A Click Chemistry Approach to Developing Molecularly Targeted DNA Scissors

Nucleic acid click chemistry was used to prepare a family of chemically modified triplex forming oligonucleotides (TFOs) for application as a new gene-targeted technology. Azide-bearing phenanthrene ligands—designed to promote triplex stability and copper binding—were ‘clicked’ to alkyne-modified parallel TFOs. Using this approach, a library of TFO hybrids was prepared and shown to effectively target purine-rich genetic elements in vitro. Several of the hybrids provide significant stabilisation toward melting in parallel triplexes (>20 °C) and DNA damage can be triggered upon copper binding in the presence of added reductant. Therefore, the TFO and ‘clicked’ ligands work synergistically to provide sequence-selectivity to the copper cutting unit which, in turn, confers high stabilisation to the DNA triplex. To extend the boundaries of this hybrid system further, a click chemistry-based di-copper binding ligand was developed to accommodate designer ancillary ligands such as DPQ and DPPZ. When this ligand was inserted into a TFO, a dramatic improvement in targeted oxidative cleavage is afforded.     

A Modular Synthetic Strategy for Functional Macrocycles

Reported here is a molecule‐Lego synthetic strategy for macrocycles with functional skeletons, involving one‐pot and high‐yielding condensation between bis(2,4‐dimethoxyphenyl)arene monomers and paraformaldehyde. By changing the blocks, variously functional units (naphthalene, pyrene, anthraquinone, porphyrin, etc.) can be conveniently introduced into the backbone of macrocycles. Interestingly, the macrocyclization can be tuned by the geometrical configuration of monomeric blocks. Linear (180°) monomer yield cyclic trimers and pentamers, while V‐shaped (120°, 90° and 60°) monomers tend to form dimers. More significantly, even heterogeneous macrocycles are obtained in moderate yield by co‐oligomerization of different monomers. This series of macrocycles have the potential to be prosperous in the near future.     

“链接”化学及其应用

介绍了“链接”化学(click chemistry)的一些基本概念, 综述了近几年来“链接”化学作为一种新的组合合成方法, 在先导的发现、优化、蛋白质组学(proteomics)和DNA的研究中的应用.     

Sunlight‐Driven Copper‐Catalyst Activation Applied to Photolatent Click Chemistry

The synthesis, full characterization, photoreduction properties, and catalytic activity for the copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC) reaction of a copper(II)–DMEDA (N,N′‐dimethylethylendiamine) complex is reported. Spectroscopic studies (UV/Vis, EPR) demonstrated that under daylight illumination highly effective copper(II) to copper(I) reduction occurs in this complex. These findings are in agreement with a high photoreduction quantum yield value of 0.22 in MeOH, and a value approaching unity as determined in THF. The reduction process, which can also be conducted by irradiation at 365 nm by using a standard TLC (thin layer chromatography) lamp, is ascribed to a highly efficient photoinduced electron transfer (PET) process mediated by the benzophenone photosensitizer present in the carboxylate counterion. Having deaerated the reaction mixture, the photogenerated copper(I) species proved to be highly active for the CuAAC reaction, demonstrated by reactions conducted with low catalyst loading (0.5 mol %) on a range of clickable protected and non‐protected mono‐ and disaccharides. Once initiated, the reaction can be stopped at any time on introducing air into the reaction medium. Deoxygenation followed by irradiation restores the activity, making the copper(II)–DMEDA complex a switchable catalyst of practical value.     

A Pyrrolysine Analogue for Protein Click Chemistry

Ignoring the STOP sign : A pyrrolysine analogue bearing a terminal alkyne was site‐specifically incorporated into recombinant calmodulin (CaM) through a UAG codon. The resulting protein was labeled with an azide‐containing dye using a copper(I)‐catalyzed click reaction. Subsequent application of an orthogonal cysteine tagging method yielded a CaM labeled with two distinct fluorophores that enabled its study by FRET spectroscopy.

     

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.     

Tandem RAFT Polymerization and Click Chemistry: An Efficient Approach to Surface Modification

PS grafted silica nanoparticles have been prepared by a tandem process that simultaneously employs RAFT polymerization and click chemistry. In a single pot procedure, azide‐modified silica, an alkyne functionalized RAFT agent and styrene are combined to produce the desired product. As deduced by thermal gravimetric and elemental analysis, the grafting density of PS on the silica in the tandem process is intermediate between analogous “grafting to” and “grafting from” techniques for preparing PS brushes on silica. Relative rates of RAFT polymerization and click reaction can be altered to control grafting density.

