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Abstract N‐phenyl dibenzothiophene sulfoximine has been demonstrated to produce phenyl nitrene and dibenzothiopheneS‐oxide upon irradiation with UV‐A light, and dibenzothiopheneS‐oxide upon further irradiation releases triplet atomic oxygen. Thus,N‐phenyl dibenzothiophene sulfoximine exhibits a rare dual‐release capability in its photochemistry. In this work,N‐substituted dibenzothiophene sulfoximine derivatives are irradiated with UV‐A light to compare their photochemistry and quantum yield of dibenzothiopheneS‐oxide production with that ofN‐phenyl dibenzothiophene sulfoximine. BothN‐aryl andN‐alkyl derivatives of dibenzothiophene sulfoximine are examined to observe their effects on the quantum yield of the photolysis reaction. Adding electron withdrawingN‐aryl substituents is shown to increase the quantum yield of dibenzothiopheneS‐oxide production, while adding electron donatingN‐aryl substituents is shown to decrease the quantum yield. The quantum yield was slightly lowered or not increased by mostN‐alkyl substituents. Furthermore, the quantum yield was not augmented by branching and steric hindrance effects associated with theN‐alkyl substituents. These results suggest that electronic modulation of the sulfoximine bonds affects the observed photolysis reaction. 

Abstract Lipid oxidation by reactive oxygen species (ROS) provide several different oxidation products that have been implicated in inflammatory responses. Ground state atomic oxygen [O(³P)] is produced by the photodeoxygenation of certain heterocyclic oxides and has a reactivity that is unique from other ROS. Due to the reactive nature of O(³P), the site of O(³P)‐generation is expected to influence the products in heterogenous solutions or environments. In this work, the oxidation of low‐density lipoprotein (LDL) by lipids with covalently bound O(³P)‐photoprecursors was compared to more hydrophilic O(³P)‐photoprecursors. Lipid oxidation products were quantified after Bligh‐Dyer extraction and pentafluorobenzyl bromide (PFB) derivatization by GC–MS. Unlike the more hydrophilic O(³P)‐photoprecursors, the oxidation of LDL during the irradiation of lipid‐(O³P)‐photoprecursor conjugates showed little quenching by the addition of the O(³P)‐scavenging sodium allyl sulfonate. This indicated that lipophilic O(³P)‐photoprecursors are expected to generate lipid oxidation products where other more hydrophilic O(³P)‐photoprecursors could be quenched by other reactive groups present in solution or the environment. 

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.