Photochemical Release of Hydropersulfides
Photochemical Release of Hydropersulfides
复制标题
氢过硫化物的光化学释放
DOI：
10.1021/acs.joc.2c01049
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Toscano, John P.
中科院分区：
文献类型：
--
作者：
Aggarwal, Sahil C.;Khodade, Vinayak S.;Porche, Sarah;Pharoah, Blaze M.;Toscano, John P.
氢过硫化物(RSSH)因其耐人寻味的生化性质，在氧化还原生物学领域引起了极大的兴趣。然而，由于RSSH天生不稳定，他们的研究具有挑战性，因此，它们的生理作用细节仍未明确。在此，我们报道了利用光可移除保护基团来释放RSSH的策略。用成熟的对羟基苯乙酰(PHP)光保护基团保护RSSH会导致低效的RSSH光释放以及复杂的化学作用。因此，我们研究了一种替代的前体，在pHP基团和RSSH之间插入了一个自焚连接物，在365 nm处光解后提供了几乎定量的RSSH释放。受此启发，我们还合成了一种类似的7-二乙氨基香豆素(DEACM)衍生化前驱体，DEACM是一种可见光可切割的光保护基团。这种前体在420 nm处的光解导致了RSSH的有效释放，体外实验证明RSSH在乳腺癌MCF-7细胞内传递。
Hydropersulfides (RSSH) have received significant interest in the field of redox biology because of their intriguing biochemical properties. However, because RSSH are inherently unstable, their study is challenging, and as a result, the details of their physiological roles remain ill-defined. Herein, we report strategies to release RSSH utilizing photoremovable protecting groups. RSSH protection with the well-establishedp-hydroxyphenacyl (pHP) photoprotecting group resulted in inefficient RSSH photorelease along with complex chemistry. Therefore, an alternative precursor was examined in which a self-immolative linker was inserted between thepHP group and RSSH, providing nearly quantitative RSSH release following photolysis at 365 nm. Inspired by these results, we also synthesized an analogous precursor derivatized with 7-diethylaminocoumarin (DEACM), a visible light-cleavable photoprotecting group. Photolysis of this precursor at 420 nm led to efficient RSSH release, and in vitro experiments demonstrated intracellular RSSH delivery in breast cancer MCF-7 cells.