Adhesive pi-clamping within synthetic multifunctional pores

Area of Science:

• Supramolecular Chemistry
• Membrane Biophysics
• Materials Science

Background:

• Synthetic pores are crucial for mimicking biological channels.
• Modifying pore interiors can tune their function and interactions.
• Naphthalenediimide (NDI) derivatives offer unique electronic properties for molecular recognition.

Purpose of the Study:

• To design and synthesize multifunctional synthetic pores incorporating adhesive naphthalenediimide (NDI) pi-clamps.
• To evaluate the impact of these pi-clamps on pore activity and blocker interactions within lipid bilayers.
• To demonstrate the functional relevance of pi-clamping using an in situ blocker screening method.

Main Methods:

• Synthesis of synthetic pores with and without internal NDI pi-clamps.
• Incorporation of pores into lipid bilayer membranes.
• Measurement of pore activity and blockage efficiency.
• Quantification of clamping factors based on blocker properties (charge, aromaticity).

Main Results:

• Synthetic pores with and without NDI pi-clamps exhibited similar nanomolar activity.
• Pi-clamping significantly influenced blockage efficiency, quantified by clamping factors.
• Clamping factors increased with increasing blocker charge, indicating ion pairing.
• Clamping factors also increased with enhanced aromatic electron donor-acceptor interactions, highlighting pi-pi interactions.

Conclusions:

• Adhesive NDI pi-clamps within synthetic pores enhance specific blocker interactions.
• The developed in situ screening method effectively demonstrates the functional relevance of pi-clamping.
• These advanced synthetic pores with tailored active sites hold promise for drug discovery and diagnostics.