Radical Caging Strategy for Cholinergic Optopharmacology

Abstract

Photo-caged methodologies have been indispensable for elucidating the functional mechanisms of pharmacologically active molecules at the cellular level. A photo-triggered removable unit enables control of the photo-induced expression of pharmacologically active molecular function, resulting in a rapid increase in the concentration of the bioactive compound near the target cell. However, caging the target bioactive compound generally requires specific heteroatom-based functional groups, limiting the types of molecular structures that can be caged. We have developed an unprecedented methodology for caging/uncaging on carbon atoms using a unit with a photo-cleavable carbon−boron bond. The caging/uncaging process requires installation of the CH 2 −B group on the nitrogen atom that formally assembles an N-methyl group protected with a photoremovable unit. N-Methylation proceeds by photoirradiation via carbon-centered radical generation. Using this radical caging strategy to cage previously uncageable bioactive molecules, we have photocaged molecules with no general labeling sites, including acetylcholine, an endogenous neurotransmitter. Caged acetylcholine provides an unconventional tool for optopharmacology to clarify neuronal mechanisms on the basis of photo-regulating acetylcholine localization. We demonstrated the utility of this probe by monitoring uncaging in HEK cells expressing a biosensor to detect ACh on the cell surface, as well as Ca 2+ imaging in Drosophila brain cells (ex vivo).

Boron-Methylated Dipyrromethene as a Green Light Activated Type I Photoinitiator for Rapid Radical Polymerizations

“…Inspired by UV-light induced β-scission observed in N -heterocyclic carbene boranes, − blue-light (440 nm) induced β-scission of boracenes, and recent utility of electron-rich boryl radicals as nucleophiles in synthetic chemistry − it was hypothesized that boron-functionalized variants of BODIPY fluorophores could provide a novel Type I photoinitiator platform for rapid and efficient free radical polymerization. Moreover, it was recently shown that boron-ethylated BODIPY could be used as a turn-on fluorescent sensor upon irradiation with a high intensity blue laser (488 nm, ≥28 W/cm 2 ), resulting in substitution of the ethyl functionality, although the mechanism was not reported .…”