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    632 results match your criteria ACS Combinatorial Science [Journal]

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    Process-Function Data Mining for the Discovery of Solid-State Iron-Oxide PV.
    ACS Comb Sci 2017 Nov 9. Epub 2017 Nov 9.
    Department of Chemistry, Institute for Nanotechnology & Advanced Materials, Bar Ilan University , Ramat-Gan 52900, Israel.
    Data mining tools have been known to be useful for analyzing large material data sets generated by high-throughput methods. Typically, the descriptors used for the analysis are structural descriptors, which can be difficult to obtain and to tune according to the results of the analysis. In this Research Article, we show the use of deposition process parameters as descriptors for analysis of a photovoltaics data set. Read More

    High-Throughput Chemical Probing of Full-Length Protein-Protein Interactions.
    ACS Comb Sci 2017 Nov 14. Epub 2017 Nov 14.
    Program in Chemical Biology and ‡Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
    Human biology is regulated by a complex network of protein-protein interactions (PPIs), and disruption of this network has been implicated in many diseases. However, the targeting of PPIs remains a challenging area for chemical probe and drug discovery. Although many methodologies have been put forth to facilitate these efforts, new technologies are still needed. Read More

    Synthesis of 2-Alkoxy/thioalkoxy Benzo[d]imidazoles and 2-Thione Benzo[d]imidazoles via phase-based Chemo-Selective reaction.
    ACS Comb Sci 2017 Nov 2. Epub 2017 Nov 2.
    2-Alkoxy/thioalkoxy benzo[d]imidazole and 2-thione benzo[d]imidazole library were constructed in solution-phase and on solid-phase, respectively. The key step in this work is reaction phase-based chemo-selective reaction of 2-mercapto benzo[d]imidazole intermediate with benzyl chloride (solution-phase) and Merrifield resin (solid-phase). In the case of solution-phase, benzyl chloride reacted with thiol group of 2-mercapto benzo[d]imidazole whereas, in the case of solid-phase, Merrifield resin was introduced at internal amine group of benzo[d]imidazole. Read More

    Stereoselective Synthesis of Benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12-diones with Two Diversity Positions.
    ACS Comb Sci 2017 Nov 2. Epub 2017 Nov 2.
    Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University , Hněvotínská 5, 779 00, Olomouc, Czech Republic.
    Herein, we report a stereoselective formation of tetrahydro-6H-benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12(11H)-diones. Their preparation consisted in solid-phase synthesis of linear intermediates starting from polymer-supported Ser(tBu)-OH. Using various 2-nitrobenzoic acids and bromoketones, the key intermediates were obtained in five steps and subjected to trifluoroacetic acid-mediated cleavage from the resin, followed by stereoselective reduction with triethylsilane. Read More

    Microwave-Facilitated SPOT-Synthesis of Antibacterial Dipeptoids.
    ACS Comb Sci 2017 Nov 7. Epub 2017 Nov 7.
    Institute of Organic Chemistry, Karlsruhe Institute of Technology , Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
    With microwave irradiation, the submonomer synthesis of dipeptoids on functionalized cellulose can be accelerated with good yields and purity. Optimization provided a library of 96 dipeptoids. From these, 29 compounds were found with an antibacterial activity against MRSA at a concentration of 25 μM. Read More

    Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and Evaluation of their Plasmodium falciparum Gametocytocidal Activities.
    ACS Comb Sci 2017 Oct 27. Epub 2017 Oct 27.
    National Center for Advancing Translational Sciences, National Institutes of Health , Bethesda, Maryland 20892, United States.
    A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual parasites using a growth inhibition assay and gametocytes using a viability assay. Read More

    Skeletal Diversity in Combinatorial Fashion: A New Format for the Castagnoli-Cushman Reaction.
    ACS Comb Sci 2017 Nov 26;19(11):702-707. Epub 2017 Oct 26.
    Saint Petersburg State University , Saint Petersburg, 199034 Russian Federation.
    A new format for the Castagnoli-Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity). The new method offers a convenient preparation of the skeletally and peripherally diverse, lead- and druglike γ- and δ-lactam carboxylic acids with high diastereoselectivity in combinatorial fashion. Read More

