Origin of Chemoselectivity of Halohydrin Dehalogenase-Catalyzed Epoxide Ring-Opening Reactions.

By performing molecular dynamics (MD), quantum mechanical/molecular mechanical (QM/MM) calculations, and QM cluster calculations, the origin of chemoselectivity of halohydrin dehalogenase (HHDH)-catalyzed ring-opening reactions of epoxide with the nucleophilic reagent NO2- has been explored. Four possible chemoselective pathways were considered, and the computed results indicate that the pathway associated with the nucleophilic attack on the Cα position of epoxide by NO2- is most energetically favorable and has an energy barrier of 12.9 kcal/mol, which is close to 14.1 kcal/mol derived from experimental kinetic data. A hydrogen bonding network formed by residues Ser140, Tyr153, and Arg157 can strengthen the electrophilicity of the active site of the epoxide substrate to affect chemoselectivity. To predict the energy barrier trends of the chemoselective transition states, multiple analyses including distortion analysis and electrophilic Parr function (Pk+) analysis were carried out with or without an enzyme environment. The obtained insights should be valuable for the rational design of enzyme-catalyzed and biomimetic organocatalytic epoxide ring-opening reactions with special chemoselectivity.

Catalytic asymmetric synthesis of planar-chiral dianthranilides via (Dynamic) kinetic resolution.

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.

Umpolung reactivity of strained C-C σ-bonds without transition-metal catalysis.

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C-C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C-C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C-C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C-C σ-bonds and provides high-value structural motifs.

Mechanism and Origin of Stereoselectivity for the NHC-Catalyzed Desymmetrization Reaction for the Synthesis of Axially Chiral Biaryl Aldehydes.

Organocatalytic desymmetrization reaction is a powerful tool for constructing axial chirality, but the theoretical study on the origin of stereoselectivity still lags behind even now. In this work, the N-heterocyclic carbene (NHC)-catalyzed desymmetrization reaction of biaryl frameworks for the synthesis of axially chiral aldehydes has been selected and theoretically investigated by using density functional theory (DFT). The fundamental pathway involves several steps, i.e., desymmetrization, formation of Breslow oxidation, esterification, and NHC regeneration. The desymmetrization and formation of Breslow processes have been identified as stereoselectivity-determining and rate-determining steps. Further weak interaction analyses proved that the C-H···O hydrogen bond and C-H···π interactions are responsible for the stability of the key stereoselective desymmetrization transition states. This research contributes to understanding the nature of NHC-catalyzed desymmetrization reactions for the synthesis of axially chiral compounds.

Active Property-Structure Integrated Reconfiguration of Individual Resonant Nanoparticles.

Property-structure reconfigurable nanoparticles (NPs) provide additional flexibility for effectively and flexibly manipulating light at the nanoscale. This has facilitated the development of various multifunctional and high-performance nanophotonic devices. Resonant NPs based on dielectric active materials, especially phase change materials, are particularly promising for achieving reconfigurability. However, the on-demand control of the properties, especially the morphology, in individual dielectric resonant NP remains a significant challenge. In this study, we present an all-optical approach for one-step fabrication of Ge2Sb2Te5 (GST) hemispherical NPs, integrated active reversible phase-state switching, and morphology reshaping. Reversible optical switching is demonstrated, attributed to reversible phase-state changes, along with unidirectional modifications to their scattering intensity resulting from morphology reshaping. This novel technology allows the precise adjustment of each structural pixel without affecting the overall functionality of the switchable nanophotonic device. It is highly suitable for applications in single-pixel-addressable active optical devices, structural color displays, and information storage, among others.

π-Electron Fluctuation-Induced P+ /C- Ambiphilic Interaction for Intramolecular CAr -H Bond Activation.

Herein, we describe how computational mechanistic understanding has led directly to the discovery of new 2H-phosphindole for C-CAr bond activation and dearomatization reaction. We uncover an unexpected intramolecular C-H bond activation with a 2H-phosphindole derivative. This new intriguing experimental observation and further theoretical studies led to an extension of the reaction mechanism with 2H-phosphindole. Through DFT calculations, we confirm that within a five-membered ring, the polarizable PC3 unit orchestrates the formation of an electrophilic phosphorus atom (P+ ) and a nucleophilic carbon atom (C- ). This kinetically accessible ambiphilic phosphorus/carbon couple is spatially separated by geometric constraints, and their reactivity is modulated through structural resonance.

