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Angewandte Chemie (International Ed. in... Jul 2021A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in...
A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine. The kinetics are on par with those of the fastest strain-promoted azide-alkyne cycloaddition reactions, the products regioselectively formed, the components sufficiently stable and easily installed, and the reaction suitable for cellular labeling.
Topics: Alkynes; Amination; Azides; Cycloaddition Reaction; Molecular Structure
PubMed: 34019705
DOI: 10.1002/anie.202104863 -
Methods in Molecular Biology (Clifton,... 2022Copper-catalyzed azide-alkyne cycloaddition (CuAAC) provides a simple and convenient strategy to synthesize diverse 1,2,3-triazoles for drug discovery. Described herein...
Copper-catalyzed azide-alkyne cycloaddition (CuAAC) provides a simple and convenient strategy to synthesize diverse 1,2,3-triazoles for drug discovery. Described herein is a protocol for the CuSO-catalyzed cycloaddition between alkynes and DNA-appended azides.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper; Cycloaddition Reaction; DNA; Triazoles
PubMed: 36083541
DOI: 10.1007/978-1-0716-2545-3_6 -
Mikrochimica Acta Dec 2023Immobilization of proteins and enzymes on solid supports has been utilized in a variety of applications, from improved protein stability on supported catalysts in...
Immobilization of proteins and enzymes on solid supports has been utilized in a variety of applications, from improved protein stability on supported catalysts in industrial processes to fabrication of biosensors, biochips, and microdevices. A critical requirement for these applications is facile yet stable covalent conjugation between the immobilized and fully active protein and the solid support to produce stable, highly bio-active conjugates. Here, we report functionalization of solid surfaces (gold nanoparticles and magnetic beads) with bio-active proteins using site-specific and biorthogonal labeling and azide-alkyne cycloaddition, a click chemistry. Specifically, we recombinantly express and selectively label calcium-dependent proteins, calmodulin and calcineurin, and cAMP-dependent protein kinase A (PKA) with N-terminal azide-tags for efficient conjugation to nanoparticles and magnetic beads. We successfully immobilized the proteins on to the solid supports directly from the cell lysate with click chemistry, forgoing the step of purification. This approach is optimized to yield low particle aggregation and high levels of protein activity post-conjugation. The entire process enables streamlined workflows for bioconjugation and highly active conjugated proteins.
Topics: Azides; Gold; Metal Nanoparticles; Proteins; Catalysis
PubMed: 38129631
DOI: 10.1007/s00604-023-06068-4 -
Journal of the American Chemical Society Nov 2022The new nonheme iron complexes Fe(BNPAO)(N) (), Fe(BNPAO)(OH)(N) (), Fe(BNPAO)(OH) (), Fe(BNPAO)(OH)(NCS) (), Fe(BNPAO)(NCS) (), Fe(BNPAO)(NCS) (), and Fe(BNPAO)(N) ()...
The new nonheme iron complexes Fe(BNPAO)(N) (), Fe(BNPAO)(OH)(N) (), Fe(BNPAO)(OH) (), Fe(BNPAO)(OH)(NCS) (), Fe(BNPAO)(NCS) (), Fe(BNPAO)(NCS) (), and Fe(BNPAO)(N) () (BNPAO = 2-(bis((6-(neopentylamino)pyridin-2-yl) methyl)amino)-1,1-diphenylethanolate) were synthesized and characterized by single crystal X-ray diffraction (XRD), as well as by H NMR, Fe Mössbauer, and ATR-IR spectroscopies. Complex was reacted with a series of carbon radicals, ArC· (Ar = -X-CH), analogous to the proposed radical rebound step for nonheme iron hydroxylases and halogenases. The results show that for ArC· (X = Cl, H, Bu), only OH· transfer occurs to give ArCOH. However, when X = OMe, a mixture of alcohol (ArCOH) (30%) and azide (ArCN) (40%) products was obtained. These data indicate that the rebound selectivity is influenced by the electron-rich nature of the carbon radicals for the azide complex. Reaction of with PhC· in the presence of Sc or H reverses the selectivity, giving only the azide product. In contrast to the mixed selectivity seen for , the reactivity of -Fe(OH)(NCS) with the X = OMe radical derivative leads only to hydroxylation. Catalytic azidation was achieved with as catalyst, λ-azidoiodane as oxidant and azide source, and PhCH as test substrate, giving PhCN in 84% (TON = 8). These studies show that hydroxylation is favored over azidation for nonheme iron(III) complexes, but the nature of the carbon radical can alter this selectivity. If an OH· transfer pathway can be avoided, the Fe(N) complexes are capable of mediating both stoichiometric and catalytic azidation.
