Homonuclear Decoupling in 1H NMR of Solids by Remote Correlation

The typical linewidths of ¹H NMR spectra of powdered organic solids at 111 kHz magic-angle spinning (MAS) are of the order of a few hundred Hz. While this is remarkable in comparison to the tens of kHz observed in spectra of static samples, it is still the key limit to the use of ¹H in solid-state NMR, especially for complex systems. Here, we demonstrate a novel strategy to further improve the spectral resolution. We show that the anti-z-COSY experiment can be used to reduce the residual line broadening of ¹H NMR spectra of powdered organic solids. Results obtained with the anti-z-COSY sequence at 100 kHz MAS on thymol, β-AspAla, and strychnine show an improvement in resolution of up to a factor of two compared to conventional spectra acquired at the same spinning rate.     

Ultra fast magic angle spinning solid – state NMR spectroscopy of intact bone

Ultra fast magic angle spinning (MAS) has been a potent method to significantly average out homogeneous/inhomogeneous line broadening in solid‐state nuclear magnetic resonance (ssNMR) spectroscopy. It has given a new direction to ssNMR spectroscopy with its different applications. We present here the first and foremost application of ultra fast MAS (~60 kHz) for ssNMR spectroscopy of intact bone. This methodology helps to comprehend and elucidate the organic content in the intact bone matrix with resolution and sensitivity enhancement. At this MAS speed, amino protons from organic part of intact bone start to appear in ¹H NMR spectra. The experimental protocol of ultra‐high speed MAS for intact bone has been entailed with an additional insight achieved at 60 kHz. Copyright © 2015 John Wiley & Sons, Ltd.     

Two-dimensional Pure Isotropic Proton Solid State NMR

One key bottleneck of solid-state NMR spectroscopy is that ¹H NMR spectra of organic solids are often very broad due to the presence of a strong network of dipolar couplings. We have recently suggested a new approach to tackle this problem. More specifically, we parametrically mapped errors leading to residual dipolar broadening into a second dimension and removed them in a correlation experiment. In this way pure isotropic proton (PIP) spectra were obtained that contain only isotropic shifts and provide the highest ¹H NMR resolution available today in rigid solids. Here, using a deep-learning method, we extend the PIP approach to a second dimension, and for samples of L-tyrosine hydrochloride and ampicillin we obtain high resolution ¹H-¹H double-quantum/single-quantum dipolar correlation and spin-diffusion spectra with significantly higher resolution than the corresponding spectra at 100 kHz MAS, allowing the identification of previously overlapped isotropic correlation peaks.     

Suitability of Different 13C Solid-state NMR Techniques in the Characterization of Humic Acids

Qualitative and quantitative analyses of humic acids (HAs) with five different ¹³C solid-state NMR techniques were assessed using HAs of various origins and locations. The NMR techniques compared are: (1) direct polarization/magic angle spinning (DP/MAS) at 13 kHz, (2) conventional cross polarization (CP)/MAS at 5 kHz, (3) ramp-CP/MAS at 8 kHz, (4) CP/total sideband suppression (TOSS) at 4.5 kHz, and (5) DP/MAS corrected by CP/spin-lattice relaxation with TOSS. The spectra from the five techniques were first compared qualitatively. Then, each spectrum was divided into eight regions for quantitative evaluation. DP/MAS spectra were used as quantitative references. Ramp-CP/MAS and CP/TOSS spectra gave consistently better results than those of the conventional CP/MAS spectra at a ¹³C frequency of 75 MHz, which were incorrect due to spinning sidebands. CP/MAS at low magnetic fields (22.6 and 50.6 MHz ¹³C frequency) indicated improved integration results but lower resolution. Correction factors calculated by comparison with DP/MAS will be useful to convert the non-quantitative peak areas in the CP/TOSS and ramp-CP/MAS spectra into more quantitative results.     

