Ultrahigh-field NMR Research Articles

Network connectivity in cesium borosilicate glasses: 17O multiple-quantum MAS and double-resonance NMR

17O solid-state NMR was used to study oxygen connectivity in ternary cesium borosilicate glasses. 17O multiple-quantum magic-angle spinning (MAS) NMR and ultrahigh-field 17O MAS NMR provide resolution of non-bridging and bridging oxygens, permitting their quantification for modeling short-range order. 17O{11B} rotational-echo double-resonance (REDOR) NMR is used to verify peak assignments for B–O–B, Si–O–B and Si–O–Si species, which agree well with a body of data from other alkali borosilicate glasses. The resulting bridging oxygen populations are in poor agreement with a model based on random network mixing, suggesting some degree of macroscopic segregation into silica-rich and borate-rich phases. Electron microprobe analysis reveals significant compositional variation between the batch and final products due to cesium volatilization at high temperatures. Both phase separation and elemental boil-off must be considered to account fully for the 17O MAS NMR results.

Ultra-high Field NMR Approaches to the Interaction between Ganglioside Clusters and Amyloid β

Ultra-high Field NMR Approaches to the Interaction between Ganglioside Clusters and Amyloid β

Chemistry in France: A Hotbed for New Schools of Thought

How is chemistry standing in the land of Lavoisier, while we re celebrating the 100th anniversary of the Nobel Prize in Chemistry to Paul Sabatier and Victor Grignard, within a rapidly changing higher education and research landscape? France has a long-standing tradition of research and innovation in chemistry, and its chemical industry (ranked fifth in the world) is still a strong pillar of French economic development. More than 3300 chemical companies directly employ 200000 people (inducing 600000 indirect jobs). Most of these are small or medium companies, together with some large industrial groups such as Total, Arkema, Rhodia, Michelin, and Air Liquide. This strong industrial activity has generated, in the first part of the 20th century, the foundation of several chemistry and chemical engineering graduate schools all over the country, attracting very good students educated as chemical engineers to amasters level. On the academic side, some 5300 researchers and 2700 technical staff work in chemistry laboratories and teams, located in the most important French academic cities. All of the main research topics are addressed in the core of chemical science and in all of its interfaces with physics (such as materials science, nanosciences, soft matter, spectroscopies), life sciences (medicinal chemistry, bioinspired chemistry, structural biology), and engineering (optoelectronic devices, energy storage, metallurgy).

NMR and mass spectrometric characterization of vinblastine, vincristine and some new related impurities—Part II

In the course of developing a new, improved process at Gedeon Richter for the production of the “bisindole” alkaloids vinblastine (VLB) and vincristine (VCR), some novel VLB/VCR-related trace impurities were detected by analytical HPLC at the production site. Repeated attempts to isolate and purify these unknown impurities by preparative liquid chromatography yielded small amounts of materials whose main components were the unknown impurities, but were still contaminated with other VLB/VCR-related compounds. In spite of these difficulties, by using a combination of high-resolution (LC–)MS/MS and off-line 1D and 2D ultra high-field NMR techniques and leaning on the relevant spectroscopic data for VLB and VCR as discussed in Part 1 [1], we could unambiguously solve the structures of, and could give a complete spectral characterization for, the trace impurities. Among these, although “cyclo-VCR” (impurity-2), “[VCR]-C(16)-COOEt” (impurity-4) and “[VLB]-C(16)-COOEt” (impurity-5) are known synthetic VLB/VCR-derivatives, and “[VLB]-C(14′)-OH(α)” is a known natural alkaloid (leurocolombine), they are new VLB/VCR impurities, and “[VCR]-N(4′)-C(21′)-iminium-salt” (impurity-3) is also a new chemical structure which provides direct proof of a hypothetic metabolic pathway of VLB/VCR. The structure determination of impurity-4 and impurity-5, and the rationalization of their origin was a particularly challenging task: since VCR is produced by the oxidation of VLB, it may be assumed that [VCR]-C(16)-COOEt (impurity-4) originates from the oxidization of [VLB]-C(16)-COOEt (impurity-5). This is consistent with the finding that [VLB]-C(16)-COOEt (impurity-5) could be detected by LC–MS/MS in the raw VLB samples in similar amounts as [VCR]-C(16)-COOEt (impurity-4) in the final VCR product. Our investigations indicate that [VLB]-C(16)-COOEt (impurity-5) does not form directly from VLB during extraction or chromatographic separation, suggesting that it may be a new natural product.

