Eudicot primary cell wall glucomannan is related in synthesis, structure, and function to xyloglucan.

Hemicellulose polysaccharides influence assembly and properties of the plant primary cell wall (PCW), perhaps by interacting with cellulose to affect the deposition and bundling of cellulose fibrils. However, the functional differences between plant cell wall hemicelluloses such as glucomannan, xylan, and xyloglucan (XyG) remain unclear. As the most abundant hemicellulose, XyG is considered important in eudicot PCWs, but plants devoid of XyG show relatively mild phenotypes. We report here that a patterned ß-galactoglucomannan (ß-GGM) is widespread in eudicot PCWs and shows remarkable similarities to XyG. The sugar linkages forming the backbone and side chains of ß-GGM are analogous to those that make up XyG, and moreover, these linkages are formed by glycosyltransferases from the same CAZy families. Solid-state nuclear magnetic resonance indicated that ß-GGM shows low mobility in the cell wall, consistent with interaction with cellulose. Although Arabidopsis ß-GGM synthesis mutants show no obvious growth defects, genetic crosses between ß-GGM and XyG mutants produce exacerbated phenotypes compared with XyG mutants. These findings demonstrate a related role of these two similar but distinct classes of hemicelluloses in PCWs. This work opens avenues to study the roles of ß-GGM and XyG in PCWs.

Polymorph Identification for Flexible Molecules: Linear Regression Analysis of Experimental and Calculated Solution- and Solid-State NMR Data.

The Δδ regression approach of Blade et al. [ J. Phys. Chem. A 2020, 124(43), 8959-8977] for accurately discriminating between solid forms using a combination of experimental solution- and solid-state NMR data with density functional theory (DFT) calculation is here extended to molecules with multiple conformational degrees of freedom, using furosemide polymorphs as an exemplar. As before, the differences in measured 1H and 13C chemical shifts between solution-state NMR and solid-state magic-angle spinning (MAS) NMR (Δδexperimental) are compared to those determined by gauge-including projector augmented wave (GIPAW) calculations (Δδcalculated) by regression analysis and a t-test, allowing the correct furosemide polymorph to be precisely identified. Monte Carlo random sampling is used to calculate solution-state NMR chemical shifts, reducing computation times by avoiding the need to systematically sample the multidimensional conformational landscape that furosemide occupies in solution. The solvent conditions should be chosen to match the molecule's charge state between the solution and solid states. The Δδ regression approach indicates whether or not correlations between Δδexperimental and Δδcalculated are statistically significant; the approach is differently sensitive to the popular root mean squared error (RMSE) method, being shown to exhibit a much greater dynamic range. An alternative method for estimating solution-state NMR chemical shifts by approximating the measured solution-state dynamic 3D behavior with an ensemble of 54 furosemide crystal structures (polymorphs and cocrystals) from the Cambridge Structural Database (CSD) was also successful in this case, suggesting new avenues for this method that may overcome its current dependency on the prior determination of solution dynamic 3D structures.

Exploring the Potential of Multinuclear Solid-State 1 H, 13 C, and 35 Cl Magnetic Resonance To Characterize Static and Dynamic Disorder in Pharmaceutical Hydrochlorides.

Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field 35 Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride (1), static disorder in promethazine hydrochloride (2), and trifluoperazine dihydrochloride (3). In all structures, the presence of crystallographic disorder was confirmed by 13 C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3, 1 H solid-state NMR provided additional confirmation. Applying 35 Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3, while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from 1 H, 13 C, and 35 Cl NMR, we show that 3 exhibits a unique case of disorder involving the + N-H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.

Nuclear spin diffusion under fast magic-angle spinning in solid-state NMR.

Solid-state nuclear spin diffusion is the coherent and reversible process through which spin order is transferred via dipolar couplings. With the recent increases in magic-angle spinning (MAS) frequencies and magnetic fields becoming routinely applied in solid-state nuclear magnetic resonance, understanding how the increased 1H resolution obtained affects spin diffusion is necessary for interpretation of several common experiments. To investigate the coherent contributions to spin diffusion with fast MAS, we have developed a low-order correlation in Liouville space model based on the work of Dumez et al. (J. Chem. Phys. 33, 224501, 2010). Specifically, we introduce a new method for basis set selection, which accounts for the resonance-offset dependence at fast MAS. Furthermore, we consider the necessity of including chemical shift, both isotropic and anisotropic, in the modeling of spin diffusion. Using this model, we explore how different experimental factors change the nature of spin diffusion. Then, we show case studies to exemplify the issues that arise in using spin diffusion techniques at fast spinning. We show that the efficiency of polarization transfer via spin diffusion occurring within a deuterated and 100% back-exchanged protein sample at 60 kHz MAS is almost entirely dependent on resonance offset. We additionally identify temperature-dependent magnetization transfer in beta-aspartyl L-alanine, which could be explained by the influence of an incoherent relaxation-based nuclear Overhauser effect.

