Green and Enantioselective Synthesis via Cascade Biotransformations: From Simple Racemic Substrates to High-Value Chiral Chemicals.

Asymmetric synthesis of chiral chemicals in high enantiomeric excess (ee) is pivotal to the pharmaceutical industry, but classic chemistry usually requires multi-step reactions, harsh conditions, and expensive chiral ligands, and sometimes suffers from unsatisfactory enantioselectivity. Enzymatic catalysis is a much greener and more enantioselective alternative, and cascade biotransformations with multi-step reactions can be performed in one pot to avoid costly intermediate isolation and minimise waste generation. One of the most attractive applications of enzymatic cascade transformations is to convert easily available simple racemic substrates into valuable functionalised chiral chemicals in high yields and ee. Here, we review the three general strategies to build up such cascade biotransformations, including enantioconvergent reaction, dynamic kinetic resolution, and destruction-and-reinstallation of chirality. Examples of cascade transformations using racemic substrates such as racemic epoxides, alcohols, hydroxy acids, etc. to produce the chiral amino alcohols, hydroxy acids, amines and amino acids are given. The product concentration, ee, and yield, scalability, and substrate scope of these enzymatic cascades are critically reviewed. To further improve the efficiency and practical applicability of the cascades, enzyme engineering to enhance catalytic activities of the key enzymes using the latest microfluidics-based ultrahigh-throughput screening and artificial intelligence-guided directed evolution could be useful approaches.

Asymmetric Paired Electrolysis: Enantioselective Alkylation of Sulfonylimines via C(sp3)-H Functionalization.

Enantioselective transformation of ubiquitous C(sp3)-H bonds into three-dimensional chiral scaffolds is of longstanding interest to synthetic chemists. Herein, an asymmetric paired electrolysis enables a highly efficient and sustainable approach to the enantioselective alkylation of sulfonylimines via C(sp3)-H functionalization. In this protocol, anodic oxidation for benzylic radical formation and Lewis acid-catalyzed sulfonylimine reduction on the cathode were seamlessly cross-coupled (up to 88% yield). Enantioenriched chiral amines containing a tetrasubstituted carbon stereocenter are accessed with high enantioselectivity (up to 96% ee). Mechanistic studies suggest that the amine generated in situ could serve as a base to deprotonate phenols and decrease the oxidation potential of the reaction, allowing phenols with lower potentials to be preferentially oxidized.

Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO2 for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes.

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

Symmetric Anion Mediated Dynamic Kinetic Asymmetric Knoevenagel Reaction for N-C and N-N Atropisomers Synthesis.

A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N-C and N-N atropisomers. The resulting highly enantio-pure pyridine-2,6(1H,3H)-diones exhibit diverse structures and functional groups. The key to excellent regio- and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst. This connected the enolate anion and iminium cation by a chiral backbone. The mechanism investigation via control experiments, correlation analysis, and density functional theory calculations further revealed how the stereochemical information was transferred from the catalyst into the axially chiral pyridine-2,6(1H,3H)-diones. The synthetic applications also demonstrated the reaction's potential.

Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C-H bond activation.

The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report an asymmetric three-component alkene dicarbofunctionalization capitalizing on the direct activation of C(sp 3)-H bonds through the combination of photocatalysed hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for installing two vicinal carbon-carbon bonds across alkenes in an atom-economic fashion, providing a wide array of high-value chiral α-aryl/alkenyl carbonyls and phosphonates, as well as 1,1-diarylalkanes from ubiquitous alkane, ether and alcohol feedstocks. This method exhibits operational simplicity, broad substrate scope and excellent regioselectivity, chemoselectivity and enantioselectivity. The compatibility with bioactive motifs and expedient synthesis of pharmaceutically relevant molecules highlight the synthetic potential of this protocol.

Characteristics of deformation and damage of surrounding rock along the top roadway in the working face of an isolated island and its evolution law.

This study investigates the deformation and damage characteristics of the surrounding rock along the top return mining roadway of an isolated island working face at different stages and reveals its damage mechanism and evolution law. Utilizing a mine in Yangquan City, Shanxi Province, China, as the engineering background, this research employs FLAC 3D numerical simulation and on-site measurements. The findings suggest that the evolution of the plastic zone along the top roadway of the 15,106 island face is largely similar during both the excavation and mining periods. The plastic zones on either side of the roadway are expanding asymmetrically and gradually merging into the plastic zone of the coal pillar. In the destructive stage, the sub-gangs of the roadway are penetrated, indicating the progression into the plastic zone. The investigation points to extensive damage on the larger side of the roadway, the development of fissures, and the significant depth of damage as primary causes of roadway deformation. Moreover, the extent of the plastic zones on both sides of the roadway correlates positively with their relative distance. Continuous monitoring reveals an ongoing increase in roadway displacement, consistent with general observations in coal mining. The results provide valuable insights for optimizing support structures in similar mining environments.