NMR and mass spectrometric characterization of vinblastine, vincristine and some new related impurities – Part I

In the course of exploring the possibilities of developing a new, improved process at Gedeon Richter for the production of the “bisindole” alkaloids vinblastine (VLB) and vincristine (VCR), some novel VLB/VCR-related trace impurities were detected by analytical HPLC. Following isolation by preparative HPLC, a combination of 1D and 2D ultra high-field NMR and high-resolution (HR) (LC-)MS/MS studies allowed the structural identification and complete spectral characterization of several hitherto unpublished VLB/VCR-analogue impurities. Since the impurities could not be isolated in entirely pure forms and were available only in minute, mass-limited quantities, accessing the spectral information needed for their ab initio structure determination was met with various practical difficulties. Successful structure determination therefore relied heavily on the availability and use of detailed and definitive spectral data for both VLB and VCR. In particular, the utilization of detailed 1H, 13C, and 15N NMR assignments as well as 1H–1H, 1H–13C and 1H–15N spin–spin connectivities pertaining to different solvents for VLB/VCR base and sulphate salt was required. Although NMR studies on VLB base and other bisindoles were reported earlier in the literature, an NMR characterization of VLB and VCR under the above-mentioned circumstances and using ultra-high field instrumentation is either scarcely available or entirely lacking, therefore the necessary data had to be obtained in-house. Likewise, a modern tandem HR-ESI-MS/MSn fragmentation study of VLB and VCR has not been published yet. In the present paper we therefore give a thorough NMR and MS characterization of VLB and VCR specifically with a view to filling this void and to provide sufficiently extensive and solid reference data for the structural investigation of the aforementioned VLB/VCR impurities. Besides being scientifically relevant in its own right, the disclosed data should be useful for anyone interested in VLB/VCR-related molecules at a structural level.

73Ge Solid-State NMR of Germanium Oxide Materials: Experimental and Theoretical Studies

A comprehensive series of crystalline germanates has been studied by ultrahigh-field 73Ge NMR and quantum chemical calculations. Despite its low gyromagnetic ratio, low natural abundance and large quadrupole moment, interpretable spectra were obtained in almost all cases, demonstrating that 73Ge is an accessible NMR nucleus. The spectra yield a wide range of quadrupole coupling constants (CQ = 9 to 35 MHz), with calculations indicating a range twice that, which are rationalized principally in terms of the variation in Ge−O bond lengths. The isotropic chemical shifts appear to fall into distinct regions for four-, five-, and six-coordinate Ge, with increasing coordination number corresponding to lower frequencies. Both CASTEP and WIEN2k consistently underestimate the CQs, suggesting that the exchange-correlation functional is poorly optimized for these systems. 73Ge NMR spectra of alkali germanate glasses are broad and featureless, rendering them difficult to interpret in terms of specific structural eleme...

Comparing quantum-chemical calculation methods for structural investigation of zeolite crystal structures by solid-state NMR spectroscopy

Combining quantum-chemical calculations and ultrahigh-field NMR measurements of (29)Si chemical shielding (CS) tensors has provided a powerful approach for probing the fine details of zeolite crystal structures. In previous work, the quantum-chemical calculations have been performed on 'molecular fragments' extracted from the zeolite crystal structure using Hartree-Fock methods (as implemented in Gaussian). Using recently acquired ultrahigh-field (29) Si NMR data for the pure silica zeolite ITQ-4, we report the results of calculations using recently developed quantum-chemical calculation methods for periodic crystalline solids (as implemented in CAmbridge Serial Total Energy Package (CASTEP) and compare these calculations to those calculated with Gaussian. Furthermore, in the context of NMR crystallography of zeolites, we report the completion of the NMR crystallography of the zeolite ITQ-4, which was previously solved from NMR data. We compare three options for the 'refinement' of zeolite crystal structures from 'NMR-solved' structures: (i) a simple target-distance based geometry optimization, (ii) refinement of atomic coordinates in which the differences between experimental and calculated (29)Si CS tensors are minimized, and (iii) refinement of atomic coordinates to minimize the total energy of the lattice using CASTEP quantum-chemical calculations. All three refinement approaches give structures that are in remarkably good agreement with the single-crystal X-ray diffraction structure of ITQ-4.

