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Daniel McNamara, Shawn Yin, Duohai Pan, George Crull, Peter Timmins, Balvinder Vig
A generalized screening approach, applying isothermal calorimetry at 37°C 100%RH, to formulations of spray dried dispersions (SDDs) for two active pharmaceutical ingredients (APIs) (BMS-903452 and BMS-986034) is demonstrated. APIs 452 and 034, with similar chemotypes, were synthesized and promoted during development for oral dosing. Both APIs were formulated as SDDs for animal exposure studies using the polymer hydroxypropylmethlycellulose acetyl succinate M grade (HPMCAS M). 452 formulated at 30% (wt/wt%) was an extremely robust SDD that was able to withstand 40°C 75%RH open storage conditions for 6 months with no physical evidence of crystallization or loss of dissolution performance...
January 9, 2017: Molecular Pharmaceutics
Paroma Chakravarty, Joseph W Lubach, Jonathan Hau, Karthik Nagapudi
The purpose of this study was to determine the drug-polymer miscibility of GENE-A, a Genentech molecule, and hydroxypropyl methylcellulose-acetate succinate (HPMC-AS), a polymer, using computational and experimental approaches. The Flory-Huggins interaction parameter,χ, was obtained by calculating the solubility parameters for GENE-A and HPMC-AS over the temperature range of 25-100°C to obtain the free energy of mixing at different drug loadings (0-100%) using the Materials Studio modeling and simulation platform (thermodynamic approach)...
January 4, 2017: International Journal of Pharmaceutics
Wei Qiang, Wai-Ming Yau, Jun-Xia Lu, John Collinge, Robert Tycko
Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions. Recent experiments suggest that variations in amyloid-β fibril structure in vivo may correlate with variations in Alzheimer's disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes...
January 12, 2017: Nature
Renu Chadha, Dimpy Rani, Parnika Goyal
PURPOSE: To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties. METHODS: Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters...
December 29, 2016: Pharmaceutical Research
Frédéric A Perras, Hao Luo, Ximing Zhang, Nathan S Mosier, Marek Pruski, Mahdi M Abu-Omar
Lignocellulosic biomass is a promising sustainable feedstock for the production of biofuels, biomaterials, and bio-specialty chemicals. However, efficient utilization of biomass has been limited by our poor understanding of its molecular structure. Here, we report a dynamic nuclear polarization (DNP)-enhanced solid-state (SS)NMR study of the molecular structure of biomass, both pre- and post-catalytic treatment. This technique enables the measurement of 2D homonuclear (13)C-(13)C correlation SSNMR spectra under natural abundance, yielding, for the first time, an atomic-level picture of the structure of raw and catalytically treated biomass samples...
December 27, 2016: Journal of Physical Chemistry. A
Helen R Thomas, Daniel J Phillips, Neil R Wilson, Matthew I Gibson, Jonathan P Rourke
The direct grafting of poly(N-isopropylacrylamide) to the basal plane of graphene oxide has been achieved in a single step: cleavage of the terminal thiocarbonylthio group on RAFT grown poly(N-isopropylacrylamide) reveals a reactive thiol that attacks the epoxides present across the surface of graphene oxide. The new composite material was characterised by a combination of SSNMR, FTIR, Raman, EDX, XPS, TGA and contact angle measurement; it shows enhanced thermal stability and solubility in water.
December 28, 2015: Polymer Chemistry
María M Quesada-Moreno, Juan Ramón Avilés-Moreno, Juan Jesús López-González, Kane Jacob, Laure Vendier, Michel Etienne, Ibon Alkorta, José Elguero, Rosa M Claramunt
1H-Indazole derivatives exhibit a remarkable property since some of them form chiral supramolecular structures starting from achiral monomers. The present work deals with the study of three perfluorinated 1H-indazoles that resolve spontaneously as conglomerates. These conglomerates can contain either a pure enantiomer (one helix) or a mixture of both enantiomers (both helices) with an enantiomeric excess (e.e.) of one of them. The difficulty of the structural analysis of these types of compounds is thus clear...
