Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications

Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the Cu^I‐catalyzed alkyne–azide cycloaddition and its strain‐promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site‐specific manner and recognized by antibody binding to demonstrate the proof‐of‐concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material.     

Click Functionalization of a Dibenzocyclooctyne‐Containing Conjugated Polyimine

A conjugated poly(phenyl‐co‐dibenzocyclooctyne) Schiff‐base polymer, prepared through polycondensation of dibenzocyclooctyne bisamine (DIBO‐(NH₂)₂) with bis(hexadecyloxy)phenyldialdehyde, is reported. The resulting polymer, which has a high molecular weight (M_n>30 kDa, M_w>60 kDa), undergoes efficient strain‐promoted alkyne–azide cycloaddition reactions with a series of azides. This enables quantitative modification of each repeat unit within the polymer backbone and the rapid synthesis of a conjugated polymer library with widely different substituents but a consistent degree of polymerization (DP). Kinetic studies show a second‐order reaction rate constant that is consistent with monomeric dibenzocyclooctynes. Grafting with azide‐terminated polystyrene and polyethylene glycol monomethyl ether chains of varying molecular weight resulted in the efficient syntheses of a series of graft copolymers with a conjugated backbone and maximal graft density.     

Post-assembly Functionalization of Organoplatinum(II) Metallacycles via Copper-free Click Chemistry

We describe the use of a strain-promoted copper-free click reaction in the post-self-assembly functionalization of organoplatinum(II) metallacycles. The coordination-driven self-assembly of a 120° cyclooctyne-tethered dipyridyl donor with 60° and 120° di-Pt(II) acceptors forms molecular rhomboids and hexagons bearing cyclooctynes. These species undergo post-self-assembly [3+2] Huisgen cycloaddition with a variety of azides to give functionalized ensembles under mild conditions.     

A Ligand System for the Flexible Functionalization of Quantum Dots via Click Chemistry

We present a novel ligand, 5‐norbornene‐2‐nonanoic acid, which can be directly added during established quantum dot (QD) syntheses in organic solvents to generate “clickable” QDs at a few hundred nmol scale. This ligand has a carboxyl group at one terminus to bind to the surface of QDs and a norbornene group at the opposite end that enables straightforward phase transfer of QDs into aqueous solutions via efficient norbornene/tetrazine click chemistry. Our ligand system removes the traditional ligand‐exchange step and can produce water‐soluble QDs with a high quantum yield and a small hydrodynamic diameter of approximately 12 nm at an order of magnitude higher scale than previous methods. We demonstrate the effectiveness of our approach by incubating azido‐functionalized CdSe/CdS QDs with 4T1 cancer cells that are metabolically labeled with a dibenzocyclooctyne‐bearing unnatural sugar. The QDs exhibit high targeting efficiency and minimal nonspecific binding.     

Functionalization of Macroporous Organic Polymer Monolith Based on Succinimide Ester Reactivity for Chiral Capillary Chromatography: A Cyclodextrin Click Approach

Macroporous cross‐linked organic polymer based on N‐acryloxysuccinimide (NAS) and ethylene dimethacrylate (EDMA) was prepared inside 75 µm id fused silica capillary as a functionalizable monolithic stationary phase for chromatographic applications. Succinimide groups on the monolith surface provide reactive sites able to react readily through standard electrophile–nucleophile chemistry. Propargylamine was used to prepare alkyne functionalized poly(NAS‐co‐EDMA). Onto this azido‐reactive polymer surface was grafted β‐cyclodextrin (CD) via a triazole ring utilizing the copper(I)‐catalyzed 1,3‐dipolar cyclo‐addition reaction. Chemical characterization was performed in situ after each synthetic step by means of Raman spectroscopy. Good enantioseparations of flavanone enantiomers, chosen as test chiral compound, were achieved under reversed phase conditions by both capillary electrochromatography and nano‐liquid chromatography (nano‐LC) techniques. These results demonstrate the potentiality and usefulness of click chemistry in the preparation of β‐CD containing chiral organic polymer monolith.

