Click Chemistry合成1,2,3-三唑氨基酸衍生物

通过W ong叠氮转化和亲核取代反应,分别合成了叠氮苯丙氨酸、叠氮丙氨酸、苄基叠氮,采用上述叠氮化物与L-炔丙基甘氨酸进行C lick反应,合成了3个1,4-取代1,2,3-三唑氨基酸衍生物:2-氨基-3-[1-(1-羧基-2-苯乙基)-1H-1,2,3-三唑-4-基]丙酸、3,3-′(1H-1,2,3-三唑-1,4-基)双(2-氨基丙酸)和2-氨基-3-(1H-1,2,3-三唑-1-苄基-4-基)丙酸,收率分别是76%、62%和68%,产物结构经核磁共振波谱、质谱、红外光谱进行了表征。1,2,3-三唑氨基酸衍生物含双功能螯合基团,是很有潜力的fac-[188Re(CO)3(H2O)3]+放射性标记配体。

Click chemistry approach to functionalize two-dimensional macromolecules of graphene oxide nanosheets

A facile "click chemistry" approach to functionalize 2D macromolecules of graphene oxide nanosheets with poly(ethylene glycol) of different molecular weights,polystyrene,palmitic acid and various amino acids was presented.FTIR,TGA,Raman spectroscopy,XPS,XRD,TEM,AFM and SEM were utilized to characterize the products.High degree of functionalization was achieved on the flat surfaces of graphene oxide,affording polymer-grafted 2D brushes and amino acids-immobilized nanosheets,which show improved solubility in organic solvents.The click chemistry strategy reported herein provides a facile and general method for functionalization of graphene oxide with macromolecules and desired biomolecules.

Development of Cardanol-Based Polyol via Click Chemistry and Crosslinking with Melamine Formaldehyde Resin for Coating Applications

The research work presented in this article deals with the synthesis of cardanol-based polyol and its curing with hexabutoxymethyl melamine(HBMM)for application in coatings.Cardanol-based polyol was prepared via thiol-ene click reaction using thioglycerol.Unsaturation present in the long chain of cardanol was successfully utilized to synthesize polyol via thiol-ene coupling.The reaction was carried out between cardanol and thioglycerol in the presence of Irgacure 184(photoinitiator)and 1,8-Diazabicyclo[5.4.0]undec-7-ene(catalyst)under UV light for 12 h at 80°C.After completion of the reaction,one mole of thioglycerol was successfully added across the double bond of a fatty chain of cardanol and confirmed by Fourier transform infrared spectroscopy(FTIR)and proton nuclear magnetic resonance spectroscopy and hydroxyl and iodine values were determined.Furthermore,the polyol thus prepared was cured with commercial HBMM in various proportions,such as 1:0.6,1:0.8 and 1:1,on an equivalent basis.The coatings were then characterized for mechanical,chemical,optical,thermal and anticorrosive properties.It was observed that coatings exhibited excellent performance properties as compared to that of its acrylic counterpart.

Preparation of novel chiral stationary phase based on click chemistry for ligand exchange chromatography

Click chemistry was applied to immobilize L-proline derivative onto azide-modified silica gel to give a novel chiral stationary phase （denoted as click-CSP） for ligand exchange chromatography. The developed protocol combines the benefits of operational simplicity, exceptionally mild conditions and high surface loadings. The enantioselectivity α of some DL-arnino acids on the click- CSP were found to be in the range from 1.13 to 3.46. The chromatographic resolutions of some DL-amino acids and the stability study firmly illustrate the potential of click chemistry for preparation chiral stationary phase for ligand exchange chromatography.

SYNTHESIS OF A HYPERBRANCHED POLY(AROYLARYLENE) CONTAINING TRIAZOLE AND FLUORENE FUNCTIONALITIES BY CLICK CHEMISTRY AND METAL-FREE,REGIOSELECTIVE POLYCYCLOTRIMERIZATION

A new bis(aroylacetylene) containing tfiazole and fluorene moieties is synthesized by click chemistry. Polycyclotrimerization of the monomer is catalyzed by piperidine in refluxed dioxane,furnishing a regioregular poly(aroylarylene) in a satisfactory yield.The hyperbranched structure of the polymer is characterized spectroscopically with satisfactory results.The polymer enjoys no metal detriment and is soluble in common organic solvents such as tetrahydrofuran (THF),chloroform,dichloromethane (DCM),and N,N-...