High-Resolution Solid-State MAS13C- and 1H-NMR Spectra of Benzenoid Aromatics Adsorbed on Alumina and Silica: Successful Applications of 1D and 2D Pulse Experiments from Liquid-State NMR

Strong line-narrowing effects in solid-state, magic-angle-spinning (MAS) ¹³C- as well as ¹H-NMR spectra of benzenoid aromatics adsorbed at alumina or silica surfAccs indicate high mobility of the organic adsorbates. Even under modest spinning rales (1 kHz), dipolar couplings are sufficiently reduced to allow scalar ^13C,¹H couplings to be measured. Hetero- and homonuclear pulse sequences known from high-resolution NMR in liquids, like SEFT, ^J-RESOLVED, DEPT, COSY, and ¹³C,¹H shift-correlation experiments are successfully applicable. ¹³C spin-lattice relaxation limes are as short as 0.5 s (CH) and 1.1 s (C_q), and T₁(¹H) values are in the order of 0.3 s.     

Pure Isotropic Proton NMR Spectra in Solids using Deep Learning

The resolution of proton solid-state NMR spectra is usually limited by broadening arising from dipolar interactions between spins. Magic-angle spinning alleviates this broadening by inducing coherent averaging. However, even the highest spinning rates experimentally accessible today are not able to completely remove dipolar interactions. Here, we introduce a deep learning approach to determine pure isotropic proton spectra from a two-dimensional set of magic-angle spinning spectra acquired at different spinning rates. Applying the model to 8 organic solids yields high-resolution ¹H solid-state NMR spectra with isotropic linewidths in the 50–400 Hz range.     

Enhanced sensitivity and resolution in (1)H solid-state NMR spectroscopy of paramagnetic complexes under very fast magic angle spinning

High-resolution NMR spectroscopy for paramagnetic complexes in solids has been rarely performed because of its limited sensitivity and resolution due to large paramagnetic shifts and associated technical difficulties. The present study demonstrates that magic angle spinning (MAS) at speeds exceeding 20 kHz provides unusually high sensitivity and excellent resolution in 1H solid-state NMR (SSNMR) for paramagnetic systems. Spinning-speed dependence of 1H MAS spectra showed that very fast MAS (VFMAS) at 24-28 kHz enhanced sensitivity by a factor of 12-18, compared with the sensitivity of 1H SSNMR spectra under moderate MAS at 10 kHz, for Cu(dl-alanine)2.H2O and Mn(acac)3, for which the spectral ranges due to 1H paramagnetic shifts reach 200 and 1000 ppm, respectively. It was theoretically and experimentally confirmed that the absolute sensitivity of 1H VFMAS for small paramagnetic complexes such as Cu(dl-alanine)2 can be an order of magnitude higher than that of equimolar diamagnetic ligands because of short 1H T1 ( approximately 1 ms) of the paramagnetic systems and improved sensitivity under VFMAS. On the basis of this demonstrated high sensitivity, 1H SSNMR micro analysis of paramagnetic systems in a nanomole scale is proposed. Applications were performed on two polymorphs of Cu(II)(8-quinolinol)2, which is a suppressor of human cancer cells. It was demonstrated that 1H VFMAS SSNMR spectra accumulated for 20 nmol of the polycrystalline samples in 10 min enabled one to distinguish alpha- and beta-forms of Cu(II)(8-quinolinol)2 on the basis of shift positions and line widths.     

High magnetic field solid‐state NMR analyses by combining MAS,MQ‐MAS,homo‐nuclear and hetero‐nuclear correlation experiments

A general strategy of structural analysis of alumina silicate by combining various solid‐state NMR measurements such as single pulse, multi‐quantum magic angle spinning, double‐quantum homo‐nuclear correlation under magic angle spinning (DQ‐MAS), and cross‐polarization hetero‐nuclear correlation (CP‐HETCOR) was evaluated with the aid of high magnetic field NMR (800 MHz for ¹H Larmor frequency) by using anorthite as a model material. The high magnetic field greatly enhanced resolution of ²⁷Al in single pulse, DQ‐MAS, and even in triple‐quantum magic angle spinning NMR spectra. The spatial proximities through dipolar couplings were probed by the DQ‐MAS methods for homo‐nuclear correlations between both ²⁷Al–²⁷Al and ²⁹Si–²⁹Si and by CP‐HETCOR for hetero‐nuclear correlations between ²⁷Al–²⁹Si in the anorthite framework. By combining various NMR methodologies, we elucidated detailed spatial correlations among various aluminum and silicon species in anorthite that was hard to be determined using conventional analytical methods at low magnetic field. Moreover, the presented approach is applicable to analyze other alumina‐silicate minerals. Copyright © 2012 John Wiley & Sons, Ltd.     

