Complex forming behaviour of {\alpha}, \b{eta} and {\gamma}-cyclodextrins with varying size probe particles in silico

TL;DR

This study uses molecular dynamics simulations with varying probe sizes to explore the flexible complex-forming behavior of alpha, beta, and gamma cyclodextrins, revealing their ability to accommodate larger molecules than previously thought.

Contribution

It provides the first systematic in silico analysis of how cyclodextrins can form complexes with larger guest molecules due to their flexibility.

Findings

Cyclodextrins can form complexes with molecules larger than their static cavity sizes.

Flexibility of CDs allows dynamic complex formation.

Simulation results challenge static cavity size assumptions.

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides composed of glucopyranose units bonded together to form a truncated cone that can make inclusion complexes with guest molecules. The {\alpha}, \b{eta}, and {\gamma}-CDs, which respectively comprise six, seven or eight glucopyranose units, are used extensively in pharmaceutical formulations as functional excipients. The cavity sizes of all three natural CDs have been approximated using static structures but a growing consensus is that the CDs are flexible; moreover, the size range of molecules that CDs can accommodate has not been systematically studied. Here the results of molecular dynamics simulations performed using spherical continuum probe particles of different sizes to observe the complex-forming behaviour of CDs are presented. Results revealed that CDs can make dynamic complexes with guest molecules that are larger than their reported cavity sizes.