     

Mono‐, Di‐, or Triazidated Cyclodextrin‐Based Polyrotaxanes for Facile and Efficient Functionalization via Click Chemistry

As a feasible way for controlling the density of ligands in polyrotaxanes, azidated polyrotaxanes comprising PEG (MW = 3 000 and 20 000 g · mol⁻¹) and mono‐, di‐, or triazidated α‐cyclodextrins are prepared in a water/DMSO solution in a one‐pot synthesis. The azidated polyrotaxanes are then allowed to conjugate with propargyl‐modified mannose as a ligand via click chemistry. As proven by FTIR spectroscopy and ¹H NMR‐spectroscopy, mannose molecules are efficiently introduced into all of the azide moieties of the polyrotaxanes. The results verify the achievement of ligand‐density‐controlled polyrotaxanes. The functionalized polyrotaxanes can be utilized for a variety of biological applications.

     

High‐Density DNA Functionalization by a Combination of Cu‐Catalyzed and Cu‐Free Click Chemistry

We report the regioselective Cu‐free click modification of styrene functionalized DNA with nitrile oxides. A series of modified oligodeoxynucleotides (nine base pairs) was prepared with increasing styrene density. 1,3‐Dipolar cycloaddition with nitrile oxides allows the high density functionalization of the styrene modified DNA directly on the DNA solid support and in solution. This click reaction proceeds smoothly even directly in the DNA synthesizer and gives exclusively 3,5‐disubstituted isoxazolines. Additionally, PCR products (300 and 900 base pairs) were synthesized with a styrene triphosphate and KOD XL polymerase. The click reaction on the highly modified PCR fragments allows functionalization of hundreds of styrene units on these large DNA fragments simultaneously. Even sequential Cu‐free and Cu‐catalyzed click reaction of PCR amplicons containing styrene and alkyne carrying nucleobases was achieved. This new approach towards high‐density functionalization of DNA is simple, modular, and efficient.     

微波促进的点击化学

自2001年Sharpless等提出点击化学概念以来,Cu(I)催化的炔与叠氮之间的1,3-偶极环加成反应(Cue-AAC)已经成为点击化学最成功的范例.Cue-AAC反应由于其良好的立体选择性、模块性以及官能团耐受性等特点迅速成为许多研究领域,例如药物化学、材料科学等领域中的有力工具.同时,微波加热作为一种高效、绿色合成技术已越来越受到人们的重视,相对于传统加热方式,它能大幅缩短反应时间,提高产率和纯度.综述了近十年来利用微波加热与点击化学相结合的策略在合成生物大分子及小分子化合物库中的应用,并对其发展前景作了展望.     

巯基-烯点击化学

点击化学自2001年由Sharpless提出后,由于其高效、可靠、高选择性的特点迅速成为药物和高分子材料合成的新方法。随着对点击化学研究的深入,其反应类型在不断增多,应用范围也在不断扩大。自由基或亲核试剂引发的巯基-烯反应作为其中一种新型的点击反应具有点击化学的所有特性。本文从点击化学的概念、特征和类型出发,重点介绍了巯基-烯反应的机理和在合成功能聚合物、制备拓扑结构高分子、表面修饰以及生物药物等方面的应用,并对巯基-烯反应的最新研究成果进行综述,最后展望了巯基-烯的点击化学的发展前景。     

Click chemistry with ynamides

A series of diversely 1-substituted 4-amino 1,2,3-triazoles were synthesized by [3+2] cycloaddition between azides and ynamides. This copper catalyzed process represents the first examples of a ‘click reaction’ employing ynamides and should expand the scope of the ynamide chemistry both synthetically and industrially. Various azides (even highly functionalized) were allowed to react with N-benzyl, N-tosyl ynamide to give the corresponding triazole adducts in high yield and with very high levels of regioselectivity.     

