Effect of Remote Silyl Groups on the Hydrolytic Stability and Rapid Photocleavage of Carbamates

Photocleavable molecules are widely used in fields such as materials science and chemical biology. In particular, coumarin-based photocleavable molecules are indispensable for photomanipulation techniques in chemical biology because of their ability to flexibly adjust the wavelength of photostimulation through straightforward structural modifications. However, traditional coumarin-based molecules have several limitations, including hydrolysis in aqueous environments and susceptibility to intracellular carboxylesterases. Additionally, substituting bonds in these molecules to enhance hydrolytic stability often decreases their photolysis efficiency. Herein, we proposed a novel molecular design concept that introduces a silyl group into coumarin-based molecules at a position remote from the photolabile bond, creating an ideal photocleavable molecule for chemical biology tools. The established orbital effect of the remotely introduced silyl group improves the photolysis efficiency of coumarin-based molecules, while its bulkiness substantially enhances their hydrolytic stability in aqueous environments and under enzymatic conditions. Furthermore, this improvement in molecular functionality contributes to the development of high-performance protein-release biomaterials.