A fast MAS 1H NMR study of amino acids and proteins

Fast sample spinning (up to 32 kHz) in tandem with delayed acquisition enabled resolved ¹H NMR spectra of solid amino acids to be recorded. The resulting spectra are, however, significantly dependent on sample crystallinity and on sample preparation conditions, e.g. sample drying. Sample heating leads to a marked increase in signal to noise ratio and enables groups with different dynamic properties to be identified. In addition, the observation of peak shifts as a function of heating allows the identification of hydrogen bonded sites. Spectral assignment of the ¹H MAS spectra is proposed for some examples based on relaxation properties, study of deuteriated samples and 2D NMR. The effects of molecular weight and sample complexity on the ¹H MAS spectra were investigated using tetraglycine, polyglycine and two proteins: a small protein (lysozyme) and a much larger protein (a cereal storage protein named high molecular weight subunit 1Dx5). Moderate spectral resolution was achieved for the peptides and lysozyme, but for 1Dx5, significant resolution enhancement was obtained enabling the identification of resonances in all regions of the spectra including the alpha region, the aromatic region and the NH backbone region.     

Solid‐state cross‐polarization magic angle spinning 13C and 15N NMR characterization of Sepia melanin,Sepia melanin free acid and Human hair melanin in comparison with several model compounds

This paper presents the high‐resolution ¹³C and ¹⁵N cross‐polarization magic angle spinning (CP/MAS) NMR spectra of three natural melanin solids: Sepia officinalis melanin, Sepia officinalis melanin free acid (MFA) and Human hair melanin. The functional group characterization of Human hair melanin by NMR is the first to date and the ¹³C CP/MAS NMR spectra reported here show improved resolution of chemically inequivalent sites. The observed spectral regions of the solid melanin samples can be assigned to the postulated structural unit of the polymer chain of Sepia MFA derived from solution‐state NMR studies. To assist in the assignment of functional groups in the spectra, the solid‐state CP/MAS NMR spectra are compared with high‐resolution ¹³C and ¹⁵N CP/MAS spectra of four model compounds, L ‐dopa, dopamine, 2‐methoxycarbonyl‐3‐ethoxycarbonyl‐4‐methylpyrrole and ethyl 5,6‐dimethoxyindole‐2‐carboxylate. To aid further in the assignment of protonated and non‐protonated carbon atoms, CP contact time dependence and non‐quaternary carbon suppression (NQS) experiments were performed on the melanin samples. The ¹⁵N CP/MAS spectra of the melanin samples confirm the presence of indole and pyrrole units in the melanin polymer chain. The NMR peaks observed in all of the melanin samples are relatively broad, presumably owing to the presence of free radicals. Electron spin resonance (ESR) data shows that all three melanin samples contain localized free radicals (g = 2.007), with the Sepia melanin containing a 10‐fold higher free radical density than Human hair melanin. Copyright © 2003 John Wiley & Sons, Ltd.     

Crystal Effects on Mesobilirubin: A Combined NMR Spectroscopic and Density Functional Theory Study

We report solid‐state NMR investigations of crystal effects in powdered mesobilirubin‐IXα, an open‐chain tetrapyrrole that is structurally related to bilirubin‐IXα but hydrogenated at the 3‐ and 18‐vinyl groups. ¹³C and ¹⁵N cross‐polarization magic‐angle spinning (CP/MAS) NMR experiments were performed on the compound at natural abundance. To facilitate the spectral analysis, density functional calculations were carried out at the B3LYP/6‐311G(d,p) level of theory, using an enneameric cluster to simulate the solid. The ¹H, ¹³C and ¹⁵N chemical shift data calculated for the enneamer are in a good agreement with those observed in the experimental spectra, and the relative order of the calculated resonances was thus used to confirm the tentative assignments obtained mainly from the heteronuclear correlation spectra. The observed signal splittings of a small subset of the ¹³C resonances in the peripheral regions of the two terminal rings provide evidence for microcrystalline heterogeneity of the powdered compound.     

