the detection of tiny signals hidden below the main resonance. Theoretical analysis based on modified Maxwell–Bloch equations shows that the presence of strong transverse magnetization creates a feedback through the coil, which influences the magnetization of all spins with overlapping resonance lines. In the time domain this leads to cross‐precession terms between magnetization densities, which ultimately cause non‐linear behavior. Numerical simulations corroborate this interpretation.     

Resolution Enhancement in SEA XLOC for Heteronuclear NMR Long-Range Correlation

It is shown how the resolution in SEA XLOC NMR spectra for distinguishing between heteronuclear two- and three-bond correlations for all ¹³C multiplicities can be improved by a modified experiment delivering absorptive profiles in the indirect dimension. The method is demonstrated with applications to ibuprofen and strychnine.     

Deuterium Quantification through Deuterium‐Induced Remote 1H and 13C NMR Shifts

Partial labeling by deuterium may be quantified through simple integrations of those ¹H (200 or 400 MHz ) and ¹³C (100.6 MHz ) NMR resonances that are split into pairs by chemical shifts ⁿΔ=δ(deuterated)?δ(nondeuterated) as induced by deuterium across n>2 chemical bonds. The relative intensities of the two components of a pair are shown to be influenced to practically equal degrees by relaxation effects, so that a deuterium fraction may be determined from ¹H and ¹³C integral pairs at more remote molecular positions under the routine conditions of fast accumulative spectral acquisition.     

Heteronuclear Cross‐Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

Dissolution dynamic nuclear polarization (DNP) enables high‐sensitivity solution‐phase NMR experiments on long‐lived nuclear spin species such as ¹⁵N and ¹³C. This report explores certain features arising in solution‐state ¹H NMR upon polarizing low‐γ nuclear species. Following solid‐state hyperpolarization of both ¹³C and ¹H, solution‐phase ¹H NMR experiments on dissolved samples revealed transient effects, whereby peaks arising from protons bonded to the naturally occurring ¹³C nuclei appeared larger than the typically dominant ¹²C‐bonded ¹H resonances. This enhancement of the satellite peaks was examined in detail with respect to a variety of mechanisms that could potentially explain this observation. Both two‐ and three‐spin phenomena active in the solid state could lead to this kind of effect; still, experimental observations revealed that the enhancement originates from ¹³C→¹H polarization‐transfer processes active in the liquid state. Kinetic equations based on modified heteronuclear cross‐relaxation models were examined, and found to well describe the distinct patterns of growth and decay shown by the ¹³C‐bound ¹H NMR satellite resonances. The dynamics of these novel cross‐relaxation phenomena were determined, and their potential usefulness as tools for investigating hyperpolarized ensembles and for obtaining enhanced‐sensitivity ¹H NMR traces was explored.     

Understanding J‐Modulation during Spatial Encoding for Sensitivity‐Optimized Ultrafast NMR Spectroscopy

Ultrafast (UF) NMR spectroscopy is an approach that yields 2D spectra in a single scan. This methodology has become a powerful analytical tool that is used in a large array of applications. However, UF NMR spectroscopy still suffers from an intrinsic low sensitivity, and from the need to compromise between sensitivity, spectral width, and resolution. In particular, the modulation of signal intensities by the spin–spin J‐coupling interaction (J‐modulation) impacts significantly on the intensities of the spectral peaks. This effect can lead to large sensitivity losses and even to missing spectral peaks, depending on the nature of the spin system. Herein, a general simulation package (Spinach) is used to describe J‐modulation effects in UF experiments. The results from simulations match with experimental data and the results of product operator calculations. Several methods are proposed to optimize the sensitivity in UF COSY spectra. The potential and drawbacks of the different strategies are also discussed. These approaches provide a way to adjust the sensitivity of UF experiments for a large range of applications.