Showing papers on "Solid-state nuclear magnetic resonance published in 2019"

DNP‐Supported Solid‐State NMR Spectroscopy of Proteins Inside Mammalian Cells

Abstract: Elucidating at atomic level how proteins interact and are chemically modified in cells represents a leading frontier in structural biology. We have developed a tailored solid-state NMR spectroscopic approach that allows studying protein structure inside human cells at atomic level under high-sensitivity dynamic nuclear polarization (DNP) conditions. We demonstrate the method using ubiquitin (Ub), which is critically involved in cellular functioning. Our results pave the way for structural studies of larger proteins or protein complexes inside human cells, which have remained elusive to in-cell solution-state NMR spectroscopy due to molecular size limitations.

Molecular Interactions in Posaconazole Amorphous Solid Dispersions from Two-Dimensional Solid-State NMR Spectroscopy.

Abstract: Molecular interactions between the active pharmaceutical ingredient and polymer have potentially substantial impacts on the physical stability of amorphous solid dispersions (ASDs), presumably by manipulating molecular mobility and miscibility. However, structural details for understanding the nature of the molecular contacts and mechanistic roles in various physicochemical and thermodynamic events often remain unclear. This study provides a spectroscopic characterization of posaconazole (POSA) formulations, a second-generation triazole antifungal drug (Noxafil, Merck & Co., Inc., Kenilworth, NJ, USA), at molecular resolution. One- and two-dimensional (2D) solid-state NMR (ssNMR) techniques including spectral editing, heteronuclear 1H-13C, 19F-13C, 15N-13C, and 19F-1H polarization transfer, and spin correlation and ultrafast magic angle spinning, together with the isotopic labeling strategy, were utilized to uncover molecular details in POSA ASDs in a site-specific manner. Active groups in triazole and difluorophenyl rings exhibited rich but distinct categories of interactions with two polymers, hypromellose acetate succinate and hypromellose phthalate, including intermolecular O-H···O═C and O-H···F-C hydrogen bonding, π-π aromatic packing, and electrostatic interaction. Interestingly, the chlorine-to-fluorine substituent in POSA, one of the major structural differences from itraconazole that could facilitate binding to the biological target, offers an additional contact with the polymer. These findings exhibit 2D ssNMR as a sensitive technique for probing sub-nanometer structures of pharmaceutical materials and provide a structural basis for optimizing the type and strength of drug-polymer interactions in the design of amorphous formulations.

Understanding hydrogen-bonding structures of molecular crystals via electron and NMR nanocrystallography

Abstract: Understanding hydrogen-bonding networks in nanocrystals and microcrystals that are too small for X-ray diffractometry is a challenge. Although electron diffraction (ED) or electron 3D crystallography are applicable to determining the structures of such nanocrystals owing to their strong scattering power, these techniques still lead to ambiguities in the hydrogen atom positions and misassignments of atoms with similar atomic numbers such as carbon, nitrogen, and oxygen. Here, we propose a technique combining ED, solid-state NMR (SSNMR), and first-principles quantum calculations to overcome these limitations. The rotational ED method is first used to determine the positions of the non-hydrogen atoms, and SSNMR is then applied to ascertain the hydrogen atom positions and assign the carbon, nitrogen, and oxygen atoms via the NMR signals for 1H, 13C, 14N, and 15N with the aid of quantum computations. This approach elucidates the hydrogen-bonding networks in L-histidine and cimetidine form B whose structure was previously unknown.

Probing O-H Bonding Through Proton Detected 1H-17O Double Resonance Solid-State NMR Spectroscopy

Abstract: The ubiquity of oxygen in organic, inorganic, and biological systems has stimulated the application and development of 17O solid-state NMR spectroscopy as a probe of molecular structure and dynamic...

De novo prediction of cross-effect efficiency for magic angle spinning dynamic nuclear polarization.

Abstract: Magic angle spinning dynamic nuclear polarization (MAS-DNP) has become a key approach to boost the intrinsic low sensitivity of NMR in solids. This method relies on the use of both stable radicals as polarizing agents (PAs) and suitable high frequency microwave irradiation to hyperpolarize nuclei of interest. Relating PA chemical structure to DNP efficiency has been, and is still, a long-standing problem. The complexity of the polarization transfer mechanism has so far limited the impact of analytical derivation. However, recent numerical approaches have profoundly improved the basic understanding of the phenomenon and have now evolved to a point where they can be used to help design new PAs. In this work, the potential of advanced MAS-DNP simulations combined with DFT calculations and high-field EPR to qualitatively and quantitatively predict hyperpolarization efficiency of particular PAs is analyzed. This approach is demonstrated on AMUPol and TEKPol, two widely-used bis-nitroxide PAs. The results notably highlight how the PA structure and EPR characteristics affect the detailed shape of the DNP field profile. We also show that refined simulations of this profile using the orientation dependency of the electron spin–lattice relaxation times can be used to estimate the microwave B1 field experienced by the sample. Finally, we show how modelling the nuclear spin–lattice relaxation times of close and bulk nuclei while accounting for PA concentration allows for a prediction of DNP enhancement factors and hyperpolarization build-up times.

