Charge‐Scaling Effect in Ionic Liquids from the Charge‐Density Analysis of N,N′‐Dimethylimidazolium Methylsulfate

The charge scaling effect in ionic liquids was explored on the basis of experimental and theoretical charge‐density analyses of [C₁MIM][C₁SO₄] employing the quantum theory of atoms in molecules (QTAIM) approach. Integrated QTAIM charges of the experimental (calculated) charge density of the cation and anion resulted in non‐integer values of ±0.90 (±0.87) e. Efficient charge transfer along the bond paths of the hydrogen bonds between the imidazolium ring and the anion was considered as the origin of these reduced charges. In addition, a detailed QTAIM analysis of the bonding situation in the [C₁SO₄]^? anion revealed the presence of negative π_O→σ*_S‐O hyperconjugation.     

High Exchange Rate Complexes of 129Xe with Water-Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI

Macrocyclic host structures for generating transiently bound ¹²⁹Xe have been used in various ultra-sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of water-soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water-soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST-based biosensing MRI.     

Screening for benfluorex and its major urinary metabolites in routine doping controls

Benfluorex [1-(m-trifluoromethylphenyl)-2-(β-benzoyloxyethyl)aminopropane] has been widely used for the treatment of atherogenic metabolic disorders and impaired carbohydrate metabolism (particularly in obese type-II diabetic patients) as well as an anorectic drug. Due to its potentially performance-enhancing properties, benfluorex has been added to the list of prohibited compounds and methods of doping by the World Anti-Doping Agency (WADA) in 2010, necessitating the implementation of the drug as well as its major metabolites into routine doping control procedures. In the present study, human urinary metabolites of benfluorex were characterized by gas chromatography–electron ionization–mass spectrometry (GC-EI-MS) as well as liquid chromatography–electrospray ionization–high resolution/high accuracy tandem mass spectrometry (LC-ESI-MS/MS). Commonly employed sports drug testing approaches consisting of liquid–liquid extraction followed by GC-MS or urine dilution and immediate LC-MS/MS analysis were expanded and validated with regard to specificity, recovery (48–54%, GC-MS only), intra- and interday precision (<25%), limits of detection (5–8 ng/mL for LC-MS/MS and 80 ng/mL for GC-MS), and ion suppression (for LC-ESI-MS/MS only) to allow the detection of benfluorex metabolites 1-(m-trifluoromethylphenyl)-2-(2-hydroxyethyl)aminopropane (M1), 1-(m-trifluoromethylphenyl)-2-(2-carboxymethyl)aminopropane (M2), and 1-(m-trifluoromethylphenyl)-2-aminopropane (M3) as well as the glucuronic acid conjugate of M1.     

Outstanding Chiroptical Properties: A Signature of Enantiomerically Pure Alleno–Acetylenic Macrocycles and Monodisperse Acyclic Oligomers

A second series of shape‐persistent alleno–acetylenic macrocycles and monodisperse acyclic oligomers with conformationally less flexible backbones were synthesized in enantiomerically pure form by short, high‐yielding routes starting from optically active 1,3‐diethynylallenes. All seven stereoisomers—two pairs of enantiomers and three achiral stereoisomers—in the macrocyclic series were separated and configurationally assigned. The electronic circular dichroism (ECD) spectra of the D₂‐symmetric, (P,P,P,P)‐ and (M,M,M,M)‐configured macrocycles display remarkably intense chiroptical responses. A strong amplification of chirality is observed in the acyclic oligomeric series. Their preference for helical secondary structures of one handedness was supported by X‐ray analysis and computational studies. This new set of data provides proof that outstanding ECD responses are a hallmark of alleno–acetylenic macrocyclic and acyclic oligomeric chromophores.     

Synthesis of Cyano‐Substituted Diaryltetracenes from Tetraaryl[3]cumulenes

A versatile, two‐step synthesis of highly substituted, cyano‐functionalized diaryltetracenes has been developed, starting from easily accessible tetraaryl[3]cumulenes. This unprecedented transformation is initiated by [2+2] cycloaddition of tetracyanoethylene (TCNE) to the proacetylenic central double bond of the cumulenes to give an intermediate zwitterion, which after an electrocyclization cascade and dehydrogenation yields 5,5,11,11‐tetracyano‐5,11‐dihydrotetracenes in a one‐pot procedure. A subsequent copper‐assisted decyanation/aromatization provided the target 5,11‐dicyano‐6,12‐diaryltetracene derivatives. All of the postulated structures were confirmed by X‐ray crystallography. The new chromophores are thermally highly stable and feature promising fluorescence properties for potential use in optoelectronic devices. They are selective chemosensors for Cu^I ions, which coordinate to one of the CN substituents and form a 1:1 complex with an association constant of K_a=1.5×10⁵ L mol^?1 at 298 K.     

General base catalysis for cleavage by the active-site cytosine of the hepatitis delta virus ribozyme: QM/MM calculations establish chemical feasibility

The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Previous experimental studies have established that the active-site nucleotide C75 is essential for self-cleavage of the ribozyme, although its exact catalytic role in the process remains debated. Structural data from X-ray crystallography generally indicate that C75 acts as the general base that initiates catalysis by deprotonating the 2'-OH nucleophile at the cleavage site, while a hydrated magnesium ion likely protonates the 5'-oxygen leaving group. In contrast, some mechanistic studies support the role of C75 acting as general acid and thus being protonated before the reaction. We report combined quantum chemical/molecular mechanical calculations for the C75 general base pathway, utilizing the available structural data for the wild type HDV genomic ribozyme as a starting point. Several starting configurations differing in magnesium ion placement were considered and both one-dimensional and two-dimensional potential energy surface scans were used to explore plausible reaction paths. Our calculations show that C75 is readily capable of acting as the general base, in concert with the hydrated magnesium ion as the general acid. We identify a most likely position for the magnesium ion, which also suggests it acts as a Lewis acid. The calculated energy barrier of the proposed mechanism, approximately 20 kcal/mol, would lower the reaction barrier by approximately 15 kcal/mol compared with the uncatalyzed reaction and is in good agreement with experimental data.     

Chemical mapping of ceramide distribution in sphingomyelin-rich domains in monolayers

The incorporation of ceramide in phase-separated monolayers of ternary lipid mixtures has been studied by a combination of atomic force microscopy (AFM), fluorescence, and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Replacement of a fraction of the sphingomyelin by ceramide in DOPC/SM/cholesterol monolayers leads to changes in the SM-cholesterol-rich liquid-ordered domains. AFM shows the formation of heterogeneous domains with small raised islands that are assigned to a ceramide-rich gel phase. ToF-SIMS provides conclusive evidence for the localization of SM and ceramide in ordered domains and shows that ceramide is heterogeneously distributed in small islands throughout the domains. The results indicate the utility of combining AFM and ToF-SIMS for understanding compositions of phase-separated membranes.     

Conductivity of oriented bis-azo polymer films.

The conductivity properties of electro-optic, photoaddressable, dense bis-azo chromophore polymer films are investigated by using samples corona poled at various temperatures. A dielectric spectrometer is applied to measure the frequency dependence of the conductivity at different temperatures before and after heating the material to above the glass transition temperature. The results show that the orientation of the chromophores changes the charge-carrier mobility. Ionic conductivity dominates in a more disordered configuration of the material, while the competing process of hole hopping takes over as a transition to a liquid-crystalline phase occurs when the material is heated to much higher than the glass transition temperature. Such microcrystallization strongly enhances the conductivity.