Optimisation of 1H PMLG homonuclear decoupling at 60 kHz MAS to enable 15N-1H through-bond heteronuclear correlation solid-state NMR spectroscopy.

The Lee-Goldburg condition for homonuclear decoupling in 1H magic-angle spinning (MAS) solid-state NMR sets the angle θ, corresponding to arctan of the ratio of the rf nutation frequency, ν1, to the rf offset, to be the magic angle, θm, equal to tan-1(√2) = 54.7°. At 60 kHz MAS, we report enhanced decoupling compared to MAS alone in a 1H spectrum of 15N-glycine with at θ = 30° for a ν1 of ∼100 kHz at a 1H Larmor frequency, ν0, of 500 MHz and 1 GHz, corresponding to a high chemical shift scaling factor (λCS) of 0.82. At 1 GHz, we also demonstrate enhanced decoupling compared to 60 kHz MAS alone for a lower ν1 of 51 kHz, i.e., a case where the nutation frequency is less than the MAS frequency, with θ = 18°, λCS = 0.92. The ratio of the rotor period to the decoupling cycle time, Ψ = τr/τc, is in the range 0.53 to 0.61. Windowed decoupling using the optimised parameters for a ν1 of ∼100 kHz also gives good performance in a 1H spin-echo experiment, enabling implementation in a 1H-detected 15N-1H cross polarisation (CP)-refocused INEPT heteronuclear correlation NMR experiment. Specifically, initial 15N transverse magnetisation as generated by 1H-15N CP is transferred back to 1H using a refocused INEPT pulse sequence employing windowed 1H decoupling. Such an approach ensures the observation of through-bond N-H connectivities. For 15N-glycine, while the CP-refocused INEPT experiment has a lower sensitivity (∼50%) as compared to a double CP experiment (with a 200 µs 15N to 1H CP contact time), there is selectivity for the directly bonded NH3+ moiety, while intensity is observed for the CH21H resonances in the double CP experiment. Two-dimensional 15N-1H correlation MAS NMR spectra are presented for the dipeptide ß-AspAla and the pharmaceutical cimetidine at 60 kHz MAS, both at natural isotopic abundance. For the dipeptide ß-AspAla, different build-up dependence on the first spin-echo duration is observed for the NH and NH3+ moieties demonstrating that the experiment could be used to distinguish resonances for different NHx groups.

Correction: Optimisation of 1H PMLG homonuclear decoupling at 60 kHz MAS to enable 15N-1H through-bond heteronuclear correlation solid-state NMR spectroscopy.

Correction for 'Optimisation of 1H PMLG homonuclear decoupling at 60 kHz MAS to enable 15N-1H through-bond heteronuclear correlation solid-state NMR spectroscopy' by Jacqueline Tognetti et al., Phys. Chem. Chem. Phys., 2022, 24, 20258-20273, https://doi.org/10.1039/D2CP01041K.

Combining heteronuclear correlation NMR with spin-diffusion to detect relayed Cl-H-H and N-H-H proximities in molecular solids.

