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Thiamine hydrochloride (THCL), also known as vitamin B1, is an active pharmaceutical ingredient (API), present on the list of essential medicines developed by the WHO, which proves its importance for public health. THCL is highly hygroscopic and can occur in the form of hydrates with varying degrees of hydration, depending on the air humidity. Although experimental characterization of the THCL hydrates has been described in the literature, the questions raised in previously published works suggest that additional research and in-depth analysis of THCL dehydration behavior are still needed. Therefore, the main aim of this study was to characterize, by means of quantum chemical calculations, the behavior of thiamine hydrates and explain the previously obtained results, including changes in the NMR spectra, at the molecular level. To achieve this goal, a series of DFT (CASTEP) and DFTB (DFTB+) calculations under periodic boundary conditions have been performed, including molecular dynamics simulations and GIPAW NMR calculations. The obtained results explain the differences in the relative stability of the studied forms and changes in the spectra observed for the samples of various degrees of hydration. This work highlights the application of periodic DFT calculations in the analysis of various solid forms of APIs. [ABSTRACT FROM AUTHOR]

Modern approaches for calculating electric field gradient (EFF) tensors in molecular solids rely upon plane-wave calculations employing periodic boundary conditions (PBC). In practice, models employing PBCs are limited to generalized gradient approximation (GGA) density functionals. Hybrid density functionals applied in the context of gauge-including atomic orbital (GIAO) calculations have been shown to substantially improve the accuracy of predicted NMR parameters. Here we propose an efficient method that effectively combines the benefits of both periodic calculations and single-molecule techniques for predicting electric field gradient tensors in molecular solids. Periodic calculations using plane-wave basis sets were used to model the crystalline environment. We then introduce a molecular correction to the periodic result obtained from a single-molecule calculation performed with a hybrid density functional. Single-molecule calculations performed using hybrid density functionals were found to significantly improve the agreement of predicted 17O quadrupolar coupling constants (C q ) with experiment. We demonstrate a 31% reduction in the RMS error for the predicted 17O C q values relative to standard plane-wave methods using a carefully constructed test set comprised of 22 oxygen-containing molecular crystals. We show comparable improvements in accuracy using five different hybrid density functionals and find predicted C q values to be relatively insensitive to the choice of basis set used in the single molecule calculation. Finally, the utility of high-accuracy 17O C q predictions is demonstrated by examining the disordered 4-Nitrobenzaldehyde crystal structure.

Classical molecular dynamics simulations have been used to investigate the structural role of Mg and its effect when it is incorporated in sodium aluminoborosilicate glasses. The simulations have been performed using three interatomic potentials; one is based on the rigid ionic model parameterized by Wang et al. (2018) and two slightly different parameterization of the core–shell model provided by Stevensson et al. (2018) and Pedone et al. (2020) The accuracies of these models have been assessed by detailed structural analysis and comparing the simulated nuclear magnetic resonance (NMR) spectra for spin active nuclei (29Si, 27Al, 11B, 17O, 25Mg, and 23Na) with the experimental counterparts collected in a previous work. Our simulations reveal that the core–shell parameterizations provide better structural models. In fact, they better reproduce the NMR spectra of all the investigated nuclei and give better agreement with known experimental data. Magnesium is found to be five coordinated on average with distances with oxygen in between a network modifier (like Na) and an intermediate network formed (like Al). It prefers to lay closer to three‐coordinated B atoms, forming B–NBO bonds, with respect to Si and especially Al. This can explain the formation of AlO5 and AlO6 units in the investigated Na‐free glass, together with a Si clusterization. [ABSTRACT FROM AUTHOR]

Lithium phosphorus oxynitride (LiPON) is an amorphous solid-state lithium ion conductor displaying exemplary cyclability against lithium metal anodes. There is no definitive explanation for this stability due to the limited understanding of the structure of LiPON. Herein, we provide a structural model of RF-sputtered LiPON. Information about the short-range structure results from 1D and 2D solid-state NMR experiments. These results are compared with first principles chemical shielding calculations of Li-P-O/N crystals and ab initio molecular dynamics-generated amorphous LiPON models to unequivocally identify the glassy structure as primarily isolated phosphate monomers with N incorporated in both apical and as bridging sites in phosphate dimers. Structural results suggest LiPON's stability is a result of its glassy character. Free-standing LiPON films are produced that exhibit a high degree of flexibility, highlighting the unique mechanical properties of glassy materials.

Turmeric is a traditional Indian spice that has recently become very popular worldwide because it contains a powerful ingredient called curcumin, which has strong anti-inflammatory properties. Hence, dietary supplements containing extracts rich in curcumin have gained great popularity. The main problems related to curcumin-containing dietary supplements are poor water solubility and the fact that they are often faked by using synthetic curcumin instead of the plant extract. In this article, we propose the use of the 13C CPMAS NMR method to control the quality of dietary supplements. The analysis of 13C CPMAS NMR spectra supported by GIPAW computations allowed us to identify a polymorphic form present in dietary supplements (which affected the solubility of curcumin) and to point out a dietary supplement that could be faked by using synthetic curcumin. Further PXRD and HPLC investigations confirmed that the examined supplement contained synthetic curcumin instead of the genuine extract. Our method can be used for routine control, especially because the investigation is performed directly from the capsule/tablet content and does not require any special sample preparation. [ABSTRACT FROM AUTHOR]

