Dioldehydratase Binds Coenzyme B12 in the “Base-On” Mode: ESR Investigations on Cob(II)alamin

Even in the enzyme-bound state the dimethylbenzimidazole ligand in the dioldehydratase from Salmonella typhimurium remains bound to the cobalt ion in contrast to some coenzyme B₁₂-dependent enzymes. Direct, ESR spectroscopic proof for this “base-on” binding mode was obtained by using a coenzyme in which one of the nitrogen atoms of the dimethylbenzimidazole ligand was ¹⁵N labeled (see schematic representation on the right).     

Multivalent Inhibitors for Carbohydrate‐Processing Enzymes: Beyond the “Lock‐and‐Key” Concept

During the last decades, tremendous chemical efforts have been dedicated to design monovalent inhibitors of carbohydrate‐processing enzymes, with comparatively few rewards in terms of marketed drugs. Recently, an alternative to the traditional “lock and key” approach has emerged. Multivalency, a widely used strategy for lectin inhibition, has been successfully applied to specific glycosidases and glycosyltransferases.     

Five Decades Ago: From the “Transuranics” to Nuclear Fission

The discovery of nuclear fission is one of the most outstanding episodes in the history of chemistry: It starts in the spring of 1934 when Enrico Fermi and his group irradiate uranium with neutrons and seem to succeed in going beyond uranium, the then heaviest known element, reaching the first transuranic element; it continues with Otto Hahn, Lise Meitner and Fritz Strassmann who believe to have found additional transuranic elements; with Irène Curie and Paul Savitch who observe an activity which somehow does not fit into that scheme; again with Otto Hahn and Fritz Strassmann who first identify this activity as radium but then on the 17th of December 1938 after rigorous chemical tests realize that the activity is instead barium, thus discovering the fission of the uranium atom into two lighter nuclei; and with Lise Meitner and Otto Robert Frisch who explain nuclear fission on the basis of an already known nuclear model; Otto Robert Frisch finally performs a physical experiment on the 13th of January 1939 which corroborates the fission of uranium. This discovery of nuclear fission is not only an event of historic dimensions, it is also an excellent example of how science evolves, not by successive logical steps but rather through strange detours.     

Design,Synthesis and Biological Evaluation of New Carbohydrate-Based Coumarin Derivatives as Selective Carbonic Anhydrase IX Inhibitors via “Click” Reaction

In this work, we designed a series of new carbohydrate-based coumarin carbonic anhydrase IX inhibitors by using 1,2,3-triazoles as linker. Next, these designed compounds were synthesized by the optimized one-pot click chemistry reaction condition. Subsequently, these target compounds were assayed for the inhibition of three carbonic anhydrase isoforms (CA I, CA II and CA IX). Intriguingly, all the compounds showed better CA IX inhibitory activity than initial coumarin fragments. Among them, compound 10a (IC₅₀: 11 nM) possessed the most potent CA IX inhibitory activity, which was more potent than the reference drug acetazolamide (IC₅₀: 30 nM). Notably, compound 10a showed 3018-fold, 1955-fold selectivity relative to CA I and CA II, respectively. Meanwhile, representative compounds could reduce tumor cell viability and the extracellular acidification in HT-29 and MDA-MB-231 cancer cell lines. Even more interestingly, our target compounds had no apparent cytotoxicity toward MCF-10A cell line. In addition, the in vitro stability assays also indicated our developed compounds possessed good liver microsomal metabolic stabilities and plasma stability. Furthermore, representative compounds revealed relatively low hERG cardiac toxicity and acute toxicity. Furthermore, docking studies were carried out to understand the interactions of our target compounds with the protein target CA IX. Collectively, our results suggest that compound 10a, as a selective CA IX inhibitor, could be an important lead compound for further optimization and development as an anticancer agent.     

125 Years of Chemistry in the Mirror of “Angewandte”

This Review investigates the development of Angewandte Chemie since the founding of the journal in 1887 and analyzes how its content reflects the changes in chemical research over these 125 years. Although Angewandte Chemie was originally founded as a journal for applied (“angewandte”)—technical and analytical—chemistry, numerous review articles and abstracts published even in its first 50 years enable the milestones in chemical research in a much broader sense to be traced nicely. With the introduction of the International Edition in 1962, the author base, which had until then been primarily limited to German‐speaking countries, became increasingly international, and the journal experienced impressive growth. Today, with its attractive layout, successful mix of articles, and high impact factor, Angewandte Chemie covers chemical research around the world in its full breadth, with its many achievements and future challenges.     

2,4,6,8-Tetracyanoazulene: A New Building Block for “Organic Metals”

Simply mixing solutions of the title compound 1 and tetrathiafulvene (TTF) in acetonitrile provides the charge-transfer complex 2 . Here, 1 functions as a novel electron acceptor and is present in the complex as a radical anion. An electrical conductivity of up to 3 S cm⁻¹ was determined for 2 with a two-point powder measurement.     

Functionalized Cross-Linked Copolymers: A “C2-Symmetric” Solid-Phase Catalyst for Enantioselective Reactions

Similar enantiomeric excesses as for analogous monomeric sulfonamides are provided by the chiral resin 1 (connections to the polymer are shown as circles) when it is used as catalyst for the reductive alkylation of aromatic aldehydes and for the cyclopropanation of cinnamyl alcohol.     

Integrative Chemical Biology Approaches for Identification and Characterization of “Erasers” for Fatty‐Acid‐Acylated Lysine Residues within Proteins

Acylation of proteins with fatty acids is important for the regulation of membrane association, trafficking, subcellular localization, and activity of many cellular proteins. While significant progress has been made in our understanding of the two major forms of protein acylation with fatty acids, N‐myristoylation and S‐palmitoylation, studies of the acylation of lysine residues, within proteins, with fatty acids have lagged behind. Demonstrated here is the use of integrative chemical biology approaches to examine human sirtuins as de‐fatty‐acid acylases in vitro and in cells. Photo‐crosslinking chemistry is used to investigate enzymes which recognize fatty‐acid acylated lysine. Human Sirt2 was identified as a robust lysine de‐fatty‐acid acylase in vitro. The results also show that Sirt2 can regulate the acylation of lysine residues, of proteins, with fatty acids within cells.     

The C-F⋅⋅⋅H-C “Anti-Hydrogen Bond” in the Gas Phase: Microwave Structure of the Difluoromethane Dimer

A shortening of the C−H bond lengths and a blue shift of the C−H stretching frequencies for the C-F⋅⋅⋅H-C groups indicates that anti-hydrogen bonds are present the difluoromethane dimer. The most stable conformer has three such interactions (shown schematically).     

Synthesis and Biological Evaluation of Several Dephosphonated Analogues of CMP‐Neu5Ac as Inhibitors of GM3‐Synthase

Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP‐Neu5Ac congeners and their anti ‐ GM3‐synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3‐synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.     

Carbocatalysis: The State of “Metal‐Free” Catalysis

The rise in global demand for crucial chemical compounds has driven immense research in the fundamental science of catalysis. Graphene and its derivatives (chemically modified graphene, CMGs) have recently emerged as a new class of heterogeneous catalyst that promises economically viable and greener routes to these compounds. Although CMGs possess unique catalytic properties, the actual active sites are often points of discussion. Current minimal understanding on the possible effects of metallic impurities on the electrocatalytic performances of these CMGs calls forth the need to raise awareness on possible metallic impurities misrepresenting the actual chemical catalytic performances of the CMGs. This Minireview highlights the latest advances in the application of CMGs as catalysts, with an emphasis on the possible effects of metallic impurities on CMG catalysis.