Cardanol-Based Polyurethane Coatings via Click Chemistry:An Eco-friendly Approach

This research work discloses the preparation of polyurethane coatings from cardanol modified using thiolene chemistry,wherein unsaturated long alkyl chain of cardanol was successfully utilized via thiol-ene click reaction to synthesize polyol.For this purpose,cardanol and thioglycerol was reacted in the presence of Irgacure 184(photoinitiator)and 1,8-Diazabicyclo[5.4.0]undec-7-ene(catalyst)and exposed to UV light for 12 h at 80℃.One mole of thioglycerol was successfully added across the double bond of fatty chain of cardanol and confirmed by chemical and spectroscopic analysis.Further,the polyol thus prepared was cured with various polyisocyanates,viz.,N-75(HDI based),L-67/BA(TDI based),Z-4470(IPDI based)and corresponding polyurethane coatings were developed.The coatings were then analyzed for mechanical,chemical,optical,thermal and anticorrosive properties.It was observed that cardanol-based PU coatings exhibited excellent mechanical,chemical and thermal and anticorrosive properties as compared to that of commercial acrylic-PU coatings.

基于SCIE的有关“Click chemistry”研究论文分析

依据Web of Science平台下的SCIE数据库中2001-2014年间有关"Click chemistry"的论文数据和文献计量方法,从发表年份、国家、机构、期刊和研究方向等进行聚类分析,研究"Click chemistry"自首次提出后的研究发展情况。结果表明,美国发表相关论文的数量和质量均位居世界第一。中国的发文量排名第二,但是论文质量和世界先进水平仍有一定差距。

Study on technetium-99m labeling of graphene oxide nanosheets through click chemistry–^(99m)Tc labeling of graphene oxide nanosheets

Graphene oxide(GO)nanosheets possess several advantages,such as a large surface,outstanding biocompatibility,and straightforward chemical modification capability.They also have great potential as a drugcarrier.In this article,we radiolabeled GO nanosheets with99mTc,which satisfies the potential needs of microSPECT imaging probes in pre-clinical and clinical research.GO nanosheets were synthesized through the modified Hummers’method,then GO nanosheets with azide group covalently functionalized in two steps were conjugated to DOTA(1,4,7,10-tetraazacyclododecane-N,N,N,N-tetraacetic acid)and functionalized with an alkynyl group by means of click chemistry.Then through the addition and reduction of technetium-99m,the99mTc-DOTA-GO were attained.DOTA-conjugated GOs with lateral dimensions of 500–600 nm were synthesized.Both atomic force microscopy(AFM)and FT-IR were performed to characterize the GO-DOTA.Labeling efficiency of GO-DOTA with99mTc was>90%and radiochemical purities were>96%with purification.We successfully synthesized graphene oxide derivatives,DOTA-conjugated GOs,via Click Chemistry,and it was labeled with99mTc for SPECT imaging.High radiolabeling efficiency makes GO nanosheets suitable platforms for future molecular imaging research.

Preparation of Hydrophilic and Shrink-Proofing Wool Fabrics Through Thiol-Ene Click Chemistry Reaction

To improve shrink-proofing performance and hydrophilicity of wool fabrics, the wool fibers were modified by poly(ethylene glycol) dimethacrylate(PEGDMA) through thiol-ene click chemistry reaction. Firstly, wool fabrics were reduced at room temperature with a high-efficiency disulfide bond reducing agent, tris(2-carbonxyethyl) phosphine hydrochloride(TCEP). Then the thiol-ene click chemistry reaction was initiated by dimethyl 2, 2’-azobis(2-methylpropionate)(AIBME) through the heating method. Fourier transform infrared(FTIR) spectroscopy, Raman spectroscopy, and scanning electron microscopy test results all showed that PEGDMA was successfully grafted onto wool fabric surface. Physical properties, hydrophilicity, and shrink-proofing performance were assessed. The wetting time of PEGDMA grafted wool fabrics decreased to about 3 s. After being grafted with PEGDMA, the felting shrinkage of wool fabrics rapidly decreased to about 8%. The anti-pilling properties of wool fabrics were also greatly improved to 5 class after 2 000 times of friction. Meanwhile, the load retention rate of fabrics could reach 90%. It provides a method of wool modification to improve hydrophilicity and anti-felting performance.

Study on radiolabeling of 1,2,3-triazole analogs with fac-[^(188)Re(CO)_3 (H_2O)_3 ]^+ via click chemistry

Click chemistry was used to study on radiolabeling of 1,2,3-triazole analogs with fac-[188 Re(CO) 3 (H 2 O) 3]+ . CuSO 4 /L-sodium ascorbate was chosen as the catalyst system, three terminal alkynes were conjugated with two different azides respectively, and then the new prepared fac-[188 Re(CO) 3 (H 2 O) 3]+ was coordinated to the six triazoles. The results showed that the radiochemical yields (RCY) of the conjugation of fac-[188 Re(CO) 3]+ with six triazoles were over 90%, and the triazoles showed high stability in phosphate-buffered saline and new-born calf serum. The preliminary biological evaluation results showed that the new 188 Re-labeling method via click chemistry could have general application in labeling bioactive molecules in high radiochemical yield and high specific activity for further SPECT research.

