Kenneth Stensrud, Jihyun Noh, Karl Kandler, Jakob Wirz, Dominik Heger, Richard S. Givens, "Competing pathways in the photo-Favorskii rearrangement and release of esters: Studies on fluorinated p-hydroxyphenacyl GABA and glutamate phototriggers", J. Org. Chem. 2009, 74, 5219-5227.


Abstract: Evidence for competing pathways between the photo-Favorskii rearrangement and an Excited State Proton Transfer (ESPT) during photolysis of p-hydroxyphenacyl (pHP) caged amino acid has been uncovered. The physical and photochemical properties of several trifluoromethylated p-hydroxyphenacyl (pHP) caged GABA derivatives were altered by replacing hydrogen with fluorine, e.g., a m-trifluoromethyl or a m-trifluoromethoxy vs m-methoxy substituents on the pHP chromophore. Modest increases in the quantum yields for release of the amino acids GABA and glutamate were realized as well as improved lipophilicity. GABA derivatives 2 - 5 are characterized by efficient intersystem crossing, short triplet lifetimes, formation of long-lived triplet hydroxyquinomethide intermediates, and rapid release of GABA by picosecond pump-probe spectroscopic studies. The competing ESPT process is unproductive, the hydroxyquinomethide reverting to the starting ketoester and therefore an 'energy wasting' alternate to the decaging reaction. An increase in the GABAA receptor response was also observed for the release of GABA from m-OCF3 (2) but not for m-CF3 (3) substituted chromophores. Additional studies suggested that pKa and lipophilicity exert significant but sometimes opposing influences on the photochemistry and biological activity of the pHP phototrigger.