Rim Binding of Cyclodextrins in Size-Sensitive Guest Recognition

Abstract

Cyclodextrins (CDs) are doughnut-shaped cyclic oligosaccharides having a cavity and two rims. Inclusion binding in the cavity has long served as a classic model of molecular recognition, and rim binding has been neglected. We found that CDs recognize guests by size-sensitive binding using the two rims in addition to the cavity, using single-molecule electron microscopy and a library of graphitic cones as a solid-state substrate for complexation. For example, with its cavity and rim binding ability combined, γ-CD can recognize a guest of radius between 4 and 9 Å with a size-recognition precision of better than 1 Å, as shown by structural analysis of thousands of individual specimens and statistical analysis of the data thereof. A 2.5 ms resolution electron microscopic video provided direct evidence of the process of size recognition. The data suggest the occurrence of the rim binding mode for guests larger than the size of the CD cavity and illustrate a unique application of dynamic molecular electron microscopy for deciphering the spatiotemporal details of supramolecular events.

Atomic-number ( Z )-correlated atomic sizes for deciphering electron microscopic molecular images

“…Fig. 5 B shows α-cyclodextrin (α-CD), a cyclic hexamer of glucose, sliding near the apex of a carbon nanohorn (CNH) ( 7 ). The ZC model matches the TEM image better than the CPK model.…”

“…The ZC model matches the TEM image better than the CPK model. The larger size of individual dark spots in the TEM image than the ZC atoms is due to blurring caused by motions of the α-CD molecule during the 0.5 s exposure time ( 7 ). Fig.…”

“…With the advent of atomic-resolution transmission electron microscopy (AR-TEM) achieving sub-Ångstrom image resolution and submillisecond time resolution ( 5 – 8 ), an era of “cinematic molecular science” has arrived, where chemists can visually study the time evolution of molecular motions and reactions at atomistic precision ( 9 – 11 ). However, experimental TEM images often differ greatly from what chemists expect using their favorite molecular models ( Fig.…”

Hydrophobic Localized Enrichment of Co-reactants to Enhance Electrochemiluminescence of Conjugated Polymers for Detecting SARS-CoV-2 Nucleocapsid Proteins

“… 23 He’s group utilized the host–guest recognition between aptamer and tris(bipyridine)ruthenium(II)-β-cyclodextrin for detecting thrombin. 24 Wei’s group utilized metal-binding sites of β-CD to bind Pb 2+ for synthesizing metal–organic frameworks (MOFs). 25 In addition, the hydrophobic nanocavity of β-CD could act as a nanoreactor, creating a restricted system to accelerate electronic excitation.…”

Efficient Persistent Luminescence Tuning Using a Cyclodextrin Inclusion Complex as Efficient Light Conversion Materials

“…To enhance the luminous intensity, supramolecular assemblies based on macro-cycles, including ionic crown ethers, , ionic macrocyclic arenes, , cyclodextrins, − cucurbiturils, , etc., have been a research hotspot topic in recent years. Because fluorescent molecules are sensitive to their steric environments, the preparation of highly fluorescent photofunctional materials by accommodating fluorophore guests in coordinating hosts and macrocyclic receptors, so-called spatial confinement, has emerged as a highly promising strategy. − Cyclodextrins (CDs) are naturally occurring water-soluble toroidally shaped polysaccharides with a hydrophobic central cavity and hydrophilic exterior. , The highly hydrophobic central cavity of CDs enables it to form inclusion complexes with a variety of substrates .…”