Broadband Cross-Polarization to Half-Integer Quadrupolar Nuclei: Wideline Static NMR Spectroscopy.

Cross-polarization (CP) is a technique commonly used for the signal enhancement of NMR spectra; however, applications to quadrupolar nuclei have heretofore been limited due to a number of problems, including poor spin-locking efficiency, inconvenient relaxation times, and reduced CP efficiencies over broad spectral bandwidths─this is unfortunate, since they constitute 73% of NMR-active nuclei in the periodic table. The Broadband Adiabatic Inversion CP (BRAIN-CP) pulse sequence has proven useful for the signal enhancement of wideline and ultra-wideline (i.e., 250 kHz to several MHz in breadth) powder patterns arising from stationary samples; however, a comprehensive investigation of its application to half-integer quadrupolar nuclei (HIQN) is currently lacking. Herein, we present theoretical and experimental considerations for applying BRAIN-CP to acquire central-transition (CT, +1/2 ↔ -1/2) powder patterns of HIQN. Consideration is given to parameters crucial to the success of the experiment, such as the Hartmann-Hahn (HH) matching conditions and the phase modulation of the contact pulse. Modifications to the BRAIN-CP sequence such as flip-back (FB) pulses and ramped contact pulses applied to the 1H spins are used for the reduction of experimental times and increased CP bandwidth capabilities, respectively. Spectra for a series of quadrupolar nuclei with broad CT powder patterns, including 35Cl (S = 3/2), 55Mn (S = 5/2), 59Co (S = 7/2), and 93Nb (S = 9/2), are acquired via direct excitation (CPMG and WCPMG) and indirect excitation (CP/CPMG and BRAIN-CP) methods. We demonstrate that proper implementation of the sequence can enable 1H-S broadband CP over a bandwidth of 1 MHz, which to the best of our knowledge is the largest CP bandwidth reported to date. Finally, we establish the basic principles necessary for simplified optimization and execution of the BRAIN-CP pulse sequence for a wide range of HIQNs.

3D relaxation-assisted separation of wideline solid-state NMR patterns for achieving site resolution.

There are currently no methods for the acquisition of ultra-wideline (UW) solid-state NMR spectra under static conditions that enable reliable separation and resolution of overlapping powder patterns arising from magnetically distinct nuclei. This stands in contrast to the variety of techniques available for spin-1/2 or half-integer quadrupolar nuclei with narrow central transition patterns under magic-angle spinning (MAS). Resolution of overlapping signals is routinely achieved in MRI and solution-state NMR by exploiting relaxation differences between nonequivalent sites. Preliminary studies of relaxation assisted separation (RAS) for separating overlapping UWNMR patterns using pseudo-inverse Laplace Transforms have reported two-dimensional spectra featuring relaxation rates correlated to NMR interaction frequencies. However, RAS methods are inherently sensitive to experimental noise, and require that relaxation rates associated with overlapped patterns be significantly different from one another. Herein, principal component analysis (PCA) denoising is implemented to increase the signal-to-noise ratios of the relaxation datasets and RAS routines are stabilized with truncated singular value decomposition (TSVD) and elastic net (EN) regularization to resolve overlapped patterns with a larger tolerance for differences in relaxation rates. We extend these methods for improved pattern resolution by utilizing 3D frequency-R1-R2 correlation spectra. Synthetic and experimental datasets, including 35Cl (I = 3/2), 2H (I = 1), and 14N (I = 1) NMR of organic and biological compounds, are explored with both regularized 2D RAS and 3D RAS; comparison of these data reveal improved resolution in the latter case. These methods have great potential for separating overlapping powder patterns under both static and MAS conditions.

Sensitivity Enhancement by Progressive Saturation of the Proton Reservoir: A Solid-State NMR Analogue of Chemical Exchange Saturation Transfer.