    Parallel Synthesis of 1H-Pyrazolo[3,4-d]pyrimidines via Condensation of N-Pyrazolylamides and Nitriles.
    ACS Comb Sci 2017 Nov 20;19(11):675-680. Epub 2017 Oct 20.
    Pfizer Worldwide Research and Development , Eastern Point Road, Groton, Connecticut 06340, United States.
    A novel parallel medicinal chemistry (PMC)-enabled synthesis of 1H-pyrazolo[3,4-d]pyrimidines employing condensation of easily accessible N-pyrazolylamides and nitriles has been developed. The presented studies describe singleton and library enablements that allowed rapid generation of molecular diversity to examine C4 and C6 vectors. This chemistry enabled access to challenging alkyl substituents, expanding the overall chemical space beyond that available via typical C(sp(2))-C(sp(2)) coupling and SNAr transformations. Read More

    Microwave-Assisted Regioselective Synthesis of 3-Functionalized Indole Derivatives via Three-Component Domino Reaction.
    ACS Comb Sci 2017 Nov 18;19(11):708-713. Epub 2017 Oct 18.
    College of Chemistry, Chemical Engineering and Materials Science, Soochow University , Suzhou 215123, P. R. China.
    A microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via a three-component domino reaction of anilines, arylglyoxal monohydrates, and cyclic 1,3-dicarbonyl compounds is described. The main advantages of this protocol are short reaction times, practical simplicity, its metal-free nature, the availability of starting materials, green solvents, and high regioselectivity. Read More

    How Many Bulk Metallic Glasses Are There?
    ACS Comb Sci 2017 Nov 27;19(11):687-693. Epub 2017 Sep 27.
    Department of Mechanical Engineering and Material Science, Yale University New Haven, Connecticut 06511, United States.
    Quantitative prediction of glass forming ability using a priori known parameters is highly desired in metallic glass development; however proven to be challenging because of the complexity of glass formation. Here, we estimate the number of potential metallic glasses (MGs) and bulk metallic glasses (BMGs) forming systems and alloys, from empirically determined alloy design rules based on a priori known parameters. Specifically, we take into account atomic size ratio, heat of mixing, and liquidus temperature, which we quantify on binary glasses and centimeter-sized BMGs. Read More

    Library Design-Facilitated High-Throughput Sequencing of Synthetic Peptide Libraries.
    ACS Comb Sci 2017 Nov 29;19(11):694-701. Epub 2017 Sep 29.
    Department of Chemistry, Massachusetts Institute of Technology , 18-563, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
    A methodology to achieve high-throughput de novo sequencing of synthetic peptide mixtures is reported. The approach leverages shotgun nanoliquid chromatography coupled with tandem mass spectrometry-based de novo sequencing of library mixtures (up to 2000 peptides) as well as automated data analysis protocols to filter away incorrect assignments, noise, and synthetic side-products. For increasing the confidence in the sequencing results, mass spectrometry-friendly library designs were developed that enabled unambiguous decoding of up to 600 peptide sequences per hour while maintaining greater than 85% sequence identification rates in most cases. Read More

    Gold-Catalyzed Solid-Phase Synthesis of 3,4-Dihydropyrazin-2(1H)-ones: Relevant Pharmacophores and Peptide Backbone Constraints.
    ACS Comb Sci 2017 Nov 12;19(11):681-686. Epub 2017 Sep 12.
    Department of Organic Chemistry, Faculty of Science, Palacký University , 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
    Here, we report the efficient solid-phase synthesis of N-propargyl peptides using Fmoc-amino acids and propargyl alcohol as key building blocks. Gold-catalyzed nucleophilic addition to the triple bond induced C-N bond formation, which triggered intramolecular cyclization, yielding 1,3,4-trisubstituted-5-methyl-3,4-dihydropyrazin-2(1H)-ones. Conformations of acyclic and constrained peptides were compared using a two-step conformer distribution analysis at the molecular mechanics level and density functional theory. Read More

