Catalytic enantioselective alkene difunctionalization represents a powerful tool for the rapid assembly of complex chiral molecules and has found wide range of applications in synthetic chemistry. Enantioselective control of the newly formed pro-chiral carbon centers using chiral cobalt catalyst, however, remains challenging. Herein, we report the first cobalt-catalyzed enantioselective difunctionalization of industry-relevant acrylates with lithium aryl boronates and alpha,alpha-dialkyl bromoacetate for the preparation of enantioenriched glutaric acid derivatives. Facile transformations of the resulting alpha-aryl esters to other functionalities have been achieved. To further showcase the synthetic utility of the current protocol, application to the enantioselective synthesis of an analog of (-)-preclamol was demonstrated.

Enantioenriched small carbocycles are key structures in numerous natural products and pharmaceutically important molecules as well as vital intermediates in organic synthesis. Although various catalytic approaches for the construction of such molecules from acyclic precursors have been developed, direct enantioselective functionalization of preformed three-membered and four-membered rings represents the most straightforward and modular strategy, enabling rapid and diversified synthesis of enantioenriched cyclopropanes and cyclobutanes from a single set of starting materials without the need for the incorporation of specific functional groups. In this Feature Article, we have summarized the recent advances in catalytic enantioselective functionalization of cyclopropenes and cyclobutenes through carbometallation. The plausible mechanisms of such reactions and future of this field are also discussed. This review discusses the recent advances in metal-catalyzed enantioselective carbometallation of small cyclic alkenes that enabled the generation of a broad scope of enantioenriched cyclopropanes and cyclobutanes.

Enhancing the DNA toolbox with innovative photochemical reactions is pivotal for advancing nucleic acid-based technologies. Aldehyde groups, versatile bioorthogonal handles for imine formation under acidic conditions, are particularly valuable due to their roles in nucleic acid epigenetics. Here, we present the first photocatalytic on-DNA aldehyde allylation, enabling precise DNA functionalization under mild, neutral aqueous conditions. Our approach utilizes a photocatalytic polarity-reversal reaction between DNA-conjugated benzaldehydes and allyl sulfones. This reaction demonstrates exceptional chemoselectivity while preserving DNA integrity. By varying allyl sulfones, we achieve site-specific labeling of non-native DNA with the aldehyde group and cross-linking with DNA-bearing allyl sulfones. Furthermore, our method facilitates selective labeling and pull-down enrichment of 5-formylpyrimidine nucleotides among complex cellular DNA. This photocatalytic on-DNA aldehyde transformation expands the limited bioorthogonal photochemical toolboxes, providing novel avenues for functionalizing both non-native and native aldehyde modifications on DNA.

The matrix and particle interface of hydroxyl-terminated polybutadiene (HTPB) propellant is the weakest part of its mechanical properties, making it prone to dewetting damage and destroying the structural integrity of the propellant. This article uses nano-indentation, gas cluster ion beam etching, and X-ray photoelectron spectroscopy experimental analyses to study the physicochemical properties of the interface and subsequently construct a microscopic model for the HTPB matrix and ammonium perchlorate particle interface. The model fully considers the existing forms of curing agent toluene diisocyanate, bonding agent Tris (2-methyl-aziridine) phosphine oxide (MAPO), and the aging products of the propellant in the interface structure. Meanwhile, the physicochemical properties, mechanical properties, and adhesive properties of the interface under different tensile loading conditions were analyzed. The results indicate that the bonding agent MAPO significantly enhances the mechanical and adhesive properties of the interface. The interface is sensitive to changes in temperature and tensile rate, and the aged interface is more fragile.

The precise control of Z and E configurations of the carbon-carbon double bond in alkene synthesis has long been a fundamental challenge in synthetic chemistry, even more pronounced when simultaneously striving to achieve enantioselectivity [(Z,R), (Z,S), (E,R), (E,S)]. Moreover, enantiopure non-natural alpha-amino acids are highly sought after in organic and medicinal chemistry. In this study, we report a ligand-controlled stereodivergent synthesis of non-natural alpha-quaternary amino acids bearing trisubstituted alkene moieties in high yields with excellent enantioselectivity and Z/E selectivities. This success is achieved through a palladium/copper-cocatalyzed three-component assembly of readily available aryl iodides, allenes, and aldimine esters by simply tuning the chiral ligands of the palladium and copper catalysts.

Although many researchers of Parkinson's disease (PD) have shifted their focus from the central nervous system (CNS) to the peripheral blood, a significant knowledge gap remains between PD severity and the peripheral immune response. In the current study, we aimed to map the peripheral immunity atlas in peripheral blood mononuclear cells (PBMCs) from PD patients and healthy controls using single-cell RNA sequencing (scRNA-seq). Our study employed scRNA-seq analysis to map the peripheral immunity atlas in PD by profiling PBMCs from PD-Early, PD-Late patients and matched controls. By enlarging the blood sample size, we validated the roles of NK cells in numerous immune-related biological processes. We also detected the infiltration of NK cells into the cerebral motor cortex as the disease progressed, using human brain sections, and elucidated the communication between the periphery and CNS and its implications for PD. As a result, cell subpopulation atlases in PBMCs from PD patients and healthy controls along with differentially expressed genes in NK cells were identified by scRNA-seq analysis, representing 6 major immune cell subsets among which NK cells declined in the progression of PD. We further validated NK cell reduction in increasing samples and found that they participated in numerous immune-related biological processes and infiltration into the cerebral motor cortex as the disease proceeded, evidencingd the close communication between the peripheral immune response and CNS. Strikingly, XCL2 positively correlated with PD severity, with good predictive performance of PD and specific expression in subclusters C2 and C5 of NK cells. All these findings delineated the critical role of peripheral immune response mediated by NK cells in the pathogenesis of PD. NK cell-specific XCL2 could be used as a diagnostic marker for treating PD. The indispensable function of NK cells and NK cell-specific molecular biomarkers highlighted the implication of the peripheral immune response in PD progression. Trial registration: ChiCTR, ChiCTR1900023975. Registered 20 June 2019 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=31035.

Understanding the nature of a transition-metal-catalyzed process, including catalyst evolution and the real active species, is rather challenging yet of great importance for the rational design and development of novel catalysts, and this is even more difficult for a bimetallic catalytic system. Pd(0)/carboxylic acid combined system-catalyzed allylic alkylation reaction of alkynes has been used as an atom-economical protocol for the synthesis of allylic products. However, the asymmetric version of this reaction is still rather limited, and the in-depth understanding of the nature of active Pd species is still elusive. Herein we report an enantioselective coupling between readily available aldimine esters and alkynes using a synergistic Cu/Pd catalyst system, affording a diverse set of alpha-quaternary allyl amino ester derivatives in good yields with excellent enantioselectivities. Mechanistic studies indicated that it is most likely a synergistic asymmetric molecular Cu catalysis with Pd nanoparticle catalysis. The Pd catalyst precursor is transformed to soluble Pd nanoparticles in situ, which are responsible for activating the alkyne to an electrophilic allylic Pd intermediate, while the chiral Cu complex of the aldimine ester enolate provides chiral induction and works in synergy with the Pd nanoparticles.