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Click chemistry is an approach to chemical synthesis that emphasizes efficiency, simplicity, selectivity, and modularity in chemical processes used to join molecular building blocks. It includes both the development and use of "click reactions", a set of simple, biocompatible chemical reactions that meet specific criteria like high yield, fast reaction rates, and minimal byproducts. It was first fully described by K. Barry Sharpless, Hartmuth C. Kolb, and M. G. Finn of The Scripps Research Institute in 2001.[1][2] In this seminal paper, Sharpless argued that synthetic chemistry could emulate the way nature constructs complex molecules, using efficient reactions to join together simple, non-toxic building blocks.

The term "click chemistry" was coined in 1998 by Sharpless' wife, Jan Dueser,[3] who found the simplicity of this approach to chemical synthesis akin to clicking together Lego blocks. In fact, the simplicity of click chemistry represented a paradigm shift in synthetic chemistry, and has had significant impact in many industries, especially pharmaceutical development. In 2022, the Nobel Prize in Chemistry was jointly awarded to Carolyn R. Bertozzi, Morten P. Meldal and Sharpless, "for the development of click chemistry and bioorthogonal chemistry".[4]

Principles

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For a reaction to be considered a click reaction, it must satisfy certain characteristics:[5]

  • modularity
  • insensitivity to solvent parameters
  • high chemical yields
  • insensitivity towards oxygen and water
  • regiospecificity and stereospecificity
  • a large thermodynamic driving force (>20 kcal/mol) to favor a reaction with a single reaction product. A distinct exothermic reaction makes a reactant "spring-loaded".

The process would preferably:

  • have simple reaction conditions
  • use readily available starting materials and reagents
  • use no solvent or use a solvent that is benign or easily removed (preferably water)
  • provide simple product isolation by non-chromatographic methods (crystallisation or distillation)
  • have high atom economy.

Many of the click chemistry criteria are subjective, and even if measurable and objective criteria could be agreed upon, it is unlikely that any reaction will be perfect for every situation and application. However, several reactions have been identified that fit the concept better than others:[clarification needed]

Specific Click Reactions

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Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)

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Main article: Azide alkyne Huisgen cycloaddition

The classic[13][14] click reaction is the copper-catalyzed reaction of an azide with an alkyne to form a 5-membered heteroatom ring: a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The first triazole synthesis, from diethyl acetylenedicarboxylate and phenyl azide, was reported by Arthur Michael in 1893.[15] Later, in the middle of the 20th century, this family of 1,3-dipolar cycloadditions took on Rolf Huisgen's name after his studies of their reaction kinetics and conditions.

A comparison of the Huisgen and the copper-catalyzed Azide-Alkyne cycloadditions

The copper(I)-catalysis of the Huisgen 1,3-dipolar cycloaddition was discovered concurrently and independently by the groups of Valery V. Fokin and K. Barry Sharpless at the Scripps Research Institute in California[16] and Morten Meldal in the Carlsberg Laboratory, Denmark.[17] The copper-catalyzed version of this reaction gives only the 1,4-isomer, whereas Huisgen's non-catalyzed 1,3-dipolar cycloaddition gives both the 1,4- and 1,5-isomers, is slow, and requires a temperature of 100 degrees Celsius.[15]

The two-copper mechanism of the CuAAC catalytic cycle

Moreover, this copper-catalyzed "click" does not require ligands on the metal, although accelerating ligands such as tris(triazolyl)methyl amine ligands with various substituents have been reported and used with success in aqueous solution.[15] Other ligands such as PPh3 and TBIA can also be used, even though PPh3 is liable to Staudinger ligation with the azide substituent. Cu2O in water at room temperature was found also to catalyze the same reaction in 15 minutes with 91% yield.[18]

The first reaction mechanism proposed included one catalytic copper atom; but isotope, kinetic, and other studies have suggested a dicopper mechanism may be more relevant.[19][20][21][22][23] Even though this reaction proceeds effectively at biological conditions, copper in this range of dosage is cytotoxic. Solutions to this problem have been presented, such as using water-soluble ligands on the copper to enhance cell penetration of the catalyst and thereby reduce the dosage needed,[24][25][26] or to use chelating ligands to further increase the effective concentration of Cu(I) and thereby decreasing the actual dosage.[27][28][29]

Although the Cu(I)-catalyzed variant was first reported by Meldal and co-workers for the synthesis of peptidotriazoles on solid support, their conditions were far from the true spirit of click chemistry and were overtaken by the publicly more recognized Sharpless. Meldal and co-workers also chose not to label this reaction type "click chemistry" which allegedly caused their discovery to be largely overlooked by the mainstream chemical society. Fokin and Sharpless independently described it as a reliable catalytic process offering "an unprecedented level of selectivity, reliability, and scope for those organic synthesis endeavors which depend on the creation of covalent links between diverse building blocks".