Nuclear quadrupole resonances for 14N and 17O nuclei are exquisitely sensitive to interactions with surrounding atoms. As a result, nitrogen and oxygen solid‐state nuclear magnetic resonance (ssNMR) provides a powerful tool for investigating structure and dynamics in complex systems. First‐principles calculations are increasingly used to facilitate spectral assignment and to evaluate and adjust crystal structures. Recent work combining the strengths of planewave density functional theory (DFT) calculations with a single molecule correction obtained using a higher level of theory has proven successful in improving the accuracy of predicted chemical shielding (CS) tensors and 17O quadrupolar coupling constants (Cq). Here we extend this work by examining the accuracy of predicted 14N and 17O electric field gradient (EFG) tensor components obtained using alternative planewave‐corrections involving cluster and two‐body fragment‐based calculations. We benchmark the accuracy of CS and EFG tensor predictions for both nitrogen and oxygen using planewave, two‐body fragment, and enhanced planewave‐corrected techniques. Combining planewave and two‐body fragment calculations reduces the error in predicted 17O Cq values by 35% relative to traditional planewave calculations. These enhanced planewave‐correction methods improve the accuracy of 17O and 14N EFG tensor components by 15% relative to planewave DFT but yield minimal improvement relative to a simple molecular correction. However, in structural environments involving either high symmetry or strong intermolecular interactions, enhanced planewave‐corrected methods provide a distinct advantage. [ABSTRACT FROM AUTHOR]

Thiamine hydrochloride (THCL), also known as vitamin B1, is an active pharmaceutical ingredient (API), present on the list of essential medicines developed by the WHO, which proves its importance for public health. THCL is highly hygroscopic and can occur in the form of hydrates with varying degrees of hydration, depending on the air humidity. Although experimental characterization of the THCL hydrates has been described in the literature, the questions raised in previously published works suggest that additional research and in-depth analysis of THCL dehydration behavior are still needed. Therefore, the main aim of this study was to characterize, by means of quantum chemical calculations, the behavior of thiamine hydrates and explain the previously obtained results, including changes in the NMR spectra, at the molecular level. To achieve this goal, a series of DFT (CASTEP) and DFTB (DFTB+) calculations under periodic boundary conditions have been performed, including molecular dynamics simulations and GIPAW NMR calculations. The obtained results explain the differences in the relative stability of the studied forms and changes in the spectra observed for the samples of various degrees of hydration. This work highlights the application of periodic DFT calculations in the analysis of various solid forms of APIs.

Ritonavir, a protease inhibitor sold under the brand name Norvir®, is an antiviral medication that effectively targets the human immunodeficiency virus (HIV). Being probably the most important and best-known example of the crystal polymorphism in the field of pharmaceutics, ritonavir has been extensively studied in the last 30 years, which eventually led to the discovery of its new polymorph, Form III, in 2023. So far, two crystal structures of both Forms I and II of ritonavir were deposited in CCDC database. The aim of this study was to revisit those crystal structures, using NMR crystallography by recording the 13 C CP/MAS NMR spectra and performing GIPAW NMR calculations with CASTEP. The obtained results revealed the major discrepancies between the calculated and experimental NMR chemical shift values. Those differences were explained at the molecular level, as resulting from the differences in the experimentally determined and DFT-optimized positions of some atoms, mostly those forming phenyl and thiazole rings. This work is an example of how NMR crystallography can be used to verify and improve the already published crystal structures., (© 2024 Wiley-VCH GmbH.)

Vitamin E consists of a group of compounds including α- β- γ- and δ-tocopherols and α- β- γ- and δ-tocotrienols, containing the chroman-6-ol system. The recognition of the structural and dynamic properties of this system, present in all vitamers, seems to be important for the full explanation of the mechanism of the biological activity of vitamin E. This paper presents results of the structural analysis of the chosen 6-chromanyl ethereal derivatives using experimental (13 C NMR-in solution and solid state, as well as variable temperature experiments; single crystal X-ray diffraction) and theoretical (DFT) methods. For one of the studied compounds, 2,2,5,7,8-pentamethyl-6-((tetrahydro-2H-pyran-2-yl)oxy) chroman, the splitting of some signals was observed in the 13C dynamic NMR spectra. This observation was explained by the application of a conformational analysis and subsequent DFT optimization, followed by the calculation of NMR properties. [ABSTRACT FROM AUTHOR]

Turmeric is a traditional Indian spice that has recently become very popular worldwide because it contains a powerful ingredient called curcumin, which has strong anti-inflammatory properties. Hence, dietary supplements containing extracts rich in curcumin have gained great popularity. The main problems related to curcumin-containing dietary supplements are poor water solubility and the fact that they are often faked by using synthetic curcumin instead of the plant extract. In this article, we propose the use of the 13C CPMAS NMR method to control the quality of dietary supplements. The analysis of 13C CPMAS NMR spectra supported by GIPAW computations allowed us to identify a polymorphic form present in dietary supplements (which affected the solubility of curcumin) and to point out a dietary supplement that could be faked by using synthetic curcumin. Further PXRD and HPLC investigations confirmed that the examined supplement contained synthetic curcumin instead of the genuine extract. Our method can be used for routine control, especially because the investigation is performed directly from the capsule/tablet content and does not require any special sample preparation.

