Controlled Irradiation of Blue and Green Light Excitable Caged Glutamate

Nishal M. Egodawaththa,^† Jingxuan Ma,^† Charitha Guruge, Oriana A. V. Marquez, Molly Likes, and Nasri Nesnas*

Department of Biomedical and Chemical Engineering and Sciences
Florida Institute of Technology, 150 West University Blvd., Melbourne, FL 32901, United States

†These authors contributed equally to this work
*Corresponding author. E-mail address: nesnas@fit.edu

Glutamate (Glu) is an excitatory neurotransmitter that plays a vital role in memory.  Brain mapping activities of such pathways depends on the ability to release Glu with spatiotemporal precision.  Several photo-protecting groups (PPGs), referred to as photocages or cages, were designed to release Glu upon irradiation.  Previously reported Glu cages responded to UV upon irradiation with single photons, which restricted their use in vivo experiments due to cytotoxicity.  Other cage designs have lower quantum efficiency (QE) of release requiring higher concentrations and/or longer photoirradiation times.  There have been very few examples of cages that respond to visible light with single photon irradiation.  Herein, we report the efficient preparation of 11 caged Glu examples that respond to two visible wavelengths, 467 nm (thiocoumarin based) and 515–540 nm (BODIPY based).  The kinetics of photo-uncaging were studied for all cage designs, and we report all quantum efficiencies, i.e., quantum yields (Φ), that ranged from 0.0001–0.65.  Two of the BODIPY cages are reported here for the first time Me-BODIPY-Br-Glu, shows the most efficient release with a QE of 0.65.  Similar cage designs can be extended to GABA, the inhibitory neurotransmitter.  This would enable the use of two visible wavelengths to modulate the release of excitatory and inhibitory neurotransmitters upon demand via optical control.