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https://www.readbyqxmd.com/read/29458211/impact-of-formulation-excipients-on-the-thermal-mechanical-and-electrokinetic-properties-of-hydroxypropyl-methylcellulose-acetate-succinate-hpmcas
#1
Tanvi M Deshpande, Anisul Quadir, Sakae Obara, Stephen W Hoag
Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely used in amorphous solid dispersions and as an enteric coating polymer. Under aqueous coating conditions and at elevated coating temperatures, HPMCAS particles tend to aggregate and clog the spray-nozzle, hence interrupting the coating process. This research focused on how plasticizers and surfactants, excipients used for aqueous coating, affect the properties and stability of HPMCAS. This information would be useful in identifying suitable excipients for developing a stable HPMCAS aqueous enteric coating formulation...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458205/developing-a-stable-aqueous-enteric-coating-formulation-with-hydroxypropyl-methylcellulose-acetate-succinate-hpmcas-mf-and-colloidal-silicon-dioxide-as-anti-tacking-agent
#2
Tanvi M Deshpande, Anisul Quadir, Sakae Obara, Ahmed Ibrahim, Stephen W Hoag
The purpose of this study was to use statistical design of experiments to develop a stable aqueous enteric coating formulation containing stabilizing excipients, such as polyethylene glycol that can minimize hydroxypropyl methylcellulose acetate succinate aggregation and minimize spray-nozzle clogging at elevated processing temperatures. The mechanisms of stabilization (i.e. charge stabilization and molecular interactions) were studied by performing zeta potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate and hydrogen bonding by polyethylene glycol provided dispersion stability and yielded a stable aqueous coating formulation that prevented spray-nozzle clogging...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458172/modelling-human-myoblasts-survival-upon-xenotransplantation-into-immunodeficient-mouse-muscle
#3
Christophe Praud, Karine Vauchez, Pascal Zongo, Jean-Thomas Vilquin
Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458078/isolation-of-intact-rna-from-murine-cd4-t-cells-after-intracellular-cytokine-staining-and-fluorescence-activated-cell-sorting
#4
Shajo Kunnath-Velayudhan, Steven A Porcelli
Intracellular cytokine staining (ICS) is a powerful method for identifying functionally distinct lymphocyte subsets, and for isolating these by fluorescence activated cell sorting (FACS). Although transcriptomic analysis of cells sorted on the basis of ICS has many potential applications, this is rarely performed because of the difficulty in isolating intact RNA from cells processed using standard fixation and permeabilization buffers for ICS. To address this issue, we compared three buffers shown previously to preserve RNA in nonhematopoietic cells subjected to intracellular staining for their effects on RNA isolated from T lymphocytes processed for ICS...
February 17, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29458062/an-unexpected-degradation-pathway-of-a-1-2-4-triazolo-4-3-a-pyridine-derivative-the-formation-of-two-cationic-pseudodimers-of-an-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor-drug-candidate-in-a-stressed-capsule-formulation
#5
Yande Huang, Qinggang Wang, Yongmei Wu
Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride salt, was observed in a capsule formulation stressed at 50°C or 40°C/75% relative humidity conditions for one month. Two unknown degradants were identified as cationic pseudodimers of the API via accurate mass liquid chromatography-mass spectrometry and one- and two-dimensional NMR analyses. A plausible degradation pathway of the API was postulated which led to the identification of two key N-oxide degradants in the stressed capsule formulation at trace levels...
February 16, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29458036/plasma-amyloid-levels-within-the-alzheimer-s-process-and-correlations-with-central-biomarkers
#6
Olivier Hanon, Jean-Sébastien Vidal, Sylvain Lehmann, Stéphanie Bombois, Bernadette Allinquant, Jean-Marc Tréluyer, Patrick Gelé, Christine Delmaire, Fredéric Blanc, Jean-François Mangin, Luc Buée, Jacques Touchon, Jacques Hugon, Bruno Vellas, Evelyne Galbrun, Athanase Benetos, Gilles Berrut, Elèna Paillaud, David Wallon, Giovanni Castelnovo, Lisette Volpe-Gillot, Marc Paccalin, Philippe-Henri Robert, Olivier Godefroy, Thierry Dantoine, Vincent Camus, Joël Belmin, Pierre Vandel, Jean-Luc Novella, Emmanuelle Duron, Anne-Sophie Rigaud, Suzanna Schraen-Maschke, Audrey Gabelle
BACKGROUNDS: Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. OBJECTIVES: To assess plasma levels of Aβ42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. METHODS: One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included...