Computational methods are increasingly used to support interpreting, assigning and predicting the solid-state nuclear resonance magnetic spectra of materials. Currently, density functional theory is seen to achieve a good balance between efficiency and accuracy in solid-state chemistry. To be specific, density functional theory allows the assignment of signals in nuclear resonance magnetic spectra to specific sites and can help identify overlapped or missing signals from experimental nuclear resonance magnetic spectra. To avoid the difficulties correlated to all-electron calculations, a gauge including the projected augmented wave method was introduced to calculate nuclear resonance magnetic parameters with great success in organic crystals in the last decades. Thus, we developed a gauge including projected augmented pseudopotentials of 21 d elements and tested them on, respectively, oxides or nitrides (semiconductors), calculating chemical shift and quadrupolar coupling constant. This work can be considered the first step to improving the ab initio prediction of nuclear magnetic resonance parameters, and leaves open the possibility for inorganic compounds to constitute an alternative standard compound, with respect to tetramethylsilane, to calculate the chemical shift. Furthermore, this work represents the possibility to obtain results from first-principles calculations, to train a machine-learning model to solve or refine structures using predicted nuclear magnetic resonance spectra. [ABSTRACT FROM AUTHOR]

Modern approaches for calculating electric field gradient (EFF) tensors in molecular solids rely upon plane-wave calculations employing periodic boundary conditions (PBC). In practice, models employing PBCs are limited to generalized gradient approximation (GGA) density functionals. Hybrid density functionals applied in the context of gauge-including atomic orbital (GIAO) calculations have been shown to substantially improve the accuracy of predicted NMR parameters. Here we propose an efficient method that effectively combines the benefits of both periodic calculations and single-molecule techniques for predicting electric field gradient tensors in molecular solids. Periodic calculations using plane-wave basis sets were used to model the crystalline environment. We then introduce a molecular correction to the periodic result obtained from a single-molecule calculation performed with a hybrid density functional. Single-molecule calculations performed using hybrid density functionals were found to significantly improve the agreement of predicted 17O quadrupolar coupling constants (Cq) with experiment. We demonstrate a 31% reduction in the RMS error for the predicted 17O Cq values relative to standard plane-wave methods using a carefully constructed test set comprised of 22 oxygen-containing molecular crystals. We show comparable improvements in accuracy using five different hybrid density functionals and find predicted Cq values to be relatively insensitive to the choice of basis set used in the single molecule calculation. Finally, the utility of high-accuracy 17O Cq predictions is demonstrated by examining the disordered 4-Nitrobenzaldehyde crystal structure.

Oxygen‐17 and deuterium are two quadrupolar nuclei that are of interest for studying the structure and dynamics of materials by solid‐state nuclear magnetic resonance (NMR). Here, 17O and 2H NMR analyses of crystalline ibuprofen and terephthalic acid are reported. First, improved 17O‐labelling protocols of these molecules are described using mechanochemistry. Then, dynamics occurring around the carboxylic groups of ibuprofen are studied considering variable temperature 17O and 2H NMR data, as well as computational modelling (including molecular dynamics simulations). More specifically, motions related to the concerted double proton jump and the 180° flip of the H‐bonded (–COOH)2 unit in the crystal structure were looked into, and it was found that the merging of the C=O and C–OH 17O resonances at high temperatures cannot be explained by the sole presence of one of these motions. Lastly, preliminary experiments were performed with a 2H–17O diplexer connected to the probe. Such configurations can allow, among others, 2H and 17O NMR spectra to be recorded at different temperatures without needing to tune or to change probe configurations. Overall, this work offers a few leads which could be of use in future studies of other materials using 17O and 2H NMR. [ABSTRACT FROM AUTHOR]

Vitamin E consists of a group of compounds including α- β- γ- and δ-tocopherols and α- β- γ- and δ-tocotrienols, containing the chroman-6-ol system. The recognition of the structural and dynamic properties of this system, present in all vitamers, seems to be important for the full explanation of the mechanism of the biological activity of vitamin E. This paper presents results of the structural analysis of the chosen 6-chromanyl ethereal derivatives using experimental (13 C NMR-in solution and solid state, as well as variable temperature experiments; single crystal X-ray diffraction) and theoretical (DFT) methods. For one of the studied compounds, 2,2,5,7,8-pentamethyl-6-((tetrahydro-2H-pyran-2-yl)oxy) chroman, the splitting of some signals was observed in the 13C dynamic NMR spectra. This observation was explained by the application of a conformational analysis and subsequent DFT optimization, followed by the calculation of NMR properties.

