Photochemical Formation of Dibenzosilacyclohept-4-yne for Cu-Free Click Chemistry with Azides and 1,2,4,5-Tetrazines

Abstract

Photochemical generation of dibenzosilacyclohept-4-yne 3 from the corresponding cyclopropenone 1 and its copper-free click reactions are reported. Steady-state irradiation, kinetic, and transient absorption spectroscopy studies revealed that strained alkyne 3 is rapidly (<5 ns) and efficiently (Φ = 0.58-0.71) photoreleased from 1 and undergoes remarkably fast, selective, and high-yielding 1,3-dipolar cycloaddition with benzyl azide (∼20 M s) or [4 + 2] inverse-electron-demand Diels-Alder reaction with 1,2,4,5-tetrazines (∼260 M s) in both methanol and acetonitrile.

Photo‐induced and Rapid Labeling of Tetrazine‐Bearing Proteins via Cyclopropenone‐Caged Bicyclononynes

“…Furthermore,a zide-modified amino acids are not completely stable towards reduction to the corresponding amine in the cytosol of E. coli and therefore our stable methyl-tetrazine amino acids make for more reliable reporters in live E. coli. Interestingly,also arecently reported dibenzoannulated and cyclopropenone-caged silicon-containing cycloheptyne (photo-13) [28] failed in reacting with tetrazine-or azide-modified proteins under identical conditions ( Supporting Information, Figures S14, S15). No cycloaddition product was observed even after overnight incubation, though decarbonylation to 12 had proceeded cleanly as proven by LC-MS, highlighting that the extra ring strain in DMBO is needed for reaction with methyl-tetrazines.…”

“…[2c, 27] Incubation of photo-12 with azide-bearing sfGFP under UV-irradiation resulted in approximately 60 %SPA AC product upon overnight incubation, demonstrating that the extra strain in DMBO results also in higher reactivity towards azides (Supporting Information, Figures S11, S13). Interestingly,also arecently reported dibenzoannulated and cyclopropenone-caged silicon-containing cycloheptyne (photo-13) [28] failed in reacting with tetrazine-or azide-modified proteins under identical conditions ( Supporting Information, Figures S14, S15).…”

Photo-controllable bioorthogonal chemistry for spatiotemporal control of bio-targets in living systems

“…26 Pioneered by this work, various photo-labile precursors of strained alkynes have been explored for photocontrollable generation of strained alkynes as the biorthogonal functionality. [27][28][29][30] Visible-light triggered active alkyne generation from cyclopropenones was established with the aid of visible light-responsive photocatalysts. 31 Caged phosphines have also been designed and prepared for UV or even visible light triggered generation of active phosphine for lightcontrollable Staudinger-Bertozzi ligation.…”

“…The photophysical and photochemical properties of these precursors have been investigated extensively to optimize the photolysis step. 26,29,30,32,33 The absorption wavelength and quantum yield are two important parameters that have been considered for the purpose of photo-release of bioorthogonal functionalities, because light with a longer wavelength and lower intensity is more compatible with living systems. Fast rates of photolysis and the following bioorthogonal ligation process are important for the spatiotemporal resolution of a photo-controlled reaction.…”

“…Fast rates of photolysis and the following bioorthogonal ligation process are important for the spatiotemporal resolution of a photo-controlled reaction. 28,29,34,35 It should be noted that this type of photocontrollable bioorthogonal reaction is only a modied version of known bioorthogonal reactions. Cross-talk of the original version and photo-controllable version of the same bioorthogonal reactions is therefore not avoidable.…”