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  • Antiproliferative Activities of Diimine-Based Mixed Ligand Copper(II) Complexes
    ACS Comb. Sci. (IF 3.200) Pub Date : 2020-01-23
    Nazanin Kordestani; Hadi Amiri Rudbari; Alexandra R. Fernandes; Luís R. Raposo; Pedro V. Baptista; Daniela Ferreira; Giuseppe Bruno; Giovanni Bella; Rosario Scopelliti; Jason D. Braun; David E. Herbert; Olivier Blacque
  • Homogeneous and Functional Group Tolerant Ring-Closing Metathesis for DNA-Encoded Chemical Libraries
    ACS Comb. Sci. (IF 3.200) Pub Date : 2020-01-21
    Olivier B. C. Monty; Pranavanand Nyshadham; Kurt M. Bohren; Murugesan Palaniappan; Martin M. Matzuk; Damian W. Young; Nicholas Simmons
  • Electrochemical screening of tungsten trioxide - nickel oxide thin film combinatorial library at low nickel concentrations.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-02-28
    Jun-Seob Lee,Cezarina Cela Mardare,Andrei Ionut Mardare,Achim Walter Hassel
  • Off-DNA DNA-Encoded Library Affinity Screening
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-31
    Amber L. Hackler; Forrest G. FitzGerald; Vuong Q. Dang; Alexander L. Satz; Brian M. Paegel
  • Oxidative Cyclization Approach to Benzimidazole Libraries
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-30
    Eric P. Arnold; Prolay K. Mondal; Daniel C. Schmitt
  • Beyond Epitope Binning: Directed in Vitro Selection of Complementary Pairs of Binding Proteins
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-24
    Eric A. Miller; Ki-Joo Sung; Patthara Kongsuphol; Subha Baniya; Hui Qi Aw-Yong; Vivian Tay; Yuxuan Tan; Farah M. Kabir; Karl Pang-Yeo; Isabel G. Kaspriskie; Hadley D. Sikes
  • Rapid Characterization and Parameter Space Exploration of Perovskites Using an Automated Routine
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-19
    Elisabeth Reinhardt; Ahmed M. Salaheldin; Monica Distaso; Doris Segets; Wolfgang Peukert
  • 更新日期:2019-12-17
  • One-Pot Synthesis of Unsymmetrical Bis-Heterocycles: Benzimidazole-, Benzoxazole-, and Benzothiazole-Linked Thiazolidines
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-09
    Hsueh-Yuan Lu, Indrajeet J. Barve, Manikandan Selvaraju, Chung-Ming Sun
  • FTO Darkening Rate as a Qualitative, High-Throughput Mapping Method for Screening Li-Ionic Conduction in Thin Solid Electrolytes
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-12-03
    Shay Tirosh, Niv Aloni, Simcha Meir, Arie Zaban, David Cahen, Diana Golodnitsky
  • Screening Yeast Display Libraries against Magnetized Yeast Cell Targets Enables Efficient Isolation of Membrane Protein Binders
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-20
    Kaitlyn Bacon, Matthew Burroughs, Abigail Blain, Stefano Menegatti, Balaji M. Rao
  • Effects of the Ion to Growth Flux Ratio on the Constitution and Mechanical Properties of Cr1–x-Alx-N Thin Films
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-19
    Lars Banko, Stefan Ries, Dario Grochla, Mostafa Arghavani, Steffen Salomon, Janine Pfetzing-Micklich, Aleksander Kostka, Detlef Rogalla, Julian Schulze, Peter Awakowicz, Alfred Ludwig
  • Interfacial Interaction between Suolunite Crystal and Silica Binding Peptide for Novel Bioinspired Cement
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-19
    Wai-Yim Ching, Lokendra Poudel, Saro San, Khagendra Baral
  • Benzimidazolyl-pyrazolo[3,4-b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-14
    Boris V. Lichitsky, Andrey N. Komogortsev, Arkady A. Dudinov, Mikhail M. Krayushkin, Evgenii N. Khodot, Alexander V. Samet, Eugenia A. Silyanova, Leonid D. Konyushkin, Alexei S. Karpov, Delphine Gorses, Thomas Radimerski, Marina N. Semenova, Alex S. Kiselyov, Victor V. Semenov
  • An Improved High-Throughput Data Processing Based on Combinatorial Materials Chip Approach for Rapid Construction of Fe–Cr–Ni Composition-Phase Map
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-12
    Zhaoyang Zhao, Ying Jin, Peng Shi, Yanpeng Xue, Bingbing Zhao, Yanpeng Zhang, Feifei Huang, Peng Bi, Qingrui Wang
  • Semiautomated Parallel RAFT Copolymerization of Isoprene with Glycidyl Methacrylate
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-11-04
    Miguel Rosales-Guzmán, Odilia Pérez-Camacho, Carlos Guerrero-Sánchez, Simon Harrisson, Román Torres-Lubián, Jürgen Vitz, Ulrich S. Schubert, Enrique Saldívar-Guerra
  • Metric Learning for High-Throughput Combinatorial Data Sets
    ACS Comb. Sci. (IF 3.200) Pub Date : 2019-10-31
    Kiran Vaddi, Olga Wodo
  • Cellular Delivery of RNA Nanoparticles.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-08-11
    Lorena Parlea,Anu Puri,Wojciech Kasprzak,Eckart Bindewald,Paul Zakrevsky,Emily Satterwhite,Kenya Joseph,Kirill A Afonin,Bruce A Shapiro

    RNA nanostructures can be programmed to exhibit defined sizes, shapes and stoichiometries from naturally occurring or de novo designed RNA motifs. These constructs can be used as scaffolds to attach functional moieties, such as ligand binding motifs or gene expression regulators, for nanobiology applications. This review is focused on four areas of importance to RNA nanotechnology: the types of RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs, the challenges of cellular delivery of RNAs in vivo, and the delivery carriers that aid in the matter. The available strategies for the design of nucleic acid nanostructures, as well as for formulation of their carriers, make RNA nanotechnology an important tool in both basic research and applied biomedical science.

