Catalyzed Azide Alkyne Cycloaddition Research Articles

One-Pot Approach for the Synthesis of Bis-indole-1,4-disubstituted-1,2,3-triazoles.

A new strategy for the synthesis of bis-indoletriazoles was developed using a sequential one-pot four-step procedure via I2 and H2SO4-SiO2 catalyzed Friedel-Crafts reactions of indole with aldehyde followed by N-alkylation with propargyl bromide, azidation, and copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). The reaction proceeded smoothly at room temperature in a short time, and a series of bis-indoletriazoles were obtained in good to excellent yields proving the generality of this one-pot methodology.

Ultrasound Assisted High-Throughput Synthesis of 1,2,3-Triazoles Libraries: A New Strategy for “Click” Copper-Catalyzed Azide-Alkyne Cycloaddition Using Copper(I/II) as a Catalyst

A series of 1,4-disubstituted 1,2,3-triazoles were prepared by a parallel synthesis protocol utilizing the 3D-supramolecular coordination polymer (SCP) {[CuI(CN)(phen)2·CuII(CN)2(phen)]·5H2O}, 1 as a catalyst under ultrasonic irradiations. This work establishes the synergistic action between the mixed valance copper catalyst SCP 1 and ultrasonic irradiation to yield a high-throughput synthesis of 1,4-disubstituted 1,2,3-triazoles libraries. This mixed valance copper(I/II) supramolecular coordination polymer catalyzed azide alkyne cycloaddition reaction protocol allowed a rapid synthesis of the target compounds (10 min) in a parallel fashion with good to excellent yields. Twelve reactions were performed in a single deep well microtiter plate, employing three alkynes and four different azide reagents. From this effort, a total of twelve 1,2,3-triazole were obtained in useful isolated yields. Moreover, unambiguous structural assignment of the obtained regioisomers was determined utilizing Heteronuclear Multiple Bond Correlation (HMBC) 2D NMR techniques as a valuable. A series of 1,4-disubstituted 1,2,3-triazoles were prepared by a parallel synthesis protocol utilizing the 3D-supramolecular coordination polymer (SCP) {[CuI(CN)(phen)2·CuII(CN)2(phen)]·5H2O}, 1 as a catalyst under ultrasonic irradiations.

Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting of galectin-3

BackgroundGalectin-3 (Gal-3) is a promising target in cancer therapy with a high therapeutic potential due to its abundant localization within the tumor tissue and its involvement in tumor development and proliferation. Potential clinical application of Gal-3-targeted inhibitors is often complicated by their insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2-hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo application due to their good water solubility and lack of toxicity and immunogenicity. Their conjugation with tailored carbohydrate ligands can yield specific glyconanomaterials applicable for targeting biomedicinally relevant lectins like Gal-3.ResultsIn the present study we describe the synthesis and the structure-affinity relationship study of novel Gal-3-targeted glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers decorated with varying amounts of Gal-3 specific epitope GalNAcβ1,4GlcNAc (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding kinetics was described by surface plasmon resonance. We showed the impact of various linker types and epitope distribution on the binding affinity to Gal-3. The synthesis of specific functionalized LacdiNAc epitopes was accomplished under the catalysis by mutant β-N-acetylhexosaminidases. The glycans were conjugated to statistic HPMA copolymer precursors through diverse linkers in a defined pattern and density using Cu(I)-catalyzed azide–alkyne cycloaddition. The resulting water-soluble and structurally flexible synthetic glyconanomaterials exhibited affinity to Gal-3 in low μM range.ConclusionsThe results of this study reveal the relation between the linker structure, glycan distribution and the affinity of the glycopolymer nanomaterial to Gal-3. They pave the way to specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal in cancerogenesis and other disorders.

