This article is a highlight of the paper by Isor et al. in this issue of
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 of
- Award ID(s):
- 1900417
- NSF-PAR ID:
- 10367790
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Photochemistry and Photobiology
- Volume:
- 97
- Issue:
- 6
- ISSN:
- 0031-8655
- Page Range / eLocation ID:
- p. 1322-1334
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Photochemistry and Photobiology . It describes the photolysis of a dibenzothiophene sulfoximine (bearingN ‐phenyl imino andS ‐oxide groups) to produce two reactive intermediates in tandem. The sulfoximine undergoes a S–N and S–O photocleavage to release phenyl nitrene and atomic oxygen [O(3P)]. The phenyl nitrene dimerizes to azobenzene or is trapped by diethylamine to reach an azepine. From there, atomic oxygen arises in a secondary photolysis of dibenzothiophene sulfoxide. A computational analysis also reveals that the S–N bond is labile for initial nitrene release, with the secondary release of atomic oxygen by S–O cleavage. Whether future sulfoximine scaffolds can produce the reverse order release of O(3P) then nitrene, or release both simultaneously, is yet to be established. Nonetheless, molecules with dual‐intermediate release, such as coupled photoaffinity labeling and cellular oxidation, are worth pursuing. -
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.more » « less
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Abstract Although alkyl azides are known to typically form imines under direct irradiation, the product formation mechanism remains ambiguous as some alkyl azides also yield the corresponding triplet alkylnitrenes at cryogenic temperatures. The photoreactivity of 3‐azido‐3‐phenyl‐3
H ‐isobenzofuran‐1‐one (1) was investigated in solution and in cryogenic matrices. Irradiation (λ = 254 nm) of azide 1 in acetonitrile yielded a mixture of imines 2 and 3. Monitoring of the reaction progress using UV‐Vis absorption spectroscopy revealed an isosbestic point at 210 nm, indicating that the reaction proceeded cleanly. Similar results were observed for the photoreactivity of azide 1 in a frozen 2‐methyltetrahydrofuran (mTHF) matrix. Irradiation of azide 1 in an argon matrix at 6 K resulted in the disappearance of its IR bands with the concurrent appearance of IR bands corresponding to imines 2 and 3. Thus, it was theorized that azide 1 forms imines 2 and 3 via a concerted mechanism from its singlet excited state or through singlet alkylnitrene11N, which does not intersystem cross to its triplet configuration. This proposal was supported by CASPT2 calculations on a model system, which suggested that the energy gap between the singlet and triplet configurations of alkylnitrene 1N is 33 kcal/mol, thus making intersystem crossing inefficient. -
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ABSTRACT Triplet arylnitrenes may provide direct access to aryl azo‐dimers, which have broad commercial applicability. Herein, the photolysis of
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Abstract Photodeoxygenation of dibenzothiophene
S ‐oxide (DBTO) is believed to produce ground‐state atomic oxygen [O(3P)] in solution. Compared with other reactive oxygen species (ROS), O(3P) is a unique oxidant as it is potent and selective. Derivatives of DBTO have been used as O(3P)‐precursors to oxidize variety of molecules, including plasmid DNA, proteins, lipids, thiols, and other small organic molecules. Unfortunately, the photodeoxygenation of DBTO requires ultraviolet irradiation, which is not an ideal wavelength range for biological systems, and has a low quantum yield of approximately 0.003. In this work, benzo[b ]naphtho[1,2‐d ]selenopheneSe ‐oxide, benzo[b ]naphtho[2,1‐d ]selenopheneSe ‐oxide, dinaphtho[2,3‐b :2’,3’‐d ]selenopheneSe ‐oxide, and perylo[1,12‐b,c,d ]selenopheneSe ‐oxide were synthesized, and their ability to utilize visible light for generating O(3P) was interrogated. Benzo[b ]naphtho[1,2‐d ]selenopheneSe ‐oxide produces O(3P) upon irradiation centered at 420 nm. Additionally, benzo[b ]naphtho[1,2‐d ]selenopheneSe ‐oxide, benzo[b ]naphtho[2,1‐d ]selenopheneSe ‐oxide, and dinaphtho[2,3‐b :2’,3’‐d ]selenopheneSe ‐oxide produce O(3P) when irradiated with UVA light and have quantum yields of photodeoxygenation ranging from 0.009 to 0.33. This work increases the utility of photodeoxygenation by extending the range of wavelengths that can be used to generate O(3P) in solution.
