- Siloxanes with pendent naphthalene diimides: Synthesis and fluorescence quenching
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Cyclic siloxanes with pendent naphthalene diimide groups were synthesized via hydrosilylation to form amorphous electron-accepting compounds. Photophysical measurements and >99.9% fluorescence quenching of well-known p-type polymers by the siloxanes demonstrate that these siloxanes form a new class of highly efficient n-type materials that provide some control over intermolecular interactions.
- Ganesan, Palaniswamy,Van Lagen, Barend,Marcelis, Antonius T. M.,Sudholter, Ernst J. R.,Zuilhof, Han
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- Liposomal FRET Assay Identifies Potent Drug-Like Inhibitors of the Ceramide Transport Protein (CERT)
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Ceramide transfer protein (CERT) mediates non-vesicular transfer of ceramide from endoplasmic reticulum to Golgi apparatus and thus catalyzes the rate-limiting step of sphingomyelin biosynthesis. Usually, CERT ligands are evaluated in tedious binding assays or non-homogenous transfer assays using radiolabeled ceramides. Herein, a facile and sensitive assay for CERT, based on F?rster resonance energy transfer (FRET), is presented. To this end, we mixed donor and acceptor vesicles, each containing a different fluorescent ceramide species. By CERT-mediated transfer of fluorescent ceramide, a FRET system was established, which allows readout in 96-well plate format, despite the high hydrophobicity of the components. Screening of a 2 000 compound library resulted in two new potent CERT inhibitors. One is approved for use in humans and one is approved for use in animals. Evaluation of cellular activity by quantitative mass spectrometry and confocal microscopy showed inhibition of ceramide trafficking and sphingomyelin biosynthesis.
- Aglar, ?znur,Arenz, Christoph,Banhart, Sebastian,Cong, Xiaojing,Hamdo, Housam H.,Heuer, Dagmar,Kleuser, Burkhard,M?ller, Heiko M.,Saied, Essa M.,Samaha, Doaa,Schumacher, Fabian
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p. 16616 - 16621
(2020/11/30)
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- Bio-based α,ω-Functionalized Hydrocarbons from Multi-step Reaction Sequences with Bio- and Metallo-catalysts Based on the Fatty Acid Decarboxylase OleTJE
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OleT from Jeotgalicoccus sp. ATCC 8456 catalyzes the decarboxylation of ω-functionalized fatty acids to the corresponding alkenols, which can themselves serve as starting material for the synthesis of polymers and fine chemicals. To show the versatility of possible reactions, a series of in vitro reaction cascades was developed where an alkenol produced by the decarboxylation of ω-hydroxy fatty acids can be further converted into alkenylamines and diols. By coupling OleT with an alcohol dehydrogenase or alcohol oxidase as well as an amino-transaminase, an oxidative decarboxylation followed by the oxidation of the terminal alcohol and a subsequent reductive transamination could be carried out. By using different cofactors or electron sources, the reactions could be performed sequentially or simultaneously. The combination of enzymatic decarboxylation with a ruthenium catalyst in a chemo-enzymatic cascade provides a novel way to synthesize long-chain diols.
- Bojarra, Samiro,Reichert, Dennis,Grote, Marius,Baraibar, álvaro Gómez,Dennig, Alexander,Nidetzky, Bernd,Mügge, Carolin,Kourist, Robert
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p. 1192 - 1201
(2018/02/13)
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- ALKYNE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
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Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I'" or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduce the excessive activation of complement.
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- ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
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- Formation of Self-Templated 2,6-Bis(1,2,3-triazol-4-yl)pyridine [2]Catenanes by Triazolyl Hydrogen Bonding: Selective Anion Hosts for Phosphate
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We report the remarkable ability of 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) compounds 2 with appended olefin amide arms to self-template the formation of interlocked [2]catenane structures 3 in up to 50 % yield when subjected to olefin ring-closing metathesis in CH2Cl2. X-ray diffraction crystallography enabled the structural characterization of both the [2]catenane 3 a and the non-interlocked macrocycle 4 a. These [2]catenanes showed selective triazolyl hydrogen-bonding interactions with the tetrahedral phosphate anion when screened against a range of ions; 3 a,b are the first examples of selective [2]catenane hosts for phosphate.
