Gas Antisolvent Fractionation: a New Method to Obtain Enantiopure Compounds, a Case Study on Mandelic Acid

Micronization processes involving supercritical carbon dioxide are rapid methods to produce fine particles. They also might offer the possibility of using less organic solvent than conventional crystallization methods leading to an environmentally friendlier processing. The separation capabilities of such processes are now demonstrated on the diastereomeric resolution of mandelic acid using (R)-1-phenylethanamine as a resolving agent, utilizing the batch type gas antisolvent fractionation as the separation method. A detailed study was conducted on the effects of the operational parameters pressure (12-20 MPa), temperature (35-55 °C) and co-solvent concentration (33-99 mg/ml). At 12 MPa, 35 °C and 99 mg/ml methanol concentration, a selectivity of 0.52 and a diastereomeric excess of 62% was reached. The same operational parameters were applied during the investigation of the recrystallization-based further purification of the diastereomeric salts, applying the resolving agent in molar equivalent quantity to a non-racemic mixture of mandelic acid. It has been found that the more stable (R)-1-phenylethylammonium-(R)-mandelate salt can be purified to de>98% through four additional recrystallization steps following the initial, half-molar equivalent resolution step

Gas Antisolvent Fractionation: A New Approach for the Optical Resolution of 4-chloromandelic Acid

A new, rapid optical resolution method of 4-chloromandelic acid is presented using (R)-1-phenylethanamine as the resolving agent. Gas antisolvent fractionation was investigated as the separation method, studying the effect of pressure, temperature and carbon dioxide to organic solvent mass ratio in details. Generally, the method offers green operation using supercritical carbon dioxide as the precipitative agent, and can be less time- and organic solvent-intensive than conventional processes. By upscaling, the possibility of controlling the crystal-morphology might also be improved. At 16 MPa, 40 °C and 7.5 carbon dioxide to methanol ratio 72 % enantiomeric excess was reached in the crystalline product, along a 73 % yield. The resolution efficiency was not affected by any of the operational parameters. Enantiomeric enrichment beyond 90 % can be carried out by repeated resolution of a scalemic mixture of the acid. Solid products were investigated using differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy confirming the formation of a crystalline (R)-1-phenylethanammonium-4-chloromandelate salt

Mode Combinability: Exploring Convex Combinations of Permutation Aligned Models

We explore element-wise convex combinations of two permutation-aligned neural network parameter vectors $\Theta_A$ and $\Theta_B$ of size $d$. We conduct extensive experiments by examining various distributions of such model combinations parametrized by elements of the hypercube $[0,1]^{d}$ and its vicinity. Our findings reveal that broad regions of the hypercube form surfaces of low loss values, indicating that the notion of linear mode connectivity extends to a more general phenomenon which we call mode combinability. We also make several novel observations regarding linear mode connectivity and model re-basin. We demonstrate a transitivity property: two models re-based to a common third model are also linear mode connected, and a robustness property: even with significant perturbations of the neuron matchings the resulting combinations continue to form a working model. Moreover, we analyze the functional and weight similarity of model combinations and show that such combinations are non-vacuous in the sense that there are significant functional differences between the resulting models

Efficacy of Coronavirus Disease (COVID-19) Safety Protocol at the 2021 Wrestling European Olympic Games Qualifier Organized in Budapest = A koronavírus-járvány (COVID-19) biztonsági protokolljának hatékonysága a 2021-es olimpiai játékok európai kvalifikációs birkózóversenyén, Budapesten

Bevezetés és cél: A COVID-19 világjárvány számos nehézséget okoz a többnapos nemzetközi sportesemények szervezésében. Ennek oka - részben - a sportolók közötti szoros fizikai kapcsolat, amely köztudottan elősegíti a vírus terjedését, még az egyéni sportágakban, például a birkózásban is. Ezért a birkózóselejtezőn rendkívül fontos volt a betegség szűrésének bevezetése, és a fertőzött résztvevők kizárása (majd elkülönítése). Az orvosi csapat és a COVID-marsallok együtt dolgoztak egy szűrési protokoll kidolgozásán, és céljuk volt, hogy a verseny során teszteljék annak hatékonyságát. Anyag és módszerek: A versenyen 37 ország 281 versenyzője vett részt. A Magyarországra való belépés kritériuma a polimeráz láncreakció (PCR) negatív tesztje, járványügyi és tüneti negativitás volt 72 órán belül. Antigén gyorsteszteket (ART) és szükség esetén újratesztelést is végeztünk. Kiutazáskor negatív PCR-teszt, vagy a karanténidőszak lejárta után kiállított igazolás volt szükséges. Eredmények: Összesen 1287 PCR-tesztet és 1250 gyorstesztet végeztünk. Érkezéskor 21 PCR-pozitív (1,4%) személy volt, akiket karanténba helyeztek. Az induláskor 6 PCR-teszt volt pozitív (0,47%). Az akkreditációkor elvégzett ART tesztek közül egy volt pozitív. Következtetés: Az egészségügyi személyzet sikeres protokollt dolgozott ki a COVID-19 szűrésére és a résztvevők izolálására, amit az induláskor tapasztalt nagyon alacsony pozitivitás is jelez. Így ez a protokoll alkalmazható többnapos nemzetközi sportesemények szervezésénél. Introduction and Aim: The pandemic Covid-19 imposes several difficulties to organize multi-day international sports events. This is - in part - due to the close physical contact among the athletes, known to promote the spread of virus, even in individual sports, such as wrestling. Thus, at the Wrestling Qualifier it was of utmost importance to introduce screening for the disease and exclude infected participants (and then isolate them). The medical team and the COVID Marshals worked together on developing a screening protocol and aimed to test the efficacy during this competition. Material and Methods: The event was attended by 281 competitors from 37 countries. The criteria to enter Hungary were a negative polymerase chain reaction (PCR) test, epidemiological and symptomatic negativity within 72 hours. We also performed Antigen rapid tests (ART, chromatographic immunoassay) and retesting if necessary. Upon departure a negative PCR test or a certificate issued after the end of the quarantine period was required. Results: In total, 1,287 PCR tests and 1,250 rapid tests were performed. At arrival, there were 21 PCR positive (1.4%) individuals, and they were quarantined. At the departure 6 PCR tests were positive (0.47%). One of the ARTs performed at the accreditation was positive. Conclusion: The medical staff has developed a successful protocol to screen for Covid-19 and isolate participants as indicated by the very low positivity for Covid-19 at departure. Thus such protocol can be used for organizing multi-day international sports events

