Direct ring-strain loading for visible-light accelerated bioorthogonal ligation via diarylsydnone-dibenzo[b,f ][1,4,5]thiadiazepine photo-click reactions.

Ultra-fast and selective covalent-bond forming reactions with spatiotemporal controllability are foundational for developing a bioorthogonal approach with high manipulability. However, it is challenging to exploit a reporter functional group to achieve these requirements simultaneously. Here, 11H-Dibenzo[c,f][1,2]diazepine and a set of heterocyclic analogues are investigated for both their photo-switching natures and their ability to serve as dipolarophiles in photo-click reactions with diarylsydnone. Sulfur-containing dibenzothiadiazepine (DBTD) is discovered to be an excellent chemical reporter in cycloaddition with visible-light excitation for in-situ ring-strain loading via its (Z) → (E) photo-isomerization. The bioorthogonal utility of the DBTD tag in spatiotemporally controlled ligation for protein modifications on live cells is also demonstrated.

Dual Colorimetric/Fluorometric Double-Throw pH-Switches: The Dimroth Rearrangement of N,9-Diaryl 8-Azaadenines.

A library of 12N,9-Diaryl 2-methyl-8-azaadenine (DAMA) compounds was designed and constructed through an aryl-pairing combination strategy for identifying a nucleobase-containing molecular switch that functions by the pH-regulated Dimroth rearrangement. By utilizing 2D thin-layer chromatography/mass spectrometry (2D-TLC-MS), the DAMA compounds were easily screened to identify which compounds could be used as molecular switches. The pH-switching ability of the DAMA was achieved by incorporating the acridine group as the key structural unit, as well as dual-modal colorimetric/fluorometric on/off properties as the probe functions. The real-time tracing of the switching process clearly indicated that the paired aromatics on both terminals of the DAMA molecule play a key role in tuning the switching kinetics.

Photo-accelerated "click" reaction between diarylsydnones and ring-strained alkynes for bioorthogonal ligation.

We constructed a library of diarylsydnone (DASyd) candidates in search of a photoclickable reaction toward alkynes, enabling an ultra-accelerated reactivity, while suppressing the background cycloaddition in the dark. The in vitro and in vivo protein labelling experiments revealed that the photo-accelerated DASyd-alkyne cycloaddition exhibits robust selectivity.