    Array-Based Rational Design of Short Peptide Probe-Derived from an Anti-TNT Monoclonal Antibody.
    ACS Comb Sci 2017 Oct 8;19(10):625-632. Epub 2017 Sep 8.
    JST, ImPACT, Sanban-cho 5, Chiyoda-ku, Tokyo 102-0075, Japan.
    Complementarity-determining regions (CDRs) are sites on the variable chains of antibodies responsible for binding to specific antigens. In this study, a short peptide probe for recognition of 2,4,6-trinitrotoluene (TNT), was identified by testing sequences derived from the CDRs of an anti-TNT monoclonal antibody. The major TNT-binding site in this antibody was identified in the heavy chain CDR3 by antigen docking simulation and confirmed by an immunoassay using a spot-synthesis based peptide array comprising amino acid sequences of six CDRs in the variable region. Read More

    Polymer-Supported Stereoselective Synthesis of Benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides.
    ACS Comb Sci 2017 Oct 31;19(10):670-674. Epub 2017 Aug 31.
    Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University , Hněvotínská 5, 779 00 Olomouc, Czech Republic.
    Herein, we report the stereoselective synthesis of trisubstituted benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides from polymer-supported Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH. After the solid-phase synthesis of N-alkylated-N-sulfonylated intermediates using various 2-nitrobenzenesulfonyl chlorides and bromoketones, the target compounds were obtained via trifluoroacetic acid (TFA)-mediated cleavage from the resin, followed by cyclization of the diazepinone scaffold. Except for the threonine-based intermediates, the inclusion of triethylsilane (TES) in the cleavage cocktail yielded a specific configuration of the newly formed C(3) chiral center. Read More

    Oligonucleotide Hybridization Combined with Competitive Antibody Binding for the Truncation of a High-Affinity Aptamer.
    ACS Comb Sci 2017 Oct 5;19(10):609-617. Epub 2017 Sep 5.
    Division of Chemistry, Faculty of Science and Technology, Thammasat University , Pathumthani 12120, Thailand.
    Truncation can enhance the affinity of aptamers for their targets by limiting nonessential segments and therefore limiting the molecular degrees of freedom that must be overcome in the binding process. This study demonstrated a truncation protocol relying on competitive antibody binding and the hybridization of complementary oligonucleotides, using platelet derived growth factor BB (PDGF-BB) as the model target. On the basis of the immunoassay results, an initial long aptamer was truncated to a number of sequences with lengths of 36-40 nucleotides (nt). Read More

    Parallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold.
    ACS Comb Sci 2017 Oct 5;19(10):646-656. Epub 2017 Sep 5.
    Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin , Milwaukee, Wisconsin 53211, United States.
    We describe the parallel synthesis of novel analogs of GW0742, a peroxisome proliferator-activated receptor δ (PPARδ) agonist. For that purpose, modified reaction conditions were applied, such as a solid-phase palladium-catalyzed Suzuki coupling. In addition, tetrazole-based compounds were generated as a bioisostere for carboxylic acid-containing ligand GW0742. Read More

    1,3-Dipolar Cycloaddition Reactions for the Synthesis of Novel Oxindole Derivatives and Their Cytotoxic Properties.
    ACS Comb Sci 2017 Oct 7;19(10):633-639. Epub 2017 Sep 7.
    Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology Hyderabad 500 007, India.
    The multicomponent reaction between isatin, amino acid, but-2-ynedioates, and phenacyl bromide has been developed using microwave irradiation under catalyst and base-free conditions in aqueous medium. This synthetic protocol is useful for the synthesis of various functionalized spirooxindole derivatives. This MCR exhibits a broad substrate scope with excellent yields and shorter reaction time. Read More

