A six-step synthesis of (S)-5-ethenyl-3-(1-methyl-2-pyrrolidinyl)pyridine (SIB-1508Y) from (S)-nicotine

The anti-Parkinson’s agent SIB-1508Y was prepared in six steps from (S)-nicotine in 20% overall yield. The strategy involves a regioselective formylation at C-5 of a 1,4-dihydronicotine intermediate.     

Negatively charged hyperbranched polyether-based polyelectrolytes

The preparation of carboxylated hyperbranched polyglycerols of narrow polydispersity was achieved by modification (78–90%) of the hydroxyl end groups via Michael addition of acrylonitrile, followed by hydrolysis. High conversion could only be achieved for low molecular weight starting materials (520 and 1,030 g mol⁻¹). The solution properties of the resulting materials were investigated by dynamic light scattering (DLS), showing the formation of large aggregates with size depending on the pH value. After deposition on a negatively charged mica surface, the structures observed by atomic force microscope (AFM) show the coexistence of aggregates and single macromolecules. Most interesting, in the case of the lower molecular weight sample (PG 520 g mol⁻¹), extended and ordered terrace structures were formed, which are unprecedented for hyperbranched polymers and are of interest for surface modification in general.     

Sample Entropy as a Tool to Assess Lumbo-Pelvic Movements in a Clinical Test for Low-Back-Pain Patients

Low back pain (LBP) obviously reduces the quality of life but is also the world’s leading cause of years lived with disability. Alterations in motor response and changes in movement patterns are expected in LBP patients when compared to healthy people. Such changes in dynamics may be assessed by the nonlinear analysis of kinematical time series recorded from one patient’s motion. Since sample entropy (SampEn) has emerged as a relevant index measuring the complexity of a given time series, we propose the development of a clinical test based on SampEn of a time series recorded by a wearable inertial measurement unit for repeated bending and returns (b and r) of the trunk. Twenty-three healthy participants were asked to perform, in random order, 50 repetitions of this movement by touching a stool and another 50 repetitions by touching a box on the floor. The angular amplitude of the b and r movement and the sample entropy of the three components of the angular velocity and acceleration were computed. We showed that the repetitive b and r “touch the stool” test could indeed be the basis of a clinical test for the evaluation of low-back-pain patients, with an optimal duration of 70 s, acceptable in daily clinical practice.     

Design of Oligourea-Based Foldamers with Antibacterial and Antifungal Activities

There is an urgent need to develop new therapeutic strategies to fight the emergence of multidrug resistant bacteria. Many antimicrobial peptides (AMPs) have been identified and characterized, but clinical translation has been limited partly due to their structural instability and degradability in physiological environments. The use of unnatural backbones leading to foldamers can generate peptidomimetics with improved properties and conformational stability. We recently reported the successful design of urea-based eukaryotic cell-penetrating foldamers (CPFs). Since cell-penetrating peptides and AMPs generally share many common features, we prepared new sequences derived from CPFs by varying the distribution of histidine- and arginine-type residues at the surface of the oligourea helix, and evaluated their activity on both Gram-positive and Gram-negative bacteria as well as on fungi. In addition, we prepared and tested new amphiphilic block cofoldamers consisting of an oligourea and a peptide segment whereby polar and charged residues are located in the peptide segment and more hydrophobic residues in the oligourea segment. Several foldamer sequences were found to display potent antibacterial activities even in the presence of 50% serum. Importantly, we show that these urea-based foldamers also possess promising antifungal properties.     

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dBcmMHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).     

Increasing Complexity: A Practical Synthetic Approach to Three-Dimensional,Cyclic Sulfoximines and First Insights into Their in Vitro Properties

A short synthetic approach with broad scope to access five- to seven-membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S-alkylation and one-pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three-dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.     

Re-Analysis of Abdominal Gland Volatilome Secretions of the African Weaver Ant,Oecophylla longinoda (Hymenoptera: Formicidae)

The African weaver ant, Oecophylla longinoda, is used as a biological control agent for the management of pests. The ant has several exocrine glands in the abdomen, including Dufour’s, poison, rectal, and sternal glands, which are associated with pheromone secretions for intra-specific communication. Previous studies have analyzed the gland secretions of Dufour’s and poison glands. The chemistry of the rectal and sternal glands is unknown. We re-analyzed the secretions from Dufour’s and poison glands plus the rectal and sternal glands to compare their chemistries and identify additional components. We used the solid-phase microextraction (SPME) technique to collect gland headspace volatiles and solvent extraction for the secretions. Coupled gas chromatography–mass spectrometry (GC-MS) analysis detected a total of 78 components, of which 62 were being reported for the first time. These additional components included 32 hydrocarbons, 12 carboxylic acids, 5 aldehydes, 3 alcohols, 2 ketones, 4 terpenes, 3 sterols, and 1 benzenoid. The chemistry of Dufour’s and poison glands showed a strong overlap and was distinct from that of the rectal and sternal glands. The different gland mixtures may contribute to the different physiological and behavioral functions in this ant species.     

Reactions of Doubly Ionized Benzene with Nitrogen and Water: A Nitrogen‐Mediated Entry into Superacid Chemistry

Even in the highly diluted gas phase, rather than electron transfer the benzene dication C₆H₆²⁺ undergoes association with dinitrogen to form a transient C₆H₆N₂²⁺ dication which is best described as a ring‐protonated phenyl diazonium ion. Isotopic labeling studies, photoionization experiments using synchrotron radiation, and quantum chemical computations fully support the formation of protonated diazonium, which is in turn a prototype species of superacidic chemistry in solution. Additionally, reactions of C₆H₆²⁺ with background water involve the transient formation of diprotonated phenol and, among other things, afford a long‐lived C₆H₆OH₂²⁺ dication, which is attributed to the hydration product of Hogeveen’s elusive pyramidal structure of C₆H₆²⁺, as the global minimum of doubly ionized benzene. Nitrogen is essential for the formation of the C₆H₆OH₂²⁺ dication in that it mediates the formation of the water adduct, while the bimolecular encounter of the C₆H₆²⁺ dication with water only leads to (dissociative) electron transfer.     

On the mechanism of the copper-mediated C-S bond formation in the intramolecular disproportionation of imine disulfides

The mechanism of the copper-mediated disproportionation of aromatic imine disulfides to benzothiazoles in the gas phase is investigated by experimental and theoretical methods. Application of infrared multiphoton dissociation and hydrogen/deuterium exchange experiments combined with density functional theory (DFT) calculations of the relevant molecular structures and the associated infrared spectra allows the identification of the observed ionic intermediates. The theoretical investigation of the possible reaction pathways supported by collision-induced dissociation experiments provides a consistent mechanistic picture of the reaction catalyzed by a single copper(I) ion. Activation of the substrate proceeds via homolytic sulfur-sulfur bond cleavage, yielding metal complexes in the formal +3 oxidation state; carbon-sulfur coupling and hydrogen-atom transfer complete the transformation to the products. Exploratory studies demonstrate that in the gas phase, the disproportionation of the imine disulfide can also be mediated by other metal ions via different either homo- or heterolytic mechanisms without involving high-valent intermediates.