Halogen, Chalcogen, Pnictogen, and Tetrel Bonding in Non-Covalent Organocatalysis: An Update.

The use of noncovalent interactions based on electrophilic halogen, chalcogen, pnictogen, or tetrel centers in organocatalysis has gained noticeable attention. Herein, we provide an overview on the most important developments in the last years with a clear focus on experimental studies and on catalysts which act via such non-transient interactions.

Elucidating the Binding Mode of Sulfur- and Selenium-Based Cationic Chalcogen-Bond Donors.

For a comparison of the interaction modes of various chalcogen-bond donors, 2-chalcogeno-imidazolium salts have been designed, synthesized, and studied by single crystal X-ray diffraction, solution NMR and DFT as well as for their ability to act as activators in an SN1-type substitution reaction. Their interaction modes in solution were elucidated based on NMR diffusion and chemical shift perturbation experiments, which were supported by DFT-calculations. Our finding is that going from lighter to the heavier chalcogens, hydrogen bonding plays a less, while chalcogen bonding an increasingly important role for the coordination of anions. Anion-π interactions also show importance, especially for the sulfur and selenium derivatives.

Structural biology of microbial gas vesicles: historical milestones and current knowledge.

Gas vesicles mediate buoyancy-based motility in aquatic bacteria and archaea and are the only protein-based structures known to enclose a gas-filled volume. Their unique physicochemical properties and ingenious architecture rank them among the most intriguing macromolecular assemblies characterised to date. This review covers the 60-year journey in quest for a high-resolution structural model of gas vesicles, first highlighting significant strides made in establishing the detailed ultrastructure of gas vesicles through transmission electron microscopy, X-ray fibre diffraction, atomic force microscopy, and NMR spectroscopy. We then survey the recent progress in cryogenic electron microscopy studies of gas vesicles, which eventually led to a comprehensive atomic model of the mature assembly. Synthesising insight from these structures, we examine possible mechanisms of gas vesicle biogenesis and growth, presenting a testable model to guide future experimental work. We conclude by discussing future directions in the structural biology of gas vesicles, particularly considering advancements in AI-driven structure prediction.

Determinants of bicycle crashes at urban signalized intersections.

PROBLEM: Bicycle volumes are increasing in many regions worldwide leading to higher relevance of an in-depth understanding of bicyclist safety mechanisms. Detailed studies on bicyclist safety that consider exposure and distinguish by intersection category and crash types are missing for urban signalized intersections, which are of particular relevance for bicyclist safety. METHOD: Based on a comprehensive dataset of motorist and bicyclist volumes and infrastructure characteristics for a sample of 269 signalized intersections in two German cities, we utilize a top-down approach to analyze firstly, bicycle crashes of all types and secondly, bicycle crashes by type including turning, right-of-way and loss-of-control. A combination of descriptive statistics and Accident Prediction Models (APM) are applied as analysis methods. RESULTS: Bicycle volumes are relevant for all types of intersections and crashes, whereas the effect of motor vehicle volumes differ between these different applications. The separation of bicyclists from motor vehicles in time and space increases their safety but also leads to behavioral adaption and risk compensation. The likelihood of right-of-way crashes even increases with more separation in the signaling scheme. The main predictor for loss-of-control crashes in terms of infrastructure are tram tracks. SUMMARY: This study provides insights on relevant determinants of bicycle crashes at urban signalized intersections at several levels of detail. Exposure variables as well as the physical separation of bicyclists from motor vehicles show consistent effects on bicycle crash numbers whereas the effects of signaling differ between crash types. PRACTICAL APPLICATIONS: The different types of intersections and crashes follow each specific mechanism of bicyclist safety. The separation of bicyclists and motorists in time and space are paramount at intersections with high bicycle volumes. Risk compensation such as red light running becomes more important as intersections get smaller and motor vehicle volumes decrease.

Long-term Results of the Treatment of Scapholunate Instability with Dynamic Extensor Carpi Radialis Brevis Tenodesis.