February 16, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29457911/preparation-of-benzo-c-carbazol-6-amines-via-manganese-catalyzed-enaminylation-of-1-pyrimidin-2-yl-1h-indoles-with-ketenimines-and-subsequent-oxidative-cyclization
#7
Xiaorong Zhou, Zhenmin Li, Zhiyin Zhang, Ping Lu, Yanguang Wang
Manganese-catalyzed C2 -H enaminylation of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. A migration of the directing group pyrimidinyl occurred during this process. The synthesized 2-enaminyl indoles could be conveniently converted into 5-aryl-7H-benzo[c]carbazol-6-amines.
February 19, 2018: Organic Letters
https://www.readbyqxmd.com/read/29457901/c-sp3-h-bond-functionalization-of-benzo-c-oxepines-via-c-o-bond-cleavage-formal-3-3-synthesis-of-multi-substituted-chromans
#8
Miao Wang, Bo-Cheng Tang, Jia-Chen Xiang, Yan Cheng, Zi-Xuan Wang, Jin-Tian Ma, Yan-Dong Wu, An-Xin Wu
An efficient base-promoted C(sp3)-H bond functionalization strategy for the synthesis of multi-substituted chromans from the formal [3+3] cycloaddition of benzo[c]oxepines and electron-rich phenols has been developed. The corresponding 4H-chromenes can be easily obtained in excellent yields by simple filtration from chromans. Preliminary mechanistic studies indicate that the C-O bond cleavage is the key step for the C(sp3)-H bond functionalization and this reaction could have occurred through a tandem C-O bond cleavage/ Michael addition/ annulation reactions...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29457899/palladium-catalyzed-selective-mono-tetraacetoxylation-of-o-carboranes-with-acetic-acid-via-cross-dehydrogenative-coupling-of-cage-b-h-o-h-bonds
#9
Tao-Tao Xu, Ke Cao, Ji Wu, Cai-Yan Zhang, Junxiao Yang
A selective mono-/tetraacetoxylation of o-carboranes with acetic acid via cross dehydrogenative coupling of cage B-H/O-H bonds has been developed, and a series of mono- and tetraacetoxylated o-carboranes have been synthesized with moderate to good yields as well as good selectivity. Mechanistic studies indicate that the acetoxyl originates from acetic acid directly, and a nucleophilic addition of PdIV -oxo species and dehydration process is proposed.
February 19, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29457891/pd-catalyzed-asymmetric-dearomative-cycloaddition-for-construction-of-optically-active-pyrroloindoline-and-cyclopentaindoline-derivatives-access-to-3a-aminopyrroloindolines
#10
Jun-Qi Zhang, Feifei Tong, Bing-Bing Sun, Wei-Tai Fan, Jun-Bo Chen, Dandan Hu, Xing-Wang Wang
Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with vinyl aziridine and vinyl cyclopropanes have been respectively successfully developed in the presence of a chiral box/Pd(0) complex. A series of enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b-nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral centers are smoothly obtained in high yields with satisfactory regio-, chemo-, and enantioselectivity. Remarkably, the synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon-carbon double bond of the desired products...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29457887/synthesis-of-highly-substituted-imidazole-uracil-containing-molecules-via-ugi-4cr-and-passerini-3cr
#11
Rudrakshula Madhavachary, Tryfon Zarganes-Tzitzikas, Pravin Patil, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, Alexander Dömling
The synthesis of uracil/thymine containing tetra/tri-substituted imidazoles were demonstrated using Ugi/Passerini-reaction fol-lowed by a post-cyclization reaction sequence. The approach enables the one-pot facile construction of diverse compounds in moderate to excellent yields (47-82%). The 5-fluorouracil and 5-methyluracil moieties afford potentially bioactive molecules with drug-like properties. These scaffolds are being utilized in the screening deck of the European Lead Factory.