  • (Chlorosulfonyl)benzenesulfonyl Fluorides-Versatile Building Blocks for Combinatorial Chemistry: Design, Synthesis and Evaluation of a Covalent Inhibitor Library.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2018-10-26
    Kateryna A Tolmachova,Yurii S Moroz,Angelika Konovets,Maxim O Platonov,Oleksandr V Vasylchenko,Petro Borysko,Sergey Zozulya,Anastasia Gryniukova,Andrey V Bogolubsky,Sergey Pipko,Pavel K Mykhailiuk,Volodymyr S Brovarets,Oleksandr O Grygorenko

    Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification of these building blocks at the sulfonyl chloride function under parallel synthesis conditions is achieved. It is shown that the reaction scope includes the use of (hetero)aromatic and electron-poor aliphatic amines (e.g., amino nitriles). Utility of the method is demonstrated by preparation of the sulfonyl fluoride library for potential use as covalent fragments, which is demonstrated by a combination of in silico and in vitro screening against trypsin as a model enzyme. As a result, several inhibitors were identified with activity on par with that of the known inhibitor.

  • How Transparent Oxides Gain Some Color: Discovery of a CeNiO3 Reduced Bandgap Phase As an Absorber for Photovoltaics.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2018-05-03
    Hannah-Noa Barad,David A Keller,Kevin J Rietwyk,Adam Ginsburg,Shay Tirosh,Simcha Meir,Assaf Y Anderson,Arie Zaban

    In this work, we describe the formation of a reduced bandgap CeNiO3 phase, which, to our knowledge, has not been previously reported, and we show how it is utilized as an absorber layer in a photovoltaic cell. The CeNiO3 phase is prepared by a combinatorial materials science approach, where a library containing a continuous compositional spread of Ce xNi1- xO y is formed by pulsed laser deposition (PLD); a method that has not been used in the past to form Ce-Ni-O materials. The library displays a reduced bandgap throughout, calculated to be 1.48-1.77 eV, compared to the starting materials, CeO2 and NiO, which each have a bandgap of ∼3.3 eV. The materials library is further analyzed by X-ray diffraction to determine a new crystalline phase. By searching and comparing to the Materials Project database, the reduced bandgap CeNiO3 phase is realized. The CeNiO3 reduced bandgap phase is implemented as the absorber layer in a solar cell and photovoltages up to 550 mV are achieved. The solar cells are also measured by surface photovoltage spectroscopy, which shows that the source of the photovoltaic activity is the reduced bandgap CeNiO3 phase, making it a viable material for solar energy.

  • Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-07
    Viswanath Arutla,Joseph Leal,Xiaowei Liu,Sriram Sokalingam,Michael Raleigh,Adejimi Adaralegbe,Li Liu,Paul R Pentel,Sidney M Hecht,Yung Chang

    Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC50) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and activates B cells.

  • One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-b]-4,7-dihydropyridines.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-11
    H Surya Prakash Rao,Lakshmi Narayana Adigopula,Krishna Ramadas

    We have achieved a facile synthesis of a combinatorial library of densely substituted pyrazolo[3,4-b]-4,7-dihydropyridines- the mimics of antigenital wart drug podophyllotoxin-from 5-aminopyrazoles and 4-(methylthio) 4H-chromenes. The C(4) pyrazolyl 4H-chromenes, which also possess structural features of podophyllotoxin, were isolable intermediates in the two-step, one-pot condensation. The condensation took place in a one-pot, multicomponent manner when 3-oxo-3-phenylpropanenitriles, hydrazine (precursors for 5-aminopyrazoles) and 4-(methylthio)-4H-chromenes were heated in refluxing ethanol. The condensation, however, stops at 4H-chromene stage when methyl hydrazine or phenylhydrazine were employed. Our findings offer an opportunity for synthesis of a combinatorial library of podophyllotoxin mimics, thus paving the way for discovery of lead candidates for cancer treatment.

  • Solid-Phase Synthesis and Antibacterial Activity of Cyclohexapeptide Wollamide B Analogs.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2018-02-13
    Lissa S Tsutsumi,John M Elmore,Uyen T Dang,Miranda J Wallace,Ravikanthreddy Marreddy,Robin B Lee,Ghee T Tan,Julian G Hurdle,Richard E Lee,Dianqing Sun

    Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollamide analogs derived from solid-phase library synthesis. Wollamide B, a cyclic hexapeptide natural product, has been previously found to have activity against Mycobacterium bovis. To further evaluate its antimycobacterial/antibacterial potential, 27 peptides including wollamides A/B, and desotamide B, were synthesized and subsequently tested against a panel of clinically significant bacterial pathogens. Biological evaluation revealed that the cyclic scaffold, amide functionality in position I, tryptophan residue in position V, and the original stereochemistry pattern of the core scaffold were key for antituberculosis and/or antibacterial activity. In addition, against M. tuberculosis and Gram-positive bacteria, residues in position II and/or VI greatly impacted antibacterial activity and selectivity. Wollamides A (3) and B (2) along with their corresponding II (l-Leu) analog 10 retained the most promising antituberculosis activity, with the lowest minimum inhibitory concentration (MIC) against virulent M. tuberculosis H37Rv (MIC = 1.56 μg/mL), as well as desirable selectivity indices (>100). Importantly, the antimicrobial activities of wollamides A and B do not result from disruption of the bacterial membrane, warranting further investigation into their mechanism of action.

