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Chemical Communications (Cambridge,... Apr 2022C-H Azidation is an increasingly important tool for bioconjugation, materials chemistry, and the synthesis of nitrogen-containing natural products. While several...
C-H Azidation is an increasingly important tool for bioconjugation, materials chemistry, and the synthesis of nitrogen-containing natural products. While several approaches have been developed, these often require exotic and energetic reagents, expensive photocatalysts, or both. Here we report a simple and general C-H azidation reaction using earth-abundant tetra--butylammonium decatungstate as a photocatalyst and commercial -acetamidobenzenesulfonyl azide (-ABSA) as the azide source. This system can azidate a variety of unactivated C(sp)-H bonds in moderate to good yields and excellent turnover numbers. Preliminary mechanistic experiments implicate a radical mechanism proceeding photo-hydrogen atom transfer (photo-HAT).
Topics: Azides; Catalysis; Hydrogen; Nitrogen
PubMed: 35348566
DOI: 10.1039/d2cc00425a -
Bioconjugate Chemistry Nov 2023The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists... (Review)
Review
The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide-alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based pretargeting.
Topics: Click Chemistry; Radiochemistry; Azides; Radiopharmaceuticals; Cycloaddition Reaction; Alkynes
PubMed: 37737084
DOI: 10.1021/acs.bioconjchem.3c00286 -
Chemical Reviews Jun 2021Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on... (Review)
Review
Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on multiple scientific disciplines, and its implementation within the nucleic acid field has enabled researchers to generate a wide variety of tools with application in biology, biochemistry, and biotechnology. Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds. Application of AAC chemistry to nucleic acids allows labeling, ligation, and cyclization of oligonucleotides efficiently and cost-effectively relative to previously used chemical and enzymatic techniques. In this review, we provide a guide to inexperienced and knowledgeable researchers approaching the field of click chemistry with nucleic acids. We discuss in detail the chemistry, the available modified-nucleosides, and applications of AAC reactions in nucleic acid chemistry and provide a critical view of the advantages, limitations, and open-questions within the field.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Nucleic Acids; Thermodynamics
PubMed: 33443411
DOI: 10.1021/acs.chemrev.0c00928 -
Chemical Reviews Jun 2021At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this... (Review)
Review
At its basic conceptualization, photoclick chemistry embodies a collection of click reactions that are performed via the application of light. The emergence of this concept has had diverse impact over a broad range of chemical and biological research due to the spatiotemporal control, high selectivity, and excellent product yields afforded by the combination of light and click chemistry. While the reactions designated as "photoclick" have many important features in common, each has its own particular combination of advantages and shortcomings. A more extensive realization of the potential of this chemistry requires a broader understanding of the physical and chemical characteristics of the specific reactions. This review discusses the features of the most frequently employed photoclick reactions reported in the literature: photomediated azide-alkyne cycloadditions, other 1,3-dipolarcycloadditions, Diels-Alder and inverse electron demand Diels-Alder additions, radical alternating addition chain transfer additions, and nucleophilic additions. Applications of these reactions in a variety of chemical syntheses, materials chemistry, and biological contexts are surveyed, with particular attention paid to the respective strengths and limitations of each reaction and how that reaction benefits from its combination with light. Finally, challenges to broader employment of these reactions are discussed, along with strategies and opportunities to mitigate such obstacles.
Topics: Alkynes; Azides; Click Chemistry; Cycloaddition Reaction; Photochemistry
PubMed: 33835796
DOI: 10.1021/acs.chemrev.0c01212 -
Molecules (Basel, Switzerland) Jan 2022The changes in the local and global dynamics of azide-labelled lysozyme compared with that of the wild type protein are quantitatively assessed for all alanine residues...
The changes in the local and global dynamics of azide-labelled lysozyme compared with that of the wild type protein are quantitatively assessed for all alanine residues along the polypeptide chain. Although attaching -N3 to alanine residues has been considered to be a minimally invasive change in the protein it is found that depending on the location of the alanine residue, the local and global changes in the dynamics differ. For Ala92, the change in the cross-correlated motions are minimal, whereas attaching -N3 to Ala90 leads to pronounced differences in the local and global correlations as quantified by the cross-correlation coefficients of the Cα atoms. We also demonstrate that the spectral region of the asymmetric azide stretch distinguishes between alanine attachment sites, whereas changes in the low frequency, far-infrared region are less characteristic.
Topics: Azides; Molecular Dynamics Simulation; Motion; Muramidase; Thermodynamics
PubMed: 35164105
DOI: 10.3390/molecules27030839 -
Nature Chemistry Aug 2021Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept...
Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with 'real time' drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy.
Topics: Animals; Antineoplastic Agents; Azides; Doxorubicin; Female; Fluorescent Dyes; Gamma Rays; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Indazoles; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Oxidation-Reduction; Prodrugs; Proof of Concept Study; Pyrimidines; Sulfonamides; X-Rays; Xenograft Model Antitumor Assays; Mice
PubMed: 34112990
DOI: 10.1038/s41557-021-00711-4 -
Molecules (Basel, Switzerland) Jun 2021Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of... (Review)
Review
Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of improving selectivity and mildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminal alpha-amine group appears a convenient solution to the issue, emerging as a useful and unique reactive site universally present in each protein molecule. Herein, we provide an updated overview of the methodologies developed until today to afford the selective modification of proteins through the targeting of the N-terminal alpha-amine. Chemical and enzymatic strategies enabling the selective labeling of the protein N-terminal alpha-amine group are described.
Topics: Amines; Azides; Binding Sites; Click Chemistry; Molecular Probe Techniques; Protein Domains; Proteins
PubMed: 34207845
DOI: 10.3390/molecules26123521 -
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 -
Current Protocols in Chemical Biology Dec 2020Reversible addition-fragmentation chain-transfer (RAFT) polymerization is a commonly used polymerization methodology to generate synthetic polymers. The products of RAFT...
Reversible addition-fragmentation chain-transfer (RAFT) polymerization is a commonly used polymerization methodology to generate synthetic polymers. The products of RAFT polymerization, i.e., RAFT polymers, have been widely employed in several biologically relevant areas, including drug delivery, biomedical imaging, and tissue engineering. In this article, we summarize a synthetic methodology to display an azide group at the chain end of a RAFT polymer, thus presenting a reactive site on the polymer terminus. This platform enables a click reaction between azide-terminated polymers and alkyne-containing molecules, providing a broadly applicable scaffold for chemical and bioconjugation reactions on RAFT polymers. We also highlight applications of these azide-terminated RAFT polymers in fluorophore labeling and for promoting organelle targeting capability. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of the azide derivatives of chain transfer agent and radical initiator Basic Protocol 2: Installation of an azide group on the α-end of RAFT polymers Alternate Protocol: Installation of an azide group on the ω-end of RAFT polymers Basic Protocol 3: Click reaction between azide-terminated RAFT polymers and alkyne derivatives.
Topics: Azides; Click Chemistry; Diagnostic Imaging; Drug Delivery Systems; Polymerization; Polymers; Tissue Engineering
PubMed: 33207082
DOI: 10.1002/cpch.85 -
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