February 19, 2018: ACS Combinatorial Science
https://www.readbyqxmd.com/read/29457884/unique-biochemical-and-sequence-features-enable-blub-to-destroy-flavin-and-distinguish-blub-from-the-flavin-monooxygenase-superfamily
#12
Amrita B Hazra, David P Ballou, Michiko E Taga
Vitamin B12 (cobalamin) is an essential micronutrient for humans that is synthesized only by a subset of bacteria and archaea. The aerobic biosynthesis of 5,6-dimethylbenzimidazole, the lower axial ligand of cobalamin is catalyzed by the "flavin destructase" enzyme BluB, which fragments reduced flavin mononucleotide following its reaction with oxygen to yield this ligand. BluB shares sequence and structural similarity with the flavin oxidoreductase superfamily, yet the flavin destruction process has remained elusive...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29457833/a-green-method-to-determine-vuv-185-nm-fluence-rate-based-on-hydrogen-peroxide-production-in-aqueous-solution
#13
Laxiang Yang, Mengkai Li, Wentao Li, James R Bolton, Zhimin Qiang
A mini-fluidic vacuum ultraviolet/ultraviolet (VUV/UV) photoreaction system (MVPS) was developed in our previous study. Based on the MVPS, a green method to determine VUV fluence rate has been developed using the production rate of H2 O2 when water is exposed to 185 nm VUV. The H2 O2 production followed pseudo-zero-order reaction kinetics well over the first 10 min of VUV/UV exposure. This new method was well calibrated with a standard cis-cyclooctene cis-trans photoisomerization actinometer as recommended by the International Union of Pure and Applied Chemistry...
February 19, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29457816/iodine-promoted-dual-oxidative-c-sp-3-h-amination-of-2-methyl-3-arylquinazolin-4-3h-ones-a-facile-route-to-1-4-diarylimidazo-1-5-a-quinazolin-5-4h-ones
#14
Kavitha Donthiboina, Hari Krishna Namballa, Siddiq Pasha Shaik, Jagadeesh Babu Nanubolu, Nagula Shankaraiah, Ahmed Kamal
An iodine promoted tandem oxidative condensation of benzylamines and 2-methylquinazolin-4-(3H)-ones was developed to yield imidazo[1,5-a]quinazolin-5(4H)-ones via dual C(sp3 )-H amination under metal free conditions in a greener way using molecular oxygen as a terminal oxidant. This tandem transformation provides an efficient approach to construct various functionalized imidazo[1,5-a]quinazolin-5(4H)-ones in a straightforward manner via a sequential amination-oxidation-annulation-aromatisation.
February 19, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29457814/an-electrophilic-reagent-for-the-synthesis-of-ochfme-containing-molecules
#15
Elodie Carbonnel, Xavier Pannecoucke, Tatiana Besset, Philippe Jubault, Thomas Poisson
Herein the synthesis of a novel and bench stable electrophilic reagent to construct the OCFHMe motif from O-nucleophiles has been described. This sulfonium salt, readily obtained in 5 steps, reacted with various phenols and alcohols. The resulting products, including complex molecules, were obtained in good yields. This reagent was also used for the functionalization of thiol derivatives.
February 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29457757/structural-variability-of-dna-containing-mg-pyrophosphate-microparticles-optimized-conditions-to-produce-particles-with-desired-size-and-morphology
#16
Vasily N Danilevich, Andrey L Mulyukin, Andrey V Machulin, Vladimir V Sorokin, Sergey A Kozlov
Our previous studies demonstrated the formation of structurally diverse DNA-containing microparticles (DNA MPs) in PCR with Mg-pyrophosphate (MgPPi) as the structure-forming component. These DNA MPs were referred to major structural types: microdisks (2D MPs) with nanometer thickness and 3D MPs with sophisticated morphology and constructed from intersecting disks and their segments. Little is known about factors that influence both the morphology and size of DNA MPs, and the present study was aimed at fulfilling this gap...
