scholarly journals Molecular Crystal Forms of Antitubercular Ethionamide with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 818
Author(s):  
Simone Bordignon ◽  
Paolo Cerreia Vioglio ◽  
Elena Amadio ◽  
Federica Rossi ◽  
Emanuele Priola ◽  
...  
Keyword(s):  
Solid State ◽  
Tartaric Acid ◽  
Fumaric Acid ◽  
Dicarboxylic Acids ◽  
Active Pharmaceutical Ingredient ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Multicomponent Systems ◽  
Crystal Forms

We report on the preparation, characterization, and bioavailability properties of three new crystal forms of ethionamide, an antitubercular agent used in the treatment of drug-resistant tuberculosis. The new adducts were obtained by combining the active pharmaceutical ingredient with three dicarboxylic acids, namely glutaric, malonic and tartaric acid, in equimolar ratios. Crystal structures were obtained for all three adducts and were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. The ethionamide-glutaric acid and the ethionamide-malonic acid adducts were thoroughly characterized by means of solid-state NMR (13C and 15N Cross-Polarization Magic Angle Spinning or CPMAS) to confirm the position of the carboxylic proton, and they were found to be a cocrystal and a salt, respectively; they were compared with two previously reported multicomponent systems of ethionamide with maleic and fumaric acid. Ethionamide-tartaric acid was found to be a rare example of kryptoracemic cocrystal. In vitro bioavailability enhancements up to a factor 3 compared to pure ethionamide were assessed for all obtained adducts.

A 13C solid-state NMR investigation of four cocrystals of caffeine and theophylline

2017 ◽  
Vol 73 (3) ◽  
pp. 234-243 ◽  
Author(s):  
Nicolas J. Vigilante ◽  
Manish A. Mehta
Keyword(s):  
Solid State ◽  
Chemical Shift ◽  
Solid State Nmr ◽  
Chemical Shifts ◽  
Active Pharmaceutical Ingredient ◽  
Magic Angle Spinning ◽  
Chemical Shift Tensor ◽  
Magic Angle ◽  
Isotropic Chemical Shifts ◽  
Angle Spinning

We report an analysis of the 13C solid-state NMR chemical shift data in a series of four cocrystals involving two active pharmaceutical ingredient (API) mimics (caffeine and theophylline) and two diacid coformers (malonic acid and glutaric acid). Within this controlled set, we make comparisons of the isotropic chemical shifts and the principal values of the chemical shift tensor. The dispersion at 14.1 T (600 MHz 1H) shows crystallographic splittings in some of the resonances in the magic angle spinning spectra. By comparing the isotropic chemical shifts of individual C atoms across the four cocrystals, we are able to identify pronounced effects on the local electronic structure at some sites. We perform a similar analysis of the principal values of the chemical shift tensors for the anisotropic C atoms (most of the ring C atoms for the API mimics and the carbonyl C atoms of the diacid coformers) and link them to differences in the known crystal structures. We discuss the future prospects for extending this type of study to incorporate the full chemical shift tensor, including its orientation in the crystal frame of reference.

scholarly journals Development of in vitro-grown spheroids as a 3D tumor model system for solid-state NMR spectroscopy

2020 ◽  
Vol 74 (8-9) ◽  
pp. 401-412 ◽  
Author(s):  
Reinier Damman ◽  
Alessandra Lucini Paioni ◽  
Katerina T. Xenaki ◽  
Irati Beltrán Hernández ◽  
Paul M. P. van Bergen en Henegouwen ◽  
...  
Keyword(s):  
Solid State ◽  
Nmr Spectroscopy ◽  
Solid State Nmr ◽  
Mammalian Cells ◽  
Magic Angle Spinning ◽  
Model System ◽  
Magic Angle ◽  
Cell Extracts ◽  
Cellular Environment

Abstract Recent advances in the field of in-cell NMR spectroscopy have made it possible to study proteins in the context of bacterial or mammalian cell extracts or even entire cells. As most mammalian cells are part of a multi-cellular complex, there is a need to develop novel NMR approaches enabling the study of proteins within the complexity of a 3D cellular environment. Here we investigate the use of the hanging drop method to grow spheroids which are homogenous in size and shape as a model system to study solid tumors using solid-state NMR (ssNMR) spectroscopy. We find that these spheroids are stable under magic-angle-spinning conditions and show a clear change in metabolic profile as compared to single cell preparations. Finally, we utilize dynamic nuclear polarization (DNP)-supported ssNMR measurements to show that low concentrations of labelled nanobodies targeting EGFR (7D12) can be detected inside the spheroids. These findings suggest that solid-state NMR can be used to directly examine proteins or other biomolecules in a 3D cellular microenvironment with potential applications in pharmacological research.

