Competing Pathways in the Photo-Favorskii Rearrangement and Releaseof Esters: Studies on Fluorinated p-Hydroxyphenacyl-Caged GABA andGlutamate Phototriggers

摘要

Three new trifluoromethylated p-hydroxyphenacyl (pHP)-caged γ-aminobutyric acid (GABA) andglutamate (Glu) derivatives have been examined for their efficacy as photoremovable pro-tecting groups in aqueous solution. Through the replacement of hydrogen with fluorine,e.g., a m-trifluoromethyl or a m-trifluoromethoxy versus m-methoxy substituents on the pHP chromo-phore, modest increases in the quantum yields for the release of amino acids GABA and glutamate aswell as improved lipophilicity were realized. The pHP triplet undergoes a photo-Favorskii rearrange-ment with concomitant release of the amino acid substrate. Deprotonation competes with therearrangement from the triplet excited state and yields the pHP conjugate base that, uponreprotonation, regenerates the starting ketoester, a chemically unproductive or °energy-wasting±process. When picosecond pump-probe spectroscopy is employed, GABA derivatives 2-5 arecharacterized by short triplet lifetimes, a manifestation of their rapid release of GABA. Thebioavailability of released GABA at the GABAA receptor improved when the release tookplace from m-OCF_3(2) but decreased for m-CF_3) when compared with the parent pHP derivative.These studies demonstrate that pK_a, and lipophilicity exert significant but sometimes opposinginfluences on the photochemistry and biological activity of pHP phototriggers.