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    655 results match your criteria ACS Combinatorial Science [Journal]

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    Synthesis of highly substituted imidazole Uracil containing molecules via Ugi-4CR and Passerini-3CR.
    ACS Comb Sci 2018 Feb 19. Epub 2018 Feb 19.
    The synthesis of uracil/thymine containing tetra/tri-substituted imidazoles were demonstrated using Ugi/Passerini-reaction fol-lowed by a post-cyclization reaction sequence. The approach enables the one-pot facile construction of diverse compounds in moderate to excellent yields (47-82%). The 5-fluorouracil and 5-methyluracil moieties afford potentially bioactive molecules with drug-like properties. Read More

    Synthesis of Cyclic Peptides as Potential Anti-Malarials.
    ACS Comb Sci 2018 Feb 15. Epub 2018 Feb 15.
    The results from the synthesis of peptides by Fmoc/SPPS on a 2-CTC resin and then lactamization in solution or solid phase for the preparation of cyclopeptides are presented. Both procedures allow the synthesis of the desired compounds in good to very good yield and with high cyclization efficiency for on-resin macrocyclization. In addition, the activities of the corresponding cyclopeptides against the chloroquine-resistant K1 strain of Plasmodium falciparum were evaluated. Read More

    Solid-Phase Synthesis of Pyrrole Derivatives through a Multicomponent Reaction Involving Lys-Containing Peptides.
    ACS Comb Sci 2018 Feb 22. Epub 2018 Feb 22.
    Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , University Road, Westville, Durban 4001, South Africa.
    The synthesis of pyrroles has received considerable attention because of their biological and pharmaceutical activities. Herein we describe a solid-phase multicomponent reaction that utilizes Lys as a N donor, β-nitrostyrenes, 1,3-dicarbonyl compounds, and FeClas an easily accessible catalyst under microwave irradiation to afford the subsequent pyrrole derivatives in high conversions. The strategy combines three of the most powerful tools in modern synthetic chemistry: the solid-phase mode, microwave activation, and a multicomponent reaction. Read More

    Solid-Phase Synthesis and Antibacterial Activity of Cyclohexapeptide Wollamide B Analogs.
    ACS Comb Sci 2018 Feb 20. Epub 2018 Feb 20.
    Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo , 34 Rainbow Drive, Hilo, Hawaii 96720, United States.
    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. Read More

    Regioselective Synthesis of Pyranone-Fused Indazoles via Reductive Cyclization and Alkyne Insertion.
    ACS Comb Sci 2018 Feb 13. Epub 2018 Feb 13.
    Department of Applied Chemistry, National Chiao-Tung University , 1001, Ta-Hseuh Road, Hsinchu 300-10, Taiwan.
    A novel and efficient method for the one-pot synthesis of 2H-indazole from readily available building blocks is reported. The reaction of 2-nitrobenzylamines with zinc and ammonium formate underwent partial reduction to nitroso-benzylamine followed by an intramolecular cyclization to afford 2H-indazole via N-N bond formation. The carboxylic acid moiety of indazole was proceeded to regioselective alkyne insertion under ruthenium catalysis to form pyranone-fused indazoles. Read More

    Rapid Construction of Fe-Co-Ni Composition-Phase Map by Combinatorial Materials Chip Approach.
    ACS Comb Sci 2018 Feb 6. Epub 2018 Feb 6.
    Materials Genome Initiative Center, Shanghai Jiao Tong University , Shanghai 200240, China.
    One hundred nanometer thick Fe-Co-Ni material chips were prepared and isothermally annealed at 500, 600, and 700 °C, respectively. Pixel-by-pixel composition and structural mapping was performed by microbeam X-ray at synchrotron light source. Diffraction images were recorded at a rate of 1 pattern/s. Read More