The 1H, 13C, 15N, and 19F nuclear magnetic resonance (NMR) spectra of 11 2,5‐diaryl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones have been acquired in DMSO‐d6 solution and the 13C, 15N, and 19F NMR spectra have also been acquired in the solid state (solid‐state nuclear magnetic resonance [SSNMR] and magic angle spinning [MAS]). The X‐ray structures of Compounds 3, 5, and 6 have been determined by X‐ray diffraction. Theoretical calculations at the gauge‐independent atomic orbital (GIAO)/B3LYP/6‐311++G(d,p) level have provided a set of 321 chemical shifts that were compared with 310 experimental values in DMSO‐d6. To obtain good agreements, some effects need to be included. The SSNMR chemical shifts have been compared with gauge‐including projector‐augmented wave (GIPAW) calculations and with the heavy atom–light atom (HALA) effects. [ABSTRACT FROM AUTHOR]

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. 1H and 13C chemical shifts as well as 14N 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 1H‐1H double‐quantum (DQ) MAS and heteronuclear 1H‐13C and 14N‐1H spectra are presented. Only small differences of up to 0.1 and 0.6 ppm for 1H and 13C 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 1H chemical shifts for isolated molecules and the full crystal structures is indicative of hydrogen bonding strength. [ABSTRACT FROM AUTHOR]

The infrared spectrum of indirubin in the solid state and the 1H, 13C and 15N NMR spectra in DMSO‐d6 solution as well as the 13C and 15N CPMAS spectra have been recorded. Different types of calculations (B3LYP, GIAO, and GIPAW) have been carried out. Experimental and calculated values were compared yielding commensurate results. E/Z isomerism was explored, as was oxo/hydroxy tautomerism. [ABSTRACT FROM AUTHOR]

The NMR chemical shifts of two azoles and one benzazole whose crystal structures present polymorphism have been computed using the GIPAW approach. 15N and 13C nuclei have been studied. Statistical analysis of the computed 13C and 15N chemical shifts indicates that the GIPAW chemical shifts reproduce with a high degree of accuracy those experimentally reported. This methodology can be used to identify other polymorphic crystal structures. [ABSTRACT FROM AUTHOR]

Lead nitrate is an inorganic salt, commonly used for the accurate temperature determination in the solid state NMR spectroscopy, due to the strong temperature dependence of the 207Pb chemical shift. As the reason for this phenomenon remained unknown, the main purpose of this study was to explain this temperature dependence at the molecular level. To achieve this, combined CASTEP geometry optimization, quantum molecular dynamics at chosen temperatures and GIPAW NMR computations were performed. Due to the previous literature reports on inaccuracy in the calculation of 207Pb NMR parameters using GIPAW, a large emphasis was put on the optimization of computational method. The application of quantum molecular dynamics provided the simulation of the temperature‐dependent vibrational motions and enabled to accurately compute the changes in the value of Pb δiso resulting from them. © 2018 Wiley Periodicals, Inc. This study aims to explain, at the molecular level, the experimentally observed temperature dependence of 207Pb isotropic chemical shift value in the solid state NMR spectra of lead nitrate. For this purpose combined CASTEP geometry optimization, quantum molecular dynamics at chosen temperatures and GIPAW calculations of NMR parameters were performed. The influence of temperature‐depending vibrational motions on the NMR parameters was precisely reflected in the calculations results. [ABSTRACT FROM AUTHOR]

Abstract The structural characterization of fluorinated zigzag (4,0), (6,0), (8,0) and (10,0) single walled carbon nanotubes (F-SWCNT) has been investigated theoretically using C 13 and F 19 NMR spectroscopy. The functional groups N H , N C H 3 , N C H 2 O H , C H 2 N H C H 2 and (C H 2 ) 2 C O O H have been attached covalently in (8,0) F-SWCNT and the corresponding changes in C 13 and F 19 chemical shift signatures have been examined. The binding energy, charge and bond length variation due to fluorination are reported. A set of isotropic and anisotropic chemical shift variables is deduced from the Gauge IncludinIncluding Projector Augmented Wave (GIPAW) computations of the F 19 and C 13 nuclei in Pristine and F-SWCNTs. We show that the F 19 chemical shift parameters are better structural markers than their C 13 counterparts to clearly reveal the nanotube diameter dependency and the type of functional groups which are attached to the fluoronanotubes. Graphical abstract Image 1 Highlights • Structure of Zigzag (4,0), (6,0), (8,0) and (10,0) Pristine and F-SWCNTs are investigated computationally. • The binding energy, charge and bond length variation due to fluorination are reported. • 13C and 19F isotropic and anisotropic chemical shifts are computed using GIPAW method. • 19F chemical shift parameters clearly reveal the diameter dispersion in nanotubes. • The anisotropy of 19F chemical shift distinctly indictates the type of functional group attached to the CNT. [ABSTRACT FROM AUTHOR]

In the following research acetylation as an unexplored factor in the anomeric effect in carbohydrate chemistry has been examined. Crystallographic data for methyl glycosides and their acetates have been compared and discussed. Some of the methyl glycosides form hydrogen bonding with the participation of acetal oxygen atoms. This seems to have the most significant influence on the structural diagnostic parameters for anomeric effect. Abbreviations: Me-α-Glc: methyl α-D-glucopyranoside; Me-β-Glc: methyl β-D-glucopyranoside; Me-α-Gal: methyl α-D-galactopyranoside; Me-β-Gal: methyl β-D-galactopyranoside; Me-α-Man: methyl α-D-mannopyranoside; Me-β-Man: methyl β-D-mannopyranoside; Ac-Me-α-Glc: methyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside; Ac-Me-β-Glc: methyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside; Ac-Me-α-Gal: methyl 2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside; Ac-Me-β-Gal: methyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside; Ac-Me-α-Man: methyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside; Ac-Me-β-Man: methyl 2,3,4,6-tetra-O-acetyl-β-D-mannopyranoside; GIPAW (Gauge Including Projector Augmented Waves) calculations: a DFT based method used for calculating nuclear magnetic resonance parameters; CP/MAS NMR: cross-polarisation (CP) magic angle spinning (MAS) NMR spectroscopy; δss: chemical shift in 13C CP/MAS NMR spectrum; δt: theoretical chemical shift: as derived from GIPAW DFT; dis: distorted multiplet in 1H NMR spectrum. [ABSTRACT FROM AUTHOR]

