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Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells

The archetype reaction of “click” chemistry, namely, the copper-promoted azide–alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interio...

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Autores principales: Miguel-Ávila, Joan, Tomás-Gamasa, María, Olmos, Andrea, Pérez, Pedro J., Mascareñas, José L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892125/
https://www.ncbi.nlm.nih.gov/pubmed/29675241
http://dx.doi.org/10.1039/c7sc04643j
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author Miguel-Ávila, Joan
Tomás-Gamasa, María
Olmos, Andrea
Pérez, Pedro J.
Mascareñas, José L.
author_facet Miguel-Ávila, Joan
Tomás-Gamasa, María
Olmos, Andrea
Pérez, Pedro J.
Mascareñas, José L.
author_sort Miguel-Ávila, Joan
collection PubMed
description The archetype reaction of “click” chemistry, namely, the copper-promoted azide–alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)–tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of “non-innocent” reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities.
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spelling pubmed-58921252018-04-19 Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells Miguel-Ávila, Joan Tomás-Gamasa, María Olmos, Andrea Pérez, Pedro J. Mascareñas, José L. Chem Sci Chemistry The archetype reaction of “click” chemistry, namely, the copper-promoted azide–alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(i)–tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of “non-innocent” reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(ii) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities. Royal Society of Chemistry 2018-01-15 /pmc/articles/PMC5892125/ /pubmed/29675241 http://dx.doi.org/10.1039/c7sc04643j Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Miguel-Ávila, Joan
Tomás-Gamasa, María
Olmos, Andrea
Pérez, Pedro J.
Mascareñas, José L.
Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title_full Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title_fullStr Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title_full_unstemmed Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title_short Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
title_sort discrete cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892125/
https://www.ncbi.nlm.nih.gov/pubmed/29675241
http://dx.doi.org/10.1039/c7sc04643j
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