Up-and-down topological mode of amyloid β-peptide lying on hydrophilic/hydrophobic interface of ganglioside clusters

Growing evidence has indicated that GM1 ganglioside specifically interacts with Amyloid beta-peptide (Abeta) and thereby promotes Alzheimer's disease-associated Abeta assembly. To characterize the conformation of Abeta bound to the ganglioside, we performed 920 MHz ultra-high field NMR analyses using isotopically labeled Abeta(1-40) in association with GM1 and lyso-GM1 micelles. Our NMR data revealed that (1) Abeta(1-40) forms discontinuous alpha-helices at the segments His(14)-Val(24) and Ile(31)-Val(36) upon binding to the gangliosidic micelles, leaving the remaining regions disordered, and (2) Abeta(1-40) lies on hydrophobic/hydrophilic interface of the ganglioside cluster exhibiting an up-and-down topological mode in which the two alpha-helices and the C-terminal dipeptide segment are in contact with the hydrophobic interior, whereas the remaining regions are exposed to the aqueous environment. These findings suggest that the ganglioside clusters serve as a unique platform for binding coupled with conformational transition of Abeta molecules, rendering their spatial rearrangements restricted to promote specific intermolecular interactions.

Application of Ultrahigh‐Field 59Co Solid‐State NMR Spectroscopy in the Investigation of the 1,2‐Polybutadiene Catalyst [Co(C8H13)(C4H6)

Highly suitable: The 1,2-polybutadiene catalyst [Co(η3:η2-C8H13)(η4-C4H6)] (1) was isolated and structurally characterized by ultrahigh-field 59Co solid-state NMR spectroscopy, demonstrating the utility of this technique. It can be applied to study the formation mechanism of syndiotactic 1,2-polybutadiene. The picture shows a QCPMG (a) and a quadrupole echo 59Co NMR spectrum (b) as well as a simulated spectrum of 1 (c).

Probing Local Structure in Zeolite Frameworks: Ultrahigh-Field NMR Measurements and Accurate First-Principles Calculations of Zeolite 29Si Magnetic Shielding Tensors

The principal components of zeolite 29Si magnetic shielding tensors have been accurately measured and calculated for the first time. The experiments were performed at an ultrahigh magnetic field of 21.1 T in order to observe the small anisotropies of the 29Si shielding interactions that arise for Si atoms in near-tetrahedral geometries. A robust two-dimensional (2D) chemical shift anisotropy (CSA) recoupling pulse sequence was employed that enables quasi-static powder patterns to be resolved according to the isotropic chemical shifts. For the zeolites Sigma-2 and ZSM-12, it is demonstrated that the 29Si chemical shift (CS) tensor components measured by the recoupling experiment are in excellent agreement with those determined from spinning sidebands in slow magic-angle spinning (MAS) experiments. For the zeolite ZSM-5, the principal components of the 29Si CS tensors of 15 of the 24 Si sites were measured using the 2D CSA recoupling experiment, a feat that would not be possible with a slow MAS experiment due to the complexity of the spectrum. A simple empirical relationship between the 29Si CS tensors and local structural parameters could not be established. However, the 29Si magnetic shielding tensors calculated using Hartree-Fock ab initio calculations on clusters derived from the crystal structures are in excellent agreement with the experimental results. The accuracy of the calculations is strongly dependent on the quality of the crystal structure used in the calculation, indicating that the 29Si magnetic shielding interaction is extremely sensitive to the local structure around each Si atom. It is anticipated that the measurement and calculation of 29Si shielding tensors could be incorporated into the "NMR crystallography" of zeolites and other related silicate materials, possibly being used for structure refinements that may lead to crystal structures with very accurate Si and O atomic coordinates.

K-39 Quadrupolar and Chemical Shift Tensors for Organic Potassium Complexes and Diatomic Molecules

Solid-state potassium-39 NMR spectra of two potassium complexes of crown-ether-based organic ligands (1.KI and 2) have been acquired at 11.75 and 21.1 T and interpreted to provide information on the 39K quadrupolar and chemical shift tensors. The analyses reveal a large potassium chemical shift tensor span of 75+/-20 ppm for 1.KI. This appears to be the first such measurement for potassium in an organic complex, thereby suggesting the utility of potassium chemical shift tensors for characterizing organic and biomolecular K+ binding environments. Compound 2 exhibits a cation-pi interaction between K+ and a phenyl group, and therefore, the 39K NMR tensors obtained for this compound must be partly representative of this interaction. Analyses of potassium-39 spin-rotation data for gaseous 39K19F and 39K35Cl available from molecular beam experiments performed by Cederberg and co-workers reveal the largest potassium CS tensor spans known to date, 84.39 and 141 ppm, respectively. Collectively, the results obtained highlight the potential of ultrahigh-field potassium-39 solid-state NMR spectroscopy and, in particular, the wide range of the anisotropy of the potassium CS tensor when organic and diatomic systems are considered.