Effects of phosphine ligands in nickel-catalyzed decarbonylation reactions of lactone.

Due to the ubiquity of carbonyl compounds and the abundance of nickel on the earth, nickel-catalyzed decarbonylation has garnered increasing attention in recent years. This type of reaction has seen significant developments in various aspects; however, certain challenges concerning reactivity, selectivity, and transformation efficiency remain pressing and demand urgent resolution. In this study, we employed DFT calculations to investigate the mechanism of nickel-catalyzed decarbonylation reactions involving lactones, as well as the effects of phosphine ligands. Mechanically, Ni(0) first activates the C(acyl)-O bond of the lactone, followed by a decarbonylation step, and ultimately results in reductive elimination under carbonyl coordination to yield the product. Through a comprehensive examination of the electronic and steric effects of the phosphine ligands, we deduced that the electronic effect of the ligand plays a dominant role in the decarbonylation reaction. By enhancing the electron-withdrawing ability of the ligand, the energy barrier of the entire reaction can be significantly reduced. The obtained insights should be valuable for understanding the detailed mechanism and the role of phosphine ligands in nickel catalysis. Moreover, they offer crucial clues for the rational design of more efficient catalytic reactions.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

Simulation of microtubule-cytoplasm interaction revealed the importance of fluid dynamics in determining the organization of microtubules.

Although microtubules in plant cells have been extensively studied, the mechanisms that regulate the spatial organization of microtubules are poorly understood. We hypothesize that the interaction between microtubules and cytoplasmic flow plays an important role in the assembly and orientation of microtubules. To test this hypothesis, we developed a new computational modeling framework for microtubules based on theory and methods from the fluid-structure interaction. We employed the immersed boundary method to track the movement of microtubules in cytoplasmic flow. We also incorporated details of the encounter dynamics when two microtubules collide with each other. We verified our computational model through several numerical tests before applying it to the simulation of the microtubule-cytoplasm interaction in a growing plant cell. Our computational investigation demonstrated that microtubules are primarily oriented in the direction orthogonal to the axis of cell elongation. We validated the simulation results through a comparison with the measurement from laboratory experiments. We found that our computational model, with further calibration, was capable of generating microtubule orientation patterns that were qualitatively and quantitatively consistent with the experimental results. The computational model proposed in this study can be naturally extended to many other cellular systems that involve the interaction between microstructures and the intracellular fluid.

CALCIUM-DEPENDENT PROTEIN KINASE32 regulates cellulose biosynthesis through post-translational modification of cellulose synthase.

Cellulose is an essential component of plant cell walls and an economically important source of food, paper, textiles, and biofuel. Despite its economic and biological significance, the regulation of cellulose biosynthesis is poorly understood. Phosphorylation and dephosphorylation of cellulose synthases (CESAs) were shown to impact the direction and velocity of cellulose synthase complexes (CSCs). However, the protein kinases that phosphorylate CESAs are largely unknown. We conducted research in Arabidopsis thaliana to reveal protein kinases that phosphorylate CESAs. In this study, we used yeast two-hybrid, protein biochemistry, genetics, and live-cell imaging to reveal the role of calcium-dependent protein kinase32 (CPK32) in the regulation of cellulose biosynthesis in A. thaliana. We identified CPK32 using CESA3 as a bait in a yeast two-hybrid assay. We showed that CPK32 phosphorylates CESA3 while it interacts with both CESA1 and CESA3. Overexpressing functionally defective CPK32 variant and phospho-dead mutation of CESA3 led to decreased motility of CSCs and reduced crystalline cellulose content in etiolated seedlings. Deregulation of CPKs impacted the stability of CSCs. We uncovered a new function of CPKs that regulates cellulose biosynthesis and a novel mechanism by which phosphorylation regulates the stability of CSCs.

Leaching kinetic mechanism of iron from the diamond wire saw silicon powder by HCl.

