Transformation of COUPY Fluorophores into a Novel Class of Visible-Light-Cleavable Photolabile Protecting Groups

Abstract

Although photolabile protecting groups (PPGs) have found widespread applications in several fields of chemistry, biology and materials science, there is a growing interest in expanding the photochemical toolbox to overcome some of the limitations of classical caging groups. In this work, the synthesis of a new class of visible-light-sensitive PPGs based on low-molecular weight COUPY fluorophores with several attractive properties, including long-wavelength absorption, is reported. Besides being stable to spontaneous hydrolysis in the dark, COUPY-based PPGs can be efficiently photoactivated with yellow (560 nm) and red light (620 nm) under physiological-like conditions, thereby offering the possibility of unmasking functional groups from COUPY photocages under irradiation conditions in which other PPGs remain stable. Additionally, COUPY photocages exhibit excellent cellular uptake and accumulate selectively in mitochondria, opening the door to the delivery of caged analogues of biologically active compounds into these organelles.