Janus hydrogel loaded with a CO2-generating chemical reaction system: Construction, characterization, and application in fruit and vegetable preservation.

In this study, we inserted a dynamic chemical reaction system that can generate CO2 into Janus hydrogel (JH) to develop a multidimensional preservation platform that integrates hygroscopicity, antibacterial activity, and modified atmospheric capacity. The double gel system developed using sodium alginate/trehalose at a 1:1 ratio effectively encapsulated 90% of citric acid. Furthermore, CO2 loss was avoided by separately embedding NaHCO3/cinnamon essential oil and citric acid microcapsules into a gelatin pad to develop JH. Freeze-dried JH exhibited a porous and asymmetric structure, very strongly absorbing moisture, conducting water, and rapidly releasing CO2 and essential oils. Furthermore, when preserving various fruits and vegetables in practical settings, JH provided several preservation effects, including color protection, microbial inhibition, and antioxidant properties. Our study findings broaden the application of JH technology for developing chemical reaction systems, with the resulting JH holding substantial promise for cold chain logistics.

Enantioselective Aminosilylation of Alkenes by Palladium/Ming-Phos-Catalyzed Tandem Narasaka-Heck/Silylation Reaction.

A Pd-catalyzed enantioselective aminosilylation of alkenes via tandem Aza-Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri-substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand.

A 3D micro-printed single cell micro-niche with asymmetric niche signals - An in vitro model for asymmetric cell division study.

Intricate microenvironment signals orchestrate to affect cell behavior and fate during tissue morphogenesis. However, the underlying mechanisms on how specific local niche signals influence cell behavior and fate are not fully understood, owing to the lack of in vitro platform able to precisely, quantitatively, spatially, and independently manipulate individual niche signals. Here, microarrays of protein-based 3D single cell micro-niche (3D-SCµN), with precisely engineered biophysical and biochemical niche signals, are micro-printed by a multiphoton microfabrication and micropatterning technology. Mouse embryonic stem cell (mESC) is used as the model cell to study how local niche signals affect stem cell behavior and fate. By precisely engineering the internal microstructures of the 3D SCµNs, we demonstrate that the cell division direction can be controlled by the biophysical niche signals, in a cell shape-independent manner. After confining the cell division direction to a dominating axis, single mESCs are exposed to asymmetric biochemical niche signals, specifically, cell-cell adhesion molecule on one side and extracellular matrix on the other side. We demonstrate that, symmetry-breaking (asymmetric) niche signals successfully trigger cell polarity formation and bias the orientation of asymmetric cell division, the mitosis process resulting in two daughter cells with differential fates, in mESCs.

Studying lipid flip-flop in asymmetric liposomes using 1H NMR and TR-SANS.

The specific spatial and temporal distribution of lipids in membranes play a crucial role in determining the biochemical and biophysical properties of the system. In nature, the asymmetric distribution of lipids is a dynamic process with ATP-dependent lipid transporters maintaining asymmetry, and passive transbilayer diffusion, that is, flip-flop, counteracting it. In this chapter, two probe-free techniques, 1H NMR and time-resolved small angle neutron scattering, are described in detail as methods of investigating lipid flip-flop rates in synthetic liposomes that have been generated with an asymmetric bilayer composition.

The use of hemifusion to create asymmetric giant unilamellar vesicles: Insights on induced order domains.

The natural asymmetry of the lipid bilayer in biological membranes is, in part, a testament to the complexity of the structure and function of this barrier limiting and protecting cells (or organelles). These lipid bilayers consist of two lipid leaflets with different lipid compositions, resulting in unique interactions within each leaflet. These interactions, combined with interactions between the two leaflets, determine the overall behavior of the membrane. Model membranes provide the most suitable option for investigating the fundamental interactions of lipids. This report describes a comprehensive method to make asymmetric giant unilamellar vesicles (aGUVs) using the technique of hemifusion. In this method, calcium ions induce the hemifusion of giant unilamellar vesicles (GUVs) with a supported lipid bilayer (SLB), both having different lipid compositions. During hemifusion, a stalk, or a more commonly seen hemifusion diaphragm, connects the outer leaflets of GUVs and the SLB. The lateral diffusion of lipids naturally promotes the lipid exchange between the connected outer leaflets. After calcium chelation to prevent further fusion, a mechanical shear detaches aGUVs from the SLB. A fluorescence quench assay is employed to test the extent of bilayer asymmetry. A fluorescence quenching assay tests bilayer asymmetry and verifies dye and lipid migration to a GUV's outer leaflet.

