Solid Phase Supported “Click”-Chemistry Approach for the Preparation of Water Soluble Gold Nanoparticle Dimers

We investigated the potential of the Cu(I) catalyzed azide-alkyne cycloaddition between water soluble azide and alkyne functionalized gold nanoparticles in terms of dimer formation via a solid phase support. Alkyne and azide lipoic acid derivatives are prepared and utilized as stabilizing ligands for 15?nm gold colloids. For the solid phase supported click reaction first citrate stabilized gold nanoparticles are immobilized on amine terminated silicon wafers. In the following step the citrate ligands of the upper free accessible nanoparticle surface are exchanged against a mixture of the alkyne derivative of lipoic acid and lipoic acid. Upon addition of lipoic acid/lipoic acid azide derivative stabilized 15?nm gold nanoparticles and the Cu(I) catalyst solution covalent interparticle coupling between immobilized and gold nanoparticles added is achieved. The formed structures are analyzed by scanning electron microscopy directly on the solid support. It is demonstrated that the yield of dimeric structures on the solid phase support increases with increased molar ratio of the catalyst, thus indicating that dimers are indeed formed by covalent bond formation. Upon treatment with ultrasound the formed structures could be released and detected with transmission electron microscopy measurements.     

Zinc azaphthalocyanines with pyridin-3-yloxy peripheral substituents

Phthalocyanines (Pc), which are peripherally substituted with pyridin-3-yloxy groups, have shown promise as sensitizers for photodynamic cancer therapy (PDT). Some aza-analogues (AzaPc) are reported here. Four monomers were synthesized, i.e. 5,6-di(pyridin-3-yloxy)pyrazine-2,3-dicarbonitrile, and three pyrazine-2,3-dicarbonitriles, substituted with pyridin-3-yloxy- in combination with H, Me and Ph groups. Cyclotetramerizations of these monomers with the reagent Zn(quinoline)₂Cl₂ yielded the targeted ZnAzaPcs in 20–40% yields.The cyclotetramerizations were accompanied, and apparently initiated, by complexation between zinc(II) and the pyridin-3-yloxy groups attached to the pyrazine-dicarbonitriles. Two such zinc(II) complexes were isolated and characterized. Identifications of all new substances were primarily based on NMR spectra, where the pulse techniques COSY, NOESY, HSQC and HMBC were applied. Molecular ions of the ZnAzaPcs were determined by mass spectrometry (MALDI-TOF). The UV–Vis spectra of these macrocycles were as expected, with Q-band absorptions at 630–650 nm and molar extinction coefficients, ε, 70 000–100 000. Eight peripheral pyridin-3-yloxy groups induced a small blue shift of the Q-band, from 636 nm for unsubstituted ZnAzaPc, to 630 nm, whereas a red shifted Q-band at 650 nm resulted from the combination of phenyl and pyridin-3-yloxy substituents. Improved solubilities were observed for the unsymmetrical ZnAzaPcs compared to octa(pyridin-3-yloxy)ZnAzaPc.     

Immobilized polytriazole complexes of copper(I) onto graphene oxide as a recyclable nanocatalyst for synthesis of triazoles

An efficient solid‐supported catalyst for the Huisgen [3 + 2] cycloaddition reaction between azides and alkynes was prepared from copper(I) iodide and 1,2,3‐triazole‐functionalized graphene oxide. This catalyst was then used for the efficient synthesis of β‐hydroxy‐1,2,3‐triazoles giving access to these products in excellent yields. In this protocol, the catalyst was shown to have high activity, air‐stability and recyclability. The formation of copper triazolide is very straightforward and energetically desirable. The catalyst can be isolated from copper‐catalysed azide–alkyne cycloaddition reactions.     

