Design, Synthesis, and Application of Sulfonium Diazo Probes for Red-Light Photocatalytic Proximity Labeling

Photocatalytic proximity labeling has become a versatile tool for probing biomolecular interactions, with growing interest in longer-wavelength activation, owing to its biocompatibility with various tissue types. Despite recent advances, highly efficient and residue-agnostic labeling systems operating under such conditions remain underdeveloped. Herein, we report the development of a novel labeling probe incorporating an α-sulfonium diazo aryl ketone (sulfonium diazo aryl ketone (SDAK)) scaffold as the reactive warhead, together with a terminal alkyne as the bioconjugation handle. Upon activation by chlorin e6 under red-light irradiation, the SDAK probe enables robust in vitro protein labeling as well as effective mapping of cellular target microenvironments with good spatial and temporal control, providing a foundation for future applications in complex biological contexts.