bluuebunny/crossref_metadata_2025 huggingface dataset:
Terpenoid‐Biosynthese abseits bekannter Wege: unkonventionelle Cyclasen und ihre Bedeutung für die biomimetische Synthese
Authors: Baunach Martin , Franke Jakob , Hertweck Christian
Published: December 2014

Cyclisierungsreaktionen von Terpenen und Terpenoiden zählen zu den komplexesten chemischen Reaktionen in der Natur und tragen maßgeblich zur enormen Strukturvielfalt dieser größten Naturstofffamilie bei. Zahlreiche Studien auf chemischer, genetischer und biochemischer Ebene wurden durchgeführt, um mechanistische Einblicke in diese faszinierenden Reaktionen zu erlangen, die von Terpen‐ und Terpenoid‐Cyclasen katalysiert werden. Eine Vielzahl dieser Enzyme konnte seither charakterisiert werden. Nach klassischer Lehrbuchmeinung werden Terpen‐/Terpenoid‐Cyclasen gemäß ihrer Struktur und ihrem Reaktionsmechanismus in zwei große Klassen eingeteilt. Jüngste Entdeckungen neuartiger Terpenoid‐Cyclasen zeigen jedoch, dass das natürliche enzymatische Repertoire deutlich vielseitiger ist, als zunächst gedacht. Dieser Aufsatz stellt eben diese Terpenoid‐Cyclasen in den Fokus, die aus dem Rahmen fallen.
Chloroacetate‐Promoted Selective Oxidation of Heterobenzylic Methylenes under Copper Catalysis
Authors: Liu Jianming , Zhang Xin , Yi Hong , Liu Chao , Liu Ren , Zhang Heng , Zhuo Kelei , Lei Aiwen
Published: December 2014

The efficient selective oxidation and functionalization of CH bonds with molecular oxygen and a copper catalyst to prepare the corresponding ketones was achieved with ethyl chloroacetate as a promoter. In this transformation, various substituted N‐heterocyclic compounds were well tolerated. Preliminary mechanistic investigations indicated that organic radical species were involved in the overall process. The N‐heterocyclic compounds and ethyl chloroacetate work synergistically to activate CH bonds in the methylene group, which results in the easy generation of free radical intermediates, thus leading to the corresponding ketones in good yields.
Stabilisierung eines cysteinreichen Kegelschneckentoxins, MrIA, in Form eines 1,2,3‐Triazol‐Disulfidbrückenmimetikums
Authors: Gori Alessandro , Wang Ching‐I A. , Harvey Peta J. , Rosengren K. Johan , Bhola Rebecca F. , Gelmi Maria L. , Longhi Renato , Christie Macdonald J. , Lewis Richard J. , Alewood Paul F. , Brust Andreas
Published: December 2014

Die Synthese von Disulfidbrückenmimetika ist eine wichtige Strategie zur Optimierung disulfidreicher Peptide beim Wirkstoff‐Design. Wir beschreiben Mimetika des Conotoxins MrIA, die durch selektiven Austausch einzelner Disulfidbindungen gegen Brücken aus einem 1,4‐disubstituierten 1,2,3‐Triazol erhalten wurden. Eine sequenzielle, Kupfer‐katalysierte Azid‐Alkin‐Klick‐Reaktion (CuAAC) mit nachfolgender Disulfidbildung führte regioselektiv zu hybriden Triazol‐Disulfid‐Analoga von MrIA. Mimetika, in denen Triazol die Cys4‐Cys13‐Disulfidbindung ersetzte, behielten ihre Tertiärstruktur sowie die volle In‐vitro‐ und In‐vivo‐Aktivität als Inhibitoren der Noradrenalin‐Wiederaufnahme bei. Diese Mimetika sind resistent gegen Reduktion mit Glutathion, was zu einer verbesserten Plasmastabilität führt und dadurch interessant für die Wirkstoff‐Entwicklung ist.
Rhodium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition
Authors: Shintani Ryo , Takagi Chihiro , Ito Tomoaki , Naito Masanobu , Nozaki Kyoko
Published: December 2014

A rhodium‐catalyzed asymmetric synthesis of silicon‐stereogenic dibenzosiloles has been developed through a [2+2+2] cycloaddition of silicon‐containing prochiral triynes with internal alkynes. High yields and enantioselectivities have been achieved by employing an axially chiral monophosphine ligand, and the present catalysis is also applicable to the asymmetric synthesis of a germanium‐stereogenic dibenzogermole. Preliminary studies on the optical properties of these compounds are also described.
Water‐Mediated Recognition of Simple Alkyl Chains by Heart‐Type Fatty‐Acid‐Binding Protein
Authors: Matsuoka Shigeru , Sugiyama Shigeru , Matsuoka Daisuke , Hirose Mika , Lethu Sébastien , Ano Hikaru , Hara Toshiaki , Ichihara Osamu , Kimura S. Roy , Murakami Satoshi , Ishida Hanako , Mizohata Eiichi , Inoue Tsuyoshi , Murata Michio
Published: December 2014

Long‐chain fatty acids (FAs) with low water solubility require fatty‐acid‐binding proteins (FABPs) to transport them from cytoplasm to the mitochondria for energy production. However, the precise mechanism by which these proteins recognize the various lengths of simple alkyl chains of FAs with similar high affinity remains unknown. To address this question, we employed a newly developed calorimetric method for comprehensively evaluating the affinity of FAs, sub‐Angstrom X‐ray crystallography to accurately determine their 3D structure, and energy calculations of the coexisting water molecules using the computer program WaterMap. Our results clearly showed that the heart‐type FABP (FABP3) preferentially incorporates a U‐shaped FA of C10–C18 using a lipid‐compatible water cluster, and excludes longer FAs using a chain‐length‐limiting water cluster. These mechanisms could help us gain a general understanding of how proteins recognize diverse lipids with different chain lengths.
Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters
Authors: Li Wei , Tan Fei , Hao Xiaoyu , Wang Gang , Tang Yu , Liu Xiaohua , Lin Lili , Feng Xiaoming
Published: December 2014