An analogous RuAAC reaction catalyzed by ruthenium, instead of copper, was reported by the Jia and Fokin groups in 2005, and allows for the selective production of 1,5-isomers.[30]

Strain-promoted azide-alkyne cycloaddition (SPAAC)

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The Bertozzi group further developed one of Huisgen's copper-free click reactions to overcome the cytotoxicity of the CuAAC reaction.[31] Instead of using Cu(I) to activate the alkyne, the alkyne is instead introduced in a strained difluorooctyne (DIFO), in which the electron-withdrawing, propargylic, gem-fluorines act together with the ring strain to greatly destabilize the alkyne.[32] This destabilization increases the reaction driving force, and the desire of the cycloalkyne to relieve its ring strain.

Scheme of the Strain-promoted Azide-Alkyne Cycloaddition

This reaction proceeds as a concerted [3+2] cycloaddition to the triple bond in a cyclooctyne in the same mechanism as the Huisgen 1,3-dipolar cycloaddition. Substituents other than fluorines, such as benzene rings, are also allowed on the cyclooctyne.

This reaction has been used successfully to probe for azides in living systems, even though the reaction rate is somewhat slower than that of the CuAAC. Moreover, because the synthesis of cyclooctynes often gives low yield, probe development for this reaction has not been as rapid as for other reactions. But cyclooctyne derivatives such as DIFO, dibenzylcyclooctyne (DIBO or DBCO) and biarylazacyclooctynone (BARAC) have all been used successfully in the SPAAC reaction to probe for azides in living systems.[33][34][35]

Strain-promoted alkyne-nitrone cycloaddition (SPANC)

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Diaryl-strained-cyclooctynes including dibenzylcyclooctyne (DIBO) have also been used to react with 1,3-nitrones in strain-promoted alkyne-nitrone cycloadditions (SPANC) to yield N-alkylated isoxazolines.[36]

The SPAAC vs SpANC reaction

Because this reaction is metal-free and proceeds with fast kinetics (k2 as fast as 60 1/Ms, faster than both the CuAAC or the SPAAC) SPANC can be used for live cell labeling. Moreover, substitution on both the carbon and nitrogen atoms of the nitrone dipole, and acyclic and endocyclic nitrones are all tolerated. This large allowance provides a lot of flexibility for nitrone handle or probe incorporation.[37]

However, the isoxazoline product is not as stable as the triazole product of the CuAAC and the SpAAC, and can undergo rearrangements at biological conditions. Regardless, this reaction is still very useful as it has notably fast reaction kinetics.[36]

The applications of this reaction include labeling proteins containing serine as the first residue: the serine is oxidized to aldehyde with NaIO4 and then converted to nitrone with p-methoxybenzenethiol, N-methylhydroxylamine and p-ansidine, and finally incubated with cyclooctyne to give a click product. The SPANC also allows for multiplex labeling.[38][39]

Reactions of strained alkenes

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Strained alkenes also utilize strain-relief as a driving force that allows for their participation in click reactions. Trans-cycloalkenes (usually cyclooctenes) and other strained alkenes such as oxanorbornadiene react in click reactions with a number of partners including azides, tetrazines and tetrazoles. These reaction partners can interact specifically with the strained alkene, staying bioorthogonal to endogenous alkenes found in lipids, fatty acids, cofactors and other natural products.[38]

Alkene and azide [3+2] cycloaddition

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Oxanorbornadiene (or another activated alkene) reacts with azides, giving triazoles as a product. However, these product triazoles are not aromatic as they are in the CuAAC or SPAAC reactions, and as a result are not as stable. The activated double bond in oxanobornadiene makes a triazoline intermediate that subsequently spontaneously undergoes a retro Diels-alder reaction to release furan and give 1,2,3- or 1,4,5-triazoles. Even though this reaction is slow, it is useful because oxabornodiene is relatively simple to synthesize. The reaction is not, however, entirely chemoselective.[40]

Alkene and tetrazine inverse-demand Diels-Alder

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A Tetrazine-Alkene reaction between a generalized tetrazine and a strained, trans-cyclooctene

Strained cyclooctenes and other activated alkenes react with tetrazines in an inverse electron-demand Diels-Alder followed by a retro [4+2] cycloaddition (see figure).[41] Like the other reactions of the trans-cyclooctene, ring strain release is a driving force for this reaction. Thus, three-membered and four-membered cycloalkenes, due to their high ring strain, make ideal alkene substrates.[41]

Similar to other [4+2] cycloadditions, electron-donating substituents on the dienophile and electron-withdrawing substituents on the diene accelerate the inverse-demand Diels-Alder. The diene, the tetrazine, by virtue of having the additional nitrogens, is a good diene for this reaction. The dienophile, the activated alkene, can often be attached to electron-donating alkyl groups on target molecules, thus making the dienophile more suitable for the reaction.[42]