Chemical exchange saturation transfer (CEST) enhances solution-state NMR signals of labile and otherwise invisible chemical sites, by indirectly detecting their signatures as a highly magnified saturation of an abundant resonance─for instance, the 1H resonance of water. Stimulated by this sensitivity magnification, this study presents PROgressive Saturation of the Proton Reservoir (PROSPR), a method for enhancing the NMR sensitivity of dilute heteronuclei in static solids. PROSPR aims at using these heteronuclei to progressively deplete the abundant 1H polarization found in most organic and several inorganic solids, and implements this 1H signal depletion in a manner that reflects the spectral intensities of the heteronuclei as a function of their chemical shifts or quadrupolar offsets. To achieve this, PROSPR uses a looped cross-polarization scheme that repeatedly depletes 1H-1H local dipolar order and then relays this saturation throughout the full 1H reservoir via spin-diffusion processes that act as analogues of chemical exchanges in the CEST experiment. Repeating this cross-polarization/spin-diffusion procedure multiple times results in an effective magnification of each heteronucleus's response that, when repeated in a frequency-stepped fashion, indirectly maps their NMR spectrum as sizable attenuations of the abundant 1H NMR signal. Experimental PROSPR examples demonstrate that, in this fashion, faithful wideline NMR spectra can be obtained. These 1H-detected heteronuclear NMR spectra can have their sensitivity enhanced by orders of magnitude in comparison to optimized direct-detect experiments targeting unreceptive nuclei at low natural abundance, using modest hardware requirements and conventional NMR equipment at room temperature.

Emergence of Coupled Rotor Dynamics in Metal-Organic Frameworks via Tuned Steric Interactions.

The organic components in metal-organic frameworks (MOFs) are unique: they are embedded in a crystalline lattice, yet, as they are separated from each other by tunable free space, a large variety of dynamic behavior can emerge. These rotational dynamics of the organic linkers are especially important due to their influence over properties such as gas adsorption and kinetics of guest release. To fully exploit linker rotation, such as in the form of molecular machines, it is necessary to engineer correlated linker dynamics to achieve their cooperative functional motion. Here, we show that for MIL-53, a topology with closely spaced rotors, the phenylene functionalization allows researchers to tune the rotors' steric environment, shifting linker rotation from completely static to rapid motions at frequencies above 100 MHz. For steric interactions that start to inhibit independent rotor motion, we identify for the first time the emergence of coupled rotation modes in linker dynamics. These findings pave the way for function-specific engineering of gear-like cooperative motion in MOFs.

Broadband adiabatic inversion experiments for the measurement of longitudinal relaxation time constants.

Accurate measurements of longitudinal relaxation time constants (T1) in solid-state nuclear magnetic resonance (SSNMR) experiments are important for the study of molecular-level structure and dynamics. Such measurements are often made under magic-angle spinning conditions; however, there are numerous instances where they must be made on stationary samples, which often give rise to broad powder patterns arising from large anisotropic NMR interactions. In this work, we explore the use of wideband uniform-rate smooth-truncation pulses for the measurement of T1 constants. Two experiments are introduced: (i) BRAIN-CPT1, a modification of the BRAIN-CP (BRoadband Adiabatic-INversion-Cross Polarization) sequence, for broadband CP-based T1 measurements and (ii) WCPMG-IR, a modification of the WURST-CPMG sequence, for direct-excitation (DE) inversion-recovery experiments. A series of T1 constants are measured for spin-1/2 and quadrupolar nuclei with broad powder patterns, such as 119Sn (I = 1/2), 35Cl (I = 3/2), 2H (I = 1), and 195Pt (I = 1/2). High signal-to-noise spectra with uniform patterns can be obtained due to signal enhancements from T2 eff-weighted echo trains, and in favorable cases, BRAIN-CPT1 allows for the rapid measurement of T1 in comparison to DE experiments. Protocols for spectral acquisition, processing, and analysis of relaxation data are discussed. In most cases, relaxation behavior can be modeled with either monoexponential or biexponential functions based upon measurements of integrated powder pattern intensity; however, it is also demonstrated that one must interpret such T1 values with caution, as demonstrated by measurements of T1 anisotropy in 119Sn, 2H, and 195Pt NMR spectra.

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.