    Machine Learning Using Combined Structural and Chemical Descriptors for Prediction of Methane Adsorption Performance of Metal Organic Frameworks (MOFs).
    ACS Comb Sci 2017 Oct 5;19(10):640-645. Epub 2017 Sep 5.
    Department of Chemical and Biomolecular Engineering, University of Connecticut , Storrs, Connecticut 06269, United States.
    Using molecular simulation for adsorbent screening is computationally expensive and thus prohibitive to materials discovery. Machine learning (ML) algorithms trained on fundamental material properties can potentially provide quick and accurate methods for screening purposes. Prior efforts have focused on structural descriptors for use with ML. Read More

    Shape Memory Micro- and Nanowire Libraries for the High-Throughput Investigation of Scaling Effects.
    ACS Comb Sci 2017 Sep 14;19(9):574-584. Epub 2017 Aug 14.
    Institute for Materials, Faculty of Mechanical Engineering, Ruhr-Universität Bochum , 44801 Bochum, Germany.
    The scaling behavior of Ti-Ni-Cu shape memory thin-film micro- and nanowires of different geometry is investigated with respect to its influence on the martensitic transformation properties. Two processes for the high-throughput fabrication of Ti-Ni-Cu micro- to nanoscale thin film wire libraries and the subsequent investigation of the transformation properties are reported. The libraries are fabricated with compositional and geometrical (wire width) variations to investigate the influence of these parameters on the transformation properties. Read More

    A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors.
    ACS Comb Sci 2017 Oct 6;19(10):657-669. Epub 2017 Sep 6.
    Department of Chemistry, Technical University of Denmark , DK-2800 Kongens Lyngby, Denmark.
    We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. Read More

    Fabrication of TiO2-Reduced Graphene Oxide Nanorod Composition Spreads Using Combinatorial Hydrothermal Synthesis and Their Photocatalytic and Photoelectrochemical Applications.
    ACS Comb Sci 2017 Sep 8;19(9):585-593. Epub 2017 Aug 8.
    Institute of Nanotechnology and Microsystems Engineering, National Cheng Kung University , No.1, University Road, Tainan City 70101, Taiwan.
    This study is the first to employ combinatorial hydrothermal synthesis and facile spin-coating technology to fabricate TiO2-reduced graphene oxide (rGO) nanorod composition spreads. The features of this study are (1) the development of a self-designed spin-coating wedge, (2) the systemic investigation of the structure-property relationship of the system, (3) the high-throughput screening of the optimal ratio from a wide range of compositions for photocatalytic and photoelectrochemical (PEC) applications, and (4) the effective coupling between the density gradient TiO2 nanorod array and the thickness gradient rGO. The formation of rGO in the fabricated TiO2-rGO sample was monitored through Fourier transform infrared spectrometry. Read More

    Fabrication of a New Lineage of Artificial Luciferases from Natural Luciferase Pools.
    ACS Comb Sci 2017 Sep 9;19(9):594-599. Epub 2017 Aug 9.
    Department of Applied Chemistry, Faculty of Science and Technology, Keio University , 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
    The fabrication of artificial luciferases (ALucs) with unique optical properties has a fundamental impact on bioassays and molecular imaging. In this study, we developed a new lineage of ALucs with unique substrate preferences by extracting consensus amino acids from the alignment of 25 copepod luciferase sequences available in natural luciferase pools. The primary sequence was first created with a sequence logo generator resulting in a total of 11 sibling sequences. Read More

    Selection of Effective HTRA3 Activators Using Combinatorial Chemistry.
    ACS Comb Sci 2017 Sep 24;19(9):565-573. Epub 2017 Aug 24.
    Faculty of Chemistry, University of Gdansk , PL80952 Gdansk, Poland.
    Herein, we report selection, synthesis, and enzymatic evaluation of a peptidomimetic library able to increase proteolytic activity of HtrA3 (high temperature requirement A) protease. Iterative deconvolution in solution of synthesized modified pentapeptides yielded two potent HtrA3 activators acting in the micromolar range (HCOO-CH2O-C6H4-OCH2-CO-Tyr-Asn-Phe-His-Asn-OH and HCOO-CH2O-C6H4-OCH2-CO-Tyr-Asn-Phe-His-Glu-OH). Both compounds increased proteolysis of an artificial HtrA3 substrate over 40-fold in a selective manner. Read More

