Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine
Engineered light-sensitive molecules offer a sophisticated toolkit for the manipulation of biological systems with both spatial and temporal precision. Notably, artificial “caged” compounds can activate specific receptors solely in response to light exposure. However, the uncaging process can lead t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-01-01
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| Series: | Journal of Xenobiotics |
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| Online Access: | https://www.mdpi.com/2039-4713/15/1/8 |
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| author | Mikhail A. Panfilov Ezhena S. Starodubtseva Tatyana Yu. Karogodina Alexey Yu. Vorob’ev Alexander E. Moskalensky |
| author_facet | Mikhail A. Panfilov Ezhena S. Starodubtseva Tatyana Yu. Karogodina Alexey Yu. Vorob’ev Alexander E. Moskalensky |
| author_sort | Mikhail A. Panfilov |
| collection | DOAJ |
| description | Engineered light-sensitive molecules offer a sophisticated toolkit for the manipulation of biological systems with both spatial and temporal precision. Notably, artificial “caged” compounds can activate specific receptors solely in response to light exposure. However, the uncaging process can lead to the formation of potentially harmful byproducts. For example, the photochemical release of adrenaline (epinephrine) is accompanied by the formation of adrenochrome, which has neuro- and cardiotoxic effects. To investigate this effect in detail, we synthesized and compared two “caged” epinephrine analogs. The first was a classical compound featuring an <i>ortho</i>-nitrobenzyl protecting group attached to the amino group of epinephrine. The second analog retained the <i>ortho</i>-nitrobenzyl group but included an additional carbamate linker. The photolysis of both compounds was conducted under identical conditions, and the resulting products were analyzed using UV–Vis spectroscopy, chromatography, and NMR techniques. Surprisingly, while the classical compound led to the formation of adrenochrome, the carbamate-type caged epinephrine did not produce this byproduct, resulting in the clean release of the active substance. Subsequently, we assessed the novel compound in an in vitro platelet activation assay. The results demonstrated that the uncaging of epinephrine significantly enhances platelet activation, making it a valuable tool for advanced signaling studies. |
| first_indexed | 2025-03-14T15:01:43Z |
| format | Article |
| id | doaj.art-262a1c44c04b4640b237694a24dde170 |
| institution | Directory Open Access Journal |
| issn | 2039-4705 2039-4713 |
| language | English |
| last_indexed | 2025-03-14T15:01:43Z |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Xenobiotics |
| spelling | doaj.art-262a1c44c04b4640b237694a24dde1702025-02-25T13:34:18ZengMDPI AGJournal of Xenobiotics2039-47052039-47132025-01-01151810.3390/jox15010008Reducing the Formation of Toxic Byproducts During the Photochemical Release of EpinephrineMikhail A. Panfilov0Ezhena S. Starodubtseva1Tatyana Yu. Karogodina2Alexey Yu. Vorob’ev3Alexander E. Moskalensky4N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, RussiaDepartment of Physics, Novosibirsk State University, 630090 Novosibirsk, RussiaN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, RussiaN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, RussiaDepartment of Physics, Novosibirsk State University, 630090 Novosibirsk, RussiaEngineered light-sensitive molecules offer a sophisticated toolkit for the manipulation of biological systems with both spatial and temporal precision. Notably, artificial “caged” compounds can activate specific receptors solely in response to light exposure. However, the uncaging process can lead to the formation of potentially harmful byproducts. For example, the photochemical release of adrenaline (epinephrine) is accompanied by the formation of adrenochrome, which has neuro- and cardiotoxic effects. To investigate this effect in detail, we synthesized and compared two “caged” epinephrine analogs. The first was a classical compound featuring an <i>ortho</i>-nitrobenzyl protecting group attached to the amino group of epinephrine. The second analog retained the <i>ortho</i>-nitrobenzyl group but included an additional carbamate linker. The photolysis of both compounds was conducted under identical conditions, and the resulting products were analyzed using UV–Vis spectroscopy, chromatography, and NMR techniques. Surprisingly, while the classical compound led to the formation of adrenochrome, the carbamate-type caged epinephrine did not produce this byproduct, resulting in the clean release of the active substance. Subsequently, we assessed the novel compound in an in vitro platelet activation assay. The results demonstrated that the uncaging of epinephrine significantly enhances platelet activation, making it a valuable tool for advanced signaling studies.https://www.mdpi.com/2039-4713/15/1/8epinephrineadrenochromecaged compoundsphotopharmacologyplatelet activation |
| spellingShingle | Mikhail A. Panfilov Ezhena S. Starodubtseva Tatyana Yu. Karogodina Alexey Yu. Vorob’ev Alexander E. Moskalensky Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine Journal of Xenobiotics epinephrine adrenochrome caged compounds photopharmacology platelet activation |
| title | Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine |
| title_full | Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine |
| title_fullStr | Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine |
| title_full_unstemmed | Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine |
| title_short | Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine |
| title_sort | reducing the formation of toxic byproducts during the photochemical release of epinephrine |
| topic | epinephrine adrenochrome caged compounds photopharmacology platelet activation |
| url | https://www.mdpi.com/2039-4713/15/1/8 |
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