Ultra-high field NMR studies of antibody binding and site-specific phosphorylation of α-synuclein

Although biological importance of intrinsically disordered proteins is becoming recognized, NMR analyses of this class of proteins remain as tasks with more challenge because of poor chemical shift dispersion. It is expected that ultra-high field NMR spectroscopy offers improved resolution to cope with this difficulty. Here, we report an ultra-high field NMR study of α-synuclein, an intrinsically disordered protein identified as the major component of the Lewy bodies. Based on NMR spectral data collected at a 920 MHz proton frequency, we performed epitope mapping of an anti-α-synuclein monoclonal antibody, and furthermore, characterized conformational effects of phosphorylation at Ser129 of α-synuclein.

Symmetry-based recoupling of proton chemical shift anisotropies in ultrahigh-field solid-state NMR

A two-dimensional NMR experiment for estimating proton chemical shift anisotropies (CSAs) in solid powders under magic-angle spinning conditions is demonstrated in which 1H CSAs are reintroduced with a symmetry-based recoupling sequence while the individual proton sites are resolved according to their isotropic chemical shifts by magic-angle spinning (MAS) or combined rotation and multiple pulse (CRAMPS) homonuclear decoupling. The experiments where carried out on an ultrahigh-field solid-state NMR instrument (900 MHz 1H frequency) which leads to increased resolution and reliability of the measured 1H CSAs. The experiment is expected to be important for investigating hydrogen bonding in solids.

Field propagation phenomena in ultra high field NMR: A Maxwell–Bloch formulation

The principal advantage of NMR at high field is the concomitant increase in signal-to-noise ratio (SNR). This can be traded for improved spatial resolution and combined with parallel imaging to achieve higher temporal resolution. At high field strength, the RF-wavelength and the dimension of the human body complicate the development of NMR coils. For example, at 7 T, the wavelength in free space corresponds to about 1 m. The dielectric constant in tissue with a high water content can be as high as 70 and at a larmor frequency of 300 MHz, this corresponds to a wavelength inside tissue of less than 15 cm. The operating wavelength is thus comparable to the diameter of most body parts. To this end, both temporal and spatial variations of the excitation field must be taken into account in addition to the expected increase in conductivity. For all these reasons, we find the propagation of radiation at ultra high fields (>4 T) new phenomena commonly observed in quantum optics but traditionally negligible in NMR such as phase modulation of the excitation field such that the identity between pulse area and flip angle is no longer valid. In this paper, the emergence of field propagation phenomena in NMR experiments is analytically and numerically demonstrated. It is shown that in addition to the well-studied dielectric resonance phenomena at high magnetic fields (>4 T), field propagation effects transform the excitation pulse into an adiabatic excitation. The high field strength also mean that nonlinear effects such as self-induced transparency are now possible in NMR experiments.

93Nb NMR chemical shift scale for niobia systems

93Nb solid-state NMR spectra of a series of inorganic niobates with Nb in different oxygen coordination environments were measured. For all studied compounds the chemical shielding and quadrupole tensor parameters were determined using conventional and ultrahigh field NMR facilities, ultrahigh speed MAS, DQ STMAS, solid-echo and computer modeling. It has been demonstrated that the 93Nb isotropic chemical shift is sensitive to the coordination number of Nb sites. For the first time the 93Nb NMR chemical shift scale for NbO x polyhedra in solid materials has been proposed: for four-coordinated Nb sites, the isotropic shifts occur from −650 to −950 ppm; five-coordinated Nb sites have the isotropic shifts in the range of –900 to –980 ppm; for six-coordinated Nb sites the isotropic shifts vary from −900 to −1360 ppm; the shifts from −1200 to −1600 ppm are typical for seven-coordinated Nb sites; for eight-coordinated Nb sites the shifts are higher than −1400 ppm. The possible correlation between the value of the isotropic chemical shift and the ionic character of the NbO x –MO y polyhedra association has been suggested. The magnitude of the 93Nb quadrupole coupling constant depends on the local symmetry of Nb sites and may vary from hundreds of kHz to hundreds of MHz.