Field-stepped ultra-wideline NMR at up to 36 T: On the inequivalence between field and frequency stepping.

Field-stepped NMR spectroscopy at up to 36 T using the series-connected hybrid (SCH) magnet at the U.S. National High Magnetic Field Laboratory is demonstrated for acquiring ultra-wideline powder spectra of nuclei with very large quadrupolar interactions. Historically, NMR evolved from the continuous-wave (cw) field-swept method in the early days to the pulsed Fourier-transform method in the modern era. Spectra acquired using field sweeping are generally considered to be equivalent to those acquired using the pulsed method. Here, it is shown that field-stepped wideline spectra of half-integer spin quadrupolar nuclei acquired using WURST/CPMG methods can be significantly different from those acquired with the frequency-stepped method commonly used with superconducting magnets. The inequivalence arises from magnetic field-dependent NMR interactions such as the anisotropic chemical shift and second-order quadrupolar interactions; the latter is often the main interaction leading to ultra-wideline powder patterns of half-integer spin quadrupolar nuclei. This inequivalence needs be taken into account to accurately and correctly determine the quadrupolar coupling and chemical shift parameters. A simulation protocol is developed for spectral fitting to facilitate analysis of field-stepped ultra-wideline NMR spectra acquired using powered magnets. A MATLAB program which implements this protocol is available on request.

A high-volume resonator for L-band DNP-NMR.

DNP-NMR and EPR experiments that operate at or greater than L-band (i.e., ν0(e-) = 1-2 GHz) are typically limited to maximum sample volumes of several hundred µL. These experiments rely on well-known resonator designs for DNP/EPR irradiation such as the loop-gap resonator and Alderman-Grant coil, where their maximum volumes limit further application to imaging experiments and high-throughput screening beyond L-band. Herein, we demonstrate a birdcage (BC) resonator design that can accommodate several mL of sample while operating around 1.5 GHz. The sample volume is maximized by using two identical BC resonators in a stacked configuration. Simulations are used to optimize the BC design and the performance is validated experimentally with liquid-state Overhauser-DNP-NMR experiments. This BC design exploits just the parasitic capacitance of conductive rings and features no fixed tuning capacitors. An enhancement of -77 is achieved on a 10 mM 4-Amino-TEMPO in H2O sample for a 5 mL sample volume. The associated sample heating is minimal due to the low-E-fields generated and the large sample mass with +3.4 K when driving 100 W for several seconds.

Structure and bonding in rhodium coordination compounds: a 103Rh solid-state NMR and relativistic DFT study.

This study demonstrates the application of 103Rh solid-state NMR (SSNMR) spectroscopy to inorganic and organometallic coordination compounds, in combination with relativistic density functional theory (DFT) calculations of 103Rh chemical shift tensors and their analysis with natural bond orbital (NBO) and natural localized molecular orbital (NLMO) protocols, to develop correlations between 103Rh chemical shift tensors, molecular structure, and Rh-ligand bonding. 103Rh is one of the least receptive NMR nuclides, and consequently, there are very few reports in the literature. We introduce robust 103Rh SSNMR protocols for stationary samples, which use the broadband adiabatic inversion-cross polarization (BRAIN-CP) pulse sequence and wideband uniform-rate smooth-truncation (WURST) pulses for excitation, refocusing, and polarization transfer, and demonstrate the acquisition of 103Rh SSNMR spectra of unprecedented signal-to-noise and uniformity. The 103Rh chemical shift tensors determined from these spectra are complemented by NBO/NLMO analyses of contributions of individual orbitals to the 103Rh magnetic shielding tensors to understand their relationship to structure and bonding. Finally, we discuss the potential for these experimental and theoretical protocols for investigating a wide range of materials containing the platinum group elements.

DESPERATE: A Python library for processing and denoising NMR spectra.

