Revisiting the bromination of 3ß-hydroxycholest-5-ene with CBr4/PPh3 and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior.

Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3ß-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3ß-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were revealed by X-ray single crystal structure analyses, and the NMR data are in agreement to the reported ones. In light of these findings, we herein correct the previous stereochemical assignments reported by one of us in the Beilstein J. Org. Chem. 2015, 11, 1922-1932 and the Monatsh. Chem. 2018, 149, 505-517.

Reshuffle Bonds by Ball Milling: A Mechanochemical Protocol for Charge-Accelerated Aza-Claisen Rearrangements.

This study presents the development of a mechanochemical protocol for a charge-accelerated aza-Claisen rearrangement. The protocol waives the use of commonly applied transition metals, ligands, or pyrophoric Lewis acids, e.g., AlMe3. Based on (heterocyclic) tertiary allylamines and acyl chlorides, the desired tertiary amides were prepared in yields ranging from 17% to 84%. Moreover, the same protocol was applied for a Bellus-Claisen-type rearrangement resulting in the synthesis of a 9-membered lactam without further optimization.

Electro-mechanochemical approach towards the chloro sulfoximidations of allenes under solvent-free conditions in a ball mill.

An electro-mechanochemical protocol for the synthesis of vinylic sulfoximines has been developed. Utilising mechanochemically strained BaTiO3 nanoparticles, the catalytic active system is generated in situ by the reduction of copper(II) chloride. Various combinations of electron-donating and -withdrawing groups are tolerated, and the approach leads to products with difunctionalised double bonds in good to excellent yields. Attempts to add a sulfoximidoyl chloride to an alkyne proved difficult. Additions of a sulfonyl iodide to allenes and alkynes proceeded smoothly in the presence of silica gel without the need for activation by a piezoelectric material.

Disentangling the Effect of Pressure and Mixing on a Mechanochemical Bromination Reaction by Solid-State NMR Spectroscopy.

Mechanical forces, including compressive stresses, have a significant impact on chemical reactions. Besides the preparative opportunities, mechanochemical conditions benefit from the absence of any organic solvent, the possibility of a significant synthetic acceleration and unique reaction pathways. Together with an accurate characterization of ball-milling products, the development of a deeper mechanistic understanding of the occurring transformations at a molecular level is critical for fully grasping the potential of organic mechanosynthesis. We herein studied a bromination of a cyclic sulfoximine in a mixer mill and used solid-state nuclear magnetic resonance (NMR) spectroscopy for structural characterization of the reaction products. Magic-angle spinning (MAS) was applied for elucidating the product mixtures taken from the milling jar without introducing any further post-processing on the sample. Ex situ 13 C-detected NMR spectra of ball-milling products showed the formation of a crystalline solid phase with the regioselective bromination of the S-aryl group of the heterocycle in position 4. Completion is reached in less than 30 minutes as deduced from the NMR spectra. The bromination can also be achieved by magnetic stirring, but then, a longer reaction time is required. Mixing the solid educts in the NMR rotor allows to get in situ insights into the reaction and enables the detection of a reaction intermediate. The pressure alone induced in the rotor by MAS is not sufficient to lead to full conversion and the reaction occurs on slower time scales than in the ball mill, which is crucial for analysing mixtures taken from the milling jar by solid-state NMR. Our data suggest that on top of centrifugal forces, an efficient mixing of the starting materials is required for reaching a complete reaction.

The Mechanochemical Synthesis and Activation of Carbon-Rich π-Conjugated Materials.

Mechanochemistry uses mechanical force to break, form, and manipulate chemical bonds to achieve functional transformations and syntheses. Over the last years, many innovative applications of mechanochemistry have been developed. Specifically for the synthesis and activation of carbon-rich π-conjugated materials, mechanochemistry offers reaction pathways that either are inaccessible with other stimuli, such as light and heat, or improve reaction yields, energy consumption, and substrate scope. Therefore, this review summarizes the recent advances in this research field combining the viewpoints of polymer and trituration mechanochemistry. The highlighted mechanochemical transformations include π-conjugated materials as optical force probes, the force-induced release of small dye molecules, and the mechanochemical synthesis of polyacetylene, carbon allotropes, and other π-conjugated materials.

Mechanochemical Syntheses of N-Containing Heterocycles with TosMIC.

A mechanochemical van Leusen pyrrole synthesis with a base leads to 3,4-disubstitued pyrroles in moderate to excellent yields. The developed protocol is compatible with a range of electron-withdrawing groups and can also be applied to the synthesis of oxazoles. Attempts to mechanochemically convert the resulting pyrroles into porphyrins proved to be difficult.

Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A-F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation.

Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt-catalyzed hydrovinylation as the chirogenic step. Other noteworthy C-C bond forming transformations include diastereoselective Lewis acid-mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4-methyl-styrene the anti-tubercular agent (+)-erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti-inflammatory activity (inhibition of LPS-induced NF-κB activation) as a natural mixture of pseudopterosins A-D or iso-pseudopterosin A, prepared by ß-D-xylosylation of the synthetic aglycone.

Perceived social support and discrimination and oral health behaviors in adolescents.

OBJECTIVES: The aims of this study were to examine the associations between perceived social support and oral health behaviors among adolescents and if this perception had a protective effect against the influence of perceived racial discrimination on oral health behaviors in this population. MATERIAL AND METHODS: Participants of this cross-sectional study were adolescents aged 12-18 years recruited from University dental clinic. They completed a questionnaire comprising three sections: demographics (14 items), oral health behaviors (6 items), and validated Personal Resource Questionnaire (25 items). Perceived discrimination was evaluated by a question asking if the adolescent had ever experienced discrimination based on their race. RESULTS: Of 252 participants, mean (SD) age of 14 (1.8) years, 60% were girls, 56% were self-identified as White, and 81% were born in Canada. Discrimination was reported by 21%. Frequency of toothbrushing and self-rated oral health were significantly associated with increased levels of perceived social support. Sugar consumption was significantly different for participants with and without perceived racial discrimination (p-value = 0.002). Perceived social support did not act as a buffer against perceived racial discrimination for sugar consumption (OR = 1.00; 95% CI: 0.98-1.01). CONCLUSIONS: Adolescents' perceived social support affected some aspects of their oral health but did not moderate the influence of perceived racial discrimination.

Electro-Mechanochemical Atom Transfer Radical Cyclizations using Piezoelectric BaTiO3.

The formation and regeneration of active CuI species is a fundamental mechanistic step in copper-catalyzed atom transfer radical cyclizations (ATRC). Typically, the presence of the catalytically active CuI species in the reaction mixture is secured by using high CuI catalyst loadings or the addition of complementary reducing agents. In this study it is demonstrated how the piezoelectric properties of barium titanate (BaTiO3 ) can be harnessed by mechanical ball milling to induce electrical polarization in the strained piezomaterial. This strategy enables the conversion of mechanical energy into electrical energy, leading to the reduction of a CuII precatalyst into the active CuI species in copper-catalyzed mechanochemical solvent-free ATRC reactions.

Biarticular muscles are most responsive to upper-body pitch perturbations in human standing.

Balancing the upper body is pivotal for upright and efficient gait. While models have identified potentially useful characteristics of biarticular thigh muscles for postural control of the upper body, experimental evidence for their specific role is lacking. Based on theoretical findings, we hypothesised that biarticular muscle activity would increase strongly in response to upper-body perturbations. To test this hypothesis, we used a novel Angular Momentum Perturbator (AMP) that, in contrast to existing methods, perturbs the upper-body posture with only minimal effect on Centre of Mass (CoM) excursions. The impulse-like AMP torques applied to the trunk of subjects resulted in upper-body pitch deflections of up to 17° with only small CoM excursions below 2 cm. Biarticular thigh muscles (biceps femoris long head and rectus femoris) showed the strongest increase in muscular activity (mid- and long-latency reflexes, starting 100 ms after perturbation onset) of all eight measured leg muscles which highlights the importance of biarticular muscles for restoring upper-body balance. These insights could be used for improving technological aids like rehabilitation or assistive devices, and the effectiveness of physical training for fall prevention e.g. for elderly people.

The nanoGRAVUR framework to group (nano)materials for their occupational, consumer, environmental risks based on a harmonized set of material properties, applied to 34 case studies.