February 19, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29457731/synthesis-of-structurally-diverse-emissive-molecular-rotors-with-four-component-ugi-stators
#17
Ma Carmen García-González, Andres Aguilar-Granda, Angel Zamudio-Medina, Luis D Miranda, Braulio Rodríguez-Molina
The use of the multicomponent Ugi reaction to rapidly prepare a library of dumbbell-like molecular rotors is highlighted here. The synthetic strategy consisted on the atom-economic access to fifteen bulky and structurally-diverse iodinated stators, which were cross coupled to the 1,4-diethynylphenylene rotator. From those experiments, up to six rotors 1a-c and 1l-n were obtained, with yields ranging from 35 to 69 % per coupled C-C bond. In addition to the frameworks diversity, five of these compounds showed Aggregate-Enhanced Emission properties thanks to their conjugated 1,4-bis-[(phenyl)ethynyl]benzene cores, a property that rises by increasing the water fraction (fw) in their THF solutions...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29457726/a-robust-oil-in-oil-emulsion-for-the-nonaqueous-encapsulation-of-hydrophilic-payloads
#18
Xiaocun Lu, Joshua S Katz, Adam Schmitt, Jeffrey S Moore
Compartmentalized structures widely exist in cellular systems (organelles) and perform essential functions in smart composite materials (microcapsules, vasculatures, and micelles) to provide localized functionality and enhance materials compatibility. An entirely water-free compartmentalization system is of significant value to the materials community as nonaqueous conditions are critical to packaging microcapsules with water-free hydrophilic payloads while avoiding energy-intensive drying steps. Few nonaqueous encapsulation techniques are known, especially when considering just the scalable processes that operate in batch mode...
February 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29457724/regio-and-stereoselective-synthesis-of-isoindolin-1-ones-through-buli-mediated-iodoaminocyclization-of-2-1-alkynyl-benzamides
#19
Dhirendra Brahmchari, Akhilesh K Verma, Saurabh Mehta
A simple and straightforward synthesis of isoindolin-1-ones is reported. Exclusive N-cyclization of the amide functional group, an ambident nucleophile, has been accomplished for the cyclization of 2-(1-alkynyl)benzamides using n-BuLi-I2 /ICl. The methodology works with the primary amide and affords the desired isoindolinones in yields of 38-94%. Interestingly, the isolated products exhibit a Z-stereochemistry across the C=C double bond. The reaction mechanism involving the formation of either a vinylic anion or an intimate ion pair intermediate is proposed...
February 19, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29457716/metal-versus-ligand-reduction-in-ln-3-complexes-of-a-mesitylene-anchored-tris-aryloxide-ligand
#20
Chad T Palumbo, Dominik P Halter, Vamsee K Voora, Guo P Chen, Alan K Chan, Megan E Fieser, Joseph W Ziller, Wolfgang Hieringer, Filipp Furche, Karsten Meyer, William J Evans
The synthesis of 4fn Ln3+ complexes of the tris(aryloxide) mesitylene ligand, ((Ad,Me ArO)3 mes)3- , with Ln = La, Ce, Pr, Sm, and Yb, and their reduction with potassium have revealed that this ligand system can be redox active with some metals. Protonolysis of [Ln(N(SiMe3 )2 )3 ] (Ln = La, Ce, Pr, Sm, Yb) with the tris(phenol) (Ad,Me ArOH)3 mes yielded the Ln3+ complexes [((Ad,Me ArO)3 mes)Ln] (Ln = La, Ce, Pr, Sm, Yb), 1-Ln. Single electron reduction of each 4fn complex, 1-Ln, using potassium yielded the reduced products, [K(2...
February 19, 2018: Inorganic Chemistry
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