Enhancing NMR Sensitivity of Natural‐Abundance Low‐γ Nuclei by Ultrafast Magic‐Angle‐Spinning Solid‐State NMR Spectroscopy

Although magic‐angle‐spinning (MAS) solid‐state NMR spectroscopy has been able to provide piercing atomic‐level insights into the structure and dynamics of various solids, the poor sensitivity has limited its widespread application, especially when the sample amount is limited. Herein, we demonstrate the feasibility of acquiring high S/N ratio natural‐abundance ¹³C NMR spectrum of a small amount of sample (≈2.0 mg) by using multiple‐contact cross polarization (MCP) under ultrafast MAS. As shown by our data from pharmaceutical compounds, the signal enhancement achieved depends on the number of CP contacts employed within a single scan, which depends on the T_1ρ of protons. The use of MCP for fast 2D ¹H/¹³C heteronuclear correlation experiments is also demonstrated. The significant signal enhancement can be greatly beneficial for the atomic‐resolution characterization of many types of crystalline solids including polymorphic drugs and nanomaterials.     

Proton high‐field NMR study of tomato juice

A detailed analysis of the proton high‐field (600 MHz) NMR spectra of tomato juice and pulp is reported for the first time. A combination of J‐resolved, COSY, TOCSY, DOSY, ¹H–¹³C HSQC and ¹H–¹³C HMBC 2D sequences was used to assign each spin system and to separate the components of the complex patterns in the 1D overlapped proton spectra. To obtain resolved proton spectra of tomato pulps the high‐resolution magic angle spinning technique was used; a comparison with the liquid‐state NMR spectra of the corresponding juices was accomplished. On the basis of the assignments made, the chemical composition of tomato juices from two cultivars (Red Setter and Ciliegino) was determined. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

Characterization of H2-Splitting Products of Frustrated Lewis Pairs: Benefit of Fast Magic-Angle Spinning

Proton spectroscopy in solid-state NMR on catalytic materials offers new opportunities in structural characterization, in particular of reaction products of catalytic reactions such as hydrogenation reactions. Unfortunately, the ¹H NMR line widths in magic-angle spinning solid-state spectra are often broadened by an incomplete averaging of ¹H-¹H dipolar couplings. We herein discuss two model compounds, namely the H₂-splitting products of two phosphane-borane Frustrated Lewis Pairs (FLPs), to study potentials and limitations of proton solid-state NMR experiments employing magic-angle spinning frequencies larger than 100 kHz at a static magnetic field strength of 20.0 T. The ¹H lines are homogeneously broadened as illustrated by spin-echo decay experiments. We study two structurally similar materials which however show significant differences in ¹H line widths which we explain by differences in their ¹H-¹H dipolar networks. We discuss the benefit of fast MAS experiments up to 110 kHz to detect the resonances of the H⁺/H⁻ pair in the hydrogenation products of FLPs.     

Fingerprints of Phalaenopsis Tissues in Growth and Spike Induction Periods—A Solid‐state 13C NMR Approach

Solid‐state Nuclear Magnetic Resonance (ss‐NMR) ¹³C single‐pulse excitation spectroscopy in combination with the magic‐angle spinning (MAS) technique was applied to a series of Phalaenopsis tissues, including the leaf, sheath, stem, and root, at different growth and spiking periods. Compared with{¹H}/¹³C cross‐polarization MAS spectra, the ¹³C single‐pulse excitation MAS spectra displayed very distinct spectral patterns, recognizable as fingerprints of the tissues studied. ¹Here, we demonstrate that solid‐state ¹³C single‐pulse excitation NMR spectroscopy provides a direct and robust analytical tool for studying the various tissues of Phalaenopsis in different growth and spiking induction periods.     

Structural studies on aryl‐substituted enaminoketones and their thio analogues. Part I. Analysis of high‐resolution 1H, 13C NMR and 13C CP MAS spectra combined with GIAO‐DFT calculations

A series of aryl‐substituted enaminoketones and their thio analogues in CDCl₃ solution and in the solid state were studied by the use of high‐resolution ¹H and ¹³C as well as ¹³C cross polarization magic angle spinning (CP MAS) NMR spectra in combination with gauge including atomic orbitals‐density functional theory (GIAO‐DFT) calculations performed at the B3PW91/6–311 + + G(d,p) level of theory using the B3PW91/6‐311 + + G(d,p)‐optimized geometries. The analysis of the ¹³C NMR spectra in solution was done by using the Incredible Natural Abundance DoublE QUAntum Transfer Experiment (INADEQUATE) technique, whereas trends observed in the ¹³C shielding constants, calculated for the compounds studied, were a great help in assigning most of the signals in the ¹³C CP MAS NMR spectra. It was established on the basis of the experimental and theoretical NMR data that both groups of compounds exist in the form of Z‐s‐Z‐s‐E isomers in CDCl₃ solution as well as in the solid state, with the NH hydrogen atom involved in intramolecular hydrogen bonding. This conclusion is in agreement with the fact that some of the compounds studied reveal liquid‐crystalline properties. Three‐bond H, H and C, H coupling constants measured in solution played a crucial role in the structure elucidation. Copyright © 2009 John Wiley & Sons, Ltd.     