The diamond wire saw silicon powder (DWSSP) is considered to be a harmful to the environment because of finer particles, the large specific surface area and flammability. Removal of Fe impurity is very essential for recovering Si from DWSSP due to the large amount of Fe introduced during the silicon powder generation process. In the study, the thermodynamics of Fe leaching with HCl was analyzed and determined iron was theoretically present as ions in solution. Furthermore, the effects of different concentrations, temperatures and liquid-solid ratios on Fe leaching from HCl were investigated. The leaching rate of Fe reached 98.37% at the optimal parameters (HCl concentration of 12 wt%, leaching temperature of 333 K, liquid-solid ratio of 15 ml/g) with 100 min. The leaching kinetics of Fe in HCl was analyzed by shrinking core model and homogeneous model, respectively. The study indicated the process of leaching Fe from DWSSP conforms to the secondary reaction model of homogeneous model which coincided with the porous structure of DWSSP due to agglomeration. The apparent activation energy required (49.398 kJ/mol) in the first stage is lower than that (57.817 kJ/mol) in the second stage because of the porous structure. In conclusion, this paper provided a suitable way to purify the diamond wire saw silicon powder. This work provides an important guide for the industrial recovery and preparation of high purity silicon from DWSSP by the most environment-friendly and low-cost approach.

A novel process to recycle coal gasification fine slag by preparing Si-Fe-Al-Ca alloy.

Maximizing the use of valuable components in coal gasification slag is of great significance for resource recovery and the environment due to the huge annual emission of coal gasification slag. This study successfully produced Si-Fe-Al-Ca alloy with a composition of 63.83 wt% Si, 19.73 wt% Fe, 7.09 wt% Al, 6.32 wt% Ca, 1.70 wt% Ti, 0.03 wt% P, 0.66 wt% Mn, 0.05 wt% Cr, 0.53 wt% C, and 0.06 wt% others through electric arc furnace smelting from mixed coal gasification fine slag. The alloy composition is close to the standard 65% ferrosilicon, which can be used in the deoxidation of the molten steel industry. Moreover, the alloy yield was increased from 20.53% to 67.78% by using the residual carbon of the coal gasification slag as the reductant directly instead of adding petroleum coke. The transformation of coal gasification fine slag during the smelting process and the formation mechanism of the alloy were studied and the carbothermal reduction mechanism of Al2O3 and CaO can be explained by the reduction and decomposition theory of carbides. The complex liquid phase of the reactant system and product system in the smelting process made the carbothermal reaction of Al2O3 and CaO easier to occur, but it also brought the problem that the reactions were not fully completed.

Efficient recycling of silicon cutting waste for producing high-quality Si-Fe alloys.

A tremendous amount of silicon cutting waste (SCW) is being produced during slicing Si ingots, which leads to a great waste of resources and serious environmental pollution. In this study, a novel method that recycling SCW to produce Si-Fe alloys was proposed, which not only provides a process with low energy consumption, low cost, and short flow for producing high-quality Si-Fe alloys but also achieves a more effective recycling of SCW. The optimal experimental condition is investigated to be a smelting temperature of 1800 °C and a holding time of 10 min. Under this condition, the yield of Si-Fe alloys and the Si recovery ratio of SCW were 88.63% and 87.81%, respectively. Compared with the present industrial recycling method that uses SCW to prepare metallurgy-grade Si ingot by an induction smelting process, this Si-Fe alloying method can achieve a higher Si recovery ratio of SCW at a shorter smelting time. The promoting mechanism of Si recovery by Si-Fe alloying is mainly expressed as follows: (1) facilitating the separation of Si from SiO2-based slag; (2) reducing the oxidization and carbonization loss of Si by accelerating the heating of raw materials and reducing the exposed area of Si.

Cofactor-Free Dioxygenases-Catalyzed Reaction Pathway via Proton-Coupled Electron Transfer.

