Rhodopsin-Mimicking Reversible Photo-Switchable Chloride Channels Based on Azobenzene-Appended Semiaza-Bambusurils...

Area of Science:

• Membrane biophysics
• Supramolecular chemistry
• Chemical biology

Background:

• Stimulus-responsive ion channels are crucial for understanding biological processes.
• Existing natural channels like channelrhodopsins offer limited control.
• A need exists for synthetic, precisely controllable ion transport systems.

Purpose of the Study:

• To develop a novel class of photo-switchable anion channels.
• To investigate the light-induced modulation of chloride transport.
• To explore the therapeutic potential of these channels in cancer treatment.

Main Methods:

• Synthesis of azo-functionalized bambusurils (azo-BUs).
• Lipid membrane reconstitution and chloride flux assays.
• Cellular studies including apoptosis induction and lysosomal acidification assays.
• Light-induced isomerization studies.

Main Results:

• The (E)-isomer of azo-BUs demonstrated efficient, light-switchable chloride transport.
• Light exposure reversibly toggled channel activity, enabling spatiotemporal control.
• The (E)-isomer induced apoptosis via mitochondrial depolarization and ROS generation.
• Disruption of lysosomal acidification through H⁺/Cl⁻ cotransport was observed.
• The (Z)-isomer showed minimal activity, serving as the inactive state.

Conclusions:

• Azo-BUs represent a new class of reversible, photo-gated anion channels.
• These channels can precisely control ion homeostasis in cellular environments.
• Azo-BUs exhibit a multifaceted cytotoxic mechanism with potential as anticancer agents.
• This platform offers new possibilities for light-responsive biomedical tools.