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The reactivity profile of atomic oxygen [O( 3 P)] in the condensed phase has shown a preference for the thiol group of cysteines. In this work, water-soluble O( 3 P)-precursors were synthesized by adding aromatic burdens and water-soluble sulphonic acid groups to the core structure of dibenzothiophene- S -oxide (DBTO) to study O( 3 P) reactivity in cell lysates and live cells. The photodeoxygenation of these compounds was investigated using common intermediates, which revealed that an increase in aromatic burdens to the DBTO core structure decreases the total oxidation yield due to competitive photodeoxygenation mechanisms. These derivatives were then tested in cell lysates and live cells to profile changes in cysteine reactivity using the isoTOP-ABPP chemoproteomics platform. The results from this analysis indicated that O( 3 P) significantly affects cysteine reactivity in the cell. Additionally, O( 3 P) was found to oxidize cysteines within peptide sequences with leucine and serine conserved at the sites surrounding the oxidized cysteine. O( 3 P) was also found to least likely oxidize cysteines among membrane proteins. 

A beneficial property of photogenerated reactive oxygen species (ROS) is the capability of oxidant generation within a specific location or organelle inside a cell. Dibenzothiophene S -oxide ( DBTO ), which is known to undergo a photodeoxygenation reaction to generate ground state atomic oxygen [O( 3 P)] upon irradiation, was functionalized to afford localization within the plasma membrane of cells. The photochemistry, as it relates to oxidant generation, was studied and demonstrated that the functionalized DBTO derivatives generated O( 3 P). Irradiation of these lipophilic O( 3 P)-precursors in the presence of LDL and within RAW 264.7 cells afforded several oxidized lipid products (oxLP) in the form of aldehydes. The generation of a 2-hexadecenal ( 2-HDEA ) was markedly increased in irradiations where O( 3 P) was putatively produced. The substantial generation of 2-HDEA is not known to accompany the production of other ROS. These cellular irradiation experiments demonstrate the potential of inducing oxidation with O( 3 P) in cells. 

Ground-state atomic oxygen [O( 3 P)] is an oxidant whose formation in solution was proposed but never proven. Polymer nanocapsules were used to physically separate dibenzothiophene S-oxide (DBTO), a source of O( 3 P), from an O( 3 P)-accepting molecule. Irradiation of polymer nanocapsules loaded with DBTO resulted in oxidation of the O( 3 P)-acceptor placed outside nanocapsules. The results rule out a direct oxygen atom transfer mechanism and are consistent with freely diffusing O( 3 P) as the oxidant. 

Abstract Sulfoximines are popular scaffolds in drug discovery due to their hydrogen bonding properties and chemical stability. In recent years, the role of reactive intermediates such as nitrenes has been studied in the synthesis and degradation of sulfoximines. In this work, the photochemistry ofN‐phenyl dibenzothiophene sulfoximine [5‐(phenylimino)‐5H‐5λ⁴‐dibenzo[b,d]thiopheneS‐oxide] was analyzed. The structure resembles a combination ofN‐phenyl iminodibenzothiophene and dibenzothiopheneS‐oxide, which generate nitrene and O(³P) upon UV‐A irradiation, respectively. The photochemistry ofN‐phenyl dibenzothiophene sulfoximine was explored by monitoring the formation of azobenzene, a photoproduct of triplet nitrene, using direct irradiation and sensitized experiments. The reactivity profile was further studied through direct irradiation experiments in the presence of diethylamine (DEA) as a nucleophile. The studies demonstrated thatN‐phenyl dibenzothiophene sulfoximine underwent S–N photocleavage to release singlet phenyl nitrene which formed a mixture of azepines in the presence of DEA and generated moderate amounts of azobenzene in the absence of DEA to indicate formation of triplet phenyl nitrene.