Abstract Piracetam, a popular nootropic drug, widely used in the treatment of age-associated mental decline and disorders of the nervous system such as Alzheimer's disease and dementia exists under normal pressure in three polymorphic forms (P1, P2 and P3) of different stability. In this work the relative stability of piracetam polymorphs depending on the temperature was studied using the ssNMR spectroscopy combined with ab initio DFT calculations. The ssNMR spectroscopy enabled the analysis of polymorphic phase transition in the case of pure active substance as well as polymorphic form identification in the analysis of the commercial solid dosage formulations. Quantum chemical calculations of phonon density of states were performed to obtain the temperature dependence of the enthalpy, entropy and free energy of the piracetam polymorphs in a quasi-harmonic approximation. GIPAW NMR calculations combined with molecular dynamics were performed to support the chemical shift assignment. The obtained results showed that DFT calculations can be used not only to obtain the NMR parameters but also to predict the influence of the temperature on the stability order of the polymorphic forms of molecular crystals. Graphical abstract Image 1 Highlights • Polymorphism of piracetam was studied using ssNMR. • Very strong residual dipolar couplings were observed. • Calculations of phonon DOS used to predict the order of polymorphic forms stability. • GIPAW calculations of NMR parameters combined with quantum molecular dynamics. [ABSTRACT FROM AUTHOR]

Magnesium oxide (MgO) can convert to different magnesium-containing compounds depending on exposure and environmental conditions. Many MgO-based phases contain hydrated species allowing 1H-nuclear magnetic resonance (NMR) spectroscopy to be used in the characterization and quantification of proton-containing phases; however, surprisingly limited examples have been reported. Here, 1H-magic angle spinning (MAS) NMR spectra of select Mg-based minerals are presented and assigned. These experimental results are combined with computational NMR density functional theory (DFT) periodic calculations to calibrate the predicted chemical shielding results. This correlation is then used to predict the NMR shielding for a series of different MgO hydroxide, magnesium chloride hydrate, magnesium perchlorate, and magnesium cement compounds to aid in the future assignment of 1H-NMR spectra for complex Mg phases.

Glycine is a common amino acid with relatively complex chemistry in solid state. Although several polymorphs (α, β, δ, γ, ε) of crystalline glycine are known, for NMR spectroscopy the most important is a polymorph, which is used as a standard for calibration of spectrometer performance and therefore it is intensively studied by both experimental methods and theoretical computation. The great scientific interest in a glycine results in a large number of crystallographic information files (CIFs) deposited in Cambridge Structural Database (CSD). The aim of this study was to evaluate the influence of the chosen crystal structure of α glycine obtained in different crystallographic experimental conditions (temperature, pressure and source of radiation of α glycine) on the results of periodic DFT calculation. For this purpose the total of 136 GIPAW calculations of α glycine NMR parameters were performed, preceded by the four approaches (“SP”, “only H”, “full”, “full+cell”) of structure preparation. The analysis of the results of those computations performed on the representative group of 34 structures obtained at various experimental conditions revealed that though the structures were generally characterized by good accuracy (R < 0.05 for most of them) the results of the periodic DFT calculations performed using the unoptimized structures differed significantly. The values of the standard deviations of the studied NMR parameters were in most cases decreasing with the number of optimized parameters. The most accurate results (of the calculations) were in most cases obtained using the structures with solely hydrogen atoms positions optimized. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This paper compares the absolute shieldings obtained by gauge‐including‐projected‐augmented‐wave (GIPAW) to those obtained by gauge‐invariant atomic orbital/Becke, 3‐parameter, Lee‐Yang‐Parr (GIAO/B3LYP)/6–311++G(d,p)‐polarizable continuum model (PCM, dimethyl sulfoxide) for nine benzazoles (benzimidazoles, indazoles, and benzotriazoles) recorded in the solid‐state. Three nuclei were explored, 13C, 15N, and 19F, and the gauge‐including‐projected‐augmented‐wave approach only proved better for 15N MAS NMR. [ABSTRACT FROM AUTHOR]

The 1H chemical shielding anisotropy (CSA) is an NMR parameter that is exquisitely sensitive to the local environment of protons in crystalline systems, but it is difficult to obtain it experimentally due to the need to concomitantly suppress other anisotropic interactions in the solid-state NMR (SSNMR) pulse sequences. The SSNMR measurements of the 1H CSA are particularly challenging if the fast magic-angle-spinning (MAS) is applied. It is thus important to confront the results of both the single-crystal (SC) and fast-MAS experiments with their theoretical counterparts. Here the plane-waves (PW) DFT calculations have been carried out using two functionals in order to precisely characterize the structures and the 1H NMR chemical shielding tensors (CSTs) of the solid forms of maleic, malonic, and citric acids, and of L-histidine hydrochloride monohydrate. The level of agreement between the PW DFT and either SC or fast-MAS SSNMR 1H CSA data has been critically compared. It has been found that for the eigenvalues of the 1H CSTs provided by the fast-MAS measurements, an accuracy limit of current PW DFT predictions is about two ppm in terms of the standard deviation of the linear regression model, and sources of this error have been thoroughly discussed.