Solid‐State NMR investigations of anhydrous proton‐conducting acid–base poly(acrylic acid)– poly(4‐vinyl pyridine) polymer blend system: A study of hydrogen bonding and proton conduction

NMR studies of the structure and dynamics of a system composed of the acidic polymer poly(acrylic acid) (PAA) and the basic polymer poly(4‐vinyl pyridine) (P4VP) are presented. This system aims at the application of anhydrous proton‐conducting membranes that can be used at elevated temperatures at which the proton conduction of hydrated membranes breaks down. The ¹H NMR measurements have been preformed under fast magic angle spinning (MAS) conditions to achieve sufficient resolution and the applied ¹H NMR methods vary from simple ¹H MAS to double‐quantum filtered methods and two‐dimensional ¹H double‐quantum spectroscopy. The dynamic behavior of the systems has been investigated via variable temperature ¹H MAS NMR. ¹³C cross‐polarization MAS NMR provides additional aspects of dynamic and structural features to complete the picture. Different types of acidic protons have been identified in the studied PAA‐P4VP systems that are nonhydrogen‐bonded free acidic protons, hydrogen‐bonded dicarboxylic dimers, and protons forming hydrogen bonds between carboxylic protons and ring nitrogens. The conversion of dimer structures in dried PAA to free carboxylic acid groups is accomplished at temperatures above 380 K. However, the stability of hydrogen‐bonding strongly depends on the hydration level of the polymer systems. The effect of hydration becomes less apparent in the complexes. An inverse proportionality between hydrogen‐bonding strength and proton conduction in the PAA‐P4VP acid–base polymer blend systems was established. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 138–155, 2009     

Cryogenic NMR spectroscopy of endohedral hydrogen-fullerene complexes

We have observed 1H NMR spectra of hydrogen molecules trapped inside modified fullerene cages under cryogenic conditions. Experiments on static samples were performed at sample temperatures down to 4.3 K, while magic-angle-spinning (MAS) experiments were performed at temperatures down to 20 K at spinning frequencies of 15 kHz. Both types of NMR spectra show a large increase in the intramolecular 1H-1H dipolar coupling at temperatures below 50 K, revealing thermal selection of a small number of spatial rotational states. The static and MAS spectra were compared to estimate the degree of sample heating in high-speed cryogenic MAS-NMR experiments. The cryogenic MAS-NMR data show that the site resolution of magic-angle-spinning NMR may be combined with the high signal strength of cryogenic operation and that cryogenic phenomena may be studied with chemical site selectivity.     

19F Magic Angle Spinning Dynamic Nuclear Polarization Enhanced NMR Spectroscopy

The introduction of high‐frequency, high‐power microwave sources, tailored biradicals, and low‐temperature magic angle spinning (MAS) probes has led to a rapid development of hyperpolarization strategies for solids and frozen solutions, leading to large gains in NMR sensitivity. Here, we introduce a protocol for efficient hyperpolarization of ¹⁹F nuclei in MAS DNP enhanced NMR spectroscopy. We identified trifluoroethanol‐d₃ as a versatile glassy matrix and show that 12 mm AMUPol (with microcrystalline KBr) provides direct ¹⁹F DNP enhancements of over 100 at 9.4 T. We applied this protocol to obtain DNP‐enhanced ¹⁹F and ¹⁹F–¹³C cross‐polarization (CP) spectra for an active pharmaceutical ingredient and a fluorinated mesostructured hybrid material, using incipient wetness impregnation, with enhancements of approximately 25 and 10 in the bulk solid, respectively. This strategy is a general and straightforward method for obtaining enhanced ¹⁹F MAS spectra from fluorinated materials.