Plasma induced acceleration and selectivity in strain-promoted azide-alkyne cycloadditions.

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.

An Entry of the Chemoselective Sulfo-Click Reaction into the Sphere of Nucleic Acids.

We report here the first example of a sulfo-click conjugation reaction to be applied to modified nucleosides. The reaction, which proceeds rapidly (k ∼ 2.0 × 10-1 M-1 s-1 at 25 °C) under aqueous biocompatible conditions in the ribo- and deoxyribonucleoside series, affords the corresponding conjugated products in excellent yields. Furthermore, we demonstrate the orthogonality of the reaction with the copper-catalyzed azide-alkyne click reaction (CuAAC) by performing a one-pot dual labeling of a nucleoside carrying two orthogonal azido groups.