Probing a Hydrogen-π Interaction Involving a Trapped Water Molecule in the Solid State

The detection and characterization of trapped water molecules in chemical entities and biomacromolecules remains a challenging task for solid materials. We herein present proton-detected solid-state Nuclear Magnetic Resonance (NMR) experiments at 100 kHz magic-angle spinning and at high static magnetic-field strengths (28.2 T) enabling the detection of a single water molecule fixed in the calix[4]arene cavity of a lanthanide complex by a combination of three types of non-covalent interactions. The water proton resonances are detected at a chemical-shift value close to zero ppm, which we further confirm by quantum-chemical calculations. Density Functional Theory calculations pinpoint to the sensitivity of the proton chemical-shift value for hydrogen-π interactions. Our study highlights how proton-detected solid-state NMR is turning into the method-of-choice in probing weak non-covalent interactions driving a whole branch of molecular-recognition events in chemistry and biology.     

Characterization of nuclear fuels by ICP mass-spectrometric techniques

Isotopic analyses of radioactive materials such as irradiated nuclear fuel are of major importance for the optimization of the nuclear fuel cycle and for safeguard aspects. Among the mass-spectrometric techniques available, inductively coupled plasma mass spectrometry (ICP-MS) and thermal ionization mass spectrometry are the most frequently applied methods for nuclear applications. Because of the low detection limits, the ability to analyze the isotopic composition of the elements and the applicability of the techniques for measuring stable as well as radioactive nuclides with similar sensitivity, both mass-spectrometric techniques are an excellent amendment to classical radioactivity counting methods. The paper describes selected applications of multicollector ICP-MS in combination with chromatographic separation techniques and laser ablation for the isotopic analysis of irradiated nuclear fuels. The advantages and limitations of the selected analytical technique for the characterization of such a heterogeneous sample matrix are discussed.     

Origin of regioselectivity in α-humulene functionalization

Humulene is a sesquiterpene with an important biochemical lead structure, consisting of an 11-membered ring, containing three nonconjugated C═C double bonds, two of them being triply substituted and one being doubly substituted. As observed by many groups, one of the two triply substituted C═C double bonds is significantly more reactive. In order to rationalize this peculiar regioselectivity, the conformational space of humulene has been explored computationally using various DFT functionals. Four different conformations were identified. Each conformation is chiral and has two enantiomeric forms, yielding a total of eight conformers. The potential energy surface for the interconversion of these conformers was characterized via intrinsic reaction coordinate analyses. Furthermore, an evaluation of the microcanonical partition functions allowed for a quantification of the entropy contributions and the calculation of the temperature dependent equilibrium composition. The results strongly suggest that the high regioselectivity is related to a strong, hyper-conjugative σ(Cα-Cβ)-π(C═C) orbital overlap in the predominant conformations that discriminates one triply substituted double bond from the other. Furthermore, the order of magnitude of the calculated activation energies for the interconversions of the conformers is supported by NMR measurements at different temperatures.     

Solid‐State NMR Spectroscopy Reveals that E. coli Inclusion Bodies of HET‐s(218–289) are Amyloids

Protein deposition frequently occurs as inclusion bodies (IBs) during heterologous protein expression in E. coli. The structure of these E. coli IBs of the prion‐forming domain from the fungal prion HET‐s is the same as that previously determined for fibrils assembled in vitro, and show prion infectivity. These results demonstrate that the IBs of HET‐s(218–289) are amyloids.

     

Cavitation-induced radical-chain oxidation of valeric aldehyde

The application of high-amplitude ultrasound to liquids triggers cavitation. By the collapse of the thereby appearing vacuum cavities, high temperatures can be reached in a transient manner. The high temperatures in these hot-spots can lead to homolytic scission of chemical bonds. The thereby generated radicals are usually utilized in aqueous systems for the degeneration of organic pollutants. In this contribution, we demonstrate that the radicals can also be used for synthetic purposes: under an oxygen atmosphere, they trigger the oxidation of an aldehyde substrate.     

Sustainable synthesis and automated deposition: an accessible discovery screening library of fragment-like purines

A sub-library of 88 information-rich lead-like purine derivatives were prepared and deposited in an open access academic screening facility. The rationale for the synthesis of these rigid low complexity structures was the privileged character of the purine heterocycle associated with its inherent probability of interactions with multiple adenine-related targets. Although generally expected to be weak binders in many assays, such fragment-like compounds are estimated to match diverse binding sites. It is suggested that heterocycles with many anchor points for hydrogen bonds can be anticipated to undergo very specific interactions to produce more negative enthalpies and thus provide superior starting points for lead optimization than compounds that owe their activity to entropic effects. The in vitro cytotoxicity of the small compounds on a panel of human cancer cell lines has been investigated and some of them showed marked unselective or selective toxicity. This data may be useful if these fragments are to be incorporated into drug-like structures via metabolically cleavable connections. The sub-library will be implemented as part of the ChemBioNet ( www.chembionet.info ) library, and it is open to screening campaigns of academic research groups striving for a fragment-based approach in their biological assays.