  • Modeling and Optimization of NLDH/PVDF Ultrafiltration Nanocomposite Membrane Using Artificial Neural Network-Genetic Algorithm Hybrid.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-06-08
    Samira Arefi-Oskoui,Alireza Khataee,Vahid Vatanpour

    In this research, MgAl-CO32- nanolayered double hydroxide (NLDH) was synthesized through a facile coprecipitation method, followed by a hydrothermal treatment. The prepared NLDHs were used as a hydrophilic nanofiller for improving the performance of the PVDF-based ultrafiltration membranes. The main objective of this research was to obtain the optimized formula of NLDH/PVDF nanocomposite membrane presenting the best performance using computational techniques as a cost-effective method. For this aim, an artificial neural network (ANN) model was developed for modeling and expressing the relationship between the performance of the nanocomposite membrane (pure water flux, protein flux and flux recovery ratio) and the affecting parameters including the NLDH, PVP 29000 and polymer concentrations. The effects of the mentioned parameters and the interaction between the parameters were investigated using the contour plot predicted with the developed model. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle techniques were applied to characterize the nanocomposite membranes and to interpret the predictions of the ANN model. The developed ANN model was introduced to genetic algorithm (GA) as a bioinspired optimizer to determine the optimum values of input parameters leading to high pure water flux, protein flux, and flux recovery ratio. The optimum values for NLDH, PVP 29000 and the PVDF concentration were determined to be 0.54, 1, and 18 wt %, respectively. The performance of the nanocomposite membrane prepared using the optimum values proposed by GA was investigated experimentally, in which the results were in good agreement with the values predicted by ANN model with error lower than 6%. This good agreement confirmed that the nanocomposite membranes prformance could be successfully modeled and optimized by ANN-GA system.

  • "On-Water" Facile Synthesis of Novel Pyrazolo[3,4-b]pyridinones Possessing Anti-influenza Virus Activity.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-06-06
    Li-Yan Zeng,Teng Liu,Jie Yang,Yueli Yang,Chun Cai,Shuwen Liu

    A facile and versatile "on-water" protocol for the synthesis of pyrazolo[3,4-b]pyridinones was developed by the unprecedented construction of two rings and five new bonds in one-pot. It was proved that water was an important promoter of the reaction and PEG2000 was found to improve the reaction in terms of yield. 32 Derivatives were newly synthesized and most of them were prepared in an hour. The scope and limitation indicated that electron withdrawing groups substituted on synthons, substituted benzoyl acetonitriles or aryl aldehydes, were helpful to construct the pyrazolo[3,4-b]pyridinones. The reaction media PEG2000/H2O was successfully recycled and reused at least 5 times without any obvious decrease in yield. The anti-influenza activities of the derivatives were evaluated and the screening results highlighted two derivatives, which exhibited strong inhibitory activity against H5N1 pseudovirus. These positive bioassay results implied that the library of potential anti-influenza virus agent candidates could be rapidly prepared in an eco-friendly manner, and provided a new insight into drug discovery for medicinal chemists.

  • High-Throughput Platform for Synthesis of Melamine-Formaldehyde Microcapsules.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-06-03
    Seda Çakir,Erwin Bauters,Guadalupe Rivero,Tom Parasote,Johan Paul,Filip E Du Prez

    The synthesis of microcapsules via in situ polymerization is a labor-intensive and time-consuming process, where many composition and process factors affect the microcapsule formation and its morphology. Herein, we report a novel combinatorial technique for the preparation of melamine-formaldehyde microcapsules, using a custom-made and automated high-throughput platform (HTP). After performing validation experiments for ensuring the accuracy and reproducibility of the novel platform, a design of experiment study was performed. The influence of different encapsulation parameters was investigated, such as the effect of the surfactant, surfactant type, surfactant concentration and core/shell ratio. As a result, this HTP-platform is suitable to be used for the synthesis of different types of microcapsules in an automated and controlled way, allowing the screening of different reaction parameters in a shorter time compared to the manual synthetic techniques.

  • Interplay Of Stereochemistry, Conformational Rigidity, And Ease Of Synthesis For 13-Membered Cyclic Peptidomimetics Containing APC Residues.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-06-01
    Dongyue Xin,Andrew Jeffries,Kevin Burgess

    As part of a program to design small molecules that bind proteins, we require cyclic peptides (or peptidomimetics) that are severely constrained such that they adopt one predominant conformation in solution. This paper describes syntheses of the 13-membered cyclic tetrapeptides 1 containing aminopyrrolidine carboxyl (APC) residues. A linear precursor was prepared and used to determine optimal conditions for cyclization of that substrate. A special linker was prepared to enable cyclization of similar linear peptidomimetics on a solid phase, and the solution-phase cyclization conditions were shown to be appropriate for this too. Stereochemical variations were then used to determine the ideal APC configuration for cyclization of the linear precursors (on a solid phase, using the conditions identified previously). Consequently, a series of compounds were prepared that are representative of compounds 1. Conformational studies of representative compounds in DMSO solution were performed primarily using (i) NOE studies, (ii) quenched molecular dynamics simulations using no constraints from experiment, and (iii) MacroModel calculations with NMR constraints. All three strategies converged to the same conclusion: the backbone of molecules based on 1 tends to adopt one preferential conformation in solution and that conformation can be predicted from the stereochemistries of the α-amino acids involved.

  • "In Water": Organocatalyzed Diastereoselective Multicomponent Reactions toward 2-Azapyrrolizidine Alkaloid Scaffolds.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-31
    Balakrishnan Rajarathinam,Kandhasamy Kumaravel,Gnanasambandam Vasuki

    Synthesis of the 2-aza analogues of pyrrolizidine and spirooxindole-2-azapyrrolizidine hybrid, a spiro-tetracyclic scaffold possessing multiple contiguous stereocenters, by an exclusive regio-, chemo-, and diastereoselective multicomponent reaction in water is reported. This logical and didactical tactic has integrated the principles of an ideal organic synthesis, privileged substructure-based diversity-oriented synthesis, and biology-oriented synthesis to access hybrid heterocyclic scaffolds.

