Photoswitching Azo Compounds in Vivo with Red Light

The photoisomerization of azobenzenes provides a general means for the photocontrol of molecular structure and function. For applications in vivo, however, the wavelength of irradiation required for trans-to-cis isomerization of azobenzenes is critical since UV and most visible wavelengths are strongly scattered by cells and tissues. We report here that azobenzene compounds in which all four positions ortho to the azo group are substituted with bulky electron-rich substituents can be effectively isomerized with red light (630–660 nm), a wavelength range that is orders of magnitude more penetrating through tissue than other parts of the visible spectrum. When the ortho substituent is chloro, the compounds also exhibit stability to reduction by glutathione, enabling their use in intracellular environments in vivo.

偶氮苯（azobenzene）的光异构化是实现分子结构与功能光控的通用策略。然而，针对体内（in vivo）应用，偶氮苯反式-顺式异构化所需的照射波长至关重要，因为紫外线及多数可见光波段会被细胞和组织强烈散射。本文报道，偶氮苯类化合物中，若偶氮基团的全部四个邻位均被大位阻富电子取代基修饰，则可通过红光（630–660 nm）实现高效异构化；该波段相较于可见光光谱其余区域，穿透组织的能力高出数个数量级。当邻位取代基为氯原子时，这类化合物还具备抗谷胱甘肽还原的稳定性，可应用于体内细胞内环境。