Clicked polycyclic aromatic hydrocarbon as a hybridization-responsive fluorescent artificial nucleobase in pyrrolidinyl peptide nucleic acids

Pyrene as well as other aromatic hydrocarbons could be successfully incorporated into pyrrolidinyl peptide nucleic acid bearing a d-prolyl-2-aminocyclopentane carboxylic acid backbone (acpcPNA) as a base surrogate via a triazole linker employing Cu-catalyzed alkyne–azide cycloaddition (click chemistry). The labeling can be performed via a pre-clicked pyrene monomer or by post-synthetic modification of azide-containing acpcPNA on solid support. Thermal denaturation experiments suggested that the pyrene–triazole unit can behave as a universal base in the acpcPNA system. The mode of base-pairing has been proposed based on molecular dynamics simulations. Importantly, the fluorescence spectra of the pyrene-labeled single stranded acpcPNA and its hybrid with DNA are quite different. The ratio of emissions at 380 and 460 nm changed significantly (up to a factor of 7) upon hybrid formation with complementary DNA.     

An efficient reagent for 5′-azido oligonucleotide synthesis

A new bromohexyl phosphoramidite was synthesized and used for the introduction of an azide function at the 5′-end of oligonucleotides after a treatment on solid support with sodium azide and sodium iodide. The corresponding 5′-azido oligonucleotide could be further used for ‘Click’ conjugation with alkyne derivatives or by Staudinger ligation.     

Orthogonal Synthesis of Xeno Nucleic Acids

Sequence‐defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid‐phase orthogonal “AB+CD” iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper‐catalyzed azide–alkyne cycloaddition (CuAAC) and acid–amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks).     

Amide-1,2,3-triazole bioisosterism: the glycogen phosphorylase case

Per-O-acetylated β-d-glucopyranosyl azide was transformed into an intermediate iminophosphorane by PMe₃ which was then acylated to N-acyl-β-d-glucopyranosylamines. The same azide and substituted acetylenes gave 1-(β-d-glucopyranosyl)-4-substituted-1,2,3-triazoles in Cu(I)-catalyzed azide–alkyne cycloadditions. Deprotection of these products by the Zemplén method furnished β-d-Glc_p-NHCO-R derivatives as well as 1-(β-d-Glc_p)-4-R-1,2,3-triazoles which were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. Pairs of amides versus triazoles with the same R group displayed similar inhibition constants. X-ray crystallographic studies on the enzyme–inhibitor complexes revealed high similarities in the binding of pairs with R = 2-naphthyl and hydroxymethyl, while for the R = Ph and 1-naphthyl compounds a different orientation of the aromatic part and changes in the conformation of the 280s loop were observed. By this study new examples of amide-1,2,3-triazole bioisosteric relationship have been provided.     

Micro solid phase spectrophotometry in a sequential injection lab-on-valve platform for cadmium,zinc, and copper determination in freshwaters

This work describes the development of a solid phase spectrophotometry method in a μSI-LOV system for cadmium, zinc, and copper determination in freshwaters. NTA (Nitrilotriacetic acid) beads with 60–160 μm diameter were packed in the flow cell of the LOV for a μSPE column of 1 cm length. The spectrophotometric determination is based on the colourimetric reaction between dithizone and the target metals, previously retained on NTA resin. The absorbance of the coloured product formed is measured, at 550 nm, on the surface of the NTA resin beads in a solid phase spectrophotometry approach.     

Clathrate formation from octaazaphthalocyanines possessing bulky phenoxyl substituents: a new cubic crystal containing solvent-filled, nanoscale voids

The synthesis of octaazaphthalocyanine (AzaPc) derivatives, with bulky phenoxyl substituents placed at eight peripheral positions and containing either H(+), Ni(2+) or Zn(2+) ions in their central cavity, is described. The required precursors, derivatives of pyrazine-2,3-dicarbonitrile, were prepared using a nucleophilic aromatic substitution reaction between 2,6-diisopropylphenol or 2,6-diphenylphenol and 5,6-dichloropyrazine-2,3-dicarbonitrile. Analysis of the resulting AzaPcs by UV/Visible and (1)H NMR spectroscopy confirms that steric isolation of the AzaPc cores was enforced both in solution and in the solid state. X-ray diffraction studies of single crystals of the AzaPcs reveal that solvent inclusion takes place in each case. Of particular significance is the finding that the zinc derivative of 2,3,9,10,16,17,23,24-octa-(2,6-diisopropylphenoxy)octaazaphthalocyanine provides nanoporous cubic crystals, containing massive (8 nm(3)) solvent-filled voids, similar to those of the analogous phthalocyanine derivative. Exchange of the included solvent within the voids can be readily achieved by using a number of alternative solvents including water. Based on the observed loading of included water, the internal volume of this nanoporous cubic crystal appears to be more hydrophilic than its phthalocyanine counterpart.     

