Bis-Acetyl Carbazole: A Photoremovable Protecting Group for Sequential Release of Two Different Functional Groups and Its Application in Therapeutic Release

In this paper, we present fluorescent photoremovable protecting groups (FPRPG) based on bis-acetyl carbazole for the release of two different functional groups such as carboxylic acids, alcohols, thiols, and amines in a sequential fashion. Dual-arm caged bis-acetyl carbazoles with different combinations of two unlike functional groups were synthesized. Photophysical studies showed that caged bis-acetyl carbazoles are blue fluorescent and their emission properties are sensitive to the environment. Sequential photorelease of two different functional groups by bis-acetyl carbazole was analyzed by HPLC, UV and emission spectroscopy. The mechanism of the dual release by bis-acetyl carbazole was investigated and supported by TD-DFT calculations. To demonstrate the applicability of the dual release ability of bis-acetyl carbazole FPRPG, we synthesized a drug delivery system (DDS) in which one arm of bis-acetyl carbazole is linked to the carboxylic functional group of chlorambucil (CBL) and the other arm is attached to the hydroxyl group of ferulic acid ethyl ester (FAEE). In vitro studies showed that our DDS presents excellent properties such as photoregulated dual drug delivery, cellular uptake, and biocompatibility.