Copper(I)-catalyzed azide–alkyne cycloaddition polymerization of N-butyl-N-ethynyl-4-azidobenzenesulfonamide

Aiming at synthesis of nonperiodic sequence-controlled polymers, we have been focusing on copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) polymerization of monomers possessing both azide and alkyne groups. For this purpose, we have chosen N-ethynyl-4-azidobenzenesulfonamide derivatives because the derivatives carrying various substituents can be prepared in a fewer steps using the corresponding starting materials, i.e., amines. In this study, we synthesized a new monomer, i.e., N-butyl-N-ethynyl-4-azidobenzenesulfonamide (BuEA), and carried out its dimerization and polymerization by CuAAC using a pair of copper(II) sulfate pentahydrate and sodium ascorbate. A dimer of BuEA was successfully obtained from the monomer precursors possessing azide and ethynyl groups, respectively. This observation indicates that N-ethynyl-4-azidobenzenesulfonamide derivatives are applicable to synthesis nonperiodic sequence-controlled polymers. The polymer obtained (poly(BuEA)) was well soluble in common organic solvents, e.g., dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran (THF), chloroform, and dichloromethane. Solution properties of poly(BuEA) were also investigated. Pulse-field-gradient spin-echo (PGSE) NMR data in THF-d8 indicated that poly(BuEA) chain takes a compact conformation. Steady state fluorescence study exhibited that poly(BuEA) emitted weak fluorescence based on the monomer unit.

Enzyme-like Click Catalysis by a Copper-Containing Single-Chain Nanoparticle.

A major challenge in performing reactions in biological systems is the requirement for low substrate concentrations, often in the micromolar range. We report that copper cross-linked single-chain nanoparticles (SCNPs) are able to significantly increase the efficiency of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions at low substrate concentration in aqueous buffer by promoting substrate binding. Using a fluorogenic click reaction and dye uptake experiments, a structure-activity study is performed with SCNPs of different size and copper content and substrates of varying charge and hydrophobicity. The high catalytic efficiency and selectivity are attributed to a mechanism that involves an enzyme-like substratebinding process. Saturation-transfer difference (STD) NMR spectroscopy, 2D-NOESY NMR, kinetic analyses with varying substrate concentrations, and computational simulations are consistent with a Michaelis-Menten, two-substrate, random-sequential enzyme-like kinetic profile. This general approach may prove useful for developing more-sustainable catalysts and agents for biomedicine and chemical biology.

Synthesis of Axially Chiral 1,2,3-Triazol-5-ylidene–Au(I) Complex and Its Application in Enantioselective [2 + 2] Cycloaddition of Alleneamides with Alkenes

A series of axially chiral bis-1,2,3-triazol-5-ylidene Au(I) complexes (R)-8a–g and one mono-1,2,3-triazol-5-ylidene Au(I) complex (R)-9a were prepared from commercially available (R)-binaphthyl-2,2-diamine (BINAM) compound, in which, transmetalation of bis(MIC)-bis[Ag(I)] intermediates to the corresponding Au(I) complexes were employed as the key synthetic step. The structures of these MIC–Au(I) complexes were diversified by using different alkyne reagents in copper catalyzed azide–alkyne cycloaddition (CAAC) step. Three chiral bis-1,2,3-triazol-5-ylidene Ag(I) complexes, (R)-7a, (R)-7c, and (R)-7d, were prepared and fully characterized. On the basis of (R)-7a’s crystal structure, a chiral tetra(MIC)-bis(Ag) structure was exhibited, with two chiral bis-1,2,3-triazol-5-ylidene ligands interconnected by two nearly linear silver atom bridges, of which, significant Ag(I)–Ag(I) bonding existed. The crystal structures of (R)-8a, (R)-8f, and (R)-8g were also obtained, which exhibit an axially chiral bis(MIC)-bi...

The Protein Microenvironment Governs the Suitability of Labeling Sites for Single-Molecule Spectroscopy of RNP Complexes.