Alkene and tetrazole photoclick reaction

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The tetrazole-alkene "photoclick" reaction is another dipolar addition that Huisgen first introduced in the late 1960s ChemBioChem 2007, 8, 1504. (68) Clovis, J. S.; Eckell, A.; Huisgen, R.; Sustmann, R. Chem. Ber. 1967, 100, 60.) Tetrazoles with amino or styryl groups that can be activated by UV light at 365 nm (365 does not damage cells) react quickly (so that the UV light does not have to be on for a long time, usually around 1–4 minutes) to make fluorogenic pyrazoline products. This reaction scheme is well suited for the purpose of labeling in live cells, because UV light at 365 nm damages cells minimally. Moreover, the reaction proceeds quickly, so that the UV light can be administered for short durations. Quantum yields for short wavelength UV light can be higher than 0.5. This allows tetrazoles to be used wavelength selectively in combination with another photoligation reaction, where at the short wavelength the tetrazole ligation reaction proceeds nearly exclusively and at longer wavelength another reaction (ligation via o-quinodimethanes) proceeds exclusively.[43] Finally, the non-fluorogenic reactants give rise to a fluorogenic product, equipping the reaction with a built-in spectrometry handle.

Both tetrazoles and the alkene groups have been incorporated as protein handles as unnatural amino acids, but this benefit is not unique. Instead, the photoinducibility of the reaction makes it a prime candidate for spatiotemporal specificity in living systems. Challenges include the presence of endogenous alkenes, though usually cis (as in fatty acids) they can still react with the activated tetrazole.[44]

Applications

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The criteria for click reactions are designed to make the chemistry biocompatible, for applications like isolating and targeting molecules in complex biological environments. In such environments, products accordingly need to be physiologically stable and any byproducts need to be non-toxic (for in vivo systems).

In many applications, click reactions join a biomolecule and a reporter molecule or other molecular probe, a process called bioconjugation.[45] The possibility of attaching fluorophores and other reporter molecules has made click chemistry a very powerful tool for identifying, locating, and characterizing both old and new biomolecules..

One of the earliest and most important methods in bioconjugation was to express a reporter gene, such as the gene green fluorescent protein (GFP), on the same genetic sequence as a protein of interest. In this way, the protein can be identified in cells and tissues by the green florescence. However, this approach comes with several difficulties, as the GFP can affect the ability of the protein to achieve its normal shape or hinder its normal expression and functions. Additionally, using this method, GFP can only be attached to proteins, leaving other important biomolecular classes (nucleic acids, lipids, carbohydrates, etc.) out of reach.

To overcome these challenges, chemists have opted to proceed by identifying pairs of bioorthogonal reaction partners, thus allowing the use of small exogenous molecules as biomolecular probes. A fluorophore can be attached to one of these probes to give a fluorescence signal upon binding of the reporter molecule to the target—just as GFP fluoresces when it is expressed with the target.

Now limitations emerge from the chemistry of the probe to its target. In order for this technique to be useful in biological systems, click chemistry must run at or near biological conditions, produce little and (ideally) non-toxic byproducts, have (preferably) single and stable products at the same conditions, and proceed quickly to high yield in one pot. Existing reactions, such as Staudinger ligation and the Huisgen 1,3-dipolar cycloaddition, have been modified and optimized for such reaction conditions. Today, research in the field concerns not only understanding and developing new reactions and repurposing and re-understanding known reactions, but also expanding methods used to incorporate reaction partners into living systems, engineering novel reaction partners, and developing applications for bioconjugation.

By developing specific and controllable bioorthogonal reactions, scientists have opened up the possibility of hitting particular targets in complex cell lysates. Recently, scientists have adapted click chemistry for use in live cells, for example using small molecule probes that find and attach to their targets by click reactions. Despite challenges of cell permeability, bioorthogonality, background labeling, and reaction efficiency, click reactions have already proven useful in a new generation of pulldown experiments (in which particular targets can be isolated using, for instance, reporter molecules which bind to a certain column), and fluorescence spectrometry (in which the fluorophore is attached to a target of interest and the target quantified or located). More recently, novel methods have been used to incorporate click reaction partners onto and into biomolecules, including the incorporation of unnatural amino acids containing reactive groups into proteins and the modification of nucleotides. These techniques represent a part of the field of chemical biology, in which click chemistry plays a fundamental role by intentionally and specifically coupling modular units to various ends.

