Calixarene‐Based Chemosensors by Means of Click Chemistry

Click chemistry, a new strategy for organic chemistry, has been widely used in the chemical modification of calixarenes because of its reliability, specificity, biocompatibility, and efficiency. Click‐derived triazoles also play a critical role in sensing ions and molecules. This in‐depth review provides an overview of calixarene‐based chemosensors that incorporate click‐derived triazoles, and their three characteristics (chromogenic, fluorescence, and wettability) are reviewed.     

A Nucleobase‐Discriminating Pyrrolo‐dC Click Adduct Designed for DNA Fluorescence Mismatch Sensing

New pyrrolo‐dC click adducts ( 4 and 5 ) tethered with a 1,2,3‐triazole skeleton were synthesized and oligonucleotides were prepared. The triazole system was either directly linked to the pyrrolo moiety ( 5 ) or connected via an n‐butyl linker ( 4 ). The quantum yield of nucleoside 5 (Φ=0.32), which is 10 times higher than those of 8‐methylpyrrolo‐dC ( 1 b , Φ=0.026) or the long linker derivative 4 (Φ=0.03), is maintained in oligonucleotides. Compound 5 was used as a nucleobase‐discriminating fluorescence sensor in duplex DNA. Excellent mismatch discrimination was observed when 5 was positioned opposite the four canonical nucleosides. Compound 5 has the potential to be used for SNP detection in long DNA targets when conventional techniques such as high resolution melt analysis fail.     

Click Polyester: Synthesis of Polyesters Containing Triazole Units in the Main Chain by Click Chemistry and Improved Thermal Property

A “click” polymerization of dialkynes that contain an ester linkages and diazides to has been performed to synthesize various polyesters, termed “click polyesters” with a high of 1.0 × 10⁴ to 7.0 × 10⁴ in an excellent yield. This polymerization accompanied a formation of 1,4‐disubstituted triazoles in the polyester main chain by a Cu^I catalyst. The triazole ring formation in the polyester main chain leads to improved thermal properties and enhancement of the even–odd effect of methylene chain length of the produced click polyesters. This report is the first report of the application of click chemistry to synthesize a series of polyesters under mild conditions.

     

ATRP和点击化学结合法制备PDMAAm—PDMS—PDMAAm嵌段聚合物

采用原子转移自由基聚合（ATRP）法制得了端基分别为烯丙基和溴原子的聚二甲基丙烯酰胺（PDMAAm），经叠氮基亲核取代后与端炔基聚二甲基硅氧烷进行点击反应，得到两亲三嵌段聚合物。利用^1HNMR、FTIR、GPC等测试方法对聚合物的结构进行了表征。结果表明：采用ATRP法合成的PDMAAm均聚物分子量分布较窄，通过点击化学法将热力学不相容的亲水性PDMAAm链段及疏水性聚二甲基硅氧烷（PDMS）链段制备PDMAAmPDMS—PDMAAm嵌段聚合物，是一种高效易行的方法。     

利用点击化学制备有机硅材料及应用

有机硅材料因其特殊结构和性能已成为材料科学研究领域的热点之一,点击化学以其反应条件温和、高效、易于进行且无副产物和高产率等优点受到化学家的广泛关注.本文综述了近年来点击化学在有机硅材料合成中的研究成果,重点介绍了利用点击化学对有机硅化合物的功能化,有机硅两亲性聚合物及有机硅弹性体的合成及在生物医学和光电材料等方面的应用,并对点击化学在新型材料领域中的应用及其发展方向进行了展望.     

Interrogating Plant-Microbe Interactions with Chemical Tools: Click Chemistry Reagents for Metabolic Labeling and Activity-Based Probes

Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes on plant growth, metabolism, and immune responses. While the majority of the studies reviewed here used chemical biology approaches to examine the effects of pathogens on plants, chemical biology will also be invaluable in future efforts to investigate mutualistic associations between beneficial microbes and their plant hosts.     

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2

Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14 , possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range.     

