Effects of photodeoxygenation on cell biology using dibenzothiophene S-oxide derivatives as O(3P)-precursors

Abstract

Photodeoxygenation of dibenzothiophene S-oxide and its derivatives have been used to generate atomic oxygen [O( 3 P)] to examine its effect on proteins, nucleic acids, and lipids. The unique reactivity and selectivity of O( 3 P) have shown distinct oxidation products and outcomes in biomolecules and cell-based studies. To understand the scope of its global impact on the cell, we treated MDA-MB-231 cells with 2,8-diacetoxymethyldibenzothiophene S-oxide and UV-A light to produce O( 3 P) without targeting a specific cell organelle. Cellular responses to O( 3 P)-release were analyzed using cell viability and cell cycle phase determination assays. Cell death was observed when cells were treated with higher concentrations of sulfoxides and UV-A light. However, significant differences in cell cycle phases due to UV-A irradiation of the sulfoxide were not observed. We further performed RNA-Seq analysis to study the underlying biological processes at play, and while UVirradiation itself influenced gene expression, there were 9 upregulated and 8 downregulated genes that could be attributed to photodeoxygenation.

Production of O Radicals from Cavitation Bubbles under Ultrasound

“…The reactivity of O radicals (oxygen atoms) in solution remains underexplored [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. One of the reasons is the lack of a clean and mild method for the generation of O radicals in solution [ 1 , 2 , 3 , 4 , 9 ]. The generation of O radicals in solutions is commonly by UV irradiation of dibenzothiophene S-oxide (DBTO) [ 2 , 9 , 13 ].…”

“…The reactivity of O radicals (oxygen atoms) in solution remains underexplored [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. One of the reasons is the lack of a clean and mild method for the generation of O radicals in solution [1][2][3][4]9]. The generation of O radicals in solutions is commonly by UV irradiation of dibenzothiophene S-oxide (DBTO) [2,9,13].…”

Pyridazine N-Oxides as Photoactivatable Surrogates for Reactive Oxygen Species

“…9,10 This photochemistry has been used to interrogate the reactivity of O( 3 P) with small organic molecules 9,11 and biomolecules in solution. 12,13 Nevertheless, the utility of 1 as a O( 3 P) surrogate is hampered by a requirement for shortwavelength light (∼300 nm) to promote deoxygenation and the poor solubility profile of 1 in aqueous media. Efforts to address these limitations have relied exclusively on tailored variants of 1 designed to be compatible with lower-energy light and/or more soluble in water (e.g., 2−4).…”

“…Efforts to address these limitations have relied exclusively on tailored variants of 1 designed to be compatible with lower-energy light and/or more soluble in water (e.g., 2−4). 13,14 In this Communication, we describe the photodeoxygenation of 3,6dichloropyridazine N-oxide (DPNO, 5a), a commercially available heterocycle that can scaffold a new class of O( 3 P) precursors with improved properties.…”

“… Similarly, singlet oxygen ( 1 O 2 ) and superoxide (O 2 •‑ ) serve as redox equivalents in vivo . , Compared to these well-studied oxidants, the chemistry of atomic oxygen [O­( 3 P)] remains underexplored, because there are few practical ways to generate this reactive species . Certain heterocyclic N -oxides release O­( 3 P) under photochemical conditions, albeit in low yield. − In contrast, the photoinduced deoxygenation of dibenzothiophene S -oxide (DBTO, 1 ) produces O­( 3 P) via cleavage of the S–O bond. , This photochemistry has been used to interrogate the reactivity of O­( 3 P) with small organic molecules , and biomolecules in solution. , Nevertheless, the utility of 1 as a O­( 3 P) surrogate is hampered by a requirement for short-wavelength light (∼300 nm) to promote deoxygenation and the poor solubility profile of 1 in aqueous media. Efforts to address these limitations have relied exclusively on tailored variants of 1 designed to be compatible with lower-energy light and/or more soluble in water (e.g., 2 – 4 ). , In this Communication, we describe the photodeoxygenation of 3,6-dichloropyridazine N -oxide (DPNO, 5a ), a commercially available heterocycle that can scaffold a new class of O­( 3 P) precursors with improved properties.…”