scholarly journals Exploring the salt–cocrystal continuum with solid-state NMR using natural-abundance samples: implications for crystal engineering

IUCrJ ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. 466-475 ◽  
Author(s):  
Lalit Rajput ◽  
Manas Banik ◽  
Jayasubba Reddy Yarava ◽  
Sumy Joseph ◽  
Manoj Kumar Pandey ◽  
...  
Keyword(s):  
Solid State ◽  
Crystal Engineering ◽  
Solid State Nmr ◽  
Active Pharmaceutical Ingredient ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Angle Spinning ◽  
Solid Form ◽  
Simple Systems ◽  
Relationship Of

There has been significant recent interest in differentiating multicomponent solid forms, such as salts and cocrystals, and, where appropriate, in determining the position of the proton in theX—H...A—YX−...H—A+—Ycontinuum in these systems, owing to the direct relationship of this property to the clinical, regulatory and legal requirements for an active pharmaceutical ingredient (API). In the present study, solid forms of simple cocrystals/salts were investigated by high-field (700 MHz) solid-state NMR (ssNMR) using samples with naturally abundant15N nuclei. Four model compounds in a series of prototypical salt/cocrystal/continuum systems exhibiting {PyN...H—O—}/{PyN+—H...O−} hydrogen bonds (Py is pyridine) were selected and prepared. The crystal structures were determined at both low and room temperature using X-ray diffraction. The H-atom positions were determined by measuring the15N—1H distances through15N-1H dipolar interactions using two-dimensional inversely proton-detected cross polarization with variable contact-time (invCP-VC)1H→15N→1H experiments at ultrafast (νR≥ 60–70 kHz) magic angle spinning (MAS) frequency. It is observed that this method is sensitive enough to determine the proton position even in a continuum where an ambiguity of terminology for the solid form often arises. This work, while carried out on simple systems, has implications in the pharmaceutical industry where the salt/cocrystal/continuum condition of APIs is considered seriously.

scholarly journals Preparation of Li3PS4–Li3PO4 Solid Electrolytes by Liquid-Phase Shaking for All-Solid-State Batteries

2021 ◽  
Vol 2 (1) ◽  
pp. 39-48
Author(s):  
Nguyen H. H. Phuc ◽  
Takaki Maeda ◽  
Tokoharu Yamamoto ◽  
Hiroyuki Muto ◽  
Atsunori Matsuda
Keyword(s):  
Solid Solution ◽  
Solid State ◽  
Liquid Phase ◽  
Room Temperature ◽  
Reaction Medium ◽  
Magic Angle Spinning ◽  
Resonance Spectroscopy ◽  
Synthesis Methods ◽  
Magic Angle ◽  
Angle Spinning

A solid solution of a 100Li3PS4·xLi3PO4 solid electrolyte was easily prepared by liquid-phase synthesis. Instead of the conventional solid-state synthesis methods, ethyl propionate was used as the reaction medium. The initial stage of the reaction among Li2S, P2S5 and Li3PO4 was proved by ultraviolet-visible spectroscopy. The powder X-ray diffraction (XRD) results showed that the solid solution was formed up to x = 6. At x = 20, XRD peaks of Li3PO4 were detected in the prepared sample after heat treatment at 170 °C. However, the samples obtained at room temperature showed no evidence of Li3PO4 remaining for x = 20. Solid phosphorus-31 magic angle spinning nuclear magnetic resonance spectroscopy results proved the formation of a POS33− unit in the sample with x = 6. Improvements of ionic conductivity at room temperature and activation energy were obtained with the formation of the solid solution. The sample with x = 6 exhibited a better stability against Li metal than that with x = 0. The all-solid-state half-cell employing the sample with x = 6 at the positive electrode exhibited a better charge–discharge capacity than that employing the sample with x = 0.

scholarly journals Combination of solid state NMR and DFT calculation to elucidate the state of sodium in hard carbon electrodes

2016 ◽  
Vol 4 (34) ◽  
pp. 13183-13193 ◽  
Author(s):  
Ryohei Morita ◽  
Kazuma Gotoh ◽  
Mika Fukunishi ◽  
Kei Kubota ◽  
Shinichi Komaba ◽  
...  
Keyword(s):  
Solid State ◽  
Solid State Nmr ◽  
Dft Calculation ◽  
Magic Angle Spinning ◽  
The State ◽  
Mas Nmr ◽  
Magic Angle ◽  
Multiple Quantum ◽  
Hard Carbon ◽  
Angle Spinning

We examined the state of sodium electrochemically inserted in HC prepared at 700–2000 °C using solid state Na magic angle spinning (MAS) NMR and multiple quantum (MQ) MAS NMR.

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