Synthesis, Properties and In Vitro Photodynamic Activity of Water-soluble Azaphthalocyanines and Azanaphthalocyanines

In this work zinc azaphthalocyanines (AzaPcs) from the group of tetrapyrazinoporphyrazines and zinc azanaphthalocyanines from the group of tetra[6,7]quinoxalinoporphyrazines (TQP) with eight diethylaminoethylsulfanyl substituents were synthesized. Tertiary amines were later quaternized with ethyl iodide to obtain water-soluble photosensitizers (PSs). Quaternized compounds showed high singlet oxygen quantum yields as determined in DMF by monitoring decomposition of 1,3-diphenylisobenzofuran. In water medium, quaternized AzaPc derivatives appeared in monomeric form in a wide range of concentrations while quaternized TQP derivatives showed aggregation at higher concentrations (over 1 μ m ). Photodynamic activity was tested on Hep2 cells using light of λ  > 640 nm. Both quaternized dyes showed high photodynamic activity (IC₅₀ = 104 and 220 n m for AzaPc and TQP, respectively). Dark toxicity was not detected even at the highest concentration used in in vitro tests (200 μ m ) which indicates a promising therapeutic index of these new substances. Tested compounds localized inside the cells mainly within the lysosomes thus suggesting an endocytic mechanism of cellular uptake. No localization within mitochondria was detected. A great advantage of TQP derivatives over other PSs is their very strong absorption at 747 nm that allows activation at wavelengths penetrating deeper into human tissues.     

Tetrazine-functionalized and vertically-aligned mesoporous silica films with electrochemical activity and fluorescence properties

In spite of their attractive physico-chemical properties making them very promising in the field of functional molecular materials, s-tetrazine derivatives remain underexploited in practical devices mainly because their immobilization in a stable form maintaining all their features is still challenging. Here, we show that combining a ‘click chemistry azide/alkyne’ approach with an electrochemically-assisted self-assembly (EASA) method, which is likely to generate azide-functionalized and vertically-aligned mesoporous silica films, and further derivatization of the ordered mesoporous material with propargyl–tetrazine via a soft Huisgen coupling reaction, enable one to reach this goal. The resulting tetrazine-functionalized films formed onto transparent indium–tin oxide (ITO) electrodes exhibit well-defined voltammetric signals, with peak currents proportional to the functionalization level and stable upon multiple potential scanning, as well as effective fluorescence properties as evidenced from fluorescence spectra with maximum emission at 555–560 nm.     

Two-step local functionalization of fluoropolymer Dyneon THV microfluidic materials by scanning electrochemical microscopy combined to click reaction

We propose an original two-step strategy combining the use of scanning electrochemical microscopy (SECM) and molecular chemistry via a “click” reaction (copper (I)-catalyzed azide alkyne cycloaddition (CuAAC)) to locally functionalize Dyneon THV surfaces, an attractive fluoropolymer for microfluidic applications. The first step consists in the local reduction of THV using a SECM tip to activate the surface by the creation of a locally carbonized zone and notably the formation of surface alkyne functions. This is then followed by a direct CuAAC reaction with an azide-bearing ligand for its local immobilization. The proof of concept is demonstrated by efficient local functionalization of the substrate with a fluorescent dye stable up to 6 months. Surface modifications were characterized by IR-ATR, XPS, and fluorescence microscopy.     