    Efficient Access to Imidazo[1,2-a]pyridines/pyrazines/pyrimidines via Catalyst-Free Annulation Reaction under Microwave Irradiation in Green Solvent.
    ACS Comb Sci 2018 Feb 7. Epub 2018 Feb 7.
    Department of Chemistry, School of Advanced Sciences, VIT University , Vellore-632014, India.
    An expeditious catalyst-free heteroannulation reaction for imidazo[1,2-a]pyridines/pyrimidines/pyrazines was developed in green solvent under microwave irradiation. Using HO-IPA as the reaction medium, various substituted 2-aminopyridines/pyrazines/pyrimidines underwent annulation reaction with α-bromoketones under microwave irradiation to provide the corresponding imidazo[1,2-a]pyridines/pyrimidines/pyrazines in excellent yields. The synthetic methodology appears to be very simple and superior to the already reported procedures with the high abundance of commercial reagents and great ability in expanding the molecular diversity. Read More

    Sortase-Mediated High-Throughput Screening Platform for Directed Enzyme Evolution.
    ACS Comb Sci 2018 Feb 2. Epub 2018 Feb 2.
    DWI-Leibniz-Institute for Interactive Materials , Forckenbeckstraße 50, 52074 Aachen, Germany.
    Sortase-catalyzed ligations have emerged as powerful tools for the site-specific ligation of peptides and proteins in material science and biocatalysis. In this work, a directed sortase evolution strategy (SortEvolve) has been developed as a general high-throughput screening (HTS) platform to improve activity of sortase A (application 1) and to perform directed laccase evolution through a semipurification process in 96-well microtiter plate (MTP) (application 2). A semipurification process in polypropylene MTP (PP-MTP) is achieved through the anchor peptide LCI, which acts as adhesion promoter. Read More

    Detection of Circulating Tumor Cells Using Microfluidics.
    ACS Comb Sci 2018 Feb 2. Epub 2018 Feb 2.
    University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania , 050097.
    Metastasis is the main cause of death in cancer patients worldwide. During metastasis, cancer cells detach from the primary tumor and invade distant tissue. The cells that undergo this process are called circulating tumor cells (CTCs). Read More

    Crystallographic Structure Analysis of a Ti-Ta Thin Film Materials Library Fabricated by Combinatorial Magnetron Sputtering.
    ACS Comb Sci 2018 Feb 15. Epub 2018 Feb 15.
    Applied Crystallography and Materials Science, Department of Earth and Environmental Sciences, Faculty of Geosciences, Ludwig-Maximilians-Universität , 80333 München, Germany.
    Ti-Ta thin films exhibit properties that are of interest for applications as microactuators and as biomedical implants. A Ti-Ta thin film materials library was deposited at T = 25 °C by magnetron sputtering employing the combinatorial approach, which led to a compositional range of TiTato TiTa. Subsequent high-throughput characterization methods permitted a quick and comprehensive study of the crystallographic, microstructural, and morphological properties, which strongly depend on the chemical composition. Read More

    Solid-Phase Synthesis of Oligopeptides Containing Sterically Hindered Amino Acids on Nonswellable Resin Using 3-Nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1-yl)phosphonium Hexafluorophosphate (PyNTP) as the Condensing Reagent.
    ACS Comb Sci 2018 Jan 30. Epub 2018 Jan 30.
    Faculty of Pharmaceutical Sciences, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
    Peptides are still difficult to synthesize when they contain sterically hindered amino acids, such as α,α-disubstituted amino acids and N-substituted amino acids. In this study, solid-phase syntheses of oligopeptides containing multiple α-aminoisobutyric acid (Aib) residues were performed in high yields by using a nonswellable resin as the solid-support and 3-nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1-yl)phosphonium hexafluorophosphate (PyNTP) as the condensing reagent. Read More

    Enediyne-Comprising Amino Aldehydes in the Passerini Reaction.
    ACS Comb Sci 2018 Jan 30. Epub 2018 Jan 30.
    Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute , Bijenička cesta 54, 10000 Zagreb, Croatia.
    Multicomponent reactions represent a highly efficient approach to a broad spectrum of structurally diverse compounds starting from simple and affordable compounds. A focused library of tweezers-like compounds is prepared by employing the multicomponent Passerini reaction comprising enediyne-derived amino aldehydes. The reaction proceeds under mild conditions yielding Passerini products in good to excellent yields. Read More

    Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines.
    ACS Comb Sci 2018 Feb 25;20(2):98-105. Epub 2018 Jan 25.
    Dipartimento di Chimica, Università degli Studi di Milano , via Golgi 19, Milano, 20133, Italy.
    We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Read More

    Solid-Phase Synthesis of β-Amino Ketones Via DNA-Compatible Organocatalytic Mannich Reactions.
    ACS Comb Sci 2018 Feb 24;20(2):55-60. Epub 2018 Jan 24.
    Department of Chemistry The Scripps Research Institute 130 Scripps Way, Jupiter, Florida 33458, United States.
    One-bead-one-compound (OBOC) libraries constructed by solid-phase split-and-pool synthesis are a valuable source of protein ligands. Most OBOC libraries are comprised of oligoamides, particularly peptides, peptoids, and peptoid-inspired molecules. Further diversification of the chemical space covered by OBOC libraries is desirable. Read More

    Construction of 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Library with a High Level of Skeletal Diversity Based on Branching Diversity-Oriented Synthesis on Solid-Phase Supports.
    ACS Comb Sci 2018 Feb 24;20(2):82-97. Epub 2018 Jan 24.
    Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
    An efficient solid-phase synthetic route for the construction of 1,3,4-oxadiazole and 1,3,4-thiadiazole libraries based on branching diversity-oriented synthesis (DOS) has been developed in this study. The core skeleton resins, 1,3,4-oxadiazole and 1,3,4-thiadiazole, were obtained through desulfurative and dehydrative cyclizations of thiosemicarbazide resin, respectively. Various functional groups have been introduced to the core skeleton resins, such as aryl, amine, amide, urea, thiourea, and an amino acid. Read More

    DNA-Compatible Solid-Phase Combinatorial Synthesis of β-Cyanoacrylamides and Related Electrophiles.
    ACS Comb Sci 2018 Feb 17;20(2):61-69. Epub 2018 Jan 17.
    Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
    We demonstrate that the Knoevenagel condensation can be exploited in combinatorial synthesis on the solid phase. Condensation products from such reactions were structurally characterized, and their Michael reactivity with thiol and phosphine nucleophiles is described. Cyanoacrylamides were previously reported to react reversibly with thiols, and notably, we show that dilution into low pH buffer can trap covalent adducts, which are isolable via chromatography. Read More

    Discrete Fourier Transform-Based Multivariate Image Analysis: Application to Modeling of Aromatase Inhibitory Activity.
    ACS Comb Sci 2018 Feb 22;20(2):75-81. Epub 2018 Jan 22.
    Unidad de Toxicología Experimental, Universidad de Ciencias Médicas "Serafín Ruiz de Zárate Ruiz" , Santa Clara, 50200 Villa Clara, Cuba.
    We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. Read More

    Application of the Open qPCR Instrument for the in Vitro Selection of DNA Aptamers against Epidermal Growth Factor Receptor and Drosophila C Virus.
    ACS Comb Sci 2018 Feb 17;20(2):45-54. Epub 2018 Jan 17.
    University of Idaho , Department of Chemistry, 875 Perimeter Drive, Moscow, Idaho 83844-2343, United States.
    The low-cost Open qPCR instrument can be used for different tasks in the aptamer selection process: quantification of DNA, cycle course optimization, screening, and final binding characterization. We have selected aptamers against whole Drosophila C virus (DCV) particles and recombinant epidermal growth factor receptor (EGFR). We performed systematic evolution of ligands by exponential enrichment (SELEX) using the Open qPCR to optimize each amplification step. Read More

    Application of High-Throughput Seebeck Microprobe Measurements on Thermoelectric Half-Heusler Thin Film Combinatorial Material Libraries.
    ACS Comb Sci 2018 Jan 21;20(1):1-18. Epub 2017 Dec 21.
    Institute of Materials Research, German Aerospace Center , D-51170 Cologne, Germany.
    In view of the variety and complexity of thermoelectric (TE) material systems, combinatorial approaches to materials development come to the fore for identifying new promising compounds. The success of this approach is related to the availability and reliability of high-throughput characterization methods for identifying interrelations between materials structures and properties within the composition spread libraries. A meaningful characterization starts with determination of the Seebeck coefficient as a major feature of TE materials. Read More

