Visible Light Induced Copper-Catalyzed Enantioselective Deaminative Arylation of Amino Acid Derivatives Assisted by Phenol

The exploration of value-added conversions of naturally abundant amino acids has received considerable attention from the synthetic community. Compared with the well-established asymmetric decarboxylative transformation, the asymmetric deaminative transformation of amino acids still remains a formidable challenge, mainly due to the lack of effective strategies for the C−N bond activation and the potential incompatibility with chiral catalysts. Here, we disclose a photoinduced Cu-catalyzed asymmetric deaminative coupling reaction of amino acids with arylboronic acids. This new protocol provides a series of significant chiral phenylacetamides in generally good yields and excellent stereoselectivity under mild and green conditions (42–85 % yields, up to 97 % ee). Experimental investigations and theoretical calculations were performed to reveal the crucial role of additional phenols in improving catalytic efficiency and enantiocontrol.     

Ortho-Alkoxy-benzamide Directed Formation of a Single Crystalline Hydrogen-bonded Crosslinked Organic Framework and Its Boron Trifluoride Uptake and Catalysis

Boron trifluoride (BF₃) is a highly corrosive gas widely used in industry. Confining BF₃ in porous materials ensures safe and convenient handling and prevents its degradation. Hence, it is highly desired to develop porous materials with high adsorption capacity, high stability, and resistance to BF₃ corrosion. Herein, we designed and synthesized a Lewis basic single-crystalline hydrogen-bond crosslinked organic framework (H_COF-50) for BF₃ storage and its application in catalysis. Specifically, we introduced self-complementary ortho-alkoxy-benzamide hydrogen-bonding moieties to direct the formation of highly organized hydrogen-bonded networks, which were subsequently photo-crosslinked to generate H_COFs. The H_COF-50 features Lewis basic thioether linkages and electron-rich pore surfaces for BF₃ uptake. As a result, H_COF-50 shows a record-high 14.2 mmol/g BF₃ uptake capacity. The BF₃ uptake in H_COF-50 is reversible, leading to the slow release of BF₃. We leveraged this property to reduce the undesirable chain transfer and termination in the cationic polymerization of vinyl ethers. Polymers with higher molecular weights and lower polydispersity were generated compared to those synthesized using BF₃ ⋅ Et₂O. The elucidation of the structure–property relationship, as provided by the single-crystal X-ray structures, combined with the high BF₃ uptake capacity and controlled sorption, highlights the molecular understanding of framework-guest interactions in addressing contemporary challenges.     

Computational Mechanism Investigation of C=C Bond Hydrogenation Catalyzed by Rhodium Hydride

The hydrogenation of unsaturated carbons is a commonly used synthetic tool in pharmaceutical and industrial production. Recently, the Norton group realized highly selective hydrogenation of C=C bonds catalyzed by a rhodium hydride. Despite the great efforts made by experimentalists, details regarding the mechanism remained unclear. In this work, detailed DFT calculations were carried out to elucidate the principal features of this transformation. For enones we find that two possible competing mechanisms proposed by the experimental groups are computationally excluded, our proposed alternative mechanism with a total barrier of 20.0 kcal mol⁻¹ is theoretically feasible, solvent methanol to also plays a crucial role in assisting β-hydrogenation in addition to being the hydrogen source for α-hydrogenation, and the cross-polarization of the substrate enone-conjugated system to result in an enhanced charge density of the α-carbon, which favors being hydrogenated first. For isolated alkenes, neither of the two possible competing mechanisms can be excluded computationally and which carbon atom is first hydrogenated depends on the electronic properties of the substrate itself. The combination of rhodium and C=C bonds changes the electronic properties of H on the rhodium hydride and enhances its hydrogenation activity.     