January 4, 2017: Physical Chemistry Chemical Physics: PCCP
David Townsend, Eleri Hughes, Rohanah Hussain, Giuliano Siligardi, Sara J Baldock, Jillian Madine, David A Middleton
Peptides derived from apolipoprotein A-I (apoA-I), the main component of high-density lipoprotein (HDL), constitute the main component of amyloid deposits that co-localise with atherosclerotic plaques. Here we investigate the molecular details of full-length, lipid-deprived apoA-I after assembly into insoluble aggregates under physiologically-relevant conditions known to induce aggregation in vitro. Unmodified apoA-I is shown to remain soluble at pH 7 for at least 3 days, retaining its native α-helical-rich structure...
December 19, 2016: Biochemistry
Luís Mafra, Tomaž Čendak, Sarah Schneider, Paul V Wiper, João Pires, José R B Gomes, Moisés L Pinto
Two-dimensional (2D) solid-state nuclear magnetic resonance (SSNMR) experiments on samples loaded with (13)C-labeled CO2, "under controlled partial pressures", have been performed in this work, revealing unprecedented structural details about the formation of CO2 adducts from its reaction with various amine-functionalized SBA-15 containing amines having distinct steric hindrances (e.g., primary, secondary) and similar loadings. Three chemisorbed CO2 species were identified by NMR from distinct carbonyl environments resonating at δC ≈ 153, 160, and 164 ppm...
December 29, 2016: Journal of the American Chemical Society
Busolo Wa Wabuyele, Sutthilug Sotthivirat, George X Zhou, Jason Ash, Sundeep S Dhareshwar
Process-induced inadvertent phase change of an active pharmaceutical ingredient in a drug product could impact chemical stability, physical stability, shelf life, and bioperformance. In this study, dispersive Raman spectroscopy is presented as an alternative method for the nondestructive, high-throughput, at-line quantification of amorphous conversion. A quantitative Raman method was developed using a multivariate partial least squares (PLS) regression calibration technique with solid-state nuclear magnetic resonance (ssNMR) spectroscopy as the reference method...
February 2017: Journal of Pharmaceutical Sciences
Marko Bertmer
Solid-state NMR (SSNMR) experiments are mainly performed on diamagnetic materials. However, the study of paramagnetic materials offers access to additional information in combination with the unpaired electron. This article discusses the experimental complications arising when considering paramagnetic materials such as large shift effects and large linewidths. A look at the theoretical description as well as experimental methods are shown and accompanied by techniques for signal assignment, also with the help of quantum-chemical calculations...
February 2017: Solid State Nuclear Magnetic Resonance
Renu Chadha, Yashika Bhalla, Avdesh Nandan, Kunal Chadha, Maninder Karan
Solvent free mechanochemical approach is utilized to synthesise new cocrystals of chrysin using supramolecular chemistry based upon reliable synthons. Chrysin, a flavone nutraceutical with wide range of beneficial effects has critically low bioavailability on account of its poor aqueous solubility and consequently poor absorption from the gastrointestinal tract. The present study focuses on this critical aspect and has exploited non covalent interactions to prepare its cocrystals with cytosine and thiamine hydrochloride...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
Abhishek Mandal, Patrick C A van der Wel
The lipid bilayer typical of hydrated biological membranes is characterized by a liquid-crystalline, highly dynamic state. Upon cooling or dehydration, these membranes undergo a cooperative transition to a rigidified, more-ordered, gel phase. This characteristic phase transition is of significant biological and biophysical interest, for instance in studies of freezing-tolerant organisms. Magic-angle-spinning (MAS) solid-state NMR (ssNMR) spectroscopy allows for the detection and characterization of the phase transitions over a wide temperature range...
November 1, 2016: Biophysical Journal
Andrea D Merg, Jennifer C Boatz, Abhishek Mandal, Gongpu Zhao, Soumitra Mokashi-Punekar, Chong Liu, Xianting Wang, Peijun Zhang, Patrick C A van der Wel, Nathaniel L Rosi
Chiral nanoparticle assemblies are an interesting class of materials whose chiroptical properties make them attractive for a variety of applications. Here, C18-(PEPAu(M-ox))2 (PEPAu(M-ox) = AYSSGAPPM(ox)PPF) is shown to direct the assembly of single-helical gold nanoparticle superstructures that exhibit exceptionally strong chiroptical activity at the plasmon frequency with absolute g-factor values up to 0.04. Transmission electron microscopy (TEM) and cryogenic electron tomography (cryo-ET) results indicate that the single helices have a periodic pitch of approximately 100 nm and consist of oblong gold nanoparticles...
