Complex forming behaviour of α, β and γ-cyclodextrins with varying size probe particles in silico

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 α, β, and γ-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. Probe particle with intermediate hydrophilicity (ϵ = 0.2 kcal mol^-1), with nominal radius in the range of 0.5 - 1.1 Å (effective radius of 2.61 - 3.41 Å), makes the complexes with α-CD. For β-CD, these values range from 0.9 - 1.9 Å (3.75 - 4.26 Å) and for γ-CD 1.4 - 2.8 Å (3.72 - 5.09 Å) respectively.