Ethanol/water solutions as certified reference materials for breath alcohol analyzer calibration

The Federal Institute for Materials Research and Testing (BAM), Germany, has issued a series of large volume ethanol in water certified reference materials (CRMs), primarily developed for the calibration of evidential breath alcohol analyzers in Germany. The certified parameter is the ethanol mass concentration at 20 °C. When used in a wet bath simulator, the solutions deliver gas samples that meet the requirements set by the Organization of Legal Metrology for calibration of breathalyzers. The materials were prepared gravimetrically by spiking of ethanol into water in single 5 L units. A complete uncertainty budget for the preparation process has been established. The purity of the commercial ethanol stock solution was identified to be the main source of uncertainty. For stability and homogeneity measurements and for the verification of the gravimetric mass concentration of the CRMs, a robust high-precision gas chromatography, with flame-ionization detection method for ethanol determination in aqueous samples was developed and validated. The good performance of this method has been demonstrated in several international comparisons organized by the Consultative Committee for Amount of Substance—Metrology in Chemistry at the International Bureau of Weights and Measures.     

Chemical biology of salinomycin

Cancer stem cells (CSC) have been shown to be refractory to conventional therapeutic agents, can promote metastasis, and have been linked to cancer relapse. The natural product Salinomycin has been identified by means of high throughput phenotypic screening as a selective killer of CSC in vitro and in vivo. In this article we comprehensively review the chemistry of Salinomycin, documenting early total syntheses, along with strategies that have been developed over the years to effectively modify this natural product at key positions with the view to establish a robust structure-activity-relationship and to delineate the complex mechanism of action of this fascinating molecule in the context of cancer research. Then, we document the biology of Salinomycin, putting forward phenotypic alterations that have been observed in the relevant biological models and highlighting how chemistry has been instrumental in discovering unprecedented physiological features of cancer stem cells that can be exploited for therapeutic benefits.     

161Dy Time‐Domain Synchrotron Mössbauer Spectroscopy for Investigating Single‐Molecule Magnets Incorporating Dy Ions

Time‐domain synchrotron Mössbauer spectroscopy (SMS) based on the Mössbauer effect of ¹⁶¹Dy has been used to investigate the magnetic properties of a Dy^III‐based single‐molecule magnet (SMM). The magnetic hyperfine field of [Dy(Cy₃PO)₂(H₂O)₅]Br₃?2 (Cy₃PO)?2 H₂O?2 EtOH is with B₀=582.3(5) T significantly larger than that of the free‐ion Dy^III with a ⁶H_15/2 ground state. This difference is attributed to the influence of the coordinating ligands on the Fermi contact interaction between the s and 4f electrons of the Dy^III ion. This study demonstrates that ¹⁶¹Dy SMS is an effective local probe of the influence of the coordinating ligands on the magnetic structure of Dy‐containing compounds.     

Boron‐Containing Probes for Non‐optical High‐Resolution Imaging of Biological Samples

Boron has been employed in materials science as a marker for imaging specific structures by electron energy loss spectroscopy (EELS) or secondary ion mass spectrometry (SIMS). It has a strong potential in biological analyses as well; however, the specific coupling of a sufficient number of boron atoms to a biological structure has proven challenging. Herein, we synthesize tags containing closo‐1,2‐dicarbadodecaborane, coupled to soluble peptides, which were integrated in specific proteins by click chemistry in mammalian cells and were also coupled to nanobodies for use in immunocytochemistry experiments. The tags were fully functional in biological samples, as demonstrated by nanoSIMS imaging of cell cultures. The boron signal revealed the protein of interest, while other SIMS channels were used for imaging different positive ions, such as the cellular metal ions. This allows, for the first time, the simultaneous imaging of such ions with a protein of interest and will enable new biological applications in the SIMS field.     

Membrane-mediated induction and sorting of K-Ras microdomain signaling platforms

The K-Ras4B GTPase is a major oncoprotein whose signaling activity depends on its correct localization to negatively charged subcellular membranes and nanoclustering in membrane microdomains. Selective localization and clustering are mediated by the polybasic farnesylated C-terminus of K-Ras4B, but the mechanisms and molecular determinants involved are largely unknown. In a combined chemical biological and biophysical approach we investigated the partitioning of semisynthetic fully functional lipidated K-Ras4B proteins into heterogeneous anionic model membranes and membranes composed of viral lipid extracts. Independent of GDP/GTP-loading, K-Ras4B is preferentially localized in liquid-disordered (l(d)) lipid domains and forms new protein-containing fluid domains that are recruiting multivalent acidic lipids by an effective, electrostatic lipid sorting mechanism. In addition, GDP-GTP exchange and, thereby, Ras activation results in a higher concentration of activated K-Ras4B in the nanoscale signaling platforms. Conversely, palmitoylated and farnesylated N-Ras proteins partition into the l(d) phase and concentrate at the l(d)/l(o) phase boundary of heterogeneous membranes. Next to the lipid anchor system, the results reveal an involvement of the G-domain in the membrane interaction process by determining minor but yet significant structural reorientations of the GDP/GTP-K-Ras4B proteins at lipid interfaces. A molecular mechanism for isoform-specific Ras signaling from separate membrane microdomains is postulated from the results of this study.     

Electronic Effects of para‐Substitution on the Melting Points of TAAILs

Owing to numerous new applications, the interest in “task‐specific” ionic liquids increased significantly over the last decade. But, unfortunately, the imidazolium‐based ionic liquids (by far the most frequently used cations) have serious limitations when it comes to modifications of their properties. The new generation of ionic liquids, called tunable aryl–alkyl ionic liquids (TAAILs), replaces one of the two alkyl chains on the imidazolium ring with an aryl ring which allows a large degree of functionalization. Inductive, mesomeric, and steric effects as well as potentially also π π and π π⁺ interactions provide a wide range of possibilities to tune this new class of ILs. We investigated the influence of electron‐withdrawing and ‐donating substituents at the para‐position of the aryl ring (NO₂, Cl, Br, EtO(CO), H, Me, OEt, OMe) by studying the changes in the melting points of the corresponding bromide and bis(trifluoromethanesulfonyl)imide, (N(Tf)₂⁻), salts. In addition, we calculated (B3LYP/6‐311++G(d,p)) the different charge distributions of substituted 1‐aryl‐3‐propyl‐imidazolium cations to understand the experimentally observed effects. The results indicated that the presence of electron‐donating and ‐withdrawing groups leads to strong polarization effects in the cations.