多肽聚合物合成新方法及生物医学应用

多肽聚合物是以多肽为主链的合成聚合物,由于其固有的生物相容性和生物降解性,在生物医学领域展现出广阔的应用前景,然而多肽聚合物的高效、快速、简便合成仍然具有很大挑战。近年来随着合成化学的快速发展,基于α-氨基酸的N-羧基环内酸酐(NCA)开环聚合法制备多肽聚合物取得了突破性进展,合成了大量基于多肽聚合物的新型材料。本文首先介绍了NCA单体的合成机理及最新改进,然后重点介绍了近年来新发展的NCA开环聚合快速、高效制备多肽聚合物的不同引发或催化体系,最后简要介绍了多肽聚合物在抗菌剂、药物递送及组织工程等领域的应用,并提出了多肽聚合物材料在生物医学领域应用所面临的挑战。     

A guide to use fluorinated aromatic bulky cations for stable and high-performance 2D/3D perovskite solar cells: The more fluorination the better?

While serious stability issues impede the commercialization of perovskite solar cells(PSCs),twodimensional(2 D) perovskites based on fluorinated bulky cations have emerged as more intrinsically stable materials.However,the influence of fluorination degree of the bulky aromatic cation on the performance of resulting PSCs has not been scrutinized.Here,2 D perovskites(FxPEA)2 PbI₄(x=1,2,3,5) are grown in situ on the surface of the three-dimensional(3 D) perovskite and demonstrate effecti...     

埋置框架质量检测的探讨

提出了埋置框架的回传射线矩阵法,研究了方波脉冲轴向作用、水平作用和斜向作用下有缺陷埋置框架和无缺陷埋置框架的速度波．结果表明;横向速度波不能识别埋置框架的基桩缺陷,轴向速度波可以识别,而且基桩缺陷信号很强烈;脉冲水平作用不能识别基桩缺陷,轴向或斜向作用可以识别．     

Synthesis of unsymmetrically tetrasubstituted pyrroles and studies of AIEE in pyrrolo[1,2-a]pyrimidine derivatives

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-a]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-a]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

A novel method for the challenging synthesis of unsymmetrically tetrasubstituted NH-pyrroles from chalcone derivatives is reported. The pyrrolo[1,2-a]pyrimidine derivatives that were synthesized from NH-pyrroles exhibit AIE and AIEE property.     

Cations Modulated Assembly of Triol-Ligand Modified Cu-Centered Anderson-Evans Polyanions

Counter-cations are essential components of polyoxometalates (POMs), which have a distinct influence on the solubility, stabilization, self-assembly, and functionality of POMs. To investigate the roles of cations in the packing of POMs, as a systematic investigation, herein, a series of triol-ligand covalently modified Cu-centered Anderson-Evans POMs with different counter ions were prepared in an aqueous solution and characterized by various techniques including single-crystal X-ray diffraction. Using the strategy of controlling Mo sources, in the presence of triol ligand, NH₄⁺, Cu²⁺ and Na⁺ were introduced successfully into POMs. When (NH₄)₆Mo₇O₂₄ was selected, the counter cations of the produced POMs were ammonium ions, which resulted in the existence of clusters in the discrete state. Additionally, with the modulation of the pH of the solutions, the modified sites of triol ligands on the cluster can be controlled to form δ- or χ-isomers. By applying MoO₃ in the same reaction, Cu²⁺ ions served as linkers to connect triol-ligand modified polyanions into chains. When Na₄Mo₈O₂₆ was employed as the Mo source to react with triol ligands in the presence of CuCl₂, two 2-D networks were obtained with {Na₄(H₂O)₁₄} or {{Na₂(H₂O)₄} sub-clusters as linkers, where the building blocks were δ/δ- and χ/χ-isomers, respectively. The present investigation reveals that the charges, sizes and coordination manners of the counter cations have an obvious influence on the assembled structure of polyanions.     

Responses of Issatchenkia terricola WJL-G4 upon Citric Acid Stress

This study aimed to elucidate the responses of a novel characterized Issatchenkia terricola WJL-G4 against citric acid stress by performing physiological analysis, morphology observation, and structural and membrane fatty acid composition analysis. The results showed that under citric acid stress, the cell vitality of I. terricola WJL-G4 was reduced. The cell morphology changed with the unclear, uncompleted and thinner cell wall, and degraded the cell structure. When the citric acid concentration was 20 g/L, I. terricola WJL-G4 could tolerate citric acid and maintain the cell structure by increasing the intracellular pH, superoxide dismutase activity, and contents of unsaturated fatty acids. As the citric acid concentration was ≥80 g/L, the stress has exceeded the cellular anti-stress ability, causing substantial cell damage. The cell membrane permeability, the content of membrane lipids, malondialdehyde and superoxide anion increased, but the intracellular pH and superoxide dismutase activities decreased, accompanying the increase of citric acid concentrations. The findings of this work provided a theoretical basis for the responsive mechanism of I. terricola WJL-G4 under high concentrations of citric acid, and can serve as a reference for biological acid reduction in fruit processing.     

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C₁₈H₁₆O₈) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.     

Design,Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains

A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation.     

Palladium-Catalyzed Aminomethylation of Nitrodienes and Dienones via Double C-N Bond Activation

A new strategy for the generation of the active Pd-alkyl species from aminal via C-N bond activation has been established,in which the formation of zwitterionic...     

Hepatoprotective Effects of Ixeris chinensis on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice: An Integrated Gut Microbiota and Metabolomic Analysis

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.