    An Efficient One-Pot Synthesis of Densely Functionalized Fused-Quinolines via Sequential Ugi4CC and Acid-Mediated Povarov-Type Reaction.
    ACS Comb Sci 2017 Sep 8;19(9):600-608. Epub 2017 Aug 8.
    Medicinal Chemistry & Biotechnology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad-500 007, India.
    A divergent synthesis of fused-quinolines has been explored by performing Ugi four-component condensation and sulfuric acid promoted deprotection/Povarov-type reaction in one-pot. The process involves Ugi condensation of propiolic acids, aldehydes/ketones, aminoaldehyde acetals and isocyanides followed by sulfuric acid promoted deprotection and Povarov-type reaction with anilines in ethanol. This method enables straightforward access to the structurally diverse 2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones (DHPQ), 3,4-dihydrobenzo[b][1,6]naphthyridin-1(2H)-ones (DHBN), and 2,3,4,5-tetrahydro-1H-azepino[4,3-b]quinolin-1-ones (THAQ), starting from readily available starting materials. Read More

    High-Throughput Structural and Functional Characterization of the Thin Film Materials System Ni-Co-Al.
    ACS Comb Sci 2017 Oct 11;19(10):618-624. Epub 2017 Aug 11.
    Institute for Materials, Ruhr-Universität Bochum , 44780 Bochum, Germany.
    High-throughput methods were used to investigate a Ni-Co-Al thin film materials library, which is of interest for structural and functional applications (superalloys, shape memory alloys). X-ray diffraction (XRD) measurements were performed to identify the phase regions of the Ni-Co-Al system in its state after annealing at 600 °C. Optical, electrical, and magneto-optical measurements were performed to map functional properties and confirm XRD results. Read More

    Microwave-Assisted Synthesis of Diversely Substituted Quinoline-Based Dihydropyridopyrimidine and Dihydropyrazolopyridine Hybrids.
    ACS Comb Sci 2017 Aug 26;19(8):555-563. Epub 2017 Jul 26.
    Department of Inorganic and Organic Chemistry, Universidad de Jaén , 23071 Jaén, Spain.
    An efficient, catalyst-free, and one-pot three-component procedure for the synthesis of novel and nitrogen rich dihydropyrido[2,3-d]pyrimidines and dihydro-1H-pyrazolo[3,4-b]pyridines bearing a quinoline pharmacophore fragment is provided. Reactions proceeded in DMF under microwave irradiation of three-component mixtures of formyl-quinoline derivatives, primary heterocyclic amines and cyclic 1,3-diketones. Interestingly, when conventional heating at reflux was used for the starting 5-amino-1-phenylpyrazole, the corresponding aromatized pyrazolopyridines were obtained as the main products. Read More

    Bias-Free Chemically Diverse Test Sets from Machine Learning.
    ACS Comb Sci 2017 Aug 27;19(8):544-554. Epub 2017 Jul 27.
    Data61 CSIRO , Molecular & Materials Modelling, Door 34, Goods Shed, Village Street, Docklands, Victoria 3008, Australia.
    Current benchmarking methods in quantum chemistry rely on databases that are built using a chemist's intuition. It is not fully understood how diverse or representative these databases truly are. Multivariate statistical techniques like archetypal analysis and K-means clustering have previously been used to summarize large sets of nanoparticles however molecules are more diverse and not as easily characterized by descriptors. Read More

    Systematic First-Principles Study of Binary Metal Hydrides.
    ACS Comb Sci 2017 Aug 25;19(8):513-523. Epub 2017 Jul 25.
    Université Paris Est , ICMPE (UMR 7182), CNRS, UPEC, F-94320 Thiais, France.
    First-principles calculations were systematically performed for 31 binary metal-hydrogen (M-H) systems on a set of 30 potential crystal structures selected on the basis of experimental data and possible interstitial sites. For each M-H system, the calculated enthalpies of formation were represented as functions of H composition. The zero-point energy correction was considered for the most stable hydrides via additional harmonic phonon calculations. Read More