A catalytic asymmetric intramolecular homologation of simple ketones with α‐diazoesters was firstly accomplished with a chiral N,N′‐dioxide–Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α‐aryl/alkyl β‐ketoesters containing an all‐carbon quaternary stereocenter. Under mild conditions, a variety of aryl‐ and alkyl‐substituted ketone groups reacted with α‐diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β‐ketoesters in high yield and enantiomeric excess.
Synthesis of Annelated Phospholes through Intramolecular CH Activation by Monovalent Phosphorus
Authors: Wei Xinda , Lu Zongming , Zhao Xu , Duan Zheng , Mathey Francois
Published: December 2014

Electrophilic terminal phosphinidene complexes [Ar‐Ar‐P‐W(CO)5] (Ar‐Ar: biaryl or an analogue thereof) undergo a spontaneous insertion of the phosphorus atom into the vicinal CH bonds to give annelated phospholes. Twelve examples are described, including biphenyl, thienyl, pyrrolyl, and benzofuryl groups as biaryl moieties. The activation energy of the insertion reaction is quite low (about 2 kcal mol−1).
Failure behavior of resorcinol–formaldehyde latex coated aramid short‐fiber‐reinforced rubber sealing under transverse tension
Authors: Zhang Bin , Gu Boqin , Yu Xiaoming
Published: December 2014

Composites composed of rubber, sepiolite fiber, and resorcinol–formaldehyde latex‐coated aramid short fibers were prepared. Mechanical and morphological characterizations were carried out. To investigate the effect of interfacial debonding on the failure behavior of short‐fiber‐reinforced rubber composites, a micromechanical representative volume element model for the composites was developed. The cohesive zone model was used to analyze the interfacial failure. We found that computational results were in good agreement with the experimental results when the interfacial fracture energy was 1 J/m2 and the interfacial strength was 10 MPa. A parametrical study on the interface and interphase of the composite was conducted. The results indicate that a good interfacial strength and a choice of interphase modulus between 40 and 50 MPa enhanced the ductile behavior and strength of the composite. The ductile properties of the composite also increased with increasing interfacial fracture energy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41672.
Direct Patterning and Biofunctionalization of a Large‐Area Pristine Graphene Sheet
Authors: Hong Daewha , Bae KiEun , Park Duckshin , Kim Houngkyung , Hong Seok‐Pyo , Kim Mi‐Hee , Lee Bong Soo , Ko Sangwon , Jeon Seokwoo , Zheng Xu , Yun Wan Soo , Kim Yang‐Gyun , Choi Insung S. , Lee Jungkyu K.
Published: December 2014

Direct patterning of streptavidin and NIH 3T3 fibroblast cells was successfully achieved over a large‐area pristine graphene sheet on Si/SiO2 by aryl azide‐based photografting with the conventional UV lithographic technique and surface‐initiated, atom transfer radical polymerization of oligo(ethylene glycol) methacrylate.
Exposure‐Based Validation List for Developmental Toxicity Screening Assays
Authors: Daston George P. , Beyer Bruce K. , Carney Edward W. , Chapin Robert E. , Friedman Jan M. , Piersma Aldert H. , Rogers John M. , Scialli Anthony R.
Published: December 2014

Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as “positive” or “negative” in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma Cmax. We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the Cmax at a dose level that produced significant teratogenicity or embryolethality, the negative being the Cmax at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no‐effect level for all positive compounds, and the negative exposure list contains Cmax values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure‐based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment
Inactivation of viruses using novel protein A wash buffers
Authors: Bolton Glen R. , Selvitelli Keith R. , Iliescu Ionela , Cecchini Douglas J.
Published: December 2014

Low pH viral inactivation is typically performed in the eluate pool following the protein A capture step during the manufacturing of monoclonal antibodies and Fc‐fusion proteins. However, exposure to low pH has the potential to alter protein quality. To avoid these difficulties, novel wash buffers capable of inactivating viruses while antibodies or Fc‐fusion proteins were bound to protein A or mixed mode resins were developed. By equilibrating the column in high salt buffer (2 M ammonium sulfate or 3 M sodium chloride) after loading, the hydrophobic interactions between antibodies and protein A ligands were increased enough to prevent elution at pH 3. The ammonium sulfate was also found to cause binding of an antibody to a mixed mode cation exchange and a mixed mode anion exchange resin at pH values that caused elution in conventional cation and anion exchange resins (pH 3.5 for Capto Adhere and pH 8.0 for Capto MMC), indicating that retention was due to enhanced hydrophobic interactions. The potential of the 2 M ammonium sulfate pH 3 buffer, a 1 M arginine buffer, and a buffer containing the detergent LDAO to inactivate XMuLV virus when used as protein A wash buffers with a 1 hour contact time were studied. The high salt and detergent containing wash buffers provided about five logs of removal, determined using PCR, and complete combined removal and inactivation (> 6 logs), determined by measuring infectivity. The novel protein A washes could provide more rapid, automated viral inactivation steps with lower pool conductivities. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:406–413, 2015
A new method for teaching microprocessors course using emulation
Authors: Qaralleh Esam A. , Darabkh Khalid A.
Published: December 2014

Microprocessors course is a challenging course for both students and instructors. The challenge arises by the nature of this course which is a combination of assembly language and hardware interface. The assembly language develops the students' ability to program in a low level programming language utilizing the instruction set of the 8086 processor, understanding the addressing modes (pointer concept), and exploring the nature of different instructions along with their execution times, dependences, implicit addressing for certain instructions, as well as flow control concerning the flags. The hardware interface helps the students in connecting various system components to build up a working system. Memory and input/output communications (read/write) operations are explained using timing diagrams and handshaking signals. In this paper, the aforementioned contents are addressed through developing an interesting project that is capable of integrating both hardware and software in an attractive environment characterized by being simple and inexpensive. In this project, the PC parallel port extension is used to emulate the microprocessor bus activity in read/write operation. The results showed an impressive students' progress whereas they were so satisfied to not only their projects, but also the conceptual basics of this course. © 2014 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:455–463, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21616
Semisynthesis and Antifungal Activity of Novel Oxime Ester Derivatives of Carabrone Modified at C(4) against Botrytis cinerea
Authors: Wang Delong , Ren Shuangxi , Wang Hao , Yan He , Feng Juntao , Zhang Xing
Published: December 2014