Loosely Bounded Exciton with Enhanced Delocalization Capability Boosting Efficiency of Organic Solar Cells.

In organic solar cells (OSCs), electron acceptors have undergone multiple updates, from the initial fullerene derivatives, to the later acceptor-donor-acceptor type non-fullerene acceptors (NFAs), and now to Y-series NFAs, based on which efficiencies have reached over 19%. However, the key property responsible for further improved efficiency from molecular structure design is remained unclear. Herein, the material properties are comprehensively scanned by selecting PC71BM, IT-4F, and L8-BO as the representatives for different development stages of acceptors. For comparison, asymmetric acceptor of BTP-H5 with desired loosely bounded excitons is designed and synthesized. It's identified that the reduction of intrinsically exciton binding energy (Eb) and the enhancement of exciton delocalization capability act as the key roles in boosting the performance. Notably, 100 meV reduction in Eb has been observed from PC71BM to BTP-H5, correspondingly, electron-hole pair distance of BTP-H5 is almost two times over PC71BM. As a result, efficiency is improved from 40% of S-Q limit for PC71BM-based OSC to 60% for BTP-H5-based one, which achieves an efficiency of 19.07%, among the highest values for binary OSCs. This work reveals the confirmed function of exciton delocalization capability quantitatively in pushing the efficiency of OSCs, thus providing an enlightenment for future molecular design.

Applications of Ene-Reductases in the Synthesis of Flavors and Fragrances.

Flavors and fragrances (F&F) are interesting organic compounds in chemistry. These compounds are widely used in the food, cosmetic, and medical industries. Enzymatic synthesis exhibits several advantages over natural extraction and chemical preparation, including a high yield, stable quality, mildness, and environmental friendliness. To date, many oxidoreductases and hydrolases have been used to biosynthesize F&F. Ene-reductases (ERs) are a class of biocatalysts that can catalyze the asymmetric reduction of α,ß-unsaturated compounds and offer superior specificity and selectivity; therefore, ERs have been increasingly considered an ideal alternative to their chemical counterparts. This review summarizes the research progress on the use of ERs in F&F synthesis over the past 20 years, including the achievements of various scholars, the differences and similarities among the findings, and the discussions of future research trends related to ERs. We hope this review can inspire researchers to promote the development of biotechnology in the F&F industry.

Creating Asymmetric Fe-N3C-N Sites in Single-Atom Catalysts Boosts Catalytic Performance for Oxygen Reduction Reaction.

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N3C-N sites with asymmetric in-plane coordinated Fe-N3C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity (E1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N4-N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density (Pmax) of 130 mW/cm2, outperforming the commercial Pt/C catalyst (OCV = 1.42 V; Pmax = 119 mW/cm2). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N3C-N structure shifted upward, which enhances its electron-donating ability, favors O2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

Advancements in Asymmetric Supercapacitors: From Historical Milestones to Challenges and Future Directions.

Numerous challenges, like the uninterrupted supply of electricity, stable and reliable power, and energy storage during non-operational hours, arise across various industries due to the absence of advanced energy storage technologies. With the continual technological advancements in portable electronics, green energy, and transportation, there are inherent limitations in their innovative production. Thus, ongoing research is focused on pursuing sustainable energy storage technologies. An emerging solution lies in the development of asymmetric supercapacitors (ASCs), which offer the potential to extend their operational voltage limit beyond the thermodynamic breakdown voltage range of electrolytes. This is achieved by employing two distinct electrode materials, presenting an effective solution to the energy storage limitations faced by ASCs. The current review concentrates on the progression of working materials to develop authentic pseudocapacitive energy storage systems (ESS). Also, evaluates their ability to exceed energy storage constraints. It provides insights into fundamental energy storage mechanisms, performance evaluation methodologies, and recent advancements in electrode material strategies. The review approaches developing high-performance electrode materials and achieving efficient ASC types. It delves into critical aspects for enhancing the energy density of ASCs, presenting debates and prospects, thereby offering a comprehensive understanding and design principles for next-generation ASCs in diverse applications.

Dual polarity open circuit voltage in triboelectric nanogenerators originated from two states series impedance.

