Detection of HER2+ Breast Cancer Cells using Bioinspired DNA-Based Signal Amplification

Cancer cell detection via amplified fluorescence signal: We developed a programmable DNA circuit system based on hybridization chain reaction (HCR); this is a bioinspired signal amplification approach that allows specific and sensitive detection of HER2+ breast cancer cells among HER2 cells, including freshly isolated peripheral blood mononuclear cells.

[Communications]

Sarah D. Rafiee, Dr. Samet Kocabey, Prof. Michael Mayer, Dr. Jonathan List, Prof. Curzio Rüegg

doi.org/10.1002/cmdc.201900697

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

DORA explorers: The orexin system plays an important role in regulating the sleep-wake cycle. Herein we report our optimization efforts toward a novel dual orexin receptor antagonist (DORA) with improved properties over compound 6. Replacing the oxadiazole by a triazole resulted in compounds (e. g. compound 33) with improved properties, such as higher intrinsic metabolic stability, lower plasma protein binding, higher brain free fraction, and increased solubility. Further optimization was needed to decrease the compounds P-glycoprotein susceptibility. Our work led to the identification of compound 42, a potent, brain-penetrating DORA with improved in vivo efficacy in dogs compared with compound 6.

[Full Papers]

Dr. Christine Brotschi, Dr. Martin H. Bolli, Dr. John Gatfield, Dr. Bibia Heidmann, Dr. Francois Jenck, Dr. Catherine Roch, Dr. Thierry Sifferlen, Dr. Alexander Treiber, Dr. Jodi T. Williams, Dr. Christoph Boss

doi.org/10.1002/cmdc.201900618

Symmetric Mixed Sulfur-Selenium Fused Ring Systems as Potential Materials for Organic Field-Effect Transistors

This study introduces a series of regioisomeric symmetric sulfur-selenium fused materials for organic field-effect transistors (OFETs). These π-conjugated materials show strong intermolecular interactions beneficial for charge carrier transport.

[Full Papers]

Dr. Brigitte Holzer, Barbara Dellago, Ann-Katrin Thamm, Dr. Thomas Mathis, Prof. Berthold Stöger, Dr. Ernst Horkel, Dr. Christian Hametner, Dr. Bertram Batlogg, Prof. Johannes Fröhlich, Dr. Daniel Lumpi

doi.org/10.1002/chem.201903958

Selective Catalytic Reduction of NO with NH3 on Cu−SSZ-13: Deciphering the Low and High-temperature Rate-limiting Steps by Transient XAS Experiments

Selective catalytic reduction: The application of non-steady state, highly time-resolved QEXAFS to the study of the selective catalytic reduction of NO over a Cu/SSZ-13 catalyst elucidates the change in the rate-limiting step between low and high temperature regime SCR. In addition, insight into the transient Cu speciation has demonstrated the presence of two additional side reactions: the parasitic oxidation of NH3 and the direct oxidation of CuI−Z to CuII−Z.

[Full Papers]

Dr. Adam H. Clark, Rob Jeremiah G. Nuguid, Dr. Patrick Steiger, Dr. Adrian Marberger, Dr. Andrey W. Petrov, Dr. Davide Ferri, Dr. Maarten Nachtegaal, Prof. Dr. Oliver Kröcher

doi.org/10.1002/cctc.201901916

Untying the Photophysics of Quinolinium-Based Molecular Knots and Links

Untying the knot: The topology of a molecule affects its physical and chemical properties in many ways. The built-in quinolinium chromophore in a family of structurally related knots and links, exhibits sharp alteration in its properties depending on the braiding tightness as uncovered by UV/Vis, transient absorption and NMR spectroscopies.