To continuously improve the potential utility of the natural lead compound of carabrone in agrochemistry, carabrone oxime and 36 novel oxime ester derivatives of carabrone modified at C(4) were synthesized, and evaluated for their antifungal activities against Botrytis cinerea in vitro and in vivo. Of these 36 oxime ester derivatives, some compounds exhibited antifungal activities in vitro or in vivo. It was found that compounds with a pyridinyl residue can either efficiently inhibit spore germination or efficiently inhibit hyphal growth of B. cinerea, and compound 9 exhibited the highest activity in vitro and in vivo with IC50 and EC50 values of 1.17 and 12.9 μg/ml, respectively. Further, the structureactivity relationships are also discussed.
Inhibitory Effects of Constituents of an Endophytic Fungus Hypoxylon investiens on Nitric Oxide and Interleukin‐6 Production in RAW264.7 Macrophages
Authors: Chang Chun‐Wei , Chang Hsun‐Shuo , Cheng Ming‐Jen , Liu Ta‐Wei , Hsieh Sung‐Yuan , Yuan Gwo‐Fang , Chen Ih‐Sheng
Published: December 2014

Three new compounds, hypoxyloamide (1), 8‐methoxynaphthalene‐1,7‐diol (2), and hypoxylonol (3), together with seven compounds isolated from nature for the first time, investiamide (4), hypoxypropanamide (5), hypoxylonol A (6), investienol (7), 2‐heptylfuran (8), (3S)‐5‐methyl‐8‐O‐methylmellein (9), (4R)‐O‐methylsclerone (10), along with 19 known compounds, 11–29, were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR‐ESI‐MS, and extensive 1D‐ and 2D‐NMR techniques. Of these isolates, 2, 8‐methoxynaphthalen‐1‐ol (15), and 1,8‐dimethoxynaphthalene (16) showed nitric oxide (NO) inhibitory activity with IC50 values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM, respectively, stronger than the positive control quercetin (IC50 36.8±1.3 μM). Compounds 2, 15, and 16 also showed interleukin‐6 (IL‐6) inhibitory activity with IC50 values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM, stronger than the positive control quercetin (IC50 31.3±1.6 μM). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6, and 7, from the genus Hypoxylon.
Anti‐Adipogenic Activity of the Naturally Occurring Phenanthroindolizidine Alkaloid Antofine via Direct Suppression of PPARγ Expression
Authors: Jang Eun Jung , Kim Hyo Kyeong , Jeong Hana , Lee Ye Seul , Jeong Mi Gyeong , Bae Su Jung , Kim Sanghee , Lee Sang Kook , Hwang Eun Sook
Published: December 2014

Antofine (ANTF) is a phenanthroindolizidine alkaloid isolated from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae), which is used as an herbal remedy for pain and inflammation. ANTF also possesses antiviral and antitumorigenic activities. In this study, we investigated the role of ANTF in adipogenesis. Chronic ABTF administration suppressed adipocyte differentiation and marker expression in a dose‐dependent manner. Furthermore, acute administration of ANTF at early stages of differentiation process inhibited lipid droplet formation and adipogenic gene expression. ANTF Treatment decreased expression of PPARγ protein, a master transcription factor in the regulation of adipocyte differentiation, leading to a suppression of aP2 promoter activity. These results suggest that ANTF exerts potent anti‐adipogenic effects via direct suppression of PPARγ protein expression, with consequent downregulation of adipogenic gene expression.
Cytotoxic Compounds from the Leaves of Garcinia polyantha
Authors: Lannang Alain Meli , Tatsimo Simplice J. N. , Fouotsa Hugues , Dzoyem Jean Paul , Saxena Ajit Kumar , Sewald Norbert
Published: December 2014

A new compound, named banganxanthone C (=12‐(1,1‐dimethylprop‐2‐en‐1‐yl)‐5,10‐dihydroxy‐9‐methoxy‐2‐methyl‐2‐(4‐methylpent‐3‐en‐1‐yl)‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one; 4), together with five known compounds, were isolated from the leaves of Garcinia polyantha. The structures of the compounds were elucidated on the basis of 1D‐ and 2D‐NMR spectroscopy. Among the known compounds, two were xanthones, one was a pentacyclic triterpene, one sterol, and one benzophenone derivative. Isoxanthochymol (2) and 4‐[(2E)‐3,7‐dimethylocta‐2,6‐dien‐1‐yl]‐1,5,8‐trihydroxy‐3‐methoxy‐9H‐xanthen‐9‐one (3) exhibited significant antiproliferative activity against the leukemia cell line TPH‐1 with IC50 inhibition values of 1.5 and 2.8 μg/ml, respectively. The cytotoxic activity was found to be related to apoptosis induction.
New Triterpenoids from the Fruiting Bodies of Ganoderma lucidum and Their Bioactivities
Authors: Liu Dong‐Ze , Zhu Yi‐Qun , Li Xiao‐Fei , Shan Wei‐Gang , Gao Peng‐Fei
Published: December 2014