    An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries.
    ACS Comb Sci 2018 Jan 27;20(1):35-43. Epub 2017 Dec 27.
    Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.
    An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. Read More

    Novel Multicomponent Synthesis of Pyridine-Pyrimidines and Their Bis-Derivatives Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on Functionalized Nanosilica.
    ACS Comb Sci 2018 Jan 27;20(1):19-25. Epub 2017 Dec 27.
    Catalysis Division, Department of Chemistry, University of Isfahan , Isfahan 81746-73441, Iran.
    In this Research Article, we report an efficient synthesis of 1,3-dimethyl-5-aryl-7-(pyridine-3(2)(4)-yl)pyrimidine-2,4(1H,3H)-diones via a three-component reaction of aryl aldehydes, 1,3-dimethyl-6-aminouracil and carbonitriles in the presences of triazine diphosphonium hydrogen sulfate ionic liquid supported on functionalized nanosilica (APTADPHS-nSiO) as a reusable catalyst under microwave irradiation and solvent-free conditions. The bis-derivatives of pyridine-pyrimidines were also efficiently prepared from dialdehydes and dinitriles. In addition, 3-methyl-1H-pyrazole-5-amine was used successfully instead of 1,3-dimethyl-6-aminouracil under the same conditions to afford the corresponding products in high yields. Read More

    Library-to-Library Synthesis of Highly Substituted α-Aminomethyl Tetrazoles via Ugi Reaction.
    ACS Comb Sci 2018 Feb 4;20(2):70-74. Epub 2018 Jan 4.
    University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
    α-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of the isocyanide component, the reactions give excellent yields. Read More

    Combinatorial Discovery of Lanthanum-Tantalum Oxynitride Solar Light Absorbers with Dilute Nitrogen for Solar Fuel Applications.
    ACS Comb Sci 2018 Jan 11;20(1):26-34. Epub 2017 Dec 11.
    Joint Center for Artificial Photosynthesis, California Institute of Technology , Pasadena, California 91125, United States.
    Oxynitrides with the photoelectrochemical stability of oxides and desirable band energetics of nitrides comprise a promising class of materials for solar photochemistry. Challenges in synthesizing a wide variety of oxynitride materials has limited exploration of this class of functional materials, which we address using a reactive cosputtering combined with rapid thermal processing method to synthesize multi-cation-multi-anion libraries. We demonstrate the synthesis of a LaTaONthin film composition spread library and its characterization by both traditional thin film materials characterization and custom combinatorial optical spectroscopy and X-ray absorption near edge spectroscopy (XANES) techniques, ultimately establishing structure-chemistry-property relationships. Read More

    Process-Function Data Mining for the Discovery of Solid-State Iron-Oxide PV.
    ACS Comb Sci 2017 Dec 9;19(12):755-762. 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 Dec 14;19(12):763-769. 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 a Phase-Based, Chemoselective Reaction.
    ACS Comb Sci 2017 Dec 30;19(12):738-747. Epub 2017 Nov 30.
    Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
    2-Alkoxy/thioalkoxy benzo-[d]-imidazole and 2-thione benzo-[d]-imidazole libraries were constructed in solution phase and on solid phase, respectively. The key step in this work is the phase-based chemoselective reaction of the 2-mercaptobenzo-[d]-imidazole intermediate with benzyl chloride (solution phase) and Merrifield resin (solid phase). In the solution-phase case, benzyl chloride reacted with the thiol group of 2-mercaptobenzo-[d]-imidazole, whereas in the solid-phase case, Merrifield resin was introduced at an 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 Dec 2;19(12):770-774. 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 Dec 7;19(12):715-737. 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 Dec 27;19(12):748-754. 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 (SAr)-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)-C(sp) coupling and SAr 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 Cchiral 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 TiO-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 TiO-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 TiOnanorod array and the thickness gradient rGO. The formation of rGO in the fabricated TiO-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-CHO-CH-OCH-CO-Tyr-Asn-Phe-His-Asn-OH and HCOO-CHO-CH-OCH-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

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