  • Synthesis and Screening of Phase Change Chalcogenide Thin Film Materials for Data Storage.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-26
    Samuel Guerin,Brian Hayden,Daniel W Hewak,Chris Vian

    A combinatorial synthetic methodology based on evaporation sources under an ultrahigh vacuum has been used to directly synthesize compositional gradient thin film libraries of the amorphous phases of GeSbTe alloys at room temperature over a wide compositional range. An optical screen is described that allows rapid parallel mapping of the amorphous-to-crystalline phase transition temperature and optical contrast associated with the phase change on such libraries. The results are shown to be consistent with the literature for compositions where published data are available along the Sb2Te3-GeTe tie line. The results reveal a minimum in the crystallization temperature along the Sb2Te3-Ge2Te3 tie line, and the method is able to resolve subsequent cubic-to-hexagonal phase transitions in the GST crystalline phase. HT-XRD has been used to map the phases at sequentially higher temperatures, and the results are reconciled with the literature and trends in crystallization temperatures. The results clearly delineate compositions that crystallize to pure GST phases and those that cocrystallize Te. High-throughput measurement of the resistivity of the amorphous and crystalline phases has allowed the compositional and structural correlation of the resistivity contrast associated with the amorphous-to-crystalline transition, which range from 5-to-8 orders of magnitude for the compositions investigated. The results are discussed in terms of the compromises in the selection of these materials for phase change memory applications and the potential for further exploration through more detailed secondary screening of doped GST or similar classes of phase change materials designed for the demands of future memory devices.

  • Development of a High-Throughput Ion-Exchange Resin Characterization Workflow.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-11
    Chun Liu,Daniel Dermody,Keith Harris,Thomas Boomgaard,Jeff Sweeney,Daryl Gisch,Bob Goltz

    A novel high-throughout (HTR) ion-exchange (IEX) resin workflow has been developed for characterizing ion exchange equilibrium of commercial and experimental IEX resins against a range of different applications where water environment differs from site to site. Because of its much higher throughput, design of experiment (DOE) methodology can be easily applied for studying the effects of multiple factors on resin performance. Two case studies will be presented to illustrate the efficacy of the combined HTR workflow and DOE method. In case study one, a series of anion exchange resins have been screened for selective removal of NO3- and NO2- in water environments consisting of multiple other anions, varied pH, and ionic strength. The response surface model (RSM) is developed to statistically correlate the resin performance with the water composition and predict the best resin candidate. In case study two, the same HTR workflow and DOE method have been applied for screening different cation exchange resins in terms of the selective removal of Mg2+, Ca2+, and Ba2+ from high total dissolved salt (TDS) water. A master DOE model including all of the cation exchange resins is created to predict divalent cation removal by different IEX resins under specific conditions, from which the best resin candidates can be identified. The successful adoption of HTR workflow and DOE method for studying the ion exchange of IEX resins can significantly reduce the resources and time to address industry and application needs.

  • Diastereoselective Synthesis of Symmetrical and Unsymmetrical Tetrahydropyridines Catalyzed by Bi(III) Immobilized on Triazine Dendrimer Stabilized Magnetic Nanoparticles.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-10
    Beheshteh Asadi,Amir Landarani-Isfahani,Iraj Mohammadpoor-Baltork,Shahram Tangestaninejad,Majid Moghadam,Valiollah Mirkhani,Hadi Amiri Rudbari

    Unsymmetrical 1,2,5,6-tetrahydropyridine-3-carboxylates were obtained for the first time from a five-component Fe3O4@TDSN-Bi(III)-catalyzed reaction of aryl aldehydes, aryl amines, and ethyl acetoacetate. This magnetically separable catalyst enabled the selective incorporation of two different aryl amines or two different aryl aldehydes into the product, and provided excellent yields, short reaction times, mild reaction conditions, satisfactory catalyst recyclability, and low catalyst loading.

  • High-Throughput Investigation of a Lead-Free AlN-Based Piezoelectric Material, (Mg,Hf)xAl1-xN.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-10
    Hung H Nguyen,Hiroyuki Oguchi,Le Van Minh,Hiroki Kuwano

    We conducted a high-throughput investigation of the fundamental properties of (Mg,Hf)xAl1-xN thin films (0 < x < 0.24) aiming for developing high-performance AlN-based piezoelectric materials. For the high-throughput investigation, we prepared composition-gradient (Mg,Hf)xAl1-xN films grown on a Si(100) substrate at 600 °C by cosputtering AlN and MgHf targets. To measure the properties of the various compositions at different positions within a single sample, we used characterization techniques with spatial resolution. X-ray diffraction (XRD) with a beam spot diameter of 1.0 mm verified that Mg and Hf had substituted into the Al sites and caused an elongation of the c-axis of AlN from 5.00 Å for x = 0 to 5.11 Å for x = 0.24. In addition, the uniaxial crystal orientation and high crystallinity required for piezoelectric materials to be used as application devices were confirmed. The piezoelectric response microscope indicated that this c-axis elongation increased the piezoelectric coefficient almost linearly from 1.48 pm/V for x = 0 to 5.19 pm/V for x = 0.24. The dielectric constants of (Mg,Hf)xAl1-xN were investigated using parallel plate capacitor structures with ∼0.07 mm2 electrodes and showed a slight increase by substitution. These results verified that (Mg,Hf)xAl1-xN is a promising material for piezoelectric-based application devices, especially for vibrational energy harvesters.

  • On-the-Fly Data Assessment for High-Throughput X-ray Diffraction Measurements.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-05-04
    Fang Ren,Ronald Pandolfi,Douglas Van Campen,Alexander Hexemer,Apurva Mehta

    Investment in brighter sources and larger and faster detectors has accelerated the speed of data acquisition at national user facilities. The accelerated data acquisition offers many opportunities for the discovery of new materials, but it also presents a daunting challenge. The rate of data acquisition far exceeds the current speed of data quality assessment, resulting in less than optimal data and data coverage, which in extreme cases forces recollection of data. Herein, we show how this challenge can be addressed through the development of an approach that makes routine data assessment automatic and instantaneous. By extracting and visualizing customized attributes in real time, data quality and coverage, as well as other scientifically relevant information contained in large data sets, is highlighted. Deployment of such an approach not only improves the quality of data but also helps optimize the usage of expensive characterization resources by prioritizing measurements of the highest scientific impact. We anticipate our approach will become a starting point for a sophisticated decision-tree that optimizes data quality and maximizes scientific content in real time through automation. With these efforts to integrate more automation in data collection and analysis, we can truly take advantage of the accelerating speed of data acquisition.

  • Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-27
    Wei-Shun Hsu,Min-Huan Tsai,Indrajeet J Barve,Gorakh S Yellol,Chung-Ming Sun

    A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles under microwave irradiation. Two nonequivalent nucleophilic centers on benzimidazole moiety were manipulated elegantly by different reaction conditions to achieve the skeletal diversity.

  • Assembly of Macrocycle Dye Derivatives into Particles for Fluorescence and Photoacoustic Applications.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-26
    Hoang D Lu,Tristan L Lim,Shoshana Javitt,Andrew Heinmiller,Robert K Prud'homme

    Optical imaging is a rapidly progressing medical technique that can benefit from the development of new and improved optical imaging agents suitable for use in vivo. However, the molecular rules detailing what optical agents can be processed and encapsulated into in vivo presentable forms are not known. We here present the screening of series of highly hydrophobic porphyrin, phthalocyanine, and naphthalocyanine dye macrocycles through a self-assembling Flash NanoPrecipitation process to form a series of water dispersible dye nanoparticles (NPs). Ten out of 19 tested dyes could be formed into poly(ethylene glycol) coated nanoparticles 60-150 nm in size, and these results shed insight on dye structural criteria that are required to permit dye assembly into NPs. Dye NPs display a diverse range of absorbance profiles with absorbance maxima within the NIR region, and have absorbance that can be tuned by varying dye choice or by doping bulking materials in the NP core. Particle properties such as dye core load and the compositions of co-core dopants were varied, and subsequent effects on photoacoustic and fluorescence signal intensities were measured. These results provide guidelines for designing NPs optimized for photoacoustic imaging and NPs optimized for fluorescence imaging. This work provides important details for dye NP engineering, and expands the optical imaging tools available for use.

  • Combinatorial Library Based on Restriction Enzyme-mediated Modular Assembly.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-25
    Cuiping Ma,Chao Liang,Yifan Wang,Mei Pan,Qianqian Jiang,Chao Shi

    Combinatorial approaches in directed evolution were proven to be more efficient for exploring sequence space and innovating function of protein. Here, we presented the modular assembly of secondary structures (MASS) for constructing a combinatorial library. In this approach, secondary structure elements were extracted from natural existing protein. The common linkers were flanking secondary structure elements, and then secondary structure elements were digested by Hinf I restriction endonuclease that was used in the construction of combinatorial library for the first time. The digested DNA fragments were randomly ligated in the sense orientation, then in sequence to be amplified by PCR and transformation. This approach showed that different DNA fragments without homologous sequences could be randomly assembled to create significant sequence space. With the structure analysis of recombinants, it would be beneficial to the rational design, even to the design of protein de novo, and to evolve any genetic part or circuit.

  • Combinatorial Library Screening with Liposomes for Discovery of Membrane Active Peptides.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-06
    Randy P Carney,Yann Thillier,Zsofia Kiss,Amir Sahabi,Jean Carlos Heleno Campos,Alisha Knudson,Ruiwu Liu,David Olivos,Mary Saunders,Lin Tian,Kit S Lam

    Membrane active peptides (MAPs) represent a class of short biomolecules that have shown great promise in facilitating intracellular delivery without disrupting cellular plasma membranes. Yet their clinical application has been stalled by numerous factors: off-target delivery, a requirement for high local concentration near cells of interest, degradation en route to the target site, and in the case of cell-penetrating peptides, eventual entrapment in endolysosomal compartments. The current method of deriving MAPs from naturally occurring proteins has restricted the discovery of new peptides that may overcome these limitations. Here, we describe a new branch of assays featuring high-throughput functional screening capable of discovering new peptides with tailored cell uptake and endosomal escape capabilities. The one-bead-one-compound (OBOC) combinatorial method is used to screen libraries containing millions of potential MAPs for binding to synthetic liposomes, which can be adapted to mimic various aspects of limiting membranes. By incorporating unnatural and d-amino acids in the library, in addition to varying buffer conditions and liposome compositions, we have identified several new highly potent MAPs that improve on current standards and introduce motifs that were previously unknown or considered unsuitable. Since small variations in pH and lipid composition can be controlled during screening, peptides discovered using this methodology could aid researchers building drug delivery platforms with unique requirements, such as targeted intracellular localization.

  • Technical Advances in Medicinal Chemistry.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-05
    M G Finn

  • Combinatorial Synthesis of Acacen-Type Ligands and Their Coordination Compounds.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-04
    Urša Tomažin,Uroš Grošelj,Marta Počkaj,Franc Požgan,Bogdan Štefane,Jurij Svete

    A highly modular synthetic method for the preparation of acacen-type ligands and their coordination compounds was developed. A series of 46 acacen-type ligands were synthesized by a combinatorial acid-catalyzed transamination between six primary diamines and eight enaminones. The bis-enaminone products were used as tetradentate ligands for coordination of copper(II), nickel(II), cobalt(II), and palladium(II). Dependence of the preferred E- or Z-configuration of the enaminone ligand on the α-substituent of the enaminone moiety in solution was determined by NMR and confirmed by X-ray diffraction. The copper(II) complexes were tested for their suitability as catalysts in 3 + 2 cycloaddition of azomethine imine to methyl propiolate.

  • A One-Pot Multicomponent 1,3-Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Dihydrothiophenone-Engrafted Dispiro Hybrid Heterocycles.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-04
    Mani Anusha Rani,Sundaravel Vivek Kumar,Karuppiah Malathi,Muthumani Muthu,Abdulrahman I Almansour,Raju Suresh Kumar,Raju Ranjith Kumar

    The combinatorial syntheses of a library of novel dihydrothiophenone-engrafted dispiro oxindole/indenoquinoxaline-pyrrolidine/pyrrolothiazole/indolizine hybrid heterocycles have been realized through a chemo-, regio-, and stereoselective multicomponent 1,3-dipolar cycloaddition strategy.