[Full Papers]

Kenji Caprice, Alexander Aster, Dr. Fabien B. L. Cougnon, Dr. Tatu Kumpulainen

doi.org/10.1002/chem.201904456

Synthesis of Iridium Nanocatalysts for Water Oxidation in Acid: Effect of the Surfactant

With or without surfactant? A simple surfactant-free and NaOH-free synthesis of small Ir nanoparticles is here detailed. The benefits and drawbacks are illustrated by comparison with nanoparticles obtained using surfactant for the oxygen evolution reaction in acidic media. Surfactant-free and NaOH-free nanoparticles show promising catalytic activity and stability.

[Communications]

José Alejandro Arminio-Ravelo, Dr. Jonathan Quinson, Mads A. Pedersen, Prof. Jacob J. K. Kirkensgaard, Prof. Matthias Arenz, Prof. María Escudero-Escribano

doi.org/10.1002/cctc.201902190

A Comparative Study of in vitro Assays for Predicting the Nonspecific Binding of PET Imaging Agents in vivo

Specific or nonspecific? The ability of a nuclear imaging agent to bind specifically to its target is critical for a good signal-to-noise ratio and clear images. CHI(IAM), LIMBA and rat fu,brain allow the measurement of nonspecific binding and its optimization during chemical optimization. A comparison of these methods shows how well they predict imaging properties and the results of positron emission tomography studies in humans.

[Full Papers]

Dr. Luca Gobbi, Dr. Joël Mercier, Dr. Benny Bang-Andersen, Dr. Jean-Marie Nicolas, Dr. John Reilly, Björn Wagner, Dr. David Whitehead, Dr. Emmanuelle Briard, Dr. R. Paul Maguire, Dr. Edilio Borroni, Dr. Yves P. Auberson

doi.org/10.1002/cmdc.201900608

Synthesis of 2-Substituted 1,2,3-Triazoles via an Intramolecular N-N Bond Formation

An intramolecular N-N bond formation leads to a wide variety of 2-aryl 1,2,3-triazoles based on an intramolecular N-N bond formation is described. The reaction likely follows an intramolecular SN2 displacement mechanism with the trimethylammonium moiety serving as a good leaving group for the intramolecular N-N bond formation.

[Communications]

Cheng-yi Chen, Xiaowei Lu, Mareike C. Holland, Shichang Lv, Xuebao Ji, Wei Liu, Jie Liu, Dominique Depre, Pieter Westerduin

doi.org/10.1002/ejoc.201901519

Expanding the Scope of Water-Stable Rhenium(V)-NHC Complexes - Synthesis, Characterization, and Derivatization

The synthesis of novel ReV complexes bearing a tridentate NHC scorpionate ligand is reported. The complexes were fully characterized, including X-ray structural analyses. Additionally, their stability towards air and moisture was investigated. The new ReV NHC scorpionate motif discussed herein is one step further in the direction towards water-stable Re-based metallodrugs.

[Communications]

Dustin Bornemann, Lukas Schlemper, Nils Trapp, Antonio Togni

doi.org/10.1002/ejic.201901077

Self-Assembly of Proteinaceous Shells around Positively Charged Gold Nanomaterials Enhances Colloidal Stability in High-Ionic-Strength Buffers

Engineered electrostatic interactions enable the self-assembly of a lumazine synthase variant on differently sized and shaped gold nanomaterials. The resulting complexes possess dramatically enhanced colloidal stability in high-ionic-strength buffers owing to the formation of a protective ≈4-nm-thick proteinaceous shell around the core particle.

[Communications]

Dr. Eita Sasaki, Ryan M. Dragoman, Dr. Shiksha Mantri, Dr. Dmitry N. Dirin, Prof. Dr. Maksym V. Kovalenko, Prof. Dr. Donald Hilvert

doi.org/10.1002/cbic.201900469

Identification of Synthetic Activators of Cancer Cell Migration by Hybrid Deep Learning

Reading the images: Neural networks are explored for their utility in the drug discovery process. In this study a convolutional neural network was trained using self-organizing maps of molecular pharmacophores. The trained network identified chemokine receptor ligands which were tested in a functional assay and then confirmed in a three-dimensional spheroid invasion assay.

