bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards polypotent natural products: The Derringer desirability approach and nonparametric ranking for multicriteria evaluation of essential oils
Authors: Andrić Filip Lj. 
Published: June 2018

AbstractChemical complexity of natural products often results in their pharmacological polypotency. However, selecting a natural product with desirable activity profile is not a straightforward task, especially if optimization of one feature results in deterioration of other facets.Recently, in the field of multiobjective optimization, the sum of ranking differences (SRD) has emerged as a simple and statistically sound method for fusion of multiple criteria. However, the data pretreatment seems to strongly influence the ranking outcome, which may lead to ambiguous or even false interpretations. Therefore, in the present study, the data of 55 essential oils originated from different plant species and tested on multiple bacterial and fungal strains as well as 4 antioxidative assays were studied. Essential oils were ranked using the classical Deringer desirability approach, and results were compared with the SRD analysis of primary activity data as well as the previously row‐wise standardized data, normalized data, and the data scaled to fit the preferences. Ultimately, the most promising candidate (polypotent) essential oils, as well as the most resilient and most sensitive bacterial and fungal strains, and antioxidative assays were identified. Data transformation based on the Deringer desirability approach, compared with the data that have not been previously transformed or those that transformed using a row‐wise standardization or normalization to the unit length vector, seemed to be the crucial step providing the sound and meaningful SRD ranking.
High Throughput Experimentation and Continuous Flow Validation of Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Jaman Zinia , Mufti Ahmed , Sah Samyukta , Avramova Larisa , Thompson David H. 
Published: June 2018

AbstractTraditional methods to discover optimal reaction conditions for small molecule synthesis is a time‐consuming effort that requires large quantities of material and a significant expenditure of labor. High‐throughput techniques are a potentially transformative approach for reaction condition screening, however, rapid validation of the reaction hotspots under continuous flow conditions remains necessary to build confidence in high throughput screening hits. Continuous flow technology offers the opportunity to upscale the screening hotspots and optimize their output of the target compounds due to the exceptional heat and mass transfer ability of flow reactions that are conducted in a smaller and safer reaction volume. We report a robotic high throughput technique to execute reactions in multi‐well plates that were coupled with fast mass spectrometric analysis using an autosampler to accelerate the reaction screening process. Palladium‐catalyzed Suzuki–Miyaura cross‐coupling reactions were screened in this system and a heat map was generated to identify the best reaction conditions for downstream scale‐up under continuous flow. Here, high throughput experimentation reactions in 96‐well plates were performed for 1 h at 50 °C, 100 °C, 150 °C, and 200 °C before diluting them into 384‐well plates for mass analysis. With the aid of high throughput tools, 648 unique experiments were conducted in duplicate. The cross‐coupling reactions were evaluated as a function of stoichiometry, temperature, concentration, order of addition, and substrate type. The hotspots from high throughput experimentation were examined using a microfluidic Chemtrix system that confirmed the positive reaction leads as true positives. Negative outcomes identified by these experiments were found to be true negatives by microfluidic reaction evaluation. Quantitation of product yields was performed using high‐performance liquid chromatography‐mass spectrometry (HPLC/MS‐MS).
Mechanism of Mechanochemical C−H Bond Activation in an Azobenzene Substrate by PdII Catalysts
Authors: Bjelopetrović Alen , Lukin Stipe , Halasz Ivan , Užarević Krunoslav , Đilović Ivica , Barišić Dajana , Budimir Ana , Juribašić Kulcsár Marina , Ćurić Manda 
Published: June 2018