Biotech company Shasqi is a company leveraging click chemistry in humans.[46][47]

Click chemistry is not limited to biological conditions: the concept of a "click" reaction has been used in chemoproteomic, pharmacological, biomimetic and molecular machinery applications.[48]


Click Chemistry is a powerful tool to probe for the cellular localization of small molecules. Knowing where a small molecules goes in the cell gives powerful insights into their mechanisms of action.[49] This approach has been used in numerous studies, and discoveries include that salinomycin localizes to lysosomes to initiate ferroptosis in cancer stem cells[50] and that metformin derivatives accumulate in mitochondria to chelate copper(II), affecting metabolism and epigenetic changes downstream in inflammatory macrophages.[51]

The commercial potential of click chemistry is great. The fluorophore rhodamine has been coupled onto norbornene, and reacted with tetrazine in living systems.[52] In other cases, SPAAC between a cyclooctyne-modified fluorophore and azide-tagged proteins allowed the selection of these proteins in cell lysates.[53]

Unnatural Amino Acids

Methods for the incorporation of click reaction partners into systems in and ex vivo contribute to the scope of possible reactions. The development of unnatural amino acid incorporation by ribosomes has allowed for the incorporation of click reaction partners as unnatural side groups on these unnatural amino acids. For example, an UAA with an azide side group provides convenient access for cycloalkynes to proteins tagged with this "AHA" unnatural amino acid.[54] In another example, "CpK" has a side group including a cyclopropane alpha to an amide bond that serves as a reaction partner to tetrazine in an inverse diels-alder reaction.[55]

Scheme of the synthesis of firefly luciferin

The synthesis of luciferin exemplifies another strategy of isolating reaction partners, which is to take advantage of rarely-occurring, natural groups such as the 1,2-aminothiol, which appears only when a cysteine is the final N' amino acid in a protein. Their natural selectivity and relative bioorthogonality is thus valuable in developing probes specific for these tags. The above reaction occurs between a 1,2-aminothiol and a 2-cyanobenzothiazole to make luciferin, which is fluorescent. This luciferin fluorescence can be then quantified by spectrometry following a wash, and used to determine the relative presence of the molecule bearing the 1,2-aminothiol. If the quantification of non-1,2-aminothiol-bearing protein is desired, the protein of interest can be cleaved to yield a fragment with a N' Cys that is vulnerable to the 2-CBT.[56]

Additional applications include:

In combination with combinatorial chemistry, high-throughput screening, and building chemical libraries, click chemistry has hastened new drug discoveries by making each reaction in a multistep synthesis fast, efficient, and predictable.

Technology license

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The Scripps Research Institute has a portfolio of click-chemistry patents.[63] Licensees include Invitrogen,[64] Allozyne,[65] Aileron,[66] Integrated Diagnostics,[67] and the biotech company baseclick,[68] a BASF spin-off created to sell products made using click chemistry.[69] Moreover, baseclick holds a worldwide exclusive license for the research and diagnostic market for the nucleic acid field. Fluorescent azides and alkynes are also produced by companies such as Cyandye.[70]