High-Resolution 17O NMR Spectroscopy of Structural Water.

Abstract: The importance of studying site-specific interactions of structurally similar water molecules in complex systems is well known. We demonstrate the ability to resolve four distinct bound water environments within the crystal structure of lanthanum magnesium nitrate hydrate via 17O solid state nuclear magnetic resonance (NMR) spectroscopy. Using high-resolution multidimensional experiments at high magnetic fields (18.8-35.2 T), each individual water environment was resolved. The quadrupole coupling constants and asymmetry parameters of the 17O of each water were determined to be between 6.6 and 7.1 MHz, 0.83 and 0.90, respectively. The resolution of the four unique, yet similar, structural waters within a hydrated crystal via 17O NMR spectroscopy demonstrates the ability to decipher the unique electronic environment of structural water within a single hydrated crystal structure.

Surface enhanced dynamic nuclear polarization solid-state NMR spectroscopy sheds light on Brønsted–Lewis acid synergy during the zeolite catalyzed methanol-to-hydrocarbon process

Abstract: After a prolonged effort over two decades, the reaction mechanism of the zeolite-catalyzed methanol-to-hydrocarbon (MTH) process is now well-understood: the so-called 'direct mechanism' (via direct coupling of two methanol molecules) is responsible for the formation of the initial carbon-carbon bonds, while the hydrocarbon pool (HCP)-based dual cycle mechanism is responsible for the formation of reaction products. While most of the reaction events occur at zeolite Bronsted acid sites, the addition of Lewis acid sites (i.e., via the introduction of alkaline earth cations like calcium) has been shown to inhibit the formation of deactivating coke species and hence increase the catalyst lifetime. With the aim to have an in-depth mechanistic understanding, herein, we employ magic angle spinning surface-enhanced dynamic nuclear polarization solid-state NMR spectroscopy to illustrate that the inclusion of Lewis acidity prevents the formation of carbene/ylide species on the zeolite, directly affecting the equilibrium between arene and olefin cycles of the HCP mechanism and hence regulating the ultimate product selectivity and catalyst lifetime.

Anthracene as a Launchpad for a Phosphinidene Sulfide and for Generation of a Phosphorus-Sulfur Material Having the Composition P2S, a Vulcanized Red Phosphorus That Is Yellow.

Abstract: Thermolysis of a pair of dibenzo-7-phosphanorbornadiene compounds is shown to lead to differing behaviors: phosphinidene sulfide release and formation of amorphous P2S. These compounds, tBuP(S)A (1, A = C14H10 or anthracene; 59% isol. yield) and HP(S)A (2; 63%), are available through thionation of tBuPA and the new secondary phosphine HPA (5), prepared from Me2NPA and DIBAL-H in 50% yield. Phosphinidene sulfide [ tBuP═S] transfer is shown to proceed efficiently from 1 to 2,3-dimethyl-1,3-butadiene to form Diels-Alder product 3 with a zero-order dependence on diene. Platinum complex (Ph3P)2Pt(η2- tBuPS) (4, 47%) is also accessed from 1 and structurally characterized. In contrast, heating parent species 2 (3 h, 135 °C) under vacuum instead produces an insoluble, nonvolatile yellow residual material 6 of composition P2S that displays semiconductor properties with an optical band gap of 2.4 eV. Material 6 obtained in this manner from molecular precursor 2 is in a poorly characterized portion of the phosphorus-sulfur phase diagram and has therefore been subjected to a range of spectroscopic techniques to gain structural insight. X-ray spectroscopic and diffraction techniques, including Raman, XANES, EXAFS, and PDF, reveal 6 to have similarities with related compounds including P4S3, Hittorf's violet phosphorus. Various possible structures have been explored as well using quantum chemical calculations under the constraint that each phosphorus atom is trivalent with no terminal sulfide groups, and each sulfur atom is divalent. The structural conclusions are supported by data from phosphorus-31 magic angle spinning (MAS) solid state NMR spectroscopy, bolstering the structural comparisons to other phosphorus-sulfur systems while excluding the formulation of P2S as a simple mixture of P4S3 and phosphorus.

Solid-state NMR of nanocrystals

Abstract: Recent advances in solid-state nuclear magnetic resonance (NMR) spectroscopy and dynamic nuclear polarization (DNP) of nanostructured materials are reviewed. A first group of materials is based on crystalline nanocellulose (CNC) or microcrystalline cellulose (MCC), which are used as carrier materials for dye molecules, catalysts or in combination with heterocyclic molecules as ion conducting membranes. These materials have widespread applications in sensorics, optics, catalysis or fuel cell research. A second group are metal oxides such as V-Mo-W oxides, which are of enormous importance in the manufacturing process of basic chemicals. The third group are catalytically active nanocrystalline metal nanoparticles, coated with protectants or embedded in polymers. The last group includes of lead-free perovskite materials, which are employed as environmentally benign substitution materials for conventional lead-based electronics materials. These materials are discussed in terms of their application and physico-chemical characterization by solid-state NMR techniques, combined with gas-phase NMR and quantum-chemical modelling on the density functional theory (DFT) level. The application of multinuclear 1H, 2H, 13C, 15N and 23Na solid state NMR techniques under static or MAS conditions for the characterization of these materials, their surfaces and processes on their surfaces is discussed. Moreover, the analytic power of the combination of these techniques with DNP for the identification of low-concentrated carbon and nitrogen containing surface species in natural abundance is reviewed. Finally, approaches for sensitivity enhancement by DNP of quadrupolar nuclei such as 17O and 51V are presented that enable the identification of catalytic sites in metal oxide catalysts.