Diosmin, a flavone glycoside frequently used in therapy of various veins diseases in monohydrate form, exhibits poor solubility in water and low bioavailability. Due to the fact that the anhydrous forms of drugs generally have better bioavailability than the corresponding hydrates, the aim of this study was to analyze the conversion of diosmin monohydrate (DSNM) to anhydrous diosmin (DSNA) that occurs upon heating. The mechanism of this transformation was examined as well as advanced structural studies of each form were performed using 13C CP/MAS SSNMR, DSC, FT-IR and PXRD techniques. Spectroscopic findings were supported by CASTEP-DFT calculations of NMR and IR parameters. The pathway of reversible transformation was specified as follows: DSNM upon heating for 24 h at temperature up to 110 °C losses non-crystalline water and converts into metastable form (DSNM*) that turns into DSNA during heating at temperature 140 °C for next 24 h. Under room temperature DSNA spontaneously absorbs moisture from air and turns into a DSNM within 72 h. The detailed analysis of CP kinetic parameters (T1ρI) revealed presence of metastable, intermediate form of diosmin (DSNM*) and allowed its characterization. The results are essential for further studies comparing dissolution and bioavailability of DSNM and DSNA. The study provided an understanding of the conversion pathway of the diosmin monohydrate into its anhydrate form when it is exposed to increased temperature. [ABSTRACT FROM AUTHOR]

With the increasing number of organocalcium and organomagnesium complexes under development, there is a real need to be able to characterize in detail their local environment in order to fully rationalize their reactivity. For crystalline structures, in cases when diffraction techniques are insufficient, additional local spectroscopies like 25Mg and 43Ca solid-state NMR may provide valuable information to help fully establish the local environment of the metal ions. In this current work, a prospective DFT investigation on crystalline magnesium and calcium complexes involving low-coordination numbers and N-bearing organic ligands was carried out, in which the 25Mg and 43Ca NMR parameters [isotropic chemical shift, chemical shift anisotropy (CSA) and quadrupolar parameters] were calculated for each structure. The analysis of the calculated parameters in relation to the local environment of the metal ions revealed that they are highly sensitive to very small changes in geometry/distances, and hence that they could be used to assist in the refinement of crystal structures. Moreover, such calculations provide a guideline as to how the NMR measurements will need to be performed, revealing that these will be very challenging. [ABSTRACT FROM AUTHOR]

We report Density Functional Theory calculations for the atomic positions and the electric-field gradients (EFG) at Zr sites in a series of Zr compounds, with the FP-LAPW and the GIPAW methods. These data are used to obtain a value for the nuclear quadrupole moments of 90Zr and 91Zr, of which the precision and reliability with respect to tabulated values is discussed. An error bar on our suggested values is provided. Good agreement is obtained between the (faster) GIPAW method and (slower yet established) FP-LAPW method, especially when identical atomic positions are imposed. This increases the confidence in GIPAW calculations for electric-field gradient and nuclear quadrupole moment determination. [ABSTRACT FROM AUTHOR]

Two polymorphs of the drug compound metergoline (C25H29N3O2) were investigated in detail by solid-state NMR measurements. The results have been analysed by an advanced procedure, which uses experimental input together with the results of quantum chemical calculations that were performed for molecular crystals. In this way, it was possible to assign the total of 40 1H–13C correlation pairs in a highly complex system, namely, in the dynamically disordered polymorph with two independent molecules in the unit cell of a large volume of 4234 Å3. For the simpler polymorph, which exhibits only small-amplitude motions and has just one molecule in the unit cell with a volume of 529.0 Å3, the values of the principal elements of the 13C chemical shift tensors were measured. Additionally, for this polymorph, a set of crystal structure predictions were generated, and the {13C, 1H} isotropic and 13C anisotropic chemical shielding data were computed while using the gauge-including projector augmented-wave approach combined with the “revised Perdew-Burke-Ernzerhof“ exchange-correlation functional (GIPAW-RPBE). The experimental and theoretical results were combined in an application of the newly developed strategy to polymorph discrimination. This research thus opens up new routes towards more accurate characterization of the polymorphism of drug formulations.