  • High-Throughput Synthesis of Support Materials for Olefin Polymerization Catalyst.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-04-04
    Patchanee Chammingkwan,Minoru Terano,Toshiaki Taniike

    Rational catalyst design necessitates fundamental knowledge on the structure-performance relationship, while the synthetic throughput for heterogeneous Ziegler-Natta olefin polymerization catalysts has long prevented the acquisition of a statistical database. In this contribution, an in-house reactor system was developed to realize the parallel synthesis of support materials for Ziegler-Natta catalysts for the first time. The developed system enabled parallel synthesis of 24 magnesium ethoxide samples with excellent reproducibility and morphological control comparable to a conventional experiment. Our demonstration revealed that the generation of diverse particle characteristics could be achieved through the addition of a third component as a structural modulator, in which the in-house parallel reactor system combined with the first principle component analysis enabled fast screening of effective modulators.

  • Titratable Avidity Reduction Enhances Affinity Discrimination in Mammalian Cellular Selections of Yeast-Displayed Ligands.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-23
    Lawrence A Stern,Clifford M Csizmar,Daniel R Woldring,Carston R Wagner,Benjamin J Hackel

    Yeast surface display selections against mammalian cell monolayers have proven effective in isolating proteins with novel binding activity. Recent advances in this technique allow for the recovery of clones with even micromolar binding affinities. However, no efficient method has been shown for affinity-based selection in this context. This study demonstrates the effectiveness of titratable avidity reduction using dithiothreitol to achieve this goal. A series of epidermal growth factor receptor binding fibronectin domains with a range of affinities are used to quantitatively identify the number of ligands per yeast cell that yield the strongest selectivity between strong, moderate, and weak affinities. Notably, reduction of ligand display to 3,000-6,000 ligands per yeast cell of a 2 nM binder yields 16-fold better selectivity than that to a 17 nM binder. These lessons are applied to affinity maturation of an EpCAM-binding fibronectin population, yielding an enriched pool of ligands with significantly stronger affinity than that of an analogous pool sorted by standard cellular selection methods. Collectively, this study offers a facile approach for affinity selection of yeast-displayed ligands against full-length cellular targets and demonstrates the effectiveness of this method by generating EpCAM-binding ligands that are promising for further applications.

  • Diversity-Oriented Synthesis of Libraries Based on Benzofuran and 2,3-Dihydrobenzofuran Scaffolds.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-18
    Liena Qin,Duc-Duy Vo,Azadeh Nakhai,C David Andersson,Mikael Elofsson

    Benzofuran and 2,3-dihydrobenzofuran scaffolds are core components in a large number of biologically active natural and synthetic compounds including approved drugs. Herein, we report efficient synthetic protocols for preparation of libraries based on 3-carboxy 2-aryl benzofuran and 3-carboxy 2-aryl trans-2,3-dihydrobenzofuran scaffolds using commercially available salicylaldehydes, aryl boronic acids or halides and primary or secondary amines. The building blocks were selected to achieve variation in physicochemical properties and statistical molecular design and subsequent synthesis resulted in 54 lead-like compounds with molecular weights of 299-421 and calculated octanol/water partition coefficients of 1.9-4.7.

  • Synthesis of 3,5-Disubstituted Isoxazoles Containing Privileged Substructures with a Diverse Display of Polar Surface Area.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-18
    Mingi Kim,Yoon Soo Hwang,Wansang Cho,Seung Bum Park

    We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.

  • Evaluating the Effect of Peptoid Lipophilicity on Antimicrobial Potency, Cytotoxicity, and Combinatorial Library Design.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-16
    Jeremy A Turkett,Kevin L Bicker

    Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity. The information gleaned from this optimization was then applied using the aforementioned screening method to examine the relative potency of peptoid libraries against Staphylococcus aureus, Acinetobacter baumannii, and Enterococcus faecalis prior to and following functionalization with long alkyl tails. The data indicate that overall peptoid hydrophobicity and not simply alkyl tail length is strongly correlated with mammalian cell toxicity. Furthermore, this work demonstrates the utility of the PLAD assay in rapidly evaluating the effect of molecular property changes in similar libraries.

  • Application of Pictet-Spengler Reaction to Indole-Based Alkaloids Containing Tetrahydro-β-carboline Scaffold in Combinatorial Chemistry.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-10
    R Nishanth Rao,Barnali Maiti,Kaushik Chanda

    Indole-based alkaloids are well-known in the literature for their diverse biological properties. Polysubstituted optically active tetrahydro-β-carboline derivatives functionalized on C-1 position are the common structural motif in most of the indole-based alkaloids, as well as highly marketed drugs. The stereoselective Pictet-Spengler reaction is one of the currently most important synthetic techniques used for the preparation of these privileged tetrahydro-β-carboline scaffolds. To date, there are numerous research reports that have been published on the synthesis of the tetrahydro-β-carboline scaffold both on solid phase, as well as in solution phase. Moreover rapid growth has been observed for the enantioselective synthesis of tetrahydro-β-carboline scaffold using chiral organocatalysts. In this Review, efforts have been taken to shed light on the latest information available on different strategies to synthesize tetrahydro-β-carboline both on solid phase and in solution phase during the last 20 years. Furthermore, we believe that the present synthetic methodologies covered in this Review will help to improve the status of this privileged tetrahydro-β-carboline scaffold in its use for drug discovery.

  • Cellular Uptake Mechanism of Cationic Branched Polypeptides with Poly[l-Lys] Backbone.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-10
    Rita Szabó,Mónika Sebestyén,György Kóczán,Ádám Orosz,Gábor Mező,Ferenc Hudecz

    Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK)). In vitro cytotoxicity and cellular uptake were characterized on HT-29 human colon carcinoma and HepG2 human hepatocarcinoma cell lines. Data indicate that the polycationic polypeptides studied are essentially nontoxic in the concentration range studied, and their uptake is very much dependent on the side chain structure (length, identity of amino acid X, and distance between the terminal positive charges) and also on the cell lines. Our findings in uptake inhibition studies suggest that predominantly macropinocytosis and caveole/lipid raft mediated endocytosis are involved. The efficacy of their internalization is markedly influenced by the hydrophobicity and charge properties of the amino acid X. Interestingly, the uptake properties of the these polypeptides show certain similarities to the entry pathways of several cell penetrating peptides.