    Poisson Statistics of Combinatorial Library Sampling Predict False Discovery Rates of Screening.
    ACS Comb Sci 2017 Aug 26;19(8):524-532. Epub 2017 Jul 26.
    Department of Chemistry and †Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
    Microfluidic droplet-based screening of DNA-encoded one-bead-one-compound combinatorial libraries is a miniaturized, potentially widely distributable approach to small molecule discovery. In these screens, a microfluidic circuit distributes library beads into droplets of activity assay reagent, photochemically cleaves the compound from the bead, then incubates and sorts the droplets based on assay result for subsequent DNA sequencing-based hit compound structure elucidation. Pilot experimental studies revealed that Poisson statistics describe nearly all aspects of such screens, prompting the development of simulations to understand system behavior. Read More

    Identification of Biologically Active Pyrimido[5,4-b]indoles That Prolong NF-κB Activation without Intrinsic Activity.
    ACS Comb Sci 2017 Aug 13;19(8):533-543. Epub 2017 Jul 13.
    Moores UCSD Cancer Center, University of California San Diego , La Jolla, California 92093, United States.
    Most vaccine adjuvants directly stimulate and activate antigen presenting cells but do not sustain immunostimulation of these cells. A high throughput screening (HTS) strategy was designed to identify compounds that would sustain NF-κB activation by a stimulus from the Toll-like receptor (TLR)4 ligand, lipopolysaccharide (LPS). Several pilot studies optimized the parameters and conditions for a cell based NF-κB reporter assay in human monocytic THP-1 cells. Read More

    Modeling and Optimization of NLDH/PVDF Ultrafiltration Nanocomposite Membrane Using Artificial Neural Network-Genetic Algorithm Hybrid.
    ACS Comb Sci 2017 Jul 23;19(7):464-477. Epub 2017 Jun 23.
    Faculty of Chemistry, Kharazmi University , 15719-14911 Tehran, Iran.
    In this research, MgAl-CO3(2-) 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. Read More

    "On-Water" Facile Synthesis of Novel Pyrazolo[3,4-b]pyridinones Possessing Anti-influenza Virus Activity.
    ACS Comb Sci 2017 Jul 23;19(7):437-446. Epub 2017 Jun 23.
    Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University , Guangzhou 510515, China.
    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. Read More

    High-Throughput Platform for Synthesis of Melamine-Formaldehyde Microcapsules.
    ACS Comb Sci 2017 Jul 15;19(7):447-454. Epub 2017 Jun 15.
    Polymer Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281 S4-bis, 9000 Ghent, Belgium.
    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. Read More

    Interplay Of Stereochemistry, Conformational Rigidity, And Ease Of Synthesis For 13-Membered Cyclic Peptidomimetics Containing APC Residues.
    ACS Comb Sci 2017 Jun 31;19(6):414-421. Epub 2017 May 31.
    Department of Chemistry, Texas A & M University , Box 30012, College Station, Texas 77842, United States.
    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. Read More

    "In Water": Organocatalyzed Diastereoselective Multicomponent Reactions toward 2-Azapyrrolizidine Alkaloid Scaffolds.
    ACS Comb Sci 2017 Jul 20;19(7):455-463. Epub 2017 Jun 20.
    Department of Chemistry, Pondicherry University , Puducherry 605 014, India.
    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. Read More

    Synthesis and Screening of Phase Change Chalcogenide Thin Film Materials for Data Storage.
    ACS Comb Sci 2017 Jul 12;19(7):478-491. Epub 2017 Jun 12.
    Ilika Technologies, Kenneth Dibben House, University of Southampton Science Park , Chilworth, Southampton, SO16 7NS, United Kingdom.
    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. Read More

    Development of a High-Throughput Ion-Exchange Resin Characterization Workflow.
    ACS Comb Sci 2017 Jun 18;19(6):422-436. Epub 2017 May 18.
    Dow Water & Process Solutions , 1801 Larkin Center Drive, Midland, Michigan 48674, United States.
    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. Read More

