Rapid preparation of multifunctional surfaces for orthogonal ligation by microcontact chemistry

Microcontact chemistry has been applied to patterned glass and silicon substrates by successive reaction of unprotected and monoprotected heterobifunctional linkers with alkene-terminated self-assembled monolayers (SAMs) to produce bi-, tri-, and tetrafunctional surfaces. Photochemical microcontact printing of an azide thiol linker followed by immobilization of an acid thiol linker on an undecenyl-terminated SAM results in a well-defined, micropatterned surface with terminal azide, acid, and alkene groups. Biologically relevant molecules (biotin, carbohydrates) have been selectively attached to the surface by means of orthogonal ligation chemistry, and the resulting microarrays display selective binding to fluorescently labeled proteins. An orthogonally addressable, tetrafunctional surface (azide, acid, alkene, and amine) can be prepared by an additional printing step of a tert-butyloxycarbonyl (Boc)-protected alkyne amine linker on the azide structures by using the copper(I)-catalyzed azide-alkyne Huisgen cycloaddition and subsequent removal of the protective group.     

The scope of catalytic enantioselective tandem carbonyl ylide formation-intramolecular [3 + 2] cycloadditions

Catalytic enantioselective tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reactions of 2-diazo-3,6-diketoesters show promising scope in terms of asymmetric induction as the tethered alkene/alkyne dipolarophile component is varied. Cycloadditions were found to occur in moderate to very good yields, with a difference in ee exhibited by the electronically different 2-diazo-3,6-diketoesters 1, 25 and 33, 34. Values for ee of up to 90% for alkene dipolarophiles and up to 86% for alkyne dipolarophiles were obtained.     

1,3-Dipolar cycloaddition for selective synthesis of functionalized spiro[indoline-3,3'-pyrrolizines]

The 1,3-dipolar cycloaddition reaction of dimethyl hex-2-en-4-ynedioate with azomethine ylides derived from reaction of L-proline with various isatins in methanol selectively resulted in the formation of functionalized spiro[indoline-3,3'-pyrrolizine]acrylates as main products and spiro[indoline-3,3'-pyrrolizine]propiolates as minor products.This result indicated that the electron-deficient alkyne has higher reactivity than that of electron-deficient alkene in 1,3-dipolar cycloaddition reaction.     

Regioselective synthesis of fluoroalkylated [1,2,3]-triazoles by Huisgen cycloaddition

A series of fluoroalkylated 1,4-disubstituted [1,2,3]-triazoles were synthesized by the 1,3-dipolar cycloaddition of fluoroalkylated azides with terminal alkynes in the presence of Cu(I) salt as catalyst at room temperature. All the reactions were performed in highly regioselective with 1,4-disubstituted, no 1,5-disubstituted product was formed. For aryl or alkyl-alkyne, triethylamine should be used as ligand. But for propiolic ester(amide), triethylamine couldn’t be used, otherwise no products was formed. A mechanism of Cu(I) inserting the internal alkyne was suggested.     

Chiral Synthesis of an α-Tetrasubstituted Proline Derivative

An efficient approach for the synthesis of a new class of triazolophanes by 1,3-dipolar cycloaddition reaction of highly reactive organic azides with dialkynes using Cu(I)-catalyzed azide–alkyne cycloaddition methodology (“click chemistry”) has been developed. All the compounds were characterized by spectral and elemental analyses.     

A stereoselective method for the synthesis of enantiopure 3-substituted 4-hydroxyproline derivatives via 1,3-dipolar cycloadditions

The stereoselective 1,3-dipolar cycloaddition between (Z)-1,4-dichloro-2-butene and a menthone-derived nitrone led to the corresponding isoxazolidine. Regioselective azidation of a single chlorine atom followed by another Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) induced enantiopure 1,2,3-triazolyl-functionalized isoxazolidines. The subsequent acidic cleavage of the menthone chiral auxiliary and reductive cleavage of the isoxazolidine N–O bond triggered an intramolecular cyclization through the displacement of the second chlorine. This rapid and stereoselective synthetic strategy provided reliable access to a series of enantiopure 3-substituted 4-hydroxyproline derivatives.     

