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Biradical vs singlet oxygen photogeneration in suprofen – cholesterol systems

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ABSTRACT

123124531221131231213123: Cholesterol (Ch) is an important lipidic building block and a target for oxidative degradation, which can be induced via free radicals or singlet oxygen (1O2). Suprofen (SP) is a nonsteroidal anti-inflammatory drug that contains the 2-benzoylthiophene (BZT) chromophore and has a π,π* lowest triplet excited state. In the present work, dyads (S)- and (R)-SP-α-Ch ( and ), as well as (S)-SP-β-Ch () have been prepared from β- or α-Ch and SP to investigate the possible competition between photogeneration of biradicals and 1O2, the key mechanistic steps in Ch photooxidation. Steady-state irradiation of and was performed in dichloromethane, under nitrogen, through Pyrex, using a 400 W medium pressure mercury lamp. The spectral analysis of the separated fractions revealed formation of two photoproducts and , respectively. By contrast, under the same conditions, did not give rise to any isolable Ch-derived product. These results point to an intramolecular hydrogen abstraction in and from the C7 position of Ch and subsequent C–C coupling of the generated biradicals. Interestingly, was significantly more photoreactive than indicating a clear stereodifferentiation in the photochemical behavior. Transient absorption spectra obtained for – were very similar and matched that described for the SP triplet excited state (typical bands with maxima at ca. 350 nm and 600 nm). Direct kinetic analysis of the decay traces at 620 nm led to determination of triplet lifetimes that were ca. 4.1 μs for and and 5.8 μs for . From these data, the intramolecular quenching rate constants in and were determined as 0.78 × 105 s−1. The capability of dyads – to photosensitize the production of singlet oxygen was assessed by time-resolved near infrared emission studies in dichloromethane using perinaphthenone as standard. The quantum yields (ΦΔ) were 0.52 for and and 0.56 for . In conclusion, SP-α-Ch dyads are unique in the sense that they can be used to photogenerate both biradicals and singlet oxygen, thus being able to initiate Ch oxidation from their triplet excited states following either of the two competing mechanistic pathways.

No MeSH data available.


Diagnostic NOE interactions in compounds 4 and 5.
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Figure 4: Diagnostic NOE interactions in compounds 4 and 5.

Mentions: The structures of compounds 4 and 5 were unambiguously assigned on the basis of their NMR spectroscopic data (1H, 13C, HSQC and NOEDIFF) and mass spectrometry analysis, including high-resolution measurements. Because of the rigidity of the steroidal skeleton, NOE experiments were necessary to assign the stereochemistry of the new chiral centers generated upon photocyclization. In both photoproducts, the most relevant interaction was found between the allylic proton at C7 and the protons of the thiophene ring (Fig. 4). More details are provided in the Supporting Information File 1.


Biradical vs singlet oxygen photogeneration in suprofen – cholesterol systems
Diagnostic NOE interactions in compounds 4 and 5.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4979683&req=5

Figure 4: Diagnostic NOE interactions in compounds 4 and 5.
Mentions: The structures of compounds 4 and 5 were unambiguously assigned on the basis of their NMR spectroscopic data (1H, 13C, HSQC and NOEDIFF) and mass spectrometry analysis, including high-resolution measurements. Because of the rigidity of the steroidal skeleton, NOE experiments were necessary to assign the stereochemistry of the new chiral centers generated upon photocyclization. In both photoproducts, the most relevant interaction was found between the allylic proton at C7 and the protons of the thiophene ring (Fig. 4). More details are provided in the Supporting Information File 1.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

123124531221131231213123: Cholesterol (Ch) is an important lipidic building block and a target for oxidative degradation, which can be induced via free radicals or singlet oxygen (1O2). Suprofen (SP) is a nonsteroidal anti-inflammatory drug that contains the 2-benzoylthiophene (BZT) chromophore and has a π,π* lowest triplet excited state. In the present work, dyads (S)- and (R)-SP-α-Ch ( and ), as well as (S)-SP-β-Ch () have been prepared from β- or α-Ch and SP to investigate the possible competition between photogeneration of biradicals and 1O2, the key mechanistic steps in Ch photooxidation. Steady-state irradiation of and was performed in dichloromethane, under nitrogen, through Pyrex, using a 400 W medium pressure mercury lamp. The spectral analysis of the separated fractions revealed formation of two photoproducts and , respectively. By contrast, under the same conditions, did not give rise to any isolable Ch-derived product. These results point to an intramolecular hydrogen abstraction in and from the C7 position of Ch and subsequent C–C coupling of the generated biradicals. Interestingly, was significantly more photoreactive than indicating a clear stereodifferentiation in the photochemical behavior. Transient absorption spectra obtained for – were very similar and matched that described for the SP triplet excited state (typical bands with maxima at ca. 350 nm and 600 nm). Direct kinetic analysis of the decay traces at 620 nm led to determination of triplet lifetimes that were ca. 4.1 μs for and and 5.8 μs for . From these data, the intramolecular quenching rate constants in and were determined as 0.78 × 105 s−1. The capability of dyads – to photosensitize the production of singlet oxygen was assessed by time-resolved near infrared emission studies in dichloromethane using perinaphthenone as standard. The quantum yields (ΦΔ) were 0.52 for and and 0.56 for . In conclusion, SP-α-Ch dyads are unique in the sense that they can be used to photogenerate both biradicals and singlet oxygen, thus being able to initiate Ch oxidation from their triplet excited states following either of the two competing mechanistic pathways.

No MeSH data available.