Closing the Ring to Bring Up the Light: Synthesis of a Hexacyclic Acridinium Cyanine Dye

The synthesis of a geometrically constrained and near‐planar hexacyclic acridinium cyanine dye 9 is reported. When compared to its unlocked and non‐fluorescent monomethine cyanine dye analogue 3 , this photostable dye emits in the green area of the spectrum with a remarkable quantum yield close to unity in organic solvents and above 0.5 in water. A detailed steady‐state and time‐resolved spectroscopic study revealed that dye 9 forms emissive aggregates in water, which are responsible for a red‐shifted and broadened emission band and longer emission lifetime, τ≈33 compared to 6.5–7.0 ns for the monomeric dye. Dye 9 also binds strongly to DNA (both duplex and quadruplex) in its monomeric form and is very efficiently taken up by cells, in which it accumulates primarily into the nucleus.     

一种具备巯基点击化学功能的二硫代酯RAFT链转移剂的合成

以2,2-二硫二吡啶,2-巯基乙醇为原料,醋酸为催化剂,合成了2-羟乙基-二硫吡啶(PⅠ)。以PⅠ、4-氰基-4-(硫代苯甲酰)戊酸(PⅡ)为原料,1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、4-二甲氨基吡啶(DMAP)为催化剂,合成了一种新的可逆加成-断裂链转移自由基聚合(RAFT)链转移剂4-氰基-4-(硫代苯甲酰)戊酸-2-二硫吡啶乙酯(PⅢ)。以PⅢ为RAFT链转移剂,偶氮二异丁腈(AIBN)为引发剂,甲基丙烯酸甲酯(MMA)为单体,采用RAFT制备了聚甲基丙烯酸甲酯(PMMA)。用1 H-NMR分析了链转移剂的的分子结构,用GPC测得PMMA聚合物的分子量及其分布。结果表明:能用于巯基点击化学的二硫吡啶基团被接到PⅡ的末端,成功制备了一种具备巯基点击化学功能的二硫代酯RAFT链转移剂(PⅢ),利用PⅢ,通过RAFT聚合制备了分子量分布狭窄的PMMA聚合物。     

Spectroscopic Study of the Interaction between New Fluorescent Dyes with Nucleic Acids

Considerableefforthasbeencofltinuingtofocusonthedevelopmentofnewfluorescentdyestorecognizenucleicacids'-'.Althoughdansylisawell-knownsensitivehydrophobicprobewhichhasbeenwidelyutilizedasafluorescentprobeforthestudyofproteins,yetlittleefforthasbeenfocusedontheexploringdansylamidederivativeswhichmayhavespecificeffectsonnucleicacids.Sincethebindingaffinityofsuchfluorophorestopolynucleotideswasgreatlyaffectedbytheirsidechainsubstitutions,inthisworkseveralnewdansylderivativeswithspecificbindingtonu…     

Key Structural Elements of Unsymmetrical Cyanine Dyes for Highly Sensitive Fluorescence Turn‐On DNA Probes

Unsymmetrical cyanine dyes, such as thiazole orange, are useful for the detection of nucleic acids with fluorescence because they dramatically enhance the fluorescence upon binding to nucleic acids. Herein, we synthesized a series of unsymmetrical cyanine dyes and evaluated their fluorescence properties. A systematic structure–property relationship study has revealed that the dialkylamino group at the 2‐position of quinoline in a series of unsymmetrical cyanine dyes plays a critical role in the fluorescence enhancement. Four newly designed unsymmetrical cyanine dyes showed negligible intrinsic fluorescence in the free state and strong fluorescence upon binding to double‐stranded DNA (dsDNA) with a quantum yield of 0.53 to 0.90, which is 2 to 3 times higher than previous unsymmetrical cyanine dyes. A detailed analysis of the fluorescence lifetime revealed that the dialkylamino group at the 2‐position of quinoline suppressed nonradiative decay in favor of increased fluorescence quantum yield. Moreover, these newly developed dyes were able to stain the nucleus specifically in fixed HeLa cells examined by using a confocal laser‐scanning microscope.     