NMR spectroscopy is an inherently insensitive technique with respect to the amount of observable signal. A common element in all NMR spectra is random thermal noise that is often characterized by a signal-to-noise ratio (SNR). SNR can be generically improved experimentally with repetitive signal averaging or during post-processing with apodization; the former of which often results in long experimental times and the latter results in the loss of spectral resolution. Denoising techniques can instead be used during post-processing to enhance SNR without compromising resolution. The most common approach relies on the singular-value decomposition (SVD) to discard noisy components of NMR data. SVD-based approaches work well, such as Cadzow and PCA, but are computationally expensive when used for large datasets that are often encountered in NMR (e.g., Carr-Purcell/Meiboom-Gill and nD datasets). Herein, we describe the implementation of a new wavelet transform (WT) routine for the fast and robust denoising of 1D and 2D NMR spectra. Several simulated and experimental datasets are denoised with both SVD-based Cadzow or PCA and WT's, and the resulting SNR enhancements and spectral uniformity are compared. WT denoising offers similar and improved denoising compared with SVD and operates faster by several orders-of-magnitude in some cases. All denoising and processing routines used in this work are included in a free and open-source Python library called DESPERATE.

An automated multi-order phase correction routine for processing ultra-wideline NMR spectra.

Efficient acquisition of wideline solid-state nuclear magnetic resonance (NMR) spectra with patterns affected by large inhomogeneous broadening is accomplished with the use of broadband pulse sequences. These specialized pulse sequences often use frequency-swept pulses, which feature time-dependent phase and amplitude modulations that in turn deliver broad and uniform excitation across large spectral bandwidths. However, the resulting NMR spectra are often affected by complex frequency-dependent phase dispersions, owing to the interplay between the frequency-swept excitations and anisotropic resonance frequencies. Such phase distortions necessitate the use of multi-order non-linear corrections in order to obtain absorptive, distortion-free patterns with uniform phasing. Performing such corrections is often challenging due to the complex interdependence of the linear and non-linear phase contributions, and how these may affect the NMR signal. Hence, processing of these data usually involves calculating the spectra in magnitude mode wherein the phase information is discarded. Herein, we present a fully automated phasing routine that is capable of processing and phase correcting such wideline NMR spectra. Its performance is corroborated via processing of NMR data acquired using both the WURST-CPMG (Wideband, Uniform-Rate, Smooth Truncation with Carr-Purcell Meiboom-Gill acquisition) and BRAIN-CP (BRoadband Adiabatic Inversion Cross Polarization) pulse sequences for a variety of nuclei (i.e., 119Sn, 195Pt, 35Cl, 87Rb, and 14N). Based on both simulated and experimental NMR datasets, it is demonstrated that automatic phase corrections up to and including second order can be readily achieved without a priori information regarding the nature of the phase-distorted NMR datasets, and independently of the exact manner in which time-domain NMR data are collected and subsequently processed. In addition, it is shown that NMR spectra acquired at both single and multiple transmitter frequencies that are processed with this automated phasing routine have improved signal-to-noise properties than those processed with conventional magnitude calculations, along with powder patterns that better match those of ideal NMR spectra, even for datasets possessing low signal-to-noise ratios and/or affected by spectral artifacts.

On the effects of quadrupolar relaxation in Earth's field NMR spectra.

There is growing interest in using low-field magnetic resonance experiments for routine chemical characterization. Earth's field NMR is one such technique that can garner structural information and enable sample differentiation with low cost and highly portable designs. The resulting NMR spectra are primarily influenced by J-couplings, resulting in so-called J-coupled spectra (JCS). Many small molecules include atoms with NMR-active nuclei that are quadrupolar either at natural abundance or are often isotopically enriched (e.g.,2H, 6Li, 11B, 14N, 17O, etc.) where the effects of quadrupolar J-couplings and relaxation on JCS of strongly- and weakly-coupled spin systems have not been explored to date. Herein, using a set of seven fluoropyridine samples with unique substitution and J-couplings, we demonstrate that the 14N relaxation rates can induce drastic line-broadening in the JCS. This includes a previously unexplored unique line broadening mechanism enabled by strongly coupled spins at low-field. Numerical simulations are used to model and refine the magnitudes and signs of J-couplings, as well as indirectly determine the 14N relaxation rates in a single 1D experiment that has a higher fidelity than observed in high-field NMR experiments.