[Full Papers]

Dominique Bruns, Erik Gawehn, Dr. Karthiga Santhana Kumar, Dr. Petra Schneider, Dr. Martin Baumgartner, Prof. Dr. Gisbert Schneider

doi.org/10.1002/cbic.201900346

Conjugating Biotin to Ruthenium(II) Arene Units via Phosphine Ligand Functionalization

Robust ruthenium(II) arene compounds incorporating biotin through a phosphine linkage were synthesized and assessed for their cytotoxicity against several cancer cell lines with different levels of biotin transporter expression, and for their apparent affinity to avidin.

[Full Papers]

Lorenzo Biancalana, Martyna Gruchała, Lucinda K. Batchelor, Andrzej Błauż, Andrea Monti, Guido Pampaloni, Błażej Rychlik, Paul J. Dyson, Fabio Marchetti

doi.org/10.1002/ejic.201900922

Modulation of Pharmacologically Relevant Properties of Piperidine Derivatives by Functional Groups in an Equatorial or Axial β-Position to the Amino Group

A set of amine basicity and lipophilicity data for β-substituted piperidine derivatives provide enhanced insight into the stereospecific modulation of pharmacologically relevant properties by small substituents and prototypic functional groups, establishing a valuable reference base for molecular design.

[Full Papers]

Dr. Patrick Schnider, Cosimo Dolente, Dr. Henri Stalder, Dr. Rainer E. Martin, Dr. Viktoria Reinmüller, Dr. Roman Marty, Dr. Caroline Wyss Gramberg, Björn Wagner, Dr. Holger Fischer, Dr. André M. Alker, Prof. (emer.) Dr. Klaus Müller

doi.org/10.1002/cbic.201900474

Synthesis and Characterization of an Epidermal Growth Factor Receptor-Selective RuII Polypyridyl-Nanobody Conjugate as a Photosensitizer for Photodynamic Therapy

Specificity comes to light: RuII polypyridyl complexes used in photodynamic therapy (PDT) can target DNA. However, because DNA is ubiquitous, the selectivity of such photosensitizers could be increased by linking them to a targeting vector. Herein we present the synthesis, characterization, and in-depth photophysical evaluation of a nanobody-containing RuII polypyridyl conjugate selective for the epidermal growth factor receptor (EGFR) in view of targeted PDT.

[Full Papers]

Johannes Karges, Marta Jakubaszek, Dr. Cristina Mari, Dr. Kristof Zarschler, Dr. Bruno Goud, Dr. Holger Stephan, Dr. Gilles Gasser

doi.org/10.1002/cbic.201900419

Characterization of an Orphan Type III Polyketide Synthase Conserved in Uncultivated “Entotheonella” Sponge Symbionts

Common ground: Few of the diverse biosynthetic gene clusters found in uncultivated “Entotheonella” sponge symbionts are shared between phylotypes, and all of these are functionally uncharacterized. Herein, the characterization of conserved type III polyketide synthase (PKS) CepA is reported and it is shown that it produces phenolic lipids.

[Full Papers]

Dr. Silke Reiter, Dr. Jackson K. B. Cahn, Vincent Wiebach, Dr. Reiko Ueoka, Prof. Dr. Jörn Piel

doi.org/10.1002/cbic.201900352

Synthesis of DNA-Encoded Disulfide- and Thioether-Cyclized Peptides

DNA-encoded cyclic peptides: A strategy for the efficient chemical synthesis of cyclic peptide-DNA conjugates was established. The peptides contain a pair of cysteine residues and are cyclized through disulfide or thioether bond formation. Key for the peptide-DNA conjugate synthesis was the use of tertbutylthio-protected Fmoc-cysteine as building block.

