Bambusuril as an effective astatide sequestrating agent by hydrogen bonding

Area of Science:

• Supramolecular Chemistry
• Radiopharmaceutical Chemistry
• Nuclear Medicine

Background:

• Astatine-211 (²¹¹At) is a promising alpha-emitting radionuclide for targeted cancer therapy.
• Developing efficient chelators for ²¹¹At is crucial for creating effective radiopharmaceuticals.
• Existing methods for ²¹¹At chelation face challenges in stability and efficiency.

Purpose of the Study:

• To report a novel molecular cage, propargylated bambus[6]uril, for strong chelation of the ²¹¹At radioanion.
• To investigate the stability and complexation properties of the developed cage with ²¹¹At.
• To explore the potential of this new system for ²¹¹At-based radiopharmaceuticals.

Main Methods:

• Synthesis of propargylated bambus[6]uril molecular cage.
• Evaluation of the cage's affinity for iodide and astatide radiohalides.
• Stability studies of inclusion complexes in phosphate-buffered saline (PBS) and human serum.
• Density Functional Theory (DFT) calculations to elucidate binding interactions.

Main Results:

• Propargylated bambus[6]uril demonstrated strong chelation of the ²¹¹At radioanion.
• The resulting inclusion complexes exhibited high stability in both PBS and human serum.
• DFT calculations confirmed the role of C-H⋯At non-covalent cooperative interactions in complex formation.

Conclusions:

• This study presents the first report of ²¹¹At labeling via encapsulation mediated by hydrogen bonds.
• The developed molecular cage offers a promising platform for the design of novel and stable ²¹¹At-based radiopharmaceuticals.
• This work opens new avenues for targeted alpha therapy development.