Water-Soluble BODIPY Photocages with Tunable Cellular Localization

Area of Science:

• Chemical Biology
• Photochemistry
• Molecular Imaging

Background:

• Photoactivation of bioactive molecules offers precise control over cellular processes.
• Visible-light excitable photoprotecting groups enhance biological applications due to better tissue penetration and lower phototoxicity.
• Hydrophobicity of visible-light photocaging groups limits their utility.

Purpose of the Study:

• To develop water-soluble visible-light excitable photocages with controlled cellular permeability.
• To overcome the limitations of hydrophobicity in BODIPY photocages.
• To enable precise spatiotemporal manipulation of cellular processes using visible-light photoactivation.

Main Methods:

• Conventional 2,6-sulfonation was found incompatible with BODIPY photocages' photoreaction.
• A novel remote sulfonation strategy was applied to BODIPY photocages.
• Synthesis and characterization of peripherally disulfonated and monosulfonated BODIPY photocages.

Main Results:

• Remote sulfonation successfully imparted water solubility to BODIPY photocages.
• Disulfonated BODIPY photocages are cell impermeable, suitable for cell-surface targeting.
• Monosulfonated BODIPY photocages retain cell permeability for intracellular targeting.
• Validated by visible-light photoactivation of signaling molecules in mammalian cells and neurons.

Conclusions:

• A generalizable method for controlling BODIPY photocage localization via sulfonation was established.
• This approach enhances the application of photoactivation strategies in chemical biology.
• Offers a versatile platform for visible-light-mediated manipulation of cellular functions.