Ssnmr

14 N NMR of magnetically oriented microcrystals is reported. With a home-built 1 H-13 C-14 N probe capable of modulating the rotation of the sample around the axis normal to the magnetic field, magnetically oriented microcrystal suspension (MOMS) of l-alanine is made. 14 N NMR spectra acquired with various timings during intermittent rotation lead to a rotation pattern of the MOMS similar to that of a single crystal. The effect of orientational distribution of the microcrystals to broadening of the resonance line is discussed...

The NMR lineshapes produced by half-integer quadrupolar nuclei are sensitive to 11 distinct fit parameters per inequivalent site. To date, automatic fitting routines have failed to replace manual parameter insertion and evaluation due to the importance of local minima and the need for fitting multiple-field magic-angle spinning (MAS) and static spectra simultaneously. Herein we introduce a new tool, AMES-Fit (Automatic Multiple Experiment Simulation and Fitting), to automatically find the global best-fit simulation parameters for a series of multiple-field NMR lineshapes...

The objective of this review is, to discuss recent advancements in screening methods for co-formers, evaluation cum confirmation methods and co-crystallization with examples. Co-crystals are considered as a new form of an old drug entity. Co-crystals improve the stability, hygroscopicity, solubility, dissolution, and physicochemical properties of pure drugs without altering chemical and pharmacological properties. Advancement in co-crystal formulation methods like electrospray and laser-irradiation methods are showing potential for solvent-free co-crystallization and tends to give better yield and lesser loss of materials...

Safety concerns of traditional liquid electrolytes, especially when paired with lithium (Li) metal anodes, have stimulated research of solid polymer electrolytes (SPEs) to exploit the superior thermal and mechanical properties of polymers. Polyphosphazenes are primarily known for their use as flame retardant materials and have demonstrated high Li-ion conductivity owing to their highly flexible P = N backbone which promotes Li-ion conduction via inter- and intrachain hopping along the polymer backbone. While polyphosphazenes are largely unexplored as SPEs in the literature, a few existing examples showed promising ionic conductivity...

Under normal experimental conditions in an achiral environment, NMR spectra of enantiomers have chemical shifts and J couplings which are not differentiable. In this work, the reproducibility of spectral intensities for pairs of amino acid enantiomers, as well as factors influencing these intensities, is assessed using 13 C and 15 N cross-polarization magic-angle spinning (CP/MAS) NMR spectroscopy. Prompted by a recent literature debate over a possible influence of the chirality-induced spin selectivity (CISS) effect on spectral intensities obtained in CP/MAS NMR experiments carried out on enantiomers, a number of control experiments were performed with recycle delays of at least 5T1 ...

The aberrant aggregation of α-synuclein (αS) into amyloid fibrils is associated with a range of highly debilitating neurodegenerative conditions, including Parkinson's disease. Although the structural properties of mature amyloids of αS are currently understood, the nature of transient protofilaments and fibrils that appear during αS aggregation remains elusive. Using solid-state nuclear magnetic resonance (ssNMR), cryogenic electron microscopy (cryo-EM), and biophysical methods, we here characterized intermediate amyloid fibrils of αS forming during the aggregation from liquid-like spherical condensates to mature amyloids adopting the structure of pathologically observed aggregates...

The aggregation of proteins into amyloid-like fibrils is seen in many neurodegenerative diseases. Recent years have seen much progress in our understanding of these misfolded protein inclusions, thanks to advances in techniques such as solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryo-EM). However, multiple repeat-expansion-related disorders have presented special challenges to structural elucidation. This review discusses the special role of ssNMR analysis in the study of protein aggregates associated with CAG repeat expansion disorders...

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue...

The fungal cell wall plays a critical role in regulating cellular integrity and communication, and serves as a frontline defense against stress. It is also a prime target for the development of antifungal agents. The cell wall is comprised of diverse polysaccharides and proteins and poses a challenging target for high-resolution structural characterization. Recently, the solid-state nuclear magnetic resonance (ssNMR) analysis of intact Aspergillus fumigatus cells has provided atomic-level insights into the structural polymorphism and functional assembly principles of carbohydrate components within the cell wall...

Terminal imido complexes containing metal-nitrogen multiple bonds have been widely used in organometallic chemistry and homogeneous catalysis. The role of terminal imido ligands spans from reactive sites to spectator motifs, largely depending on the nature of the metal center and its specific coordination sphere. Aiming at identifying reactivity descriptors for M-N multiple bonds, we herein explore solid-state 15 N NMR spectroscopy (ssNMR) on early transition metal terminal imido complexes augmented by computational studies and show that the asymmetry parameter, κ (skew, 1 ≥ κ ≥ -1), readily available from experiments or calculations, is diagnostic for the reactivity of M-N multiple bonds in imido complexes...

