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.     

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.     

1H magic angle rotation NMR in polymer studies

The principles of the method of NMR line narrowing by measurement with spinning of the sample about the magic axis (MAR-NMR) are introduced, with particular emphasis on the effects of internal motion upon the possibilities and limitations of the method. The applications of the method in ¹H-NMR studies of polymer structure and dynamics are then reviewed. Due to both theoretical and experimental limitations, narrowing of dipolar broadened NMR lines by MAR can be observed in ¹H NMR spectra only in those cases where internal motion is anisotropic, or in heterogeneous systems where line width is limited by differences of magnetic susceptibility. In polymers, both solid and liquid, the method makes possible differentiation between isotropic and anisotropic internal motion. In systems with anisotropic internal motion, MAR-NMR makes possible a characterization of motional codes which normally are obscured by residual dipolar interactions, as well as of geometrical restrictions upon these motions.     

Observation of (31)P-(31)P Indirect Spin-Spin Coupling in Copper-Bis(phosphine) Complexes by Two-Dimensional Solid-State NMR

The first observations of (31)P-(31)P indirect spin-spin (J) coupling in copper(I) phosphine complexes are reported for solid Cu(PPh(3))(2)X (X = NO(3)(-), BH(4)(-)). Values of (2)J((31)P,(31)P), 157 +/- 5 and 140 +/- 5 Hz for Cu(PPh(3))(2)NO(3) and Cu(PPh(3))(2)BH(4), respectively, have been obtained from two-dimensional (2D) J-resolved (31)P NMR spectra obtained under slow magic-angle spinning (MAS) conditions. In both complexes, the two phosphine ligands are crystallographically equivalent; thus, the two (31)P nuclei have identical isotropic chemical shifts. Under rapid sample spinning conditions, the (31)P MAS NMR spectra exhibit relatively sharp overlapping asymmetric quartets arising from (1)J((63/65)Cu,(31)P) and residual (63/65)Cu-(31)P dipolar interactions. No evidence of (2)J((31)P,(31)P) is apparent from the spectra obtained with rapid MAS; however, under slow MAS conditions there is evidence of homonuclear J-recoupling. Peak broadening due to heteronuclear dipolar interactions precludes measurement of (2)J((31)P,(31)P) from standard 1D (31)P MAS NMR spectra. It is shown that this source of broadening can be effectively eliminated by employing the 2D J-resolved experiment. For the two copper(I) phosphine complexes investigated in this study, the peak widths in the f(1) dimension of the 2D J-resolved (31)P MAS NMR spectra are about three times narrower than those found in the corresponding 1D (31)P MAS NMR spectra.     

NMR methods for studying the structure and dynamics of oncogenic and antihistaminic peptides in biomembranes

We present several applications of both wide-line and magic angle spinning (MAS) solid-state NMR of bicelles in which are embedded fragments of a tyrosine kinase receptor or enkephalins. The magnetically orientable bicelle membranes are shown to be of particular interest for studying the functional properties of lipids and proteins in a state that is very close to their natural environment. Quadrupolar, dipolar and chemical shielding interactions can be used to determine minute alterations of internal membrane dynamics and the orientation of peptides with respect to the membrane plane. MAS of bicelles can in turn lead to high-resolution proton spectra of hydrated membranes. Using deuterium-proton contrast methods one can then obtain pseudo-high-resolution proton spectra of peptides or proteins embedded in deuterated membranes and determine their atomic 3D structure using quasi-conventional liquid-state NMR methods.     

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.     

Sensitivity enhancement and heteronuclear distance measurements in biological 17O solid-state NMR

In this contribution we present a comprehensive approach to study hydrogen bonding in biological and biomimetic systems through 17O and 17O-1H solid-state NMR combined with density functional theory calculations of 17O and 1H NMR parameters. We explore the signal enhancement of 17O in L-tyrosine.HCl using repetitive double-frequency swept radio frequency pulses in solid-state NMR. The technique is compatible with high magnetic fields and fast magic-angle spinning of the sample. A maximum enhancement by a factor of 4.3 is obtained in the signal-to-noise ratio of the selectively excited 17O central transition in a powdered sample of 17Oeta-L-tyrosine.HCl at an external field of 14.1 T and a spinning frequency of 25 kHz. As little as 128 transients lead to meaningful 17O spectra of the same sample at an external field of 18.8 T and a spinning frequency of 50 kHz. Furthermore we employed supercycled symmetry-based pulse sequences on the protons to achieve heteronuclear longitudinal two-spin-order (IzSz) recoupling to determine 17O-1H distances. These sequences recouple the heteronuclear dipolar 17O-1H couplings, where dipolar truncation is absent, while decoupling the homonuclear proton dipolar interactions. They can be applied at fast magic-angle-spinning frequencies up and beyond 50 kHz and are very robust with respect to 17O quadrupolar couplings and both 17O and 1H chemical shift anisotropies, which makes them suitable for the use at high external magnetic fields. The method is demonstrated by determining the 17Oeta-1H distance in L-tyrosine.HCl at a spinning frequency of 50 kHz and an external field of 18.8 T.     