Topics: Iron; Azides; Catalysis; Magnetic Resonance Spectroscopy; Carbon; Ferrous Compounds; Isothiocyanates; Ligands
PubMed: 36382466
DOI: 10.1021/jacs.2c07224 -
Organic Letters Jun 2023An oxidative azido-difluoromethylthiolation of alkenes by employing TMSN as the azide source and PhSOSCFH as the difluoromethylthiolation reagent is reported. The...
An oxidative azido-difluoromethylthiolation of alkenes by employing TMSN as the azide source and PhSOSCFH as the difluoromethylthiolation reagent is reported. The present method is characterized by good functional group tolerance, broad substrate scope, and short reaction time, thereby providing an efficient access to synthetically useful β-difluoromethylthiolated azides. Mechanistic studies indicate a radical pathway involved in the reaction.
Topics: Alkenes; Azides; Catalysis; Indicators and Reagents
PubMed: 37288936
DOI: 10.1021/acs.orglett.3c01562 -
Bioorganic Chemistry Feb 2024Antibody-Drug Conjugates (ADC) are a new class of anticancer therapeutics with immense potential. They have been rapidly advancing in the last two decades. This fast... (Review)
Review
Antibody-Drug Conjugates (ADC) are a new class of anticancer therapeutics with immense potential. They have been rapidly advancing in the last two decades. This fast speed of development has become possible due to several new technologies and methods. One of them is Click Chemistry, an approach that was created only two decades ago, but already is actively utilized for bioconjugation, material science and drug discovery. In this review, we researched the impact of Click Chemistry reactions on the synthesis and development of ADCs. The information about the most frequently utilized reactions, such as Michael's addition, Copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC), Strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), oxime bond formation, hydrazine-iso-Pictet-Spengler Ligation (HIPS), Diels-Alder reactions have been summarized. The implementation of thiol-maleimide Click Chemistry reaction in the synthesis of numerous FDA-approved Antibody-Drug Conjugates has been reported. The data amassed in the present review provides better understanding of the importance of Click Chemistry in the synthesis, development and improvement of the Antibody-Drug Conjugates and it will be helpful for further researches related to ADCs.
Topics: Click Chemistry; Azides; Alkynes; Cycloaddition Reaction; Copper; Maleimides; Sulfhydryl Compounds
PubMed: 37995642
DOI: 10.1016/j.bioorg.2023.106982 -
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 -
Nature Communications Nov 2022Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous...
Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering α-acylamino amides and α-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.).
Topics: Cobalt; Azides; Stereoisomerism; Catalysis; Cyanides
PubMed: 36400776
DOI: 10.1038/s41467-022-34887-1 -
Molecules (Basel, Switzerland) Oct 20191-Amino-2-nitroguanidine (ANQ) is a high-energy nitrogen-rich compound with good detonation properties and low sensitivities. ANQ has only a central carbon atom with... (Review)
Review
1-Amino-2-nitroguanidine (ANQ) is a high-energy nitrogen-rich compound with good detonation properties and low sensitivities. ANQ has only a central carbon atom with three small groups around it, including an amino, a hydrazine and a nitroxyl group. Though the molecular structure of ANQ is very simple, its reactivity is surprisingly abundant. ANQ can undergo various reactions, including reduction reaction, acylation reaction, salification reaction, coordination reaction, aldimine condensation reaction, cyclization reaction and azide reaction. Many new energetic compounds were purposely obtained through these reactions. These reactions were systematically summarized in this review, and detonation properties of some energetic compounds were compared. In the field of energetic materials, ANQ and some derivatives exhibit good application prospects.
Topics: Azides; Cyclization; Guanidines; Molecular Structure; Oxidation-Reduction
PubMed: 31597251
DOI: 10.3390/molecules24193616 -
Basic & Clinical Pharmacology &... Mar 2021Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a...
Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0-100 µg/mL for both analytes, and azide was stable in human plasma at -20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.
Topics: Adult; Azides; Chromatography, Gas; Cyanides; Female; Humans
PubMed: 33090684
DOI: 10.1111/bcpt.13523