AbstractMechanism of C−H bond activation by various PdII catalysts under milling conditions has been studied by in situ Raman spectroscopy. Common PdII precursors, that is PdCl2, [Pd(OAc)2]3, PdCl2(MeCN)2 and [Pd(MeCN)4][BF4]2, have been employed for the activation of one or two C−H bonds in an unsymmetrical azobenzene substrate. The C−H activation was achieved by all used PdII precursors and their reactivity increases in the order [Pd(OAc)2]3<PdCl2(MeCN)2<PdCl2<[Pd(MeCN)4][BF4]2. In situ Raman monitoring in combination with stepwise ex situ NMR, IR and PXRD experiments has provided direct probing of the reaction mechanism and kinetics, and revealed how liquids of different acid‐base properties and proticity as well as selected solids used as additives modify precursors or intermediates and their reactivity. Reaction intermediates that were isolated and structurally characterized agree with the observed species during reaction. In situ Raman spectroscopy has also enabled the derivation of reaction profiles suggesting an electrophilic process which proceeds via a coordination complex (adduct) undergoing deprotonation by a bound or an external base depending on the used PdII precursor. Slow step of the first palladation for two chloride precursors and [Pd(MeCN)4][BF4]2 is the C−H bond cleavage whereas palladation using [Pd(OAc)2]3 depends primarily on breaking of its trimeric structure by the azobenzene substrate and/or liquid additives.
Ruthenium‐Catalyzed Cycloisomerization of 2‐Alkynylstyrenes via 1,2‐Carbon Migration That Leads to Substituted Naphthalenes
Authors: Watanabe Takuma , Abe Haruka , Mutoh Yuichiro , Saito Shinichi 
Published: June 2018

AbstractA ruthenium‐catalyzed carbocyclization of 2‐alkynylstyrenes that involves a very rare 1,2‐carbon migration of internal alkynes is reported. Various 1,2‐di ‐and 1,4,7‐trisubstituted naphthalenes are synthesized. Mechanistic studies revealed that this reaction proceeds via a disubstituted vinylidene complex as the key intermediate by 1,2‐carbon migration of the 2‐alkynylstyrenes.
Synthesis of α‐Aminophosphines by Copper‐Catalyzed Regioselective Hydroamination of Vinylphosphines
Authors: Takata Tatsuaki , Nishikawa Daiki , Hirano Koji , Miura Masahiro 
Published: June 2018

AbstractA copper‐catalyzed net hydroamination of vinylphosphine boranes with hydrosilanes and O‐benzoylhydroxylamines has been developed. The reaction proceeds regioselectively to form the corresponding α‐aminophosphine boranes of potent interest in medicinal and pharmaceutical chemistry. This copper catalysis is based on an umpolung, electrophilic amination strategy and provides a new electrophilic amination approach to α‐aminophosphine derivatives. Additionally, although still preliminary, asymmetric synthesis has also been achieved by judicious choice of a chiral bisphosphine‐ligated copper complex.
Theoretical Studies on the Hydroaminoalkylation of Alkenes with Primary and Secondary Amines
Authors: Stelter Luisa , Teusch Thomas , Bielefeld Jens , Doye Sven , Klüner Thorsten 
Published: June 2018

AbstractThe α‐alkylation of amines with alkenes catalyzed by early transition‐metal complexes represents an efficient and atom economic method for the synthesis of functionalized amines from simple and easily available starting materials. While the successful use of secondary amines, such as dimethylamine, strongly underlines the enormous industrial potential of this reaction, the analogous intermolecular α‐alkylation of primary amines, especially methylamine, remains an unsolved synthetic task to this day. Based on calculated thermodynamic data, these experimental findings can now be explained for the first time, whereby several competing reactions, which are explained in detail, are of crucial importance for the different behavior of primary and secondary amines.
Helicenes as Chirality‐Inducing Groups in Transition‐Metal Catalysis: The First Helically Chiral Olefin Metathesis Catalyst
Authors: Karras Manfred , Dąbrowski Michał , Pohl Radek , Rybáček Jiří , Vacek Jaroslav , Bednárová Lucie , Grela Karol , Starý Ivo , Stará Irena G. , Schmidt Bernd 
Published: June 2018

AbstractHelical chirality is a novel enantioselectivity‐inducing property in transition‐metal‐catalyzed transformations. The principle is illustrated herein for the example of asymmetric olefin metathesis. This work reports the synthesis of the first helically chiral Ru‐NHC alkylidene complex from an aminohelicene‐derived imidazolium salt, which was ligated to the first generation Hoveyda–Grubbs catalyst. Kinetic data were acquired for benchmark test reactions and compared to an achiral catalyst. The helically chiral Ru‐catalyst was evaluated in asymmetric ring‐closing metathesis (RCM) and ring‐opening metathesis–cross‐metathesis (ROM/CM) reactions, which proceeded with promising levels of enantioselectivity. Extensive NMR‐spectroscopic investigations and a DFT geometry optimization were performed. These results led to a topographic steric map and calculation of percent‐buried‐volume values for each quadrant around the metal center.
Mixed X‐Site Formate–Hypophosphite Hybrid Perovskites
Authors: Wu Yue , Halat David M. , Wei Fengxia , Binford Trevor , Seymour Ieuan D. , Gaultois Michael W. , Shaker Sammy , Wang John , Grey Clare P. , Cheetham Anthony K. 
Published: June 2018

