Rim Binding of Cyclodextrins in Size-Sensitive Guest Recognition.

Area of Science:

• Supramolecular Chemistry
• Nanotechnology
• Biochemistry

Background:

• Cyclodextrins (CDs) are cyclic oligosaccharides with a hydrophobic cavity and hydrophilic exterior.
• Molecular recognition by CDs has traditionally focused on guest inclusion within the cavity.
• Rim binding of CDs has been largely overlooked in molecular recognition studies.

Purpose of the Study:

• To investigate the role of cyclodextrin rims in molecular recognition.
• To explore size-sensitive binding mechanisms of cyclodextrins.
• To demonstrate the utility of single-molecule electron microscopy in supramolecular studies.

Main Methods:

• Utilized single-molecule electron microscopy (SME-EM) for high-resolution imaging.
• Employed a library of graphitic cones as a solid-state substrate for complexation.
• Analyzed thousands of individual CD-guest complexes using structural and statistical methods.
• Recorded dynamic supramolecular events using 2.5 ms resolution electron microscopy video.

Main Results:

• Demonstrated that cyclodextrins bind guests using both cavity and rim interactions.
• Showcased size-sensitive binding with precision better than 1 Å for γ-CD.
• Observed rim binding for guests larger than the CD cavity.
• Provided direct visual evidence of the size recognition process.

Conclusions:

• Cyclodextrin molecular recognition involves a previously underappreciated rim binding mode.
• The combination of cavity and rim binding allows for precise size discrimination.
• Dynamic SME-EM is a powerful tool for elucidating spatiotemporal details of supramolecular complexation.