Solid-state 13C-NMR analysis of hypercrosslinked polystyrene

Hypercrosslinked polystyrenes, synthesized by reaction of linear or lightly crosslinked polystyrene with chloromethyl methyl ether (CME) and a Lewis acid in a good solvent, swell even in nonsolvents for polystyrene. Structures and dynamics of hypercrosslinked polystyrenes in both dry solid and solvent-swollen gel states have been determined by ¹³C-NMR spectroscopy. Deconvolution of ¹³C solid-state CP/MAS spectra gave the relative numbers of quaternary carbon atoms in monosubstituted and disubstituted benzenes. A typical sample, crosslinked by reaction of a mixture containing 0.5 mol of CME per mol of repeat units, contains 35% of unreacted and 65% of crosslinked aromatic rings, and no residual chloromethyl groups. Gels swollen in CDCl₃ and in CH₃OH have residual static dipolar interactions enabling crosspolarization and require magic angle spinning (MAS) and high power ¹H decoupling to reduce chemical shift anisotropy from ∼ 10⁴ Hz to ∼ 10³ Hz. A single proton spin-lattice relaxation time in the rotating frame measured from all peaks in the ¹³C spectra of dry samples indicates homogeneity on a nanometer scale. Proton NMR line widths indicate no substantial molecular motions in a dry hypercrosslinked polystyrene up to at least 200°C. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 695–701, 1997     

Satellite transitions acquired in real time by magic angle spinning (STARTMAS): "ultrafast" high-resolution MAS NMR spectroscopy of spin I=3/2 nuclei

The satellite transitions acquired in real time by magic angle spinning (STARTMAS) NMR experiment combines a train of pulses with sample rotation at the magic angle to refocus the first- and second-order quadrupolar broadening of spin I=3/2 nuclei in a series of echoes, while allowing the isotropic chemical and quadrupolar shifts to evolve. The result is real-time isotropic NMR spectra at high spinning rates using conventional MAS equipment. In this paper we describe in detail how STARTMAS data can be acquired and processed with ease on commercial equipment. We also discuss the advantages and limitations of the approach and illustrate the discussion with numerical simulations and experimental data from four different powdered solids.     

Homonuclear J-couplings and rotationally induced sideband enhancements in NMR spectra of rotating solids

We demonstrate direct detection of ¹³C-¹³C J-couplings in magic angle sample spinning NMR spectra despite the presence of the much larger homogeneous broadening caused by the homonuclear dipolar couplings. Carbon-carbon J-couplings were observed in doubly ¹³C-enriched samples of sodium acetate, glycine and glucose. The resolved J-coupling permits carbon-carbon connectivities to be established with standard two-dimensional techniques. Interesting spectral features are observed when the rotational sidebands of the coupled spins overlap: when a sideband from a dipolar-coupled pair approaches the centerband of its partner, a significant enhancement in sideband intensity is observed as well as small shifts in the resonance frequency.     

On the orientational dependence of resolution in 1H solid-state NMR, and its role in MAS, CRAMPS and delayed-acquisition experiments

Numerical simulations and experiments are used to show that the spin dynamics of the dipolar-coupled networks in solids is often strongly dependent on crystallite orientation. In particular, different rates of dephasing of the magnetisation mean that NMR signals obtained at longer dephasing times are dominated by orientations in which the local dipolar coupling strength is relatively weak. This often leads to a distinct improvement in spectral resolution as the dephasing time is increased. The effects are particularly noticeable under magic-angle spinning (MAS), but are also observed when homonuclear decoupling is used to reduce the rate of dipolar dephasing. Numerical simulation is seen to be a powerful and easily used tool for understanding the behaviour of solid-state NMR experiments involving dipolar-coupled networks. The implications for solid-state NMR spectra of abundant spins acquired under MAS and homonuclear decoupling are discussed, as well as insights provided into the performance of 'delayed-acquisition' and 'constant-time' experiments.     