A convenient method for constructing novel tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]-pyrimidinones-carbohydrate and amino acid conjugates via copper(I)-catalyzed alkyne-azide ‘Click Chemistry’

Novel conjugates of tetrahydropyridothienopyrimidones and carbohydrates or amino acids linked by 1,2,3-triazoles were synthesized. After establishing the tetrahydropyridothienopyrimidones ring system by ring closure, propargyl groups were introduced by N-alkylation. Cu-catalyzed cycloaddition of the propargyl products with azido group containing hexoses or amino acids gives the corresponding 1,2,3-triazoles in high yields. This methodology also allowed attaching two carbohydrate molecules to the tetrahydropyridothienopyrimidone core. Interesting dependence of the regioselectivity of the N-propargylation of the pyrimidone ring on the exocyclic substituent found adjacent to the pyrimidine-N-atom was observed. A remarkable case of a non-catalyzed intramolecular [3+2]-cycloaddition of an alkyne with an azide to a 1,2,3-triazole was observed, which occurred in the solid state at rt or below.     

ZnO hollow nanospheres via Laux-like oxidation of Zn0 nanoparticles

Zinc oxide hollow nanospheres were obtained via a Laux-like oxidation of zinc nanoparticles using nitrobenzene as oxidizing agent. The ZnO hollow nanospheres exhibit an outer diameter of 10.4 ± 1.3 nm and a well crystallized sphere wall with a thickness of 2.9 ± 0.4 nm. Laux-like oxidation and formation of the ZnO hollow nanospheres were performed instantaneously after sodium naphthalenide ([NaNaph]) driven reduction of ZnCl₂ to Zn⁰ nanoparticles in the liquid phase without any separation of the intermediate Zn⁰ nanoparticles. The diameter of the resulting ZnO hollow nanospheres (10.4 ± 1.3 nm) reflects the diameter of the intermediate Zn⁰ nanoparticles (10.1 ± 2.3 nm). In accordance with the small diameter of the ZnO sphere wall, quantum-size effects occur with a band gap that is blue-shifted by 0.2 eV in comparison to bulk-ZnO.     

Surface patterning using scanning electrochemical microscopy to locally trigger a “click” chemistry reaction

We report on the surface micropatterning of conductive surfaces via the electrochemical triggering of a click reaction, the copper(I) catalyzed azide–alkyne cycloaddition reaction (CuAAC) by SECM via a two-step approach: (i) functionalization on the entire surface with azido-aryl groups by using the diazonium approach followed by (ii) the covalent linkage of alkyne-bearing ferrocene by CuAAC within a local area by SECM. More precisely, the click reaction was triggered by Cu(I) catalyst generation for 30 min at the SECM tip positioned ≈ 10 μm above the azido-aryl modified surface. The dimension of the spot obtained under these conditions was ≈ 75 μm. The electrochemical imaging by SECM of the ultra thin area locally clicked with ferrocene moieties was made thanks to the electrocatalytic properties of the ferrocene modified surface towards ferrocyanide electrooxidation. This local clicking procedure opens the gate to further controlled functionalization of restricted small substrates.     

Synthesis and photoresponsive behavior of azobenzene‐containing side‐chain liquid crystalline diblock polymers with polypeptide block

Well‐defined azobenzene‐containing side‐chain liquid crystalline diblock copolymers composed of poly[6‐(4‐methoxy‐azobenzene‐4′‐oxy) hexyl methacrylate] (PMMAZO) and poly(γ‐benzyl‐L ‐glutamate) (PBLG) were synthesized by click reaction from alkyne‐ and azide‐functionalized homopolymers. The alkyne‐terminated PMMAZO homopolymers were synthesized by copper‐mediated atom transfer radical polymerization with a bromine‐containing alkyne bifunctional initiator, and the azido‐terminated PBLG homopolymers were synthesized by ring‐opening polymerization of γ‐benzyl‐L ‐glutamate‐N‐carboxyanhydride in DMF at room temperature using an amine‐containing azide initiator. The thermotropic phase behavior of PMMAZO‐b‐PBLG diblock copolymers in bulk were investigated using differential scanning calorimetry and polarized light microscopy. The PMMAZO‐b‐PBLG diblock copolymers exhibited a smectic phase and a nematic phase when the weight fraction of PMMAZO block was more than 50%. Photoisomerization behavior of PMMAZO‐b‐PBLG diblock copolymers and the corresponding PMMAZO homopolymers in solid film and in solution were investigated using UV–vis. In solution, trans–cis isomerization of diblock copolymers was slower than that of the corresponding PMMAZO homopolymers. These results may provide guidelines for the design of effective photoresponsive anisotropic materials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Properties of ZnO nanocrystals prepared by radiation method