AbstractFollowing the recent discovery of a new family of hybrid ABX3 perovskites where X=(H2POO)− (hypophosphite), this work reports a facile synthesis for mixed X‐site formate perovskites of composition [GUA]Mn(HCOO)3−x(H2POO)x, with two crystallographically distinct, partially ordered intermediate phases with x=0.84 and 1.53, corresponding to ca. 30 and 50 mol % hypophosphite, respectively. These phases are characterised by single‐crystal XRD and solid‐state NMR spectroscopy, and their magnetic properties are reported.
Aggregate structures formed by hyperbranched functionalized polyethylene (HBfPE) treatment of oil sands tailings
Authors: Costine Allan D. , Vajihinejad Vahid , Botha Linda , Fawell Phillip D. , Soares João B. P. 
Published: June 2018

AbstractThe unique chemical and physical properties of oil sands tailings require the development of new classes of polymer flocculants to achieve efficient flocculation and dewatering. Fast and direct performance measurements of flocculation and dewatering efficiency are essential for the development of new polymer flocculants. The microscopic characterization of settling velocity and size for free settling aggregates then allows the derivation of the aggregate density as a function of size. Aggregate density is an indication of the internal aggregate structure that directly influences sedimentation, resistance to shear, and dewatering. Aggregate structures formed during oil sands tailings flocculation with a commercially‐available anionic polyacrylamide (A‐PAM) were compared with that of novel hyperbranched functionalized polyethylene (HBfPE) flocculants, showing that aggregates made with some HBfPE formulations were denser and settled faster than those formed with A‐PAM. This paper demonstrates that this approach can usefully quantify the structure of aggregates formed during the treatment of oil sands tailings with polymer flocculants.
Replacement and desmoplastic histopathological growth patterns: A pilot study of prediction of outcome in patients with uveal melanoma liver metastases
Authors: Barnhill Raymond , Vermeulen Peter , Daelemans Sofie , van Dam Pieter‐Jan , Roman‐Roman Sergio , Servois Vincent , Hurbain Ilse , Gardrat Sophie , Raposa Graça , Nicolas André , Dendale Rémi , Pierron Gaëlle , Desjardins Laurence , Cassoux Nathalie , Piperno‐Neumann Sophie , Mariani Pascale , Lugassy Claire 
Published: June 2018

AbstractUp to 50% of uveal melanomas (UM) metastasise to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal. As histopathological growth patterns (HGPs) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006–2017. Twenty patients underwent enucleation while 21 had radiation therapy. Analysis of UM by array comparative genomic hybridisation revealed: 25 (64%) patients with high risk (monosomy3/8q gain); 13 (33%) intermediate risk (M3/8normal or disomy3/8q gain); and 1 low risk (disomy3/8normal). The principal HGP was replacement in 30 (73%) cases and desmoplastic in 11 (27%) cases. Cases with replacement demonstrated striking vascular co‐option/angiotropism. With the development of liver metastasis, only the replacement pattern, largest primary tumour diameter, and R2 (incomplete resection) status predicted diminished overall survival (OS; p < 0.041, p < 0.017, p < 0.047, respectively). On multivariate analysis, only HGP (hazard ratio; HR = 6.51, p = 0.008) and resection status remained significant. The genomic high‐risk variable had no prognostic value at this stage of liver metastasis. Chi‐square test showed no association of HGP with monosomy 3 or 8q gain. Eighteen of 41 (44%) patients are alive with disease and 23 (56%) patients died with follow‐up ranging from 12 to 318 months (mean: 70 months, median: 47 months). In conclusion, we report for the first time the frequency of the replacement and desmoplastic HGPs in liver UM metastases resected from living patients, and their potential important prognostic value for UM patients, as in other solid cancers. These results may potentially be utilised to develop radiological correlates and therapeutic targets for following and treating patients with UM metastases.
Design and Synthesis of Pyrophosphate‐Targeting Vancomycin Derivatives for Combating Vancomycin‐Resistant Enterococci
Authors: Guan Dongliang , Chen Feifei , Faridoon  , Liu Junjie , Li Jian , Lan Lefu , Huang Wei 
Published: June 2018