  • Efficient Synthesis of Fused Oxazepino-isoquinoline Scaffolds via an Ugi, Followed by an Intramolecular Cyclization.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-09
    Yong Li,Jiang-Ping Meng,Jie Lei,Zhong-Zhu Chen,Dian-Yong Tang,Jin Zhu,Jin Zhang,Zhi-Gang Xu

    A mild and efficient protocol was developed for the synthesis of oxazepino-isoquinolines via a one-pot Ugi four-component reaction, followed by the intramolecular addition of the resulting alcohol to an alkyne moiety under microwave irradiation conditions. Notably, this process only required one purification step, providing facile access to two series of complex and potentially interesting biologically active scaffolds.

  • Encoded Silicon-Chip-Based Platform for Combinatorial Synthesis and Screening.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-03-07
    Julian Vastl,Tina Wang,Thi B Trinh,David A Spiegel

    Solid-supported chemical libraries have proven useful for the rapid and cost-effective discovery of bioactive compounds. However, traditional on-bead screening involves time-intensive chemical characterization of hit compounds and high false positive rates. Herein, we report a new platform for encoded chemical synthesis and solid-supported screening using p-Chips, microsized silicon microtransponders capable of storing and emitting unique numerical identifiers (IDs). By encoding the structures of library members using p-Chip IDs, we can track compound identities throughout both split-and-pool synthesis and protein binding assays without destructive cleavage. Thanks to the numerical IDs, our p-Chip platform can provide binding constants for library members simply by stripping and reprobing with different protein concentrations, unlike traditional on-bead assays. To showcase these features, we synthesized a library of 108 hemagglutinin (HA) peptide variants using split-and-pool approach, and measured EC50s for each variant directly on p-Chips. On-chip EC50s obtained from these studies showed excellent correlation (80%) with those obtained using traditional ELISA methods. Our screen also yielded a false positive rate of 14%, markedly superior to that reported for conventional bead-based binding studies (66-96%).1-9 On the basis of these results, we believe the p-Chip platform has the potential to improve the effectiveness of solid-supported high-throughput screening by a significant margin.

  • Ammonia-Promoted One-Pot Tetrazolopiperidinone Synthesis by Ugi Reaction.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-02-28
    Pravin Patil,Katarzyna Kurpiewska,Justyna Kalinowska-Tłuścik,Alexander Dömling

    Ammonia in the tetrazole Ugi variation together with α-amino acid methyl ester-derived isocyanides provides tetrazolopiperidinones in good to high yields in one pot. The scope and limitations of this reaction were investigated by performing >70 reactions. The scaffold is useful to fill high-throughput screening decks and in structure-based drug design.

  • An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-02-16
    Andrew B MacConnell,Alexander K Price,Brian M Paegel

    DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing.

  • High-Throughput Continuous Hydrothermal Synthesis of Transparent Conducting Aluminum and Gallium Co-doped Zinc Oxides.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2017-02-16
    Dougal P Howard,Peter Marchand,Liam McCafferty,Claire J Carmalt,Ivan P Parkin,Jawwad A Darr

    High-throughput continuous hydrothermal flow synthesis was used to generate a library of aluminum and gallium-codoped zinc oxide nanoparticles of specific atomic ratios. Resistivities of the materials were determined by Hall Effect measurements on heat-treated pressed discs and the results collated into a conductivity-composition map. Optimal resistivities of ∼9 × 10-3 Ω cm were reproducibly achieved for several samples, for example, codoped ZnO with 2 at% Ga and 1 at% Al. The optimum sample on balance of performance and cost was deemed to be ZnO codoped with 3 at% Al and 1 at% Ga.

  • Synthesis and Evaluation of a Library of Trifunctional Scaffold-Derived Compounds as Modulators of the Insulin Receptor.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-12-13
    Benjamin Fabre,Jan Pícha,Václav Vaněk,Irena Selicharová,Martina Chrudinová,Michaela Collinsová,Lenka Žáková,Miloš Buděšínský,Jiří Jiráček

    We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds were proposed to mimic insulin receptor (IR)-binding epitopes in the insulin molecule and bind to and activate this receptor. This work has enabled us to test our synthetic and biological methodology and to prove its robustness and reliability for the solid-phase synthesis and testing of combinatorial libraries of the trifunctional scaffold-derived compounds. Our effort resulted in the discovery of two compounds, which were able to weakly induce the autophosphorylation of IR and weakly bind to this receptor at a 0.1 mM concentration. Despite these modest biological results, which well document the well-known difficulty in modulating protein-protein interactions, this study represents a unique example of targeting the IR with a set of nonpeptide compounds that were specifically designed and synthesized for this purpose. We believe that this work can open new perspectives for the development of next-generation insulin mimetics based on the scaffold structure.

  • Magnetically Retrievable Nanocomposite Based on Thiosemicarbazide-Formaldehyde Resin as a Versatile Nucleophilic Scavenger.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-12-13
    Maomin Zhen,Danfeng Zhang,Zeyu Zhang,Yanqing Peng

    A magnetically retrievable nanocomposite was prepared by in situ polycondensation and entrapment of iron oxide nanoparticles. This material was found to be efficient in trapping excess electrophilic reagents such as carbonyl compounds, acid chlorides and isothiocyanates. Advantages of the new scavenger include facile preparation, high loading capacity, low cost, satisfactory swelling properties in polar solvents, and convenient magnetic recovery.