Zinc oxide nanoparticles were prepared by irradiation of aqueous solutions containing zinc(II) ions, propan-2-ol, polyvinyl alcohol, and hydrogen peroxide. Zinc oxide was found in solid phase either directly after irradiation, or after additional heat treatment. Various physicochemical parameters, including scintillation properties of prepared materials, were studied. After decomposition of impurities and annealing of oxygen vacancies, the samples showed intensive emission in visible spectral range and well-shaped exciton luminescence at 390–400 nm. The best scintillating properties had zinc oxide prepared from aqueous solutions containing zinc formate as initial precursor and hydrogen peroxide. Size of the crystalline particles ranged from tens to hundreds nm, depending on type of irradiated solution and post-irradiation thermal treatment.     

Brush‐first and Click: Efficient Synthesis of Nanoparticles that Degrade and Release Doxorubicin in Response to Light

New strategies for the synthesis of multifunctional particles that respond to external stimuli and release biologically relevant agents will enable the discovery of new formulations for drug delivery. In this article, we combine two powerful methods: brush‐first ring‐opening metathesis polymerization and copper‐catalyzed azide–alkyne cycloaddition click chemistry, for the synthesis of a novel class of brush‐arm star polymers (BASPs) that simultaneously degrade and release the anticancer drug doxorubicin (DOX) in response to 365 nm light. In vitro cell viability studies were performed to study the toxicity of azide‐ and DOX‐loaded BASPs. The former were completely nontoxic. The latter showed minimal toxicity in the absence of light; UV‐triggered DOX release led to IC₅₀ values that were similar to that of free DOX.     

Azide–Alkyne Interactions: A Crucial Attractive Force for Their Preorganization for Topochemical Cycloaddition Reaction

A new class of attractive intermolecular interaction between azide and ethynyl structural entities in a wide range of molecular crystals is reported. This interaction was systematically evaluated by using 11 geometrically different structural motifs that are preorganized to direct a solid-state topochemical azide–alkyne cycloaddition (TAAC) reaction. The supramolecular features of the azide–alkyne interaction were mapped by various crystallographic and quantum chemical approaches. Topological analysis shows the noticeable participation of electron density in the azide⋅⋅⋅alkyne interactions. Interestingly, reorientation of the atomic polarizabilities in vicinal azide and alkyne groups upon interaction in crystals favors soft orbital-guided TAAC reactions. Moreover, various solid-state and gas-phase energy decomposition methods of individual azide⋅⋅⋅alkyne interactions summarize that the strength (varies from −5.7 to −30.1 kJ mol⁻¹) is primarily guided by the dispersion forces with a influencing contribution from the electrostatics.     

Easy preparation of 1,4,5-trisubstituted 5-(2-alkoxy-1,2-dioxoethyl)-1,2,3-triazoles by chemoselective trapping of copper(I)–carbon bond with alkoxalyl chloride

We found that alkoxalyl chloride (ClCOCO₂R) did not carry out an acylation on 1-copper(I) alkyne in solvent without additives, but chemoselectively on 5-copper(I) 1,2,3-triazole (an intermediate in cycloaddition of 1-copper(I) alkyne and azide). Thus, a one-pot preparation of 1,4,5-trisubstituted 5-(2-alkoxy-1,2-dioxoethyl)-1,2,3-triazole was achieved by simply stirring the mixture of 1-copper(I) alkyne, azide, and alkoxalyl chloride at room temperature for 4 h.