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Organic Letters Jun 2021Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore,...
Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.
Topics: Alkynes; Azides; Azo Compounds; Catalysis; Click Chemistry; Molecular Structure; Triazoles
PubMed: 34019429
DOI: 10.1021/acs.orglett.1c01230 -
Journal of the American Chemical Society Aug 2022An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling...
An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.
Topics: Alkynes; Allyl Compounds; Catalysis; Ethers; Iridium; Stereoisomerism
PubMed: 35976157
DOI: 10.1021/jacs.2c07297 -
Langmuir : the ACS Journal of Surfaces... Jun 2021Self-assembling colloidal particles into clathrate hydrates requires the particles to have tetrahedral bonds in the eclipsed conformation. It has been suggested that...
Self-assembling colloidal particles into clathrate hydrates requires the particles to have tetrahedral bonds in the eclipsed conformation. It has been suggested that colloidal particles with eclipsed triangular-shaped patches can form clusters in the eclipsed conformation that leads to colloidal clathrate hydrates. However, in experiments, patches have been limited to circular shapes due to surface energy minimization. Here, we extend the particle synthesis strategy and show that colloidal particles with triangular patches can be readily fabricated by controlling the viscosity of the liquid oil droplets during a colloidal fusion process. The position, orientation, curvature, shape, and size of the patches are all exclusively determined by the intrinsic symmetry of the colloidal clusters, resulting in dipatch particles with eclipsed patches and tetrahedral patchy particles with patch vertices pointing toward each other. Patch curvature can be controlled by tuning the viscosity of the oil droplets and using different surfactants. Using strain-promoted azide-alkyne cycloaddition, single-stranded DNA can be selectively functionalized on the patches. However, after annealing these particles, dipatch particles form chains because the patches are too small to form clathrate hydrates. Under certain conditions, tetrahedral triangular patchy particles should prefer the eclipsed conformation, as it maximizes DNA hybridization. However, we observe random aggregates, which result from having triangular patches that are too big. We estimate that tetrahedral patchy particles that can crystallize need to be less than 1 μm in diameter.
Topics: Alkynes; Azides; Colloids; Cycloaddition Reaction
PubMed: 34081481
DOI: 10.1021/acs.langmuir.1c00877 -
Biochimie Mar 2023Along with bright fluorescence in the near-IR range, heptamethine carbocyanine dyes possess affinity to cancer cells. Thus, these dyes could be utilized as fluorescent...
Along with bright fluorescence in the near-IR range, heptamethine carbocyanine dyes possess affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery as covalent conjugates with cytotoxic compounds. To test the properties, structure-activity relationship, and scope of such conjugates, we synthesized drug-dye dyads of tricarbocyanine dyes with anthracycline drug daunorubicin. We used hydrophilic zwitterionic and hydrophobic positively charged benzoindoline-benzothiazole-based heptamethine dyes as terminal alkyne derivatives and N-acylated or oxime-linked daunorubicin as azido-derivatives. These two alkynes and two azides were coupled to each other by Cu-catalyzed Huisgen-Meldal-Sharpless cycloaddition (click reaction) to afford four conjugates. Molecules based on hydrophobic dyes possess submicromolar cytotoxicity to HCT116 cells. Cytotoxicity, cell penetration, intracellular distribution, apoptosis induction and the effect of antioxidants on toxicity were evaluated. The results show that the structure of the cyanine-anthracycline conjugate (hydrophilicity/hydrophobicity, charge, linker, attachment site) is important for its biological activity, thus, expansion of the chemical space of such conjugates could provide new molecular research tools for diagnostics and therapy.
Topics: Fluorescent Dyes; Anthracyclines; Carbocyanines; Alkynes; Daunorubicin; Azides; Click Chemistry
PubMed: 36179940
DOI: 10.1016/j.biochi.2022.09.015 -
Langmuir : the ACS Journal of Surfaces... Aug 2022Gold nanoparticles (AuNPs) are currently intensively exploited in the biomedical field as they possess interesting chemical and optical properties. Although their...
Gold nanoparticles (AuNPs) are currently intensively exploited in the biomedical field as they possess interesting chemical and optical properties. Although their synthesis is well-known, their controlled surface modification with defined densities of ligands such as peptides, DNA, or antibodies remains challenging and has generally to be optimized case by case. This is particularly true for applications like in vivo drug delivery that require AuNPs with multiple ligands, for example a targeting ligand and a drug in well-defined proportions. In this context, we aimed to develop a calixarene-modification strategy that would allow the controlled orthogonal conjugation of AuNPs, respectively, via amide bond formation and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). To do this, we synthesized a calix[4]arene-tetradiazonium salt bearing four PEG chains ended by an alkyne group () and, after optimization of its grafting on 20 nm AuNPs, we demonstrated that CuAAC can be used to conjugate an azide containing dye (N-cya7.5). It was observed that AuNPs coated with (AuNPs-) can be conjugated to approximately 600 N-cya7.5 that is much higher than the value obtained for AuNPs decorated with traditional thiolated PEG ligands terminated by an alkyne group. The control over the number of molecules conjugated via CuAAC was even possible by incorporating a non-functional calixarene () into the coating layer. We then combined with a calix[4]arene-tetradiazonium salt bearing four carboxyl groups () that allows conjugation of an amine (NH-cya7.5) containing dye. The conjugation potential of these bifunctional AuNPs-/ was quantified by UV-vis spectroscopy: AuNPs decorated with equal amount of and could be conjugated to approximately 350 NH-dyes and 300 N-dyes using successively amide bond formation and CuAAC, demonstrating the control over the orthogonal conjugation. Such nanoconstructs could benefit to anyone in the need of a controlled modification of AuNPs with two different molecules via two different chemistries.