Supercritical carbon dioxide assisted synthesis of ultra-stable sulfur/carbon composite cathodes for Li– S batteries

To mitigate the shuttle effect and enhance the electrical conductivity in lithium battery cathode, the unique characteristics of supercritical CO2 solvent (SC–CO2) and the distinctive porous and layered microstructure of reduced graphene oxide (rGO) are exploited in the fabrication of a high-performance rGO/sulfur composite cathode. Exploiting SC-CO2 technology can realize highly efficient sulfur transfer and precise microstructure regulation of S/C composite cathodes for Li–S batteries. On exposure, due to the sudden pressure release process, the SC-CO2 expands the interlayers of rGO rendering plenty of storage space for small sulfur allotropes in carbon matrices which increases the active sulfur loading. Being a remarkable hydrophobic solvent, the wetting properties of SC-CO2 are excellent, ensuring sulfur dissolution and penetration deep into the voids and interlayers of rGO. This creates intimate contact of sulfur with rGO interlayers, guaranteeing precise sulfur content, uniform sulfur distribution, and strong interaction between sulfur and carbon leading to enhanced electrical conductivity and sulfur utilization efficiency. Another important feature is that the S/C composites can be prepared at room temperature, unlike other conventional techniques which require a higher temperature. Moreover, the product mixture can be separated simply by de-pressuring SC-CO2. Herein, the rGO/sulfur composite cathode prepared on a lab scale showed an initial discharge capacity of 1024 mAh/g at 0.1C rate with capacity retention of 92.2% and coulombic efficiency of 99% even after 200 charge-discharge cycles. The developed cells showed excellent performance (929 mAh/g at 1 C rate) with an ultralow decay of 0.04% per cycle even after 200 charge-discharge cycles. Through this work, we believe that the synergistic effect of SC-CO2 technology and rGO as sulfur host will open up a promising future for the synthesis of efficient S/C composite cathodes with ultra-high cycling stability

The role of detours in individual human navigation patterns of complex networks

Despite their importance for public transportation, communication within organizations or the general understanding of organized knowledge, our understanding of how human individuals navigate in complex networked systems is still limited owing to the lack of datasets recording sufficient amount of navigation paths of individual humans. Here, we analyze 10587 paths recorded from 259 human subjects when navigating between nodes of a complex word-morph network. We find the clear presence of systematic detours organized around individual hierarchical scaffolds guiding navigation. Our dataset is the first enabling the visualization and analysis of scaffold hierarchies whose presence and role in supporting human navigation is assumed in existing navigational models. By using an information-theoretic argumentation, we argue that taking short detours following the hierarchical scaffolds is a clear sign of human subjects simplifying the interpretation of the complex networked system by an order of magnitude. We also discuss the role of these scaffolds in the phases of learning to navigate a network from scratch

Experimental Determination of a Chiral Ternary Solubility Diagram and Its Interpretation in Gas Antisolvent Fractionation

Although crystallization has been widely applied for the enantiomeric enrichment of non-racemates both in research and in industrial applications, the physical–chemical background of chiral crystallizations is not as frequently discussed. A guide for the experimental determination of such phase equilibrium information is lacking. In the current paper, the experimental investigation of chiral melting phase equilibria, chiral solubility phase diagrams and their application in atmospheric and supercritical carbon dioxide-assisted enantiomeric enrichment is described and compared. Benzylammonium mandelate is a racemic compound; it shows eutectic behavior when molten. A similar eutonic composition was observed in its methanol phase diagram at 1 °C. The influence of the ternary solubility plot could be unequivocally discovered in atmospheric recrystallization experiments, which proved that the crystalline solid phase and the liquid phase were in an equilibrium. The interpretation of the results obtained at 20 MPa and 40 °C, using the methanol–carbon dioxide mixture as a pseudo-component, was more challenging. Although the eutonic composition was found to be the limiting enantiomeric excess value in this purification process as well, the high-pressure gas antisolvent fractionation results were only clearly thermodynamically controlled in certain concentration ranges

A new, automated method for the investigation of melting point depression under carbon dioxide pressure

The aim of this work was to develop a new, automated method for the detection of solid-liquid phase transitions in the presence of high-pressure carbon dioxide. This is allowed because of the dissolution of the medium in the sample during the solid-liquid-gas equilibrium measurement. The pressure of an empty reference cell and one containing a solid sample is compared by a differential pressure transmitter. A gradual heating program is conducted after their equal pressurization. The solid-liquid transition of the sample is marked by a sharp decrease in the pressure of the sample holder (compared to the reference cell). A processing algorithm for the recorded time – temperature – pressure-difference data was implemented, to determine the melting temperature range accurately and automatically. The apparatus was validated with racemic ibuprofen and benzoic acid, and provides a new, objective, and easy-to-automate alternative to determine the melting temperature in high-pressure carbon dioxide