Single-molecule techniques allow unique insights into biological systems as they provide unrivaled access to structural dynamics and conformational heterogeneity. One major bottleneck for reliable single-molecule Förster resonance energy transfer (smFRET) analysis is the identification of suitable fluorophore labeling sites that neither impair the function of the biological system nor cause photophysical artifacts of the fluorophore. To address this issue, we identified the contribution of virtually all individual parameters that affect Förster resonance energy transfer between two fluorophores attached to a ribonucleoprotein complex consisting of the RNA-binding protein L7Ae and a cognate kink turn containing RNA. A non-natural amino acid was incorporated at various positions of the protein using an amber suppression system (pEVOL) to label the protein via copper(I)-catalyzed alkyne-azide cycloaddition. On the basis of simulations followed by functional, structural, and multiparameter fluorescence analysis of five different smFRET RNPs, new insights into the design of smFRET RNPs were obtained. From this, a correlation between the photophysical properties of fluorophores attached to the protein and the predictability of the corresponding smFRET construct was established. Additionally, we identify a straightforward experimental method for characterizing selected labeling sites. Overall, this protocol allows fast generation and assessment of functional RNPs for accurate single-molecule experiments.

Ultrasound Promoted Step‐Growth Polymerization and Polymer Crosslinking Via Copper Catalyzed Azide–Alkyne “Click” Reaction

AbstractMechano‐activated chemistry is a powerful tool for remodeling of synthetic polymeric materials, however, few reactions are currently available. Here we show that using piezochemical reduction of a CuII‐based pre‐catalyst, a step‐growth polymerization occurs via the copper catalyzed azide–alkyne cycloaddition (CuAAC) reaction to form a linear polytriazole. Furthermore, we show that a linear polymer can be crosslinked mechanochemically using the same chemistry to form a solid organogel. We envision that this chemistry can be used to harness mechanical energy for constructive purposes in polymeric materials.

Ultrasound Promoted Step-Growth Polymerization and Polymer Crosslinking Via Copper Catalyzed Azide-Alkyne "Click" Reaction.

Mechano-activated chemistry is a powerful tool for remodeling of synthetic polymeric materials, however, few reactions are currently available. Here we show that using piezochemical reduction of a CuII -based pre-catalyst, a step-growth polymerization occurs via the copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction to form a linear polytriazole. Furthermore, we show that a linear polymer can be crosslinked mechanochemically using the same chemistry to form a solid organogel. We envision that this chemistry can be used to harness mechanical energy for constructive purposes in polymeric materials.

Click Reaction Assisted By Cu Electro-Oxidation

The click chemistry is a green, selective, qualitative, pH-sensitive and economical approach, suitable characteristics for use in the synthesis of a variety of bioconjugates including peptides, proteins, polysaccharides, etc. The purpose of the click chemistry reactions is to bind two molecular building blocks, selectively and under mild reaction conditions, obtaining high yields, generating only harmless byproducts of reaction and easy to separate by non-chromatographic methods. In 2002, Sharpless's research group reported the 1,3-dipolar Copper catalyzed Alkyne Azide Cycloaddition (CuAAC) reaction, which is regioselective for the formation of 1,4-disubstituted triazoles, becoming the best known click reaction.The reaction is carried out at room temperature and has high conversions at shorter times, compared to the uncatalyzed (not regioselective) cycloaddition reported by Huisgen in 1963. Other strategies have been reported to perform the cycloaddition of alkynes and azides without the use of a copper catalyst, however, for these reactions the kinetics are slow and do not present regioselectivity. Hence, the process catalyzed by copper is still preferred. Intending to improve the green chemistry procedure to synthesize triazoles, considering that electrons as redox reactants instead of polluting reducing/oxidizing reagents, it is propose to assist a conventional click reaction by electrochemical methods. Since a metallic species as Cu is relatively easy to oxidize by an electrolysis, the main objective is to generate ionic species of Cu as Cu+1 serving to catalyze the click reaction. For this purpose a suitable electrolytic media as well as a proper electrochemical cell configuration (Cu-working electrode, Ag/AgCl/Cl- (tert-butylalcohol/water) reference electrode and Pt-counter electrode) were used to test the reaction improvement by the in-situ electro-oxidation of Cu. The synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole, 3-(1-benzyl-1H-1,2,3-triazol-4-yl)phenol and 1-benzyl-4-(naphthalen-1-yl)-1H-1,2,3-triazole derivatives via the in-situ preparation of Cu+1 by an electrochemical process, was very efficient, safe and inexpensive, since catalyst was obtained under soft conditions reaction generating extremely small amounts of electrooxidized Cu (~4.3x10-3 mol in one hour). Conventional and electrochemical methods were compared, the last method yielded 78-90% in one hour of reaction and the conventional method produced only 56-60% at the same time, therefore, the electro-Click reaction is faster and more efficient.

FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1.

In the rapidly developing field of targeted cancer therapy there is growing interest towards therapeutics combining two or more compounds to achieve synergistic action and minimize the chance of cancer resistance to treatment. We developed a fibroblast growth factor 2 (FGF2)-conjugate bearing two cytotoxic drugs with independent mode of action: α-amanitin and monomethyl auristatin E. Drugs are covalently attached to the targeting protein in a site-specific manner via maleimide-thiol conjugation and Cu(I)-catalyzed alkyne-azide cycloaddition. The dual warhead conjugate binds to FGF receptor 1 (FGFR1) and utilizes receptor-mediated endocytosis for selective internalization into cancer cells with FGFR1. The developed conjugate displays high cytotoxicity towards all tested FGFR1-positive cell lines. Most importantly, the improved cytotoxic effect of both drugs is observed for lung cancer cell line NCI-H446. The single drug-FGF2 conjugates have no impact on the viability of NCI-H446 cells, whereas the dual warhead-FGF2 conjugate selectively and efficiently kills these FGFR1 positive cancer cells. Due to the diversified mode of action the dual warhead-FGF2 conjugate may overcome the potential acquired resistance of FGFR1-overproducing cancer cells towards single cytotoxic drugs.

Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer's interaction with cells, but does not minimize its inherent inflammation-targeting abilities.

Design, synthesis and biological evaluation of novel 1,2,3-triazole linked coumarinopyrazole conjugates as potent anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase and anti-cancer agents

A series of new 1,2,3-triazole linked coumarinopyrazole conjugates 4a-e and 5a-e have been synthesized via the Copper(I)-catalysed Alkyne-Azide Cycloaddition (CuAAC). Going through the reaction of compound 2 with the 3-propargyl bromide gave a mixture of propargylated regioisomers 3 + 3′ used as a dipolarophile to access to triazoles 4a-e and 5a-e. The structures of the prepared cycloadducts were determined by 1H, 13C and 2D-NMR techniques and by HRMS analysis. All the synthesized derivatives have been evaluated for their anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase, and cytotoxic activities.

Solid State Phase Transitions in Poly(ethylene oxide) Crystals Induced by Designed Chain Defects

We have used Cu(I)-catalyzed azide–alkyne cycloaddition to synthesize a new series of poly(ethylene oxide)s having in the center of their chains two 1,2,3-triazole (TR) rings separated by (CH2)n spacers with 2 ≤ n ≤ 4 (PEO11-TR-(CH2)n-TR-PEO11). The degree of crystallinity obtained by temperature-dependent WAXS measurements indicates that only one out of the two PEO11 chains of the three polymers forms a 72 helix upon cooling to −10 °C and crystallizes into a monoclinic unit cell known from PEO homopolymer. A solid-state phase transition occurs for all samples during heating below their melting temperature. Solid-state 13C MAS cross-polarization and single-pulse NMR spectroscopy indicate the complete incorporation of the chain defects into the PEO crystals (PEO-TR phase) during this transition. The 2D WAXS pattern of an oriented PEO11-TR-(CH2)2-TR-PEO11 sample generates a structural model where the crystal lattice of the initial PEO phase becomes highly distorted during the solid-state phase transition du...

Dual-Responsive Polyphosphoester-Doxorubicin Prodrug Containing a Diselenide Bond: Synthesis, Characterization, and Drug Delivery.