References

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  1. ^ H. C. Kolb; M. G. Finn; K. B. Sharpless (2001). "Click Chemistry: Diverse Chemical Function from a Few Good Reactions". Angewandte Chemie International Edition. 40 (11): 2004–2021. doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5. PMID 11433435.
  2. ^ R. A. Evans (2007). "The Rise of Azide–Alkyne 1,3-Dipolar 'Click' Cycloaddition and its Application to Polymer Science and Surface Modification". Australian Journal of Chemistry. 60 (6): 384–395. doi:10.1071/CH06457.
  3. ^ Nobel Prize lecture: Barry Sharpless, Nobel Prize in Chemistry 2022, retrieved 2024-01-04
  4. ^ "The Nobel Prize in Chemistry 2022". NobelPrize.org. Retrieved 2022-10-05.
  5. ^ a b Wang, Xifan; Schmidt, Franziska; Hanaor, Dorian; Kamm, Paul H.; Li, Shuang; Gurlo, Aleksander (May 6, 2019). "Additive manufacturing of ceramics from preceramic polymers: A versatile stereolithographic approach assisted by thiol-ene click chemistry". Additive Manufacturing. 27: 80–90. arXiv:1905.02060. doi:10.1016/j.addma.2019.02.012. S2CID 104470679.
  6. ^ Spiteri, Christian; Moses, John E. (2010). "Copper-Catalyzed Azide–Alkyne Cycloaddition: Regioselective Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles". Angewandte Chemie International Edition. 49 (1): 31–33. doi:10.1002/anie.200905322. PMID 19921729.
  7. ^ Hoyle, Charles E.; Bowman, Christopher N. (2010). "Thiol–Ene Click Chemistry". Angewandte Chemie International Edition. 49 (9): 1540–1573. doi:10.1002/anie.200903924. PMID 20166107.
  8. ^ Lowe, A. B. Polymer Chemistry 2010, 1 (1), 17–36. DOI: 10.1039/B9PY00216B
  9. ^ Blackman, Melissa L.; Royzen Maksim; Fox, Joseph M. (2008). "Tetrazine Ligation: Fast Bioconjugation Based on Inverse-Electron-Demand Diels−Alder Reactivity". Journal of the American Chemical Society. 130 (41): 13518–13519. doi:10.1021/ja8053805. PMC 2653060. PMID 18798613.
  10. ^ Devaraj, Neal K.; Weissleder Ralph & Hilderbrand, Scott A. (2008). "Tetrazine Based Cycloadditions: Application to Pretargeted Live Cell Labeling". Bioconjugate Chemistry. 19 (12): 2297–2299. doi:10.1021/bc8004446. PMC 2677645. PMID 19053305.
  11. ^ Stöckmann, Henning; Neves, Andre; Stairs, Shaun; Brindle, Kevin; Leeper, Finian (2011). "Exploring isonitrile-based click chemistry for ligation with biomolecules". Organic & Biomolecular Chemistry. 9 (21): 7303–5. doi:10.1039/C1OB06424J. PMID 21915395.
  12. ^ Kashemirov, Boris A.; Bala, Joy L. F.; Chen, Xiaolan; Ebetino, F. H.; Xia, Zhidao; Russell, R. Graham G.; Coxon, Fraser P.; Roelofs, Anke J.; Rogers Michael J.; McKenna, Charles E. (2008). "Fluorescently labeled risedronate and related analogues: "magic linker" synthesis". Bioconjugate Chemistry. 19 (12): 2308–2310. doi:10.1021/bc800369c. PMID 19032080.
  13. ^ Gregory C., Patton (November 8, 2004). "Development and Applications of Click Chemistry" (PDF). Department of Chemistry. College of Liberal Arts & Sciences, University of Illinois at Urbana-Champaign. Archived from the original (PDF) on 2010-07-09. {{cite journal}}: Cite journal requires |journal= (help)
  14. ^ Kolb, H.C.; Sharpless, B.K. (2003). "The growing impact of click chemistry on drug discovery". Drug Discov Today. 8 (24): 1128–1137. doi:10.1016/S1359-6446(03)02933-7. PMID 14678739.
  15. ^ a b c L. Liang and D. Astruc: "The copper(I)-catalysed alkyne-azide cycloaddition (CuAAC) "click" reaction and its applications. An overview", 2011; 255, 23–24, 2933–2045, p. 2934
  16. ^ Rostovtsev, Vsevolod V.; Green, Luke G; Fokin, Valery V.; Sharpless, K. Barry (2002). "A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of Azides and Terminal Alkynes". Angewandte Chemie International Edition. 41 (14): 2596–2599. doi:10.1002/1521-3773(20020715)41:14<2596::aid-anie2596>3.0.co;2-4. PMID 12203546.
  17. ^ Tornoe, C. W.; Christensen, C.; Meldal, M. (2002). "Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides". Journal of Organic Chemistry. 67 (9): 3057–3064. doi:10.1021/jo011148j. PMID 11975567. S2CID 11957672.
  18. ^ K. Wang, X. Bi, S. Xing, P. Liao, Z. Fang, X. Meng, Q. Zhang, Q. Liu, Y. Ji Green Chem., 13 (2011), p. 562
  19. ^ B. T. Worrell, J. A. Malik, V. V. Fokin 2013, 340, 457–459 ; J.E. Hein, V.V. Fokin, Chem. Soc. Rev. 39 (2010) 1302.
  20. ^ Rodionov, Valentin O.; Fokin, Valery V.; Finn, M. G. (2005-04-08). "Mechanism of the Ligand-Free CuI-Catalyzed Azide–Alkyne Cycloaddition Reaction". Angewandte Chemie International Edition. 44 (15): 2210–2215. doi:10.1002/anie.200461496. ISSN 1521-3773. PMID 15693051.
  21. ^ Iacobucci, Claudio; Reale, Samantha; Gal, Jean-François; De Angelis, Francesco (2015-03-02). "Dinuclear Copper Intermediates in Copper(I)-Catalyzed Azide–Alkyne Cycloaddition Directly Observed by Electrospray Ionization Mass Spectrometry". Angewandte Chemie International Edition. 54 (10): 3065–3068. doi:10.1002/anie.201410301. ISSN 1521-3773. PMID 25614295.
  22. ^ Özkılıç, Yılmaz; Tüzün, Nurcan Ş. (2016-08-22). "A DFT Study on the Binuclear CuAAC Reaction: Mechanism in Light of New Experiments". Organometallics. 35 (16): 2589–2599. doi:10.1021/acs.organomet.6b00279. ISSN 0276-7333.
  23. ^ Ziegler, Micah S.; Lakshmi, K. V.; Tilley, T. Don (2017-04-19). "Dicopper Cu(I)Cu(I) and Cu(I)Cu(II) Complexes in Copper-Catalyzed Azide–Alkyne Cycloaddition" (PDF). Journal of the American Chemical Society. 139 (15): 5378–5386. doi:10.1021/jacs.6b13261. ISSN 0002-7863. PMID 28394586.
  24. ^ Brotherton, W. S.; Michaels, H. A.; Simmons, J. T.; Clark, R.J.; Dalal, N. S.; Zhu, L. Org. Lett. 2009, 11, 4954.
  25. ^ Kuang, G.-C.; Michaels, H. A.; Simmons, J. T.; Clark, R. J.; Zhu, L" J. Org. Chem. 2010; 75, 6540.
  26. ^ Uttamapinant, C.; Tangpeerachaikul, A.; Grecian, S.; Clarke, S.; Singh, U.; Slade, P.; Gee, K. R.; Ting, A. Y" Angew. Chem. Int. Ed. 2012; 51, 5852
  27. ^ Alder, K.; Stein, G.; Finzenhagen, H. Justus Liebigs Ann.Chem 1931, 485, 211.
  28. ^ Alder, K.; Stein, G. Justus Liebigs Ann. Chem. 1933, 501, 1.
  29. ^ Wittig, G.; Krebs, A. Chem. Ber. 1961, 94, 3260.
  30. ^ Zhang, Li; Chen, Xinguo; Xue, Peng; Sun, Herman H. Y.; Williams, Ian D.; Sharpless, K. Barry; Fokin, Valery V.; Jia, Guochen (November 2005). "Ruthenium-Catalyzed Cycloaddition of Alkynes and Organic Azides". Journal of the American Chemical Society. 127 (46): 15998–15999. doi:10.1021/ja054114s. PMID 16287266.
  31. ^ Huisgen, R. Angew. Chem. Int. Ed. Engl. 1963, 2, 565