- Byrne, Joseph P.,Blasco, Salvador,Aletti, Anna B.,Hessman, Gary,Gunnlaugsson, Thorfinnur
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p. 8938 - 8943
(2016/07/26)
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- Poly(phosphorodiamidate)s by Olefin Metathesis Polymerization with Precise Degradation
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Degradable polymers are a currently growing field of research for biomedical and materials science applications. The majority of such compounds are based on polyesters and polyamides. In contrast, their phosphorus-containing counterparts are much less studied, in spite of their potential precise degradation profile and biocompatibility. Herein, the first library of poly(phosphorodiamidate)s (PPDAs) with two P?N bonds forming the polymer backbone and a pendant P?OR group is prepared through acyclic diene metathesis polymerization. They are designed to vary in their hydrophilicity and are compared with the structural analogues poly(phosphoester)s (PPEs) with respect to their thermal properties and degradation profiles. The degradation of PPDAs can be controlled precisely by the pH: under acidic conditions the P?N linkages in the polymer backbone are cleaved, whereas under basic conditions the pendant ester is cleaved selectively and almost no backbone degradation occurs. The PPDAs exhibit distinctively higher thermal stability (from thermogravimetric analysis (TGA)) and higher glass transition and/or melting temperatures (from differential scanning calorimetry (DSC)) compared with analogous PPEs. This renders this exotic class of phosphorus-containing polymers as highly promising for the development of future drug carriers or tissue engineering scaffolds.
- Steinmann, Mark,Wagner, Manfred,Wurm, Frederik R.
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p. 17329 - 17338
(2016/11/23)
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- Epoxy-terminated self-assembled monolayers containing internal urea or amide groups
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We report the synthesis of new coupling agents with internal amide or urea groups possessing an epoxy-terminal group and trimethoxysilyl-anchoring group. The structural characterizations of the corresponding self-assembled monolayers (SAMs) were performed by polarization modulation infrared reflection adsorption spectroscopy (PM-IRRAS). The molecular assembly is mainly based on the intermolecular hydrogen-bonding between adjacent amide or urea groups in the monolayers. Because of the steric hindrance of amide or urea groups, the distance between the alkyl chains is too large to establish van der Waals interactions, inducing their disorder. The reactivity of the epoxy-terminal groups was successfully investigated through reaction with a fluorescent probe. We show that SAMs containing internal urea or amide groups exhibited a higher density of accessible epoxide groups than the corresponding long-chain (C22) glycidyl-terminated SAM.
- Ramin, Micha?l A.,Le Bourdon, Gwéna?lle,Heuzé, Karine,Degueil, Marie,Buffeteau, Thierry,Bennetau, Bernard,Vellutini, Luc
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p. 2783 - 2789
(2015/03/18)
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- Instability of Surface-Grafted Weak Polyacid Brushes on Flat Substrates
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We study the stability of weak polyacid brush (WPAB) gradients in aqueous media covering a range in grafting density (σ) spanning 0.05-0.5 chains/nm2 using two analogous surface-anchored bromoisobutyrate-based initiators for atom transfer radical polymerization (ATRP) bearing either an ester or amide linker. Variations in dry thickness of ester-based WPABs as a function of time and pH are consistent with WPAB degrafting via linker hydrolysis catalyzed by mechanical tension in the grafted chains. Sources of tension considered include high σ, as well as swelling and electrostatic repulsion associated with increasing degree of deprotonation (α) of repeat units in the WPAB. Normalized thickness of the WPAB decreases by a maximum amount at intermediate σ between ~0.05-0.15 chains/nm2, implying that contributions to tension by α are counterbalanced by charge regulation in the WPAB at high σ. Amide-based WPABs are more stable up to 264 h incubation, suggesting that commonly used ester-bearing ATRP initiators are more susceptible to hydrolysis over the time scales examined. (Figure Presented).
- Galvin, Casey J.,Bain, Erich D.,Henke, Adam,Genzer, Jan
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p. 5677 - 5687
(2015/09/02)
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- Novel fluorescent ceramide derivatives for probing ceramidase substrate specificity
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Ceramidases are key regulators of cell fate. The biochemistry of different ceramidases and of their substrate ceramide appears to be complex, mainly due to specific biophysical characteristics at the water-membrane interface. In the present study, we describe the design and synthesis of a set of fluorescently labeled ceramides as substrates for acid and neutral ceramidases. For the first time we have replaced the commonly used polar NBD-dye with the lipophilic Nile Red (NR) dye. Analysis of kinetic data reveal that although both the dyes do not have any noticeable preference for the substitution at acyl or sphingosine (Sph) part in ceramide towards hydrolysis by acid ceramidase, the ceramides with acyl-substituted NBD and Sph-substituted NR dyes have been found to be a better substrate for neutral ceramidase.