The development of novel stimuli-responsive and biodegradable polyphosphoester-anticancer prodrugs is of importance in designing water-soluble prodrugs utilized in the field of drug delivery. In this study, the focus is on the synthesis of biocompatible and biodegradable diselenide-containing polyphosphoester [PEEP-b-PBYP-Se]2 using reduction-responsive di(1-hydroxylundecyl) diselenide as an initiator to polymerize 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane (BYP) and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EOP). After that, a doxorubicin (DOX) derivative containing an azide group was linked onto the side chain of [PEEP-b-PBYP-Se]2 via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction to yield a pH/reduction-responsive polymeric prodrug, namely [PEEP-b-(PBYP-hyd-DOX)-Se]2. The chemical structures of various polymers were characterized by nuclear magnetic resonance spectroscopy, ultraviolet-visible spectrophotometer, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. The self-assembly behavior measured by dynamic light scattering and transmission electron microscopy clearly supported the formation of the prodrug nanoparticles (NPs). The results indicated that the polymeric prodrug NPs were relatively uniform spheres that could maintain stability in a physiological condition but be cleaved in acidic or reductive medium. Furthermore, the pH- and reduction-responsive properties of the prodrug NPs were investigated via drug release in vitro in different media. It turned out that the drug was efficiently released in acidic or reductive medium compared with that under physiological conditions. The results of methyl thiazolyl tetrazolium assays confirmed the favorable biocompatibility of [PEEP-b-PBYP-Se]2. Moreover, the cell cytotoxicity and intracellular uptake experiments were carried out to verify the efficient cellular proliferation inhibition. This finding contributes to the design of a novel diselenide-containing polyphosphoester-doxorubicin prodrug.

Multifunctional, High Molecular Weight, Post-Translationally Modified Proteins through Oxidative Cysteine Coupling and Tyrosine Modification.

Glycoproteins and their mimics are challenging to produce via chemical or biological methods because of their long protein backbones and large number of polysaccharide side chains that form a densely grafted protein-polysaccharide brush architecture. Herein, we demonstrate a new approach to protein bioconjugate synthesis that can approach the molar mass and functionalization densities of natural glycoproteins such as mucins and aggrecans. In this method, a tyrosine-enriched protein sequence is engineered and synthesized in E. coli, and sugars or other functional moieties can be efficiently and polyvalently grafted to the backbone through tyrosine modification chemistry. Cysteine residues on the chain ends are used for oxidative chain polymerization into high molar mass chains larger than can be easily expressed in the host. The effects of tyrosine-enrichment and cysteine-incorporation on the physical and expression properties on a model protein are explored. Elastin-like peptides (ELPs) are chosen because of their high expression yields, repetitive sequence, substitutable amino acids, and well-studied physical properties. The sequence modifications to mimic glycoproteins are shown to affect the maximum length of expressible sequence but not yield. The tyrosine modification chemistry is shown to functionalize up to 73% of all tyrosines on the peptide, and the scope of functional groups that can be mass conjugated to proteins is expanded through multistep conjugation strategies involving copper(I)-catalyzed alkyne-azide cycloaddition showing up to 97% alkyne functionalization. All of the functionalization chemistries preserve the ability to polymerize the backbone.

Development of direct contact-killing non-leaching antimicrobial polyurethanes through click chemistry

A robust, efficient, and orthogonal click chemistry (copper (I)-catalyzed alkyne-azide cycloaddition) was used to prepare an antimicrobial polymer and precisely control the conjugation ratio of antibiotic molecules to polymer. Antimicrobial polyurethanes with pendant benzisothiazolinone (PU-BIT) were synthesized using click chemistry to connect azide functional polyurethane (PU-N3) and alkyne functional benzisothiazolinone (BIT-Al). The direct contact-killing and non-leaching antimicrobial properties of PU-BIT were verified by both antimicrobial drop and disk diffusion. This approach provides a new methodology and platform for the development of contact-killing and non-leaching antimicrobial materials for a variety of practical applications. This research is the first to demonstrate that the broad-spectrum BIT antibiotic is a selective antibiotic for Gram-positive bacteria when covalently linked to a polymer. PU-BIT film containing 0.8 wt% BIT exhibited a selective antimicrobial performance with bactericidal efficacy of 91.6% and 30% against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, respectively. The mechanism of the selective antimicrobial activity of PU-BIT is also discussed.