Understanding the general mechanism of the metal-free and cofactor-free oxidases and oxygenases catalyzed activation of triplet O2 is one of the most challenging questions in the field of enzymatic catalysis. Herein, we have performed Quantum Mechanics/Molecular Mechanics (QM/MM) multiscale simulations to reveal the detailed mechanism of the HOD catalyzed (i.e., 1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase from Arthrobacter nitroguajacolicus Rü61a) decomposition of N-heteroaromatic compounds. The complete catalytic mechanism includes four steps: (1) proton transfer from 1-H-3-hydroxy-4-oxoquinaldine (QND) substrate to His251 residue coupled with an electron transfer from QND to triplet O2 (i.e., PCET), (2) formation of C-O bond via an open-shell singlet diradical recombination pathway, (3) ring-closure to form a bicyclic ring, and (4) dissociation of CO. The dissociation of CO is determined as the rate-limiting step, and its calculated energy barrier of 14.9 kcal/mol is consistent with the 15.5 kcal/mol barrier derived from experimental kinetic data. The mechanistic profile is not only valuable for understanding the fundamental pathway of cofactor-free oxidases and oxygenases-catalyzed reactions involving the triplet O2 activation but also discloses a new pathway that undergoes the processes of PCET and open-shell singlet transition state.

Time Under 90% Oxygen Saturation and Systemic Hypertension in Patients with Obstructive Sleep Apnea Syndrome.

Purpose: The diagnosis and severity of obstructive sleep apnea (OSA) are commonly based on the apnea hypopnea index (AHI). However, patients with similar severity AHIs may show widely varying comorbidities and risks for cardiovascular disease, which may be associated with different severities of nocturnal hypoxia. The percentage of cumulative time with oxygen saturation below 90% in total sleep time (T90) is receiving increasing attention in OSA research because it describes the duration and degree of hypoxia during the whole sleep. This study aimed to explore the distribution of T90 in OSA patients with similar severity and to evaluate the relationship between T90 and hypertension. Patients and Methods: A total of 775 patients with OSA were enrolled in this study, all participants were divided into groups according to the T90 value: light hypoxia (T90≤5%), mild hypoxia (T90 accounted for 5-10%), moderate hypoxia (T90 accounted for 10-25%), and severe hypoxia (T90>25%). Multivariate logistic regression analysis was performed to assess the association between T90 and hypertension. Results: Of the patients with mild OSA, 94.33% had light hypoxia, and 88.64% of moderate OSA patients had light hypoxia. The proportions of light, mild, moderate, and severe hypoxia among patients with severe OSA were 28.60%, 17.69%, 21.40%, and 32.31%, respectively. After adjustment for potential confounders, the risk of hypertension in patients with severe OSA increased according to the severity categories of T90. The odds ratio for T90 accounting for 10-25% relative to T90≤5% was 2.544 (95%confidence interval, 1.254-5.164; P=0.010) and as high as 2.692 (95%confidence interval, 1.403-5.166; P=0.003) in patients with T90>25%. Conclusion: OSA patients with similar degree of AHI may have different T90 values, especially in severe OSA. A higher T90 was independently associated with the risk of hypertension after adjustment for traditional risk factors in patients with severe OSA. Our findings highlight the potential role for T90 in predicting hypertension in patients severe OSA.

Rigid P-Chiral Phosphorus Ligands for Highly Selective Palladium-Catalyzed (4+2) and (4+4) Annulations.

We developed novel shackled P-chiral ligands based on 1-phosphanorbornenes and oxazolines. They were subsequently evaluated in palladium-catalyzed (4+2) annulations, producing enantioenriched tetrahydropyran scaffolds in good yields with high site selectivity and enantioselectivity. Moreover, chemoselective (4+4) products were also achieved by using acyclic imines. In addition, density functional theory calculations were performed to afford the energy profile of the Michael addition step and ring formation step. This demonstrated that the enantioselective (4+2) annulations and the chemoselective reaction between (4+2) and (4+4) products were mostly under thermodynamic control.

Atroposelective Synthesis of Triaryl α-Pyranones with 1,2-Diaxes by N-Heterocyclic Carbene Organocatalysis.

Atropisomers bearing multiple stereogenic axes are of increasing importance to the field of material science, pharmaceuticals, and catalysis. However, the atroposelective construction of multi-axis atropisomers remains rare and challenging, due to the intrinsical difficulties in the stereo-control of the multiple stereogenic axes. Herein, we demonstrate a single-step construction of a new class of 1,2-diaxially chiral triaryl α-pyranones by an N-heterocyclic carbene organocatalytic asymmetric [3+3] annulation of well-designed alkynyl acylazolium precursors and enolizable sterically hindered 2-aryl ketones. The protocol features broad substrate scope (>50 examples), excellent stereo-control (most cases >20 : 1 dr, up to 99.5 : 0.5 er), and potentially useful synthetic applications. The success of this reaction relies on the rational design of structurally matched reaction partners and the careful selection of the asymmetric catalytic system. DFT calculations have also been performed to discover and rationalize the origin of the high stereoselectivity of this reaction.