Analysis of short-to-intermediate range intermolecular interactions offers a great way of characterizing the solid-state organization of small molecules and materials. This can be achieved by two-dimensional (2D) homo- and heteronuclear correlation NMR spectroscopy, for example, by carrying out experiments at high magnetic fields in conjunction with fast magic-angle spinning (MAS) techniques. But, detecting 2D peaks for heteronuclear dipolar coupled spin pairs separated by greater than 3 Å is not always straightforward, particularly when low-gamma quadrupolar nuclei are involved. Here, we present a 2D correlation NMR experiment that combines the advantages of heteronuclear-multiple quantum coherence (HMQC) and proton-based spin-diffusion (SD) pulse sequences using radio-frequency-driven-recouping (RFDR) to probe inter and intramolecular 1H-X (X = 14N, 35Cl) interactions. This experiment can be used to acquire 2D 1H{X}-HMQC filtered 1H-1H correlation as well as 2D 1H-X HMQC spectra. Powder forms of dopamine·HCl and l-histidine·HCl·H2O are characterized at high fields (21.1 T and 18.8 T) with fast MAS (60 kHz) using the 2D HMQC-SD-RFDR approach. Solid-state NMR results are complemented with NMR crystallography analyses using the gauge-including projector augmented wave (GIPAW) approach. For histidine·HCl·H2O, 2D peaks associated with 14N-1H-1H and 35Cl-1H-1H distances of up to 4.4 and 3.9 Å have been detected. This is further corroborated by the observation of 2D peaks corresponding to 14N-1H-1H and 35Cl-1H-1H distances of up to 4.2 and 3.7 Å in dopamine·HCl, indicating the suitability of the HMQC-SD-RFDR experiments for detecting medium-range proximities in molecular solids.

Importance of Water in Maintaining Softwood Secondary Cell Wall Nanostructure.

Water is one of the principal constituents by mass of living plant cell walls. However, its role and interactions with secondary cell wall polysaccharides and the impact of dehydration and subsequent rehydration on the molecular architecture are still to be elucidated. This work combines multidimensional solid-state 13C magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) with molecular dynamics modeling to decipher the role of water in the molecular architecture of softwood secondary cell walls. The proximities between all main polymers, their molecular conformations, and interaction energies are compared in never-dried, oven-dried, and rehydrated states. Water is shown to play a critical role at the hemicellulose-cellulose interface. After significant molecular shrinkage caused by dehydration, the original molecular conformation is not fully recovered after rehydration. The changes include xylan becoming more closely and irreversibly associated with cellulose and some mannan becoming more mobile and changing conformation. These irreversible nanostructural changes provide a basis for explaining and improving the properties of wood-based materials.

A toolbox for improving the workflow of NMR crystallography.

NMR crystallography is a powerful tool with applications in structural characterization and crystal structure verification, to name two. However, applying this tool presents several challenges, especially for industrial users, in terms of consistency, workflow, time consumption, and the requirement for a high level of understanding of experimental solid-state NMR and GIPAW-DFT calculations. Here, we have developed a series of fully parameterized scripts for use in Materials Studio and TopSpin, based on the .magres file format, with a focus on organic molecules (e.g. pharmaceuticals), improving efficiency, robustness, and workflow. We separate these tools into three major categories: performing the DFT calculations, extracting & visualizing the results, and crystallographic modelling. These scripts will rapidly submit fully parameterized CASTEP jobs, extract data from the calculations, assist in visualizing the results, and expedite the process of structural modelling. Accompanied with these tools is a description on their functionality, documentation on how to get started and use the scripts, and links to video tutorials for guiding new users. Through the use of these tools, we hope to facilitate NMR crystallography and to harmonize the process across users.

35 Cl-1 H Heteronuclear correlation magic-angle spinning nuclear magnetic resonance experiments for probing pharmaceutical salts.

Heteronuclear multiple-quantum coherence (HMQC) pulse sequences for establishing heteronuclear correlation in solid-state nuclear magnetic resonance (NMR) between 35 Cl and 1 H nuclei in chloride salts under fast (60 kHz) magic-angle spinning (MAS) and at high magnetic field (a 1 H Larmor frequency of 850 MHz) are investigated. Specifically, recoupling of the 35 Cl-1 H dipolar interaction using rotary resonance recoupling with phase inversion every rotor period or the symmetry-based SR42 1 pulse sequences are compared. In our implementation of the population transfer (PT) dipolar (D) HMQC experiment, the satellite transitions of the 35 Cl nuclei are saturated with an off-resonance WURST sweep, at a low nutation frequency, over the second spinning sideband, whereby the WURST pulse must be of the same duration as the recoupling time. Numerical simulations of the 35 Cl-1 H MAS D-HMQC experiment performed separately for each crystallite orientation in a powder provide insight into the orientation dependence of changes in the second-order quadrupolar-broadened 35 Cl MAS NMR lineshape under the application of dipolar recoupling. Two-dimensional 35 Cl-1 H PT-D-HMQC MAS NMR spectra are presented for the amino acids glycine·HCl and l-tyrosine·HCl and the pharmaceuticals cimetidine·HCl, amitriptyline·HCl and lidocaine·HCl·H2 O. Experimentally observed 35 Cl lineshapes are compared with those simulated for 35 Cl chemical shift and quadrupolar parameters as calculated using the gauge-including projector-augmented wave (GIPAW) method: the calculated quadrupolar product (PQ ) values exceed those measured experimentally by a factor of between 1.3 and 1.9.