    Agard, N. J.; Baskin, J. M.; Prescher, J. A.; Lo, A.; Bertozzi, C. R. (2006). "A Comparative Study of Bioorthogonal Reactions with Azides". ACS Chem. Biol. 1 (10): 644–648. doi:10.1021/cb6003228. PMID 17175580.
  32. ^ Agard, N. J.; Baskin, J. M.; Prescher, J. A.; Lo, A.; Bertozzi, C. R. (2006). "A Comparative Study of Bioorthogonal Reactions with Azides". ACS Chem. Biol. 1 (10): 644–648. doi:10.1021/cb6003228. PMID 17175580.
  33. ^ Codelli, J. A.; Baskin, J. M.; Agard, N. J.; Bertozzi, C. R. (2008). "Second-Generation Difluorinated Cyclooctynes for Copper-Free Click Chemistry". J. Am. Chem. Soc. 130 (34): 11486–11493. doi:10.1021/ja803086r. PMC 2646667. PMID 18680289.
  34. ^ Ning, X.; Guo, J.; Wolfert, M. A.; Boons, G.-J. (2008). "Visualizing Metabolically Labeled Glycoconjugates of Living Cells by Copper-Free and Fast Huisgen Cycloadditions". Angew. Chem. Int. Ed. 47 (12): 2253–2255. doi:10.1002/anie.200705456. PMC 2835304. PMID 18275058.
  35. ^ Gordon, C. G.; Mackey, J. L.; Jewett, J. C.; Sletten, E. M.; Houk, K. N.; Bertozzi, C. R. (2012). "Reactivity of Biarylazacyclooctynones in Copper-Free Click Chemistry". J. Am. Chem. Soc. 134 (22): 9199–9208. doi:10.1021/ja3000936. PMC 3368396. PMID 22553995.
  36. ^ a b MacKenzie, DA; Sherratt, AR; Chigrinova, M; Cheung, LL; Pezacki, JP (Aug 2014). "Strain-promoted cycloadditions involving nitrones and alkynes—rapid tunable reactions for bioorthogonal labeling". Curr Opin Chem Biol. 21: 81–8. doi:10.1016/j.cbpa.2014.05.023. PMID 25022431.
  37. ^ (64) (a) Ning, X.; Temming, R. P.; Dommerholt, J.; Guo, J.; Ania, D.B.; Debets, M. F.; Wolfert, M. A.; Boons, G.-J.; van Delft, F. L" Angew. Chem. Int. Ed. 2010; 49, 3065. (b) McKay, C. S.; Moran, J.; Pezacki, J. P. Chem. Commun. (Cambridge, U. K.) 2010, 46, 931. (c) Debets, M. F.; van Berkel, S. S.; Dommerholt, J.; Dirks, A. T. J.; Rutjes, F. P. J. T.; van Delft, F. L. Acc. Chem. Res. 2011, 44, 805. (d) McKay, C. S.; Chigrinova, M.; Blake, J. A.; Pezacki, J. P. Org. Biomol. Chem. 2012, 10, 3066.
  38. ^ a b Lang, K.; Chin, J. (2014). "Bioorthogonal Reactions for Labeling Proteins". ACS Chem. Biol. 9 (1): 16–20. doi:10.1021/cb4009292. PMID 24432752.
  39. ^ MacKenzie, DA; Pezacki, JP (2014). "Kinetics studies of rapid strain- promoted [3+2] cycloadditions of nitrones with bicyclo[6.1.0]nonyne". Can J Chem. 92 (4): 337–340. doi:10.1139/cjc-2013-0577.
  40. ^ (67) (a) van Berkel, S. S.; Dirks, A. T. J.; Meeuwissen, S. A.; Pingen, D. L. L.; Boerman, O. C.; Laverman, P.; van Delft, F. L.; Cornelissen, J. J. L. M.; Rutjes, F. P. J. T. ChemBioChem 2008, 9, 1805. (b) van Berkel, S. S.; Dirks, A. T. J.; Debets, M. F.; van Delft, F. L.; Cornelissen, J. J. L. M.; Nolte, R. J. M.; Rutjes, F. P. J. T. ChemBioChem 2007, 8, 150
  41. ^ a b Liu, Fang; Paton, Robert S.; Kim, Seonah; Liang, Yong; Houk, K. N. (2013). "Diels–Alder Reactivities of Strained and Unstrained Cycloalkenes with Normal and Inverse-Electron-Demand Dienes: Activation Barriers and Distortion/Interaction Analysis". J. Am. Chem. Soc. 135 (41): 15642–15649. doi:10.1021/ja408437u. PMID 24044412.
  42. ^ Rieder, Ulrike; Luedtke, Nathan W. (25 August 2014). "Alkene-tetrazine ligation for imaging cellular DNA". Angew Chem Int Ed Engl. 53 (35): 9168–9172. doi:10.1002/anie.201403580. PMID 24981416.