October 11, 2016: Journal of the American Chemical Society
Tobias Schubeis, Madhu Nagaraj, Christiane Ritter
Solid-state NMR spectroscopy (ssNMR) is uniquely suited for atomic-resolution structural investigations of large protein assemblies, which are notoriously difficult to study due to their insoluble and non-crystalline nature. However, assignment ambiguities because of limited resolution and spectral crowding are currently major hurdles that quickly increase with the length of the polypeptide chain. The line widths of ssNMR signals are independent of proteins size, making segmental isotope labeling a powerful approach to overcome this limitation...
2017: Methods in Molecular Biology
David A Hirsh, Aaron J Rossini, Lyndon Emsley, Robert W Schurko
In this work, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced (35)Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. (35)Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS)...
September 21, 2016: Physical Chemistry Chemical Physics: PCCP
Paolo Cerreia Vioglio, Luca Catalano, Vera Vasylyeva, Carlo Nervi, Michele R Chierotti, Giuseppe Resnati, Roberto Gobetto, Pierangelo Metrangolo
Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a versatile characterization technique that can provide a plethora of information complementary to single crystal X-ray diffraction (SCXRD) analysis. Herein, we present an experimental and computational investigation of the relationship between the geometry of a halogen bond (XB) and the SSNMR chemical shifts of the non-quadrupolar nuclei either directly involved in the interaction ((15) N) or covalently bonded to the halogen atom ((13) C). We have prepared two series of X-bonded co-crystals based upon two different dipyridyl modules, and several halobenzenes and diiodoalkanes, as XB-donors...
November 14, 2016: Chemistry: a European Journal
Alysha Dicke, Tata Gopinath, Yingjie Wang, Gianluigi Veglia
Water plays a central role in membrane protein folding and function. It not only catalyzes lipid membrane self-assembly, but it is also affects the structural integrity and conformational dynamics of membrane proteins. Magic angle spinning (MAS) solid-state NMR is the technique of choice for measuring water accessibility of membrane proteins in a site-specific manner, providing a ruler for membrane protein topology and insertion within lipid bilayers. However, sensitivity and resolution of membrane protein samples for MAS experiments is often dictated by hydration levels, which affect membrane proteins structural dynamics...
October 5, 2016: Journal of Physical Chemistry. B
Keisuke Kishida, Yoshikuni Okumura, Yoshihiro Watanabe, Megumi Mukoyoshi, Silvia Bracco, Angiolina Comotti, Piero Sozzani, Satoshi Horike, Susumu Kitagawa
The separation of 1,3-butadiene from C4 hydrocarbon mixtures is imperative for the production of synthetic rubbers, and there is a need for a more economical separation method, such as a pressure swing adsorption process. With regard to adsorbents that enable C4 gas separation, [Zn(NO2 ip)(dpe)]n (SD-65; NO2 ip=5-nitroisophthalate, dpe=1,2-di(4-pyridyl)ethylene) is a promising porous material because of its structural flexibility and restricted voids, which provide unique guest-responsive accommodation. The 1,3-butadiene-selective sorption profile of SD-65 was elucidated by adsorption isotherms, in situ PXRD, and SSNMR studies and was further investigated by multigas separation and adsorption-desorption-cycle experiments for its application to separation technology...
October 24, 2016: Angewandte Chemie
Daniel Saliba, Mazen Al-Ghoul
We report the synthesis of magnesium-aluminium layered double hydroxide (LDH) using a reaction-diffusion framework (RDF) that exploits the multiscale coupling of molecular diffusion with chemical reactions, nucleation and growth of crystals. In an RDF, the hydroxide anions are allowed to diffuse into an organic gel matrix containing the salt mixture needed for the precipitation of the LDH. The chemical structure and composition of the synthesized magnesium-aluminium LDHs are determined using powder X-ray diffraction (PXRD), thermo-gravimetric analysis, differential scanning calorimetry, solid-state nuclear magnetic resonance (SSNMR), Fourier transform infrared and energy dispersive X-ray spectroscopy...
November 13, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
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