Structure Effects on the Ionicity of Protic Ionic Liquids.

We report on the characterisation of 16 protic ionic liquids (PILs) prepared by neutralisation of primary or tertiary amines with a range of simple carboxylic acids, or salicylic acid. The extent of proton transfer was greater for simple primary amine ILs compared to tertiary amines. For the latter case, proton transfer was increased by providing a better solvation environment for the ions through the addition of a hydroxyl group, either on the tertiary amine, or by formation of PIL/molecular solvent mixtures. The library of PILs was characterised by differential scanning calorimetry and a range of transport properties (i. e. viscosity, conductivity and diffusivity) were measured. Using the (fractional) Walden rule, the conductivity and viscosity results were analysed with respect to their deviation from ideal behaviour. The validity of the Walden plot for PILs containing ions of varying sizes was also verified for a number of samples by directly measuring self-diffusion coefficients using pulsed-field gradient spin-echo (PGSE) NMR. Ionicity was found to decrease as the alkyl chain length and degree of branching of both the cations and anions was increased. These results aim to develop a better understanding of the relationship between PIL properties and structure, to help design ILs with optimal properties for applications.

Revealing Intermolecular Hydrogen Bonding Structure and Dynamics in a Deep Eutectic Pharmaceutical by Magic-Angle Spinning NMR Spectroscopy.

Liquid forms of pharmaceuticals (ionic liquids and deep eutectic solvents) offer a number of potential advantages over solid-state drugs; a key question is the role of intermolecular hydrogen bonding interactions in enabling membrane transport. Characterization is challenging since high sample viscosities, typical of liquid pharmaceutical formulations, hamper the use of conventional solution NMR at ambient temperature. Here, we report the application of magic-angle spinning (MAS) NMR spectroscopy to the deep eutectic pharmaceutical, lidocaine ibuprofen. Using variable temperature MAS NMR, the neat system, at a fixed molar ratio, can be studied over a wide range of temperatures, characterized by changing mobility, using a single experimental setup. Specific intermolecular hydrogen bonding interactions are identified by two-dimensional 1H-1H NOESY and ROESY MAS NMR experiments. Hydrogen-bonding dynamics are quantitatively determined by following the chemical exchange process between the labile protons by means of line-width analysis of variable temperature 1H MAS NMR spectra.

Conformations in Solution and in Solid-State Polymorphs: Correlating Experimental and Calculated Nuclear Magnetic Resonance Chemical Shifts for Tolfenamic Acid.

A new approach for quantitively assessing putative crystal structures with applications in crystal structure prediction (CSP) is introduced that is based upon experimental solution- and magic-angle spinning (MAS) solid-state NMR data and density functional theory (DFT) calculation. For the specific case of tolfenamic acid (TFA), we consider experimental solution-state NMR for a range of solvents, experimental MAS NMR of polymorphs I and II, and DFT calculations for four polymorphs. The change in NMR chemical shift observed in passing from the solution state to the solid state (ΔδExperimental) is calculated as the difference between 1H and 13C experimental solid-state chemical shifts for each polymorphic form (δSolid expt) and the corresponding solution-state NMR chemical shifts (δSolution expt). Separately, we use the gauge-included projector augmented wave (GIPAW) method to calculate the NMR chemical shifts for each form (δSolid calc) and for TFA in solution (δSolution calc) using the dynamic 3D solution conformational ensemble determined from NMR spectroscopy. The calculated change in passing from the solution state to the solid state (ΔδCalculated) is then calculated as the difference of δSolid calc and δSolution calc. Regression analysis for ΔδCalculated against ΔδExperimental followed by a t-test for statistical significance provides a robust quantitative assessment. We show that this assessment clearly identifies the correct polymorph, i.e., when comparing ΔδExperimental based on the experimental MAS NMR chemical shifts of form I or II with ΔδCalculated based on calculated chemical shifts for polymorphs I, II, III, and IV. Complementarity to the established approach of comparing δSolid expt to δSolid calc is explored. We further show that our approach is applicable if there are no solid-state crystal structure data. Specifically, δSolid calc in ΔδCalculated is replaced by the chemical shift for an isolated molecule with a specific conformation. Sampling conformations at specific 15° angle values and comparing them against experimental 13C chemical shift data for forms I and II identifies matching narrow ranges of conformations, successfully predicting the conformation of tolfenamic acid in each form. This methodology can therefore be used in crystal structure prediction to both reduce the initial conformational search space and also quantitatively assess subsequent putative structures to reliably and unambiguously identify the correct structure.