[Full Papers]

Dr. Manh V. Pham, Dr. Milan Bergeron-Brlek, Prof. Christian Heinis

doi.org/10.1002/cbic.201900390

Probing for Thiol-Mediated Uptake into Bacteria

In or out? Cyclic oligochalcogenides (COCs), inhibit, rather than mediate, uptake into bacteria. This conclusion, resulting from the synthesis and evaluation of a series of COC-antibiotic conjugates, supports that COCs penetrate mammalian cells along nontrivial uptake pathways involving dynamic covalent exchange chemistry, mobility along disulfide tracks, and adaptive micellar pores.

[Communications]

Quentin Laurent, Dr. Mathéo Berthet, Dr. Yangyang Cheng, Dr. Naomi Sakai, Dr. Sofia Barluenga, Prof. Nicolas Winssinger, Prof. Stefan Matile

doi.org/10.1002/cbic.201900378

Nucleotide Binding Modes in a Motor Protein Revealed by 31P- and 1H-Detected MAS Solid-State NMR Spectroscopy

Protein-nucleotide contacts in a noncrystalline bacterial DnaB helicase sedimented in the NMR rotor were probed by 31P- and 1H-detected solid-state NMR spectroscopy. The sensitivity of 1H chemical shifts to hydrogen bonding was explored and used to identify residues involved in nucleotide coordination.

[Communications]

Dr. Thomas Wiegand, Maarten Schledorn, Alexander A. Malär, Riccardo Cadalbert, Alexander Däpp, Dr. Laurent Terradot, Prof. Dr. Beat H. Meier, Dr. Anja Böckmann

doi.org/10.1002/cbic.201900439

Reductive Amination and Enantioselective Amine Synthesis by Photoredox Catalysis

The recently discovered photochemical reductive amination and the enantioselective amine synthesis by combined photoredox/enzymatic catalysis is reviewed.

[Minireview]

Xingwei Guo, Yasunori Okamoto, Mirjam R. Schreier, Thomas R. Ward, Oliver S. Wenger

doi.org/10.1002/ejoc.201900777

Copper Catalyzed Direct Synthesis of Nitriles from Acyl Azides

A novel and general protocol for the copper catalyzed reductive elimination of acyl azides to nitriles using triethoxysilane is reported. Various nitriles are obtained in moderate to excellent yields with good functional group tolerance and high chemoselectivity.

[Communications]

Prof. Yang Chen, Yu Liu, Xiao Zhang, Da Lu, Lixin Yang, Junfeng Deng, Prof. Shengqi Deng

doi.org/10.1002/slct.201802918

Aerobic Oxidation of Methyl-substituted β-Carbolines Catalyzed by N-Hydroxyphthalimide and Metal Catalyst

Carboxylic functionalized β-carbolines have been synthesized in good to excellent yields and high selectivity by oxygen in the presence of NHPI and transition metal salt under mild conditions

[Communications]

Hongda Qiu, Weida Liang, Dr. Gongjun Zhang, Miaoman Lin, Wanmin Liu, Prof. Zhanghua Gao, Dr. Wenting Wei, Dr. Chunlan Tang, Dr. Haixiao Jin, Prof. Hongze Liang, Prof. Xiaojun Yan

doi.org/10.1002/slct.201803007

Betti Bases from 4-(3-Pyridazo)-1-naphthol: Synthesis, Coordination Behaviour and Unusual Substitution Reactions

Synthesis, characterization and complexation ability study of a series of Betti bases from 4-(3-pyridyl)azo-1-naphthol dye, possessing flexible methylene or more constrained aryl-methyne spaced NH-containing side-chains, is presented. An unexpected result with side-chain pyridyl group replacement was obtained and the product was analysed by XRD. A possible pathway was suggested and synthetically confirmed.

[Full Papers]

Prof. Dr. Vanya B. Kurteva, Dr. Lubomir A. Lubenov, Prof. Dr. Boris L. Shivachev, Prof. Dr. Rositsa P. Nikolova, Prof. Dr. Katharina M. Fromm

doi.org/10.1002/slct.201802745