A fluorogenic 1,3-dipolar cycloaddition reaction of 3-azidocoumarins and acetylenes

Copper(I)-catalyzed 1,3-dipolar cycloaddition reaction of nonfluorescent 3-azidocoumarins and terminal alkynes afforded intense fluorescent 1,2,3-triazole products. The mild condition of this reaction allowed us to construct a large library of pure fluorescent coumarin dyes. Since both azide and alkyne are quite inert to biological systems, this reaction has potential in bioconjugation and bioimaging applications. [reaction: see text]     

Construction of polymeric Cu(I) N-heterocyclic carbene complex utilizing terpyridine-Fe(II) as linkers: formation of an efficient and recyclable catalyst

A metal-coordination-driven self-assembly using the predesigned building block has been developed. Herein, the catalytic active NHC–Cu(I) units were introduced into the terpyridine metal coordination polymers. The self-assembled architecture, as a heterogeneous catalyst, was successfully used to catalyze the A³-coupling reaction of aldehyde, alkyne, and amine and Huisgen 1,3-dipolar cycloaddition reaction of azide and alkyne in high yields.     

Functional aliphatic polyesters and nanoparticles prepared by organocatalysis and orthogonal grafting chemistry

We describe the use of organic catalysis for the ring‐opening polymerization of functionalized lactones and conversion of the resulting aliphatic polyesters into crosslinked nanoparticles that carry additional functional groups amenable to further modification. Specifically, highly functional aliphatic polyester homopolymers, as well as random and block copolymers, were prepared by 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene catalysis, giving polyesters with pendent alkene and alkyne groups. Azide‐alkyne click and thiol‐ene chemistries were used for postpolymerization modification of diblock copolymers possessing alkene groups on one block and alkyne groups on the other block. The polyesters were crosslinked using azide/alkyne cycloaddition, by reaction of α,ω‐diazides with the pendent alkynes on the polyester backbone. This gave polyester nanoparticles possessing alkene functionality, which were subjected to further modification using thiol‐ene reactions to introduce additional functionality. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of coumarin-nucleoside conjugates via Huisgen 1,3-dipolar cycloaddition

An efficient synthesis of fluorescent coumarin-nucleoside conjugates via Cu(I) catalysed Huisgen 1,3-dipolar cycloaddition is described. Starting from azidonucleosides and coumarin derivatives, products are obtained in good yields. The fluorescent properties of the newly prepared coumarin-nucleoside conjugates are determined.     

Synthesis and regiochemistry of spiro indane-1,3-dione compounds

Spiro indane-1,3-dione compounds have been synthesized by 1,3-dipolar cycloaddition of ninhydrin, l-proline, and an alkene (either a chalcone or an (E)-??-arylnitrostyrene). All these reactions proceed with good yield and with high regioselectivity and stereoselectivity. The structures were studied by NMR spectroscopy, MS, and X-ray diffraction analysis. It was found that these two kinds of alkene lead to different regioselectivity. This study has provided information about the regioselectivity of 1,3-dipolar cycloaddition reactions: regioselectivity may be controlled by ?ШC?? stacking state; the order of stability of stacking of the Ar and EWG part with the indane-1,3-dione part is: benzoyl group?>?phenyl group?>?nitro group.     

New insights into the water-solubilisation of fluorophores by post-synthetic "click" and Sonogashira reactions

New synthetic methodologies for the efficient chemical conversion of hydrophobic fluorescent dyes into bioconjugable and water-soluble derivatives are described. The combined use of an original sulfonated terminal alkyne and a metal-mediated reaction, namely the copper-catalysed Huisgen 1,3-dipolar cycloaddition ("click" reaction) or the Sonogashira cross-coupling, is the cornerstone of these novel post-synthetic sulfonation approaches.     

脱质子化1,3环加成石墨烯外在固定位上的贵金属纳米线(英文)

为研究纳米线的形成机理,通过密度泛函理论(DFT)研究了贵金属(铂)在脱质子化1,3-环加成石墨烯上的吸附.研究发现:(1)吸附在1,3-环加成石墨烯上的铂原子引起该结构的脱质子化过程并形成脱质子化1,3-环加成石墨烯;(2)贵金属在脱质子化1,3-环加成石墨烯上的锚定位是氮原子邻位的碳原子,这在邻位碳原子的平均巴德电荷分析(高达1.0e)中得到进一步的证实;(3)铂原子在相邻的脱质子化吡啶炔单元上形成金属纳米线,并且该纳米线比相应的铂团簇稳定得多;(4)电子结构分析表明,铂的吸附并没有从根本上改变脱质子化1,3-环加成石墨烯的电子性质.铂金属的掺杂使得Pt6团簇吸附形成的复合物呈现金属性,而Pt6纳米线形成的复合物则为半金属性.     