Scapholunate dissociation is the most common form of carpal instability. This retrospective case series aimed to assess long-term results obtained by treating scapholunate instability with dynamic tenodesis using the entire extensor carpi radialis brevis tendon, which is detached from the base of the third metacarpal, rerouted in the third extensor compartment, and fixed at the distal portion of the scaphoid to maintain reduced rotatory subluxation. Methods: Nine patients with scapholunate instability were treated. We reviewed eight patients with a mean follow-up of 12 years. One subgroup of four patients was affected by static scapholunate instability, and the other by dynamic scapholunate instability. Disability of the Arm, Shoulder, and Hand score, Patient Rated Wrist Evaluation score, modified Mayo score, and radiographs were used to determine functional and anatomical outcomes. Results: Excellent functional results did not correlate with radiological outcome in patients with static scapholunate instability. In this subgroup, scapholunate angle and gap and radiolunate angle improved in average but remained in the pathologic range. In only one of these patients, osteoarthritis was observed. In the subgroup of patients affected by dynamic instability, very good functional outcomes correlate with radiological results, except in one patient who developed arthritic changes. Conclusions: Dynamic tethering of the scaphoid with the extensor carpi radialis brevis tendon might be indicated in the treatment not only in patients affected by dynamic scapholunate instability but also in patients with static instability. Prospective studies with a larger number of patients are required to evaluate this method.

Cryo-EM structure of gas vesicles for buoyancy-controlled motility.

Gas vesicles are gas-filled nanocompartments that allow a diverse group of bacteria and archaea to control their buoyancy. The molecular basis of their properties and assembly remains unclear. Here, we report the 3.2 Å cryo-EM structure of the gas vesicle shell made from the structural protein GvpA that self-assembles into hollow helical cylinders closed off by cone-shaped tips. Two helical half shells connect through a characteristic arrangement of GvpA monomers, suggesting a mechanism of gas vesicle biogenesis. The fold of GvpA features a corrugated wall structure typical for force-bearing thin-walled cylinders. Small pores enable gas molecules to diffuse across the shell, while the exceptionally hydrophobic interior surface effectively repels water. Comparative structural analysis confirms the evolutionary conservation of gas vesicle assemblies and demonstrates molecular features of shell reinforcement by GvpC. Our findings will further research into gas vesicle biology and facilitate molecular engineering of gas vesicles for ultrasound imaging.

Chalcogen bonding in the solid-state structures of 1,3-bis(benzimidazoliumyl)benzene-based chalcogen-bonding donors.

1,3-Bis(benzimidazoliumyl)benzene-based chalcogen-bonding catalysts were previously successfully applied in different benchmark reactions. In one of those examples, i.e. the activation of quinolines, sulfur- and selenium-based chalcogen-bonding catalysts showed comparable properties, which is unexpected, as the selenium-containing catalysts should show superior catalytic properties due to the increased polarizability of selenium compared to sulfur. Herein, we present four crystal structures of the respective 1,3-bis(benzimidazoliumyl)benzene-based chalcogen-bonding catalyst containing sulfur (3S) and selenium (3Se, three forms) as Lewis acidic centres. The sulfur-containing catalyst shows weaker chalcogen bonding compared to its selenium analogue, as well as anion-π interactions. The selenium-based analogues, on the other hand, show stronger chalcogen-bonding motifs compared to the sulfur equivalent, depending on the crystallization conditions, but in every case, the intermolecular interactions are comparable in strength. Other interactions, such as hydrogen bonding and anion-π, were also observed, but in the latter case, the interaction distances are longer compared to those of the sulfur-based equivalent. The solid-state structures could not further explain the high catalytic activity of the sulfur-containing catalysts. Therefore, a comparison of their σ-hole depths from density functional theory (DFT) gas-phase calculations was performed, which are again in line with the previously found properties in the solid-state structures.

Task-synchronized eye blink modulation neither requires visual stimulation nor active motor response and is modulated by task predictability.

It has been repeatedly shown that temporal task features are reflected in eye blink dynamics during attention tasks. Eye blinks occur with increased likeliness particularly when demands on external attention allocation are low. Both predictive, top-down and reactive, bottom-up processes were shown to be involved in blink regulation. However, whether temporal stimulus prediction is a generally active component of the attention system or rather specific to the visual domain has not been fully elaborated yet. By monitoring eye blinking of 99 students during an auditory attention task and analyzing particularly the dynamics of eye blink onsets relative to stimuli timings, we show here that prediction does, in principle, not require visual stimulation, and is also not merely a consequence of the involvement of manual responses during the task. We further show that both the inclusion of manual response to stimuli and elevated task predictability enhance the prediction component reflected in eye blink dynamics, whereas for the latter we experimentally manipulate objective task predictability by adjusting the frequency dependence of the power spectral densities of the series of inter-stimulus time intervals. This allows us finally to explain why, for specific choices of experimental conditions, the generally active and present prediction component involved in attention can become difficult to detect in non-visual, auditory tasks. Conversely, this comes with the important implication that, if tasks aim for elaborating particularly temporal prediction, distributing stimuli over time such that inter-stimulus-intervals conform to a sample of Gaussian noise represents a specifically unfavorable choice.

