Substituent Effects on the Sensitivity of a Quinoline Photoremovable Protecting Group to One- and Two-Photon Excitation

Photoremovable protecting groups that can reveal biologically important functional groups through one- and two-photon excitation (1PE and 2PE, respectively) have promise in regulating physiological function in a temporally and spatially restricted manner. Only a few chromophores have sufficient sensitivity to 2PE suitable for use as caging groups in physiology experiments. It Would be useful to develop structure-property relationships of chromophores, so that chromophores with high two-photon uncaging action cross-sections (delta(u)) can be designed. The 8-bromo-7-hydroxyquinolinyl chromophore (BHQ) releases a variety of functional groups through 1PE and 2PE. Swapping the bromine substituent for a nitro (NHQ), cyano (CyHQ), or chloro (CHQ) or exchanging the hydroxy for dimethylamino (DMAQ and DMAQ-Cl) or sulfhydryl (TQ) significantly alters the photochemical and photophysical properties of the quinoline chromophore. CyHQ-OAc demonstrated a 3-fold increase in sensitivity for acetate release, whereas NHQ-OAc was photochemically insensitive. The quantum efficiencies (Q(u)) of the amino and sulfhydryl derivatives were about an order of magnitude lower than that of BHQ-OAc. All of the chromophores showed diminished sensitivity to 2PE compared to BHQ-OAc, but the CyHQ, DMAQ, and DMAQ-Cl chromophores are sufficiently sensitive for physiological use. The high sensitivity of CyHQ to 1PE will be useful in biological applications requiring short exposure with low light intensity.