Exploring Exchange Bias Coupling in Fe3−δO4@CoO Core–Shell Nanoparticle 2D Assemblies

AbstractCore‐shell ferro(i)magnetic@antiferromagnetic (F(i)M@AFM) nanoparticles exhibiting exchange bias coupling are very promising to push back the superparamagnetic limits. However, their intrinsic magnetic properties can be strongly affected by interparticle interactions. This work reports on the collective properties of Fe3–dO4@CoO core‐shell nanoparticles as function of the structure of their assembly. The structure of nanoparticle assembly is controlled by a copper (I) catalyzed alkyne–azide cycloaddition (CuAAC) “click” reaction between complementary functional groups located at the surface of both substrates and nanoparticles. 2D arrays of nanoparticles with tunable sizes ranging from clusters of few nanoparticles to a dense and homogenous monolayer were prepared. The spatial arrangement of nanoparticles strongly influences the exchange bias coupling which is significantly enhanced for large 2D nanoparticle assemblies and, even more in 3D assemblies such as powder, which favour weak and random dipolar interactions.

Synthesis of bottlebrush polymers with v-shaped side chains

Bottlebrush polymers with v-shaped side chains were fabricated via “grafting onto” method by a combination of reversible addition fragmentation chain transfer polymerization (RAFT), atom transfer radical polymerization (ATRP)/ring opening polymerization (ROP), and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. RAFT was used to prepare poly(glycidyl methacrylate) backbones with an azide side group on each repeating unit (PGMA-N3). ATRP/ROP was used to synthesize a diversity of v-shaped side chains with an alkynyl group in the middle of polymer chain including poly(methyl methacrylate) (v(PMMA)2), poly(tert-butyl acrylate) (v(PtBA)2), polystyrene (v(PS)2), and poly(ε-caprolactone)-block-polystyrene (v(PCL-b-PS)). CuAAC reaction was then conducted to graft the alkynyl-functionalized side chains onto azide containing backbones and produce the corresponding bottlebrush polymers with varied v-shaped side chains such as PGMA283-g-v(PtBA22)2, PGMA100-g-v(PtBA22)2, PGMA100-g-v(PtBA35)2, PGMA100-g-v(PS10)2, PGMA100-g-v(PMMA30)2, and PGMA100-g-v(PCL10-b-PS24). For all these bottlebrush polymers with varied v-shaped polymer side chains, a high side chain grafting density was obtained with a value above ca. 80% based on the “grafting onto” method developed in this study.

Versatile Click Cyanine Amino Acid Conjugates Showing One‐Atom‐Influenced Recognition of DNA/RNA Secondary Structure and Mitochondrial Localisation in Living Cells

By a simple click CuAAC (copper(I)‐catalysed azide alkyne cycloaddition) procedure several cyanine dye analogues have been attached to the side‐chain of an amino acid to yield chromophore amino acid conjugates with the potential to fluoresce upon binding to a target. Due to the availabiltiy of the amino acid C and N termini for peptide coupling, these conjugates are suitable for easy incorporation into the backbone of peptides. The novel amino acid dyes prepared in this work, although intrinsically non‐fluorescent, gave rise to strong fluorimetric responses upon binding to double‐stranded (ds) DNA or RNA, the emission response to various polynucleotide secondary structures being controlled either by linker length or a halogen atom located on the cyanine part of the molecule. Molecular modelling confirmed the mode of binding to different polynucleotides, which was responsible for the recognition. Interestingly, cell localisation experiments showed that the dyes were specifically localised in mitochondria at variance with the localisation of the parent dyes, which accumulate in cell nuclei, which suggests that the amino acid tail (containing a triazole ring) might function as a novel mitochondria‐directing appendage.