Phytochemical investigation of the AcOEt extract of G. Lucidum has led to the isolation of two new triterpenoids, 1 and 2, together with five known ones, 3–7. The structures of the new compounds were identified as 12β‐acetoxy‐3β,7β‐dihydroxy‐11,15,23‐trioxolanost‐8‐en‐26‐oic acid butyl ester (1) and 12β‐acetoxy‐3,7,11,15,23‐pentaoxolanost‐8‐en‐26‐oic acid butyl ester (2) on the basis of detailed spectroscopic analysis (mass spectrometry, and 1D‐ and 2D‐NMR experiments). The antimicrobial activities of 1 and 2 were also evaluated.
Kinetic Analysis of the Interaction of Mos1 Transposase with its Inverted Terminal Repeats Reveals New Insight into the Protein–DNA Complex Assembly
Authors: Esnault Charles , Jaillet Jérôme , Delorme Nicolas , Bouchet Nicolas , Renault Sylvaine , Douziech‐Eyrolles Laurence , Pilard Jean‐François , Augé‐Gouillou Corinne
Published: December 2014

Transposases are specific DNA‐binding proteins that promote the mobility of discrete DNA segments. We used a combination of physicochemical approaches to describe the association of MOS1 (an eukaryotic transposase) with its specific target DNA, an event corresponding to the first steps of the transposition cycle. Because the kinetic constants of the reaction are still unknown, we aimed to determine them by using quartz crystal microbalance on two sources of recombinant MOS1: one produced in insect cells and the other produced in bacteria. The prokaryotic‐expressed MOS1 showed no cooperativity and displayed a Kd of about 300 nM. In contrast, the eukaryotic‐expressed MOS1 generated a cooperative system, with a lower Kd (∼2 nm). The origins of these differences were investigated by IR spectroscopy and AFM imaging. Both support the conclusion that prokaryotic‐ and eukaryotic‐expressed MOS1 are not similarly folded, thereby resulting in differences in the early steps of transposition.
Distribution of telomeres in the tobacco meiotic nuclei during cytomixis
Authors: Mursalimov Sergey , Sidorchuk Yuri , Baiborodin Sergey , Deineko Elena
Published: December 2014

Cytomixis is the migration of nuclei from one cell to another in higher plants, most frequently observable during microsporogenesis, which has a potential evolutionary significance. Currently, a major challenge is to label the chromatin migrating between cells to clarify its further fate. We have for the first time succeeded in visualizing the telomeric chromatin regions in the nuclei migrating between cells using fluorescent in situ hybridization. It has been shown that the telomeric signals in tobacco microsporocytes are randomly distributed in migrating nuclei without any deviations from their normal meiotic dynamics. According to our data, the chromatin migrating during cytomixis always contains telomeres and the telomeric signals are retained in the micronuclei formed after cytomixis.
Blockage of protease‐activated receptor 1 ameliorates heat‐stress induced intestinal high permeability and bacterial translocation
Authors: Xu Qiu‐lin , Guo Xiao‐hua , Liu Jing‐xian , Chen Bin , Liu Zhi‐feng , Su Lei
Published: December 2014

Accumulated evidences indicate intestinal lesions play an important role in the pathogenesis of heatstroke. However, the underlying mechanisms by which heat stress causes intestinal barrier dysfunction and bacterial translocation remain unclear. In this study, we investigated the role of protease‐activated receptor 1 (PAR1) in heat stress‐induced intestinal hyper‐permeability and bacterial translocation. Intestinal permeability in heat stressed mouse was evaluated by determining plasma endotoxin concentration and urinal lactulose/mannitol (L/M) ratio with gastric administration of L/M solution. Venous blood, liver, spleen and mesenteric lymph node tissues were collected for bacterial load test. Real time PCR was used to determine ileum PAR1 mRNA expression. In vitro study, permeability was assessed by determining trans‐epithelial electrical resistance (TEER) in human intestinal Caco‐2 cell line. RWJ‐58259, a selective antagonist of PAR1, was used both in vivo and in vitro studies. The results showed that heat stress could increase ileum PAR1 mRNA level, urinal L/M ratio, plasma endotoxin concentration and bacterial load in the blood, spleen and mesenteric lymph nodes. Blocking PAR1 with RWJ‐58259 (10 mg/kg) pretreatment could significantly reduce heat stress‐induced above changes, but have no role to PAR1 mRNA level. In Caco‐2 cells, heat stress‐induced high permeability could also be reduced by RWJ‐58259 (5–20 µmol/L). In summary, our results demonstrated that PAR1 signaling pathway may play an important role in the heat stress‐induced elevation of intestinal permeability, bacterial translocation and the occurrence of endotoxemia.
Growth factors mediated differentiation of mesenchymal stem cells to cardiac polymicrotissue using hanging drop and bioreactor
Authors: Konstantinou Dimitrios , Lei Ming , Xia Zhidao , Kanamarlapudi Venkateswarlu
Published: December 2014

Heart disease is the major leading cause of death worldwide and the use of stem cells promises new ways for its treatment. The relatively easy and quick acquisition of human umbilical cord matrix mesenchymal stem cells (HUMSCs) and their properties make them useful for the treatment of cardiac diseases. Therefore, the main aim of this investigation was to create cardiac polymicrotissue from HUMSCs using a combination of growth factors [sphingosine‐1‐phosphate (S1P) and suramin] and techniques (hanging drop and bioreactor). Using designated culture conditions of the growth factors (100 nM S1P and 500 µM suramin), cardiomyocyte differentiation medium (CDM), hanging drop, bioreactor and differentiation for 7 days, a potential specific cardiac polymicrotissue was derived from HUMSCs. The effectiveness of growth factors alone or in combination in differentiation of HUMSCs to cardiac polymicrotissue was analysed by assessing the presence of cardiac markers by immunocytochemistry. This analysis demonstrated the importance of those growth factors for the differentiation. This study for the first time demonstrated the formation of a cardiac polymicrotissue under specific culture conditions. The polymicrotissue thus obtained may be used in future as a ‘patch’ to cover the injured cardiac region and would thereby be useful for the treatment of heart diseases.
Down‐regulation of G protein‐coupled receptor 137 by RNA interference inhibits cell growth of two hepatoma cell lines
Authors: Shao Xin , Liu Yong , Huang Hai , Zhuang Linyuan , Luo Tianping , Huang Huping , Ge Xinguo
Published: December 2014