Effects of external electric fields on 1H, 19F,and 14N NMR spectra of 2, 4, 6-trifluoronitrobenzene

When a polar liquid is subjected to an electric field, the dipoles obtain a small average orientation. At sufficiently high field strengths direct spin—spin dipolar and quadrUpolar electric field interactions may modify the NMR spetrum.NMR electric field experiments are reported for the proton, fluorine, and nitrogen NMR spectra of neat 2, 4, 6-trifluoronitrobenzene. The observed alignment values are smaller than those predicted on the basis of Onsager's theory.The ¹⁴N quadrupole coupling constant as been deduced from a comparison of the qUadrupolar and dipolar electric field effects.An upper limit of the absolute value of the anisotropy of the para-¹⁹F chemical shift has been inferred from the absence of a detectable displacement of the resonance on application of an electric field.     

The dynamics of the CH3CN molecule in the isotropic phase and in a nematic solution

Abstract

NMR lineshape studies of acelonitrile in the isotropic and the liquid-crystalline nematic phase of PCH have been performed. The scalar relaxation of the second kind due to the presence of the ¹⁴N quadrupolar nucleus has been confirmed as the most important relaxation mechanism for this molecule in both the isotropic and the anisotropic phase. It has been found largely responsible for the selective broadening on ¹³C and ¹H transitions. A minor contribution arising from intramolecular dipolar relaxation mechanism has also been investigated. Linewidth analysis of the NMR spectra allowed us to determine the quadrupolar relaxation time T _IN of the ¹⁴N nucleus. This is connected to the correlation time for rotational diffusion perpendicular to the molecular symmetry axis. A possible explanation of a residual selective broadeining which effects the ¹³C and ¹H NMR transitions and is not taken into account by this mechanism, is also given.     

Solid-state NMR fermi contact and dipolar shifts in organometallic complexes and metalloporphyrins

We have used density functional theory methods to investigate the solid-state "magic-angle" spinning (MAS) NMR and single-crystal NMR/ENDOR spectra of paramagnetic organometallic complexes and metalloporphyrins. The solid-state MAS NMR chemical shifts (including both diamagnetic and hyperfine contributions) are predicted with a slope of 1.007 and an R2 = 0.967, corresponding to a 28 ppm (or 6.3%) error over the entire 442 ppm range. Single-crystal ENDOR hyperfine values, including both isotropic Fermi contact and dipolar couplings, are predicted with a slope of 1.009 and an R2 = 0.998, corresponding to a 0.93 MHz (or 1.2%) error over the entire 78.37 MHz range. In addition, single-crystal NMR shifts (including both hyperfine terms) are predicted with an R2 = 0.961. The ability to compute solid-state MAS NMR and single-crystal NMR/ENDOR data should facilitate the use of these techniques in investigating paramagnetic metal complexes and should be of particular use in studying paramagnetic metalloproteins, where structures are less accurately known.     

Self-Assembly of DNA and RNA Building Blocks Explored by Nitrogen-14 NMR Crystallography: Structure and Dynamics

The isotopic enrichment of nucleic acids with nitrogen-15 is often carried out by solid-phase synthesis of oligonucleotides using phosphoramidite precursors that are synthetically demanding and expensive. These synthetic challenges, combined with the overlap of chemical shifts, explain the lag of nitrogen-15 NMR studies of nucleic acids behind those of proteins. For the structural characterization of DNA and RNA-related systems, new NMR methods that exploit the naturally occurring 99.9 % abundant nitrogen-14 isotope are therefore highly desirable. In this study, we have investigated nitrogen-14 spectra of self-assembled quartets based on the nucleobase guanine in the solid state by means of magic-angle spinning NMR spectroscopy. The network of dipolar proton–nitrogen couplings between neighboring stacked purine units is probed by 2D spectra based on ¹H→¹⁴N→¹H double cross-polarization. Interplane dipolar contacts are identified between the stacked G quartets. The assignment is supported by density functional theory (DFT) calculations of the anisotropic chemical shifts and quadrupolar parameters. The experimental spectra are fully consistent with internuclear distances obtained in silico. Averaging of chemical shifts due to internal motions can be interpreted by semiempirical calculations. This method can easily be extended to synthetic G quartets based on nucleobase or nucleoside analogs and potentially to oligonucleotides.     

