Caged Protons as Tools for Studying Transport of Protons along Lipid Bilayers

Photocleavable groups ("caging groups") allow control of (bio-)molecular processes with high spatiotemporal precision. Upon light irradiation, these compounds undergo irreversible photocleavage, thereby releasing a previously concealed ("caged") substance. Hydrophobic caged protons may be used to deliver protons to the lipid bilayer surface. The charged derivatives of these coumarin-based phototriggers acidify only one side of a lipid membrane, while the uncharged derivatives are membrane-permeant and deliver protons to both sides of the lipid bilayer. Consequently, the hydrophobic caged protons are ideal tools to study proton migration along the membrane surface which appears to play a preeminent role in chemiosmotic phosphorylation and other proton driven processes (3). Unfortunately, only hydrophilic and poorly light-responsive caged protons (like nitrophenylethylsulfate) are commercially available at present. For this reason, we reestablished the synthesis of coumarin-based caged protons and extended the spectrum of membrane impermeable hydrophobic caged protons by [7-(diethylamino)coumarin-4-yl]methyl-sulfate. The lipophilic caged protons were used in new studies of surface-confined proton transport.