Two-Photon Excitable Photoremovable Protecting Groups Based on the Quinoline Scaffold for Use in Biology

Anna Lisa K. Hennig, Davide Deodato, Naeem Asad, Cyril Herbivo, Timothy M. Dore

Research output: Contribution to journalArticle

Abstract

Photoremovable protecting groups (PPGs) are powerful tools for physiological studies, harnessing light as an on/off switch to provide tight spatio-temporal control over the release of biological effectors through two-photon excitation (2PE) in tissue culture and whole-animal studies. We carried out a series of systematic structural modifications to the (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ) chromophore to conduct an SAR study with the aim of enhancing its photochemical properties, especially its two-photon uncaging action cross section (δu). The best results were obtained when substituents were added at the C4 position, which improved δu for release of acetate up to 7-fold, while retaining all the other excellent properties of the CyHQ PPG, including high quantum yield (φu), low susceptibility to spontaneous hydrolysis in the dark, and good aqueous solubility. Hammett correlation analysis suggested that photolysis efficiency is favored by electron-rich substituents at C4, giving important insights into the mechanism of the photolysis reaction. The four best CyHQ derivatives were used to mediate the efficient release of homopiperonylic acid in high yield under simulated physiological conditions. Our efforts have led to the development of 2PE-sensitive PPGs with remarkable δu values (up to 2.64 GM), excellent quantum yields (up to 0.88), and high-yielding effector release (up to 92%).

Original languageEnglish (US)
Pages (from-to)726-744
Number of pages19
JournalJournal of Organic Chemistry
Volume85
Issue number2
Early online dateDec 6 2019
DOIs
StatePublished - Jan 17 2020

    Fingerprint

ASJC Scopus subject areas

  • Organic Chemistry

Cite this