Cross-polarization/magic-angle spinning NMR studies of polymorphism: Cortisone acetate

¹³C CPMAS spectra have been recorded for nine samples of cortisone acetate (21-acetoxy-17α-hydroxy-4-pregnene-3,11,20-trione, C₂₃H₃₀O₆) and the observed resonances are attributed to six crystalline forms. Two of these forms are novel. The spectra of all six are entirely distinct. The resonances are assigned to individual carbon atoms on the basis of previously-determined solution-state spectra together with dipolar dephasing experiments and observations of shielding anisotropies as reflected in spinning sideband manifolds. The results are interpreted in relation to known crystal structures. The value of solid-state NMR for analysis of polymorph mixtures is emphasized.     

Solid State NMR of Drugs: Soluble Aspirin

Abstract

Natural abundance ¹³C NMR spectra of a soluble aspirin and model mixtures of acetylsalicylic acid with buffering components have been recorded in the solid state by using the combined techniques of cross polarization, high-power decoupling and magic-angle spinning. The solid-state spectrum of the soluble aspirin tablet showed more resonances than the solution spectrum. These multiplicities were originated in the buffer mixture containing citric and tartaric acid, as well as their salts. Solid-state ¹³C NMR was therefore found to provide information that is lost in the solution spectrum due to the fast proton exchange between the organic acids and their conjugated salts.     

The structure and conformation of a mesogenic compound between almost zero and almost complete orientational order

The conformational distributions in molecules that form liquid crystalline phases are predicted to depend strongly on orientational order. Results are presented here to test this hypothesis. The mesogen 4‐hexyloxy‐4′‐cyanobiphenyl (6OCB) has been studied by NMR spectroscopy in the isotropic phase and in the nematic phase. In the isotropic phase the field‐induced orientational ordering produces small dipolar couplings between ¹³C and ¹H nuclei, which were determined from the ¹³C spectra. Couplings between ¹H nuclei were also obtained using 2D selective refocusing experiments. In the nematic phase, both ¹H–¹H dipolar couplings and quadrupolar splittings for deuterium nuclei were measured for partially‐deuterated samples. Both proton and deuterium spectra were also obtained for 6OCB in an equimolar mixture with 4‐(ethoxybenzylidene)‐4′‐butylaniline (EBBA). This mixture exhibits SmA and SmB phases. The data obtained from these experiments has been analysed to yield the probability distribution of the conformations in this molecule generated by rotations about bonds. It is found that there is a substantial influence of the orientational order of the molecules on these distributions.     

High-resolution characterization of liquid-crystalline [60]fullerenes using solid-state nuclear magnetic resonance spectroscopy

Liquid-crystalline materials containing fullerenes are valuable in the development of supramolecular switches and in solar cell technology. In this study, we characterize the liquid-crystalline and dynamic properties of fullerene-containing thermotropic compounds using solid-state natural abundance (13)C NMR experiments under stationary and magic angle spinning sample conditions. Chemical shifts spectra were measured in isotropic, liquid-crystalline nematic and smectic A and crystalline phases using one-dimensional (13)C experiments, while two-dimensional separated local-field experiments were used to measure the (1)H- (13)C dipolar couplings in mesophases. Chemical shift and dipolar coupling parameters were used to characterize the structure and dynamics of the liquid-crystalline dyads. NMR data of fullerene-containing thermotropic liquid crystals are compared to that of basic mesogenic unit and mesomorphic promoter compounds. Our NMR results suggest that the fullerene-ferrocene dyads form highly dynamic liquid-crystalline phases in which molecules rotate fast around the symmetry axis on the characteristic NMR time scale of approximately 10 (-4) s.     

Solid-state high-resolution 29Si NMR in zunyite

High-resolution ²⁹Si NMR spectra of zunyite Si₅Al₁₃O₂₀ (OH,F)₁₈Cl have been studied by magic-angle sample spinning in combination with high-power proton decouplina and polarization transfer. The isotropic ²⁹Si chemical shift depends mainly on the number of Si-O-Si bridges and the bond angles in these bridges connecting the different SiO₄ tetrahedra.