点击化学简介

点击化学是2001年诺贝尔化学奖获得者美国化学家Sharpless提出的一种快速合成大量化合物的新方法。介绍了点击化学的概念及其主要反应类型,综述了点击化学作为一种新的合成方法在药物开发、聚合物合成和表面修饰等领域的应用,并对其发展前景进行了展望。     

点击化学最新进展

点击化学(click chemistry)是由2001年诺贝尔化学奖获得者美国化学家 Sharpless首次提出。最主要的一类点击化学反应是Cu(Ⅰ)化合物催化叠氮化合物与炔基化合物反应生成1,2,3-三唑五元环化合物,它能够将两种不同物质通过五元环共价结合起来。该方法具备产量高、效率高、副反应少、反应条件温和、分离提纯简单、环境污染小等优点,因此得到了广泛的应用。目前点击化学的发展极为迅速,涉及到了各个领域,特别是在功能聚合物、表面修饰、生物大分子、DNAs,生物与化学传感器等方面取得了瞩目的成就。本文论述了点击化学反应的基本概念、特点及优势,对近几年点击化学的发展状况,以及一些最新研究成果作一简要概述,并展望了点击化学的发展前景。     

Click Chemistry with Polysaccharides

Summary: The copper‐catalyzed Huisgen reaction as a typical example of click chemistry was realized with the polysaccharide cellulose for the first time. The generality, selectivity, and the efficiency of click chemistry perfectly fit the requirements of polysaccharide modification, which is demonstrated by the introduction of triazole‐spacer bound functional groups, i.e., carboxylic ester, thiophene, and aniline moieties. Azide moieties introduced into cellulose via the tosyl derivative were simply transferred with ethynyl compounds under Cu(I) catalysis and mild and easily applicable conditions. Hydrolytically stable cellulose derivatives soluble in organic solvents, e.g., DMSO or DMF with DS up to 0.9 are obtained. The triazole substituted cellulose derivatives were characterized by elemental analysis, FTIR, ¹H NMR, and ¹³C NMR spectroscopies and show no impurities or substructures resulting from side reactions.

6‐Azido‐6‐deoxy cellulose.     

Hydrogel-Based Macroscopic Click Chemistry

The click reaction has found good utility across various fields due to the characteristics of high efficiency, atom economy, simple and mild reaction conditions. Click chemistry is usually utilized for connecting components of microscopic level, while it is still unable for joining macroscopic building blocks. Materials consisting of macroscopic building blocks realize the flexible fabrication of three-dimensional structures at macroscopic level, exerting significance on parallel manufactures. In this work, we reported macroscopic click chemistry utilizing hydrogel as macroscopic building blocks. Hydrogels G1 and G2 were prepared by incorporating M1 (N,N′-dimethyl-1,2-ethanediamine) and P1 (alkyne functionalized polyethylene glycol) respectively, where polymer chains formed through diffusion-induced amino-yne click reaction entangled different hydrogel networks together. Additionally, chain-like aggregates and complicated 3D structures such as tetrahedron and quadrangular pyramid were constructed based on the adhesion of the hydrogel blocks. The approach enables us to find more possibilities in the delicate designation of 3D aggregations as well as large-scale manufacturing.     

巯基点击反应研究进展

巯基参与的点击反应具有简单、快速、无金属催化等优点。本文介绍了巯基点击反应的反应机理,着重对近年来新出现的巯基点击反应的概念、特点进行分类介绍,并综述了巯基点击反应在材料与分子设计方面的应用,最后对其发展前景进行了展望。     

Click chemistry to functionalise peptidomimetics

Sharpless modified Huisgen’s [2+3] cycloaddition of azide and acetylenic derivatives was employed as an efficient and simple method to conjugate azabicycloalkane amino acids, mimics of a homoSer-Pro dipeptide, with biologically relevant partners.