Plasma induced acceleration and selectivity in strain-promoted azide–alkyne cycloadditions. Issue 23 (24th May 2021)

• Record Type: Journal Article
• Authors: Warther, David; Dursun, Enes; Recher, Marion; Ursuegui, Sylvain; Mosser, Michel; Sobska, Joanna; Krezel, Wojciech; Chaubet, Guilhem; Wagner, Alain
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 23(2021)
• Page Start: 5063
• Page End: 5067
• Publication Date: 2021-05-24
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00529d
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : We report the unexpected acceleration of strain-promoted azide–alkyne cycloaddition in human plasma compared to classical solvent systems. Besides fast kinetics, human plasma also allows for discrimination between two azides in competition reaction. Abstract : Strain-promoted azide–alkyne cycloaddition (SPAAC) is an important member of the bioorthogonal reaction family. Over the past decade, much work has been dedicated to the generation of new strained alkynes with improved reactivity. While kinetics studies of SPAAC are often conducted in organic solvents, buffered solutions or mixtures, these media do not reflect the complexity of in vivo systems. In this work, we show that performing SPAAC in human plasma leads to intriguing kinetics and selectivity effects. In particular, we observed that reactions in plasma could be accelerated up to 70-fold compared to those in methanol, and that selective couplings between a pair of reagents could be possible in competition experiments. These findings highlight the value of evaluating bioorthogonal reactions in such a complex medium, especially when in vivo applications are planned, as unsuspected behaviour can be observed, disrupting the usual rules governing the reactivity in simple solvent systems.