Remote Silyl Groups Enhance Hydrolytic Stability and Photocleavage Efficiency in Carbamates for Protein Release

Abstract Photocleavable molecules are valuable tools for biological studies, enabling spatiotemporal activation of molecular functions within cellular environments. In particular, coumarin‐based photolytic molecules are useful because of their ability to flexibly tune the wavelength of photostimulation through their structural modifications. Ideal photocleavable molecular tools require hydrolytic stability and selective susceptibility to photo stimuli. However, conventional coumarin‐based molecules have not simultaneously achieved both highly efficient photocleavage and hydrolysis resistance. 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.