  Understanding the atomic level interactions and the resulting structural
characteristics is required for developing beta-cyclodextrin ($\beta$CD)
derivatives for pharmaceutical and other applications. The effect of four
different solvents on the structures of the native $\beta$CD and its
hydrophilic (methylated $\beta$CD; ME$\beta$CD and hydroxypropyl $\beta$CD;
HP$\beta$CD) and hydrophobic derivatives (ethylated $\beta$CD; ET$\beta$CD)
were explored using molecular dynamics (MD) simulations and solvation free
energy calculations. The native $\beta$CD, 2-ME$\beta$CD, 6-ME$\beta$CD,
2,6-DM$\beta$CD, 2,3,6-TM$\beta$CD, 6-HP$\beta$CD, 2,6-HP$\beta$CD and
2,6-ET$\beta$CD in non-polar solvents (cyclohexane; CHX and octane; OCT) were
stably formed in symmetric cyclic cavity shape through their intramolecular
hydrogen bonds. In contrast, $\beta$CDs in polar solvents (methanol; MeOH and
water; WAT) exhibited large structural changes and fluctuations leading to
significant deformations of their cavities. Hydrogen bonding with polar
solvents was found to be one of the major contributors to this behavior:
solvent-\b{eta}CD hydrogen bonding strongly competes with intramolecular
bonding leading to significant changes in structural stability of $\beta$CDs.
The exception to this is the hydrophobic 2,6-ET$\beta$CD which retained its
spherical cavity in all solvents. Based on this, it is proposed that
2,6-ET$\beta$CD can act as a sustained release drug carrier.

Soft Condensed Matter;Biological Physics;Chemical Physics