G protein‐coupled receptors (GPCRs) are important signal transduction mediators and pharmacological therapeutic targets. G protein‐coupled receptor 137 (GPR137) was initially reported as a novel orphan GPCR around 10 years ago. Some orphan GPCRs have been implicated in cancer cell proliferation and migration. The aim of this study is to investigate the role of GPR137 in hepatocellular carcinoma (HCC). GPR137 is widely expressed in several human HCC cell lines, as determined by real‐time PCR. We then applied lentivirus mediated RNA interference (RNAi) to knock down GPR137 expression in two HCC cell lines HepG2 and Bel7404. Depletion of GPR137 remarkably inhibited cell proliferation and colony formation capacity. Knockdown of GPR137 in HepG2 cells led to cell cycle arrest at G0/G1 phase and G2/M phase, and induced cell apoptosis, as determined by flow cytometry analysis, which contributed to cell growth inhibition. Our findings suggested that GPR137 could facilitate HCC cell proliferation and thus promote hepatocarcinogenesis. Cell Biol Int XX (2014) XXXX–XXXX © 2014 International Federation for Cell Biology
Retrofitting of the Heat Exchanger Network with Steam Generation in a Crude Oil Distillation Unit
Authors: Gu Wugen , Chen Xiaozhong , Liu Kai , Zhang Bingjian , Chen Qinglin , Hui Chi‐Wai
Published: December 2014

Steam generation through hot streams has an important impact on the utility consumption of a crude oil distillation unit. Retrofitting of the heat exchanger network with steam generation in a crude oil distillation unit is studied with regard to efficient energy usage. The grand composite curve is employed to provide insights into the steam generation problem, and a mixed‐integer linear programming model, presented previously for heat integration through hot discharges/feeds and steam generation, is used to obtain the optimal parameters for steam generation. Three heuristic rules are then proposed to determine suitable hot streams for steam generation. Finally, the heat exchanger network is modified based on pinch technology. After the retrofit, the hot and cold utility decrease.
The Formation of High‐Order Polybromides in a Room‐Temperature Ionic Liquid: From Monoanions ([Br5]− to [Br11]−) to the Isolation of [PC16H36]2[Br24] as Determined by van der Waals Bonding Radii
Authors: Easton Max E. , Ward Antony J. , Hudson Toby , Turner Peter , Masters Anthony F. , Maschmeyer Thomas
Published: December 2014

An unprecedented diversity of high‐order bromine catenates (anionic polybromides) was generated in a tetraalkylphosphonium‐based room temperature ionic liquid system. Raman spectroscopy was used to identify polybromide monoanions ranging from [Br5]− to [Br11]− in the bulk solution, while single‐crystal X‐ray diffraction identified extended networks of linked [Br11]− units, forming a previously unknown polymeric [Br24]2− dianion. This represents the largest polybromide species identified to date. In combination with recent work, this suggests that other, higher order molecular polybromide ions might be isolated.
When Self‐Assembly Fails: Stepwise Metal‐Directed Synthesis of [2]Catenanes
Authors: López‐Vidal Eva M. , García Marcos D. , Peinador Carlos , Quintela José M.
Published: December 2014

On the attempted synthesis of a series of homo‐ and heterotrimetallic [2]catenanes by the self‐assembly of a 2‐(pyridin‐4‐ylmethyl)‐2,7‐diazapyrenium ligand, (ethylenediamine)palladium(II) or platinum(II) nitrate, and a dioxoaryl bis(N‐monoalkyl‐4,4′‐bipyridinium) salt as building blocks, both the one‐pot direct self‐assembly of the components and the so called “magic ring” approach fail to produce the expected trinuclear [2]catenanes under thermodynamically driven conditions. However, one of the target supramolecules is obtained by following a stepwise protocol, consisting of the threading of a dinuclear PtII metallacycle and the dioxoaryl bis(N‐monoalkyl‐4,4′‐bipyridinium) axle, followed by kinetically controlled PtII‐directed cyclization of the corresponding pseudorotaxane.
Structural and Kinetic Dissection of the endo‐α‐1,2‐Mannanase Activity of Bacterial GH99 Glycoside Hydrolases from Bacteroides spp.
Authors: Hakki Zalihe , Thompson Andrew J. , Bellmaine Stephanie , Speciale Gaetano , Davies Gideon J. , Williams Spencer J.
Published: December 2014

Glycoside hydrolase family 99 (GH99) was created to categorize sequence‐related glycosidases possessing endo‐α‐mannosidase activity: the cleavage of mannosidic linkages within eukaryotic N‐glycan precursors (Glc1–3Man9GlcNAc2), releasing mono‐, di‐ and triglucosylated‐mannose (Glc1–3‐1,3‐Man). GH99 family members have recently been implicated in the ability of Bacteroides spp., present within the gut microbiota, to metabolize fungal cell wall α‐mannans, releasing α‐1,3‐mannobiose by hydrolysing αMan‐1,3‐αMan→1,2‐αMan‐1,2‐αMan sequences within branches off the main α‐1,6‐mannan backbone. We report the development of a series of substrates and inhibitors, which we use to kinetically and structurally characterise this novel endo‐α‐1,2‐mannanase activity of bacterial GH99 enzymes from Bacteroides thetaiotaomicron and xylanisolvens. These data reveal an approximate 5 kJ mol−1 preference for mannose‐configured substrates in the −2 subsite (relative to glucose), which inspired the development of a new inhibitor, α‐mannopyranosyl‐1,3‐isofagomine (ManIFG), the most potent (bacterial) GH99 inhibitor reported to date. X‐ray structures of ManIFG or a substrate in complex with wild‐type or inactive mutants, respectively, of B. xylanisolvens GH99 reveal the structural basis for binding to D‐mannose‐ rather than D‐glucose‐configured substrates.
Mesoporous Bubble‐like Manganese Silicate as a Versatile Platform for Design and Synthesis of Nanostructured Catalysts
Authors: Zhan Guowu , Yec Christopher C. , Zeng Hua Chun
Published: December 2014