  43. ^ Menzel, Jan P.; Feist, Florian; Tuten, Bryan; Weil, Tanja; Blinco, James P.; Barner‐Kowollik, Christopher (2019). "Light-Controlled Orthogonal Covalent Bond Formation at Two Different Wavelengths". Angewandte Chemie International Edition. 58 (22): 7470–7474. doi:10.1002/anie.201901275. hdl:21.11116/0000-0003-99B4-5. PMID 30916368.
  44. ^ Ramil, Carlo P; Lin, Qing (August 2014). "Photoclick chemistry: a fluorogenic light-triggered in vivo ligation reaction". Current Opinion in Chemical Biology. 21: 89–95. doi:10.1016/j.cbpa.2014.05.024. PMC 4149939. PMID 25022432.
  45. ^ B. Stump (2022). "Click Bioconjugation: Modifying Proteins Using Click-Like Chemistry". ChemBioChem. 23 (16): e202200016. doi:10.1002/cbic.202200016. PMID 35491526. S2CID 248494718.
  46. ^ "The bioorthogonal revolution". Chemistry World. Retrieved 2022-11-11.
  47. ^ "'Honeymoon-Phase' Chemical Partners Deliver a Toxic Drug to Tumors". Discover Magazine. Retrieved 2022-11-11.
  48. ^ Carroll, G. T.; London, G.; Fernandez-Landaluce, T.; Rudolf, P.; Feringa, B. L. (2011). "Adhesion of Photon-Driven Molecular Motors to Surfaces via 1,3-Dipolar Cycloadditions: Effect of Interfacial Interactions on Molecular Motion" (PDF). ACS Nano. 5 (1): 622–630. doi:10.1021/nn102876j. PMID 21207983. S2CID 39105918.
  49. ^ Cañeque, Tatiana; Müller, Sebastian; Rodriguez, Raphaël (2018). "Visualizing biologically active small molecules in cells using click chemistry". Nature Reviews Chemistry. 2 (9): 202–215. doi:10.1038/s41570-018-0030-x. S2CID 91366817.
  50. ^ Mai, Trang Thi; Hamaï, Ahmed; Hienzsch, Antje; Cañeque, Tatiana; Müller, Sebastian; Wicinski, Julien; Cabaud, Olivier; Leroy, Christine; David, Amandine; Acevedo, Verónica; Ryo, Akihide; Ginestier, Christophe; Birnbaum, Daniel; Charafe-Jauffret, Emmanuelle; Codogno, Patrice; Mehrpour, Maryam; xRodriguez, Raphaël Rodriguez (Oct 2017). "Salinomycin kills cancer stem cells by sequestering iron in lysosomes". Nature Chemistry. 9 (10): 1025–1033. doi:10.1038/nchem.2778. PMC 5890907. PMID 28937680.
  51. ^ Solier, Stéphanie; Müller, Sebastian; Tatiana, Cañeque; Antoine, Versini; Arnaud, Mansart; Fabien, Sindikubwabo; Leeroy, Baron; Laila, Emam; Pierre, Gestraud; G. Dan, Pantoș; Vincent, Gandon; Christine, Gaillet; Ting-Di, Wu; Florent, Dingli; Damarys, Loew; Sylvain, Baulande; Sylvère, Durand; Valentin, Sencio; Cyril, Robil; François, Trottein; David, Péricat; Emmanuelle, Näser; Céline, Cougoule; Etienne, Meunier; Anne-Laure, Bègue; Hélène, Salmon; Nicolas, Manel; Alain, Puisieux; Sarah, Watson; Mark A., Dawson; Nicolas, Servant; Guido, Kroemer; Djillali, Annane; Raphaël, Rodriguez (2023). "A druggable copper-signalling pathway that drives inflammation". Nature. 617 (7960): 386–394. doi:10.1038/s41586-023-06017-4. PMC 10131557. PMID 37100912.
  52. ^ Devaraj, Neal K.; Weissleder, Ralph; Hilderbrand, Scott A. (December 2008). "Tetrazine-based cycloadditions: application to pretargeted live cell imaging". Bioconjugate Chem. 19 (12): 2297–2299. doi:10.1021/bc8004446. PMC 2677645. PMID 19053305.
  53. ^ Ding, H.; Demple, B (2000). "Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5146–5150. Bibcode:2000PNAS...97.5146D. doi:10.1073/pnas.97.10.5146. PMC 25796. PMID 10805777.