A Potent Auto-Umpolung Ligand for Conjugative Radical Stabilization.

Carbenes with conjugatively connected redox system act as "auto-umpolung" ligands. Due to their electronic flexibility, they should also be particularly suitable to stabilize open-shell species. Herein, the first neutral radical of such sort is described in form of a dialkylamino-substituted bis(dicyanomethylene)cyclopropanide. Despite the absence of steric shielding, the radical is stable for an extended amount of time and was consequently characterized in solution via EPR measurements. These data and accompanying X-ray structural analyses indicate that the radical species is in equilibrium with aggregates (formed via π-stacking) and dimers (obtained via σ-bond formation between methylene carbons).

A Quantum-chemical Analysis on the Lewis Acidity of Diarylhalonium Ions.

Cyclic diaryliodonium compounds like iodolium derivatives have increasingly found use as noncovalent Lewis acids in the last years. They are more stable toward nucleophilic substitution than acyclic systems and are markedly more Lewis acidic. Herein, this higher Lewis acidity is analyzed and explained via quantum-chemical calculations and energy decomposition analyses. Its key origin is the change in energy levels and hybridization of iodine's orbitals, leading to both more favorable electrostatic interaction and better charge transfer. Both of the latter seem to contribute in similar fashion, while hydrogen bonding as well as steric repulsion with the phenyl rings play at best a minor role. In comparison to iodolium, bromolium and chlorolium are less Lewis acidic the lighter the halogen, which is predominantly based on less favorable charge-transfer interactions.

Wakeful resting and listening to music contrast their effects on verbal long-term memory in dependence on word concreteness.

Wakeful resting and listening to music are powerful means to modulate memory. How these activities affect memory when directly compared has not been tested so far. In two experiments, participants encoded and immediately recalled two word lists followed by either 6 min wakefully resting or 6 min listening to music. The results of Experiment 1 show that both post-encoding conditions have a similar effect on memory after 1 day. In Experiment 2, we explored the possibility that less concrete words, i.e. lower in imageability than in Experiment 1, are differently affected by the two post-encoding conditions. The results of Experiment 2 show that, when words are less concrete, more words are retained after 1 day when encoding is followed by wakeful resting rather than listening to music. These findings indicate that the effects of wakeful resting and listening to music on memory consolidation are moderated by the concreteness of the encoded material.

Catalytic Activation of Imines by Chalcogen Bond Donors in a Povarov [4+2] Cycloaddition Reaction.

Recently, chalcogen bonding has been investigated in more detail in organocatalysis and the scope of activated functionalities continues to increase. Herein, the activation of imines in a Povarov [4+2] cycloaddition reaction with bidentate cationic chalcogen bond donors is presented. Tellurium-based Lewis acids show superior properties compared to selenium-based catalysts and inactive sulfur-based analogues. The catalytic activity of the chalcogen bonding donors increases with weaker binding anions. Triflate, however, is not suitable due to its participation in the catalytic pathway. A solvent screening revealed a more efficient activation in less polar solvents and a pronounced effect of solvent (and catalyst) on endo : exo diastereomeric ratio. Finally, new chiral chalcogen bonding catalysts were applied but provided only racemic mixtures of the product.

Nanofluidic chips for cryo-EM structure determination from picoliter sample volumes.

Cryogenic electron microscopy has become an essential tool for structure determination of biological macromolecules. In practice, the difficulty to reliably prepare samples with uniform ice thickness still represents a barrier for routine high-resolution imaging and limits the current throughput of the technique. We show that a nanofluidic sample support with well-defined geometry can be used to prepare cryo-EM specimens with reproducible ice thickness from picoliter sample volumes. The sample solution is contained in electron-transparent nanochannels that provide uniform thickness gradients without further optimisation and eliminate the potentially destructive air-water interface. We demonstrate the possibility to perform high-resolution structure determination with three standard protein specimens. Nanofabricated sample supports bear potential to automate the cryo-EM workflow, and to explore new frontiers for cryo-EM applications such as time-resolved imaging and high-throughput screening.