Manganese silicate in bubble‐like morphology was used as a versatile platform to prepare a new class of yolk–shell hybrids. The mesoporosity of the shell was generated from the interbubble space and the bubble structure of manganese silica was used to hold and support nanoparticles (e.g., Au, Ag, Pt, Co, Ni, Au–Pd alloy, MoO2, Fe3O4, carbon nanotubes and their combinations). We also used heterogeneous catalysis reactions to demonstrate the workability of these catalysts in both liquid and gas phases.
Investigation of Alkyne Regioselectivity in the Ni‐Catalyzed Benzannulation of Cyclobutenones
Authors: Stalling Timo , Harker Wesley R. R. , Auvinet Anne‐Laure , Cornel Erik J. , Harrity Joseph P. A.
Published: December 2014

A Ni‐catalyzed benzannulation reaction of cyclobutenones and alkynes provides a rapid synthesis of heavily substituted phenols. The regioselectivity of this reaction can be modulated by variation of substituents on the alkyne. Though the incorporation of Lewis basic donors provides modest selectivities, the use of aryl substituents can provide high levels of regiocontrol. Finally, alkynylboronates derived from alkyl‐substituted acetylenes provide both high yields and regioselectivities. This study suggests that alkynes bearing one sp2‐ and one sp3‐based substituent can undergo benzannulation with high levels of regiocontrol whereby the sp3‐based group is incorporated ortho‐to the phenolic OH.
Macrocycle Embrace: Encapsulation of Fluoroarenes by m‐Phenylene Ethynylene Host
Authors: Popov Ilya , Chen Teng‐Hao , Belyakov Sergey , Daugulis Olafs , Wheeler Steven E. , Miljanić Ognjen Š.
Published: December 2014

We report structural characterization of a new member of m‐phenylene ethynylene ring family. This shape‐persistent macrocycle also co‐crystallizes with hexafluoro‐, 1,2,4,5‐tetrafluoro‐, 1,3,5‐trifluoro, and 1,4‐difluorobenzene. The four complexes are almost isostructural, and all show the fluoroarene included into the central cavity of the macrocycle. Characterized by multiple short CH⋅⋅⋅FC contacts, these inclusion complexes further dimerize in the solid state into a 2+2 assembly, in which the two macrocycles embrace each other by their large hydrophobic groups that are rotated by 60° relative to one another.
Enhancing Effects of Salt Formation on Catalytic Activity and Enantioselectivity for Asymmetric Hydrogenation of Isoquinolinium Salts by Dinuclear Halide‐Bridged Iridium Complexes Bearing Chiral Diphosphine Ligands
Authors: Kita Yusuke , Yamaji Kenta , Higashida Kosuke , Sathaiah Kandula , Iimuro Atuhiro , Mashima Kazushi
Published: December 2014

Invited for the cover of this issue is the group of Kazushi Mashima at Osaka University. The image depicts a novel six‐membered outer sphere transition state—the substrate and product are represented by locomotives with a six‐membered rail, and chiral induction by a signal. Read the full text of the article at 10.1002/chem.201405408.
Platinum trans‐Bis(borirene) Complexes Displaying Coplanarity and Communication Across a Platinum Metal Center
Authors: Braunschweig Holger , Damme Alexander , Dewhurst Rian D. , Kelch Hauke , Macha Bret B. , Radacki Krzysztof , Vargas Alfredo , Ye Qing
Published: December 2014

Invited for the cover of this issue is the group of Holger Braunschweig at the Julius‐Maximilians‐Universität Würzburg. The image depicts a “fight” for coplanarity in platinum­ trans‐bis(borirene) complexes. Read the full text of the article at 10.1002/chem.201405803.
Novel Magnetic Cross‐Linked Lipase Aggregates for Improving the Resolution of (R, S)‐2‐octanol
Authors: Liu Ying , Guo Chen , Liu Chun‐Zhao
Published: December 2014

Novel magnetic cross‐linked lipase aggregates were fabricated by immobilizing the cross‐linked lipase aggregates onto magnetic particles with a high number of ‐NH2 terminal groups using p‐benzoquinone as the cross‐linking agent. At the optimal fabrication conditions, 100% of immobilization efficiency and 139% of activity recovery of the magnetic cross‐linked lipase aggregates were achieved. The magnetic cross‐linked lipase aggregates were able to efficiently resolve (R, S)‐2‐octanol, and retained 100% activity and 100% enantioselectivity after 10 cycles of reuse, whereas the cross‐linked lipase aggregates only retained about 50% activity and 70% enantioselectivity due to insufficient cross‐linking. These results provide a great potential for industrial applications of the magnetic cross‐linked lipase aggregates. Chirality 27:199–204, 2015. © 2014 Wiley Periodicals, Inc.
Die Selivanov‐Probe auf Fructose
Authors: Shuklov Ivan A. , Boeck Gisela
Published: December 2014

Auch wenn die Selivanov‐Probe heute in der reinen präparativen Chemie auf dem Gebiet der Kohlenhydrate eine untergeordnete Rolle spielt, ist sie in der Analytik der Biochemie und der Lebensmittelchemie bis heute als Nachweis für Fructose von Bedeutung. In diesem Beitrag wurde der Werdegang von Fédor Fédorovic̆ Selivanov, des aus einer Adelsfamilie stammenden, mit volkstümlerischen Gedanken konfrontierten, in Russland, in der Schweiz und in Deutschland ausgebildeten Chemikers dargestellt. Auf seinem Lebensweg begegnete er in verschiedenen Ländern vielen Chemikern, die in weit größerem Ausmaß als Selivanov selbst Spuren hinterlassen haben. Seine Publikationen zeugen von einem regen Wissensaustausch zwischen den Chemie‐ bzw. Agrochemiezentren in Russland und Deutschland. Zu Selivanovs wesentlichen Leistungen zählen neben dem Fructose‐Nachweis wichtige Arbeiten auf dem Gebiet der Halogenstickstoffe, besonders auch die erste Synthese von N‐Bromsuccinimid. Als zeitweiliger Vorgesetzter von Arbuzov ermöglichte er ihm, experimentelle Arbeiten durchzuführen, von denen die sogenannte Michaelis‐Arbuzov‐Reaktion in die Geschichte eingegangen ist.
Profragrances – Riechstoffvorstufen
Authors: Herrmann Andreas
Published: December 2014