  54. ^ Dieterich; et al. (2007). "Labeling, detection and identification of newly synthesized proteomes with bioorthogonal non-canonical amino-acid tagging". Nature Protocols. 2 (3): 532–540. doi:10.1038/nprot.2007.52. PMID 17406607. S2CID 2833184.
  55. ^ Yu; et al. (2012). "Genetically Encoded Cyclopropene Directs Rapid, Photoclick-Chemistry-Mediated Protein Labeling in Mammalian Cells". Angew Chem Int Ed Engl. 51 (42): 10600–10604. doi:10.1002/anie.201205352. PMC 3517012. PMID 22997015.
  56. ^ (a) Liang, G.; Ren, H.; Rao, J. Nat. Chem. 2010, 2, 54. (b) Ren, H.; Xiao, F.; Zhan, K.; Kim, Y.-P.; Xie, H.; Xia, Z.; Rao, J. Angew.Chem., Int. Ed. 2009, 48, 9658.
  57. ^ Ilya A. Osterman; Alexey V. Ustinov; Denis V. Evdokimov; Vladimir A. Korshun; Petr V. Sergiev; Marina V. Serebryakova; Irina A. Demina; Maria A. Galyamina; Vadim M. Govorun; Olga A. Dontsova (January 2013). "A nascent proteome study combining click chemistry with 2DE" (PDF). Proteomics. 13 (1): 17–21. doi:10.1002/pmic.201200393. PMID 23161590. S2CID 9002232. Archived from the original (PDF) on 2015-06-30. Retrieved 2015-02-11.
  58. ^ Cox, Courtney L.; Tietz, Jonathan I.; Sokolowski, Karol; Melby, Joel O.; Doroghazi, James R.; Mitchell, Douglas A. (17 June 2014). "Nucleophilic 1,4-Additions for Natural Product Discovery". ACS Chemical Biology. 9 (9): 2014–2022. doi:10.1021/cb500324n. PMC 4168802. PMID 24937678.
  59. ^ Michael Floros; Alcides Leão; Suresh Narine (2014). "Vegetable Oil Derived Solvent, and Catalyst Free "Click Chemistry" Thermoplastic Polytriazoles". BioMed Research International. 2014: 1–14. doi:10.1155/2014/792901. PMC 4085725. PMID 25032224.
  60. ^ London, Gábor; Chen, Kuang-Yen; Carroll, Gregory T.; Feringa, Ben L. (2013). "Towards Dynamic Control of Wettability by Using Functionalized Altitudinal Molecular Motors on Solid Surfaces". Chemistry: A European Journal. 19 (32): 10690–10697. doi:10.1002/chem.201300500. PMID 23784916. S2CID 5759186.
  61. ^ John E. Moses; Adam D. Moorhouse (2007). "The growing applications of click chemistry". Chem. Soc. Rev. 36 (8): 1249–1262. doi:10.1039/b613014n. PMID 17619685.
  62. ^ Jean-François Lutz; Zoya Zarafshani (2008). "Efficient construction of therapeutics, bioconjugates, biomaterials and bioactive surfaces using azide–alkyne "click" chemistry". Advanced Drug Delivery Reviews. 60 (9): 958–970. doi:10.1016/j.addr.2008.02.004. PMID 18406491.
  63. ^ "Click Chemistry". Archived from the original on 2012-05-15. Retrieved 2012-06-05.
  64. ^ "Invitrogen Exclusively Licenses Novel Click Chemistry-Based Cell Proliferation Assays from Harvard University (NASDAQ:LIFE)". Archived from the original on 2012-12-17. Retrieved 2012-06-05.
  65. ^ "Xconomy: Allozyne Licenses Scripps Chemistry". 2010-07-15.
  66. ^ "Xconomy: Aileron and Scripps Ink Deal". 2010-11-30.
  67. ^ "Integrated Diagnostics Licenses "Click Chemistry" from the Scripps Research Institute, Strengthening Partner Network". Archived from the original on 2012-04-30. Retrieved 2012-06-05.
  68. ^ "baseclick GmbH :: We enable nucleic acid labeling bioconjugation". baseclick GmbH. Retrieved 2022-03-21.
  69. ^ http://www.basf.com/group/pressrelease/P-10-427 [permanent dead link]
  70. ^ "CYANDYE". 2018-10-03. Archived from the original on 3 October 2018. Retrieved 2022-03-21.
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