Comprehensive Mechanism for CO Electroreduction on Dual-Atom-Catalyst-Anchored N-Doped Graphene

Carbon neutrality has drawn increasing attention for realizing the carbon cyclization and reducing the greenhouse effect. Although the C1 products, such as CO, can be achieved with a high Faraday efficiency, the targeted production of C2 fuels as well as the mechanism have not been systematically investigated. In this work, we carry out a first-principles study to screen dual-atom catalysts (DACs) for producing C2 fuels through the electrocatalytic carbon monoxide reduction reaction (e-CORR). We find that methanol, ethanol and ethylene can be produced on both DAC−Co and DAC−Cu, while acetate can be achieved on DAC−Cu only. Importantly, methanol and ethylene are preferred on DAC−Co, while acetate and ethylene on DAC−Cu. Furthermore, we show that the explicit solvent can enhance the adsorption and influence the protonation steps, which subsequently affects the protonation and dimerization behavior as well as the performance and selectivity of e-CORR on DACs. We further demonstrate that the C−C coupling is easy to be formed and stabilized if the Integrated Crystal Orbital Hamilton Population (ICOHP) is low because of the low energy barrier. Our findings provide not only guidance on the design of novel catalysts for e-CORR, but an insightful understanding on the reduction mechanism.     

Biomarkers based on multiplatform comprehensive analysis: A systematic analysis of Geng-Nian-Shu in perimenopausal syndrome

Although Geng-Nian-Shu has been shown to be clinically effective in perimenopausal syndrome, its active components and mechanism have not yet been elucidated. To demonstrate the mechanism-based biomarkers of Geng-Nian-Shu in treating perimenopausal syndrome, a total of 135 chemical constituents including 52 prototype blood constituents were identified via high-performance liquid chromatography-quadrupole-time of flight/mass spectrometry. Then, network pharmacology showed significant enrichment for the PhosphoInositide-3 Kinase/Akt pathway, suggesting that it may be the main regulatory pathway for the Geng-Nian-Shu treatment of the perimenopausal syndrome. Subsequently, multivariate analysis was performed between the Geng-Nian-Shu sham-treated and Geng-Nian-Shu ovariectomy-treated groups and further screened out 18 prototype blood constituents by correlation analysis with plasma estrogen levels to identify potential biomarkers associated with Geng-Nian-Shu treat the ovariectomy-induced perimenopausal syndrome. Finally, the results of pharmacological experimental verification and Pearson correlation analysis indicated that catalpol, ligustilide, paeoniflorin, and gallic acid were selected as biomarkers of Geng-Nian-Shu which were strongly and positively correlated with PhosphoInositide-3 Kinase/Akt signaling pathway. In this study, based on high-performance liquid chromatography-quadrupole-time of flight/mass spectrometry combined with pharmacodynamics, network pharmacology, pharmacology, and other disciplines, we explored the effects and mechanisms of Geng-Nian-Shu in the treatment of perimenopausal syndrome at multiple levels. Using multiplatform technology to investigate the role of Geng-Nian-Shu represents a new strategy for the selection and verification of biomarkers of Geng-Nian-Shu and provides a basis for further development and utilization of Geng-Nian-Shu.     

An efficient high-speed counter-current chromatography method for the preparative separation of sesquiterpenoids from the rhizomes of Cyperus rotundus L. combined with evaluation of the anti-inflammation activity in vitro and molecular docking

Cyperus rotundus L. has been extensively used in ancient medication for the treatment of different disorders worldwide, in which sesquiterpenes are the most representative components. In this study, sesquiterpenes were effectively purified by two-dimensional counter-current chromatography in combination with continuous injection and inner-recycling mode with a solvent system of n-hexane/ethyl acetate/methanol/water (1:0.2:1:0.2, v/v/v/v). For one-dimension separation, continuous injection mode was used with three times injection and the inner-recycling mode was adopted for the separation of two mixtures for two-dimensional separation. Finally, four sesquiterpenoids, including scariodione ( 1 ), cyperenoic acid ( 2 ), scariodione ( 3 ), and α-cyperone ( 4 ), were obtained with purities over 98%. Mass spectrometry and nuclear magnetic resonance were applied to identify their structures. The results from the anti-inflammation effect with zebrafish demonstrated that cyperenoic acid exhibited stronger anti-inflammation activity. Molecular docking results suggested that cyperenoic acid possessed lower binding energies –9.4545 kcal/mol with 1CX2 to form formed hydrogen bond interaction with ARG120. In general, all the obtained findings proved that the strong anti-inflammation capacity of cyperenoic acid can have the potential of being adopted for treating diseases resulting from inflammation.     