Experimental and simulation studies demonstrated that the initial voltage setting significantly influences the open-circuit voltage (VOC) in triboelectric nanogenerators (TENGs). Utilizing diode configurations, we consistently observed two distinct VOCs independent of the initial settings. A lower VOC corresponded to the surface voltage (VSurface), while a higher VOC was amplified by the product of the VSurface and the TENG's characteristic impedance ratio. Notably, a lower measurement system capacitance provided a more precise representation of the inherent characteristics of the TENG. Conversely, an increase in system impedance led to a convergence of the two VOCs and a reduction in their magnitudes relative to VSurface. These findings suggest that optimizing the initial/repeated charge balancing and minimizing capacitive loads are crucial for maximizing TENG output power in practical applications.

Asymmetric analogous hyperbola model of overburden movement and its verification.

The extraction of underground coal resources induces the fracture and movement of overlying strata, leading to geological hazards such as surface deformation, cracks, and even subsidence. Utilizing the analogous hyperbola model of overlying strata movement, we conducted a mechanical analysis to examine the asymmetric fracture mechanism resulting from coal seam mining in thick loose strata. An asymmetric analogous hyperbola model was established by introducing distinct virtual half-axis lengths (b). The thickness impact of thick loose layers (H) and bedrock layer (h) on the asymmetric movement of overlying rock during mining was also discussed. Similarity model tests were conducted to research the migration characteristics and surface subsidence patterns of overburdened rock and thick loose layers at different mining stages and validate the hypothesis of asymmetric overburdened rock migration. Additionally, the discrete element numerical model for thick and loose layers mining was established by using UDEC and discussed the asymmetric analogous hyperbola behaviour of overburden movement and surface subsidence. The comparison results show that the established asymmetric hyperbolic model can effectively predict the movement law of overlying strata and surface subsidence characteristics. Therefore, the proposed model can provide valuable theoretical support for predicting the movement patterns of overburden under thick loose layers and mitigating surface subsidence disasters.

Spatio-Temporal Regulation of Notch Activation in Asymmetrically Dividing Sensory Organ Precursor Cells in Drosophila melanogaster Epithelium.

The Notch communication pathway, discovered in Drosophila over 100 years ago, regulates a wide range of intra-lineage decisions in metazoans. The division of the Drosophila mechanosensory organ precursor is the archetype of asymmetric cell division in which differential Notch activation takes place at cytokinesis. Here, we review the molecular mechanisms by which epithelial cell polarity, cell cycle and intracellular trafficking participate in controlling the directionality, subcellular localization and temporality of mechanosensitive Notch receptor activation in cytokinesis.

Relationship between the left-right asymmetric motor-related conformation and the orientation of facial hair whorls in Japanese Kiso horses.

We examined the relationship between inherited motor-related conformation and orientation of facial hair whorls in Japanese Kiso horses. Eleven horses were divided into clockwise, counterclockwise, and radial groups according to facial hair whorls. We placed six markers on anatomical landmarks of each lateral side in a horse and measured the height of the landmarks, the distance between adjacent landmarks, and the angle of the adjacent landmarks. In the counterclockwise group, the horses tended to exhibit higher values on the left side than on the right side, and the comparison of the height of landmarks revealed a significant difference between both sides. Therefore, the orientation of facial hair whorls may suggest the tendency of motor-related conformation, at least in counterclockwise group.

α-Halocarbonyls as a Valuable Functionalized Tertiary Alkyl Source.

This review introduces the synthetic organic chemical value of α-bromocarbonyl compounds with tertiary carbons. This α-bromocarbonyl compound with a tertiary carbon has been used primarily only as a radical initiator in atom transfer radical polymerization (ATRP) reactions. However, with the recent development of photo-radical reactions (around 2010), research on the use of α-bromocarbonyl compounds as tertiary alkyl radical precursors became popular (around 2012). As more examples were reported, α-bromocarbonyl compounds were studied not only as radicals but also for their applications in organometallic and ionic reactions. That is, α-bromocarbonyl compounds act as nucleophiles as well as electrophiles. The carbonyl group of α-bromocarbonyl compounds is also attractive because it allows the skeleton to be converted after the reaction, and it is being applied to total synthesis. In our survey until 2022, α-bromocarbonyl compounds can be used to perform a full range of reactions necessary for organic synthesis, including multi-component reactions, cross-coupling, substitution, cyclization, rearrangement, stereospecific reactions, asymmetric reactions. α-Bromocarbonyl compounds have created a new trend in tertiary alkylation, which until then had limited reaction patterns in organic synthesis. This review focuses on how α-bromocarbonyl compounds can be used in synthetic organic chemistry.