Nuclear quadrupole resonances for 14 N and 17 O nuclei are exquisitely sensitive to interactions with surrounding atoms. As a result, nitrogen and oxygen solid-state nuclear magnetic resonance (ssNMR) provides a powerful tool for investigating structure and dynamics in complex systems. First-principles calculations are increasingly used to facilitate spectral assignment and to evaluate and adjust crystal structures. Recent work combining the strengths of planewave density functional theory (DFT) calculations with a single molecule correction obtained using a higher level of theory has proven successful in improving the accuracy of predicted chemical shielding (CS) tensors and 17 O quadrupolar coupling constants ( C q ). Here we extend this work by examining the accuracy of predicted 14 N and 17 O electric field gradient (EFG) tensor components obtained using alternative planewave-corrections involving cluster and two-body fragment-based calculations. We benchmark the accuracy of CS and EFG tensor predictions for both nitrogen and oxygen using planewave, two-body fragment, and enhanced planewave-corrected techniques. Combining planewave and two-body fragment calculations reduces the error in predicted 17 O C q values by 35% relative to traditional planewave calculations. These enhanced planewave-correction methods improve the accuracy of 17 O and 14 N EFG tensor components by 15% relative to planewave DFT but yield minimal improvement relative to a simple molecular correction. However, in structural environments involving either high symmetry or strong intermolecular interactions, enhanced planewave-corrected methods provide a distinct advantage., (© 2022 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.)

We introduce two open source tools to aid the processing and visualisation of ab-initio computed solid-state NMR parameters. The Magres file format for computed NMR parameters (as implemented in CASTEP v8.0 and QuantumEspresso v5.0.0) is implemented. MagresView is built upon the widely used Jmol crystal viewer, and provides an intuitive environment to display computed NMR parameters. It can provide simple pictorial representation of one- and two-dimensional NMR spectra as well as output a selected spin-system for exact simulations with dedicated spin-dynamics software. MagresPython provides a simple scripting environment to manipulate large numbers of computed NMR parameters to search for structural correlations. [ABSTRACT FROM AUTHOR]

13 C/ 15 N (experimental and ab initio ) solid-state NMR was used to achieve an affordable way to improve hydrogen refinement of 6-aminopenicillanic acid (6-APA) structure. The lattice effect on the isotropic chemical shifts was probed by using two different magnetic shielding calculations: isolated molecules and periodic crystal structure. The electron density difference maps of optimized and non-optimized structures were calculated in order to investigate the interactions inside the 6-APA unit cell. The 13 C and 15 N chemical shifts assignments were unambiguously stablished. In addition, some of the literature 13 C resonances ambiguities could be properly solved. [ABSTRACT FROM AUTHOR]

29Si and 31P magnetic-shielding tensors in covalent network solids have been evaluated using periodic and cluster-based calculations. The cluster-based computational methodology employs pseudoatoms to reduce the net charge (resulting from missing co-ordination on the terminal atoms) through valence modification of terminal atoms using bond-valence theory (VMTA/BV). The magnetic-shielding tensors computed with the VMTA/BV method are compared to magnetic-shielding tensors determined with the periodic GIPAW approach. The cluster-based all-electron calculations agree with experiment better than the GIPAW calculations, particularly for predicting absolute magnetic shielding and for predicting chemical shifts. The performance of the DFT functionals CA-PZ, PW91, PBE, rPBE, PBEsol, WC, and PBE0 are assessed for the prediction of 29Si and 31P magnetic-shielding constants. Calculations using the hybrid functional PBE0, in combination with the VMTA/BV approach, result in excellent agreement with experiment. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In this article we report the results of combined theoretical and experimental structural studies on cinnamic acid derivatives (CADs), one of the main groups of secondary metabolites present in various medicinal plant species and food products of plant origin. The effects of structural differences in CADs on their spectroscopic properties were studied in detail by both: solid-state NMR and GIAO/GIPAW calculations. Theoretical computations were used in order to perform signal assignment in 13 C CP/MAS NMR spectra of the cinnamic, o-coumaric, m-coumaric, p-coumaric, caffeic, ferulic, sinapic and 3,4-dimethoxycinnamic acids, and to evaluate the accuracy of GIPAW and GIAO methodology. [ABSTRACT FROM AUTHOR]

