Boron Dipyrromethene As a Fluorescent Caging Group for Single-Photon Uncaging with Long-Wavelength Visible Light

Abstract

Caged compounds are useful tools for precise spatiotemporal modulation of cell functions, but in most cases uncaging requires ultraviolet (UV) light, which is cytotoxic and has limited tissue penetration. Therefore, caged compounds that can be activated by longer-wavelength light are required. Here we describe a novel photoelimination reaction of 4-aryloxy boron dipyrromethene (BODIPY) derivatives and show that BODIPY can function as a caging group for phenol groups. We developed a novel BODIPY-caged histamine compound, which is photoactivatable with blue-green visible light to stimulate cultured HeLa cells in a spatiotemporally well-controlled manner. This caging strategy is expected to be widely applicable to develop tools for probing various cellular functions.

Boron chemistry in a new light

“…The group of Urano from the University of Tokyo was the first to discover by serendipity that, in some cases, 4-aryloxy BODIPY derivatives could release their tethered phenol moiety upon blue-green light irradiation. 60 The biological potential of employing BODIPY as a caging group for phenol was exemplified by the photo-release of a relevant biogenic molecule in a two-step tandem process. As outlined in Scheme 27, BODIPY-caged histamine compound was shown to undergo first the photo-cleavage of its phenol part that further decomposed to generate the free biological amine alongside CO 2 and quinone methide.…”

Calcium Uncaging with Visible Light

“…Subsequently several chromophores have been used for uncaging of biological signaling molecules with blue light 16–21 . Photochemical protecting groups sensitive to green light have also been reported 22–24 , but to our knowledge no biological studies have appeared with these probes. Some of these probes are very important additions to the arsenal of caged compounds available for use by biologists, however none of them offer the same generality of carbon-heteroatom bond scission that is part of ortho -nitrobenzyl photochemistry.…”

A New Photocage Derived from Fluorene

“…were the first to report a new photocage based on visible‐light‐absorbing fluorophores . Since then, promising new PPGs have been developed based on the boron‐dipyrromethene (BODIPY) fluorophore . However, so far, BODIPY photocages are limited to the direct release of a good leaving group (LG).…”