建议将click chemistry译作“配搭化学”

学界通常将click chemistry翻译成"点击化学",有望文生义之嫌。笔者分析此术语提出者的原意--一是具有高度的双向选择性,二是如同搭扣"咔嗒"扣起来一样简单,再结合自己对此化学反应的深刻理解,建议将其译为形神兼备的"配搭化学"。

化学术语click chemistry和one-pot synthesis 的中文译法刍议

当前中文化学术语中存在粗疏翻译的现象,对click chemistry和one-pot synthesis的翻译即为两例。文章根据术语翻译信达雅的原则,建议将这两个英文化学术语分别译为"迅接化学"和"烩法合成",以取代在中文文献中常见的不甚合理的译法。

基于点击化学和非巯基DNA修饰纳米金的维生素C检测

目的建立一种基于点击化学和非巯基DNA修饰的叠氮纳米金的可视化维生素C(vitaminC,VC)检测方法。方法用一端有多个腺嘌呤核苷酸的非巯基DNA修饰纳米金,再与一端有叠氮基的互补链杂交,形成表面暴露出叠氮基团的叠氮纳米金。在VC的存在下,将Cu^(2+)还原成Cu^(+),催化叠氮纳米金与三炔丙基胺发生点击化学反应,使叠氮纳米金聚集,引起光谱和颜色的变化。通过光谱和颜色的变化进行VC检测。结果在pH为7、Cu^(2+)浓度为100μmol/L、三炔丙基胺浓度为3μmol/L和反应时间12 min的最优条件下,用分光光度计检测VC的检出限为0.042mg/L,目视的检出限为0.05mg/L。该方法成功用于饮料中VC的测定,呈现了良好的回收率,从而验证了该方法的可靠性和可行性。结论这项研究提供了一种简便、超灵敏的VC检测方法,可用于VC的微量可视化检测。

基于点击化学的酸敏感性聚合物前药的设计与合成

基于点击化学反应,将姜黄素和己烷-1,6-二丙炔酸二酯直接共聚,制备了酸敏感性主链型聚合物前药,并采用紫外可见吸收光谱法、荧光光谱法、红外光谱法、扫描电子显微镜、粒径分布及Zeta电位对其结构进行了表征。结果表明,聚合物前药为粒径100~200 nm的球形纳米粒子,形状均匀,分散性良好;聚合物前药在肿瘤微环境下通过酸触发聚合物主链降解,实现对药物的可控性释放。为提升常规化疗药物疗效并降低其毒副作用研究提供了参考。

A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.

Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

“Click”化学在药物发现中的应用

“click”化学是最近几年发展起来的一种新技术,它在药物发现的许多方面均有着广泛的应用:快速合成小分子化合物库并从中筛选先导化合物、进行靶标导向的活性小分子合成以及在生物耦联技术等方面的应用。

贻贝仿生聚酚胺涂层固定REDV短肽促内皮化探究

药物洗脱支架(DES)的发展显著降低了支架的再狭窄率,但引入的药物会不可避免地造成内皮层的损伤,从而影响病灶部位内皮屏障的完整性和功能性。结构完整及功能正常的血管内皮细胞层是维持血管组织稳态以及凝血系统平衡的重要保障。使用兼具优良血液相容性及促内皮化功能的涂层对支架进行预处理,是改善血管支架等心血管植入器械并发症的有效策略。本研究选用氧化剂高碘酸钠加速多巴胺自聚合,使其在支架材料表面快速形成聚酚胺涂层PDA,制备方法简单且省时;随后通过迈克尔加成反应点击接枝功能性短肽REDV,构建促内皮化涂层P-REDV,REDV肽接枝效率高且接枝密度大(9.84 ng/cm^(2))。该涂层在体外细胞培养实验中对内皮细胞粘附具有选择性促进作用,同时显示出优异的血液相容性,为解决药物洗脱支架及心血管植入器械延迟内皮化的问题提供了一种新的策略。

木质素单体跨膜转运的技术研究进展

木质素(lignin)作为一种重要的可再生资源,主要集中在植物的次生细胞壁中,在植物的营养物质运输、机械支持和病原体防御等生理过程中发挥着关键作用。木质素的形成过程包括3个主要环节:单体的胞内合成、跨膜转运以及胞外聚合。深入探究木质素单体跨膜转运的分子机制,对揭示细胞壁形成分子机制及木材改良具有重要意义。基于此,本综述从转录组学、基因工程、点击化学、荧光显微成像、分子模拟等技术角度,对木质素单体跨膜转运的相关进展和最新技术进行了梳理和总结,阐述了木质素单体跨膜转运相关研究的新技术和存在的技术瓶颈,并对比分析了不同技术之间的优缺点,最后提出了木质素单体跨膜转运机制研究中仍存在的问题和面临的挑战。相信随着成像技术、结构生物学、人工智能等科技的飞速发展,将为进一步阐明木质素单体跨膜转运的分子机理提供有效的技术手段。期望本综述为木质素单体的相关研究提供新的思路和方法。