Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council (CNR), via P. Gobetti 101, 40129, Bologna, Italy.
Department of Pharmacognosy, Semmelweis University, Üllői út 26., 1085, Budapest, Hungary.
Chemistry. 2023 May 22;29(29):e202300511. doi: 10.1002/chem.202300511. Epub 2023 Mar 31.
In the quest for new therapies targeting hypoxia, aromatic endoperoxides have intriguing potential as oxygen releasing agents (ORAs) able to free O in tissues upon suitable trigger. Four aromatic substrates were synthesized and the formation of their corresponding endoperoxides was optimized in organic solvent upon selective irradiation of Methylene Blue, a low-cost photocatalyst, producing the reactive singlet oxygen species. Complexation of the hydrophobic substrates within a hydrophilic cyclodextrin (CyD) polymer allowed their photooxygenation in homogeneous aqueous environment using the same optimized protocol upon dissolution in water of the three readily accessible reagents. Notably, reaction rates were comparable in buffered D O and organic solvent and, for the first time, the photooxygenation of highly hydrophobic substrates was achieved for millimolar solutions in non-deuterated water. Quantitative conversion of the substrates, straightforward isolation of the endoperoxides and recovery of the polymeric matrix were achieved. Cycloreversion of one ORA to the original aromatic substrate was observed upon thermolysis. These results hold great potential for the launch of CyD polymers both as reaction vessels for green, homogeneous photocatalysis and as carrier for the delivery of ORAs in tissues.
在寻找针对缺氧的新疗法的过程中，芳香内过氧化物作为能够在适当的触发下释放组织中氧气的氧释放剂（ORAs）具有有趣的潜力。合成了四种芳香底物，并在有机溶剂中优化了它们相应的内过氧化物的形成，通过选择性辐照亚甲蓝（一种低成本的光催化剂）产生活性单线态氧。将疏水性底物络合在亲水性环糊精（CyD）聚合物内，允许它们在均相水环境中进行光氧化，使用相同的优化方案，将三种易于获得的试剂溶解在水中。值得注意的是，在缓冲的 D2O 和有机溶剂中的反应速率相当，并且首次实现了高疏水性底物在非氘化水中毫摩尔溶液中的光氧化。通过定量转化底物、直接分离内过氧化物并回收聚合物基质，实现了目标产物。在热解过程中观察到一个 ORA 到原始芳香底物的环回转化。这些结果为 CyD 聚合物作为绿色均相光催化的反应容器和在组织中输送 ORAs 的载体的应用提供了巨大的潜力。