The project nanoGRAVUR (BMBF, 2015-2018) developed a framework for grouping of nanomaterials. Different groups may result for each of the three distinct perspectives of occupational, consumer and environmental safety. The properties, methods and descriptors are harmonised between the three perspectives and are based on: Tier 1 intrinsic physico-chemical properties (what they are) or GHS classification of the non-nano-form (human tox, ecotox, physical hazards); Tier 2 extrinsic physico-chemical properties, release from nano-enabled products, in vitro assays with cells (where they go; what they do); Tier 3 case-specific tests, potentially in vivo studies to substantiate the similarity within groups or application-specific exposure testing. Amongst all properties, dissolution and transformation are least modulated by different nanoforms within one substance, whereas dustiness, dispersion stability, abiotic and especially in vitro surface reactivity vary more often between different nanoforms. The methods developed or selected by nanoGRAVUR fill several gaps highlighted in the ProSafe reviews, and are useful to implement (i) the concept of nanoforms of the European Chemicals Agency (ECHA) and (ii) the concept of discrete forms of the United States Environmental Protection Agency (EPA). One cannot assess the significance of a dissimilarity, if the dynamic range of that property is unknown. Benchmark materials span dynamic ranges that enable us to establish bands, often with order-of-magnitude ranges. In 34 case studies we observed high biological similarity within each substance when we compared different (nano)forms of SiO2, BaSO4, kaolin, CeO2, ZnO, organic pigments, especially when we compared forms that are all untreated on the surface. In contrast, different Fe2O3 or TiO2 (nano)forms differ more significantly. The same nanoforms were also integrated in nano-enabled products (NEPs) for automotive coatings, clinker-reduced cements, cosmetic sunscreen, and lightweight polymers.

Cyanomethyl anion transfer reagents for diastereoselective Corey-Chaykovsky cyclopropanation reactions.

A readily available and bench-stable cyanomethyl sulfonium salt was used in highly diastereoselective Corey-Chaykovsky cyclopropanation reactions of electron-poor olefins. This efficient method provides a rapid route to access densely functionalized cyclopropyl nitriles.

Mechanochemical dehydrocoupling of dimethylamine borane and hydrogenation reactions using Wilkinson's catalyst.

Mechanochemistry enabled the selective synthesis of the recherché orange polymorph of Wilkinson's catalyst [RhCl(PPh3)3]. The mechanochemically prepared Rh-complex catalysed the solvent-free dehydrogenation of Me2NH·BH3 in a ball mill. The in situ-generated hydrogen (H2) could be utilised for Rh-catalysed hydrogenation reactions by ball milling.

Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario for the Synthesis of α-Amino Acid Derivatives.

Mechanochemical activation of iron cyano complexes by ball milling results in the formation of HCN, which can be trapped and incorporated into α-aminonitriles. This prebiotic impact scenario can be extended by mechanochemically transforming the resulting α-aminonitriles into α-amino amides using a chemical route related to early Earth conditions.

Sensor-Motor Maps for Describing Linear Reflex Composition in Hopping.

In human and animal motor control several sensory organs contribute to a network of sensory pathways modulating the motion depending on the task and the phase of execution to generate daily motor tasks such as locomotion. To better understand the individual and joint contribution of reflex pathways in locomotor tasks, we developed a neuromuscular model that describes hopping movements. In this model, we consider the influence of proprioceptive length (LFB), velocity (VFB) and force feedback (FFB) pathways of a leg extensor muscle on hopping stability, performance and efficiency (metabolic effort). Therefore, we explore the space describing the blending of the monosynaptic reflex pathway gains. We call this reflex parameter space a sensor-motor map. The sensor-motor maps are used to visualize the functional contribution of sensory pathways in multisensory integration. We further evaluate the robustness of these sensor-motor maps to changes in tendon elasticity, body mass, segment length and ground compliance. The model predicted that different reflex pathway compositions selectively optimize specific hopping characteristics (e.g., performance and efficiency). Both FFB and LFB were pathways that enable hopping. FFB resulted in the largest hopping heights, LFB enhanced hopping efficiency and VFB had the ability to disable hopping. For the tested case, the topology of the sensor-motor maps as well as the location of functionally optimal compositions were invariant to changes in system designs (tendon elasticity, body mass, segment length) or environmental parameters (ground compliance). Our results indicate that different feedback pathway compositions may serve different functional roles. The topology of the sensor-motor map was predicted to be robust against changes in the mechanical system design indicating that the reflex system can use different morphological designs, which does not apply for most robotic systems (for which the control often follows a specific design). Consequently, variations in body mechanics are permitted with consistent compositions of sensory feedback pathways. Given the variability in human body morphology, such variations are highly relevant for human motor control.

Synthesis and biological evaluation of novel teixobactin analogues.

The cyclic depsipeptide, teixobactin, possesses promising activity against a range of antimicrobial-resistant (AMR) pathogenic bacteria, including Staphylococcus aureus and Mycobacterium tuberculosis. Teixobactin contains a number of non-canonical residues, including the synthetically challenging amino acid, l-allo-enduracididine, complicating clinical application of this peptide. Herein, we report the synthesis of six analogues of teixobactin, in which the non-canonical l-allo-enduracididine amino acid is replaced by isosteric, commercially available Fmoc-amino acid building blocks. Biological evaluation of the analogues has revealed promising activity, particularly for guanidine isosteres, against AMR strains of S. aureus and Enterococcus faecalis, highlighting the potential for this class of cyclic depsipeptides in the treatment of Gram-positive infections.

