Thermally Triggered Triazolinedione-Tyrosine Bioconjugation with Improved Chemo- and Site-Selectivity.

A bioconjugation strategy is reported that allows the derivatization of tyrosine side chains through triazolinedione-based "Y-clicking". Blocked triazolinedione reagents were developed that, in contrast to classical triazolinedione reagents, can be purified before use, can be stored for a long time, and allow functionalization with a wider range of cargoes and labels. These reagents are bench-stable at room temperature but steadily release highly reactive triazolinediones upon heating to 40 °C in buffered media at physiological pH, showing a sharp temperature response over the 0 to 40 °C range. This conceptually interesting strategy, which is complementary to existing photo- or electrochemical bioorthogonal bond-forming methods, not only avoids the classical synthesis and handling difficulties of these highly reactive click-like reagents but also markedly improves the selectivity profile of the tyrosine conjugation reaction itself. It avoids oxidative damage and "off-target" tryptophan labeling, and it even improves site-selectivity in discriminating between different tyrosine side chains on the same protein or different polypeptide chains. In this research article, we describe the stepwise development of these reagents, from their short and modular synthesis to small-molecule model bioconjugation studies and proof-of-principle bioorthogonal chemistry on peptides and proteins.

Site selective gold(i)-catalysed benzylic C-H amination via an intermolecular hydride transfer to triazolinediones.

Triazolinediones are known as highly reactive dienophiles that can also act as electrophilic amination reagents towards enolisable C-H bonds (ionic pathway) or weak C-H bonds (free radical pathway). Here, we report that this C-H amination reactivity can be significantly extended and enhanced via gold(i)-catalysis. Under mild conditions, several alkyl-substituted aryls successfully undergo benzylic C-H aminations at room temperature. The remarkable site selectivity that is observed points towards strong electronic activation and deactivation effects, that go beyond a simple weakening of the C-H bond. The observed catalytic C-H aminations do not follow the expected trends for a free radical-type C-H amination and show complementarity to existing methods. Density functional theory (DFT) calculations and distinct experimental trends provide a clear mechanistic rationale for observed selectivity patterns, postulating a novel pathway for triazolinedione-induced aminations via a carbon-to-nitrogen hydride transfer.

PMO-Immobilized AuI -NHC Complexes: Heterogeneous Catalysts for Sustainable Processes.

A stable periodic mesoporous organosilica (PMO) with accessible sulfonic acid functionalities is prepared via a one-pot-synthesis and is used as solid support for highly active catalysts, consisting of gold(I)-N-heterocyclic carbene (NHC) complexes. The gold complexes are successfully immobilized on the nanoporous hybrid material via a straightforward acid-base reaction with the corresponding [Au(OH)(NHC)] synthon. This catalyst design strategy results in a boomerang-type catalyst, allowing the active species to detach from the surface to perform the catalysis and then to recombine with the solid after all the starting material is consumed. This boomerang behavior is assessed in the hydration of alkynes. The tested catalysts were found to be active in the latter reaction, and after an acidic work-up, the IPr*-based gold catalyst can be recovered and then reused several times without any loss in efficiency.