Combining proline and ‘click chemistry’: a class of versatile organocatalysts for the highly diastereo- and enantioselective Michael addition in water

Based on ‘click chemistry’ conditions, a class of novel, facile, versatile pyrrolidine-based triazole derivatives were prepared, and proved to be efficient catalysts for the highly diastereoselective and enantioselective Michael addition of ketones to nitroalkenes. The Cu(I)-catalyzed 1,3-dipolar ‘click’ azide–alkyne cycloaddition provides modular and tunable features for the pyrrolidine-based triazole organocatalysts, and the resulting triazole moiety can serve as a phase tag to complete the reaction in water with an excellent yield and high enantiomeric excess.     

A method of printing uniform protein lines by using flat PDMS stamps

In this paper, we report a method of printing uniform protein lines on glass slides by using UV-treated flat PDMS stamps. Unlike traditional microcontact printing (μCP) which requires microstructured PDMS stamps, this μCP method only requires a flat PDMS stamp, an UV lamp and a number of straight needles. Our results show that lines of bovine serum albumin (BSA), immunoglobin (IgG), anti-biotin, anti-human IgG and anti-mouse IgG can be printed evenly on glass slides by using this μCP method. We also demonstrate that the printed protein lines are suitable for applications such as microfluidic immunoassays.     

In situ Raman monitoring triazole formation from self-assembled monolayers of 1,4-diethynylbenzene on Ag and Au surfaces via "click" cyclization

We prepared acetylenyl-terminated aromatic self-assembled monolayers (SAMs) of 1,4-diethynylbenzene on silver and gold. After the fabrication of pendent acetylenyl SAMs, the formation of triazoles was performed via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition "click" chemistry. A density functional theory (DFT) calculation of Raman frequencies showed good agreement with our experimental data to provide evidence of the formation of the triazole molecule. Our results indicated that "click" chemistry could be successfully applied to simple aromatic SAMs proximate (<1 nm) to roughened gold surfaces. The reaction process could be monitored in real time by measuring intensity changes of the nu(CC)(free) band in surface-enhanced Raman scattering (SERS) spectra.     

Construction of di-scFv through a trivalent alkyne-azide 1,3-dipolar cycloaddition

Heterofunctional azide and alkyne PEG-linkers have been synthesized and site specifically conjugated to scFv via a reactive thiol functionality; two scFv were coupled by copper catalyzed 1,3-dipolar cycloaddition to make divalent scFv (di-scFv) with an inter-scFv distance defined to provide divalent binding; antigen binding was maintained for the di-scFv construct and increased several times compared to that of the parent scFv; the cycloaddition reaction reported herein represents an important ligation strategy to covalently link macromolecular proteins and retain sensitive structural conformations.     

Modular synthesis of block copolymers via cycloaddition of terminal azide and alkyne functionalized polymers

Polymeric building blocks containing terminal azide and alkyne functionalities are prepared via atom transfer radical polymerization (ATRP) and used to modularly synthesize block copolymers via 1,3-dipolar cycloaddition reactions, which are quantitative according to SEC measurements.     

Efficient and widely applicable method of constructing neo-proteoglycan utilizing copper(I) catalyzed 1,3-dipolar cycloaddition

Efficient constructions of two types of neo-proteoglycan are described. Enzymatically prepared alkyne containing chondroitin 6-sulfate chains and chemically synthesized azido group having compounds are linked by utilizing the copper(I) catalyzed 1,3-dipolar cycloaddition.     

Synthesis of new azaphthalocyanine dark quencher and evaluation of its quenching efficiency with different fluorophores

New unsymmetrical zinc azaphthalocyanine (AzaPc) was synthesized using statistical condensation of two precursors. Postsynthetic modifications led to incorporation of azide group that efficiently underwent Cu(I)-catalyzed azide/alkyne 1,3-dipolar cycloaddition with terminal alkyne on a solid phase. The modified solid phase was then used for synthesis of oligodeoxyribonucletides labeled with AzaPc. DNA hybridization assays confirmed high quenching efficiency (QE>96%) of zinc AzaPc quencher with six different fluorophores ranging in emission maxima from 517 nm to 701 nm (FAM, HEX, Cy3, Cy3.5, Cy5, and Cy5.5).