Profragrances und Proparfüme setzen Riechstoffe mittels einer kovalenten Bindungsspaltung aus nichtflüchtigen Vorstufen frei, um die Dauer der Duftwirkung in Anwendungen der funktionellen Parfümerie zu verlängern. Freisetzungssysteme, die auf Riechstoffvorläufern basieren, benötigen Reaktionsbedingungen, die mit den milden Umgebungsbedingungen in unserem Alltagsleben vereinbar sind. Riechstoffvorstufen werden typischerweise durch enzymatische Umwandlungen, Hydrolysen (z. B. ausgelöst durch einen pH‐Wechsel), Oxidationen mit Luftsauerstoff, milde Temperaturunterschiede oder durch Tageslicht gespalten. Erfolgreiche Riechstoffvorläufer sind preisgünstig, lagerungsstabil und setzen den entsprechenden Riechstoff effizient nach ihrer Ablagerung auf der Zieloberfläche frei. Dies sind Anforderungen, die in der Praxis nicht immer leicht zu erfüllen sind.
Ultraschnelle Dynamik von Strukturen und Schwingungen
Authors: Elsaesser Thomas
Published: December 2014

Aufgrund der begrenzten Bindungsstärke von Wasserstoffbrücken unterliegen wässrige Systeme ultraschnellen strukturellen Fluktuationen im Zeitbereich zwischen 10–14 und 10–11 s. Schwingungsanregungen von Wasserstoffbrücken zerfallen ebenfalls in diesem Zeitbereich. Die mehrdimensionale Ultrakurzzeit‐Infrarotspektroskopie erlaubt eine zeitaufgelöste Beobachtung dieser elementaren Dynamik in Wasser, hydratisierten DNA‐Oligomeren und Phospholipiden. Neben Kopplungen zwischen Schwingungsfreiheitsgraden des hydratisierten Systems lässt sich die Wasserdynamik an Grenzflächen und im Volumen direkt aufzeichnen. Strukturelle Fluktuationen im Volumen von H2O treten im Zeitbereich zwischen 5×10–14 und 10–12 s auf, Wasserstoffbrücken werden im Takt von 10–12 s gebrochen und neu geformt. An den Grenzflächen zu DNA und Phospholipiden existieren Hydratisierungsgeometrien, die bei geringen Fluktuationen länger als 10–11 s aufrecht erhalten werden. Ein langlebiges ‘Gedächtnis’ des Wassers existiert jedoch nicht.
Ein neuer Molekülbaukasten
Authors: Groß Michael
Published: December 2014

Chemie wäre viel einfacher, wenn man Moleküle einfach zusammenstöpseln könnte wie Legosteine – ohne gefährliche Reagenzien und Nebenprodukte. Durch cleveres Design der Bausteine haben Chemiker jetzt eine neue Gruppe von vielfältig variierbaren Synthesen entwickelt, die diesem Ideal der Klick‐Chemie [4] entsprechen und den Zugang zu vielfältigen, auch pharmakologisch interessanten Produkten eröffnen.
Solubility Of CO2 and C2H6 in heavy Oil and its Sara fractions
Authors: Marufuzzaman Mohammad , Henni Amr
Published: December 2014

Solvent‐based recovery is one of the most promising techniques to enhance heavy oil/bitumen recovery as an alternative to thermal methods. Phase behaviour study of light gases in heavy oil is therefore very important when designing operation and surface facilities for heavy oil recovery. In this study, the original oil (Cactus Lake) was first characterized into saturate, aromatic, resin, asphaltene, and maltene fractions (0.0 wt. % asphaltene). An intelligent gravimetric microbalance was used to measure the solubility of carbon dioxide and ethane in the heavy oil and its saturate, aromatic, resin, asphaltene, and maltene fractions. The measurements were carried out at 288, 294, 299, and 303 K, and at pressures from 200 to 2000 kPa. The standard Peng‐Robinson equation of state was used to correlate the experimental results. The associated Henry's law constants were regressed and reported. The adsorbed amounts of carbon dioxide and ethane on asphaltene were correlated using the Freundlich isotherm. As for the given heavy oil sample and its fractions, carbon dioxide showed lower solubility than ethane at constant temperature, even at high pressures. It was observed that the asphaltene content affects ethane solubility quite significantly in this heavy oil when compared to carbon dioxide.
Chemical‐Looping Reforming of Methane Using Iron Based Oxygen Carrier Modified with Low Content Nickel
Authors: Wei Guoqiang , He Fang , Huang Zhen , Zhao Kun , Zheng Anqing , Li Haibin
Published: December 2014

Fe2O3/Al2O3 and Fe2O3/Al2O3 modified by low content of Ni (below 2% in weight) oxygen carriers were prepared by mechanical mixing and impregnation method. The synthesized oxygen carriers were characterized by means of X‐ray diffraction (XRD), X‐ray fluorescence (XRF), scanning electron microscopy (SEM), BET‐surface area and temperature programmed reduction (TPR). Besides, redox cyclic reactivity and the performance of chemical looping reforming of methane of the oxygen carriers were studied in a thermal gravimetrical analysis (TGA) and fixed bed at 850°C. It was observed that the redox reactivity of the oxygen carriers is improved by Ni addition because synergic effect may occur between NiO and Fe2O3/Al2O3 to form NiFe2O4 and NiAl2O4 spinel phases. However, the improvement was not apparent as Ni addition reached 1 wt% or more because more nickel loaded resulted in methane decomposition into H2 and carbon leading to carbon deposition. The SEM and BET analysis showed that NiFe2O4 and NiAl2O4 particles dispersed into the pores of the Fe2O3/Al2O3 particles in the course of preparation. In addition, the resistance to sintering of the modified samples increased with the Ni addition increasing. The results of successive redox cycles showed that the Ni modified Fe2O3/Al2O3 oxygen carriers have good regenerability. With integration of reactivity and carbon deposition, the content 1.04 wt% of nickel doping was an optimal amount in the three modified samples.
Continuous Dehydrogenation of n‐Pentanol over a Cr Modified Cu/γ‐Al2O3‐La2O3 Catalyst
Authors: Liu Chen , Wang Yalong , Chu Hailong , Qiu Mande , Niu Libo , Bai Guoyi
Published: December 2014