Weak Intermolecular CH···N Hydrogen Bonding: Determination of 13CH-15N Hydrogen-Bond Mediated J Couplings by Solid-State NMR Spectroscopy and First-Principles Calculations.

Weak hydrogen bonds are increasingly hypothesized to play key roles in a wide range of chemistry from catalysis to gelation to polymer structure. Here, 15N/13C spin-echo magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) experiments are applied to "view" intermolecular CH···N hydrogen bonding in two selectively labeled organic compounds, 4-[15N] cyano-4'-[13C2] ethynylbiphenyl (1) and [15N3,13C6]-2,4,6-triethynyl-1,3,5-triazine (2). The synthesis of 2-15N3,13C6 is reported here for the first time via a multistep procedure, where the key element is the reaction of [15N3]-2,4,6-trichloro-1,3,5-triazine (5) with [13C2]-[(trimethylsilyl)ethynyl]zinc chloride (8) to afford its immediate precursor [15N3,13C6]-2,4,6-tris[(trimethylsilyl)ethynyl]-1,3,5-triazine (9). Experimentally determined hydrogen-bond-mediated 2hJCN couplings (4.7 ± 0.4 Hz (1) and 4.1 ± 0.3 Hz (2)) are compared with density functional theory (DFT) gauge-including projector augmented wave (GIPAW) calculations, whereby species-independent coupling values 2hKCN (29.0 × 1019 kg m-2 s-2 A-2 (1) and 27.9 × 1019 kg m-2 s-2 A-2 (2)) quantitatively demonstrate the J couplings for these "weak" CH···N hydrogen bonds to be of a similar magnitude to those for conventionally observed NH···O hydrogen-bonding interactions in uracil (2hKNO: 28.1 and 36.8 × 1019 kg m-2 s-2 A-2). Moreover, the GIPAW calculations show a clear correlation between increasing 2hJCN (and 3hJCN) coupling and reducing C(H)···N and H···N hydrogen-bonding distances, with the Fermi contact term accounting for at least 98% of the isotropic 2hJCN coupling.

Investigating discrepancies between experimental solid-state NMR and GIPAW calculation: NC-N 13C and OH⋯O 1H chemical shifts in pyridinium fumarates and their cocrystals.

An NMR crystallography analysis is presented for four solid-state structures of pyridine fumarates and their cocrystals, using crystal structures deposited in the Cambridge Crystallographic Data Centre, CCDC. Experimental one-dimensional one-pulse 1H and 13C cross-polarisation (CP) magic-angle spinning (MAS) nuclear magnetic resonance (NMR) and two-dimensional 14N-1H heteronuclear multiple-quantum coherence MAS NMR spectra are compared with gauge-including projector augmented wave (GIPAW) calculations of the 1H and 13C chemical shifts and the 14N shifts that additionally depend on the quadrupolar interaction. Considering the high ppm (>10 â€‹ppm) 1H resonances, while there is good agreement (within 0.4 â€‹ppm) between experiment and GIPAW calculation for the hydrogen-bonded NH moieties, the hydrogen-bonded fumaric acid OH resonances are 1.2-1.9 â€‹ppm higher in GIPAW calculation as compared to experiment. For the cocrystals of a salt and a salt formed by 2-amino-5-methylpyridinium and 2-amino-6-methylpyridinium ions, a large discrepancy of 4.2 and 5.9 â€‹ppm between experiment and GIPAW calculation is observed for the quaternary ring carbon 13C resonance that is directly bonded to two nitrogens (in the ring and in the amino group). By comparison, there is excellent agreement (within 0.2 â€‹ppm) for the quaternary ring carbon 13C resonance directly bonded to the ring nitrogen for the salt and cocrystal of a salt formed by 2,6-lutidinium and 2,5-lutidinium, respectively.

5-amino-2-methylpyridinium hydrogen fumarate: An XRD and NMR crystallography analysis.