    Diastereoselective Synthesis of Symmetrical and Unsymmetrical Tetrahydropyridines Catalyzed by Bi(III) Immobilized on Triazine Dendrimer Stabilized Magnetic Nanoparticles.
    ACS Comb Sci 2017 Jun 22;19(6):356-364. Epub 2017 May 22.
    Catalysis Division, Department of Chemistry, University of Isfahan , Isfahan 81746-73441, Iran.
    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. Read More

    High-Throughput Investigation of a Lead-Free AlN-Based Piezoelectric Material, (Mg,Hf)xAl1-xN.
    ACS Comb Sci 2017 Jun 16;19(6):365-369. Epub 2017 May 16.
    Department of Robotics, Tohoku University , 980-8577 Sendai, Japan.
    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. Read More

    On-the-Fly Data Assessment for High-Throughput X-ray Diffraction Measurements.
    ACS Comb Sci 2017 Jun 24;19(6):377-385. Epub 2017 May 24.
    Stanford Synchrotron Radiation Lightsource , SLAC National Accelerator Laboratory, Menlo Park, California 94025, United States.
    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. Read More

    Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence.
    ACS Comb Sci 2017 Jul 3;19(7):492-499. Epub 2017 May 3.
    Department of Applied Chemistry, 1001 Ta-Hseuh Road, National Chiao-Tung University , Hsinchu 300-10, Taiwan.
    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. Read More

    Assembly of Macrocycle Dye Derivatives into Particles for Fluorescence and Photoacoustic Applications.
    ACS Comb Sci 2017 Jun 15;19(6):397-406. Epub 2017 May 15.
    Department of Chemical and Biological Engineering, Princeton University , Princeton, New Jersey 08544, United States.
    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). Read More

    Combinatorial Library Based on Restriction Enzyme-mediated Modular Assembly.
    ACS Comb Sci 2017 Jun 28;19(6):351-355. Epub 2017 Apr 28.
    College of Life Sciences, Qingdao University , Qingdao, 266071, P.R. China.
    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. Read More

    Speeding up Early Drug Discovery in Antiviral Research: A Fragment-Based in Silico Approach for the Design of Virtual Anti-Hepatitis C Leads.
    ACS Comb Sci 2017 Aug 1;19(8):501-512. Epub 2017 May 1.
    LAQV@REQUIMTE/Department of Chemistry and Biochemistry, University of Porto , 4169-007 Porto, Portugal.
    Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions, such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen because of the appearance of multidrug resistance (MDR) and the side effects especially associated with long-term treatments. Read More

    One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-b]-4,7-dihydropyridines.
    ACS Comb Sci 2017 May 18;19(5):279-285. Epub 2017 Apr 18.
    Center for Bioinformatics, Pondicherry University , Puducherry-605 014, India.
    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. Read More

    Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.
    ACS Comb Sci 2017 May 17;19(5):286-298. Epub 2017 Apr 17.
    Minneapolis Medical Research Foundation , Minneapolis, Minnesota 55404, United States.
    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. Read More

    Combinatorial Library Screening with Liposomes for Discovery of Membrane Active Peptides.
    ACS Comb Sci 2017 May 13;19(5):299-307. Epub 2017 Apr 13.
    Department of Biochemistry and Molecular Medicine, University of California Davis , 2700 Stockton Boulevard, Sacramento, California 95817, United States.
    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. Read More

    Combinatorial Synthesis of Acacen-Type Ligands and Their Coordination Compounds.
    ACS Comb Sci 2017 Jun 13;19(6):386-396. Epub 2017 Apr 13.
    Faculty of Chemistry and Chemical Technology, University of Ljubljana , Večna pot 113, SI-1000 Ljubljana, Slovenia.
    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). Read More

    A One-Pot Multicomponent 1,3-Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Dihydrothiophenone-Engrafted Dispiro Hybrid Heterocycles.
    ACS Comb Sci 2017 May 11;19(5):308-314. Epub 2017 Apr 11.
    Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University , Madurai-625021, Tamil Nadu, India.
    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. Read More

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