- Bhabak, Krishna P.,Proksch, Denny,Redmer, Susanne,Arenz, Christoph
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p. 6154 - 6161
(2012/11/07)
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- Stereochemical effects of chiral monolayers on enhancing the resistance to mammalian cell adhesion
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This work describes the different durations of surface confinement of adhered mammalian cells by monolayers comprised of enantiomers of bio-inert polyol-terminated alkanethiols. Enhanced resistance to protein adsorption and cell adhesion is obtained on monolayers formed by a racemic mixture of the enantiomeric alkanethiols.
- Bandyopadhyay, Debjyoti,Prashar, Deepali,Luk, Yan-Yeung
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p. 6165 - 6167
(2011/07/30)
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- Preparation of multifunctional supported metallocene catalyst using organic multifunctional modifier for synthesizing polyethylene/clay nanocomposites via in situ intercalative polymerization
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A new type of multifunctional ammonium modifier with carbonyl group and vinyl group was synthesized to prepare multifunctional montmorillonites (F-MMTs), which were used as multifunctional catalyst supports for in situ ethylene polymerization. High loading of metallocene catalyst in the galleries of F-MMT had been achieved due to the presence of carbonyl group in the multifunctional modifier. XRD profiles and TEM images showed that polyethylene/montmorillonite (PE/F-MMT) nanocomposites with exfoliated structure could be synthesized using the intercalated catalyst described above, even when the content of MMT was very high (more than 15.1 wt%). The as-produced PE/F-MMTs nanocomposites were composed of flower-like particles with a diameter of about 5 μm. A thermal stable monoclinic phase was observed in PE/F-MMT nanocomposites. Comparatively, the resultant PE/F-MMT nanocomposites showed low gas permeability. Interfacial interaction between PE matrix and F-MMT was enhanced due to the chemical linking between the two components via copolymerization of ethylene with vinyl group of F-MMT. Thus the resultant PE/F-MMT nanocomposites showed good structural stability.
- Ren, Changyi,Du, Xiaohua,Ma, Li,Wang, Yanhui,Zheng, Jun,Tang, Tao
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experimental part
p. 3416 - 3424
(2011/12/02)
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- Versatile and efficient synthesis of a new class of aza-based phosphinic amide ligands via unusual P-C cleavage
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A new class of bidentate, aza-based phosphinic amide ligands of the type RN(H)P(=O)(2-py)2 (2-py=2-pyridyl) was synthesized within minutes via a one-pot process including Staudinger reaction of an organic azide (RN 3) with 2-pyridylphosphines, followed by partial, unprecedented hydrolysis under loss of one aromatic substituent. The structure of the unusual-hydrolysis product H2C=CH(CH2)9N(H)P(= O)(2-py)2 (5a) was characterized by IR, 1H- and 31P-NMR, as well as by X-ray crystal-structure analysis (Figure). The tetrahedral P-atom was found to be surrounded by a trigonal-pyramidal arrangement of the substituents. To gain insight into the formation of these novel phosphinic amides, a series of intermediate iminophosphoranes, H 2C=CH(CH2)9N=P(Ar)n(2-py) 3-n (n = 0-3), compounds 1a-1f, were synthesized, and their hydrolyses were studied. All tested compounds followed the classical hydrolysis route of P=N cleavage under acidic conditions. Sequential hydrolysis to 5a-5d only occurred under either basic conditions or in wet MeCN as solvent. Notably, H2C=CH(CH2)9N=P(C6H 5)(4-MeO-2-py)2 (1c) was hydrolyzed at a much slower rate compared to its analogue 1b lacking the MeO group. On the contrary, the halogenated compounds H2C=CH(CH2)9N=P(4-X- C6H4)3 (1f,g) (X = F, Cl) were hydrolyzed at a notably faster rate relative to the non-halogenated congener 1e (X = H).
- Tsai, Shih-Chung,Fu, Yaw-Shien,Liao, Ju-Hsiou,Yu, Shuchun Joyce
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p. 3007 - 3017
(2007/10/03)
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