Zeolite Nanoclusters Coated onto the Mesopore Walls of SBA-15

Ultrahigh-field 27Al MAS and MQMAS NMR and 129Xe NMR were used to characterize the zeolite-coated SBA-15 materials. This study shows evidence that zeolite nanoclusters are coated on the mesopore surface of SBA-15. These techniques are useful for the detection of zeolite nanoclusters and different aluminum environments in zeolite/aluminosilicate composites, which are difficult or even impossible to detect by conventional techniques.

Using simple 13C NMR linewidth and relaxation measurements to make detailed chemical shift assignments in triacylglycerols and related compounds

Two simple experiments measuring the 13C linewidths ν 1/2 and spin–lattice relaxation times T 1 of each of the signals in the spectrum of trilinolein indicate that the ν 1/2 and T 1 values are consistent with the different degrees of motional freedom expected for the various 13C nuclei. However, for each chain, the ν 1/2 and T 1 measurements indicate a small reversal in mobility at C-10 relative to C-9 before motional freedom again steadily increases on each chain starting at C-11. The T 1 experiment allows unambiguous assignments of the C-8 signal and C-14 signal, which differ by only 0.010 ppm. Measurements of 13C ν 1/2 and T 1 values on tripalmitin provide secure assignments for the C-5 and C-6 signals, for which conflicting assignments have been reported. The T 1 measurements also show that among the tightly clustered C-8 through C-12 signals, the C-11 signals are the most downfield, while the C-12 signals are the most upfield, again contrary to a previous report. Similar measurements of 13C ν 1/2 and T 1 values on other triacylglycerols or related compounds may prove equally useful in making chemical shift assignments and detecting any discontinuities in motional freedom along a chain. The benefits and possible limitations of ultrahigh field NMR for studying triacylglycerols and related compounds are discussed.

MAS NMR Studies on the Dealumination of Zeolite MCM-22

The dealumination of Zeolite MCM-22 by calcination or hydrothermal treatment was investigated by conventional multinuclear solid-state NMR and checked by an ultrahigh-field NMR experiments (19.6 T) with a very fast spin rate (19.1 kHz). The presence or variation of different species (e.g. silanol nest, 4-coordinated framework, 6-coordinated and 5-coordinated extraframework aluminum) during or after dealumination was detected, and their changes were followed. Four tetrahedral framework aluminum sites were identified upon the 27Al MAS NMR experiments showing chemical shifts at 61.5, 57.0, 53.5, and 50.0 ppm, respectively. After hydrothermal treatment, aluminum at 57.0 ppm which corresponded to T3, T4, T7, T10, and T12 sites in the orthorhombic model is preferentially expelled from the zeolitic framework. Moreover, a dehydroxylation process without the release of four-coordinated framework Al also happened, resulting in the presence of a tricoordinated framework aluminum species, which, together with the formation of tetrahedral framework aluminum species, may serve as the Lewis acid site of the zeolite.

Isolation and identification by 2D NMR of two new complex saponins from Michrosechium helleri

Two complex saponins, amole F and G, were characterized and their spectra were assigned using only 1D and 2D 1H and NMR methods. Amole F and G have seven and six monosaccharides, respectively, linked to the triterpene aglycone bayogenin. In addition to standard 2D methods, a series of TOCSY spectra with different mixing times and a high-resolution coupled HSQC spectrum were particularly useful for assigning the monosaccharide units. It is concluded that saponins of this complexity are approaching the limit of structural complexity that can be solved by NMR alone, although the limit might be pushed further by access to ultra-high field NMR spectrometers. © 1998 John Wiley & Sons, Ltd.

Isolation and identification by 2D NMR of two new complex saponins fromMichrosechium helleri

Two complex saponins, amole F and G, were characterized and their spectra were assigned using only 1D and 2D 1H and NMR methods. Amole F and G have seven and six monosaccharides, respectively, linked to the triterpene aglycone bayogenin. In addition to standard 2D methods, a series of TOCSY spectra with different mixing times and a high-resolution coupled HSQC spectrum were particularly useful for assigning the monosaccharide units. It is concluded that saponins of this complexity are approaching the limit of structural complexity that can be solved by NMR alone, although the limit might be pushed further by access to ultra-high field NMR spectrometers. © 1998 John Wiley & Sons, Ltd.