The oxidant‐free dehydrogenation of n‐pentanol over copper based catalysts was investigated in this paper. The effect of metal modification on the activity and stability of the copper catalyst supported on γ‐Al2O3 and La2O3 (Cu/γ‐Al2O3‐La2O3) was clarified and a Cr modified Cu/Al2O3‐La2O3 (Cu‐Cr/γ‐Al2O3‐La2O3) showed the best catalytic performance. The conversion of n‐pentanol was 70.0% and the selectivity for n‐pentanal increased to 97.1% over Cu‐Cr/γ‐Al2O3‐La2O3. X‐ray diffraction and temperature programmed reduction of H2 indicated that the addition of Cr favors the formation and reduction of the copper oxide, and the dispersion of the active Cu0 species, accounting for the good activity and stability of this catalyst. Furthermore, the lower amount of acidic sites in Cu‐Cr/γ‐Al2O3‐La2O3 is suggested to suppress the dehydration in oxidant‐free dehydrogenation of n‐pentanol, accounting for the higher selectivity for n‐pentanal.
Site‐specific Analysis of Amyloid Assemblies by Using Scanning Tunneling Microscopy
Authors: Yu Yue , Yang Yanlian , Wang Chen
Published: December 2014

The assembly of amyloid peptides into highly organized fibrils is one of the major characteristics of many degenerative diseases such as Alzheimer's disease and type II diabetes. Assembly structures of amyloid peptides at liquid‐solid interface can be visualized by scanning tunneling microscopy (STM) with site‐specific resolution. The STM analysis can provide valuable information on the folding mechanism of amyloid peptides based on the correlation of surface assembly structures and fibrillation behaviors. Cases on mutational analysis of amyloid peptides by STM are also reviewed which illustrate the capacities of STM studies on amyloid assemblies.
A Fluorescent Chemosensor for Dihydrogen Phosphate Ion Based on 2‐[2‐Hydroxy‐4‐(diethylamino) phenyl]‐1H‐imidazo[4,5‐b]phenazine‐Fe3+ Ensemble
Authors: Wei Taibao , Wu Guiyuan , Shi Bingbing , Lin Qi , Yao Hong , Zhang Youming
Published: December 2014

A long wavelength emission fluorescent (612 nm) chemosensor with high selectivity for H2PO4− ions was designed and synthesized according to the excited state intramolecular proton transfer (ESIPT). The sensor can exist in two tautomeric forms ('keto' and 'enol') in the presence of Fe3+ ion, Fe3+ may bind with the 'keto' form of the sensor. Furthermore, the in situ generated GY‐Fe3+ ensemble could recover the quenched fluorescence upon the addition of H2PO4− anion resulting in an off‐on‐type sensing with a detection limit of micromolar range in the same medium, and other anions, including F−, Cl−, Br−, I−, AcO−, HSO4−, ClO4− and CN− had nearly no influence on the probing behavior. The test strips based on 2‐[2‐hydroxy‐4‐(diethylamino) phenyl]‐1H‐imidazo[4,5‐b]phenazine and Fe3+ metal complex (GY‐Fe3+) were fabricated, which could act as convenient and efficient H2PO4− test kits.
Direct Myocardial Ischemia Imaging: a New Cardiovascular Nuclear Imaging Paradigm
Authors: Jain Diwakar , He Zuo‐Xiang , Lele Vikram , Aronow Wilbert S.
Published: December 2014

Myocardial perfusion imaging (MPI), using radiotracers, has been in routine clinical use for over 40 years. This modality is used for the detection of coronary artery disease (CAD), risk stratification, optimizing therapy, and follow‐up of patients with CAD. Molecular cardiovascular imaging using targeted radiotracers provides a unique opportunity for imaging biochemical and metabolic processes, and cell membrane transporter and receptor functions at a cellular and molecular level in experimental animal models as well as in humans. Cardiac imaging using radiolabeled free fatty acid analogues and glucose analogues enable us to image myocardial ischemia directly as an alternative to stress‐rest MPI. Direct ischemia imaging techniques can avoid and overcome some of the limitations of standard stress‐rest MPI. This article describes recent studies using 18F‐fluorodeoxyglucose (18FDG) for myocardial ischemia imaging.
Promiscuity and the Conformational Rearrangement of Drug‐Like Molecules: Insight from the Protein Data Bank
Authors: He Michael W. , Lee Patrick S. , Sweeney Zachary K.
Published: December 2014

Selectivity is a central aspect of lead optimization in the drug discovery process. Medicinal chemists often try to decrease molecular flexibility to improve selectivity, given the common belief that the two are interdependent. To investigate the relationship between polypharmacology and conformational flexibility, we mined the Protein Data Bank and constructed a dataset of pharmaceutically relevant ligands that crystallized in more than one protein target while binding to each co‐crystallized receptor with similar in vitro affinities. After analyzing the molecular conformations of these 100 ligands, we found that 59 ligands bound to different protein targets without significantly changing conformation, suggesting that there is no distinct correlation between conformational flexibility and polypharmacology within our dataset. Ligands crystallized in similar proteins and highly ligand‐efficient compounds with five or fewer rotatable bonds were less likely to adjust conformation when binding.