AbstractAs the last resort for intractable Gram‐positive bacterial infections, vancomycin is losing efficacy with the emergence of vancomycin‐resistant bacteria, especially vancomycin‐resistant Enterococci (VRE). To combat this threat, we rationally designed and synthesized 39 novel vancomycin derivatives by respective or combined modifications using metal‐chelating, lipophilic, and galactose‐attachment strategies for extensive structure–activity relationship (SAR) analysis. In a proposed mechanism, the conjugation of dipicolylamine on the seventh amino acid resorcinol position or C‐terminus endowed the vancomycin backbone with binding capacity for the pyrophosphate moiety in lipid II while maintaining the intrinsic binding affinity for the dipeptide terminus of the bacterial cell wall peptidoglycan precursor. The in vitro antibacterial activities were evaluated, and the optimal compounds indicated 16‐ to 1024‐fold higher activity against VRE than that of vancomycin. Compound 11 b (3′,5′‐bis(dipicolylaminomethyl)tyrosine [1,2,3]triazolylmethoxylethyoxyl ethylaminomethyl‐N‐decylvancomycin) was found to have particularly potent activity against VRE through synergistic effects brought about by combining two peripheral modifications.
Effects of Intrinsic Factors on the Clinical Pharmacokinetics of Vortioxetine
Authors: Chen Grace , Nomikos George G. , Affinito John , Jacobson William , Zhao Zhen , Wang Shining , Xie Jinhui 
Published: June 2018

AbstractVortioxetine is an antidepressant agent with multimodal activity that is approved for the treatment of major depressive disorder at doses of 5 to 20 mg once daily. Vortioxetine is a medium‐clearance drug that undergoes extensive metabolism via several cytochrome P450 isozymes. A series of single‐ and multiple‐dose pharmacokinetic studies were performed to evaluate the impact of intrinsic (ie, subject‐related) factors, such as age, sex, race, and renal and hepatic function, on the pharmacokinetics of vortioxetine. The point estimates on the ratios and their 90% confidence intervals (CIs) for the central values of AUC (area under the concentration‐time curve) and Cmax (maximum plasma concentration) were obtained by taking the antilog of the differences and 90%CIs in the log‐transformed least‐squares means. The results demonstrate that there were no clinically meaningful differences (defined as exposure difference between 50% and 2‐fold change) in the exposure to vortioxetine (as assessed by AUC and Cmax) between elderly and younger subjects, men and women, and blacks and whites and among subjects with varying degrees of renal or hepatic impairment. These results suggest that no dosing adjustments of vortioxetine are required for the intrinsic factors investigated in these studies.
Ternary Polymeric Composites Exhibiting Bulk and Surface Quadruple‐Shape Memory Properties
Authors: Buffington Shelby L. , Posnick Benjamin M. , Paul Justine , Mather Patrick T. 
Published: June 2018

AbstractWe report the design and characterization of a multiphase quadruple shape memory composite capable of switching between 4 programmed shapes, three temporary and one permanent. Our approach combined two previously reported fabrication methods by embedding an electrospun mat of PCL in a miscible blend of epoxy monomers and PMMA as a composite matrix. As epoxy polymerization occurred the matrix underwent phase separation between the epoxy and PMMA materials. This created a multiphase composite with PCL fibers and a two‐phase matrix composed of phase‐separated epoxy and PMMA. The resulting composite demonstrated three separate thermal transitions and amenability to mechanical programming of three separate temporary shapes in addition to one final, equilibrium shape. In addition, quadruple surface shape memory abilities are successfully demonstrated. The versatility of this approach offers a large degree of design flexibility for multi‐shape memory materials.
Protein−Protein Interfaces Probed by Methyl Labeling and Proton‐Detected Solid‐State NMR Spectroscopy
Authors: Zinke Maximilian , Fricke Pascal , Lange Sascha , Zinn‐Justin Sophie , Lange Adam 
Published: June 2018