     

New Route to Polymeric Nanoparticles by Click Chemistry Using Bifunctional Cross-Linkers

A new route to functional polymeric nanoparticles (PNPs) of different chemical nature in the 3 to 20 nm size range is reported by combining both radical addition fragmentation chain transfer (RAFT) polymerization and “click” chemistry (CC) techniques. RAFT polymerization was employed for the synthesis of well-defined statistical copolymers with pending –Cl groups along the macromolecular chain. After transformation of the –Cl groups to –N₃ groups by treatment with sodium azide, an appropriate bifunctional cross-linker is employed to obtain PNPs under CC conditions promoting intramolecular cycloaddition (cross-linking). Following this new route, polystyrene, poly(alkyl (meth)acrylate), polymethacrylic acid, poly(sodium styrenesulfonate) and poly(N-isopropyl) NPs have been synthesized and in-deep characterized.     

Modular Synthesis of Thermosensitive P(NIPAAm‐co‐HEMA)/β‐CD Based Hydrogels via Click Chemistry

Two kinds of representative polymers, poly(N‐isopropylacrylamide) (PNIPAAm) and β‐cyclodextrin (β‐CD) were selected and modified with azide and alkyne fucntional groups, respectively. When the solutions of these two modified polymers were mixed together, a cross‐linking reaction, a type of Huisgen's 1,3‐dipolar azide‐alkyne cycloaddition, occurred in the presence of Cu(I) catalyst. The strategy described here provides several advantages for the hydrogel formation including mild reaction conditions and controllable gelation rate. The resulted hydrogels were studied in terms of scanning electric microscopy (SEM), equilibrium swelling ratio and swelling/shrinking kinetics. The data obtained demonstrated the hydrogels had a porous structure as well as favorable thermosensitivity.

     

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.     

A Modular Approach to Inorganic Phosphazane Macrocycles

Inorganic macrocycles, based on non‐carbon backbones, present exciting synthetic challenges in the systematic assembly of inorganic molecules, as well as new avenues in host–guest and supramolecular chemistry. Here we demonstrate a new high‐yielding modular approach to a broad range of trimeric and hexameric S‐ and Se‐bridged inorganic macrocycles based on cyclophosphazane frameworks, using the building blocks [S=(H)P(μ‐NR)]₂. The method involves the in situ generation of the key intermediate [E (S )P(μ‐NR)]₂²⁻(E=S, Se) dianion, which can be reacted with electrophilic [ClP(μ‐NR)]₂ to give P^III/P^V hexameric rings or reacted with I₂ to give trimeric P^V variants. Important issues which are highlighted in this work are the competitive bridging ability of S versus Se in these systems and the synthesis of the first air‐stable and chiral inorganic macrocycles.     

Spectroscopic Tracking of Molecular Transport Junctions Generated by Using Click Chemistry

Click to fill the gap : The in situ modular fabrication of molecular transport junctions in nanogaps generated by on‐wire lithography is achieved by using click chemistry (see picture). The formation of molecular junctions proceeds in high yields and can be used to test different molecules; the triazole group also maintains conjugation in the molecular wires. Raman spectroscopy is used to characterize the molecular assembly processes.

     

Solvent‐Resistant Nanofiltration for Product Purification and Catalyst Recovery in Click Chemistry Reactions

The quickly developing field of “click” chemistry would undoubtedly benefit from the availability of an easy and efficient technology for product purification to reduce the potential health risks associated with the presence of copper in the final product. Therefore, solvent‐resistant nanofiltration (SRNF) membranes have been developed to selectively separate “clicked” polymers from the copper catalyst and solvent. By using these solvent‐stable cross‐linked polyimide membranes in diafiltration, up to 98 % of the initially present copper could be removed through the membrane together with the DMF solvent, the polymer product being almost completely retained. This paper also presents the first SRNF application in which the catalyst permeates through the membrane and the reaction product is retained.     

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.     

A Click Approach to Chiral‐Dendronized Polyfluorene Derivatives

A new kind of chiral‐dendronized binaphthyl‐containing polyfluorene derivatives has been synthesized through “click chemistry” efficiently. The resulting copolymers exhibited desirable properties, such as excellent solubility, good thermal stability, and considerably high molecular weights. The photophysical properties of the copolymers were investigated in details, and the results indicated that the combination of chiral binaphthyl unit and bulky dendron could effectively suppress intermolecular packing and aggregation. In addition, the investigation of circular dichroism behavior of these chiral‐dendronized copolymers showed a strong Cotton effect at long wavelength (373–379 nm), indicating that the chirality of the binaphthyl units was transferred to the whole polyfluorene backbone.