Noise Reduction in Solid-State NMR Spectra Using Principal Component Analysis.

Abstract: A noise reduction method was developed for solid-state nuclear magnetic resonance spectroscopy using multivariate analysis. Principal component analysis was first applied for cross-polarization/mag...

One- and Two-Dimensional High-Resolution NMR from Flat Surfaces

Abstract: Determining atomic-level characteristics of molecules on two-dimensional surfaces is one of the fundamental challenges in chemistry. High-resolution nuclear magnetic resonance (NMR) could deliver r...

Electronic active defects and local order in doped ZnO ceramics inferred from EPR and 27Al NMR investigations

Abstract: Doped ZnO based ceramics were fabricated by using a solid state reaction of ZnO co-doped by TiO2, Al2O3 and MgO and sintered in different atmospheres (Air, N2, N2 + CO). The crystalline structures consist in wurtzite ZnO and a minor spinel phase Zn2TiO4. The electrical conductivity is modulated by the sintering conditions with the highest value (˜105 S m−1) obtained in the reducing atmosphere (N2 + CO). The role of defects and vacancies on the electrical behavior was exhaustively investigated by Raman, electron paramagnetic resonance (EPR) and solid state NMR methods. The paramagnetic centres inferred from EPR studies show a Pauli-like spin susceptibility. Their origin was assigned to shallow donors from interstitial defects (Zni) favored by substitutional Al ions (AlZn). The NMR spectral features with a characteristic 185 ppm line which correlates with the electrical conductivity are presumed to be caused by the Knight shift effect from the conduction electrons and the involved paramagnetic centres.

Synthesis, structural, optical and solid state NMR study of lead bismuth titanate borosilicate glasses

Abstract: Various compositions (0.0 ≤ x ≤ 1.0) in the glassy system 55[(PbxBi1-x)TiO3]-44[2SiO2.B2O3] doped with one mol percent of graphene nanoplatlets (GNPs) have been synthesized using the conventional melt-quenching technique. X-ray diffraction (XRD) study revealed the formation of bulk and transparent lead bismuth titanate borosilicate glasses. Density and molar volume were determined using the liquid displacement method. Structural analyses were carried out in detail using different characterization techniques such as infrared spectroscopy, Raman spectroscopy, UV–vis spectroscopy and solid state nuclear magnetic resonance (SSNMR) spectroscopy. 29Si and 11B-MAS-NMR-spectral analysis for five glass samples with different fraction of PbO reveal that as increases the content of PbO, the silicate and borate network become more polymerized.

Understanding Overhauser dynamic nuclear polarisation through NMR relaxometry.

Abstract: Overhauser dynamic nuclear polarisation (DNP) represents a potentially outstanding tool to increase the sensitivity of solution and solid state NMR experiments, as well as of magnetic resonance ima...

Structural characterization of an amorphous VS4 and its lithiation/delithiation behavior studied by solid-state NMR spectroscopy

Abstract: Vanadium sulfide (VS4) is one of the promising positive electrode materials for next-generation rechargeable lithium-ion batteries because of its high theoretical capacity (1196 mA h g−1). Crystalline VS4 has a unique structure, in which the Peierls-distorted one-dimensional chains of V–V bonds along the c axis are loosely connected to each other through van der Waals interactions. In this study, an amorphous VS4 is prepared by mechanical milling of the crystalline material, and its lithiation/delithiation behavior is investigated by solid-state nuclear magnetic resonance (NMR) spectroscopy. The amorphous VS4 shows a chain structure similar to that of crystalline VS4. The amorphous host structure is found to change drastically during the lithiation process to form Li3VS4: the V ions become tetrahedrally coordinated by S ions, in which the valence states of V and S ions simultaneously change from V4+ to V5+ and S− to S2−, respectively. When the Li insertion proceeds further, the valence state of V ions is reduced. After the 1st cycle, the amorphous VS4 recovers to the chain-like structure although it is highly disordered. No conversion to elemental V is observed, and a high capacity of 700 mA h g−1 is reversibly delivered between 1.5 and 2.6 V.

CO2 Behavior in a Highly Selective Ultramicroporous Framework: Insights from Single-Crystal X-ray Diffraction and Solid-State Nuclear Magnetic Resonance Spectroscopy

Abstract: Metal–organic frameworks (MOFs) are a class of porous materials that have attracted much attention for gas adsorption applications. The ultramicroporous SIFSIX-3-Zn MOF, made up of zinc and pyrazin...