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
More Like this
-
more » « less
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. -
more » « less
Abstract This article is a highlight of the paper by Isor et al. in this issue of
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
-
more » « less
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. -
more » « less
ABSTRACT Triplet arylnitrenes may provide direct access to aryl azo‐dimers, which have broad commercial applicability. Herein, the photolysis of
p ‐azidostilbene (1 ) in argon‐saturated methanol yielded stilbene azo‐dimer (2 ) through the dimerization of tripletp ‐nitrenostilbene (31N ). The formation of31N was verified by electron paramagnetic resonance spectroscopy and absorption spectroscopy (λ max ~ 375 nm) in cryogenic 2‐methyltetrahydrofuran matrices. At ambient temperature, laser flash photolysis of1 in methanol formed31N (λ max ~ 370 nm, 2.85 × 107 s−1). On shorter timescales, a transient absorption (λ max ~ 390 nm) that decayed with a similar rate constant (3.11 × 107 s−1) was assigned to a triplet excited state (T) of1 . Density functional theory calculations yielded three configurations for T of1 , with the unpaired electrons on the azido (TA) or stilbene moiety (TTw, twisted and TFl, flat). The transient was assigned to TTwbased on its calculated spectrum. CASPT2 calculations gave a singlet–triplet energy gap of 16.6 kcal mol−1for1 N ; thus, intersystem crossing of11N to31N is unlikely at ambient temperature, supporting the formation of31N from T of1 . Thus, sustainable synthetic methods for aryl azo‐dimers can be developed using the visible‐light irradiation of aryl azides to form triplet arylnitrenes.