Topics: Alkynes; Amides; Azides; Calixarenes; Coloring Agents; Gold; Ligands; Metal Nanoparticles; Phenols; Polyethylene Glycols
PubMed: 35866876
DOI: 10.1021/acs.langmuir.2c01122 -
The Journal of Organic Chemistry May 2022A series of [2]rotaxanes with various functional groups in the axle component was synthesized by the oxidative dimerization of alkynes, which is mediated by a...
A series of [2]rotaxanes with various functional groups in the axle component was synthesized by the oxidative dimerization of alkynes, which is mediated by a macrocyclic phenanthroline-Cu complex. The rotaxanes were fully characterized by spectroscopic methods, and the structure of a rotaxane was determined by X-ray crystallographic analysis. The interaction between the ring component and the axle component was studied in detail to understand the conformation of the rotaxanes. The presence of the hydrogen bond between the phenanthroline moiety in the macrocyclic component and the acidic proton in the axle component influenced the conformation of rotaxane.
Topics: Alkynes; Hydrogen Bonding; Molecular Conformation; Phenanthrolines; Rotaxanes
PubMed: 35389647
DOI: 10.1021/acs.joc.2c00086 -
ACS Macro Letters Jul 2022Terminal alkynes display high reactivity toward Ru-carbene metathesis catalysts. However, the formation of a less reactive bulky carbene hinders their...
Terminal alkynes display high reactivity toward Ru-carbene metathesis catalysts. However, the formation of a less reactive bulky carbene hinders their homopolymerization. Simultaneously, the higher reactivity of alkynes does not allow efficient cross propagation with sterically less-hindered cycloalkene monomers, resulting in inefficient copolymerization. Nonetheless, terminal alkynes undergo rapid cross-metathesis with vinyl ethers. Therefore, an efficient cross propagation can be achieved with terminal alkynes and cyclic enol ether monomers. Here, we show that terminal alkyne derivatives can be copolymerized in an alternating fashion with 2,3-dihydrofuran using Grubbs' third generation catalyst (). A linear relationship of the number-average molecular weight versus monomer to initiator ratio and block copolymer synthesis confirmed a controlled copolymerization. The SEC and NMR analyses of the synthesized copolymers confirmed the excellent control over molecular weight and exclusive alternating nature of the copolymer. The regioselective chain transfer of to vinyl ether and the high reactivity of the Fischer-type Ru carbene toward terminal alkynes was also exploited for polymer conjugation. Finally, the presence of an acid labile backbone functionality in the synthesized alternating copolymers allowed complete degradation of the copolymer within a short time interval which was confirmed by SEC analyses.
Topics: Alkynes; Catalysis; Polymerization; Polymers
PubMed: 35736023
DOI: 10.1021/acsmacrolett.2c00258 -
Organic & Biomolecular Chemistry Apr 2020Nanographenes are a popular area of research due to their promising properties for electronics. Over the last twenty years there has been a significant increase in... (Review)
Review
Nanographenes are a popular area of research due to their promising properties for electronics. Over the last twenty years there has been a significant increase in interest in the development of contorted nanographenes. While many top-down techniques are employed in the synthesis of these planar nanographenes, the use of alkynes in bottom-up syntheses allows for easy functionalization and the development of contorted nanographenes. The syntheses of contorted nanographenes with a focus on utilizing alkynes is reviewed here.
Topics: Alkynes; Cyclization; Graphite; Molecular Conformation; Nanostructures
PubMed: 32196052
DOI: 10.1039/d0ob00182a -
Chemical Communications (Cambridge,... Nov 2021Sodium pyruvate, a natural intermediate produced during cellular metabolism, is commonly used in buffer solutions and media for biochemical applications. Here we show...
Sodium pyruvate, a natural intermediate produced during cellular metabolism, is commonly used in buffer solutions and media for biochemical applications. Here we show the use of sodium pyruvate (SP) as a reducing agent in a biocompatible aqueous photoinduced azide-alkyne cycloaddition (CuAAC) reaction. This copper(I)-catalyzed 1,3-dipolar cycloaddition is triggered by SP under UV light irradiation, exhibits oxygen tolerance and temporal control, and provides a convenient alternative to current CuAAC systems, particularly for biomolecular conjugations.
Topics: Alkynes; Azides; Biocompatible Materials; Copper; Cycloaddition Reaction; Molecular Structure; Photochemical Processes; Pyruvates; Ultraviolet Rays
PubMed: 34787596
DOI: 10.1039/d1cc05566f -
European Journal of Medicinal Chemistry May 2023Currently, bioorthogonal coupling reactions have garnered considerable interest due to their high substrate selectivity and less restrictive reaction conditions. During... (Review)
Review
Currently, bioorthogonal coupling reactions have garnered considerable interest due to their high substrate selectivity and less restrictive reaction conditions. During recent decades, bioorthogonal coupling reactions have emerged as powerful tools in drug development. This review describes the current applications of bioorthogonal coupling reactions in compound library building mediated by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and in situ click chemistry or conjunction with other techniques; druggability optimization with 1,2,3-triazole groups; and intracellular self-assembly platforms with ring tension reactions, which are presented from the viewpoint of drug development. There is a reasonable prospect that bioorthogonal coupling reactions will accelerate the screening of lead compounds, the designing strategies of small molecules and expand the variety of designed compounds, which will be a new trend in drug development in the future.
Topics: Copper; Drug Development; Cycloaddition Reaction; Azides; Click Chemistry; Alkynes; Catalysis
PubMed: 37037138
DOI: 10.1016/j.ejmech.2023.115338