  • Screening Libraries of Semifluorinated Arylene Bisimides to Discover and Predict Thermodynamically Controlled Helical Crystallization.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-11-01
    Ming-Shou Ho,Benjamin E Partridge,Hao-Jan Sun,Dipankar Sahoo,Pawaret Leowanawat,Mihai Peterca,Robert Graf,Hans W Spiess,Xiangbing Zeng,Goran Ungar,Paul A Heiney,Chain-Shu Hsu,Virgil Percec

    Synthesis, structural, and retrostructural analysis of a library containing 16 self-assembling perylene (PBI), 1,6,7,12-tetrachloroperylene (Cl4PBI), naphthalene (NBI), and pyromellitic (PMBI) bisimides functionalized with environmentally friendly AB3 chiral racemic semifluorinated minidendrons at their imide groups via m = 0, 1, 2, and 3 methylene units is reported. These semifluorinated compounds melt at lower temperatures than homologous hydrogenated compounds, permitting screening of all their thermotropic phases via structural analysis to discover thermodynamically controlled helical crystallization from propeller-like, cogwheel, and tilted molecules as well as lamellar-like structures. Thermodynamically controlled helical crystallization was discovered for propeller-like PBI, Cl4PBI and NBI with m = 0. Unexpectedly, assemblies of twisted Cl4PBIs exhibit higher order than those of planar PBIs. PBI with m = 1, 2, and 3 form a thermodynamically controlled columnar hexagonal 2D lattice of tilted helical columns with intracolumnar order. PBI and Cl4PBI with m = 1 crystallize via a recently discovered helical cogwheel mechanism, while NBI and PMBI with m = 1 form tilted helical columns. PBI, NBI and PMBI with m = 2 generate lamellar-like structures. 3D and 2D assemblies of PBI with m = 1, 2, and 3, NBI with m = 1 and PMBI with m = 2 exhibit 3.4 Å π-π stacking. The library approach applied here and in previous work enabled the discovery of six assemblies which self-organize via thermodynamic control into 3D and 2D periodic arrays, and provides molecular principles to predict the supramolecular structure of electronically active components.

  • Solid-Phase Parallel Synthesis of N-Substituted-2-aminothiazolo[4,5-b]pyrazine Derivatives via Tandem Reaction of Isothiocyanate Terminated Resin with o-Bromo-2-Aminopyrazines.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-10-27
    Aizhan Abdildinova,Seung-Ju Yang,Young-Dae Gong

    A novel solid-phase synthesis methodology of N-substituted-2-aminothiazolo[4,5-b]pyrazine derivatives was developed. The key step in this synthesis strategy is the tandem reaction of isothiocyanate terminated resin 2 with o-bromo-2-aminopyrazine, affording cyclized 2-aminothiazolo[4,5-b]pyrazine resin 4. To increase the diversity of our library, Suzuki coupling reaction was performed at the position C6. Further functionalization of 2-aminothiazolo[4,5-b]pyrazine core skeleton with various electrophiles such as alkyl halides, acyl chlorides, and sulfonyl chlorides and cleavage from the resin with TFA in DCM generated N-alkyl-, N-acyl-, and N-sulfonyl-2-aminothiazolo[4,5-b]pyrazine derivatives. The physicochemical properties and the polar surface areas of synthesized compounds were evaluated.

  • Facile Synthesis of Azaarene-Substituted Hydroxycoumarins Possessing High Biological Activities via Three-Component C(sp(3))-H Functionalization.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-08-16
    Haoxun Dong,Lubin Xu,Shuai-Shuai Li,Liang Wang,Chang-Lun Shao,Jian Xiao

    An unprecedented three-component C(sp(3))-H functionalization of 2-alkylazaarenes with aryl aldehydes and 4-hydroxycoumarins was realized, providing azaarene-substituted 3-benzyl-4-hydroxycoumarins in good to excellent yields. These new target compounds displayed broad-spectrum antibacterial activities, providing a new type of antibacterial skeleton.

  • Efficient Routes to a Diverse Array of Amino Alcohol-Derived Chiral Fragments.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-08-16
    Sina Haftchenary,Shawn D Nelson,Laura Furst,Sivaraman Dandapani,Steven J Ferrara,Žarko V Bošković,Samuel Figueroa Lazú,Adrian M Guerrero,Juan C Serrano,DeMarcus K Crews,Cristina Brackeen,Jeffrey Mowat,Thomas Brumby,Marcus Bauser,Stuart L Schreiber,Andrew J Phillips

    Efficient syntheses of chiral fragments derived from chiral amino alcohols are described. Several unique scaffolds were readily accessed in 1-5 synthetic steps leading to 45 chiral fragments, including oxazolidinones, morpholinones, lactams, and sultams. These fragments have molecular weights ranging from 100 to 255 Da and are soluble in water (0.085 to >15 mM).

  • Three-Component, Diastereoselective Prins-Ritter Reaction for cis-Fused 4-Amidotetrahydropyrans toward a Precursor for Possible Neuronal Receptor Ligands.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2016-05-11
    Manami Chiba,Yuichi Ishikawa,Ryuichi Sakai,Masato Oikawa

    Here, we report an unprecedented, highly diastereoselective Prins-Ritter reaction of aldehydes, homoallylic alcohols, and nitriles in a three-component coupling reaction for the synthesis of tetra-cis-substituted 4-amidotetrahydropyrans. In this study, the reaction was not only applied for carbohydrate-based heterobicycles but also for more complex heterotricycles, showing acceptable levels of conversion yield (42-97% BRSM) and exclusive diastereoselectivity. Furthermore, the latter heterotricycles were converted to nine analogues of our neuronal receptor ligands IKM-159 and MC-27. An in vivo assay by intracerebroventricular injection in mice suggested that the substituent at C9 of the novel analogues interferes with the molecular interactions with the AMPA receptor, which was originally observed in the complex of IKM-159 and the GluA2 ligand binding domain. Our research has thus shown the power of a multicomponent coupling reaction for the preparation of a structurally diverse compound collection to study structure-activity relationships of biologically active small molecules.

  • Virtual Issue on Materials Genomics.
    ACS Comb. Sci. (IF 3.200) Pub Date : 2015-12-15
    M G Finn,Jillian M Buriak

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