Accurate signal assignments can be challenging for congested solid-state NMR (ssNMR) spectra. We describe an automatic sequential assignment program (ASAP) to partially overcome this challenge. ASAP takes three input files: the residue type assignments (RTAs) determined from the better-resolved NCACX spectrum, the full peak list of the NCOCX spectrum, and the protein sequence. It integrates our auto-residue type assignment strategy (ARTIST) with the Monte Carlo simulated annealing (MCSA) algorithm to overcome the hurdle for accurate signal assignments caused by incomplete side-chain resonances and spectral congestion...

77Se-NMR is used to characterise several chalcogen bonded complexes of derivatives of the organoselenium drug ebselen, exploring a range of electron demand. NMR titration experiments support the intuitive understanding that chalcogen bond donors bearing more electron withdrawing substituents give rise stronger chalcogen bonds. The chemical shift of the selenium nucleus is also shown to move upfield as it participates in a chalcogen bond. Solid-state NMR is used to explore chalcogen bonding in co-crystals...

Piperine, an alkaloid found in black pepper fruits, has the properties of promoting the absorption of other substances (e.g. curcumin), therefore it is used in solid forms of dietary supplements as an additive increasing bioavailability. The aim of the study was to analyze piperine in a solid state and then to use it in the analysis of solid dietary supplements with the addition of piperine as an absorption promoter. The 13 C CP MAS NMR spectra were recorded using variable contact time and dipolar dephasing experiment...

Double-rotation (DOR) solid-state NMR spectroscopy is a high-resolution technique developed in the late 1980s. Although multiple-quantum magic-angle spinning (MQMAS) became the most widely used high-resolution method for half-integer spin quadrupoles after 1995, development and application of DOR NMR to a variety of chemical and materials science problems has endured. This Trend article recapitulates the development of DOR NMR, discusses various applications, and describes possible future directions. The main technical limitations specific to DOR NMR are simply related to the size of the double rotor system...

Sensitivity enhanced dynamic nuclear polarization solid-state NMR is emerging as a powerful technique for probing the structural properties of conformationally homogenous and heterogenous biomolecular species irrespective of size at atomic resolution within native environments. Herein we detail advancements that have made acquiring such data, specifically within the confines of intact bacterial and eukaryotic cell a reality, and further discuss the type of structural information that can be presently garnered by the technique's exploitation...

The cyclodextrin-based metal-organic frameworks (CD MOFs) are a suitable molecular platform for drug delivery systems of various active pharmaceutical ingredients (APIs). The low toxicity and cost-efficient synthesis make CD MOFs an attractive host for the encapsulation of APIs. In this study, we created a model system based on γCD-K MOFs with widely used drugs carmofur (HCFU), 5-fluorouracil (5-FU), and salicylic acid (HBA) to study host-guest encapsulation methods using different crystallization protocols...

The development of NMR crystallography methods requires a reliable database of chemical shifts measured for systems with known crystal structure. We measured and assigned carbon and hydrogen chemical shifts of twenty solid natural amino acids of known polymorphic structure, meticulously determined using powder X-ray diffraction. We then correlated the experimental data with DFT-calculated isotropic shieldings. The small size of the unit cell of most amino acids allowed for advanced computations using various families of DFT functionals, including generalized gradient approximation (GGA), meta-GGA and hybrid DFT functionals...

This study describes the discovery of a unique ionic cocrystal of the active pharmaceutical ingredient (API) ponatinib hydrochloride ( pon·HCl ), and characterization using single-crystal X-ray diffraction (SCXRD) and solid-state NMR (SSNMR) spectroscopy. Pon·HCl is a multicomponent crystal that features an unusual stoichiometry, with an asymmetric unit containing both monocations and dications of the ponatinib molecule, three water molecules, and three chloride ions. Structural features include (i) a charged imidazopyridazine moiety that forms a hydrogen bond between the ponatinib monocations and dications and (ii) a chloride ion that does not feature hydrogen bonds involving any organic moiety, instead being situated in a "square" arrangement with three water molecules...

Deuterium rotating frame solid-state NMR relaxation measurements (2 H R1ρ ) are important tools in quantitative studies of molecular dynamics. We demonstrate how 2 H to 13 C cross-polarization (CP) approaches under 10-40 kHz magic angle spinning rates can be combined with the 2 H R1ρ blocks to allow for extension of deuterium rotating frame relaxation studies to methyl groups in biomolecules. This extension permits detection on the 13 C nuclei and, hence, for the achievement of site-specific resolution...

The Poaceae family of plants provides cereal crops that are critical for human and animal nutrition, and also, they are an important source of biomass. Interacting plant cell wall components give rise to recalcitrance to digestion; thus, understanding the wall molecular architecture is important to improve biomass properties. Xylan is the main hemicellulose in grass cell walls. Recently, we reported structural variation in grass xylans, suggesting functional specialisation and distinct interactions with cellulose and lignin...