Substituent Effect on the Structural Behavior of Modified Cyclodextrin: A Molecular Dynamics Study on Methylated β-CDs

A series of methylated and non-methylated β-cyclodextrin (β-CD) structures in three macrocyclic configurations (<i>a</i>–<i>c</i>) were studied with molecular dynamics (MD) simulations to elucidate the dynamic behavior of the different CD structures using a continuum water model with the AMBER* force field. A set of parameters were defined to describe the geometric dimensions of the CD, such as its cavity shape, the upper and lower rim sizes, and the tilting of each of the glucose rings. Correlation analyses between the different parameters were carried out, and they have provided insights into the different dynamic behaviors for the different CD structures. Detailed analyses on the crystal structures of the different methylated and non-methylated β-CD complexes were also carried out using the defined parameters. Correlation of parameters from crystal structures and MD simulations has allowed us to identify the effect that crystal packing/guest inclusion has on the CD geometries. The overall analysis approach can be a useful tool for other related macrocyclic structures, such as modified α-, β-CDs or even calixarenes