Chalcogen vs Halogen Bonding Catalysis in a Water-Bridge-Cocatalyzed Nitro-Michael Reaction.

Recently, a tellurium-based chalcogen-bond-catalyzed nitro-Michael reaction was reported ( Angew. Chem. Int. Ed. 2019, 58, 16923), taking advantage of the strong Lewis acidity of the catalyst. This species was found to be more effective than an analogous iodine-based halogen bond organocatalyst. Herein, we present a detailed mechanistic and kinetic analysis of these catalytic cycles including the influence of the solvent (and the performance of different intrinsic solvation models). While the chalcogen bonding interaction is fundamental to activate the C-C bond formation, we found that the presence of a two-water molecular bridge is critical to allow the following, otherwise high-energy proton transfer step. Even though the iodine-based halogen bonding interaction is stronger than the tellurium-based chalcogen bonding one, which makes the former a stronger Lewis acid and hence in principle a more efficient catalyst, solvation effects explain the smaller energy span of the latter.

Patterns of eye blinks are modulated by auditory input in humans.

Previous studies could elaborate a link between attentional processes and eye blinking in both visual and auditory attention tasks. Here we show that this link is active at a fundamental level of perception: presentation of a series of bare sine tones is sufficient to induce a modulation of temporal blink patterns, allowing to determine which series was presented to participants even when they are not required to interactively engage in processing the auditory input. In particular, we monitored eye blinking during an auditory attention task using two series of sine tones, differing in the predictability of the timing of tone onsets. Whereas inter-onset intervals in one tone series corresponded to uncorrelated samples from a normal distribution, they were distributed according to a Gaussian random walk in the other tone series. We find that blink patterns are dynamically modulated by both purely auditory inputs. The magnitude, form, and coherence of the temporal associations between tone onsets and blink events depend strongly on the requirement to respond to the presented stimuli. The predictability of the tone series appears to modulate pre-stimulus blink inhibition given that a response is required. Altogether, these findings suggest eye blink as a readily available, non-invasive behavioral marker for context-sensitive, moment-to-moment allocation of attention.

Synthesis, Crystal and Electronic Structures of a Thiophosphinoyl- and Amino-Substituted Metallated Ylide.

Invited for this month's cover is the group of Viktoria H. Gessner at the Ruhr-University in Bochum (Germany). The cover shows the structure of the newly reported, isolated metallated ylide. Due to the high negative charge at the ylidic carbon center this compound is "on fire", but can be stabilized by smart molecular design. Structure analyses of the different alkali metal complexes combined with computational studies provide insights into the electronic structure of the compounds Read the full text of their Communication at 10.1002/open.202100178.

Synthesis, Crystal and Electronic Structures of a Thiophosphinoyl- and Amino-Substituted Metallated Ylide.

α-Metallated ylides have revealed themselves to be versatile reagents for the introduction of ylide groups. Herein, we report the synthesis of the thiophosphinoyl and piperidyl (Pip) substituted α-metallated ylide [Ph2 (Pip)P=C-P(S)Ph2 ]M (M=Li, Na, K) through a four-step synthetic procedure starting from diphenylmethylphosphine sulfide. Metallation of the ylide intermediate was successfully accomplished with different alkali metal bases delivering the lithium, sodium and potassium salts, the latter isolable in high yields. Structure analyses of the lithium and potassium compounds in the solid state with and without crown ether revealed different aggregates (monomer, dimer and hexamer) with the metals coordinated by the thiophosphoryl moiety and ylidic carbon atom. Although the piperidyl group does not coordinate to the metal, it significantly contributes to the stability of the yldiide by charge delocalization through negative hyperconjugation.

"Anti-electrostatic" Halogen Bonding between Ions of Like Charge.

Halogen bonding occurs between molecules featuring Lewis acidic halogen substituents and Lewis bases. It is often rationalized as a predominantly electrostatic interaction and thus interactions between ions of like charge (e. g., of anionic halogen bond donors with halides) seem counter-intuitive. Herein, we provide an overview on such complexes. First, theoretical studies are described and their findings are compared. Next, experimental evidences are presented in the form of crystal structure database analyses, recent examples of strong "anti-electrostatic" halogen bonding in crystals, and the observation of such interactions also in solution. We then compare these complexes to select examples of "counter-intuitive" adducts formed by other interactions, like hydrogen bonding. Finally, we comment on key differences between charge-transfer and electrostatic polarization.