AbstractProton detection and fast magic‐angle spinning have advanced biological solid‐state NMR, allowing for the backbone assignment of complex protein assemblies with high sensitivity and resolution. However, so far no method has been proposed to detect intermolecular interfaces in these assemblies by proton detection. Herein, we introduce a concept based on methyl labeling that allows for the assignment of these moieties and for the study of protein−protein interfaces at atomic resolution.
Design of Active Sites on Nickel in the Anode of Intermediate‐Temperature Solid Oxide Fuel Cells using Trace Amount of Platinum Oxides
Authors: Rednyk Andrii , Mori Toshiyuki , Yamamoto Shunya , Suzuki Akira , Yamamoto Yuta , Tanji Takayoshi , Isaka Noriko , Kúš Peter , Ito Shigeharu , Ye Fei 
Published: June 2018

AbstractInvited for this month's cover is the group of Prof. Dr. Toshiyuki Mori at National Institute for Materials Science (NIMS), Japan. The front cover picture shows the formation of new active sites on Ni in the anode of a solid oxide fuel cell (SOFC), which displays high performance at intermediate temperature. The combination of processing route design, microanalysis, and surface atomistic simulation provides us with a new design paradigm for fabrication of high‐performance SOFCs. Read the full text of the article at 10.1002/cplu.201800170.
CAPTURE: In Situ Analysis of Chromatin Composition of Endogenous Genomic Loci by Biotinylated dCas9
Authors: Liu Xin , Zhang Yuannyu , Chen Yong , Li Mushan , Shao Zhen , Zhang Michael Q. , Xu Jian 
Published: June 2018

AbstractCis‐regulatory elements (CREs) play a pivotal role in spatiotemporal control of tissue‐specific gene expression, yet the molecular composition of the vast majority of CREs in native chromatin remains unknown. In this article, we describe the clustered regularly interspaced short palindromic repeats (CRISPR) affinity purification in situ of regulatory elements (CAPTURE) approach to simultaneously identify locus‐specific chromatin‐regulating protein complexes and long‐range DNA interactions. Using an in vivo biotinylated nuclease‐deficient Cas9 (dCas9) protein and programmable single guide RNAs (sgRNAs), this approach allows for high‐resolution and locus‐specific isolation of protein complexes and long‐range chromatin looping associated with single copy CREs in mammalian cells. Unbiased analysis of the compositional structure of developmentally regulated or disease‐associated CREs identifies new features of transcriptional regulation. Hence, CAPTURE provides a versatile platform to study genomic locus‐regulating chromatin composition in a mammalian genome. © 2018 by John Wiley & Sons, Inc.
A generalized family of memristor‐based voltage controlled relaxation oscillator
Authors: Hezayyin Haneen G. , Ahmed Gehad M. , Fouda Mohammed E. , Said Lobna A. , Madian Ahmed H. , Radwan Ahmed G. 
Published: June 2018

SummaryRecently, memristive oscillators are a significant topic in the nonlinear circuit theory where there is a possibility to build relaxation oscillators without existence of reactive elements. In this paper, a family of voltage‐controlled memristor‐based relaxation oscillator including two memristors is presented. The operation of two memristors‐based voltage relaxation oscillator circuits is demonstrated theoretically with the mathematical analysis and with numerical simulations. The generalized expressions for the oscillation frequency and conditions are derived for different cases, where a closed form is introduced for each case. The effect of changing the circuit parameters on the oscillation frequency and conditions is investigated numerically. In addition, the derived equations are verified using several transient PSPICE simulations. The power consumption of each oscillator is obtained numerically and compared with its PSPICE counterpart. Furthermore, controlling the memristive oscillator with a voltage grants the design an extra degree of freedom which increases the design flexibility. The nonlinear exponential model of memristor is employed to prove the oscillation concept. As an application, two examples of voltage‐controlled memristor‐based relaxation oscillator are provided to elaborate the effect of the reference voltage on the output voltage. This voltage‐controlled memristor‐based relaxation oscillator has nano size with storage property that makes it more efficient compared with the conventional one. It would be helpful in many communication applications.