Roy Biswajit, Kojima Ryota, Shah Obaed, Shieh Meg, Das Eshani, Ezzatpour Shahrzad, Sato Emiko, Hirata Yusuke, Lindahl Stephen, Matsuzawa Atsushi, Aguilar Hector C, Xian Ming
Department of Chemistry, Brown University, Providence, RI, 02912, USA.
Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
Redox Biol. 2025 Feb;79:103475. doi: 10.1016/j.redox.2024.103475. Epub 2024 Dec 18.
Thiyl radicals are important reactive sulfur species and can cause cis to trans isomerization on unsaturated fatty acids. However, biocompatible strategies for the controlled generation of thiyl radicals are still lacking. In this work, we report the study of a series of naphthacyl-derived thioethers as photo-triggered thiyl radical precursors. Tertiary naphthacyl thioether was identified to be a suitable template that could be used to produce both aryl and alkyl thiyl radicals under ultraviolet (UV) light or sunlight. The effective cis-to trans-isomerization of unsaturated fatty acid models (methyl oleate, methyl linoleate) and a natural phospholipid (cardiolipin) using these photo-triggered substrates was demonstrated. This reaction was also proved to proceed effectively in cells to produce thiyl radicals and subsequent fatty acid isomerization. Additionally, the most promising thiyl radical precursor showed antiviral activity in a pseudotyped virus model, likely due to disrupting viral lipid membranes upon UV activation. These findings highlight the potential of thiyl radicals for both biochemical and antiviral applications.
硫自由基是重要的活性硫物种，可导致不饱和脂肪酸发生顺反异构化。然而，目前仍缺乏用于可控生成硫自由基的生物相容性策略。在这项工作中，我们报道了一系列萘酰基衍生的硫醚作为光触发硫自由基前体的研究。叔萘酰基硫醚被确定为一种合适的模板，可用于在紫外光（UV）或阳光下产生芳基和烷基硫自由基。使用这些光触发底物对不饱和脂肪酸模型（油酸甲酯、亚油酸甲酯）和天然磷脂（心磷脂）进行了有效的顺反异构化。该反应也被证明在细胞中能有效进行，以产生硫自由基并随后导致脂肪酸异构化。此外，最有前景的硫自由基前体在假型病毒模型中显示出抗病毒活性，这可能是由于在紫外线激活后破坏了病毒脂质膜。这些发现突出了硫自由基在生化和抗病毒应用方面的潜力。
