Mechanistic studies have shown that these reactions do not proceed through stepwise oxidation and nucleophilic addition (Scheme 5B), indicating that the formed reactive species are electrophilic. There was a demand for nucleophiles that can efficiently capture these active species, as such nucleophiles enable various tagging applications. According to a few studies comparing different nucleophiles, 3-ethynylaniline demonstrated higher reactivity compared to other anilines, amines, and phenylhydrazines. Additionally, 1-methyl-4-arylurazole (MAUra), with a pKa of 4.7, 76 predominantly exists in its anionic (N -) form at neutral pH, enhancing its nucleophilicity and thereby facilitating the efficient capture of oxidized histidine. This strategy for protein modification, known as proximity labeling (PL), exploits the proximity-dependent nature of photocatalysis and the brief lifespan of 1 O2. By generating 1 O2 and capturing oxidative intermediates nucleophilically (Scheme 5C), it facilitates a wide range of applications. These include identifying RNA-binding proteins, site-selective modification of antibodies, controlling reactivity within cells for subcellular proteomic mapping, analyzing histidine on aggregated proteins after catalytic photo-oxygenation, examining metalbinding histidines, controlling surface reactions for cell-cell interaction studies, and interactome analyses in live mouse brains. While this review primarily focuses on protein bioconjugation, it is notable that the concept of using photocatalysts to generate reactive oxygen species, thereby oxidizing and degrading proteins, has been well-established in techniques such as chromophore/fluorophore-assisted laser inactivation (CALI/FALI). Scheme 5. Protein modification utilizing 1 O2 generation from a photocatalyst. (A) Generation of 1 O2 through energy transfer reactions between an excited photosensitizer and oxygen molecules. (B) A technique involving the capture of electrophilic intermediates produced by Diels-Alder reactions between His residues and 1 O2 using nucleophiles. (C) The structure and reactivity of the nucleophiles used in this method.