Theoretical Design and Synthesis of Caged Compounds Using X-Ray-Triggered Azo Bond Cleavage

Caged compounds are frequently used in life science research. However, the light used to activate them is commonly absorbed and scattered by biological materials, limiting their use to basic research in cells or small animals. In contrast, hard X-rays exhibit high bio-permeability due to the difficulty of interacting with biological molecules. With the main goal of developing X-ray activatable caged compounds, azo compounds are designed and synthesized with a positive charge and long pi-conjugated system to increase the reaction efficiency with hydrated electrons. The azo bonds in the designed compounds are selectively cleaved by X-ray, and the fluorescent substance Diethyl Rhodamine is released. Based on the results of experiments and quantum chemical calculations, azo bond cleavage is assumed to occur via a two-step process: a two-electron reduction of the azo bond followed by NN bond cleavage. Cellular experiments also demonstrate that the azo bonds can be cleaved intracellularly. Thus, caged compounds that can be activated by an azo bond cleavage reaction promoted by X-ray are successfully generated. Hydrated electrons are highly reactive species produced by X-ray irradiation. By suitably designing azo compounds, azo bonds can be efficiently cleaved by the hydration electrons generated upon X-ray irradiation. This cleavage reaction is thought to progress in two steps: an NN bond cleavage following a two-electron reduction. Furthermore, X-ray-induced azo bond cleavage reactions can also efficiently occur in cells.image