Solid-state NMR is an excellent and useful method for analyzing solid-state forms of drugs. In the 13 C CP/MAS NMR spectra of the solid dosage forms many of the signals originate from the excipients and should be distinguished from those of active pharmaceutical ingredient (API). In this work the most common pharmaceutical excipients used in the solid drug formulations: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon ® were analyzed. Their 13 C CP/MAS NMR spectra were recorded and the signals were assigned, employing the results (R 2 : 0.948–0.998) of GIPAW calculations and theoretical chemical shifts. The 13 C ssNMR spectra for some of the studied excipients have not been published before while for the other signals in the spectra they were not properly assigned or the assignments were not correct. The results summarize and complement the data on the 13 C ssNMR analysis of the most common pharmaceutical excipients and are essential for further NMR studies of API-excipient interactions in the pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Ab initio methods for predicting NMR parameters in the solid state are an essential tool for assigning experimental spectra and play an increasingly important role in structural characterizations. Recently, a molecular correction (MC) technique has been developed which combines the strengths of plane-wave methods (GIPAW) with single molecule calculations employing Gaussian basis sets. The GIPAW + MC method relies on a periodic calculation performed at a lower level of theory to model the crystalline environment. The GIPAW result is then corrected using a single molecule calculation performed at a higher level of theory. The success of the GIPAW + MC method in predicting a range of NMR parameters is a result of the highly local character of the tensors underlying the NMR observable. However, in applications involving strong intermolecular interactions we find that expanding the region treated at the higher level of theory more accurately captures local many-body contributions to the N 15 NMR chemical shielding (CS) tensor. We propose alternative corrections to GIPAW which capture interactions between adjacent molecules at a higher level of theory using either fragment or cluster-based calculations. Benchmark calculations performed on N 15 and C 13 data sets show that these advanced GIPAW-corrected calculations improve the accuracy of chemical shielding tensor predictions relative to existing methods. Specifically, cluster-based N 15 corrections show a 24% and 17% reduction in RMS error relative to GIPAW and GIPAW + MC calculations, respectively. Comparing the benchmark data sets using multiple computational models demonstrates that N 15 CS tensor calculations are significantly more sensitive to intermolecular interactions relative to C 13. However, fragment and cluster-based corrections that include direct hydrogen bond partners are sufficient for optimizing the accuracy of GIPAW-corrected methods. Finally, GIPAW-corrected methods are applied to the particularly challenging NMR spectral assignment of guanosine dihydrate which contains two guanosine molecules in the asymmetric unit. [Display omitted] • Combining GIPAW with cluster or fragment calculations improves the accuracy of 15N chemical shielding calculations relative to both GIPAW and existing molecular correction techniques. • Fragment-corrected GIPAW calculations employing electrostatic embedding match the accuracy of computationally demanding cluster-correction methods in the prediction of 15N CSA tensor elements. • On the basis of fragment-corrected GIPAW calculations we assign all six experimentally resolved 13C resonances and six of the ten 15N resonances for guanosine dihydrate. [ABSTRACT FROM AUTHOR]

New salts of teriflunomide TFM (drug approved for Multiple Sclerosis treatment) with inorganic counterions: lithium (TFM_Li) , sodium (TFM_Na) , potassium (TFM_K) , rubidium (TFM_Rb) , caesium (TFM_Cs) and ammonium (TFM_NH 4) were prepared and investigated employing solid state NMR Spectroscopy, Powder X-ray Diffraction PXRD and Single Crystal X-ray Diffraction (SC XRD). Crystal and molecular structures of three salts: TFM_Na (CCDC: 2173257), TFM_Cs (CCDC: 2165288) and TFM_NH 4 (CCDC: 2165281) were determined and deposited. Compared to the native TFM , for all crystalline salt structures, a conformational change of the teriflunomide molecule involving about 180-degree rotation of the end group, forming an intramolecular hydrogen bond N–H⋯O is observed. By applying a complementary multi-technique approach, employing 1D and 2D solid state MAS NMR techniques, single and powder X-ray diffraction measurements, as well as the DFT-based GIPAW calculations of NMR chemical shifts for TFM_Na and TFM_Cs allowed to propose structural features of TFM_Li for which it was not possible to obtain adequate material for single crystal X-Ray measurement. [Display omitted] • Applying the NMR crystallography approach allowed to systematically study the teriflunomide salts. • The common feature of teriflunomide salts is the conformational change of its skeleton comparing to native form. • Based on the multi-nuclear solid state NMR results, we were able to present structural models for teriflunomide salts. [ABSTRACT FROM AUTHOR]

Time-differential perturbed angular correlations spectroscopy of palladium in doped germanium has identified palladium-vacancy pairing in n-type antimony-doped, p-type gallium-doped and undoped germanium. In contrast, an equivalent study of palladium defects in doped silicon suggests a different scenario for the silicon host. Palladium-vacancy pairing has been proposed in n-type silicon irrespective of the dopant type (phosphorous, arsenic or antimony) but palladium–boron pairing has been speculated to occur in p-type boron-doped silicon. This thus raises the question: why does palladium pair with a dopant atom in p-type silicon, but with a vacancy in p-type germanium? Based on the density functional theory calculations carried out in this work, it is suggested that the size of the dopant and the host material both play a crucial role in determining the type of palladium-defect complex that is formed. The calculations predict a configuration with the palladium atom on a bond-centered interstitial site pairing with a semi-vacancy on either side in gallium-doped and antimony-doped silicon and germanium, respectively. Whereas, a configuration with the palladium atom on a bond-centered interstitial site pairing with the dopant was proposed in boron-doped silicon and germanium. In further support of the argument, in n-type phosphorous-doped materials the calculations predict a configuration with the palladium atom on a bond-centered interstitial site pairing with a semi-vacancy on either side in silicon, but a configuration with the palladium atom on a bond-centered interstitial site pairing with the phosphorous dopant in germanium. [ABSTRACT FROM AUTHOR]

43 Ca MQMAS NMR spectra of three silica-based glasses in which Ca 2+ ions play different structural roles have been collected and processed in order to extract the underlying NMR parameter distributions. The NMR parameters have been interpreted with the help of molecular dynamics simulations and DFT-GIPAW calculations. This synergetic experimental–computational approach has allowed us to investigate the Ca environment, to estimate Ca coordination numbers from MD-derived models, and to push further the discussion about 43 Ca NMR sensitivity to the first and second coordination spheres: 43 Ca δ iso and Ca–O distance can be successfully correlated as a function of Ca coordination number. [ABSTRACT FROM AUTHOR]