Synthesis and Characterization of Some Novel Glycodendrimers and N-alkyldendrimers with Amide Core and Triazole Functionality through Click Chemistry

The syntheses of various types of 1,2,3-triazole-based dendrimers 1–4 with sugar pyranosylazides and N-ethyl and N-heptylazides as a surface unit and benzene-1,3,5-tricorboxlyic amide as core unit through click chemistry approach are described.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

An Optimized Protocol for the Synthesis of Peptides Containing trans-Cyclooctene and Bicyclononyne Dienophiles as Useful Multifunctional Bioorthogonal Probes

Despite the great advances in solid-phase peptide synthesis (SPPS), the incorporation of certain functional groups into peptide sequences is restricted by the compatibility of the building blocks with conditions used during SPPS. In particular, the introduction of highly reactive groups used in modern bioorthogonal reactions into peptides remains elusive. Here, we present an optimized synthetic protocol enabling installation of two strained dienophiles, trans-cyclooctene (TCO) and bicyclononyne (BCN), into different peptide sequences. The two groups enable fast and modular post-synthetic functionalization of peptides, as we demonstrate in preparation of peptide-peptide and peptide-drug conjugates. Due to the excellent biocompatibility, the click-functionalization of the peptides can be performed directly in live cells. We further show that the introduction of both clickable groups into peptides enables construction of smart, multifunctional probes that can streamline complex chemical biology experiments such as visualization and pull-down of metabolically labeled glycoconjugates. The presented strategy will find utility in construction of peptides for diverse applications, where high reactivity, efficiency and biocompatibility of the modification step is critical.     

Synthesis of Hydrophobic Polymer Brushes on Silica Nanoparticles Via the Combination of Surface-Initiated ATRP,ROP and Click Chemistry

A fascinating nanoobject, hydrophobic polymer brushes with a hard core of silica nanoparticles and a relatively soft shell of polystyrene-block-poly(? -caprolactone) (PS-b-PCL), was easily constructed by surface-initiated atom transfer radical polymerization (ATRP) of styrene, ring-opening polymerization (ROP) of ?-caprolactone and click reaction. The structure and morphology of the as-prepared hybrid nanomaterials were characterized and confirmed by FTIR, ¹H-NMR, TGA and TEM. We believe that the breakthrough associated with formation of such a complex nanoobject would open a door for the fabrication of novel functional nanomaterials or nanodevices with designable structure and tailor-made properties.     

Bioconjugatable Azo‐Based Dark‐Quencher Dyes: Synthesis and Application to Protease‐Activatable Far‐Red Fluorescent Probes

We describe the efficient synthesis and one‐step derivatization of novel, nonfluorescent azo dyes based on the Black Hole Quencher‐3 (BHQ‐3) scaffold. These dyes were equipped with various reactive and/or bioconjugatable groups (azido, α‐iodoacetyl, ketone, terminal alkyne, vicinal diol). The azido derivative was found to be highly reactive in the context of copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions and allowed easy synthetic access to the first water‐soluble (sulfonated derivative) and aldehyde‐modified BHQ‐3 dyes, the direct preparation of which failed by means of conventional azo‐coupling reactions. The aldehyde‐ and α‐iodoacetyl‐containing fluorescence quenchers were readily conjugated to aminooxy‐ and cysteine‐containing peptides by the formation of a stable oxime or thioether linkage, respectively. Further fluorescent labeling of the resultant peptide conjugates with red‐ or far‐red‐emitting rhodamine or cyanine dyes through sequential and/or one‐pot bioconjugations, led to novel Förster resonance energy transfer (FRET) based probes suitable for the in vivo detection and imaging of urokinase plasminogen activator, a key protease in cancer invasion and metastasis.     

A Versatile Approach for the Site‐Specific Modification of Recombinant Antibodies Using a Combination of Enzyme‐Mediated Bioconjugation and Click Chemistry

A unique two‐step modular system for site‐specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide–alkyne cycloaddition click reaction. The versatility of the two‐step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron‐emitting copper‐64 radiotracer for fluorescence and positron‐emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor‐made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules.     

功能性硫化镉纳米荧光探针荧光猝灭法测定核酸

报道了无机纳米溶胶CdS的合成，并对其进行了功能化修饰。研究了功能性CdS纳米溶胶的荧光性质。对小牛胸腺DNA进行了定量测定，考察了各种影响因素，在最佳实验条件下，该方法的线性区间0.1-1.5mg/L，检测限为0.018mg/L。与传统的有机染料相比，该方法简单、快速、灵敏度高。