Infection Microenvironment-Sensitive Photothermal Nanotherapeutic Platform to Inhibit Methicillin-Resistant Staphylococcus aureus Infection

Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple inflammations. The biofilm formed by MRSA is resistant to a variety of antibiotics and is extremely difficult to cure, which seriously threatens human health. Herein, a nanoparticle encapsulating berberine with polypyrrole core and pH-sensitive shell to provide chemo-photothermal dual therapy for MRSA infection is reported. By integrating photothermal agent polypyrrole, berberine, acid-degradable crosslinker, and acid-induced charge reversal polymer, the nanoparticle exhibited highly efficient MRSA infection treatment. In normal uninfected areas and bloodstream, nanoparticles showed negatively charged, demonstrating high biocompatibility and excellent hemocompatibility. However, once arriving at the MRSA infection site, the nanoparticle can penetrate and accumulate in the biofilm within 2 h. Simultaneously, berberine can be released into biofilm rapidly. Under the combined effect of photothermal response and berberine inhibition, 88.7% of the biofilm is removed at 1000 µg mL⁻¹. Moreover, the nanoparticles have an excellent inhibitory effect on biofilm formation, the biofilm inhibition capacity can reach up to 90.3%. Taken together, this pH-tunable nanoparticle can be employed as a new generation treatment strategy to fight against the fast-growing MRSA infection.     

Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy

Chemotherapy drugs continue to be the main component of oncology treatment research and have been proven to be the main treatment modality in tumor therapy. However, the poor delivery efficiency of cancer therapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. The recent integration of biological carriers and functional agents is expected to camouflage synthetic biomimetic nanoparticles for targeted delivery. The promising candidates, including but not limited to red blood cells and their membranes, platelets, tumor cell membrane, bacteria, immune cell membrane, and hybrid membrane are typical representatives of biological carriers because of their excellent biocompatibility and biodegradability. Biological carriers are widely used to deliver chemotherapy drugs to improve the effectiveness of drug delivery and therapeutic efficacy in vivo, and tremendous progress is made in this field. This review summarizes recent developments in biological vectors as targeted drug delivery systems based on microenvironmental stimuli-responsive release, thus highlighting the potential applications of target drug biological carriers. The review also discusses the possibility of clinical translation, as well as the exploitation trend of these target drug biological carriers.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

Preparation of ZSM‐5 Coated on Monolithic Interconnected Macroporous Al2O3 Using Cheap n‐Butylamine as Template

Using cheap n‐butylamine as template, ZSM‐5 zeolites have been successfully synthesized and coated on monolithic interconnected macroporous Al₂O₃ by the secondary growth method. The use of cheap n‐butylamine could significantly reduce the synthesis cost. Hierarchical monolithic ZSM‐5 zeolites were prepared from synthetic mixtures with different H₂O/Na₂O or SiO₂/Al₂O₃ ratio. The synthesized samples were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FT‐IR) and N₂ adsorption‐desorption. The results show that the hierarchical monolithic zeolites were obtained with cheap n‐butylamine template as template. During the hydrothermal reaction process, the morphology of the micrometer‐sized support was well maintained. The irregular crystals were formed in a wide range of the H₂O/Na₂O or SiO₂/Al₂O₃ ratio of synthetic mixtures and coated on monolithic Al₂O₃. The relative crystallinity of the zeolites was highest at H₂O/Na₂O=250 or SiO₂/Al₂O₃=160. This type of composites exhibited hierarchical porous structures and relatively high specific surface areas.