Single-crystal X-ray diffraction structures of the 5-amino-2-methylpyridinium hydrogen fumarate salt have been solved at 150 and 300 K (CCDC 1952142 and 1952143). A base-acid-base-acid ring is formed through pyridinium-carboxylate and amine-carboxylate hydrogen bonds that hold together chains formed from hydrogen-bonded hydrogen fumarate ions. 1 H and 13 C chemical shifts as well as 14 N shifts that additionally depend on the quadrupolar interaction are determined by experimental magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) and gauge-including projector-augmented wave (GIPAW) calculation. Two-dimensional homonuclear 1 H-1 H double-quantum (DQ) MAS and heteronuclear 1 H-13 C and 14 N-1 H spectra are presented. Only small differences of up to 0.1 and 0.6 ppm for 1 H and 13 C are observed between GIPAW calculations starting with the two structures solved at 150 and 300 K (after geometry optimisation of atomic positions, but not unit cell parameters). A comparison of GIPAW-calculated 1 H chemical shifts for isolated molecules and the full crystal structures is indicative of hydrogen bonding strength.

Modulation of Transmembrane Domain Interactions in Neu Receptor Tyrosine Kinase by Membrane Fluidity and Cholesterol.

The activation mechanism of the ErbB family of receptors is of considerable medical interest as they are linked to a number of human cancers, including an aggressive form of breast cancer. In the rat analogue of the human ErbB2 receptor, referred to as Neu, a point mutation in the transmembrane domain (V664E) has been shown to trigger oncogenic transformation. While the structural impact of this mutation has been widely studied in the past to yield models for the active state of the Neu receptor, little is known about the impact of cholesterol on its structure. Given previous reports of the influence of cholesterol on other receptor tyrosine kinases (RTKs), as well as the modulation of lipid composition in cancer cells, we wished to investigate how cholesterol content impacts the structure of the Neu transmembrane domain. We utilized high-resolution magic angle spinning solid-state NMR to measure 13C-13C coupling of selectively labelled probe residues in the Neu transmembrane domain in lipid bilayers containing cholesterol. We observe inter-helical coupling between residues that support helix-helix interactions on both dimerization motifs reported in the literature (A661-XXX-G665 and I659-XXX-V663). We further explore how changes in cholesterol concentration alter transmembrane domain interactions and the properties and mechanics of the bilayer. We interpret our results in light of previous studies relating RTK activity to cholesterol enrichment and/or depletion, and propose a novel model to explain our data that includes the recognition and binding of cholesterol by the Neu transmembrane domain through a putative cholesterol-recognition/interaction amino acid consensus sequence.

An NMR crystallography investigation of furosemide.

This paper presents an NMR crystallography study of three polymorphs of furosemide. Experimental magic-angle spinning (MAS) solid-state NMR spectra are reported for form I of furosemide, and these are assigned using density-functional theory (DFT)-based gauge-including projector augmented wave (GIPAW) calculations. Focusing on the three known polymorphs, we examine the changes to the NMR parameters due to crystal packing effects. We use a recently developed formalism to visualise which regions are responsible for the chemical shielding of particular sites and hence understand the variation in NMR parameters between the three polymorphs.

The use of variable temperature 13 C solid-state MAS NMR and GIPAW DFT calculations to explore the dynamics of diethylcarbamazine citrate.

Experimental 13 C solid-state magic-angle spinning (MAS) Nuclear Magnetic Resonance (NMR) as well as Density-Functional Theory (DFT) gauge-including projector augmented wave (GIPAW) calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+ (citrate)- . This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13 C─1 H dipolar-coupling-mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules. Secondly, we investigate the dynamic behavior of (DEC)+ (citrate)- by varying the temperature and correlating the experimental MAS NMR results with DFT GIPAW calculations that consider two (DEC)+ conformers (in a 70:30 ratio) for crystal structures determined at 293 and 235 K. Solid-state NMR provides insights on slow exchange dynamics revealing conformational changes involving particularly the DEC ethyl groups.

A Tautoleptic Approach to Chiral Hydrogen-Bonded Supramolecular Tubular Polymers with Large Cavity.

A new strategy towards tubular hydrogen-bonded polymers based on the self-assembly of isocytosine tautomers in orthogonal directions is proposed and experimentally verified, including by 1 H fast magic-angle spinning (MAS) solid-state NMR. The molecular tubes obtained possess large internal diameter and tailor-made outer functionalities rendering them potential candidates for a number of applications.