Reducing the effects of weak homonuclear dipolar coupling with CPMG pulse sequences for static and spinning solids.

The Carr-Purcell/Meiboom-Gill (CPMG) pulse sequence, initially introduced for measuring transverse relaxation time constants (T2), can provide significant signal enhancements for solid-state NMR (SSNMR) spectra. The proper implementation of CPMG for acquiring spectra influenced by chemical shift anisotropies (CSAs), first and/or second order quadrupolar interactions, or paramagnetic broadening has been well documented to date, as have the effects of heteronuclear dipolar coupling on CPMG echo trains and T2 lifetimes. Homonuclear dipolar coupling can also impact T2 lifetimes and CPMG echo trains; these effects have been thoroughly investigated for spectra of homonuclear dipolar coupled spin-1/2 nuclei typically acquired under static conditions that are predominantly influenced by dipolar broadening (e.g., 1H, 19F, etc.). In particular, it has been shown that short refocusing pulses with small flip angles can extend the effective T2 (T2eff, the observed T2 constant as impacted by experimental conditions) measured by CPMG sequences for strong homonuclear dipolar coupled spin-1/2 pairs under static conditions. To date, these effects have not been explored for (i) spin-1/2 nuclei that have significant CSAs and simultaneously feature weak homonuclear dipolar couplings, (ii) for quadrupolar nuclei that are also weakly homonuclear dipolar coupled, and (iii) for either of these cases under magic-angle spinning (MAS) conditions. Herein, we demonstrate that short refocusing pulses that cause small flip angles can reduce the attenuation of signal in CPMG echo trains resulting from dipolar dephasing caused by the weak homonuclear dipolar couplings. For both spin-1/2 and quadrupolar nuclei, this can lead to significant extensions in T2eff and signal enhancements of up to three times compared to conventional CPMG in favourable cases. These phenomena can occur under both static and magic-angle spinning (MAS) conditions, in the latter of which homonuclear couplings are reintroduced by rotational resonance (R2) recoupling. Experimental examples of 13C (I = 1/2), 2H (I = 1), 87Rb (I = 3/2), 23Na (I = 3/2), and 35Cl (I = 3/2) NMR under static and MAS conditions, as well as simulations of these phenomena, are shown and discussed.

On the use of frequency-swept pulses and pulses designed with optimal control theory for the acquisition of ultra-wideline NMR spectra.

Frequency-swept (FS) pulses, such as wideband uniform-rate smooth-truncation (WURST) pulses, have found much success for the acquisition of ultra-wideline (UW) solid-state NMR spectra. In this preliminary study, new pulses and pulse sequences are explored in simulation and experimentally for several nuclei exhibiting UWNMR powder patterns under static conditions, including 119Sn (I = 1/2), 195Pt (I = 1/2), 2H (I = 1), and 71Ga (I = 3/2). First, hyperbolic secant (HS) and tanh/tan (THT) pulses are tested and implemented as excitation and refocusing pulses in spin-echo and Carr-Purcell/Meiboom Gill (CPMG)-type sequences, and shown to have comparable performances to analogous WURST pulses. Second, optimal control theory (OCT) is utilized for the design of new Optimal Control Theory Optimized Broadband Excitation and Refocusing (OCTOBER) pulses, using carefully parameterized WURST, THT, and HS pulses as starting points. Some of the new OCTOBER pulses used in spin-echo sequences are capable of efficient broadband excitation and refocusing, in some cases resulting in spectra with increased signal enhancements over those obtained in experiments using conventional FS pulses. Finally, careful consideration of the spin dynamics of several systems, by monitoring of the time evolution of the density matrix via the Liouville-von Neumann equation and analysis of the time-resolved Fourier transforms of the pulses, lends insight into the underlying mechanisms of the FS and OCTOBER pulses. This is crucial for understanding their performance in terms of generating uniformly excited patterns of high signal intensity, and for identifying trends that may offer pathways to generalized parameterization and/or new pulse shapes.