Thermoelectric power factor of ternary single-crystalline Sb2Te3- and Bi2Te3-based nanowires.

Nanowires of bismuth antimony telluride and bismuth telluride selenide (Bi15Sb29Te56 and Bi38Te55Se7) were grown by template-based pulsed electrodeposition. The composition and the crystallinity of the nanowires were determined by high-resolution transmission electron microscopy. The thermoelectric properties (Seebeck coefficient and electrical conductivity) of single p- and n-type nanowires, with diameter 80 nm and 200 nm, respectively, were determined as a function of temperature before and during heating in a helium atmosphere up to 300 K along the growth direction of the nanowires. After additional annealing in a tellurium atmosphere at 525 K, significantly enhanced transport properties are observed. Bulk-like power factors are achieved. In Bi38Te55Se7 nanowires, the Seebeck coefficients increase to -115 µV K(-1) and the thermoelectric power factors increase to 2820 µW K(-2) m(-1) at room temperature. In Bi15Sb29Te56 nanowires, Seebeck coefficients of up to S = +156 µV K(-1) and power factors of up to 1750 µW K(-2) m(-1) are obtained at room temperature.

Young-onset Parkinson's disease: hospital utilization and medical comorbidity in a nationwide survey.

BACKGROUND/AIMS: 10% of Parkinson's disease (PD) patients have young-onset PD (YOPD). We compared YOPD patients to control patients in terms of hospital utilization and outcomes and medical comorbidities during hospitalization. METHODS: The Nationwide Inpatient Sample (NIS) provides yearly data on hospital admissions and discharges from approximately 1,000 hospitals. NIS data sets (1998-2003) were used to identify persons aged 18-40 years, including 714 PD patients and 2,007 randomly selected control patients (1:3 matching). RESULTS: Hospital length of stay (p < 0.001) and number of discharge diagnoses (p < 0.001) were higher in PD patients than controls. PD patients were more likely than controls to be discharged to a short-term hospital (odds ratio, OR, 2.23, 95% confidence interval, CI, 1.30-3.84, p = 0.004) or a skilled nursing facility (OR 4.14, 95% CI 3.06-5.61, p < 0.001); 20.4% required transfer to a short-term hospital or another facility. The most common discharge Diagnosis-Related Group code in PD patients was psychosis (23% of patients) whereas pneumonia and hip or pelvic fractures were not associated with PD. CONCLUSIONS: YOPD patients had greater healthcare utilization and hospital morbidity than controls. Upon discharge, 1 in 5 required transfer to a short-term hospital or another facility. Psychosis was the most common comorbidity whereas several comorbidities associated with older PD patients were not common.

Generation of atomistic models of periodic mesoporous silica by kinetic Monte Carlo simulation of the synthesis of the material.

We have developed a molecular simulation method for the generation of realistic atomic-level models for periodic mesoporous silicas. Using simplified interaction potentials and simplified representations of the templating micelles, the simulation follows the reaction path of the hydrothermal synthesis and calcination of the silica material in a kinetic Monte Carlo (kMC) simulation. The only input to the simulation is the geometry of the micelle and the number of silicic acid monomers at the beginning of the synthesis. We simulated the adsorption properties of the PMS models using Grand Canonical Monte Carlo simulation. With use of MCM-41 materials of different pore sizes as a prototype material, experimental and simulated adsorption isotherms for nitrogen, ethane, and carbon dioxide were compared, showing good agreement between simulation and experiment.

Packing of adsorbed molecules in microporous polymorphs aluminium methylphosphonates alpha and beta.

The adsorption of N2 and CO2 in the microporous aluminium methylphosphonate polymorphs alpha and beta is investigated by adsorption experiments in combination with Monte Carlo (MC) simulations. We find that close steric matching of N2 and polymorph alpha causes a packing transition not observed for the other pairs of adsorbate and adsorbent. This strong effect on adsorption behaviour of small differences in the adsorbent structure and adsorbent-adsorbate interactions suggests that microporous, hybrid inorganic organic materials of this type offer opportunities for highly selective adsorptive separations. The realism of the MC simulations is extraordinarily dependent upon the molecular size parameters used.