Cigarette smoke extract stimulates human pulmonary artery smooth muscle cell proliferation: Role of inflammation and oxidative stress.

Objectives: Cigarette smoke may play a direct role in proliferation of human pulmonary artery smooth muscle cells (HPASMCs). However, the mechanism involved and the effect of interventions remain unclear. We aimed to evaluate the effect of cigarette smoke extract (CSE) on HPASMCs, explore the role of inflammation and oxidative stress, and the effects of Tempol and PDTC in this process. Materials and Methods: HPASMCs were subjected to normal control (NC), CSE, CSE+Tempol (CSE+T), and CSE+PDTC (CSE+P) groups. Proliferation of HPASMCs was measured by CCK-8 and Western blot. TNF-α, IL-6, MDA, and SOD levels were determined by ELISA and commercial kits. Nuclear translocation of NF-κB p65 was evaluated by western blot. Results: 1%, 2.5%, and 5% CSE all promoted proliferation of HPASMCs, and effect of 1% CSE was the most significant, however, 7.5% and 10% CSE inhibited viability of cells (all P<0.05). Compared with the NC group, TNF-α, IL-6, and MDA levels increased, SOD activity decreased (all P<0.05), and NF-κB p65 expression in nuclei increased (P=0.04) in the CSE group. Tempol and PDTC inhibited the proliferation of HPASMCs induced by CSE (all P<0.05). And compared with the CSE group, TNF-α, IL-6, and MDA levels in CSE+T and CSE+P groups decreased, while SOD activity increased (all P<0.05). Tempol reduced the expression of NF-κB p65 in nuclei but did not achieve a significant difference (P=0.08). PDTC inhibited the nuclear translocation of NF-κB p65 (P=0.03). Conclusion: CSE stimulates HPASMCs proliferation in a certain concentration range. The CSE-induced proliferation of HPASMCs involved excessive inflammatory response and oxidative stress. Tempol and PDTC attenuate these effects of CSE on HPASMCs.

One Stone Three Birds: Regiodivergent Access to Amino-Substituted Benzophospholes and Their Structure-Property Relationships.

Three series new NH2-benzophosphole oxides were synthesized from cycloaddition of o-aminophenyl phosphine oxide with alkynes. The relationship between the location of the amino group and the photophysical properties were studied by absorption and emission spectroscopies and theoretical calculation. 4-NH2-benzophosphole oxides show strong fluorescence emission and high fluorescence quantum efficiency. This "One stone three birds" process provides rapid access to multiple organophosphorus-based luminogens for the structure-property relationship study.

Cofactor-free ActVA-Orf6 monooxygenase catalysis via proton-coupled electron transfer: a QM/MM study.

Uncovering the comprehensive catalytic mechanism for the activation of triplet O2 through metal-free and cofactor-free oxidases and oxygenases remains one of the most challenging problems in the area of enzymatic catalysis. Herein, we performed multiscale simulation with molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) techniques to reveal the detailed mechanism of ActVA-Orf6 monooxygenase catalyzed oxygenation of phenols to quinones from Streptomyces coelicolor, such as the oxidation of 6-deoxydihydrocarafungin (DDHK) to dihydrocarafungin (DHK). The entire catalytic mechanism consists of three steps: (1) proton-coupled electron transfer (PCET) from the substrate DDHK to triplet O2 with the aid of an explicit water molecule, (2) the formation of a C-O bond via an open-shell singlet diradical complexation pathway, and (3) dehydration via a six-membered ring mode assisted by one water molecule. The complete energetic profiles show that the rate-determining step is the dehydration with an energy barrier of 20.7 kcal mol-1, which is close to that of 19.7 kcal mol-1 derived from experimental kinetic data. Our mechanistic study not only helps to deeply understand the fundamental mechanism of metal-free and cofactor-free oxidase and oxygenase catalyzed different reactions, but also discloses a new route that proceeds through the processes of PCET and the open-shell singlet transition state.